BioScience Today 14

BIO

SCIENCETODAY

| BIOSCIENCE TODAY SEPTEMBER•OCTOBER 2018 |

SEPTEMBEROCTOBER2018

improving patient care...

News • biodigestables • diagnostic devices • finance & funding • intellectual property • respiratory • clinical trials • cleanrooms

| BIOSCIENCE TODAY SEPTEMBER•OCTOBER 2018 |

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| BIOSCIENCE TODAY SUMMER 2018 |

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| welcome |

Welcome Take a breath…

Ellen Rossiter Editor in chief

Editor Ellen Rossiter ellen.rossiter@distinctivepublishing.co.uk

Design Distinctive Publishing, 3rd Floor, Tru Knit House, 9-11 Carliol Square, Newcastle, NE1 6UF Tel: 0191 580 5990 www.distinctivepublishing.co.uk

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Distinctive Publishing or BioScience Today cannot be held responsible for any inaccuracies that may occur, individual products or services advertised or late entries. No part of this publication may be reproduced or scanned without prior written permission of the publishers and BioScience Today.

Take a seat and when you’re sitting comfortably - we’ll begin.

Welcome to our latest edition of BioScience Today, in this issue, we consider an action that many of us take for granted – breathing.

It’s not uncommon for people not to like needles, so it was with interest that we heard about a high-precision laser device that has the capacity to carry out a range of health checks using beams of light. Again the benefits seem to be three-fold delivering a better, speedier service for patients, more cost-effectively.

Taking a breath is something we do every minute of every day – unthinkingly for the most part. Though I am embarrassed to admit that walking up the stairs to our office is more difficult than it should be – breathing is something I very much take for granted.

With budgets constraints never far from our minds, it’s all the more important that we make the best possible use of the medicines available, so we also learn how drug re-purposing is paving the way to improve patient care by providing more treatment options.

But what happens when that’s not the case.

Can’t breathe easily? There can be few things as scary as not being able to catch your breath, so we take a look at the work that is in progress to improve treatments for respiratory diseases.

We take a look at a collaborative project that is speeding up the adoption of re-purposed medicines for use in the NHS. Already the findings have been shown to be both lifeextending and cost-effective.

The challenge to enable everyone to breathe clean air, effortlessly, is a huge one, but with the collaborative work that is ongoing progress is being made, with the hope that in the future, no one will be left gasping for breath.

As we’ve noted in Bioscience Today before, the model of drug discovery and development is changing, with more independent bioscience businesses playing a part, so we gain an insight into the crucial role of bioscience incubators in galvanising advances in these fields. We also examine some of the nuts and bolts of finance, funding and protecting your intellectual property.

When we’re not well, an early diagnosis and swift treatment are paramount, so in this issue, we also focus on how PET imaging is being used to see deep into the body before any structural changes have occurred – providing a three-dimensional map of the chemical changes within. Though this technology has been around for a while, we learn how it is being applied in new areas to improve patient diagnosis and treatment.

Recognising the patient as a partner in research is a priority, we see how patient advocacy organisations not only facilitate patient involvement in research but also help steer the priorities of that research to assist in identifying and addressing unmet needs.

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Bringing a drug candidate to clinical trial is a huge task and a risky one, with around 10% of candidates making it through to final approval, so in this issue, we hear about the external resources available to help with the process.

You’ll also notice – if you give this edition a close reading – which we’re sure you do – that not all of the views expressed are entirely consistent. Is the UK a great place to develop your career as a scientist or not? Read on and join in the debate.

| contents |

| BIOSCIENCE TODAY SEPTEMBER•OCTOBER 2018 |

features

Helping everyone breathe easier – finding new approaches to treating respiratory disease

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10 Wellcome launches £250m Leap Fund to place big bets on bold research

Radiation in cancer diagnosis – keeping your enemies closer

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| BIOSCIENCE TODAY SEPTEMBER•OCTOBER 2018 |

| contents |

contents

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www.biosciencetoday.co.uk / issue 14 /september•october 2018

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Introduction/Foreword

4-5

Contents

6-7

Industry Contributors

8-9 Biodigestables 10-19 News

Wellcome launches £250m Leap Fund to place big bets on bold research

20-27

Diagnostic Devices

30-32

Big Interview

36-41

Finance & Funding

42-45

Intellectual Property

Meeting contemporary medical challenges

Why life science incubators are crucial

Patient capital is the key to unlocking growth in the life sciences sector

46-52

54-59

Life sciences – developments from the IPO’s perspective

Advances in treatment of Respiratory diseases

Helping everyone breathe easier – finding new approaches to treating respiratory disease

Clinical Trials Stay future-ready: Running parallel operations with a CDMO

during clinical trials

60-63 66

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Study provides first evidence that psychological therapy can be successfully delivered automatically in virtual reality (VR)

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Gastrointestinal Disorders

Engaging the patient as partner

Cleanrooms

Economy Secretary welcomes £4m ICS Clean Room

| industry contributors |

Daniel Oliver CEO, Capital Cell

| BIOSCIENCE TODAY SEPTEMBER•OCTOBER 2018 |

Miss Afrin Zohura Bioprocess Research Engineer, Ultra Scale-Down (USD) Technologies, Department of Biochemical Engineering, UCL

Dr Christine J McNamee, Manager of the Pharmacogenetics and Stratified Medicine Network

Daniel is a crowdfunding expert, advisor to the European Commission’s Crowdfunding Stakeholders Forum, former President of the Spanish Crowdfunding Association and Board Member at the European Equity Crowdfunding Association. A Biology graduate from the University of Barcelona, he is also a member of the Leadership Board of the Cambridge Centre for Alternative Finance.

Afrin has worked within the automotive sector, with experience in component engineering and project management. At UCL, she is leading the commercialisation of Ultra Scale-Down (USD) technologies and the development of future USD devices for industrial and academic use.

Umay Saplakoglu, Ph.D. General Manager, Fast Trak at GE Healthcare

Ian Jarrold Head of Research at the British Lung Foundation (BLF)

Dr Glenn Crocker MBE Chief Executive Officer – BioCity Group

Umay joined GE Healthcare in 2002 as a scientific support specialist. As General Manager for Fast Trak, Umay oversees process development, training, and clinical manufacturing offerings.

She helps biomanufacturers increase process productivity, reduce cost and bring product to market faster.

Ian Jarrold has a Master’s degree in Biochemistry and has worked in the medical research charity sector for over a decade. As Head of Research at the BLF, Ian works on all aspects of the charity’s support for research into lung disease. This includes research strategy, managing the allocation of research funds to UK researchers and gathering information on the outcomes of this research.

Glenn Crocker is an experienced CEO, company founder, non-executive director and investor in the life sciences sector. He has a DPhil in Immunology from Oxford University and qualified as a chartered accountant, before working with biotech companies in California and the UK. In 2014 Glenn received an MBE for services to the biotechnology industry.

Divya Chadha Manek Head of Business Development and Marketing

Andrea Gruber, IATA Head, Special Cargo at International Air Transport Association (IATA)

Professor Phil Blower Professor of Imaging Chemistry - King’s College London

Andrea is Head of Special Cargo at IATA. In this capacity she is responsible for leading IATA’s Cargo governing bodies, comprised of airlines and air cargo supply chain stakeholders in the development of regulations for the air transportation of Live Animals, Perishables and Healthcare Products.

Head of Department of Imaging Chemistry and Biology in the School of Biomedical Engineering and Imaging Sciences. Phil’s work for the last 30 years has focused on the development of novel radiopharmaceutical chemistry for medical imaging, always at the interface between academia and hospital medicine.

Divya’s role is to maintain strategic relationships with Global and UK life sciences companies. Divya facilitates key discussions between life sciences industry and the Clinical Research Network. Divya provides advice and works collaboratively with companies on how they are able to tap into the Clinical Research Network services to ensure clinical studies are set up quickly and effi ciently so that they recruit to time and target.

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Linking multidisciplinary sectors of the personalised medicine community through an informative website. Organising events that bring leading experts together to address the challenges of moving personalised medicine forward into the clinic so as to provide patients with improvements in their healthcare.

| BIOSCIENCE TODAY SEPTEMBER•OCTOBER 2018 |

Martin Gosling Chief Scientific Officer, Enterprise Therapeutics & Professor of Molecular Pharmacology, University of Sussex Martin has devoted his research career to realising the therapeutic potential of ion channels in both academic, industrial and biotech settings. Martin is co-founder and CSO of Enterprise Therapeutics, a Sussexbased biotech focused upon the discovery of new drugs for respiratory diseases.

Keith Morgan CEO, British Business Bank

| industry contributors |

Paul Horner International Air Transport Association Manager, Dangerous Goods Standards Paul joined IATA in January 2016 as the Manager, Dangerous Goods Standards. The role includes authoring the text for the IATA dangerous goods regulations and other technical publications, answering technical emails through a dedicated hotline, working with the IATA Dangerous Goods Board, attending ICAO and UN dangerous goods meetings, supporting industry events and acting as the subject matter expert for the Association.

Ceciel T. Rooker President, International Foundation for Gastrointestinal Disorders (IFFGD)

Keith Morgan led the planning and establishment of the British Business Bank from January 2013, and was appointed CEO in December 2013. Prior to this, Keith was an Executive Director of UK Financial Investments (UKFI). Keith holds an MA in Philosophy, Politics and Economics from University College, Oxford and an MBA from Harvard Business School.

With over a decade of experience in the field of functional gastrointestinal and motility disorders, Ceciel joined the International Foundation for Gastrointestinal Disorders (IFFGD) in 2017 as President to champion the needs of patients and families affected by these chronic and often misunderstood conditions.

Liz Coleman Divisional Director at the Intellectual Property Office

Paul Chrisp Programme Director of the Mecicines and Technologies Programme

Liz Coleman is the Divisional Director at the Intellectual Property Office responsible for patents, trade marks and designs policy including European and international negotiations in these areas. Her background is in natural sciences and she joined the then Department of Trade and Industry as a patent examiner last century.

Paul Chrisp has been with NICE since March 2009. He is Programme Director of the Medicines and Technologies Programme, which supports the appropriate uptake and use of medicines and technologies. He also set up the Institute’s accreditation programme, which evaluates the processes used by organisations to develop guidance.

From September 2018 Paul will join the NICE Board as Director for the Centre for Guidelines.

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Catherine Walker Inward Investment Director, Invest Newcastle Catherine is at the helm of Newcastle’s drive to attract inward investment. Invest Newcastle is a service delivered by NewcastleGateshead Initiative on behalf of Newcastle City Council, to attract and secure new investment and jobs for the city. Catherine is responsible for developing and delivering ambitious plans to attract new businesses and support businesses to grow. These plans are strongly aligned with the city’s wider commitment to support economic development, innovation and growth within life sciences.

Mike Jennings Partner, AA Thornton Mike is a Partner and patent attorney at IP law firm AAThornton. A member of the Computer Technology Committee of CIPA and the EPO’s Standing Advisory Committee quality working group. Mike contributed to AIPPI’s international study of patentability of computer-implemented inventions in 2017.

Catrin Rutland BSc PGCHE MSc MMedSci PhD SFHEA FAS Associate Professor in Anatomy and Developmental Genetics Catrin undertakes research and teaching at the School of Veterinary Medicine and Science, University of Nottingham. Her research revolves around improving health by understanding the genetics behind disorders and developing prognostic and therapeutic technologies in both animals and humans.

| biodigestables |

| BIOSCIENCE TODAY SEPTEMBER•OCTOBER 2018 |

BIODIGESTABLES

Lower risk of serious bleeding

Dementia caused 13% of UK deaths in 2017

Changes in cancer treatment?

New drugs used to treat serious blood clots, known as direct oral anticoagulants (DOACs), are associated with reduced risks of major bleeding compared with the older anti-clotting drug, warfarin, according to a new study by researchers at the University of Nottingham. The findings, published in the BMJ, provide initial reassurance about the safety of DOACs as an alternative to warfarin for all new patients.

Alzheimer’s Research UK is calling for urgent investment in dementia research, following new statistics that show the condition accounted for 13% of all UK deaths last year. The figures have recently been released by the Office for National Statistics today (Wednesday 18 July).

Researchers at the University of Dundee have developed new drug modelling systems that could herald changes in the way patients are treated for the UK’s deadliest form of cancer. A team at the University’s School of Medicine say they have established a more accurate process of mimicking how anti-cancer medication metabolises in the human body, a move that could significantly benefit patients.

Need to improve treatment

Ancient snake embryo found

Nine in ten people with coronary heart disease in the UK are living with at least one other long-term condition, such as stroke, dementia and high blood pressure, according to alarming figures released by the British Heart Foundation. he charity warns that a growing number of people living with interrelated health conditions – or multi-morbidities – represents a grave challenge for a health system focused on treating individual illnesses.

First fossilized embryo rewrites what paleontologists know about ancient snakes. An ancient snake embryo, preserved in 105-million year-old amber, provides important new information on the evolution of modern snakes, according to a new study led by University of Alberta paleontologists. The fossil is the first baby snake to yet be found.

Data for 2017 shows that in total, there were 67,641 deaths attributed to Alzheimer’s disease or other forms of dementia – 13% of the total deaths recorded that year. This is a rise from 2016, when there were 62,948 deaths from dementia (12% of all those recorded).

Boosting efforts to fight antibiotic resistance, Stanford researchers have found that a thin membrane, thought to be just a shrink wrap around some bacterial cell walls, has structural properties critical for survival. Drugs that destroy the membrane could be a new approach to treating infection.

Parrot secret revealed

4,000 strokes prevented Pollinators and food security Four thousand strokes were prevented in England between 2015 and 2016 due to the increased use of anticoagulant drugs amongst patients with a common heart rhythm disorder, according to new analysis part-funded by British Heart Foundation (BHF) and published in the European Heart Journal (EHJ). The BHF say the findings highlight the urgent need for better screening and diagnosis of AF to ensure patien

Bacterial armor

Supplies of chocolate, strawberries and coffee could be limited if pollinators, such as bees, continue to decline – according to pollination expert Dr Lynn Dicks at the University of East Anglia. Dr Dicks is an expert in the effects of pollinator decline and how we can stop it. Her research has identified which crops are vulnerable to pollinator decline, and a product found to be at significant risk is cocoa.

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University of Alberta neuroscientists have identified the neural circuit that may underlay intelligence in birds, according to a new study. The discovery is an example of convergent evolution between the brains of birds and primates, with the potential to provide insight into the neural basis of human intelligence.

| BIOSCIENCE TODAY SEPTEMBER•OCTOBER 2018 |

| biodigestables |

BIODIGESTABLES

Focussed ultrasound and New way to regenerate nanomedicine hearts after a heart attack Researchers funded by the British Heart Foundation have identified how a new treatment in mice can regenerate the heart after a heart attack – preventing the onset of heart failure. The team from the University of Oxford found that injecting a protein called VEGF-C after heart attacks in mice significantly reduced the amount of damaged heart muscle, and allowed the heart to recover almost all of its pumping function. In comparison, untreated mice lost almost half of their heart function after a heart attack.

Low quality healthcare

Better risk prediction

Poor quality health services are holding back progress on improving health in countries at all income levels, according to a new joint report by the OECD, World Health Organization (WHO) and the World Bank.

Knowing your risk factors is key when it comes to preventing heart attack and stroke, and now researchers at Baylor College of Medicine have found that testing a specific type of triglyceride may be a better indicator for predicting the risk of cardiovascular disease and stroke compared to just traditional risk factors. The findings, which also point to a potential new treatment target to help prevent cardiovascular disease, appear in the latest issue of the Journal of the American College of Cardiology.

Today, inaccurate diagnosis, medication errors, inappropriate or unnecessary treatment, inadequate or unsafe clinical facilities or practices, or providers who lack adequate training and expertise prevail in all countries.

Mutations that drive precancerous blood condition A new study led by researchers at Harvard Medical School and the Harvard T.H. Chan School of Public Health has identified some of the first known inherited genetic variants that significantly raise a person’s likelihood of developing clonal hematopoiesis, an age-related white blood cell condition linked with higher risk of certain blood cancers and cardiovascular disease. The findings, published online in Nature, should help illuminate several questions about clonal hematopoiesis.

“We only learn when there is uncertainty, and that is a good thing,” said Daeyeol Lee, Yale’s Dorys McConnell Duberg Professor of Neuroscience and professor of psychology and psychiatry. “We really don’t want to be learning all the time.”

Lee and Yale colleagues presented monkeys with tasks where outcome probability was either constant or fluctuating and detected fundamental differences in brain activity during those two conditions, they reported in the journal Neuron.

Friendly bacteria help superbug Antimicrobial resistant pathogens crowdsource friendly bacteria to survive in immune cells and cause disease, a new study by the University of Sheffield has revealed. Scientists have discovered the human pathogen Staphylococcus aureus (S.aureus), uses benign bacteria present in the skin to initiate infection.

ts receive the clot-busting treatment which could prevent a devastating stroke.

Diabetes raises risk of cancer

Short story or article to share?

A global review involving almost 20 million people has shown that having diabetes significantly raises the risk of developing cancer, and for women the risk is even higher. The findings published in Diabetologia (the journal of the European Association for the Study of Diabetes [EASD]) highlight the need for more research into the role diabetes plays in developing cancer. They also demonstrate the increasing importance of sex specific research.

Send them to our Editor, Ellen Rossiter, at ellen.rossiter@distinctivepublishing.co.uk

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BIO

SCIENCETODAY

Researchers have made a breakthrough in more precisely targeting drugs to cancers. Using ultrasound and lipid drug carriers (liposomes), a multi-disciplinary team of biomedical engineers, oncologists, radiologists and anaesthetists at the University of Oxford have developed a new way to improve the targeting of cancer drugs to tumours.

The new technology has been used in humans for the very first time, with ultrasound remotely triggering and enhancing the delivery of a cancer drug to the tumour.

Aren’t sure?

| news |

| BIOSCIENCE TODAY SEPTEMBER•OCTOBER 2018 |

Wellcome launches £250m Leap Fund to place big bets on bold research Wellcome is to launch a new £250m fund that will place big bets on ambitious research programmes with the potential to fundamentally change science or transform health over a five- to ten-year horizon.

The Wellcome Leap Fund will support scientists, technologists and innovators from around the world to pursue bold ideas that would fall outside the remit of conventional life sciences funding. This is because they are deemed too high risk, need to overcome a major scientific or technical hurdle to turn a theoretical goal into reality, or because the individual does not have an academic background in the life sciences.

The not-for-profit Leap Fund draws inspiration from the technology and venture capital industries – taking on early stage, high-risk ideas and funding at scale – and applies these principles to charitable programme investments in the health and life sciences.

It will back unconventional ideas and bring together outstanding individuals from a range of disciplines and sectors, anywhere in the world, to work in parallel and solve problems differently. The Wellcome Leap Fund aims to deliver breakthroughs as transformative as the development of nanopore genome sequencing or cryoelectron microscopy, but on a vastly accelerated timescale.

The Leap Fund will broaden Wellcome’s overall charitable activity, which already provides more than £1bn a year to support science, research, innovation and public engagement around the world.

The fund will be led by a CEO who will decide which ideas to back and will set the level of ambition and risk.

They will have the autonomy to shape the portfolio and reallocate funds as needed to take advantage of the most promising programmes or opportunities as they arise.

If successful, by 2030 the Wellcome Leap Fund will have produced a small number of breakthroughs that open up entirely new areas of research, allow new scientific questions to be answered, change existing practice within a field or deliver transformative health benefits.

Wellcome Director Jeremy Farrar said: “Blue skies, curiosity-driven research is the bedrock of every major scientific and technological breakthrough of the past 100 years. It’s essential to the process of innovation.

“But many scientists have ambitious, potentially transformational ideas that don’t fit the standard funding model. They require unconventional and disruptive thinking, backed by funders with the scale and risk appetite to make big bets on something they know may not succeed, but would be transformational if it did. As an independent charitable foundation, Wellcome is well placed to enter this space and to deliver significant leaps in progress, by taking a longterm view and providing the freedom to pursue a bold vision at scale and speed.”

The intention is to establish the Wellcome Leap Fund as a wholly owned, charitable subsidiary of Wellcome, governed by an independent board. This structure will allow it to draw on the extensive depth of experience and networks that Wellcome has in the health and life sciences, whilst giving the CEO the freedom to act in the agile, risk-taking way needed to succeed.

It is anticipated that the search for a CEO will begin shortly and, once recruited, that the first research programmes will begin in late 2020. The £250m allocated to the Leap Fund over five years will account for about 5% of Wellcome’s total spending over that period.

“Blue skies, curiosity-driven research is the bedrock of every major scientific and technological breakthrough of the past 100 years.

It’s essential to the process of innovation.”

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| BIOSCIENCE TODAY SEPTEMBER•OCTOBER 2018 |

| news |

Complementary medicine for cancer can decrease survival New Haven, Conn.— People who received complementary therapy for curable cancers were more likely to refuse at least one component of their conventional cancer treatment, and were more likely to die as a result, according to researchers from Yale Cancer Center and the Cancer Outcomes, Public Policy and Effectiveness Research Center (COPPER) at Yale School of Medicine. The findings were reported today online in JAMA Oncology.

Use of complementary medicine — medical therapies that fall beyond the scope of scientific medicine — is growing in the United States and often used by patients with cancer. Although many patients believe that a combination of complementary medicine and conventional cancer treatment will provide the greatest chance at a cure, there is limited research evaluating the effectiveness of complementary medicines. It is also unknown whether patients who use complementary medicines use them to improve their response to conventional medical therapies, or use them in lieu of recommended conventional therapies.

“Past research into why patients use non-medical complementary treatments has shown the majority of cancer patients who use complementary medicines believe their use will result in improved survival,” said the study’s senior author, James Yu, M.D., associate professor of therapeutic radiology at Yale Cancer Center. “We became interested in this topic after we reviewed the literature, and found that there was scant evidence to support this belief.”

To investigate complementary medicine use and its impact on survival and treatment adherence, the researchers studied 1,290 patients with breast, prostate, lung, or colorectal cancer in the National Cancer Database (NCDB) — a joint project of the Commission on Cancer of the American College of Surgeons and the American Cancer

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Society. The NCDB represents approximately 70% of newly diagnosed cancers nationwide. Researchers compared 258 patients who used complementary medicine to 1,032 who did not.

The researchers studied de-identified patients diagnosed over a 10-year period, from 2004 to 2013. By collecting the outcomes of patients who received complementary medicine in addition to conventional cancer treatments, they found a greater risk of death. Interestingly, they noted, despite having received some conventional cancer therapy, these patients were more likely to refuse other aspects of recommended care like chemotherapy, surgery, radiation and/or hormone therapy. The researchers concluded patients who chose to use complementary medicines as a cancer treatment, were more likely to refuse other conventional cancer treatments and as a result, had a higher risk of death than those who used no complementary medicine.

“The fact that complementary medicine use is associated with higher refusal of proven cancer treatments as well as increased risk of death should give providers and patients pause,” said lead author Skyler Johnson, M.D., chief resident in radiation oncology at Yale School of Medicine.

“Unfortunately, there is a great deal of confusion about the role of complementary therapies. Although they may be used to support patients experiencing symptoms from cancer treatment, it looks as though they are either being marketed or understood to be effective cancer treatments.”

Cary Gross, M.D., co-author of the study, called for further research, “The sources of misinformation need to be better understood, so that patients aren’t being sold a false bill of goods.”

Henry Park, M.D., is also a study author.

| news |

| BIOSCIENCE TODAY SEPTEMBER•OCTOBER 2018 |

Rare amur leopard born at Highland Wildlife Park One of the rarest cats in the world has been born at the Royal Zoological Society of Scotland’s Highland Wildlife Park and could be released into the wild in Russia in the future.

It would be the first ever reintroduction to the wild of a critically-endangered Amur leopard.

Highland Wildlife Park is home to the zoo world’s only purpose-built Amur leopard habitat which is not on public view. This habitat has been designed solely to breed Amur leopards and maximise the possibility of their being released into the wild, to add to the very limited existing population.

With minimal human contact, it is not yet known if more than one cub has been born.

Douglas Richardson, head of living collections at the park, at Kincraig, near Kingussie, said, “Our approach to managing this highly threatened cat is globally unique, with the zoo and conservation community watching what we do with a view to following our lead.

in Russia, we hope to introduce cubs born at the park to a region northeast of Vladivostok, in the Russian Far East.

“A phased approach would be needed, with young leopards spending several months acclimatising and sharpening their survival skills in a contained, naturalistic environment within the proposed location of Lazovsky Zapovednik, before being released and monitored.

“Introducing such a large predator to the wild is incredibly complex but, all being well, we hope this may be possible in the next few years.

“This is incredibly exciting and again demonstrates the vital role zoos and conservation breeding programmes have in protecting threatened species.”

The park’s breeding complex was completed last year and funded by an anonymous donation. Freddo, the father, arrived from Tallinn Zoo in Estonia, while the mother, Arina, was born at Twycross Zoo in the Midlands.

“Initially we confirmed the birth by observing the behaviour of the mother, as Arina had become increasingly secretive,” said Mr Richardson.

“Being able to send captive-bred Amur leopards back to a part of their historic wild range in Russia would represent an extraordinary conservation success.

“We have since heard cub vocalisations and one of our keepers caught a fleeting glimpse of Arina moving a cub from a distance.

“Although progress has been made in recent years, habitat loss, poaching and conflict with humans remain threats to the Amur leopard, with only around 100 remaining in the wild.

“At this early stage we do not know if Arina has had more than one cub and we also need to emphasise that the first few weeks are a vulnerable time in a cub’s life. We have motion sensitive cameras in place and hope these will tell us everything is okay and that we have healthy offspring.

“We have the only specially designed off-show breeding habitat in the zoo world, which ensures minimal interaction with humans and no contact with our visitors.

“Working with conservation partners, including ZSL (Zoological Society of London) and conservation authorities

“A cub’s first physical check-up would be when they are around three months old, at which point we would discover their gender.”

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INTRODUCING SUCH A LARGE PREDATOR TO THE WILD IS INCREDIBLY COMPLEX BUT, ALL BEING WELL, WE HOPE THIS MAY BE POSSIBLE IN THE NEXT FEW YEARS.

| BIOSCIENCE TODAY SEPTEMBER•OCTOBER 2018 |

| news |

Engineering Immune Cells to Treat Cancers AMSBIO produce a growing range of experimental cell lines, recombinant proteins and screening services to advance the search for new Chimeric Antigen Receptor (CAR T) cell therapies to treat cancers.

For years, the foundations of cancer treatment were surgery, chemotherapy, and radiation therapy. Over the last twenty years, therapeutic drugs that target cancer cells by homing in on specific molecular changes seen primarily in those cells, have also become standard treatments for many cancers. In the last few years - immunotherapies that enlist and strengthen the power of a patient’s immune system to attack tumors have emerged as a new and very promising cancer treatment.

Until recently, the use of CAR T-cell immunotherapy has been restricted to small clinical trials, largely in patients with advanced blood cancers. However, these treatments have created great interest because of the remarkable responses they have produced in some children and adults for whom all other treatments had stopped working. In 2017, two CAR T-cell therapies were approved by the Food and Drug Administration (FDA), one for the treatment of children with acute lymphoblastic leukemia (ALL) and the other for adults with advanced lymphomas.

A therapeutic CAR is a transmembrane protein designed with an extracellular domain based on an antibody single-chain variable fragment (scFv) and intracellular signaling domains derived from the TCR g chain, along with other costimulatory receptors. The scFv provides a specific binding domain that recognizes target proteins on cancer cells. A patient’s own T cells are isolated and activated, then transfected with a gene expressing the CAR. This reprograms the T cells to identify and attack tumor cells expressing the target protein, creating personalized immune cells designed to specifically target the patient’s cancer.

For further information on AMSBIO's growing range of experimental cell lines, recombinant proteins and screening services to help develop new CAR T cell therapies please visit http://www.amsbio.com/car-t-cell-research.aspx or contact the company on +44-1235-828200/ +1-617-9455033 / info@amsbio.com.

Founded in 1987, AMS Biotechnology (AMSBIO) is recognized today as a leading company contributing to

the acceleration of discovery through the provision of cutting-edge life science technology, products and services for research and development in the medical, nutrition, cosmetics and energy industries. AMSBIO can draw upon in-depth expertise in extracellular matrices to provide elegant solutions for studying cell motility, migration, invasion and proliferation. Widely acknowledged as an expert in cell culture, AMSBIO partners with clients in tailoring cell systems to enhance organoid and spheroid type screening outcomes from a technological and costeffective perspective.

Bowel cancer charity award grants to fund research worth nearly £440,000 Bowel Cancer UK and Beating Bowel Cancer is funding six bowel cancer research projects totalling nearly £440,000, part of the charity’s investment to support research with the greatest benefits for those at risk and affected by the disease. All the research projects support the charity’s vision that by 2050 no one will die from bowel cancer.

The disease is the second biggest cancer killer in the UK. However, it shouldn’t be because it is treatable and curable especially if diagnosed early.

Deborah Alsina MBE, Chief Executive of Bowel Cancer UK and Beating Bowel Cancer, says: “This is one of the charity’s most exciting announcements as this is our first round of grant awards.

This is part of our commitment to invest in high quality, innovative

and creative solutions to help lead a step change in the number of people surviving bowel cancer.

“We’ve been at the forefront of campaigning for improvements for earlier diagnosis. Whilst there have been important steps forward, there are still many unanswered research questions, which if addressed could help accelerate our progress further and ultimately save more lives. Through strategic investment in targeted research, we aim to drive positive change for patients and help to deliver improvements in bowel cancer survival in our lifetime.”

For more information about our research grants, visit: bowelcanceruk.org.uk/research

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| news |

| BIOSCIENCE TODAY SEPTEMBER•OCTOBER 2018 |

UK adults differ from NHS England boss on health priorities A recent poll shows UK adults believe dementia is in the top three health areas the NHS should focus on in the next 10 years. The survey commissioned by Alzheimer’s Research UK shows starkly different public priorities to those outlined today in an interview with NHS England’s Chief Executive Simon Stevens, which failed to acknowledge the harm dementia presents to the UK’s economy, health services, and lives of people living with condition and carers.

The survey asked people to consider how they would like resources, innovation and funding to be prioritised in the next 10 years. The top disease areas identified in an openended question were dementia and Alzheimer’s, cancer and mental health.

dementia risk reduction, and preparing today for future dementia treatments so they can reach people without unnecessary delay.

Hilary Evans, Chief Executive at Alzheimer’s Research UK, said: “Dementia is the leading cause of the death in the UK and is expected to impact more and more people each year. Dementia must be given due resource and attention, not in 10 years’ time but now if we are to improve the lives of people with dementia. To dismiss dementia by failing to include it as a major national health priority is to dismiss the incredible personal and societal cost of this condition.

In an interview, Mr Stevens outlined five health areas that will make up the priorities for the NHS in the next 10 years including, stroke, heart disease, and mental health – all health issues that typically appear alongside dementia.

“Today there are 850,000 people with dementia in the UK, but this number is expected to reach one million in just three years. Dementia is expected to cost the UK economy £30bn each year by 2021. We simply cannot afford to wait any longer to address the challenges presented by dementia or our health system will not be able to cope.”

Alzheimer’s Research UK, the UK’s leading dementia research charity, is calling on the government and NHS England to make dementia a major priority in the forthcoming 10-year plan. This includes fostering innovation through increased funding for dementia research, working to detect the diseases that cause dementia 10-15 years sooner, increasing awareness of

The survey also showed one in four UK adults say they believe dementia is the biggest health challenge facing the NHS in the next 70 years in terms of the cost to the NHS and the number of people affected in each of eight disease areas, including cancer, heart disease and mental health conditions. A quarter of adults selected dementia, the highest percentage for any disease area.

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How fast is too fast? Population declines of mammals and birds linked to rapid warming of climate New global assessments from ZSL investigates how climate and land-use change impact wildlife populations THE RATE at which our planet is warming has been found to be a critical factor in explaining the decline of bird and mammal species, reveals new research published today in Global Change Biology by international conservation charity ZSL’s (Zoological Society of London) Institute of Zoology.

Scientists studied 987 populations of 481 species across the globe, to investigate how the rate of climate change and land-use change (from natural to human-dominated landscapes) interact to affect the rate of decline on mammals and birds, as well as whether species located in protected areas and body size had an influence. The rate at which our climate is warming was found to be the best explanation for the observed rate of population declines.

Birds were one of the worst affected by rapid climate warming, with effects being twice as strong in birds over mammals, as well as populations located outside of protected areas being more severely impacted. Species such as the black-tailed godwit (Limosa limosa) in Germany and Senegal, pink-footed Geese in Canada (Anser brachyrhynchus) and black-backed jackal (Canis mesomelas) in Tanzania were just some of the species highlighted to be in population decline.

Lead-author, Fiona Spooner from the Institute of Zoology and UCL’s Centre of Biodiversity and Environment Research said: “The reason we think birds might be worse off in particular is due to birds breeding seasons being particularly sensitive to temperature changes. We think this could be leading to a desynchronisation of their reproduction cycle, leading to the negative impacts we’re seeing. Mammal breeding seasons are a lot more flexible, and this is reflected in the data.”

This finding is crucial, because if the rate at which the climate warms, exceeds the maximum possible rate

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of animals being able to adapt to the changes in their environment - local extinctions of animals will start to become more prominent. The research stresses the urgency of understanding the vulnerability of animals to temperature increases and provides a snapshot of what may come to pass if we don’t slow down climate change.

Senior co-author, Dr Robin Freeman head of the Indicators and Assessment Unit at ZSL’s Institute of Zoology said: “Our research shows that in areas where the rate of climate warming is worse, we see more rapid bird and mammal population declines. Unless we can find ways to reduce future warming, we can expect these declines to be much worse”.

“Importantly, our finding does not suggest that human land-use changes, such as for agriculture, development or deforestation do not play a role in the decline of birds and mammals, or that because the decline is climate change related, it’s somehow something for future generations to deal with. Rather, this finding suggests that additional data including higher resolution landscape data is needed to understand the mechanisms driving these declines”.

Gareth Redmond-King, Head of Climate and Energy Policy at WWF said: “This report provides further evidence of the growing threat that climate change poses to our wildlife, not only around the world but also right here on our doorsteps such as bees and the much-loved puffin.

“That’s why we urgently need the UK Government to take action to meet current targets to cut greenhouse gas emissions, but also to increase ambition to build a sustainable, climate-resilient future in which we restore nature, not destroy it”.

For more information on the work of ZSL’s Indicators and Assessments Unit. The department publishes the Living Planet Index Report alongside WWF every two years. This paper provides a snapshot into the exciting work that will published come October 2018. Find out more here: https:// www.zsl.org/global-biodiversity-monitoring/indicatorsand-assessments-unit/living-planet-index

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UK Pharmacogenetics and Stratified Medicine Network support for the introduction of personalised medicine into the clinic to help improve patient healthcare outcomes The bioscience sector is playing an important role in improving the way patients are prescribed their medication.

The development of new sequencing techniques, data analysis software tools, and companion diagnostics for novel drugs by the bioscience sector are allowing clinicians to offer their patients a more precise diagnosis based on the molecular and genetic profile of their disease, rather than the traditional way of prescribing treatment based on the signs and symptoms of disease displayed by the patient.

Advances at the pace of sequencing technologies increase the opportunity to incorporate pharmacogenomics (the understanding of how the patient’s genomic profile affects their response to drug therapies) into the prescribing process. The combination of a more precise diagnosis and the inclusion of pharmacogenomics data enables physicians to offer their patients the most appropriate drug, at the optimum dose, safely, and takes into account any polypharmacy requirements. Providing patients the

drug most likely to be of benefit at the onset of treatment is described as offering personalised / precision / stratified / P4 medicine.

Personalised medicine has the potential not only to significantly improve patient outcomes but also in some cases to make savings on the costs of their healthcare.

Improving patient safety by reducing the number of patients at risk of adverse drug reactions (ADRs) is one area where pharmacogenomics makes a valuable contribution to improving patient care that offers cost saving opportunities.

It has been estimated that ~8,000 hospital beds are occupied at any one time by patients who have suffered ADRs placing a significant financial burden on the NHS. Identifying these patients and offering them a safer alternative therapy would potentially reduce the 6% of all hospital admissions, and 13% of extended stays, that are directly due to ADRs. For example, using genomic data has predicted which patients are likely to suffer life threatening ADRs to the HIV drug abacavir. Variants in the HLA region of chromosome 6 have been linked to ADRs for ~ 30 different drugs. Another area where personalised medicine offers the potential to improve healthcare is by incorporating genomic data into family history records to predict those individuals at greater risk of common diseases such as cancer, heart disease etc. and then offering them lifestyle choices, or preventative therapies, to reduce their risk of disease. The NHS 5 year Forward View produced by Dame Sue Hill (NHS chief scientist) and the Genomic Medicine report by Dame Sally Davis (NHS chief medical officer) both support offering a more personalised medicine approach to patient care within the NHS. The pharmaceutical industry is also recognising the importance of pharmacogenomics when designing clinical trials for the novel drugs of the future. It is well acknowledged that most block buster drugs are not effective

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for a significant proportion of individuals and many drugs fail on demonstrating efficacy during phase 2/3 clinical trials. Improving the design of clinical trials by using pharmacogenomics to select those patients most likely to receive benefit from a novel drug reduces the number of patients required to demonstrate efficacy in a clinical trial.

Reducing the number of patients that are required for a clinical trial not only lowers the high cost of the trial but also raises the possibility of speeding up the time it takes to get a novel drug to market.

The government Life Science Strategy, produced by Sir John Bell, was published in August 2017. The strategy sets out a vision of how the UK might exploit its existing strength and provides recommendations for the long term success of the life biosciences sector. However, the biosciences sector cannot work in isolation to move personalised medicine forward. Academic scientific research input is required to first determine the molecular and genetic basis to disease for the pharma industry to go on and develop the novel drugs of the future. Clinicians then play an essential role in conducting the clinical trials to determine which patients will benefit from new drug treatments, whilst the regulators oversee the process to ensure patient safety.

Patients providing their samples, access to their data, and contributing to determining a research strategy relevant to the needs of their condition, are a vital part of the process of developing more personalised drug treatments. Providing links across these different sectors to maximise the potential of personalised medicine in the UK is challenging. The UK Pharmacogenetics and Stratified Medicine Network is a not-for-profit organisation set up to help overcome that challenge and deliver personalised medicine into the clinic.

The Network was first set up in 2010 by Professor Sir Munir Pirmohamed and has the support of a steering committee made up of a cross section of experts from all sectors involved in the delivery of personalised medicine to patients. Since 2014 the Network has recruited ~1,000 members from academia, the bioscience, clinical and regulatory sectors, as well as patients. Our website http:// www.uk-pgx-stratmed.co.uk/ attracts global attention, with many visitors returning regularly to browse our pages.

Valuable information on the latest news on developments in the field, events taking place, and details of current funding opportunities are all provided on the website to create a “one stop shop” for all those interested in personalised medicine. Membership is free of charge and by adding their details to our online collaborator’s database individuals have the opportunity to highlight their expertise, and the interests of their organisation, to the wider community.

Search facilities within the collaborators database offer members the opportunity to find colleagues from different sectors to develop multidisciplinary research partners to move their research forward. Important links to progress within the sector are promoted through social media and our blogs attract both UK and overseas followers.

Every year the Network holds an annual open meeting in March that highlights the cutting edge advances in the field of personalised medicine. The high quality of the speakers at these meetings, and opportunities to meet colleagues

from other sectors, attract a diverse audience of those wishing to follow the progress of personalised medicine.

However, it is recognised that the progress in the adoption of personalised medicine into the clinic is not without its challenges. By collaborating with Government and NHS affiliated organisations, such as the Academic Health Science Network, Academy of Medical Sciences, Genomics England, Medicines and Healthcare products Regulatory Agency, National Institute for Health and Care Excellence, National Institute of Health Research Clinical Research Network, the Pharmacogenetics and Stratified Medicine Network aims to address some of these challenges through focused workshops. These workshops bring together key opinion leaders from across all disciplines to discuss, and offer solutions to, the many different barriers faced in offering patients a personalised medicine approach to their healthcare. Reports from these workshops are sent for publication in peer reviewed journals to inform how personalised medicine moves forward into the clinic.

Recordings of the presentations given at annual events and focused workshops are available on our website.

Engaging with the Network is an ideal way for the bioscience sector to make contact with colleagues from other sectors to develop collaborative partnerships and enhance research output. International links with other similar organisations, such as the European Society of Pharmacogenomics and Personalised Therapy, International Union of Basic and Clinical Pharmacology, European Ubiquitous Pharmacogenomics project and US Pharmacogenomics Research Network, have been established to develop a global approach for supporting the adoption of personalised medicine into the clinic.

Plans are in place to develop an international network in which experiences of pharmacogenomics and advances in personalised medicine are shared across all nations. Browse the website or contact Christine McNamee cjmcn@liv.ac.uk for more information about our organisation.

Currently the Network receives generous financial support from the National Institute of Health Research-Clinical Research Network, the Northern Health Science Alliance and UCB pharma.

“Engaging with the Network is an ideal way for the bioscience sector to make contact with colleagues from other sectors to develop collaborative partnerships and enhance research output.”

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New type of photosynthesis discovered The discovery changes our understanding of the basic mechanism of photosynthesis and should rewrite the textbooks.

It will also tailor the way we hunt for alien life and provide insights into how we could engineer more efficient crops that take advantage of longer wavelengths of light.

The discovery, published today in Science, was led by Imperial College London, supported by the BBSRC, and involved groups from the ANU in Canberra, the CNRS in Paris and Saclay and the CNR in Milan.

The vast majority of life on Earth uses visible red light in the process of photosynthesis, but the new type uses nearinfrared light instead. It was detected in a wide range of cyanobacteria (blue-green algae) when they grow in nearinfrared light, found in shaded conditions like bacterial mats in Yellowstone and in beach rock in Australia.

As scientists have now discovered, it also occurs in a cupboard fitted with infrared LEDs in Imperial College London.

PHOTOSYNTHESIS BEYOND THE RED LIMIT The standard, near-universal type of photosynthesis uses the green pigment, chlorophyll-a, both to collect light and use its energy to make useful biochemicals and oxygen.

The way chlorophyll-a absorbs light means only the energy from red light can be used for photosynthesis.

Since chlorophyll-a is present in all plants, algae and cyanobacteria that we know of, it was considered that the energy of red light set the ‘red limit’ for photosynthesis; that is, the minimum amount of energy needed to do the demanding chemistry that produces oxygen. The red limit is used in astrobiology to judge whether complex life could have evolved on planets in other solar systems.

However, when some cyanobacteria are grown under near-infrared light, the standard chlorophyll-a-containing systems shut down and different systems containing a different kind of chlorophyll, chlorophyll-f, takes over.

Until now, it was thought that chlorophyll-f just harvested the light. The new research shows that instead chlorophyll-f plays the key role in photosynthesis under shaded conditions, using lower-energy infrared light to do the complex chemistry. This is photosynthesis ‘beyond the red limit’.

Lead researcher Professor Bill Rutherford, from the Department of Life Sciences at Imperial, said: “The new form of photosynthesis made us rethink what we thought was possible. It also changes how we understand the key events at the heart of standard photosynthesis. This is textbook changing stuff.”

The chlorophyll-f based photosynthesis reported today represents a third type of photosynthesis that is widespread. However, it is only used in special infraredrich shaded conditions; in normal light conditions, the standard red form of photosynthesis is used.

It was thought that light damage would be more severe beyond the red limit, but the new study shows that it is not a problem in stable, shaded environments.

Co-author Dr Andrea Fantuzzi, from the Department of Life Sciences at Imperial, said: “Finding a type of photosynthesis that works beyond the red limit changes our understanding of the energy requirements of photosynthesis. This provides insights into light energy use and into mechanisms that protect the systems against damage by light.”

These insights could be useful for researchers trying to engineer crops to perform more efficient photosynthesis by using a wider range of light. How these cyanobacteria protect themselves from damage caused by variations in the brightness of light could help researchers discover what is feasible to engineer into crop plants.

TEXTBOOK-CHANGING INSIGHTS More detail could be seen in the new systems than has ever been seen before in the standard chlorophyll-a systems. The chlorophylls often termed ‘accessory’ chlorophylls were actually performing the crucial chemical step, rather than the textbook ‘special pair’ of chlorophylls in the centre of the complex.

This indicates that this pattern holds for the other types of photosynthesis, which would change the textbook view of how the dominant form of photosynthesis works.

Dr Dennis Nürnberg, the first author and initiator of the study, said: “I did not expect that my interest in cyanobacteria and their diverse lifestyles would snowball into a major change in how we understand photosynthesis. It is amazing what is still out there in nature waiting to be discovered.”

Peter Burlinson, lead for frontier bioscience at BBSRC – UKRI says, “This is an important discovery in photosynthesis, a process that plays a crucial role in the biology of the crops that feed the world.

Discoveries like this push the boundaries of our understanding of life and Professor Bill Rutherford and the team at Imperial should be congratulated for revealing a new perspective on such a fundamental process.”

PREVENTING DAMAGE BY LIGHT Another cyanobacterium, Acaryochloris, is already known to do photosynthesis beyond the red limit. However, because it occurs in just this one species, with a very specific habitat, it had been considered a ‘one-off’. Acaryochloris lives underneath a green sea-squirt that shades out most of the visible light leaving just the near-infrared.

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Scientists test new technology for same-day diagnostics A new lab at St Thomas’ Hospital has opened to test whether new nanopore-based DNA sequencing technology could support same day diagnosis of infections such as sepsis in NHS hospitals. The research at St Thomas’ Hospital in London will see if the technology could help clinicians prescribe the right antibiotics straight away, and ensure antibiotics are only prescribed when needed, with ongoing considerations around the reduction of spread of antibiotic resistance.

seek to translate this assessment to a clinical setting. The team will assess this by comparing the results from samples run through the sequencers, with the results from existing culture and sequencing methods. This is essential before they are used to make decisions on antibiotic treatment.

The NIHR Guy’s and St Thomas’ Biomedical Research Centre has opened a fully automated molecular lab with Oxford Nanopore Technology sequencers.

“The speed at which this technology provides DNA sequence information is really exciting. But what we want to know is, can this technology process samples taken from patients quickly and accurately enough for clinical use?

The DNA of pathogens can provide important information about their identity and their drug resistance. Scientists at St Thomas’ Hospital will test whether the sequencers can provide genetic results fast enough to allow doctors to reliably diagnose patients with bacterial infections in one day.

They will then assess whether this could benefit patients by reducing the number of unnecessary antibiotic prescriptions, a major factor in the spread of antibiotic resistance.

Antibiotic resistance occurs when bacteria acquire genetic changes that make them resistant to antibiotic treatments.

It is estimated that in the US and Europe, antimicrobialresistant infections currently cause at least 50,000 deaths per year1. The problem is worsened by overprescribing of antibiotics when there is no bacterial infection. Currently, diagnosing infections can take between three to five days and doctors often need to give antibiotics while waiting for laboratory results.

The compact sequencers in the new lab have the potential to change this. They can analyse samples and produce DNA sequences in real time. These are then matched up to a library of bacterial sequences to show which infection a person has acquired, and what resistance genes are present.

This would allow doctors to administer the most appropriate, targeted antibiotic to the patient to treat the infection.

The sequencers have been shown to identify pathogens and their drug resistance in many research studies. The new lab will assess the sequencers for accuracy and speed at scale in a diagnostic laboratory, and if successful will

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Dr Alka Saxena, Head of the Genomics Platform at the NIHR Biomedical Research Centre at Guy’s and St Thomas’ said:

“We are specifically looking at whether it can help doctors make better decisions about how they use antibiotics to treat infectious diseases. If the technology passes this crucial test, it has the potential to change the way we diagnose and treat patients with infection.”

Professor Jonathan Edgeworth, Director of the Centre for Clinical Infection and Diagnostics Research and Viapath Medical Director, said: “We are doing this research jointly from the start with front-line clinicians, research scientists and healthcare scientists to speed up the moving of scientific discovery and technological advance to the bed-side.

“We want to find out quickly whether Nanopore-based sequencing improves antibiotic treatment decisions on the wards, so that ultimately patients get faster targeted treatment of sepsis whilst also reducing exposure to unnecessary antibiotics so they don’t develop resistance to antibiotics. If our research shows that the technology can support faster diagnosis, we will then need to find a path through to routine use.”

The research will be conducted jointly by research scientists at Guy’s and St Thomas’ BRC and healthcare scientists at Viapath with the intention that, if it turns out to have patient benefit, Viapath will then deliver the diagnostic service for patient samples. Acquiring the technology was made possible by funding from the Department for Health and Social Care. The team expect results of the assessment to be available in the next year.

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Meeting contemporary medical challenges In this issue of BioScience Today, we speak to Professor Phil Blower, Chair in Imaging Chemistry at King’s College London about why a multidisciplinary approach is crucial to meeting the medical challenges of today.

“I work in a branch of imaging that uses nuclear medicine or positron emission tomography (PET) to diagnose a range of diseases, to understand their severity and to treat them too.

“PET technology has been around for a while and is used by most big hospitals dozens of times a week, but we are trying to extend its application to new areas, so it can be used to diagnose and treat a greater range of diseases.

“We design molecules that bind to a particular property of a disease so an image can be taken by the PET scanner which shows the pathological chemistry going on in a patient. The images show us where a tumour is, non-invasively, without having to open up a patient or do a biopsy.

“Recently we’ve been working on a project supported

by The National Institute for Health Research (NIHR) Biomedical Research Centre (BRC) at Guy’s and St Thomas’ NHS Foundation Trust and King’s College London. We’re developing a radioactive tracer for use in prostate cancer screening, which allows for simple, safe single step labelling with gallium 68 and we are just moving into phase two clinical trials.

“Cancer cells, for example, take up glucose more efficiently than other cells, so by using a radioactive type of glucose we light up the tumour, making it stand out against the background, producing an image.

“The advantage of using radioactivity is that you see deep into the body – you are not just looking at the surface; and unlike other kinds of imaging such as X-rays or CT for example, you are not just looking at the structure - you get a three dimensional map of the chemistry that is happening in the body.

“The great advantage of the technique is that you see chemical changes long before any structural change has happened in the body, meaning you pick up on changes that wouldn’t be detected by an MRI or CT scan.

“Ultimately, this technology enables clinicians to diagnose and treat conditions sooner, and see how that treatment is progressing. You can see whether a tumour is alive or dead and how it is responding to treatment.

“In addition to this, we are looking at the imaging of heart problems, how imaging can be used to gauge brain chemistry in dementia patients and how tracers can be used to kill cancer cells selectively.

“The radioactive tracers we use in PET imaging have a short half-life of just a few minutes and you have to make them on the premises immediately before the scan, it is a complex process.

“We know that patients are frustrated by the lack of nationwide availability of the latest scanning techniques and the fact that the tracer production sometimes doesn’t work as well as they could. This can mean their scan is cancelled and their treatment potentially delayed. At King’s College London and Guy’s and St Thomas’ we’re aiming to make the process simpler and more reliable, so that it takes just five minutes rather than several hours and can be

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Professor Phil Blower © King’s College London

used by more hospitals, regardless of whether they have the highly-skilled staff or the expensive equipment on site.

“Producing the tracers, simply and quickly will have real patient benefits, helping to reduce waiting lists and making it easier for the technology to be adopted in developing countries too. We want the tracers to work every time, everywhere.

“I was always curious and wanting to find things out. I started out on the academic side of inorganic chemistry; in my PhD and early postdoctoral years the application of the research was far in the future.

“I then took up a joint University of Kent / NHS academic post, as I wanted my academic interests to have a practical application. Moving to the NHS was a jump out of my comfort zone, but since that moment, I’ve never looked back, it was the turning point in my career.

“Having a foot in both research and teaching is extremely varied and rewarding; and though it can be difficult to strike the right balance, you’ll find that one sphere informs the

other. Now a great motivator of mine daily is mentoring my students, who in turn go out into the world and make a difference independently.

“What I would say to young people who are interested in making a difference is that this isn’t only achieved by being a doctor, there are many other ways in which a scientist can help. There are an awful lot of things going on in hospitals behind the scenes, biologists, statisticians and computer scientists, all have a part to play.

“Our approach to meeting medical challenges today is much more multidisciplinary than was once the case and there are lots of different specialists who have something to contribute. We won’t achieve what we need to achieve, by working alone.

“By working in both academia and the NHS you gain a better understanding of what the real problems are that need solving and what the practical solutions are going to be. The NHS is all about solving real world problems and if you bring your scientific knowledge, you can have an impact too.”

“What I would say to young people who are interested in making a difference is that this isn’t only achieved by being a doctor, there are many other ways in which a scientist can help. There are an awful lot of things going on in hospitals behind the scenes, biologists, statisticians and computer scientists, all have a part to play.”

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Radiation in cancer diagnosis – keeping your enemies closer

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It’s a remarkable paradox of cancer treatment that radiation, a well-known cause of cancer, is also a cornerstone treatment. Safe doses of radiation can also play a part in diagnosis.

Scientists working within the NIHR Biomedical Research Centre (BRC) at Guy’s and St Thomas’ NHS Foundation Trust and King’s College London have been working to improve diagnosis and treatment for cancer though the use of radiotracers – radioactive molecules that bind to cancer cells.

Positron emission Tomography (PET) scans are routinely used in the process of diagnosing cancer. The patient is injected with a safe dose of the radiotracers, designed to collect around tumours. The patient is then scanned to see where radiation accumulates, which highlights the area of cancer cells. This creates detailed and accurate images of tumours that can be used to guide treatment, while leaving the healthy tissue unharmed.

SUGAR OR SPICE The standard radiotracer for PET scans is Fluorodeoxyglucose (FDG) a substance similar to glucose.

It tags cells in the body that are using a lot of glucose, such as tumour cells which grow quickly and therefore use more sugar than most cells.

Researchers at the King’s College London School of Biomedical Engineering and Imaging Sciences are looking at ways to tag the radioactivity specifically to the tumour cells, and not just any cell with a high sugar uptake.

As part of a project funded by the NIHR Guy’s and St Thomas’ BRC, Professor Phil Blower’s lab have been developing several new radiotracers, including one, designed to scan men with prostate cancer.

The radiotracer is based on Gallium-68, a positron emitting radionuclide. The team have developed a technique to quickly and easily bind Gallium-68 to a urea based small molecule. This molecule in turn binds strongly to Prostatespecific membrane antigen (PSMA) that is strongly expressed in all prostate tissue cells, and particularly cancer cells. This combination forms the compound GalliumPSMA which binds specifically to prostate cancer cells and can help create detailed images.

A particular advantage of the method developed by Professor Blower to make Gallium-PSMA is that the urea based small molecule can be labelled in minutes in a single step using a freeze dried kit, unlike other types of PSMA which are more difficult to make. This may seem like a minor moderation to the methodology, but the positive impacts from removing a stage from the production process

can make a big difference. Existing methods of producing radiotracers take longer, meaning much of the radiation is lost from the Gallium. This in turn means the scans are less effective, and that fewer scans can be completed with a batch of radiotracer.

The simplified method for producing the Gallium PSMA could improve on the current techniques, resulting in shorter waiting times, faster and more accurate diagnosis and reduced staff time producing the radioactive tracer.

ALL HANDS ON DECK Imaging with radioactivity involves scientists from different fields to bring this technology to the clinic. Professor Blower, as a chemist, works on the radioactive material itself.

Biologists are then involved to ensure the radioactivity tags to the right cells, and check that it has no other effects on living tissue.

Then a host of radiopharmacists, technologists, radiographers and physicists and are required behind the scenes, to produce the tracers, take the scans and ensure that the image quality is of the highest possible standard.

The Gallium-PSMA technique has gone through clinical trials to test its safety and efficacy. People might more commonly think of clinical trials as being used to develop new treatments, but they’re needed for improving imaging techniques and diagnosis of disease too.

At Guy’s and St Thomas’, the technology is now being actively used as part of routine practice for diagnosing prostate cancer, as the Trust is in the unique position of having both the scanning and the radiopharmacy facilities to deliver it.

IN THE CLINIC Professor Gary Cook, Professor of Clinical PET Imaging and Dr Victoria Warbey, Consultant in PET Imaging at the King’s College London and Guy’s and St Thomas’ PET Centre have been using the Gallium-PSMA radiotracer in the clinic for over a year and have scanned more than 250 patients.

Professor Cook highlighted how important it is to have the right infrastructure in place to apply this technique.

“Every morning Vickie Gibson, lead radiopharmacist, and her team produce the tracer in the Nuclear Medicine Radiopharmacy at Guy’s Hospital. It’s then transported to us over at St Thomas’, where we use it to scan patients. In addition, we’re lucky that we have two scanners, so we can have two patients being scanned at the same time. This maximises the efficiency of the tracer production.”

Patients who undergo PET scans with the Gallium-PSMA fall into two groups: those who have just been diagnosed with prostate cancer, and those whose prostate cancer was in remission, but their doctors think the cancer may have returned.

Continued on page 24

“In the case of patients whose cancer has returned, we think as many as a third may have had their treatment plan changed as a result of the information provided by Gallium-PSMA scans in addition to our standard MRI and bone scans. Time will tell, but it looks like this could make a huge difference to patients.”

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Left: A patient with rising PSA after previous prostatectomy for prostate cancer. The scan shows several PSMA-positive lymph nodes in the abdomen and left lower neck (red arrows). Normal excretion of the PSMA tracer in the urine in the kidneys and ureters (blue arrows)

Left: A patient with high-risk prostate cancer recently diagnosed. The PSMA scan shows areas of cancer in the prostate gland (black arrow) with spread of cancer to several lymph nodes in the abdomen (red arrows). Normal urinary excretion in the kidneys and ureters (blue arrows)

In patients who are newly diagnosed with cancer, doctors are choosing between a range of treatments, balancing the likelihood of success with the impact on the patient.

It might be that in a smaller tumour, surgery or radical radiotherapy will be enough. If it has spread, chemotherapy may be needed to shrink the tumour before surgery. If it has spread very significantly, doctors might not be able to do surgery, and recommend hormone therapy or other treatments.

an initiative to ensure there’s a standard for sites taking part in multicentre trials. The Core lab works to harmonise practice across the UK and ensure images are of sufficiently high quality to all be used in the trials to investigate new treatment approaches.

“It’s early days, but we think the Gallium PSMA is showing an improvement on the current PET methods, as it can detect much smaller volumes of cancer”, says Professor Cook.

An exciting new area is developing tracers that tag to oxygen-deprived cells. Some tumours grow very big and because they have a disrupted blood supply, the cells at their centres are starved of oxygen. Instead of simply dying away, these tumour cells seem to be able to survive and are likely to be resistant to radiotherapy.

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“We think as many as a fifth of newly diagnosed patients who had a Gallium-PSMA scan may have been given a different treatment in light of the additional information the scans gave us. This might mean we found out they needed more treatment, or it may mean we found they didn’t need as much treatment, so patients didn’t have to go through unnecessary treatment and the associated side effects.

“In the case of patients whose cancer has returned, we think as many as a third may have had their treatment plan changed as a result of the information provided

by Gallium-PSMA scans in addition to our standard MRI and bone scans.

Time will tell, but it looks like this could make a huge difference to patients.”

THE FUTURE OF PET Doctors are already using these methods to personalise treatment. Professor Sally Barrington has spent much of her career looking at how PET scans can help guide clinicians in how they treat cancer. Early in her career, she worked on two trials to see if taking a PET scan early on in treatment could improve outcomes for lymphoma patients, reducing side-effects and improving survival.

She found that conducting trials using PET imaging could be challenging. Based on her experience, she and colleagues founded the UK PET Core Lab based at St Thomas’ Hospital,

In 2017, she was awarded an NIHR Research Professorship to expand this work, and to help improve how PET scans are used by clinicians across the country.

“We’re working with Professor Blower’s lab to develop tracers that tag to these cells, which could help us identify tumours that are more likely to be resistant to radiotherapy.” says Professor Barrington. “Then we would know in advance where a patient might need a higher radiotherapy dose or that we need to use another treatment.”

Professor Barrington is also working to adapt existing methods to monitor patients’ treatment.

“We’re now looking at many different therapies that are available for cancer treatment, and we need to develop the way we read PET scans to adjust to this.

“Immunotherapies, for instance are a major development. These therapies boost the immune system and enable immune cells to attack the tumour. However, we don’t know much about how a PET scan should look in a patient who has just had this treatment. The tumour might get bigger before it gets smaller because of the immune cells. We need to understand how to read what’s happening in patients who have had these treatments.

“There are so many exciting developments, and as researchers we need to constantly adapt our methods so that we’re providing the most accurate information possible, and guiding doctors to make the best decisions for patients’ treatment.”

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| diagnostic devices |

Research finds three major failings in some apps used for the diagnosis of skin cancer In the scramble to bring successful apps for the diagnosis of skin cancer to market there is a concern that a lack of testing is risking public safety, according to research led by the University of Birmingham.

The research, outlined at the British Association of Dermatologists’ Annual Meeting in Edinburgh, reviewed the medical literature on skin cancer apps to explore the number of apps on the market, ascertain how accurate they are, and what the benefits and limitations of these technological solutions are. Examples of apps include tele-dermatology (which involves sending an image directly to a dermatologist), photo storage (which can be used by individuals to compare photos monthly to look for changes in a mole), and risk calculation (based on colour and pattern recognition, or on fractal analysis).

The researchers found that some of these apps have a comparatively high success rate for the diagnosis of skin cancer. Teledermatology correctly identified 88 per cent of people with skin cancer and 97 per cent of those with benign lesions. Apps which use fractal theory analysis algorithms (detecting irregularities in a fractal pattern) were the next most successful category, these correctly identified 73 per cent of people with skin cancer and 83 per cent of people with benign lesions. These types of technology have huge potential, as 50 per cent of dermatology referrals in the UK relate to skin cancer. Early diagnosis results in up to 100 per cent five-year survival, compared with 25 per cent in women and 10 per cent in men diagnosed at a later stage.

Technology that can help with triaging would help alleviate pressure on dermatology departments and could also increase survival rates.

However, the researchers point to three major failings with some of the apps: a lack of rigorous published trials to show they work and are safe; a lack of input during the app development from specialists to identify which lesions are suspicious; and flaws in the technology used, namely how the photos are analysed.

The researchers explain that, without specialist input, the apps may not recognise rarer or unusual cancers.

Even where the technology is efficient, if it has not been combined with specialist input from a dermatologist, it may not pick up on all red-flag symptoms.

In terms of technology, an area where colour and pattern recognition software apps seem to particularly struggle currently, is in recognising scaly, crusted, ulcerated areas or melanomas which do not produce pigment (amelanotic melanomas). This increases the number of false negatives and delays treatment.

Some apps that compare images on a monthly basis or ‘advise’ users to seek dermatologist review, based on a risk

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calculation, are not able to differentiate between finer details which would be identified using a dermatoscope (a magnifier that can be handheld or attached to a phone), or in person when touched by a dermatologist. If the app is based on advising patients whether to seek professional advice, then they may advise wrongly as they have not correctly identified finer details which may point to a more sinister lesion.

There are also certain criteria that an app cannot always register, for example if a person aged over 40 develops a new mole which has grown. In clinic this person would be advised that the mole should be removed, however, an app may not be able to provide such personalised advice.

Maria Charalambides, of the University of Birmingham’s College of Medical and Dental Sciences, who conducted the literature review, said: “Future technology will play a huge part in skin cancer diagnosis.

“However, until adequate validation and regulation of apps is achieved, members of the public should be cautious when using such apps as they come with risk.

“Any software that claims to provide a diagnostic element must be subject to rigorous testing and ongoing monitoring.

“Apps specifically based on patient education of skin cancer can offer public health benefits in terms of how to stay safe in the sun, or the warning signs to look out for.

“But as per the British Association of Dermatologists recommendations, most apps cannot currently substitute dermatologist review when it comes to actual diagnosis.”

Matthew Gass of the British Association of Dermatologists, said: “These new technologies for the diagnosis of skin cancer are exciting, but the varying quality available makes it a difficult landscape for people to navigate.

“These apps are not a replacement for an expert dermatologist, but they can be a useful tool in the early detection of skin cancer.

“We urge people who are thinking about using these apps to research how they work and to be cautious regardless of their recommendations.

“If a patch of skin such as a mole is changing in shape or size, not healing or just doesn’t seem right, go and see your GP regardless of what any app tells you.”

Skin cancer is the most common cancer in the UK and rates have been climbing since the 1960s. Every year over 230,000 new cases of non-melanoma skin cancer (NMSC) – the most common type – are diagnosed in the UK. In addition to NMSC, there are approximately 16,000 new cases of melanoma every year, resulting in around 2,285 UK deaths annually.

| diagnostic devices |

| BIOSCIENCE TODAY SEPTEMBER•OCTOBER 2018 |

Cutting costs, saving time and doing away with needles: Laser technology promises a triple whammy of benefits in blood testing Blood tests: They’re not only extremely common and, let’s face it, not particularly popular with patients, they are also a huge drain on health service resources.

Blood samples make up a significant proportion of the 2million pathology tests conducted daily in the NHS, tests which cost up to £3bn a year by some estimates.

And, inevitably, there’s controversy around the costs. A full decade ago, Labour peer Lord Carter highlighted ‘wide variations’ in the costs of pathology tests at laboratories throughout England, and he estimated £500million could be saved if such services were rationalised.

But many of the labs themselves are under intense pressure.

Last year, The Guardian published an inside account of working life at an inner-city pathology lab, with claims of ‘crumbling floors’, staff and equipment shortages, and under-funding.

The system, then, like so many parts of the NHS, is under extreme pressure. It’s not surprising but what can be done about it?

At least part of the answer lies with technology, and this summer Health and Social Care Secretary Matt Hancock announced a cash injection of almost £500million to help transform the use of technology in the NHS… the same amount Lord Carter estimated could be saved by transforming pathology services.

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| BIOSCIENCE TODAY SEPTEMBER•OCTOBER 2018 |

| diagnostic devices |

“The machine does away with the need for needles, blood samples, laboratory analysis – the potential cost savings are obvious. A machine such as this could be used to perform initial tests on a patient and, where further investigation was deemed necessary, more traditional tests could be carried out.”

When it comes to services as simple as blood tests, we have recently seen some great examples of the ways that technology can take the strain off both patients and the NHS. Diabetics can now have under-skin implants that analyse their blood without any need for fingerprick tests, with results sent to their mobile phone. Parents can monitor a diabetic child’s glucose levels remotely – in fact, in the US, there have been almost 900 patent applications this year alone relating to glucose monitoring.

was deemed necessary, more traditional tests could be carried out.

‘Even taking a little pressure off pathology labs would help the hard-pressed teams who work there. And, of course, patients don’t have to endure a nervous wait for results to be known.’

The Aston machine has already proved its worth in trials at Dundee’s Ninewells Hospital.

In the UK, scientists at Aston University’s School of Engineering and Applied Science, in Birmingham, have a remarkable machine which can carry out a battery of health checks with beams of light.

As well as helping analyse blood content, it has been used as part of the diagnostic procedure for strokes and skin cancers. For example, it can constantly monitor blood delivery above the eyebrows, helping doctors mitigate the risk of stroke in patients with hypertension.

The Aston system uses lasers to perform painless, non-invasive checks on medical indicators such as cardiovascular performance and other key metabolic information, which can be useful when looking at energy levels or diet balance.

The laser device is also a high-precision way of identifying the boundaries of head and neck skin cancers, helping surgeons avoid tumour reoccurrence and reducing the need for additional cosmetic surgery.

The tests take just minutes, and they can help assess variables such as regulatory rhythms, the metabolic activity of tissue (eg how effectively tissues are consuming oxygen) and a range of tissue biomarkers (providing evidence of a particular disease or physiological state).

This technology also has the potential to cross over into non-medical applications. For example, the data it provides can help athletes determine their optimal levels of physical exercise, helping to prevent stress and exhaustion and finetuning exercise regimes in real time.

No needles are necessary, which is good news for patients.

A prototype of a wearable monitor has been developed that athletes can simply wear on their wrists, like other fitness monitoring devices.

But, perhaps more significantly, the tests and delivery of results take just a few minutes and no blood has to be sent to a pathology lab for analysis. You can almost hear the NHS cash registers ringing at that news.

Professor Edik Rafailov, of Aston Institute of Photonic Technologies (AIPT), said: ‘This machine makes great use of our growing understanding of the technology around lasers to carry out straightforward tests without having to involve a laboratory.

‘The whole process is completely painless – there is absolutely no reason for patients to feel nervous. And the results are available there and then, which is better for patients and more efficient for healthcare providers.’

The device uses three separate lasers and several techniques to carry out its analysis: Laser doppler flowmetry to look at variables such as how effectively a subject’s blood is being delivered to their tissue Tissue oxymetry to measure levels of oxygen in blood vessels and tissue Tissue fluorescence to assess cell metabolism, a technique useful in areas such as obesity prognosis and cancer diagnosis The tests involve nothing more stressful than laser beams being shone on a patient’s skin – the patient feels nothing.

The results are processed by a computer there and then, and displayed as easy-to-interpret graphs.

Dr Sergei Sokolovsky, Senior Research Fellow at AIPT, said: ‘The machine does away with the need for needles, blood samples, laboratory analysis – the potential cost savings are obvious. A machine such as this could be used to perform initial tests on a patient and, where further investigation

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Such a device could also be extremely useful for diagnostic work away from surgeries and hospitals, taking us closer to the ‘medical tricorder’ device made famous by the Star Trek series.

Much of the technology is ready to go into production now, and Aston recently launched Aston Medical Technology to commercialise inventions such as this.

With the cost of common blood tests still ranging from a few pennies to more than £13, it’s highly likely that health authorities could benefit from the additional cost control that in-house laser testing could bring.

And the rest of us can thank science for helping to reduce the number of needles we must endure.

LIVE LONG AND PROSPER

| BIOSCIENCE TODAY SEPTEMBER•OCTOBER 2018 |

Urban development is attracting leading scientists and ambitious companies to the north Newcastle Helix is the UK’s biggest urban development of its kind outside of London and has entered its next phase of development.

science research and development. As well as satisfying commercial laboratory demand, the new conferencing space will create a hub for the sector to meet, share ideas, collaborate and innovate.

The £350m flagship project, brings together a community of academics, industry leaders, businesses and top researchers.

It combines prestigious commercial and residential space with first-class research and education facilities – right in the heart of Newcastle’s city centre. All 24-acres is dedicated to helping everyone live better lives.

The Biosphere will also offer a bespoke programme of support, including expert advice and industry knowledge to help businesses to grow and develop – supporting the journey from world-class research to the commercialisation of products and services.

It is a partnership between Newcastle University, Newcastle City Council and Legal & General and is already home to the Newcastle University’s award-winning Urban Sciences Building and The Core - a seven-floor home for science, digital and innovation-led businesses. Construction is well underway for a new £29m Learning and Teaching Centre and a £50m building that will house three national centres - the National Innovation Centre for Ageing (NICA), National Innovation Centre for Data (NICD) and the National Institute for Health Research (NIHR) Innovation Observatory. The Biosphere will be the next building to open its doors to businesses. www.newcastlehelix.com

A NEW HOT SPOT FOR LIFE SCIENCES The Biosphere will provide a brand-new home for life science and innovation companies. Opening in November 2018, this new 90,000 sq. ft purpose-built £25m facility will provide high quality lab and Grade A offices for companies involved in the application and commercialisation of life

In addition, a strategic relationship has been formed with One Nucleus – a not-for-profit international membership organisation that supports organisations working within life sciences. This relationship means new and existing tenants will receive complimentary membership, giving them access to a wider life science network. It will also support them to raise their profile within the sector and provide additional benefits such as discounts.

You can’t deny the impressive technical specification of this £25m project - developed by a design team led by Aura alongside award-winning architects Ryder, who have been supported by leading industry specialists including CAM-SCI, ensuring the building meets the needs of the life science sector.

This hot spot for life science companies is already proving to be popular, not only because of its technical specification, but because it’s at the heart of the North East’s £1.1bn life sciences ecosystem and based in of one of the fastest growing cities in the UK - Newcastle.

The fact that it is based on Newcastle Helix means

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businesses can access expertise from onsite neighbours such as the NICD and NICA, both nationally significant centres of excellence in their fields, as well as the NIHR Innovation Observatory – a world-first in using big data analytics and machine learning to study global health innovation. The opportunity to locate alongside digital SMEs in adjacent tech hubs and like-minded businesses also provides added value for businesses.

The Biosphere

For the life sciences sector the facility is close to Newcastle upon Tyne Hospitals NHS Foundation Trust, a leader in clinical trials and Newcastle and Northumbria universities.

The city is nationally and internationally connected, and the fact that it is in close proximity to Newcastle International Airport (20 minutes) and 2hrs 45mins away from London on the train is also an advantage.

Life science businesses have easy access to assets that support the whole bench to bedside pathway. From support networks such as Bionow and First for Pharma, to four world-class universities, to the UK’s top performing Clinical Research Network, to CROs and CDMOs, and centres of excellence in precision medicine, MedTech, and clinical trials. It is also home to CPI’s National Biologics Manufacturing Centre, which is within an hour’s drive.

Catherine Walker, Inward Investment Director, Invest Newcastle said: “The network of expertise and community of like-minded people is really adding value for businesses who are choosing to base themselves on Newcastle Helix. The Biosphere has already exceeded occupancy expectations with a significant proportion of the facility already assigned to life science companies. This unique facility has really helped to complement our offer to the life sciences sector. It really is so much more than a building, it is a place where business can learn, grow and innovate.”

AT A GLANCE: n Purpose-built 90,000 sq. facility for ambitious life science companies n High quality laboratory and office space n Three floors of containment level 2 fitted labs and write up areas with shared wash-up facilities n One unfitted floor remaining, suitable for bespoke chemistry labs n Grade A office suite and conference space (for up to 80 people). n Arranged over seven floors, based on a 6.6m grid layout Not only is The Biosphere nearing completion, work has also started on a £65m private-sector funded building.

The Lumen is a flagship 108,000 sq. ft grade A office development aimed at scientific and tech businesses. This will complement the like-minded community on site, providing collaboration and growth opportunities within the Newcastle Helix eco-system.

THE VALUE OF COLLABORATION More than 200 life science and healthcare companies base themselves in the North East, including Newcastlebased QuantuMDx, who are dedicated to improving and democratising global health by providing transformative diagnostics. They benefited from basing themselves in the city and collaborating with both Newcastle and Northumbria University.

“Locating our HQ in the innovative North East - in preference to the ‘biotech golden triangle” of Oxford/ Cambridge/London - was a conscious decision,” said Elaine Warburton, QuantuMDx’s Chief Executive.

“When we arrived in Newcastle six years ago, we found a city with an incredible genetics network alongside an excellent network of academic, industrial and key opinion leaders, all seeking to support a forward-looking young biotech, with a global vision, that wanted to change the world.

“We were looking for, and continue to do so, research scientists who can take pure research and apply it to everyday life. Newcastle and Northumbria Universities focus on this skill-set offering numerous high calibre graduates and postgraduates from all scientific disciplines including engineering, biology, chemistry, software development.

“This multidisciplinary approach is vital to be able to design and develop such a ground-breaking device as our Q-POC™ portable lab for low resource settings. Newcastle is also a wonderful city to attract staff from all over the globe - with such friendly people and a real buzz.”

A GROWING REPUTATION It’s not just Newcastle Helix that is attracting businesses to the north, it’s the city’s growing reputation for research excellence in life sciences and innovation. It is home to one of the UK’s largest NHS trusts, with more specialist services than any other group of hospitals outside London. It has built a global reputation as a UK hotspot for clinical trials supported by pioneers at Newcastle and Northumbria University. The North East is also one of the strongest regions in the UK for exports of medical and pharmaceutical products, with the commercial base underpinned by a broad range of expertise in biotechnology and novel therapeutics.

Building on their reputation, Newcastle expects to attract further innovative businesses to the city, many of whom will call Newcastle Helix home.

If you are looking to expand or relocate your business contact Invest Newcastle on 0191 440 5761 or email invest@ngi.org.co.uk. www.investnewcastle.com @Tynetoinvest

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| big interview |

| BIOSCIENCE TODAY SEPTEMBER•OCTOBER 2018 |

Why life science incubators are crucial In this issue of BioScience Today, we speak to Dr Glenn Crocker MBE, Chief Executive Officer of BioCity – the largest life science incubator business in the UK. THE LOWDOWN ON LIFE SCIENCE INCUBATORS “A life science incubator can mean different things to different people,” explains Glenn. “There are several components that make up our business. Firstly, our team of skilled professionals from the life sciences, pharmaceutical and business sectors, who are on hand to enable the creation of new start-ups.

“As part of this activity, the team at BioCity regularly run an eight to ten-week business accelerator programme at each location with a cohort of five to ten of the start-ups companies in attendance, coaching them in entrepreneurial excellence, advising them on the likely routes to investment and how best to bring their products or services to the market.”

MENTORS AT THE READY “As well as our experienced in-house team, this accelerator programme is underpinned by an extensive network of over 200 leaders in the pharmaceutical and investment sectors, who are available at the end of the phone to mentor and advise these early-stage companies. Attendees benefit from this mentoring, and the network of businesses around them, from those learning alongside them to those in the broader BioCity community.

“In addition, BioCity provides around 325,000 sq ft of laboratories, a physical base where entrepreneurs, researchers and universities can find a home in which to start-up and grow their companies. Central laboratory facilities accessed on a pay-as-you-go basis include NMR and Mass Spectrometry. Having facilities that are fit for purpose from day one is a huge advantage for these companies.”

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| big interview |

“BioCity provides around 325,000 sq ft of laboratories, a physical base where entrepreneurs, researchers and universities can find a home in which to start-up and grow their companies.”

Dr Glenn Crocker MBE

INVESTMENT OPPORTUNITIES

MORE THAN THE SUM OF ITS PARTS

“The final facet of the business is that we not only advise but also provide crucial investment for promising start-ups.

Some of the investment is provided by a joint venture with AstraZeneca, specifically to support early stage life science companies, whilst some of the investment comes from our own funds. We receive an income from the facilities we provide allowing us to make further investments.”

“The benefits of starting up a company in cohort with others, and as part of a broader life science community, can’t be underestimated. All of the companies here are together worth more than the sum of their parts. It’s amazing what goes on here on a daily basis and you simply wouldn’t have that if you were to set up a business alone.”

A JOINT ENTERPRISE BioCity itself is jointly owned by Nottingham University, Nottingham Trent University and all of its staff. “It is one of the oldest and the most established companies that does what we do,” explains Glenn.

“Starting up a business is a difficult thing to do and it can be a very solitary thing, but we can make it much easier than would ever be the case if you were to do it on your own,” adds Glenn.

“However, businesses that have set up elsewhere, can still become a part of our community and benefit from our network,” adds Glenn.

SUCCESS OVER ADVERSITY Originating in the disused former Boots (later BASF) facility at Pennyfoot Street in Nottingham, the site is most well-known as the laboratory in which Dr Stewart Adams discovered Ibuprofen. Yet its distinguished tradition of innovation continues today in a different way.

Continued on page 32

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

| big interview |

| BIOSCIENCE TODAY SEPTEMBER•OCTOBER 2018 |

 Continued from page 30 Founded as a result of the dilemma posed by the closure of the former research facility by the then owners BASF, BioCity has since grown to become by far the largest life science incubator in the UK and potentially in Europe too – which just goes to show that necessity can indeed be the mother of invention.

FROM PENNYFOOT TO FURTHER AFIELD BioCity is thriving at the Pennyfoot site and has expanded to such an extent that today it has five centres: two in Nottingham, two in Glasgow and one at Alderley Park. The sites are home to up and coming businesses, which benefit from having all of the facilities, expertise and contacts they need to hand, enabling them to thrive.

“Biocity has become a driving force for developing successful life science companies and it is now home to over 200 companies, employing thousands of people,” explains Glenn. These companies are diverse as BioCity welcomes those that specialise in biotechnology, life science products and diagnostics, contract research, medical devices and industrial biotechnology, and there are some notable examples within their alumni.

INCUBATOR SUCCESS STORIES First up, Sygnature Discovery, which began with a team of just four people and has grown to employ over 200, including many chemists and biologists. They have become one of the leading medicinal chemistry companies in the UK and their mission is to accelerate the discovery and development of new medicines to treat patients with a range of debilitating and fatal diseases.

Such is their success that they’ve just moved into a new, dedicated building on the BioCity Nottingham site, a reflection of their achievement in delivering multiple drug candidates on client projects, currently there are 8 drug candidates in the clinic invented at Sygnature since 2011.

TARGETED CANCER TREATMENT Another company to watch is BiVictriX Therapeutics Ltd, a biotech firm founded in 2016, based at the Alderley Park site, which is focused on developing and licensing novel, highly-selective, bispecific Antibody Drug Conjugates (ADCs) to target unmet medical need in blood cancer.

They’ve just been successful in securing funding to perform early Proof of Concept studies on BiVictriX’s Lead Candidate, a dual targeting ADC targeting Acute Myeloid Leukemia (AML). Their work has the potential to see the development of a targeted treatment for cancer cells, which would avoid many of the side effects of existing treatments.

TIMED DRUG RELEASE A third notable example is BDD Pharma, a drug formulation and delivery company based at BioCity Glasgow, who have

just raised investment to progress Oralogik™, their timed drug release technology, which could allow a drug to be taken once, orally, but which would be timed to release several times at different intervals.

This technology has the potential to revolutionise the way in which pain is managed in Rheumatoid Arthritis, for example, allowing a patient to take medication before they go to bed and wake up pain-free. These are just a few of the success stories that have emanated from the incubator, visit their website to find out more.

LIFE SCIENCE AND THE ECONOMY The success of BioCity is an indication of the huge contribution that life science makes to the UK economy.

As the government recently highlighted, the life sciences sector has enjoyed a record turnover of over £70 billion and significantly, SMEs account for 82% of these businesses and 24% of all UK life sciences employment - which underlines the importance of life science incubators in supporting new start-ups and SME’s.

FROM LAB BENCH TO BUSINESS Glenn has been at the helm for 15 years, almost from day one, becoming the very first employee of BioCity.

He is almost uniquely placed to do what he does, with a DPhil in immunology from Oxford and a career that has encompassed both working at a lab bench and a career in business.

Qualifying as a chartered accountant, after a sojourn in a lab, Glenn worked with many biotech companies in California, before returning to the UK to head up the Biotech division of Ernst & Young in Cambridge, from which he was headhunted for his current role.

In 2014, Glenn received an MBE for services to the biotechnology industry, whilst Chairman of the Board of Directors, Dr John Brown, received a CBE for services to science in 2011, in addition to his many other accolades.

IN TO THE FUTURE As for the future, BioCity is hoping to expand both at the sites at which they currently operate; and at other key locations around the country. Hand in hand with this, they plan to increase their investment in start-up companies – at which they have proven very successful - facilitating further investment, in more new life science companies in the future.

“Early stage companies are a massive source of innovation,” observes Glenn and that being the case, it will be fascinating to see what innovations emerge from the incubator next – we’ll have to wait and see.

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AS THE GOVERNMENT RECENTLY HIGHLIGHTED, THE LIFE SCIENCES SECTOR HAS ENJOYED A RECORD TURNOVER OF OVER £70 BILLION

| BIOSCIENCE TODAY SEPTEMBER•OCTOBER 2018 |

| news |

Ultra Scale-Down – Is this the answer to accelerated access of new medicines?

Afrin Zohura, USD Bioprocess Research Engineer, University College London (UCL) How to develop new drugs, therapies and technologies in a timely manner is one of the most pressing concerns of our time. Recently, UK Business Secretary Greg Clark highlighted that with over 10 million people in Britain alive today expected to live to 100, it is more important than ever to develop treatments faster and better than has previously been possible. Moreover, with the UK Government now announcing the selection of medicines and devices for fast-track access to patients, it is vital that the bioprocessing industry is able to keep up with these increasing demands.

One research team leading the field when it comes to helping biopharmaceuticals to accelerate bioprocess development is the Department of Biochemical Engineering at UCL, who announced in June the well-timed launch of a commercially available ultra scale-down (USD) shear device (kompAs ™ Ultra Scale-Down Innovation - Using small stuff to tackle big problems, 22 June).

The USD approach pioneered by the Biochemical Engineering research team at UCL aims to reproduce fullscale manufacturing at a laboratory scale. The department is leading the development of proprietary USD devices and laboratory methodologies to address scaling bottlenecks seen in industry. These technologies have the potential to transform and accelerate bioprocess development, enabling biotech companies to achieve robust manufacturing design for the production of enzymes, biopharmaceuticals, cell and gene therapies, vaccines and other biochemicals as building blocks for food, energy, and other products.

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The kompAs™ device, recently licenced through Gowerlabs (a UCL spinout company), is able to mimic large-scale manufacture through the introduction of shear on a biological sample using just millilitres of material. In practical terms, using low volumes like this in the early-stage development phase could mean reduced overall costs of projects and an increased capacity for biotech companies to take on additional projects using multiple drug candidates.

Simulating large-scale shear at the lab scale means that projects can be delivered through shortened development timelines, and a significant reduction in industrial Costof-Goods (COGs) at full-scale could mean that affordable, effective medicines can be made available to patients faster.

Academics from the department, including Professor Nigel Titchener-Hooker (Dean of Faculty), explains how USD applications can influence the way we deliver new and urgent medicines to patients: “The idea is to move companies forward with confidence to enable biopharmaceuticals to move to manufacturing at lower cost, and as a consequence to enable greater populations of patients to benefit.”

Dr Andrea Rayat, the USD Tech Transfer Lead, highlights the future of USD technology applications in bioprocessing: “The demands for personalised medicines, for example, consequently demands targeted manufacturing, and this is an exciting area for next generation USD devices.”

The work carried out at UCL Biochemical Engineering may be a gateway into revolutionising the way early-stage bioprocessing development occurs as various studies have already been carried out which show the numerous uses and applications of the shear device.

To find out more, contact usdtechnologies@ucl.ac.uk

| BIOSCIENCE TODAY SEPTEMBER•OCTOBER 2018 |

antimicrobial New database launches in a bid to develop new drugs in the fight against antimicrobial resistance A new and first of its kind database has been launched listing compounds that could be used to develop new antibiotics in a bid to tackle the global issue of antimicrobial resistance (AMR).

The new resource, outlined in the Journal of Antimicrobial Chemotherapy, is the result of a collaboration between the University of Birmingham, the John Innes Centre and the British Society for Antimicrobial Chemotherapy.

It comes after the World Health Organization in 2009 declared AMR one of the biggest threats to mankind and, if not addressed, by 2050 it could kill millions of people - more than from cancer or road traffic accidents.

The free, open-access, searchable database called AntibioticDB brings together antibacterial compound discoveries that were once-promising leads from the past 40 years which have, for various reasons, been dropped or stalled, and may otherwise be overlooked by drugdevelopment companies.

Lead author Professor Laura Piddock, of the University of Birmingham’s Institute of Microbiology and Infection, said: “Antimicrobial resistance (AMR) threatens the effective prevention and treatment of an ever-increasing range of infections caused by bacteria, parasites, viruses and fungi.

The database includes links to data on discovery, research and clinical trials, compounds awaiting approval and discontinued compounds, providing a platform for future research, antibiotic discovery and development in the hope this will inspire the lifesaving drugs of tomorrow.

One of the authors of the study, Professor Tony Maxwell of the John Innes Centre, adds: “We wanted to establish the current status of the drug-discovery pipeline in antibiotic development - particularly to look at compounds that might have been dropped in the past to see if they could be resuscitated.

“We also went back to 1960 and uncovered details of old compounds and drugs that were not developed. These could form the basis for new development to treat today’s infections.”

The research team used a range of sources to identify compounds of interest, including key opinion leaders in the pharmaceutical industry and leading agencies in this research area.

Information on each compound or drug was obtained using online searches, literature archives and interviewing prominent experts. Further information such as reasons for the lack of development is also included.

The study highlights examples from the past where drugs have been dropped on safety grounds, only to be re-introduced successfully years later after new research showed them to be safe at different dosages.

“New resistance mechanisms are emerging and spreading globally, threatening our ability to treat common infectious diseases, resulting in prolonged illness, disability, and death.

While other pay-per-view resources exist for researchers, AntibioticDB is the first free database designed to appeal to small and medium-sized enterprises or academia.

“One answer to the crisis seems simple: to generate new antibiotics. However, it can take up to 15 years and cost up to $5 billion from the discovery of a compound to progress through pre-clinical and clinical development before a medicine can be licensed and then marketed.

Rebecca Lo, a post-graduate researcher from the University of East Anglia who carried out work on the project while she was an intern at the John Innes Centre, said: “We hope this might lead to more joined-up drug discovery in this area, encouraging companies, academics and governments to work together.

“There is no doubt that the antibiotic pipeline needs revitalization; however, the answer may be not only the development of new drugs, but also re-investigating compounds previously discontinued.

“It would be fantastic if the database could stimulate new initiatives to investigate forgotten antibiotics.”

“For this reason, we have developed and populated an easy to use database of antibiotics that can be accessed for free by anybody; we hope this will help both academia and commercial companies with their drug-discovery efforts.”

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resistance “One answer to the crisis seems simple: to generate new antibiotics. However, it can take up to 15 years and cost up to $5 billion from the discovery of a compound to progress through pre-clinical and clinical development before a medicine can be licensed and then marketed.”

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| finance and funding |

| BIOSCIENCE TODAY SEPTEMBER•OCTOBER 2018 |

Patient capital is the key to unlocking growth in the life sciences sector economic impact could be made if the availability of patient capital in the UK was increased to the same level as the US. Recent data has shown that the supply and diversity of the patient capital available to the life sciences sector has begun to increase. The British Business Bank’s Small Business Equity Tracker, published in July 2018, reported that the amount of equity investment into life sciences businesses in the UK grew by 19% between 2016 and 2017. While this is encouraging, much of the increase was down to larger deal sizes rather than many more smaller businesses getting the finance they need - in the same period, the number of equity deals in the sector grew by only 3%.

Much more therefore remains to be done. The government’s Patient Capital Review, published last autumn, showed that a lack of longer-term investment was holding back such young innovative firms. This ‘patient capital gap’ slows firms’ growth, dampens their ambition and means that some are sold to trade buyers rather than growing to maturity in the UK. Developing a company to be able to list on the stock market requires more funding than developing a company for a trade sale, taking 3.5 funding rounds on average to exit via an Initial Public Offering (IPO) compared to 2.4 for a trade sale.

Keith Morgan, CEO, British Business Bank The British Business Bank, as the UK’s national economic development bank, has a mission to make finance markets for smaller businesses operate more effectively, enabling those businesses to prosper, grow and build UK economic activity.

Part of this mission is to ensure that the UK small business finance market provides the right kind of finance to enable the UK’s innovative and high-growth start-ups to become the global success stories of tomorrow.

For many UK smaller businesses with ambitions to grow, the finance they need is patient capital – longer-term finance that will enable them to navigate research rounds and product development that may take years and decades to reach fruition rather than months. Patient capital is particularly vital for the life sciences and biotech sector, where development lifecycles can be complex and last for a significant amount of time.

Historically, research-intensive smaller businesses in the UK have had to look abroad and particularly to the US for the patient capital necessary to fund expansion or growth. The UK is well established as a start-up factory, with impressive rates of business births, but has lagged behind the US in financing for scale ups. Research shows that a significant

36

That’s why we are proud to be taking forward recommendations from the Patient Capital Review to deliver an additional £13bn of patient capital to such firms, including through establishing a new member of the British Business Bank family – British Patient Capital.

A separate subsidiary of the British Business Bank, British Patient Capital launched in June 2018 and has been given £2.5bn of new resources by the Government. In line with the ambitions of the Industrial Strategy, it will deliver a programme designed to support UK bus inesses with high growth potential to access the long-term financing they need to scale up.

British Patient Capital builds on a successful 10-year heritage of the Bank’s programmes investing into UK venture and growth capital. The new programme is designed to support just the kind of scale-up businesses found in the life sciences sector. Our venture capital programmes have historically supported the sector - up to March 2018, we had supported 312 smaller businesses in the life sciences sector with funding of £322m - and we expect further commitments to be made to life sciencesfocused funds and businesses.

One of the life sciences businesses to benefit from previous British Business Bank activity is Cambridge-based Exonate.

The company aims to introduce a revolutionary, game changing eye drop for the treatment of retinal vascular Continued on page 38



| BIOSCIENCE TODAY SEPTEMBER•OCTOBER 2018 |

| finance and funding |

“we are proud to be taking forward recommendations from the Patient Capital Review to deliver an additional £13bn of patient capital to such firms, including through establishing a new member of the British Business Bank family – British Patient Capital.”

Keith Morgan, CEO, British Business Bank

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| finance and funding |

| BIOSCIENCE TODAY SEPTEMBER•OCTOBER 2018 |

 Continued from page 36 disease including Wet Age-Related Macular Degeneration (WAMD) and diabetic macular oedema.

were aware of a basket of six alternative finance products that might help them grow and succeed.

Exonate needed patient capital to help it navigate research, optimise compounds, and proceed with a pre-clinical safety and toxicity development programme before entering clinical trials in 2020. The company was able to raise £2.8m equity funding from angels, supported by funding from the Universities of Nottingham and Bristol, and the British Business Bank-sponsored Angel CoFund.

To address this, we provide businesses with free and impartial information on their finance options.

We believe that the new British Patient Capital programme will be particularly beneficial to similar high-growth life sciences businesses.

When British Patient Capital was launched, we were proud that one of our first investments was a £9m commitment to the Dementia Discovery Fund, a specialist venture fund.

The fund benefits from a diverse range of strategic investors including private investors, pharmaceutical companies and the Department of Health and Social Care and the charity Alzheimer’s Research UK (ARUK).

The goal of the fund is to discover and develop new medicines that have the potential to transform the treatment of dementia by slowing or stopping disease progression. It specifically aims to increase the flow of financial capital to fill the funding gap in pre-clinical research for dementia, enabling further progression through the research and development pipeline to human testing.

As well as making this additional finance available, we also want to equip smaller businesses with the information they need to seek the finance best suited to their needs. Our recent Small Business Finance Markets report, published in February 2018, found that only 50% of smaller business

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For several years we’ve provided the Business Finance Guide (published in partnership with the ICAEW and a further 21 leading business and finance organisations) which impartially sets out the range of finance options available to businesses at all stages – from start-ups to SMEs and growing mid-sized companies. Businesses can take the interactive journey at www.thebusinessfinanceguide.co.uk/bbb.

In a significant step-up in our efforts, this summer we’ve launched the new British Business Bank Information Hub, www.financeyourgrowth.co.uk, specifically designed for high-growth businesses such as many of those found in the life sciences sector. The digital hub provides everything a business looking to scale up might need to know about their finance options, featuring short films, expert guides, checklists and articles from finance providers to help make their application a success. The new site also features case studies and learnings from real businesses to guide businesses through the process of applying for growth finance.

We believe that 2018 has the potential to be a pivotal year for ambitious UK life sciences businesses who want to grow to scale. With our new British Patient Capital programme and Information Hub now launched, we look forward to helping them to do so.

| BIOSCIENCE TODAY SEPTEMBER•OCTOBER 2018 |

| finance and funding |

Life sciences – what’s the big deal?

People often ask me why life sciences are so important.

For me, important things are those which have a clear impact on the future. Things to be addressed now rather than later. Things such as using life sciences to help address some of the medical and environmental challenges we face in our world.

Emerging life sciences technologies help address a major problem in our society; with an ageing population and a dramatic rise in chronic diseases, our healthcare systems are no longer sustainable. The working population is no longer able to support those not working. Without biotech advances to improve diagnostics and cures and IT advances to improve efficiency, we have an important problem. We need to discover ways to keep people healthier for longer, detect diseases earlier and manage those diseases better.

Biotech and life sciences advances reach beyond the medical world and impact other critical areas of our future. They include the drive for more efficient food production, growing crops more successfully without fertilisers or pesticides, developing biodegradable plastics and producing cleaner energy to name a few.

WHERE DOES CAPITAL CELL FIT INTO ALL OF THIS?

But, in addition to the benefits to society, investing in life sciences can offer attractive financial returns. The total market for Biotech is set to reach $272bn by 2025, which makes the life sciences sector an interesting and appealing place to invest.

Back in 2015 we noticed a bizarre problem with life sciences startups: despite offering a tempting return and a decent survival rate, over and over again their CEOs failed to generate any significant funding interest.

Despite investment forums and pitching events, many great ideas were left unsupported and unfunded. It surprised me because they were often the most interesting companies in the room with bags of exciting potential.

n Biotech assets outperformed the S&P500 from 2008 to 2017 by a multiplier of almost three. n Biotech has been the most profitable investment sector in the world

by ROI between 2008 and 2016.

The issue it seems was that the average life sciences investment pitch was incomprehensible to the average human. An overabundance of technical terms mixed up with data and obscure graphs overwhelmed non scientific investors paralyzing their decision making, and the CEOs were oblivious to this.

n Healthcare VC investment reached $15bn in 2017 (18% of overall VC investment). n Q1 2018 saw more than $10bn invested into healthcare and the sector is heading for another record year.

That’s why we founded Capital Cell. We created a platform where science and its impact on the capital you invest could be explained with the clarity to make it understandable (and tempting) for non-scientists.

n Time to exit in BioPharma deals hit an all-time low in 2017, at three and a half years after Series A

With Capital Cell all deals are screened and backed by our network of top scientists and doctors. Our specialists evaluate the opportunity, unravel the jargón and translate the relative merits into an offering more easily digested by potential investors.

n Nearly 40% of Biopharma deals hit an IPO valuation of more than $100m. n Biopharma products achieve astronomical sales in the market. The top 20 pharma products have sales in excess of $4bn each year, with up to 25% royalties going to investors.

That is how Capital Cell is built. We combine the technical knowledge of world-class scientists with the legal and financial knowledge of an expert investment team and offer opportunities to invest in deals using our secure online platform. We give everyone access to the kind of highly complex, highly profitable and socially rewarding investment that life sciences offer.

A quick look at these figures tells us that investing in life sciences can offer shorter exit times, higher exit valuations and the realistic possibility of investing in game-changing new drugs. No wonder savvy investors are in on it.

Some 25 investment rounds later, we continue to help scientists shape up their investment propositions (often translating them into plain English). We continue to gather expert knowledge to find the best possible investment deals and the scientific ecosystem continues to value Capital Cell as central to the early-stage financing of life sciences deals.

We’re helping early-stage companies whose innovative solutions will transform healthcare, create new ways to recycle, reduce pollution and create green energy.

Our values as a company are those of equality, honesty, progress, integration and innovation and we are deeply committed to them. We are closing the distance between science and the general public; helping people to understand how their money is related to the society they live in and opening up profitable investment opportunities to all.

It’s important for all of us that we do

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| your guide to r&d tax relief |

| BIOSCIENCE TODAY SEPTEMBER•OCTOBER 2018 |

Eligible costs for R&D Tax Relief – it’s not just for those people in white coats!

For my fellow professionals who work with businesses to support them with claims for Research and Development Tax Relief, one of our common mantras when explaining to manufacturing businesses, engineering firms and software developers that they may very well be eligible to make a claim, is that the tax relief ‘isn’t just for those companies employing people in white coats.’

Even though it is the companies in the BioScience community that we are referring to in that statement, the irony is, that the same applies to your business as well.

The costs that we will be able to claim for aren’t just your scientists or your doctors, there are a vast array of people within your company who will be eligible for inclusion in the claim. Even the person who cleans the clean room can be included in a claim.

There are a variety of costs that can be included in a claim, but there are also some surprising costs that can’t be included, we’ll come on to the latter in the next article.

WITH R&D TAX RELIEF SIZE MATTERS To qualify as a Small or Medium sized Entity (if you are part of a group it relates to the size of your group and if you have VC investment there are complicated rules about linked and partner enterprises which might make you part of a larger group of businesses without the level of co-ordination a group may bring) and to claim under the more rewarding SME scheme then your group must employ less than 500 Full-time Equivalent staff, and have either a turnover of less than €100m or a balance sheet less than €86m then you can claim for the following costs Staff costs – Wages and Salaries, bonuses, Employers NI, Employers Pension Contributions, Reimbursed staff expenses linked to R&D activity and Employee Share option costs.

Externally Provided Workers – individuals working for you through an agency Subcontractor costs – payments to third parties for Research and Development activity Consumable Material costs – if you are developing a prototype you will often have to use materials to develop it. If you can’t reuse these materials after they have been incorporated into the prototype and you don’t sell the prototype, then the materials will have been consumed and can be included in the claim.

Software costs – If you have to use specialist software in your research or you are using project management software to manage the R&D team, then you can include a portion of the software costs.

I’M NOT SMALL! WHAT’S THE ALTERNATIVE? If you don’t meet the criteria for the SME Scheme then you are eligible to claim under RDEC, the eligible costs are the same as above but you won’t be able to claim for the subcontractor costs.

When the top company in a subcontract arrangement is a large company it is the low man on the totem poll i.e. the person that is actually doing the work that can claim for the costs under the RDEC Scheme.

So for Clinical Research Organisations there is a constant requirement to claim under the RDEC scheme for all of their qualifying projects (unless they are developing IT Systems internally), but to identify a qualifying project there is a need to identify who the ultimate customer is, if the ultimate customer is a large or indeed foreign (outside the UK) entity or a non-corporate entity not chargeable to UK Corporation Tax then the CRO will be able to claim for their qualifying projects.

One of the interesting things to consider as a CRO is that if you don’t have coverage in a particular country and you need to work with a partner CRO, you may wish to consider whether you are using them as a subcontractor or as an agency, if you are working with a particular Clinical Research Associate to perform tasks in country then they maybe an externally provided worker.

As with many things the devil is in the detail, if you want to have a free no obligation chat with an expert to see whether it’s worth claiming please give Simon Bulteel a call on 01424 225345, or visit our website www.coodentaxconsulting.co.uk.

Utility costs – You can include a proportion of light, heat and water in the R&D claim, provided that some of the R&D has been performed in-house.

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| BIOSCIENCE TODAY SEPTEMBER•OCTOBER 2018 |

| finance and funding |

Metrion Biosciences awarded £637k funding under Innovate UK Biomedical Catalyst Primer Award for ion channel drug discovery n Funding will support project aiming to identify novel oral therapeutics for the auto-immune disease psoriasis n Adds to Innovate UK funding awarded in February 2018 for research on potassium channel inhibitors Cambridge, UK: Metrion Biosciences Limited (“Metrion”), the specialist ion channel contract research and drug discovery company has announced it has been awarded £637k funding under the Innovate UK Biomedical Catalyst Primer Award scheme. The funding will be used to support further research on orally available potassium channel inhibitors for treatment of psoriasis, a common autoimmune disease for which improved treatments are much needed.

The project will commence in September 2018, and will focus on the further optimisation of a set of key compounds, and their characterisation in disease relevant models. The compounds are taken from the portfolio acquired by Metrion in January this year of more than 2,000 small molecule inhibitors of a voltage-gated potassium channel known to be involved in the development of auto-immune disease. Metrion has already confirmed the potent in vitro activity of the selected key compounds, and has filed a new patent application covering a series of these active drug leads.

market is expected to be valued at $13 billion by 2024 with a CAGR of 7.26% (GlobalData, 2016). A novel efficacious oral drug at a cost effective price-point has the potential to profoundly reduce healthcare costs.

Dr Keith McCullagh, Chairman, Metrion Biosciences, said: “As well as being a specialist ion channel contract research organisation, Metrion also has valuable intellectual property in the potassium channel field which we are keen to see commercialised. The funding received from Innovate UK will enable us to determine the potential value of this novel therapeutic approach to auto-immune conditions.

If successful, we will seek appropriate industry partners to fund further development and commercialisation."

Alongside this project, Metrion is also conducting research with its compounds in other auto-immune conditions, partially funded by an Innovate UK Biomedical Catalyst Feasibility Award, announced in February.

If successful, the project may lead to the selection of one or more novel oral drug candidates suitable for development as potential new therapeutics for the treatment of psoriasis and other auto-immune disorders. The cost of biologics for treatment of a patient with moderate-severe psoriasis is approximately $70K per year, and the global psoriasis drugs

RESEARCH & DEVELOPMENT TAX RELIEF SPECIALISTS

GET YOUR CASH FROM HMRC

Call COODEN TAX CONSULTING NOW!

Validate your claim,

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East Sussex TN40 1JA 22/02/2016 17:41

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| intellectual property |

| BIOSCIENCE TODAY SEPTEMBER•OCTOBER 2018 |

Life sciences – developments Liz Coleman, Divisional Director at the Intellectual Property Office Welcome to our new regular feature on IP issues in the life sciences. Our aim is to keep you up to date on key IP issues in the sector, identifying new developments or reflecting on recent activities.

While case law drives much of the discussion around developments in life sciences, our first piece will, instead, focus on three topical issues in which the IPO is directly involved: the export waiver for supplementary protection certificates (SPCs); the unitary patent and Unified Patent Court (UPC), and what might happen post-Brexit; and the processing of biotech/pharma searches on patent applications to the IPO. After extensive debate on health care initiatives under the Dutch Presidency of the EU Council of Ministers, and a stakeholder consultation at European level, the EU Commission published their proposal for an SPC export waiver at the end of May. This would allow EU manufacturers to produce products for export under certain conditions without infringing the relevant SPC. The proposal appears to have two objectives: first to mitigate competitive disadvantage for EU manufacturers in third countries where the product concerned is not protected; and second to facilitate earlier generic entry to the EU market. This last issue has been a long-standing concern of the EU Commission and was picked up in their pharmaceutical sector enquiry of 2009.

For the proposed system to meet either of these objectives it needs to be workable in practice. This is where national delegations have to take into account the needs of their own administrative processes as well as the requirements of stakeholders. The UK delegation has been participating in Council working groups under the Austrian Presidency to help bring this about. The Commission’s aim will be for the proposal to reach agreement in both the Council and the Parliament before EU elections in 2019.

Meanwhile, returning to a slightly longer-running project, the unitary patent and Unified Patent Court took a step further towards completion with the UK’s ratification on

World IP Day, 26 April. This package will set up a single patent court covering multiple European states, with jurisdiction over European patents and the future Unitary Patent, which will be granted by the European Patent Office.

The central division of the UPC, which will deal mainly with revocation cases, will be based in Paris with a section in Munich and one for life sciences in London. The UPC Appeal Court will be in Luxembourg.

For the system to come into force Germany’s ratification of the Unified Patent Court Agreement is needed. This is awaiting the outcome of a complaint before the German Federal Constitutional Court. Should that be resolved, the UPC implementation teams will be working during a provisional application phase of several months to make sure that all systems are in place for the Court to open for business. This phase will include the interviewing, recruitment and training of judges as well as the finalisation of the IT tools for the UPC and its users.

While the UPC is not an EU body, the underlying Agreement is based on contracting states being members of the EU. We expect that under the UK-EU withdrawal agreement, currently close to finalisation, the UK will be able to continue to participate in the UPC and the unitary patent system at least until the end of the implementation period set out in that agreement. The future after that will depend on the outcome of European negotiations, but the UK has made clear in the White Paper on the Future Relationship between the UK and the EU published on 12 July that we intend to explore staying in the system after we leave the EU. We will work with other contracting states to ensure that the UPC Agreement can continue on a firm legal basis.

Finally, the UK is one of the 38 states of the European Patent Organisation and regularly participates in meetings of the EPO Administrative Council. We are pleased that the Council agreed in its June meeting that the EPO and the UK could open negotiations on a bilateral cooperation agreement under which the EPO would carry out some searches in the biotech area, where the UK IPO is heavily loaded and currently not able to deliver the timeliness that we want for our customers. This agreement has now been signed and teams on both sides are working to make sure we have a seamless electronic document exchange system in place, meeting the necessary requirements of confidentiality before 18 month publication. Once this is in place, we will be able to start the bilateral cooperation and the first searches under this agreement are likely to be delivered in 2019.

Intellectual Property Office is an operating name of the Patent Office

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| BIOSCIENCE TODAY SEPTEMBER•OCTOBER 2018 |

| intellectual property |

from the IPO’s perspective “Protecting your intellectual property makes it easier to take legal action against anyone who Uses or copies it.”

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| intellectual property |

| BIOSCIENCE TODAY SEPTEMBER•OCTOBER 2018 |

What is the best time to file a patent application?

Katherine Wright, Pharmaceutical Patent Attorney at Adamson Jones Determining the best time to file a patent application is one of the first and sometimes one of the most difficult questions that patent applicants face, and its importance should not be overlooked.

Two criteria which a patent application must meet are novelty (the invention is not made public before the application is filed) and sufficiency (the application would enable a person skilled in the technical field to practise the invention). When filing a patent application, a balance must be found between filing earlier, when adequate data to ensure sufficiency may not be available, and filing later, when more data is available but there is a greater risk that a third party will have got there first.

The risks of filing a patent application too early have recently been highlighted in Regeneron v Kymab & Novo Nordisk [2018] EWCA Civ 671.

Regeneron’s European patents EP1360287 and EP2264163 relate to transgenic mice that produce partially humanised monoclonal antibodies. Monoclonal antibodies are widely used for the treatment of an extensive range of diseases, including cancer and autoimmune diseases. Regeneron developed a method for developing humanised antibodies using transgenic mice in which parts of the mouse genes are replaced with the equivalent parts of the human genes. This technology became the basis for Regeneron’s commercially successful VelocImmune technology.

During an attempt to enforce their patents against an alleged infringement by Kymab and Novo Nordisk, it became clear from expert evidence that the method of carrying out the invention taught in Regeneron’s patents would not work as described. This might have occurred because the method had not been confirmed by experiment before the patent application was filed, for example. The High Court found that Regeneron’s patents did not enable the invention to be put into practice and found the patents invalid for lack of sufficiency.

Regeneron appealed, arguing that the patents were sufficient as the described method could be used if several adjustments were made, and these adjustments would have been common general knowledge for a person working in this field at the filing date of Regeneron’s patents. The Court of Appeal agreed, and decided that a skilled team would have found it obvious and technically feasible to modify the described method as indicated. The Court therefore found Regeneron’s patents sufficient.

Regeneron were fortunate in that the deficiencies in their described method could be rectified using knowledge commonly available at the filing date, but this is likely to be a rare circumstance for technical processes that have not been confirmed by experiment before a patent application was filed.

While it is certainly desirable to file a patent application as early as possible, it is nevertheless advisable to delay filing until you are in a position to describe a specific method for putting the invention into effect that you know works, together with evidential data to support a claimed chemical or biological effect, if appropriate.

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REGENERON WERE FORTUNATE IN THAT THE DEFICIENCIES IN THEIR DESCRIBED METHOD COULD BE RECTIFIED USING KNOWLEDGE COMMONLY AVAILABLE AT THE FILING DATE

| BIOSCIENCE TODAY SEPTEMBER•OCTOBER 2018 |

| intellectual property |

Preparations for AI patenting in Europe PATENTING AI

Mike Jennings, Partner and patent attorney at IP law firm AA Thornton The current era of rapid technological development requires industry to be quick to respond to challenges and opportunities, with many choosing to exploit new AI technologies rather than wait to be disrupted by competitors.

Intellectual property law firms need to be just as prompt, flexible and proactive as their industry clients. But are they able to do this despite European constraints on patenting computer programs and mathematical methods? Are these laws and procedures suitable for the accelerating pace of technological change?

TIMELINESS Historically, the European Patent Office was criticised for long delays examining patent applications, but this is changing. Starting in 2014, the EPO has made real progress against aggressive timeliness targets - now issuing European substantive search opinions within 5 months, and completing a major reorganisation that will achieve faster grant, reduce costs for some applicants and improve opposition handling. The EPO granted more patents and reduced average pendency times in 2017. Their target is to grant patents within 3 years of filing by 2020 – faster than what some pharmaceutical companies want.

The EPO is well prepared for the current generation of AI-related patent applications in which AI tools support human ingenuity and a vast number of patents are granted in Europe for new computer-implemented solutions to technical problems. In fact, EPO practice on computerimplemented inventions including software (CIIs) has been stable for a decade (unlike the USPTO and IP Australia), so we can accurately predict outcomes, before costs are incurred, based on a large body of case law and consistent practice.

Looking ahead, many AI-related patent applications, including some applications of AI technologies in healthcare and biosciences, will be handled under the established CII practice. The EPO has consulted with representatives from industry, the judiciary, academia and private practice as it prepares for further growth in AI patenting. Examiners and our attorneys in life sciences have been trained on CII practice and new guidelines with AI examples in healthcare will be published soon.

Legislation will be needed for future generations of AI however, including inventions made autonomously by AI systems without human inventors. Meanwhile, we will obtain European patents more quickly for many AI inventions, and we can predict outcomes for challenging cases.

Should you have any queries on this topic please get in touch with Mike at mjj@aathornton.com

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| advances respiratoryin| treatment of respiratory diseases |

| BIOSCIENCE TODAY SEPTEMBER•OCTOBER 2018 |

Helping everyone

brea t h e easier

– finding new approaches to treating respiratory disease

Ian Jarrold, Head of Research at the British Lung Foundation (BLF), outlines the work that they are doing to help improve the lives of people with lung disease.

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| BIOSCIENCE TODAY SEPTEMBER•OCTOBER 2018 |

| advances in treatment of respiratory | respiratory diseases |

Everyone should be able to breathe clean air with healthy lungs, yet sadly far too many people continue to gasp for breath because of lung disease. In the UK, one in five people develop some form of lung condition in their lifetime.

The challenge of developing better diagnostics, treatments and cures is one that faces us all, and the British Lung Foundation (BLF) is here to provide hope, help and a voice to everyone who is left breathless by a lung condition.

Our understanding of how different types of lung disease develop has improved in recent years, which is accelerating the development of better care for more and more people.

For example, innovative approaches to understanding how lung cancer develops and changes over time is paving the way for new treatments that will hopefully replicate the success seen in treating other cancer types. Efforts by governments across the UK to ban smoking in cars and in public places has reduced people’s exposure to secondhand smoke, helping to clear the air for everyone to breathe easier in their daily lives.

Although advances have been made in diagnosis and treatment, too many types of lung disease remain without adequate care or cure. To take just one example, idiopathic pulmonary fibrosis (IPF) has no cure and limited treatment options, with 3 years the average length of time that patients have left to live after their diagnosis. With 20% of all deaths in the UK resulting from various forms of lung disease, it’s never been more urgent for lung disease research to receive the priority and support that it deserves.

Since the BLF was formed over 30 years ago, we have spent over £30 million on research grants for a wide range of forms of lung disease – focusing our efforts on diseases which receive much less attention, like mesothelioma, IPF and chronic obstructive pulmonary disease (COPD). We are committed to funding outstanding research which offers real hope to patients right across the UK – research supported by the thousands of generous donations we received from people whose lives, or the lives of their loved ones, have been devastated by lung disease.

PERSONALISED APPROACHES TO TACKLING IPF Idiopathic pulmonary fibrosis (IPF) causes scars to form on lung tissue over time, which hardens the lungs and makes breathing more and more difficult. It is not clear what causes IPF to develop, but what is clear is that it blights the lives of 32,500 people every year in the UK. Understanding the biological processes that lead to the scarring of lung tissue, and ultimately preventing, halting or reversing them, is therefore a top priority in tackling this horrendous disease.

With advances in genomics and DNA technology, we have unprecedented opportunities to look at the full range of genes which are expressed in patients with IPF and understand the role our genes play in the cellular processes which cause scar tissue to form and spread.

Professor Louise Wain, our BLF Chair at the University of Leicester, has analysed the genomes of patients with IPF in the UK and found that the A-Kinase Anchoring Protein 13 (AKAP13) gene is more strongly expressed in patients with IPF. Since AKAP13 is already understood to be involved in tissue fibrosis, there is an exciting opportunity for new drugs to be targeted to inhibit this protein, and therefore

47

the tissue fibrosis pathway in the epithelial cells of the lung. In turn, this could halt the development of scar tissue and offer a new treatment for patients with IPF. Analysing and understanding the genome, and the patterns of gene expression associated with respiratory disease, has uncovered new and, in some cases, unexpected factors at play in the development of lung disease. Understanding how and why the genome operates in the way that it does is crucial in finding clinically effective treatments for IPF and other forms of lung disease.

The goal of personalised IPF treatment is within sight, aided by a growing understanding of the biological mechanisms which causes scar tissue to form in the epithelial cells in the lungs. Professor Toby Maher, another of our BLF Chairs, has made important strides in understanding the underlying cellular processes that causes IPF to take hold. Professor Maher has extensively studied the presence and variety of bacteria in the alveoli of patients with IPF. Examination of patients with IPF has shown that they have higher numbers of harmful bacteria in their lungs, which helps us understand which proteins are manufactured by the body in response.

Professor Maher has also identified elevated levels of epithelium-specific proteins in the blood of patients with IPF – a finding which enhances our understanding of the role of epithelial cell damage in the development and worsening of symptoms of IPF. This research paves the way for new treatments which can tackle the underlying processes that drive IPF and eventually will bring forward the day when IPF is no longer the death sentence that it is currently.

ALLEVIATING INFLAMMATION FROM BRONCHIECTASIS Bronchiectasis occurs when the lungs become permanently enlarged, which results in abnormally high levels of mucus forming in the lungs. Inflammation in the airways, caused by infections facilitated by the increased mucus production, can cause permanent tissue damage. Although not usually fatal on its own, the excess mucus that builds up in the lungs from bronchiectasis can leave people vulnerable to other serious infections, like tuberculosis and pneumonia. BLF statistics suggest that 210,000 people are living with bronchiectasis in the UK, with many cases going undiagnosed for several years. Professor James Chalmers, BLF Chair at the University of Dundee, is seeking to change the prospects for people living with bronchiectasis by examining the phenotypes and bacterial infections associated with bronchiectasis, so that treatments can be targeted more effectively.

Professor Chalmers’ research has also shone a light on the impact of bronchiectasis on quality of life for patients and how their living environment affects their ability to cope with their disease. By analysing the detailed medical records of patients in Dundee and Perth and comparing it with data on air pollution levels in the city, Professor Chalmers has demonstrated that high air pollution levels correlate with increased admissions to hospital and GP practices in NHS Tayside. This research has made a real difference to the public understanding of the dangers of air pollution to public health and is shaping the public debate on measures to reduce air pollution in towns and cities in the UK. Making a compelling case for curbs on polluting vehicles to be the priority of governments across the UK is now one of our top priorities, thanks to the high-quality evidence provided by the scientists we fund.

Building a world where everyone can breathe clean air with healthy lungs will continue to be a major challenge in the years to come. Thanks to the promising efforts of our researchers, the future looks much more hopeful for people with lung disease, although there is much more work to be done to find new treatments and cures. With the continued generous support of our patients, supporters and donors, we will strive to find safe and effective cures for all forms of lung disease, so that everyone can breathe easier for generations to come.

| advances in treatment of respiratory diseases |

| BIOSCIENCE TODAY SEPTEMBER•OCTOBER 2018 |

Getting more out of our medicines – re-purposing drugs to improve patient care Paul Chrisp, Programme Director Medicines and Technologies, NICE Developing new medicines and then ensuring they are used appropriately is a costly and drawn out process. The NHS needs to make sure that alongside the development of drugs it can optimise the use of existing medicines. The aim being to find more efficient ways to use effective treatments for conditions like cancer, heart disease, Parkinson’s and multiple sclerosis. Discovering new uses for drugs already being used to treat other diseases could offer people more treatment options, improve access and deliver significant healthcare benefits. If a medicine has already been through the regulatory steps to get from the laboratory bench to the patient it may be easier to carry out further research into any added benefits it has and find alternative ways it could be used. As a result, medical research is becoming more interested in how existing medicines can be used to treat other conditions, beyond those they are already licensed for, so-called ‘drug re-purposing’. Many of the medicines where information is emerging about new uses are generic, non-branded ‘off patent’ drugs.

NICE has been part of an important, collaborative project to help speed up the adoption of re-purposed medicines for use in the NHS. After attempts by MPs to bring in new regulations to widen access to off patent use of drugs, ministers saw a growing public desire to tackle the issue. They also recognised that this is a complex problem with many different factors which legislation could not solve. These factors include regulatory process; commercial incentives for manufacturers to stick to single indications; the need for clearer information to support researchers; NHS commissioning and costing pressures; prescribers’ responsibilities for advising patients; and how evidence about re-purposing is used effectively to support clinical decision making.

In 2015 the then Minister for Life Sciences asked the Association of Medical Research Charities (AMRC) to convene a group to explore this issue in more detail, support prescribers’ clinical decisions and improve patient access. Chaired by the AMRC, members of the group included NICE, the Medicines and Healthcare products Regulatory Agency, General Medical Council, pharmaceutical industry, NHS England. Crucially the medical research charities were also well represented including by Breast Cancer Now, Prostate Cancer UK and Parkinson’s UK. Any solutions proposed could not undermine existing regulations for assuring the safety, effectiveness and quality of new medicines used by the NHS. The group therefore looked at how medicines regulation could enable drug re-purposing, where there is strong evidence to support use in patient care and it is felt clinically appropriate. Where research shows benefits of using drugs to treat other conditions, clear advice and support is needed to re-purpose licensed medicines. All the group’s findings and recommendations were published in December 2017 in a report

One example is our 2013 recommendation that women with a family history of breast cancer could be offered preventive treatment with tamoxifen or raloxifen. This marked a major shift in breast cancer treatment, giving women at high or moderate risk of developing breast cancer an alternative to a double mastectomy. At that time, neither medicines were licensed as preventative treatments in the UK although they were approved in the United States after several studies showed they could reduce a person’s risk of developing breast cancer by around a third. Our recommendation broke new ground for the NHS and to support it, we produced a series of decision aids for healthcare professionals to use with patients that outlined the pros and cons of preventative treatment for breast cancer. On the back of taking this action a manufacturer has since sought a variation on its tamoxifen licence from the MHRA to include breast cancer prevention.

The variation was approved in April which is good news for breast cancer patients.

The Drug Re-purposing Group’s report features similar forward thinking examples showing how re-purposing can work.

Bisphosphonates are licensed to treat osteoporosis and reduce the damage to the bones caused by cancer that has spread there. A Lancet study showed that giving a bisphosphonate to post-menopausal women with primary breast cancer could reduce the risk of it spreading to the bone and other areas of the body and in some cases reduce the risk of dying. NICE provided its own commentary on the Lancet study to raise awareness of the benefits among prescribers and commissioners and provide necessary rigour and reassurance that the decisions clinicians took were the right ones for their patients. For docetaxel, which is used with hormone therapy to treat metastatic prostate cancer, NICE published a rapid evidence review that showed the benefits of having access to the drug earlier. The NICE rapid review was used to inform commissioning of docetaxel by NHS England helping to bring this medicine to more people who need it.

Both of these examples and our guidance around tamoxifen demonstrate the clear cost-effective and life-extending benefits to patients of drug re-purposing. Further research is starting to indicate that there could be many other disease areas and patient groups that could benefit from the use of re-purposed medicines including neurological conditions like multiple sclerosis and Parkinson’s disease.

The recommendations in the working group’s report reflect the coming together of all stakeholder opinion, expertise and experience involved in re-purposing off-patent drugs use and medicines regulation. What this important work shows is that when new research comes to light, the system can work together across the medicines life cycle to realise opportunities to enhance medicines uptake, supported by clear evidence of their potential to improve patient care.

To help improve patient access and support effective clinical decision making, NICE provides advice on therapeutic use, makes recommendations in our guidelines and raises awareness through our evidence summaries, and via our medicines and prescribing networks.

We also provide resources to support shared decision making between doctor and patient, and ensure the British National Formulary includes information on off-label use of medicines.

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| advances in treatment of respiratory diseases |

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| advances in treatment of respiratory diseases |

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Forging advances in the treatment of

respiratory diseases In this issue of BioScience Today, we speak to Professor Martin Gosling, about the inspiration behind his work, what motivates him daily, and the advances in the treatment of respiratory diseases that he is working to bring about.

Martin is Professor of Molecular Pharmacology at the University of Sussex and Chief Scientific Officer at Enterprise Therapeutics.

“As a child, I always found science interesting. My mother was a pharmacy technician and she’d talk to me about her work, which I found fascinating. For good or for bad, I always wanted to know how things worked.

“Spending a year working in the pharmaceutical industry before I went to university was a turning point and I knew then that developing new treatments that would benefit people was my ambition. Research that was translational rather than purely academic was what I wanted to focus on, developing drug treatments that could make a difference – so I read pharmacology at university.

“The action of drugs on physiological systems has always interested me and I soon found my niche researching ion channels – which I focused on for my PhD studies.

Expressed by every cell of the body, ion channels are discrete holes in the membranes of cells that allow the flow of ions such as chloride and potassium into and out of cells. They are involved in many cellular processes such as nerve conduction and muscle contraction, and as such ion channels have long been explored as a conduit for new drug treatments.

“I researched the role of ion channels in bone cells for my doctorate and later I researched the role they play in blood vessels. In 2001, I joined Novartis specifically to research respiratory diseases - now nearly 20 years later, I’m looking

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at how ion channels could be used therapeutically to deliver new treatments for respiratory diseases including cystic fibrosis. I moved back into academia, joining the University of Sussex not long after Novartis moved their respiratory research centre to the United States.

“Academia can provide more latitude in terms of research area albeit grant funding is highly competitive. Working in the private sector resources may be more plentiful, but you have to put together a very strong commercial case for research to begin, plus companies can change strategic direction very quickly, like when there is a change of leadership for example.

“In the last 15 years drug discovery in the UK has changed dramatically and now very few major pharmaceutical companies have research facilities in the UK, with thousands of jobs which were once here now based abroad.

This has to raise the question of how we train the next generation of drug discovery scientists and where talented UK scientists will progress their careers.

“At the same time, the model of research and development has changed dramatically and many smaller biotech companies are taking up the reins, but they simply don’t have the resources to train Continued on page 52 

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| advances in treatment of respiratory diseases |

“Our drug discovery research is entirely focused on respiratory diseases; with the hope of improving the quality of life, and reduce the susceptibility to infections of those with cystic fibrosis, asthma and chronic obstructive pulmonary disease (COPD). We are working on new disease-modifying therapies with the aim of targeting the underlying mechanisms of mucus congestion.”

Professor Martin Gosling

 Continued from page 50 as many scientists as the large pharmaceuticals firms once did. At Novartis, for example, we had 15 apprenticeship places within the respiratory disease group alone, all of whom were studying for a degree part-time too.

“Before I returned to academia, I co-founded a biotech start-up, Enterprise Therapeutics, along with two former colleagues from Novartis, enabling me to carry out precisely the research that I wanted to. Ion channels had become much more tangible and feasible drug targets and were once again the focus of my research.

“Our biotech company is based at the university, within the Sussex Innovation Centre, and it is really beneficial to be working within a renowned research facility and to have such a close working relationship with the School of Life Sciences. Some of the postdoctoral research scientists from the university come and work with us too, so together we are doing our best to nurture the next generation of scientists.

“Our drug discovery research is entirely focused on respiratory diseases; with the hope of improving the quality of life, and reduce the susceptibility to infections of those with cystic fibrosis, asthma and chronic obstructive pulmonary disease (COPD). We are working on new disease-modifying therapies with the aim of targeting the underlying mechanisms of mucus congestion.

“Mucus is a key part of the lung’s defence system, catching harmful particles and moving them up to the top of your lungs, thence to your stomach so they can be destroyed.

Ideally, this mucus is a low viscosity gel of about 3% solids and 97% water. However, if there is too much mucus or too little fluid, it becomes sticky and can plug the airways.

Patients with cystic fibrosis typically have mucus that is 15% solids; this causes their airways to become blocked and harmful pathogens, such as bacteria, are no longer cleared leading to infections and destruction of the lung.

“Though the genetic reason for cystic fibrosis was identified back in 1989, it took until 2012 for the first drug to be registered that addressed that genetic defect (Kalydeco).

We are looking to tackle this and other respiratory diseases with two strategies. The first is to exploit the activity of ion channels that control the amount of fluid in the airways –

this approach will increase airway hydration, reduce the stickiness of the mucus and make it easier to clear.

“We have discovery programs to find drugs which switch on the activity of a chloride channel (TMEM16A) and also to switch off the activity of a sodium channel (ENaC) in the lung – both effects will increase the amount of fluid available to thin mucus. Our second strategy is to reduce the number of mucus-producing cells, complementing these mucus hydration therapies,” explains Martin.

“The challenge in pharmacology is finding a drug that does what you want it to do and ideally only what you want it to do. You know what your target is, but finding the right molecule, that is the difficult part. You can look at hundreds of thousands of compounds to find a chemical starting point to switch your target on or off and that is precisely what we are working on now.”

To put this research into perspective, there are an estimated 70,000 patients worldwide with cystic fibrosis, and though their life expectancy is improving, it is currently around 40 years. COPD is reported to affect over 300 million people in 2012 alone it was the world’s third highest killer and the estimated economic cost of COPD is in excess of $2 trillion.

In addition, there are an estimated 300 million asthma patients globally, of whom, 5% are classed as suffering from severe asthma, which is either refractory or poorly managed by current therapies (bronchodilators, steroids).

The novel therapies being explored by Martin and his colleagues are at an early stage, but these statistics show just how important research in this area is and what a huge impact, such research, could potentially have worldwide.

Enterprise Therapeutics has recently attracted £29 million in funding from an international consortium of top-tier venture capital investors to help develop these new drug therapies and fight respiratory diseases. The investment syndicate includes Versant Ventures, the Novartis Venture Fund, Forbion, Epidarex Capital and IP Group.

It is good to know the work of Martin and his colleagues has been given a huge vote of confidence and that hope is on the horizon for the development of new treatments for respiratory diseases.

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COPD IS REPORTED TO AFFECT OVER 300 MILLION PEOPLE - IN 2012 ALONE IT WAS THE WORLD’S THIRD HIGHEST KILLER AND THE ESTIMATED ECONOMIC COST OF COPD IS IN EXCESS OF $2 TRILLION.

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| news |

Activity the key to optimising stroke recovery Emphasising the importance of sustained rehabilitation can help health services cope with rising numbers of people surviving a stroke, a University of Dundee expert has said.

Dr Jacqui Morris, Reader in Rehabilitation Research at the University’s School of Nursing and Health Sciences, said that providing long-lasting support for those living with the aftermath of the condition is now more essential than ever.

It comes as Dundee prepares to welcome delegates attending the annual conference of the Scottish Stroke Allied Health Professions Forum (SSAHPF), which takes place on Wednesday 13 June.

With healthcare researchers and practitioners joining people affected by a stroke for the event, Dr Morris, chair of the SSAHPF, said that the delivery of sustained rehabilitation therapy was crucial for those recovering from the condition.

“Getting people moving and helping them to continue being active is absolutely crucial when they are recovering from a stroke,” she said.

“We have done a lot of research on the barriers people face to being more active, and on what more can be done to improve the effectiveness of rehabilitation therapy, because activity plays a massive role in optimising a patient’s recovery.

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“Some people are also more motivated to participate in physical activity and other types of rehabilitation than others, so we have to develop ways of encouraging them and matching exercise and activity to their interests.”

Around 100,000 people in the UK suffer from a new stroke every year, with a further 1.2 million people living with the consequences of the condition.

What is effectively an attack on the brain when its blood supply is interrupted, stroke can be fatal or disabling, often having a lasting impact on mobility, speech, memory and vision.

Medical advances mean that while more people are surviving a stroke, effective rehabilitation has become even more important to lessen the burden on healthcare services.

Delegates will travel from across Scotland to attend Wednesday’s event in the University’s Dalhousie Building, taking part in a series of discussions and workshops throughout the day.

“As more people live with the after effects of stroke, improving recovery and quality of life for patients is something that we should all be interested in, as this will help to ease the strain on health services,” added Dr Morris.

“Events such as this are a great way to share our research and influence how the healthcare sector can adapt to these future challenges.”

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| BIOSCIENCE TODAY SEPTEMBER•OCTOBER 2018 |

Stay future-ready: Running parallel operations with a CDMO during clinical trials Bringing a drug candidate through clinical trials is a challenging and high-risk process, since only 10% of candidates actually reach final approval. Both established pharma companies and small startups are often faced with this dilemma: they want to delay capital investment in manufacturing infrastructure on an investigational therapy until there is greater certainty of safety and efficacy, and ultimately approval. However, at the same time they must also plan for success to avoid delaying market entry for the successful candidate. Fortunately, external resources can help you maintain small-batch manufacturing in parallel with clinical trials, develop commercial-scale processes, build physical capacity and upskill internal teams. In this article, I offer tips on how to leverage outside resources to help you cost-effectively and strategically prepare for clinical or commercial manufacturing while you move a new therapy through clinical trials.

TIP #1: PLAN FOR SUCCESS FROM THE OUTSET The first, most immediate manufacturing challenge is securing sufficient supply, or sufficient capacity, for the clinical trials. This may also entail process development work to scale up from lab-scale to small-batch manufacturing. At this point, rather than scale up internal resources, drug developers will often turn to external partners such as contract development and manufacturing organizations (CDMOs) for supplemental capabilities and capacity. As clinical trials progress through Phases II and III, biopharma companies will need increasingly large quantities of the drug. A CDMO has built flexibility for this into their business model and their physical facility and has worked through this process many times.

Particularly for a young company that does not have established partnerships in place, selection of a CDMO will be one of the most critical decisions they have yet faced.

While your immediate objective is to obtain a supply of your drug candidate for clinical trials, keep an eye to the future,

as well. If your drug candidate is successful, the journey from clinical trials to market will be lengthy, and your needs will evolve along the way. Using the best-case scenario when selecting your CDMO can help you avoid costly stops-andstarts and mis-matches down the road. Ideally, a CDMO is not just a service provider, but a partner and collaborator in the clinical trial journey.

TIP #2: WORK IN PARALLEL WITH A CDMO TO DELAY CAPITAL INVESTMENT As Phase III clinical trials progress, and there are good indications of efficacy, the probability of regulatory approval increases. This triggers some of the trickiest and most critical timing decisions: when and how to proceed to commercial-scale manufacturing. Process development to scale up the manufacture is itself a major project with significant cost, but the bet-your-business decision is when and how to invest in manufacturing capacity.

Most companies do not have idle capacity, and they will want to delay this major investment as long as possible.

Trial results and regulatory approval provide certainty as well as a clearer picture of the market, making it easier to secure financing for the capital investment required to build manufacturing capacity. Delaying investment, however, can also delay market entry, which can result in smaller market share in a competitive market. Again, a CDMO can fill the gap with biomanufacturing capabilities, enabling a biopharma organization to enter the market while building out manufacturing capacity in parallel.

TIP #3: CAPACITY ISN’T JUST ABOUT CAPACITY. PAY ATTENTION TO THE HOW. If your CDMO can reliably supply your clinical trials, and can scale up quickly when regulatory approval is achieved, does it matter how they do it? In a word, yes.

Shepherding a drug through clinical trials and bringing

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| clinical trials |

it to market involves several complex transitions before a steady state is achieved. There are at least two process development steps along the way: the first when scaling up from laboratory scale to small-batch manufacturing, and the second when scaling up to commercial manufacturing.

One way to drive risk and complexity out of these transitions is to use the same type of equipment across the manufacturing environment, from small batch to commercial scale. While cells may notoriously behave differently at different scale, even in a similar type of bioreactor, utilizing similar equipment will nevertheless minimize the variations and complexity.

TIP #4: ALIGN MANUFACTURING METHODS AND SYSTEMS The final, and perhaps most sensitive, transition will be bringing your manufacturing operations in-house. This transition will be much easier if you have planned in advance for infrastructure alignment and staff training.

Matching your biomanufacturing equipment to that of your CDMO’s plant will save both time and money by eliminating a process development step. While you will still need to validate your new process train, you can be confident that the process itself can be transferred oneto-one. Working with a CDMO that can train up your staff will further facilitate a smooth transfer. Failure to plan for this from the outset can add time, cost and unnecessary risk to your manufacturing operations start-up. Alignment of manufacturing methods and systems with your CDMO will have an additional benefit: potential supplemental manufacturing capacity should the need arise.

TIP #5: LEVERAGE INDUSTRY KNOWLEDGE AND EXPERIENCE TO NAVIGATE GLOBAL MARKETS AND REQUIREMENTS When initiating clinical trials you may be focused on pilot studies that are locally implemented, but as the likelihood of approval increases you will also want to take into account global considerations. A supplier or CDMO with a global presence can be invaluable, helping ensure that your

process is up to snuff on regulatory requirements in your intended markets. For example, China, a large and rapidly emerging market, has very specific requirements regarding data from foreign clinical trials. Though they have recently streamlined their approval process in order to accelerate new drug approvals, the devil is in the details. A supplier or partner with a local presence can bring to the table. A supplier or partner with a local facility can bring to the table not only knowledge of regulatory requirements and processes, but also local contacts, language, and familiarity with local administrative procedures.

When hiring an external partner, you will have a list of capabilities and services that you require, but, just as when hiring an employee, don’t forget the “soft skills.” Trust is paramount. If your drug candidate is successful, you will be working with that partner for years. You will be sharing your most closely-held scientific discoveries and collaborating on multiple technology transfers. As you move into commercial manufacturing, you may lean on that external partner to train your in-house staff and work closely with you as you plan, build and start up a new manufacturing facility or process. The right organization can facilitate these complex transitions and position you for ongoing manufacturing success.

“Matching your biomanufacturing equipment to that of your CDMO’s plant will save both time and money by eliminating a process development step.”

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| clinical trials |

Virtual Me | BIOSCIENCE TODAY SEPTEMBER•OCTOBER 2018 |

Study provides first evidence that psychological therapy can be successfully delivered automatically in virtual reality (VR)

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Medicine | BIOSCIENCE TODAY SEPTEMBER•OCTOBER 2018 |

The Lancet Psychiatry has just published details of a pioneering clinical trial of automated virtual reality (VR) psychological therapy for fear of heights.

Fear of heights is a significant problem for one in five people at some point in their lives, and most never receive treatment. Although VR has been used in the past for phobias, it has always required a therapist to guide the user through the treatment. Now a team led

by Professor Daniel Freeman from the University of Oxford’s Department of Psychiatry has developed a VR programme in which psychological therapy is delivered by a computer-generated virtual coach. Treatment is personalised, with users able to interact with the virtual coach using voice recognition technology.

In one of the largest ever randomised controlled trials of fear of heights treatments, one hundred people with a fear of heights were randomly allocated to the VR therapy or to no treatment. Participants had on average lived with a fear of heights for 30 years. Those who received the therapy spent an average of two hours in VR over five treatment sessions. All participants in the VR group showed a reduction in fear of heights, with the average reduction being 68.0%. Half of the participants in the VR group had a reduction in fear of heights by over three quarters. These results are better than those expected with the best psychological intervention delivered face to face with a therapist.

Professor Freeman’s VR therapy, which was produced by the University of Oxford spinout Oxford VR and tested in association with the NIHR Oxford Health Biomedical Research Centre, took users wearing an HTC Vive headset to a computer-generated ten-storey office building. Guided by Nic, the virtual coach, users undertook a series of activities, which increased in difficulty the higher they went.

Professor Freeman said: “We designed the treatment to be as imaginative, entertaining, and easy to navigate as possible. So the tasks the participants were asked to complete included crossing a rickety walkway, rescuing a cat from a tree in the building’s atrium, painting a picture and playing a xylophone on the edge of a balcony, and finally riding a virtual whale around the atrium space!”

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Professor Freeman, who is also a clinical psychologist in Oxford Health NHS Foundation Trust, said: “The results are extraordinarily good. We were confident the treatment would prove effective, but the outcomes exceeded our expectations. Over three quarters of the participants receiving the VR treatments showed at least a halving of their fear of heights. Our study demonstrates that virtual reality can be an extremely powerful means to deliver psychological therapy. We know that the most effective treatments are active: patients go into the situations they find difficult and practise more helpful ways of thinking and behaving.

This is often impractical in face-to-face therapy, but easily done in VR.” He continued: “When VR is done properly, the experience triggers the same psychological and physiological reactions as real-life situations. And that means that what people learn from the VR therapy can help them in the real world.”

Users were enthusiastic about the treatment. Sarah commented: “What I’m noticing is that in day-to-day life I’m much less averse to edges, and steps, and heights, and I’m noticing in myself that when I’m doing the VR and out in the real-world I’m able to say hello to the edge instead of bracing against it and backing up. I feel as if I’m making enormous progress.”

Nico said: “It’s absolutely brilliant, honestly, I do think it’s made a huge difference. Everything I thought it was going to be, it wasn’t. I anticipated it was just going to be like a game, it was going to be something that wasn’t going to arouse my senses. I found myself even after the third floor, fourth floor, going up, feeling nervous, anxious about what’s about to happen next. It definitely pushed the limits in terms of what I thought I would be able to achieve, and then got me to go past that.”

Maurice said: “Last week, after my third session, I went up to Westgate [shopping centre]; the difference in my mental capacity to deal with heights was amazing.

Previously I wouldn’t go anywhere near the edges, I was almost hanging right off, looking vertically down.

The sessions I’ve had here have given me a lot to think about, and certainly with regards to my fear of heights it feels like it’s helped a lot.”

Professor Freeman commented: “The advent of consumer VR equipment means that automated treatment can potentially be made available to millions. But what’s even more exciting is the prospect of using VR to tackle serious and widespread mental health problems, such as depression, psychosis, and addictions. Rigorous testing will be vital but it feels as though we may be looking at a big part of the future of mental health treatments.”

| clinical trials |

| BIOSCIENCE TODAY SEPTEMBER•OCTOBER 2018 |

Gene therapy applications in medicine Over the last few decades advances in genetics and more recently gene therapy have accelerated. Not only have they been used in vitro and animal models but now the initial studies in humans and larger mammals are starting to be published. These applications present many complex ideas which must be solved before successful use. The decisions of which genes to use or target, the delivery methods, fully understanding the disorders, disease or injuries and working out the mechanisms of action of the therapy itself once trials are underway. In addition to understanding the background science the clinical trials must be carefully applied and compared to the most recent treatments available.

tissue in the horse. Their approach was design a dual expression cassette plasmid DNA (pDNA) containing equine vascular endothelial growth factor A (VEGFA164) and basic fibroblast growth factor (FGF2) sequences.

These were under the control of the eukaryotic promoters EF-1alpha and CMV. VEGF is known to stimulate DNA synthesis and cell proliferation, is involved in angiogenesis and attracts endothelial progenitor cells in addition to stabilising blood vessels. VEGF also attracts macrophages, monocytes, smooth muscle cells and granulocytes which are necessary for wound healing and increases vascular permeability following wounding. In turn FGF2 is mitogenic and is also involved in angiogenesis, helps to develop connective tissue and is involved with wound healing and stimulates cell proliferation. The authors concluded that all of these factors would assist with tissue regeneration and repair in cases of torn ligaments and tendons in equine lameness.

Lameness in horses, and other animals, presents a significant problem. Not only is it a very commonly occurring problem, it also causes significant pain, is presently difficult to treat and even successful treatment can be short lived with high levels of relapse. This was what Professor Albert Rizvanov set out to investigate when starting the gene therapy programme at Kazan Federal University. The type of lameness was related to torn tendons and ligaments, which is a problem seen in many conditions in humans and animals throughout the body. In addition his work set out to investigate a type of gene therapy which could be adapted to help conditions in all parts of the body ranging from reproductive issues through to spinal problems.

The plasmid construct pBUDK-ecVEGF164-ecFGF2 was generated on the base of pBudCE4.1 in line with recommendations given by the US Food and Drug Administration (FDA), the European Medicine Agency (EMA) and the ‘Content and Review of Chemistry, Manufacturing, and Control (CMC) gene therapy documents. Their initial paper describes not only how this was designed and created but also how it was tested in vitro (Litvin et al., 2016). The recombinant plasmid was sequenced, underwent restriction analysis and gel electrophoresis of the restriction fragments. HEK293FT cells were transfected. Fluorescence immunohistochemistry and western blot analysis showed expression of VEGFA164 and FGF2.

Professor Rizvanov, his research team and collaborators started their work by developing a plasmid gene delivery system which would help regenerate ligament and tendon

Once this plasmid construct had been created the team worked to start using it in naturally occurring equine cases of tendon and ligament injuries. Their results represented

Catrin S Rutland, Albert A Rizvanov and Milomir Kovac

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VEGF IS KNOWN TO STIMULATE DNA SYNTHESIS AND CELL PROLIFERATION, IS INVOLVED IN ANGIOGENESIS AND ATTRACTS ENDOTHELIAL PROGENITOR CELLS IN ADDITION TO STABILISING BLOOD VESSELS.

| BIOSCIENCE TODAY SEPTEMBER•OCTOBER 2018 |

Catrin Rutland BSc PGCHE MSc MMedSci PhD SFHEA FAS Associate Professor in Anatomy and Developmental Genetics

Albert A Rizvanov PhD Dr. Sci (habitation) Professor, Kazan Federal University.

Milomir Kovac DVM MSc PhD Specialist equine surgeon and Professor honoris causa at Moscow State Academy.

| clinical trials |

the first successful trial of gene therapy in equine lameness.

The plasmid DNA was injected directly into the torn ligament/tendon tissue. In this case the suspensory ligament branch and the superficial digital flexor tendon as these represent the most common and serious injuries in horses. Ligament healing is also made more complex by the formation of scar tissue, in these cases type III collagen formation is problematic. In normal tendons type III collagen comprises around 5% of the tissue but in scar tissue this can increase to 30% and in turn reduce elasticity and strength which means that the injury is more likely to reoccur.

Alongside an appropriate exercise rehabilitation plan the results from the trial in injured horses (Kovac et al., 2017) showed that tissue regeneration occurred. The treatment also worked quickly (2-3 months) with complete functionality restored to the animals. Throughout the follow up period of 12 months both horses returned to their pre-injury exercise levels and neither suffered from relapse. It was also noted that scar tissue did not form at the sites of injury and neither horses had negative side effects from the treatment. Conventional therapies often result in tissue scarring and therefore relapse rates upon resuming exercise can be high (up to 60% in some cases).

Regenerative medicine techniques can take 4-6 months for restoration but relapse rates drop to around 20%. It should be noted that many of these studies are in high workload animals such as racehorses, therefore differing conditions and workloads must be considered.

Nearly a year later the collaborative team from Kazan Federal University, Moscow State University and University of Nottingham have published the results from a larger study containing ten injured horses (Kovac et al., 2018) and the results support the first study. Eight of the ten horses made a full clinical recovery. The ninth horse showed full tissue regeneration but sustained an unrelated injury to another limb and therefore could not be described as not lame. The tenth horse the lameness did not significantly improve as the tissue did not fully regenerate back to pre-injury levels. On average the other eight horses saw successful tissue regeneration within just 20 days. The levels of injury and lameness affected the speed of recovery. All of the horses resumed their pre-injury activities and level of fitness/competition. One horse showed a slight reaction (swelling) at the site of infection which subsided quickly and none of the other horses showed negative side effects.

A combination of veterinary examinations, ultrasound and colour Doppler ultrasonography was used to assess the outcomes. In addition own opinion on pre-injury and posttreatment fitness was sought.

In addition to looking at tissue repair and lameness levels, the team saw that blood vessels developed following

Milomir Kovac DVM MSc PhD injection with the species-specific plasmid construct but then regressed following tissue regeneration. In addition scar tissue was not present in the treated areas.

This research represents a significant advancement in regenerative medicine and gene therapy. By understanding the mechanisms of action and the process of healing the team have created a gene therapy which is very promising. They recently wrote an editorial on gene therapy, regenerative medicine and some of the factors which must be considered when considering this as a therapeutic medicine (Rizvanov et al., 2018). In addition they have also carried out similar work in a veterinary case in a tear present in a canine cruciate ligament (Zakirova et al., 2014). Whilst this represents exciting research the authors acknowledge that more studies are required before this gene therapy can be used in medical practice. In addition training would be required for clinicians who will use these technologies. It is also hoped that as veterinary and human gene therapy treatments progress, the information can be used to improve clinical efficacy and outcomes.

The work in these studies was funded by a Program of Competitive Growth of Kazan Federal University and subsidy allocated to Kazan Federal University for the state assignment in the sphere of scientific activities 20.5175.2017/6.7, The Ministry of Education (RFMEFI59414X0003), Interdisciplinary Center for Analytical Microscopy, Pharmaceutical Research and Education Center, Kazan.

“Lameness in horses, and other animals, presents a significant problem. Not only is it a very commonly occurring problem, it also causes significant pain, is presently difficult to treat and even successful treatment can be short lived with high levels of relapse.”

Kovac, M., Litvin, Y., Aliev, R. O., Zakirova, E., Rutland, C. S., Kiyasov, A. P., and Rizvanov, A. A. (2018). Gene Therapy Using Plasmid DNA Encoding VEGF164 and FGF2 Genes: A Novel Treatment of Naturally Occurring Tendinitis and Desmitis in Horses. Frontiers in Pharmacology, 9, 978. doi: 10.3389/ fphar.2018.00978 Kovac, M., Litvin, Y. A., Aliev, R. O., Zakirova, E. Y., Rutland, C. S., Kiyasov, A. P., and Albert A Rizvanov. (2017). Gene therapy using plasmid DNA encoding vascular endothelial growth factor 164 and fibroblast growth factor 2 genes

for the treatment of Horse Tendinitis and Desmitis: case reports. Front. Vet. Sci. 4:168. doi: 10.3389/fvets.2017.00168 Litvin, Y. A., Zakirova, E. Y., Zhuravleva, M. N., and Rizvanov, A. A. (2016).

Generation of plasmid DNA expressing species-specific horse VEGF164 and FGF2 factors for gene therapy. Bionanoscience 6, 550–553. doi: 10.1007/ s12668-016-0273-2 Rizvanov, A. A., Kovac, M., and Rutland, C. S. (2018). Advancing modern equine medicine using gene therapy. Equine Vet. Educ. doi: 10.1111/eve.12912

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Zakirova, E. Y., Vasin, N. N., Zhuravleva, M. N., and Rizvanov, A. A. (2014).

Case report of application gene construction with VEGF and BMP2 in restoration of tear in the anterior cruciate ligament of a large breed dog.

Genes Cells 9, 93–95.

For updates on the research a dedicated Twitter (@KFU_UoNResearch), Facebook (KFUUoNResearch) and a website (https://www.kfuuonresearch. com) are available.

| gastrointestinal disorders |

| BIOSCIENCE TODAY SEPTEMBER•OCTOBER 2018 |

Engaging the

patient as Ceciel T. Rooker, President, IFFGD There is growing recognition in the research community of the role of the patient as partner – not only in the outcomes of medical research, but in its practice, as well. As a meeting place for all stakeholders – investigators, drug developers and manufacturers, governmental agencies, and patients and their families – patient advocacy organizations like the International Foundation for Gastrointestinal Disorders (IFFGD) are uniquely positioned to facilitate patient involvement in research.

Additionally, bringing together and concentrating the perspectives of patients, IFFGD partners with investigators on research that can uncover real-world treatment solutions that meet patients’ real-life needs. By activating patient voices in research and elevating patient perspectives through research undertaken by IFFGD, we strengthen the patient/researcher partnership and pave the way for collaborations that lead to a greater understanding of how patients experience their condition and treatments that address their needs and, ultimately, improve outcomes.

As the role of the patient as an active member of their health care team and an equal partner in their own personal health care decisions is increasingly realized, the potential for patients to contribute to the design and practice of research that furthers the development of real-world solutions is also gaining momentum. This is evident in the development of health-related quality of life (HRQOL) instruments, increasing use of patient-reported outcome (PRO) measures in clinical trials, and expanding opportunities to participate in clinical research, drug approval, and health policy decisions through government-supported initiatives such as the INVOLVE program in the U.K.; the three year Patient Partner initiative funded by the European Commission; and the U.S. Food and Drug Administration’s five year PatientFocused Drug Development Initiative (PFDDI).

of the patient in research has encouraged investigators, regulators, and drug developers to look at patients, and thus, clinical trials, differently. For example, inclusion of patient insights into their own health experiences and care preferences challenged the traditional concept of the patient as “subject” – as a passive entity on whom treatments are performed. Patients exert considerable control over their own personal care and, subsequently, over treatment outcomes. From drug adherence to health care selection, patients determine for themselves how they will be treated. This observation has led to greater emphasis on shared decision making and improved patient-doctor communication in clinical settings, and has encouraged drug developers to address treatment burden and treatment fatigue to improve adherence by the patient.

Insights gathered from patients about their lived experiences and goals for treatment can help researchers identify and address unmet needs, the balance of treatment risks and benefits, treatment burden and fatigue, and the symptoms most needed to treat to improve quality of life. By partnering with researchers and drug developers, patients help shape clinical development to meet their real-world needs based on real-life experiences, shifting the research and drug development process from one directed by sponsors or investigators to one informed by patients.

I, THE PATIENT For functional gastrointestinal disorders (FGIDs), the involvement of the patient experience and perspective in research is especially critical.

FGIDs describe a group of chronic and often disabling conditions characterized by the lack of objective measures of disease. The absence of diagnosing tests or biomarkers complicates and often prolongs diagnosis and appropriate treatment. As a result, those affected often suffer for years or even decades before obtaining an accurate diagnosis and the legitimization that comes with it. During this ‘diagnostic journey’ patients commonly endure one or more misdiagnoses and numerous hospitalizations and investigations in their quest for answers. This experience often leaves patients and their families to piece together the limited information available to them on their own, with many patients resorting to self-treatment.

Despite the logistical (and sometimes existential) challenges that have emerged in the process, greater involvement

Continued on page 63

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

| BIOSCIENCE TODAY SEPTEMBER•OCTOBER 2018 |

| gastrointestinal | what disorders is life? |

s partner “Insights gathered from patients about their lived experiences and goals for treatment can help researchers identify and address unmet needs, the balance of treatment risks and benefits, treatment burden and fatigue, and the symptoms most needed to treat to improve quality of life.”

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| gastrointestinal disorders |

| BIOSCIENCE TODAY SEPTEMBER•OCTOBER 2018 |

 Continued from page 60 This was my own experience with a functional gastrointestinal disorder. As a young adult, I was diagnosed with irritable bowel syndrome (IBS), a highly prevalent but then understudied and misunderstood FGID. I underwent extensive testing and workups for many years in a costly and, ultimately, fruitless effort to discover what was causing my symptoms and how to treat them. Eventually, I ended up as many patients do: self-treating as best as I could and trying to teach myself how to “just live” with my illness.

Since becoming president of IFFGD, I have heard my story echoed back to me by thousands of others.

Founded in 1991 by a single person struggling with the challenges posed by a FGID, IFFGD works to support and assist patients around the world affected by FGIDs and other chronic digestive conditions. We do this by raising global awareness of the burden these conditions pose and drawing attention to the unmet needs of those affected, by supporting and encouraging research that will improve outcomes, and by meeting the information needs of patients and their families. And, critically, recognizing the value patients bring to the research process, we work to empower patients to take an active role in shaping the future of the care and treatment of these conditions.

PUTTING PARTNERSHIPS IN PRACTICE: THE ROLE OF PATIENT ADVOCACY ORGANIZATIONS While symptom severity often guides clinical decision making in the diagnosis and treatment of disease, it is an understudied measure and is often replaced by the easierto-assess disease severity, which looks at the presence and extensiveness of a disease in the body. But, in the case of the FGID patient, whose illness burden is not associated with any observable disease, this metric cannot effectively describe their severity.

So, how do researchers measure severity?

For those with IBS, severity doesn’t mean how much disease is present, but how much their daily life has been impacted.

IBS is a highly prevalent digestive disorder characterized by recurring or chronic bouts of abdominal pain in association with a change in bowel habit (such as diarrhea or constipation). Symptoms of IBS can flare-up unexpectedly and can change over time or even from day to day. Other symptoms may also occur, such as bloating, gas, or urgency.

While no objective markers of disease exist, the symptoms, coupled with the uncertainty and fluctuation of symptoms, can significantly impair the quality of life of those affected.

Complicating this, bowel symptoms present unique difficulties for those affected and can mean a disruption to self-image, personal relationships, levels of intimacy, and ability to navigate work and school environments.

To capture the IBS lived experience and translate it into an instrument that could be used to quantify severity in clinical studies, IFFGD partnered on a research study with the Rome Foundation (https://theromefoundation.org/), the international non-profit organization responsible for developing the Rome Criteria – a set of symptom-based criteria used by clinicians to diagnose FGIDs like IBS. By involving the patient perspective through a series of focus groups that examined the symptoms experienced in IBS and factors contributing to self-perceived severity, we learned the following: Consistent with previous observations, IBS symptom severity was found to be multidimensional and is informed by factors such as IBS symptoms, HRQOL, health care utilization, disability due to symptoms, extra-intestinal symptoms, resistance to treatment (refractoriness), and the patient’s own thoughts about his or her severity.

IBS was not only described in terms of symptoms (predominantly abdominal pain) but also as it affects daily functions, including uncertainty and unpredictability of symptoms; thoughts and feelings, such as fearfulness, shame, and embarrassment; and behaviors, including avoidance of activities perceived to worsen symptoms and adaptation behaviors.

Perceptions of social stigma and a lack of understanding from family, friends, and physicians of the effects of IBS on the patient and the legitimacy of his or her feelings or health-related behaviors also contributed to severity.

This study – a collaboration between a patient-driven organization and one that is made up of researchers and clinicians – illustrates how strong patient-researcher partnerships can support research that leads to a better understanding of the patient – his or her illness experience and treatment needs. By elevating the role of the patient perspective in research, patient advocacy organizations like IFFGD can help investigators and drug developers identify knowledge gaps and develop clinical solutions that are supported by a deeper understanding of the real-world needs of patients. Partnering together, we can engage in research that asks the right questions for the patient – questions that will ultimately inform the development of treatments that improve outcomes.

For a chronic and often unpredictable illness like IBS, understanding how the everyday lives of those affected have been impacted is central to understanding their needs and developing treatments that address those needs. But, this can only be accomplished through the involvement of the patients themselves. Focusing on questions that highlighted the daily challenges patients with IBS face and how these challenges contribute to their burden of illness, research undertaken by IFFGD and the Rome Foundation described how severity is experienced by patients with IBS and provided the foundation for the development of health status and severity instruments for clinical research. Thus, by bringing a patient-focused perspective to the research process, patient advocacy organizations help researchers and drug developers peel back the layers of the patient experience to uncover unmet needs and identify research priorities.

As a patient myself, hearing from other patients about their illness journey and treatment needs has helped me to better understand my own needs and has strengthened my commitment to growing collaborative research partnerships that encourage patient-focused solutions. Partnering with patients, investigators, and drug developers, we can engage in research that addresses the real-life needs of patients and leads to better outcomes. www.iffgd.org

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| BIOSCIENCE TODAY SEPTEMBER•OCTOBER 2018 |

| gastrointestinal disorders |

Europe is “failing” to deal with chronic digestive disease burden Europe is currently failing to manage the increasing burden inflicted by chronic digestive diseases, according to leading digestive health experts.

A report1, published today during the launch of MEP Digestive Health Group, reveals alarming issues, challenges and inequalities in a range of chronic digestive-related diseases, including digestive cancers, alcohol-related digestive diseases, paediatric digestive diseases and functional gastrointestinal (GI) disorders. Upon reviewing the latest statistics from across the continent and canvassing the opinions of both policymakers and scientific experts, the report reveals: 59% of men and 45% of women in the EU aged 18 and above are overweight Digestive cancers represent 28% of all cancer-related deaths in the EU (365,000 deaths) One in four deaths from gastrointestinal diseases are directly attributed to alcohol Inflammatory bowel disease diagnosis can commonly take up to five years The five most common digestive cancers – colorectal, gastric, pancreatic, liver and oesophageal cancer – are responsible for over 590,000 cases each year in the EU. If current population trends continue, the number of deaths from these cancers across the EU per year will increase by over 40% by 2035. Approximately half of all cancers are preventable and their significant burden could be reduced by addressing lifestyle factors, such as rising levels of obesity and heavy alcohol consumption. Obesity, for example, is quickly overtaking tobacco as a health risk and is the leading preventable cause of cancer and substantially threatens the sustainability of public healthcare systems.

In addition to the threat posed from digestive cancers and obesity, experts are also warning of the socioeconomic burden inflicted by functional GI disorders, such as irritable bowel syndrome (IBS) and constipation. Functional GI disorders are common conditions that can be extremely disabling for patients, yet sufferers often do not consult their physician about their symptoms.

They are associated with educational and occupational absenteeism, imposing high costs to society, and are expensive to treat and manage. Treating IBS in Germany alone, for example, is estimated to cost over € 3.2 billion per year.

Professor Markus Peck, of United European Gastroenterology, which represents over 22,000 digestive health specialists, comments, “The impact inflicted by digestive diseases continues to increase

63

across Europe. With chronic digestive diseases, our society fails and the burden is only going to become greater.

We’re seeing notable increases in the incidence of most gastrointestinal disorders, from digestive cancers to liver disease. The current outlook for young people’s health, for example, is extremely alarming, with childhood obesity rates expected to almost double by 2025.”

Current predictions, trends and attitudes demonstrate that the challenge presented by obesity, heavy alcohol consumption and poor nutritional choices is increasing and urgent action is required to reduce this burden and improve health outcomes in generations to come.

To address this difficult challenge, policymakers and digestive health experts will meet today in the European Parliament to inaugurate the MEP Digestive Health Group. The group’s overarching mission is to ensure that continually improving digestive health becomes and remains an integral part of the EU health agenda, serving as a platform of exchange between the scientific community and policymakers.

“Rising obesity levels, functional GI-disorders and heavy alcohol consumption across Europe have major implications for future healthcare provision and it is essential that these largely preventable issues are tackled through health policy and action” adds Professor Peck.

“United European Gastroenterology welcome the MEP Digestive Health Group and look forward to close collaboration in achieving the mission of tackling the burden of chronic digestive diseases across Europe.”

| BIOSCIENCE TODAY SEPTEMBER•OCTOBER 2018 |

Air Cargo Safe and Cool with IATA standards

The International Air Transport Association (IATA) is the industry’s global trade association and represents some 290 airlines comprising 82% of global air traffic. Its mission is to represent, lead and serve the air transport industry. Air cargo is essential to many facets of modern life. The pharmaceutical industry relies on air transport for its speed and efficiency in transporting high-value, time and temperature sensitive cargo.

The healthcare industry is increasingly using monitoring systems, which may be placed in individual packages, to track the temperature or other parameters of the product throughout its journey across the whole distribution chain.

These track and trace devices, such as electronic temperature data loggers are used on or in passive packages. Different types of active transmitting devices with advanced monitoring and tracing real time functionalities are also available on the market. It is important to understand that temperature monitoring devices containing lithium cells or batteries (commonly lithium metal cells/batteries) are classified as dangerous goods in air transport. Lithium batteries represent a significant safety concern. Incorrectly manufactured and/or tested lithium batteries pose a fire risk in transport.

Subsection 38.3 of the UN Manual of Tests and Criteria.

Transporting lithium cells and batteries or lithium battery powered equipment is complex, but the following information and other guidance provided by IATA will assist stakeholders involved in supply chain to be fully compliant.

HOW TO IDENTIFY IF LITHIUM CELLS OR BATTERIES ARE DANGEROUS GOODS AND HOW TO PACK THEM? The extent to which the lithium cells or batteries are regulated as dangerous goods depends on: (a) the lithium metal content for lithium metal cells or batteries; or (b) the Watt-hour (Wh) rating for lithium ion cells or batteries.

Packages containing lithium batteries installed in equipment such as a data logger must bear the lithium battery mark as shown in Figure 7.1.C of the IATA DGR, see Figure 1.

IATA DANGEROUS GOODS REGULATIONS (DGR) All lithium batteries must be transported in accordance with the provisions set out in the IATA Dangerous Goods Regulations (DGR) for air transport, which are based on the ICAO Technical Instructions for the Safe Transport of Dangerous Goods by Air (Technical Instructions). IATA also produces the Lithium Battery Shipping Guidelines (LBSG), a guidance document assisting the industry step by step throughout the shipping process. The LBSG also demonstrate how to safely and efficiently prepare lithium battery shipments in compliance with international air transport regulations. The LBSG provides all the relevant content from the DGR with additional classification flowcharts and detailed packing and documentation examples specifically for lithium batteries.

SUPPORTING THE SAFE TRANSPORTATION OF LITHIUM BATTERIES BY AIR Lithium cells and batteries are classified as dangerous goods and can pose a safety risk if not prepared and shipped in compliance with the applicable provisions of the DGR when transported by air. This applies regardless of whether the lithium cells or batteries are shipped as cargo in their own right or whether the lithium cells or batteries are installed in a small device such as a data logger that is placed inside or attached to packages of cargo. In addition, to be permitted in transport all lithium cell and battery types must have passed the applicable tests set out in

EXCEPTIONS: 1. the lithium battery mark is not required on packages where the data loggers are powered by only button (coin) cells (regardless of the quantity of data loggers in a particular package or the number of packages in a consignment); 2. the lithium battery mark is not required on packages where there are no more than 4 cells or 2 batteries

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| BIOSCIENCE TODAY SEPTEMBER•OCTOBER 2018 |

contained in equipment in each package and there are no more than two packages in the consignment.

Where the packages are of dimensions such that they cannot bear the full size lithium battery mark, the mark dimensions may be reduced to 105 mm wide × 74 mm high.

The design specifications otherwise remain the same.

The lithium battery mark must bear the UN number and a telephone number of a person knowledgeable of the shipment, but is not intended to be for the purposes of obtaining immediate emergency response guidance, and is therefore not required to be monitored at all times while the package is in transit.

Training of employees involved in preparing packages with temperature monitoring devices is key to ensuring full compliance with the regulations. For packages bearing the lithium battery mark, employees must be provided with “adequate instructions”.

The following is offered as a starting point for an employer on what could be considered as being adequate instruction: 1. The employer must identify the different configurations of lithium batteries that they ship, i.e. lithium batteries and/or lithium batteries packed with equipment and/or lithium batteries contained in equipment; lithium metal batteries and/or lithium ion batteries.

2. The employer must document the procedures that apply to the configurations and battery types that they ship as determined in 1, above. IATA Battery Powered Data Logger Guidance Document – 2017V1 APCS/Cargo Page 5 31/01/2017 3. The procedures should be written up as a clear work instructions or other form of information that is available to all employees responsible for the preparation of lithium battery shipments.

4. All employees that are involved in the process of preparing lithium battery shipments must be taken through the procedure to ensure that they understand and can demonstrate the correct application of documented procedures for the packing, labelling, marking and documentations requirements, as applicable to their job function.

5. A record must be maintained that identifies each applicable employee and the date(s) that this instruction was provided.

6. Employees should be given periodic refresher, or at least demonstrate that they remain “adequately” instructed on how to perform the task. This should be done at least every two years or whenever the procedure is revised, or regulations are changed, whichever is sooner.

7. Companies that are involved in reverse logistics, i.e. arranging for returns of lithium batteries, lithium batteries packed with equipment or lithium batteries contained in equipment must develop a clear instruction for consumers on the process to be followed for returning products. This instruction must include packaging materials and lithium battery marks, as necessary. The instruction must also include the transport method and mode of transport to be followed; this must include a clear statement on applicable prohibitions.

CHALLENGES Data loggers and cargo tracking devices have the potential to interfere with aircraft navigation or communication systems since they are designed to remain active throughout their entire transport from the shipper to the consignee, including when on board an aircraft.

Because they cannot be turned off manually in the event of an emergency, the device manufacturers and aircraft operators must ensure certain design and operational

65

considerations are addressed. Areas for consideration include: •

RF radiated emissions limits

•

the device is designed with a minimum of two independent means to turn off completely turn off cellular or mobile functions, or a combination of both when airborne

•

the device must not be capable of generating a dangerous evolution of heat

•

the device must not be capable of emitting disturbing signals, such as buzzing alarms or strobe lights, during transport.

It is recommended that manufacturers of devices that are intended to be placed into, or attached to cargo, make contact with operators in advance so that the approval / authorization can be coordinated. This will avoid the need for multiple individual shippers to seek approval / authorization for the same device.

NEW DEVELOPMENTS Effective 1 January 2020, manufacturers and subsequent distributors of cells or batteries manufactured after 30 June 2003 must make available the test summary as specified in the UN Manual of Tests and Criteria, Part III, sub-section 38.3, paragraph 38.3.5. The test summary must include the following information: Lithium cell or battery test summary in accordance with sub-section 38.3 of Manual of Tests and Criteria The following information shall be provided in this test summary: (a) Name of cell, battery, or product manufacturer, as applicable; (b) Cell, battery, or product manufacturer’s contact information to include address, phone number, email address and website for more information; (c) Name of the test laboratory to include address, phone number, email address and website for more information; (d) A unique test report identification number; (e) Date of test report; (f) Description of cell or battery to include at a minimum: (i) Lithium ion or lithium metal cell or battery; (ii) Mass; (iii) Watt-hour rating, or lithium content; (iv) Physical description of the cell/battery; (v) Model numbers; and (vi) Design types. (g) List of tests conducted and results (i.e., pass/fail); (h) Reference to assembled battery testing requirements, if applicable (i.e. 38.3.3 (f) and 38.3.3 (g)); (i) Reference to the revised edition of the Manual of Tests and Criteria used and to amendments thereto, if any; and (j) Signature with name and title of signatory as an indication of the validity of information provided.

Finally, IATA is working with the industry for the industry.

There will be continuous development of the standards to reinforce IATA’s objective to be the force for value creation and innovation, driving a safe, secure and sustainable air transport industry that connects and enriches our world.

| cleanrooms |

| BIOSCIENCE TODAY SEPTEMBER•OCTOBER 2018 |

Economy Secretary welcomes £4m ICS Clean Room Economy Secretary Ken Skates has welcomed Cardiff University’s new refurbished £4m Institute for Compound Semiconductors Clean Room.

Local business leaders across South Wales attended the launch of the new facility, which offers a range of solutions for companies working to develop 21st century technologies.

Guests were able to learn more about the refurbished 225 square metre Clean Room and the role it plays in assisting businesses across South Wales as part of CS Connected – the world’s first Compound Semiconductor cluster.

The ICS Clean Room, situated in the University’s Queen’s Building, has undergone a £600,000 refit to improve room conditioning in preparation for new equipment.

And in addition to the clean room upgrade, ICS has invested in new equipment to bring a small area to 6-inch fabrication capability online, with support from both the Engineering and Physical Sciences Research Council (EPSRC) and the Welsh Government via European Regional Development Funds totalling £3.3m.

ICS will see further improvements, including state-ofart laboratory space and an increased 8-inch fabrication capability, when it moves into the new Translational Research Facility on Maindy Road – part of Cardiff Innovation Campus.

Economy Secretary, Ken Skates said: “The ICS Clean Room is an outstanding example of a leading edge facility being developed with Welsh Government support. The project

helps to bridge the gap between research and commercial solutions, taking ideas from the lab bench into our boardrooms and on to the shop floors of companies across Wales, so that the economic benefits are felt in communities across Wales. It is encouraging exactly the kind of cutting edge innovation and technology that Wales needs in order to compete globally and thrive.”

Professor Peter Smowton, Director of the Institute of Compound Semiconductors said: “The Institute for Compound Semiconductors (ICS) provides cutting-edge facilities that help researchers and industry work together to translate the science into a commercial production environment and the clean room is a critical part of that.

Many advances in our daily lives depend upon compound semiconductor (CS) technology. The EPSRC funding allows ICS and its partner companies to continue to develop technology that enables emerging trends, such as self-drive vehicles and 5G communications.”

ICS turns its laboratory research into products and services by working with commercial partners to lead in developing one of the world’s key enabling technologies and along with the Compound Semiconductor Centre – a joint business venture with Cardiff-based IQE which forms part of CS Connected.

Clean room manager, Dr Angela Sobiesierski said: “The upgrade and new equipment has transformed the ICS cleanroom into a robust, fit for purpose facility that is well placed to meet the requirements of Academic driven research projects and also meet the demands of our commercial customers and project partners.”

“The ICS Clean Room is an outstanding example of a leading edge facility being developed with Welsh Government support.”

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THE ICS CLEAN ROOM, SITUATED IN THE UNIVERSITY’S QUEEN’S BUILDING, HAS UNDERGONE A £600,000 REFIT TO IMPROVE ROOM CONDITIONING IN PREPARATION FOR NEW EQUIPMENT.

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91

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108

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144.242

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92

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rod

2 8

Ne 20.1797

Cl

32.065

121.76

207.2

2 8 18 32 32 18 3

2 8 18 5

10

Fluorine

Selenium

Sb

83

17

2 7

18.9984032

S

Antimony 2 8 18 32 18 4

2 8 6

F

Sulfur

74.9216

51

9

15.9994

Arsenic 2 8 18 18 4

2 6

Oxygen

P

Lead

Ununtrium

164.93032

Dysprosium 2 8 18 32 27 8 2

Ho

2 8 18 29 8 2

33

Tin

Thallium 2 8 18 32 32 18 2

2 8 18 4

118.71

2 8 18 32 18 3

16

30.973762

72.64

50

2 8 5

O

Phosphorus

Germanium 2 8 18 18 3

8

14.0067

28.0855

204.3833

Mercury

15

Silicon

114.818

81

2 8 4

N

Helium

2 5

Nitrogen

Si

Indium 2 8 18 32 18 2

7

12.0107

69.723

2 8 18 18 2

2 4

Carbon

Gallium

Cadmium

Gold

111

Al

Zinc

196.966569

2 8 18 32 32 17 1

2 8 18 2

65.38

Silver

Platinum 2 8 18 32 32 15 2

2 8 18 1

107.8682

2 8 18 32 17 1

14

10.811

Boron 13

26.9815386

63.546

2 8 18 18

2 8 3

C

Aluminum

Copper

Palladium

192.217

Pu Am Cm Plutonium

46

Iridium

Europium 2 8 18 32 24 8 2

2 8 18 16 1

6

2

He 4.002602

nanodispersions

TM

advanced polymers

tering targets

77

Cu

Nickel

102.9055

single crystal silicon

rbium doped fiber optics

Rh

29

58.6934

Rhodium

151.964

Samarium

Ni

2 8 16 2

B

2 3

aluminum nanoparticles

63

150.36

Promethium

45

Hassium

62

(145)

Neodymium

2 8 18 15 1

190.23

Nd Pm Sm Eu

refractory metals 232.03806

61

76

28

Cobalt

Osmium

107

Seaborgium

2 8 18 22 8 2

Ru

2 8 15 2

58.933195

101.07

186.207

quantum dots 2 8 18 19 9 2

44

Rhenium 2 8 18 32 32 11 2

Co

Ruthenium 2 8 18 32 13 2

Re

27

Iron

(98.0)

183.84

106

Fe

2 8 14 2

55.845

Technetium

Tungsten 2 8 18 32 32 12 2

26

54.938045

95.96

2 8 18 32 11 2

Mn

2 8 13 2

Manganese

Molybdenum

180.9488

diamond micropowder 90

42

2 8 18 12 1

Tantalum 2 8 18 32 32 10 2

25

51.9961

92.90638

2 8 18 32 10 2

Cr

2 8 13 1

Chromium

Niobium

Hafnium

Actinium

58

2 8 18 10 2

178.48

Lanthanum 2 8 18 32 18 8 2

50.9415

Zirconium

138.90547

Barium

Fr Ra tantalum (223)

2 8 18 18 8 2

V

24

2 8 11 2

Vanadium

91.224

Yttrium

137.327

Cesium 87

88.90585

Strontium

23

Titanium

Rb Sr Y Zr rhodium sponges Rubidium

2 8 10 2

47.867

Scandium 2 8 18 8 2

5

surface functionalized nanoparticles

9.012182

Lithium

11

Be

2 2

2

dysprosium metal

99.999% ruthenium spheres

1.00794

Hydrogen

praseodymium

gadolinium acetate

ultra high purity ma

europium phosphors

platinum ink solar energy

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