BioMatters - Special COVID-19 Edition

SPECIAL EDITION ®

A magazine showcasing Michigan’s biosciences industry

WHEN LIFE STOOD STILL,

SCIENCE STEPPED UP

C O V I D -19

WHEN LIFE STOOD STILL,

SCIENCE STEPPED UP

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PRESIDENT’S MESSAGE By any standard, 2020 was a very tough and sobering year — certainly unlike anything most of us had witnessed in our lifetimes.

When the lockdown was invoked a year ago in March, it was difficult to imagine that the virus would still be here in December. Even MichBio naively thought we could reschedule spring events to June or early fall. In the midst, we saw offices emptied as workers were sent home, goods flew off shelves as people panicked and hoarded, hospital wards filled up with patients who’d contracted a virus that was alien to health system workers, and a national healthcare system and government ill-prepared to deal with a pandemic.

As an industry, the biosciences was more fortunate than most. Deemed essential, our work largely continued despite some temporary delays, initial production losses, and pivots in business models, workforce dynamics, and organizational cultures.

Not surprisingly, and as only it could, it was the biosciences industry that answered the call at scale to develop diagnostics, life-saving treatments, personal protection equipment (PPE), and especially, an anti-SARS-CoV-2 vaccine, in response to the pandemic.

“Not surprisingly, it was the biosciences industry that answered the call at scale to develop diagnostics, life-saving treatments, personal protection equipment (PPE), and especially, an antiSARS-CoV-2 vaccine, in response to the pandemic.”

Immediately upon lockdown, Michigan’s bio-industry (and many other players) came together to produce ventilators and related components, protective masks, gowns, and shields, disinfectant agents and equipment, polymerase chain reaction (PCR), antigen and antibody test kits, diagnostic analyzers and testing services to better trace the virus — all in a compassionate bid to simply help during a time of desperate need.

Supply chains were mobilized in the face of global economic and social perturbations, manufacturing collaborations developed with unlikely partners, and an all-hands-ondeck attitude permeated. In the heat of the moment it seemed like chaos, and MichBio witnessed that first-hand as it played facilitator and matchmaker to the State of Michigan, health systems, companies, and so many others. Yet, the many stakeholders persevered, because there was no other choice…lives, humanity depended on it.

As you will see in this special BioMatters® edition, responding to COVID-19 has not been the work of a single organization, or even a single sector of the bio-industry.

Rather it has been the collective work of hundreds of companies, research institutions, regulatory and funding organizations, and thousands of industry workers, that have come together as part of a global effort capable of tackling the largest public health crisis of the last century.

These are a just a sampling of the many narratives from the last year, and they’re still being written today. From multi-national to startup bioscience players, from suppliers to small mom-and-pop providers — all taught us that Michigan’s bio-industry is at its best when working together. These are their stories.

Stay well, get vaccinated, continue with personal protective measures as deemed appropriate, and let’s keep everyone safe. We will endure.

Sincerely,

STEPHEN RAPUNDALO, PHD President and CEO, MichBio BIOMATTERS ® | COVID -19 SPECIAL EDITION

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TREASURER Sandra Pennell, CPA Vericel Controller

MICHBIO BOARD DIRECTORS Fredrick Molnar, MBA Michigan Economic Development Corporation Vice President, Entrepreneurship and Business Development

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Charles Hasemann, PhD Michigan State University Assistant Vice President for Innovation and Economic Development

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Ron Perry, MBA Emergent BioSolutions Vice President and General Manager

Jamie Kemler, MBA, CLP, RTTP Stryker Corporation Vice President, Intellectual Property Business Strategy

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Anna Langerveld, PhD Genemarkers, LLC President and Chief Scientific Officer

Randel Richner, BSN, MPH Richner Consultants Founder and President

Ken Massey, PhD Wayne State University Senior Director, Venture Development, Technology Commercialization

Tom Ross Grand River Aseptic Manufacturing President and CEO

Kevin McLeod C2Dx Founder, President and CEO

John J.H. Schwarz, MD Former U.S. Representative Uma Sharma, PhD MMS Chief Scientific Officer

BioMatters® is published bi-annually to showcase Michigan’s bioscience industry. Much of the content is submitted by MichBio member companies. Interested in submitting an article or advertising in a future issue? CONTACT ALISHA BROWN AT ALISHA@MICHBIO.ORG. BIOMATTERS ® | COVID -19 SPECIAL EDITION

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The MichBio Preferred Purchasing Program leverages the collective purchasing power of our member companies to obtain steep discounts from our vetted and endorsed vendor portfolio. Members have saved upwards of 900 times their annual membership dues.

FOR MORE INFORMATION VISIT MICHBIO.ORG

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SPECIAL EDITION

C O V I D -19 ®

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Vaccine and Treatment Development

30-43 Disease Management

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3 57 | New MichBio Member Spotlight 60 | RippleScience

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Public Health Management

After the Elevator Pitch Emerging Companies

Michigan Biosciences: By the Numbers MichBio

BIOMATTERS ® | COVID -19 SPECIAL EDITION

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Vaccine and Treatment Development

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Development of Vaccines and Treatments for COVID-19 Relies on Industry-Wide Urgency, Collaboration, and Innovation CAYMAN CHEMICAL

MICHIGAN STATE UNIVERSITY

ASALYXA BIO

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Existing Drugs Investigated for Use in the COVID-19 Fight

UNIVERSITY OF MICHIGAN

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A Drug Repurposing Story

ADVAITABIO

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Convalescent Plasma: A Century Old Therapy is a Part of the Effort to Reduce COVID-19 Mortality

MICHIGAN STATE UNIVERSITY

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Trailblazing Through Uncertain Times

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Unraveling Long-Haul COVID-19 One Sample at a Time

FUNCTIONAL FLUIDICS

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Michigan-Made Manufacturing Excellence

EMERGENT BIOSOLUTIONS

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Michigan Manufacturing Center Plays Pivotal Role in Distribution of Pfizer-BioNTech Vaccine

MMS

PFIZER-BIONTECH

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How do Vaccines and Viruses Work?

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Par Sterile Fights COVID-19 Through Innovative and Collaborative Manufacturing

ENDO PHARMACEUTICAL

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West Michigan CDMO Partners on the Manufacture of COVID-19 Vaccine Candidate

GRAND RIVER ASEPTIC MANUFACTURING

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Offering Critical Support During COVID-19

NEOGEN®

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VACCINE AND TREATMENT DEVELOPMENT

Development of Vaccines and Treatments for COVID-19 Relies on Industry-Wide Urgency, Collaboration, and Innovation

BY ALISHA BROWN, MARKETING AND COMMUNICATIONS DIRECTOR, MICHBIO

1 2 M O N T H S — that’s the

amount of time that lapsed between the identification of COVID-19 in China in late 2019 and the approval of the first vaccine in the United States.

That makes the Pfizer and BioNTech, and Moderna COVID-19 vaccines the most quickly developed vaccines in history, beating the nearest competitor — the Mumps vaccine — by three years, and the industry average for vaccine development by eight to ten years. That timeline has many asking, how is that even possible? The short answer, public pressure, combined with a headstart from other coronavirus research — MERS, SARS, etc, unprecedented industry collaboration, funding support from the government and private sector, regulatory fast-tracking, and innovation at every level all came together to create the synergy required to move at record-breaking speed.

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What does that actually look like?

Fundamentally, the bio-industry had to answer two questions — how to effectively help people who are sick, or will get sick, with COVID-19, and how to prevent infection altogether - in other words, the industry focused on developing both treatments and vaccines.

At the outset, those two processes are based on intensive research of the pathogen — for example, understanding the mechanism of infection and identifying possible avenues for treatment, such as was aided by the antiviral screening efforts conducted

by Cayman Chemical that sought to identify therapeutic compounds (opposite) or the study of virus mutations and the impact of those mutations on treatment efficacy, such as what was conducted

by Dr. Guowei Wei in the Mathematics Department at Michigan State University (opposite) - but later diverge based on specialty.

VACCINE AND TREATMENT DEVELOPMENT

SARS-CoV-2 Mutation Impacts on COVID-19 Diagnostics, Vaccines, Drugs, and Infectivity Submitted by Guowei Wei, MSU Foundation Professor, Mathematics, Electrical and Computer Engineering, Biochemistry and Molecular Biology, Michigan State University

The development of diagnostic tests, preventive vaccines, and therapeutic medicines for COVID-19 is of paramount importance to human health and the global economy.

SARS-CoV-2 has substantially evolved due to the geographically and demographically wide-spread COVID-19 transmission in the past year. A crucial question is what is the ramification of viral mutations for COVID-19 diagnostics, vaccines, drugs, and infectivity.

Mutations change virus genetic information and serve as a primary source for viral evolution, infectivity variation, and natural selection. SARS-CoV-2 has a genetic proofreading mechanism and thus has a higher fidelity in its transcription and replication process than that of other single-stranded RNA viruses, such as flu virus and HIV. Nonetheless, as found by Dr. Wei and his coworkers at Michigan State University, more than 25,000 unique mutations have occurred to over 100,000 SARS-CoV-2 genome isolates from patients compared to the first SARS-CoV-2 genome recorded in early January 2020 in Wuhan (https://users.math.msu.edu/users/weig/SARSCoV-2_Mutation_Tracker.html). Dr. Wei’s team has shown that about 65% of SARS-CoV-2 mutations were due to host immune responses, namely gene editing.

The other two major sources of mutations are random genetic drift and the viral correction mechanism. Note that most viral mutations are benign or even virulencereducing. Mutations have occurred on essentially all diagnostic targets, which could compromise current

COVID-19 testing. By integrating genetics, biophysics, artificial intelligence, and algebraic topology for SARSCoV-2 spike protein and human ACE2 interaction that initiates the viral entry of host cells (see Figure 1), the Wei team reports that mutations have made SARS-CoV-2 more infectious.

The Wei team shows that the existing thousands of mutations on the spike protein might pose threats to COVID-19 antibody therapies and vaccines. They recommend either a cocktail strategy or alternative designs to mitigate these mutation threats.

MATH.MSU.EDU

Figure 1. Illustration of topology-based convolutional neural network (CNN) analysis of mutation-induced binding free energy changes of ACE2 and spike (S) protein receptor-binding domain (RBD) interactions that directly affect SARS-CoV-2 infectivity.

Cayman Chemical Supports COVID-19 Research Submitted by Olivia May, PhD, Scientific Content Developer, Cayman Chemical Company

Scientists at Cayman Chemical are devoting their expertise to developing new products and services to support coronavirus research. These products include antiviral screening libraries to help identify compounds with therapeutic efficacy for COVID-19 and antiviral drug standards for use as internal standards for therapeutic monitoring and quantitative analysis. SARS-CoV-2 proteins and host receptor angiotensin-converting enzyme 2 (ACE2) antibodies are available to study the process of the viral spike protein binding the ACE2 receptor as the mechanism of viral entry into the body, and a specific assay platform enables the identification of novel inhibitors of the virushost cell interaction. Cayman’s serological tests can detect

SARS-CoV-2 neutralizing antibodies, which are critical for epidemiological studies, therapy and vaccine development, workforce testing, and immune response monitoring.

Additionally, Cayman’s in silico modeling contract services are being used to identify drug-SARS-CoV-2 protein interactions to predict binding of investigational therapeutics.

CAYMANCHEM.COM/CORONAVIRUS BIOMATTERS ® | COVID -19 SPECIAL EDITION

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VACCINE AND TREATMENT DEVELOPMENT

For example, in the area of treatments, the examination of existing drugs or drug combinations for possible repurposing as treatments for COVID-19, such as the research conducted at Advaita Corporation on existing FDA-approved drugs using their proprietary iPathwayGuide software (pg 13) or that conducted by Dr. Johnny Sexton in the Center for Drug Repurposing at the University of Michigan that compiled a database of more than 10,000 commercially available compounds for possible applications for COVID-19 (pg 12).

Or, less broadly, the focus on a specific, particularlyproblematic aspect of how COVID-19 presents and how to address it, for example, the work done by Asalyxa Bio on combatting the overactive immune response — or cytokine storms — that lead to dangerous systemic inflammation and, in some cases, death (below).

ASALYXA BIO Combats Cytokine Storms Submitted by John Freshley, Head of Corporate Development, Asalyxa Bio

Asalyxa Bio, a University of Michigan spin-out, is focused on addressing patients’ over-reactive innate immune responses to severe inflammatory and autoimmune diseases. Asalyxa regulates these immune responses using its PANTHER platform, which enables the delivery of bioactive drug particles directly into immune cells in the blood to deliver a potent anti-inflammatory effect.

Asalyxa’s lead product, ASX-100, is in late preclinical development for the treatment of the over-reactive immune responses to acute disease or tissue injuries.

Millions of patients die each year from such diseases (examples include ARDS, influenza, acute kidney injury, and liver failure). These responses are often referred to as “cytokine storms”.

The Panther platform goes beyond ASX-100 and includes additional planned programs in chronic inflammatory diseases. Particles can be designed in various sizes and shapes or loaded with additional drugs to enable precision targeting of various immune responses.

ASALYXABIO.COM

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For some organizations, research for treatments meant examining established therapies for efficacy with COVID-19, such as research into convalescent plasma — using plasma from recovered COVID-19 patients as a supplement for the immune systems of those currently infected with the virus. A group of scientists from around the country, including Dr. Nigel Paneth of Michigan State University created the National COVID-19 CP Project that examined the effectiveness of the century old therapy with the newest pathogen (pg 14).

For still others, treatment research meant using existing, seemingly unrelated expertise in new ways to unpack the mechanisms of the virus. At Functional Fluidics, that took the shape of analysis of red blood cells of COVID-19 patients looking for biomarkers that would indicate the likelihood of that patient developing long-haul symptoms (pg 16).

Throughout the state, the country, and around the globe countless organizations have, and continue to, look at COVID-19 treatments and it is through that combined effort, the collaboration around research, and the urgent need for effective therapies that led to quick adoption of possible patient care techniques by health care professionals, that created an environment ripe for advancements at a record pace.

Similarly, in the area of vaccine development, industry partnerships, sharing of research and risk, and the availability of funding, made advancements in vaccine technology possible.

MMS, among others, provided funding support for industry organizations working toward a vaccine as well as partnered with IBM to create a database of known vaccine studies for easy access by researching organizations (pg 15). Neogen enabled research by providing decontamination products to lab employees and others so that they could work safely and continuously, in addition to providing access to its cold storage facility for compounds needing careful temperature regulation (pg 26).

In every aspect of vaccine development, innovation has been made and dedicated, collaborative industry effort has led to the creation of novel vaccines using first-of-their-kind mRNA technology all in record time. Pfizer and BioNTech pledged in early 2020 to create a COVID-19 vaccine within a year. In just ten short months, that pledge turned into the first approved vaccine with a 95% effective rate and a major manufacturing roll-out here in Michigan. By December 23, 2020, more than 1.8 million doses of the Pfizer/BioNTech vaccine had been administered in the United States. (pg 20) Michigan manufacturing has played a key role in the distribution of vaccines with several organizations in the State providing fill and finish services that takes the

VACCINE AND TREATMENT DEVELOPMENT

Emergent BioSolutions provided manufacturing services for vaccine and treatment candidates as they entered clinical trails using their expertise and industry-leading technologies to digitize aspects of the manufacturing process that enabled rapid ramp up of production (pg 18).

manufactured vaccine and packages it in its ready-to-use form. Grand River Aseptic Manufacturing (pg 24) and Endo Pharmaceutical, a subsidiary of Par Sterile Products (pg 22) have both been able to provide essential fill and finish services while maintaining their existing production of urgent medical products.

From initial research, to drug-repurposing efforts, development of a national convalescent plasma project, focus on long haul COVID treatments, and vaccine development and manufacturing, Michigan has been a heavyweight in the COVID-19 response effort and it is that same collaborative and innovative mindset that enables the Michigan bio-industry to respond to health emergencies the world over.

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UNIVERSIT Y OF MICHIGAN

Existing Drugs Investigated for Use in the COVID-19 Fight

BY ALISHA BROWN, MARKETING AND COMMUNICATIONS DIRECTOR, MICHBIO BASED ON SOURCE MATERIAL PROVIDED BY THE UNIVERSITY OF MICHIGAN

Researchers at the University of Michigan likely did not envision the appearance of a novel coronavirus that would lead to a global pandemic and significant loss of life when they proposed the Center for Drug Repurposing (UM-CDR).

When the Center was launched in late 2019 the virus had yet to make headlines in China, let alone spread to the 191 (of 193 total) nations that it has today. In a coincidence of timing, the Center came in to existence at exactly the right time to take on the challenge of finding a drug previously approved by the FDA — or a cocktail of several drugs — to battle COVID-19.

A joint venture of the Michigan Institute for Clinical & Health Research (MICHR) and the Life Sciences Institute, the UM-CDR is led by Jonny Sexton, George Mashour, and Kevin Weatherwax and was created to address a critical gap in drug repurposing by developing a comprehensive database containing the structures, mechanism of action/ target, associated pre-clinical safety, and phase-I clinical trial outcomes of the more than 10,000 drugs that have reached the clinic in the United States and Europe. Even though half of those 10,000 molecules are commercially available as individual compounds, a comprehensive library formatted for bioassay screening did not exist and posed a considerable hindrance to drug repurposing efforts.

When it became clear that fighting COVID-19, and saving hundreds of thousands of lives, would require a research and innovation at a speed never before seen, the newly-minted UM-CDR became an essential resource.

“Even with fast-track approval processes initiated during a pandemic, the race for a vaccine will likely take 12-18 months,” said Sexton, assistant professor in Internal Medicine at Michigan Medicine, in April 2020. “So, finding pre-approved drugs that might treat symptoms, reduce the

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length and severity of the illness, and save lives is our focus.

We can conduct a rapid drug screening in days.”

Traditional drug discovery typically involves screening hundreds of thousands of compounds to find an active substance for development. The process of bringing a novel drug to market has a very high failure rate, a timeline of 11-18 years, and costs of approximately $1-3 billion dollars.

One important alternative, especially in a pandemic, is drug repurposing, which is the discovery of new uses for existing compounds that have cleared key steps in the drug development process.

The UM-CDR mobilized its resources to begin rapidly identifying and screening drugs from their library of thousands that are most likely to be effective as therapeutic interventions for COVID-19 in the clinical setting. With the use of AI, the team began screening a library of more than 1,400 FDA approved drugs and extended the screening to experimental compounds from a library of nearly 7,000 compounds in search of an antiviral drug or drug cocktail that could be used against COVID-19.

After only a few short months, the team had uncovered 16 compounds that had antiviral indications for COVID-19.

Though research is ongoing for COVID-19, the team is working to identify drugs that could be effective for a host of other conditions — notably for cancer treatment. This innovative approach to uncovering treatments is one part of the life science industry’s response to COVID-19.

DRUGREPURPOSING.UMICH.EDU

VACCINE AND TREATMENT DEVELOPMENT

A D V A I TA B I O

A Drug Repurposing Story

BY SORIN DRAGHICI, PRESIDENT AND CEO, ADVAITABIO

The Nobel laureate and molecular biologist Joshua Lederberg once said “The single biggest threat to man’s continued dominance on the planet is the virus.” The current pandemic of COVID-19 represents an acute and still developing global health crisis.

AdvaitaBio’s existing SaaS platform, iPathwayGuide, was designed to help researchers analyze and understand their omics data. Existing capabilities include helping the researchers identify the pathways that are significantly impacted, identify the biological processes that are significantly perturbed, understand the mechanisms of disease, and identify existing chemicals, toxicants or drugs that are relevant in the given phenotype. Advaita’s proprietary impact analysis has been extensively tested and validated and recently shown to be the most accurate pathway analysis approach currently available [1].

As early as March 2020, when the first data sets from COVID-19 patients became available, Advaita’s scientists realized the iPathwayGuide technology could also be used to address the COVID-19 challenge. Given the built-in knowledgebase and a set of differentially expressed genes or proteins, iPathwayGuide’s AI could identify FDA-approved drugs that could diminish the impact of COVID-19. After two weeks of analyzing data from COVID-19, together with data from cell cultures, cell lines, and even other viruses like H1Ni, Advaita’s scientists were able to identify several existing drugs that could potentially revert the changes included by COVID-19.

Those potentially effective drugs were brought to critical care doctors, led by Dr. Mayur Ramesh, at the Henry Ford Health System where a clinical study including 231 patients demonstrated methylprednisolone’s efficacy. Thirty-day all-cause mortality occurred at a significantly lower rate (approximately 44% lower) in the methylprednisolone treated group compared to the control group.

UNLIKE MANY OTHER EFFORTS RELATED TO COVID19, THIS APPROACH FOCUSED ON:

1. Understanding the host response 2. Providing drugs that would mitigate or alleviate some of the devastating over-reactions of the host’s immune system (e.g. cytokine storms) that lead to poor outcomes including death These efforts are complementary to the other existing efforts but more general. Unlike a vaccine or specific antiviral, a better understanding of the acute reaction of the immune systems and having more tools with which to mitigate and/ or avoid a cytokine storm will be important for any future pandemic regardless of the virus strain.

The work outlined here is expected to have a significant impact across the world, as follows. First, identifying one or more FDA approved drugs that could help COVID-19 patients is expected to save lives. Second, reducing the mortality rate and/or the severity of the symptoms is expected to offer a significant relief to society by diminishing or eliminating the need for the measures that led to the severe economic slowdown that we are experiencing. Third, the availability of such drugs can also mitigate the effects of the expected re-occurrence of SARSCoV2 in the next flu season.

ADVAITABIO.COM 1. T.M. Nguyen, A. Shafi, T. Nguyen, and S. Draghici. Identifying significantly impacted pathways: a comprehensive review and assessment. Genome Biology, 20(1):1-15, 2019

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M I C H I G A N S TAT E U N I V E R S I T Y

CONVALESCENT PLASMA: A Century Old Therapy is a Part of the Effort to Reduce COVID-19 Mortality

BY NIGEL PANETH, MD, MPH, UNIVERSITY DISTINGUISHED PROFESSOR, DEPARTMENTS OF EPIDEMIOLOGY & BIOSTATISTICS AND PEDIATRICS & HUMAN DEVELOPMENT, MICHIGAN STATE UNIVERSITY, COLLEGE OF HUMAN MEDICINE

In March, as the COVID-19 epidemic was in its early stages, a group of scientists from around the country, including Nigel Paneth, MD, MPH of MSU, met to consider their eventual role in what they realized was about to become a major public health problem.

Stimulated by a paper authored by Arturo Casadevall of Johns Hopkins University and Liise-anne Pirofski of the Albert Einstein College of Medicine arguing that an old therapy — convalescent plasma (CP) — might prove useful to treat or prevent COVID-19 disease, the group quickly coalesced around the purpose of understanding what, if any, role CP could play in ameliorating the effects of the pandemic. The National COVID-19 CP project was established.

Convalescent Plasma therapy is one of three forms of passive antibody therapy. Unlike vaccination, which is designed to create antibodies and immunologic memory in the recipient, passive antibody therapy transfers preformed antibodies to recipients either before or in the early stages of disease. CP therapy has its roots in the late 1800’s with the recognition that serum from laboratory animals recovering from infection could prevent or ameliorate the same disease in other animals. That discovery was quickly translated into humans in the form of two highly effective products diphtheria and tetanus antitoxins - discoveries which led to the awarding of the first Nobel prize in medicine, in 1901.

When serum or plasma from recovering patients is sterilized and distilled down to obtain concentrated antibodies, the product is referred to as hyperimmune globulin, a mainstay in the prevention of hepatitis, measles and other infectious diseases. More recently, monoclonal antibodies have been prepared in the laboratory, and, after at least one successful trial in out-patients with mild disease, have been given emergency use authorization by the FDA.

As the National COVID-19 CP project progressed, Dr. Paneth, with the help of Amazon Web Services (who donated their time) and MSU Information technologies, created a website — ccpp19.org — devoted to providing information about CP to both the public and professionals. The website lists all known US randomized trials - providing study protocols, where possible, to encourage new sites to join - interprets the meaning and value of antibody tests and viral diagnoses, and, especially in the early days, helped potential plasma donors find out how and where to provide plasma. That latter function has now been largely turned over to the blood banking world.

Since March, CP has been shown to be safe and effective if used early in the course of disease and if it contains sufficient antibody content. Nine, mostly small, randomized trials of CP have been published with seven of them showing lower mortality in treatment and, when pooled together, the nine show a significant mortality reduction of 26%. Observational studies, as well as studies showing that patients receiving high antibody titer plasma have better survival than recipients of low antibody titer plasma also support the conclusion that CP can significantly reduce COVID-19 mortality. The FDA gave emergency use authorization to CP on August 23rd and mandated that all CP units be labelled as to antibody content.

Currently, the National COVID-19 CP project is focused on continued research on CP and in encouraging plasma donations with special focus on a planned Big Ten blood drive intended to increase the supply of all blood components, now in short supply because of the pandemic, along with convalescent plasma.

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VACCINE AND TREATMENT DEVELOPMENT

AN MMS STORY

Trailblazing Through Uncertain Times

BY CRYSTAL ALEXANDER, MARKETING AND COMMUNICATIONS SPECIALIST, GLOBAL MARKETING AND COMMUNICATIONS, MMS HOLDINGS

Over the last several years, MMS (based in Canton, Mich.) has been at the forefront of the pharmaceutical industry as an innovative, datafocused CRO with a proven, scientific approach to complex trial data and regulatory submission challenges, strong industry experience, and a data-driven approach to drug development, creating compelling submissions that meet rigorous regulatory standards.

When the pandemic of 2020 caused by COVID-19 struck the globe, MMS was properly positioned to answer the call with an embedded sense of urgency to aid in finding treatments and a possible cure to SARS-CoV-2, a strain of coronavirus that causes COVID-19. Within a very short timeframe, MMS made significant contributions to combat COVID-19.

Offering a $1M grant MMS created a $1M grant for the development of a vaccine for COVID-19 within a week of the world beginning work from home. The award came in the form of data and related services to qualified pharmaceutical and clinical research companies supporting the commercial development of a vaccine for approval in the United States and/or other global health authorities.

The award aided in drawing support in areas like regulatory and medical writing, data science, clinical trial transparency, biometrics, and other areas within the pharmaceutical industry to help further to find treatments and or a vaccine.

Partnering with a tech giant Partnering with IBM Watson Health, MMS established the ambitious goal of building and launching integrated datasets for sponsor trials within three business days. As part of the global therapeutics accelerator effort, the team supported multiple studies around the world including a promising trial that is studying novel agents among high-risk outpatients in adults across three geographies.

Helping stop the spread To help control and block the spread of coronavirus, MMS is collaborating with IGY Life Sciences towards the development of IgY-110, an anti-CoV-2 therapeutic antibody with a focus on a nasal spray application. This novel approach of an IgY antibody in a nasal spray will be complementary to any vaccine developed.

Ensuring the health of colleagues MMS Chief Operating Officer, Prasad M. Koppolu, issued a public note to address the company’s commitment to ensuring the health and safety of MMS colleagues, Sponsors and public, amidst the outbreak of COVID-19. In his note, Koppolu addressed the importance of MMS taking the necessary precautions to ensure that every colleague remains healthy, productive, and committed to those the company serves. He also stated that the organization was able to make a swift response to this pandemic, allowing all colleagues globally to work from home immediately following the pandemic announcement.

While the company has helped make other significant contributions that cannot be discussed due to confidentiality, the group looks toward 2021 with a renewed sense of purpose.

Since the onset of the global pandemic, MMS has maintained its core values and dedication to providing a sense of urgency and leadership (SOUL), taking the lead in the pursuit to find treatments and vaccines for this disease.

MMSHOLDINGS.COM

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VACCINE AND TREATMENT DEVELOPMENT

FUNCTIONAL FLUIDICS

Unraveling Long-Haul COVID-19 One Sample at a Time

BY ALISHA BROWN, MARKETING AND COMMUNICATIONS DIRECTOR, MICHBIO, BASED ON MATERIAL PROVIDED BY FUNCTIONAL FLUIDICS

Blood, specifically red blood cells (RBCs), is essential to human health. In fact, to the trained observer, aspects of a sample of RBCs can be used to diagnose risk for severe illness and give doctors vital information for treatment.

That’s exactly what the staff at Functional Fluidics are experts in — analyzing blood samples for key characteristics that can indicate a person’s health and predict their risk for future health conditions if their RBCs do not change.

“If you think of a sample of red blood cells as a snapshot,” says Patrick Hines, MD, PhD Functional Fluidics’ Founder and CEO, “then you can think of it as a momentary depiction of the overall health of the patient. We all know that there are many factors affect health including genetics, environment, nutrition, socio-economic status and more. It is precisely because there are so many factors that it is difficult to use them in any meaningful way to understand and help a patient right now — they are useful for identifying trends, but less valuable for treating an isolated individual.”

He continued, “That’s why analysis of blood cells is so important, it enables you to look at a person right now — the current conclusion of all of those factors together that describes a patient’s health and enables a doctor to devise an appropriate treatment plan.”

Functional Fluidics measures RBC adhesion — i.e. stickiness — and fragility with their proprietary biomarker assays that replicate the environment RBCs experience in the body. Those biomarkers, the level of adhesion and fragility, can change with the introduction of a pathogen or the existence of a disease. For example, Sickle Cell Disease causes RBCs to change shape and become sticky making

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them significantly less able to transport oxygen throughout the body and at higher risk of clumping together and decreasing the flow of the remaining healthy cells.

“Through years of analyzing blood samples from Sickle Cell patients,” says Hines, “we know that certain levels of adhesion and fragility are associated with disease maintenance and others are associated with a patient in crisis. Where a patient falls on that continuum is a key indicator of how well their condition is controlled and what additional interventions might be necessary.”

Earlier this year, when Functional Fluidics responded to the urgent need for diagnostic and serology — i.e. antibody testing for COVID-19, the staff, rather serendipitously, began to examine samples of RBC’s from children in the ICU with COVID-19 complications. Those samples showed major damage to RBC’s similar to the increased adhesion and fragility that is evident in Sickle Cell patients.

“When COVID-19 first appeared,” says Hines, “it was widely accepted to be a respiratory disease since the vast majority of deaths came from pneumonia or acute respiratory distress syndrome. As time has progressed, it has become clear that while many suffer from respiratory-related symptoms, COVID-19 also attacks the heart and major organs, and causes widespread blood clotting.”

He continued, “what’s more, while most COVID-19 patients recover within a matter of weeks, some have symptoms that persist for months and leave them unable to return to their normal lives. That got us thinking — what if COVID-19 fatigue, body pain and other symptoms were not the result of poor lung function, but rather the result of inefficient oxygen transportation from damaged RBCs?”

VACCINE AND TREATMENT DEVELOPMENT

Given their expertise in blood cell analysis and the readily available samples from known COVID-19 cases, Functional Fluidics has begun looking for predictive biomarkers that could help individuals and health care professionals know which patients are at higher risk for life-threatening symptoms and can help them to design interventions appropriate to their individual situation.

“If you consider that most treatment plans are enacted only after a patient has developed symptoms,” continued Hines, “for example, dialysis as a treatment for kidney damage after a patient presents with fatigue, decreased urine output, headaches, and other symptoms, then you can appreciate that most treatments are in reaction to damage in the body that has already occurred and may not be able to be healed. If you had the ability, through analysis of red blood cells, or some other means, to detect damage before a person develops symptoms, then you could potentially address the root cause of the problem and prevent the damage altogether.”

In the case of COVID-19 patients, especially those with long-term symptoms, this could be the difference between a lifetime of conditions brought about by damaged organs and inefficient oxygen transportation or a return to pre-COVID levels of health. What’s more, solving the long-term COVID problem could mitigate the economic impact of thousands of previously young and healthy members of the workforce being removed from the economy through disability and becoming a significant, and continuing, burden on the healthcare system.

Research into the long-term implications of COVID-19 is in its infancy, but Functional Fluidics intends to employ its expertise in RBC health to help solve the riddle of the long-haul COVID-19 patient and help doctors, and the healthcare system, prepare for the future.

FUNCTIONALFLUIDICS.COM

BIOMATTERS ® | COVID -19 SPECIAL EDITION

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VACCINE AND TREATMENT DEVELOPMENT

EMERGENT BIOSOLUTIONS

Michigan-Made Manufacturing Excellence

BY EMERGENT BIOSOLUTIONS COMMUNICATIONS STAFF

Lansing, Michigan is where Emergent BioSolutions’ story began more than 22 years ago. The initial footprint was impressed from a partnership formed with the U.S. government to supply BioThrax® (Anthrax Vaccine Adsorbed) for military members.

With 19 global locations, 10 marketed products and a robust pipeline of products in development, Emergent has a longstanding and successful history partnering with governments to meet their preparedness, response and national security needs.

Best known for developing and manufacturing vaccines, therapeutics, and drug-device combination products that address public health threats, Emergent has keenly focused on addressing the opioids epidemic, biologic threats like anthrax, smallpox, and botulism, chemical warfare agents, and emerging infectious diseases like COVID-19, influenza, Ebola, and Zika. Having four distinct business units, including Devices, Vaccines, Therapeutics and CDMO, or contract development and manufacturing, the latter of which has the ability to partner with pharmaceutical or biotechnology companies to help in terms of the drug development and manufacturing processes. When it comes to pandemic preparedness, Emergent is built to combat public health threats.

Nowadays, tackling some of the world’s most complex public health threats is what fuels the organization — embedded within one singular mission — to protect and enhance life.

The novel coronavirus is one example at the top of the list that has spotlighted the company’s ability to provide preparedness and response solutions, diversified clinical and manufacturing expertise, and rapid deployment of capabilities and services to support manufacturing goals.

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“We are proud of our Michigan roots, and that Lansing is home to hundreds of dedicated employees who strive to help people live healthier and safer lives, to the best of their ability,” said Dino Muzzin, Emergent’s senior vice president, manufacturing operations. “For over two decades, our Michigan-made manufacturing excellence has served as our North Star — affording us the opportunity to facilitate stateof-the-art expansions, inspire industry-leading innovation, grow leadership and be a trusted contract development and manufacturing partner.”

Muzzin oversees operations of a network of Emergent’s manufacturing facilities. He has been with the company for 17 years and prior to his current role, he led the Lansing site operations for four years, where he has helped create a fabric of culture, empathy, and superior quality work from his team. With the heightened focus on COVID-19, operations across the site have continued seamlessly, with limited issues and delays, while across the country at its sister sites, Emergent has stepped in to join the U.S. government to accelerate the development and manufacturing of COVID-19 investigational vaccines. Emergent has secured numerous private-public collaborations with Johnson & Johnson, AstraZeneca, Novavax, and Vaxart to develop and manufacture COVID-19 vaccine candidates. Most recently, Emergent announced a seventh COVID-19 collaboration with Humanigen, for the drug product manufacturing of their therapeutic candidate, lenzilumab™.

VACCINE AND TREATMENT DEVELOPMENT

Emergent’s integrated network provides development services from its Gaithersburg facility, drug substance manufacturing at its Baltimore Bayview facility, and drug product manufacturing at its Baltimore Camden and Rockville facilities, all in Maryland. Employees from the Lansing facility are supporting COVID-related projects, as well. “We have employees from other locations who have been deployed to the facilities that are focused on COVID vaccine manufacturing. This is the kind of ‘One Emergent’ culture that we have,” said Muzzin.

Muzzin says that Emergent is harnessing its decades of experience in vaccine and hyperimmune development and manufacturing, as well as its molecule-to-market CDMO services to provide comprehensive medical countermeasure solutions in response to COVID-19.

Emergent has facilities that will support the vaccine supply goals for Johnson & Johnson and AstraZeneca.

For both, the agreements are around large-scale drug substance manufacturing. They are also working with Novavax, Vaxart and Humanigen on their COVID-19 therapeutic candidate, lenzilumab™.

Emergent has lived its mission by addressing broad public health crises with both the opioid epidemic and COVID-19. They also have two plasma-based therapeutics being developed to tackle the pandemic. One candidate is being evaluated as a treatment in a phase 3 study in hospitalized patients who have COVID-19 as well as for prophylaxis in a Phase 1 study for frontline healthcare

providers who could take this therapeutic to prevent them from getting infected with the virus. The second candidate is in earlier stages in development.

Their work doesn’t stop here. In order to be a highly competitive CDMO powerhouse, Emergent has leaned on innovative ways to optimize and enhance manufacturing operations, quality assurance, global operational excellence though cutting-edge technology.

“Digitization across manufacturing is a bit of an anomaly,” explained Muzzin. “As an early adopter of new tools, such as virtual (VR) and augmented reality (AR) technologies or commonly known as extended reality (ER), Emergent’s staff has identified and implemented new ways of training, to shake up the more conventional approaches — we are tapping opportunities to give us meaningful and relevant expertise.”

ARVR manufacturing training tools, such as HoloLens for guided aseptic gowning training, have revolutionized the way Emergent has taken steps toward leading and accelerating Industry 4.0 Manufacturing efforts — where leaders see the future ahead and can offer breakthrough technologies to solve issues or anticipated challenges. It’s just part of the focus of the Lansing site, where the company is putting a significant focus on ways in which innovation can enhance key areas across the manufacturing spectrum, and is what Muzzin believes will continue to pave the way for greater success right here in the heart of Michigan.

EMERGENTBIOSOLUTIONS.COM BIOMATTERS ® | COVID -19 SPECIAL EDITION

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VACCINE AND TREATMENT DEVELOPMENT

PFIZER -BIONTECH

Michigan Manufacturing Center Plays Pivotal Role in Distribution of Pfizer-BioNTech Vaccine

BY ALISHA BROWN, MARKETING AND COMMUNICATIONS DIRECTOR, MICHBIO

You might say that Pfizer’s journey to a COVID-19 vaccine began in March of 2020 when CEO Albert Bourla, DVM, PhD declared the bold ambition that the company would develop a vaccine and have data to submit to the FDA before the end of the year.

Or you could make the argument that Pfizer’s journey began in August of 2018 when the company initiated a partnership with BioNTech to develop mRNA vaccines for the prevention of influenza (flu) — mRNA would ultimately become the technology used in the Pfizer-BioNTech COVID-19 vaccine.

Or you could look to more than 170 years ago when Charles Pfizer and cousin Charles Erhart founded the company and set off on the path that would start with a pioneering method of producing citric acid with large-scale fermentation, to mass production of penicillin and an instrumental role in the development of antibiotics, and the subsequent creation of countless pharmaceuticals that have improved and saved lives the world over.

Regardless of where the journey began, Dr. Bourla understood the challenge he set for the company when he made that declaration in March 2020 and knew that Pfizer had the expertise and unrelenting drive necessary to meet it.

Along with that declaration, in March 2020, Dr. Bourla announced Pfizer’s five-point plan for combating the evolving pandemic. That plan relied on sharing tools and insights with the broader bioscience community for the purpose of furthering all research, demonstrated an understanding that expertise and manpower were essential to the process — Pfizer has both — and showed a commitment to combating both COVID-19 and future global health threats by offering up the company’s manufacturing capabilities and working to build a cross-industry response team of scientists, clinicians, and technicians able to swing into action immediately when the need arises in the future.

It was in that same month that Pfizer and BioNTech announced their intent to co-develop mRNA-based vaccine candidate BNT162.

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OVER THE NEXT NINE MONTHS, PFIZER AND BIONTECH: 2020: Gained regulatory ° APRIL approval to begin trials in Germany and tested their first human subjects, 2020: Began testing in the ° MAY United States, 2020: Were granted fast track ° JUNE designation after showing positive early data from the ongoing Phase 1-2 clinical trials in the US, 2020: Selected and began a ° JULY global phase 2/3 clinical trial of their lead vaccine candidate, 2020: Announced phase ° NOV 3 study results and submitted a request for an Emergency Use Authorization to the US FDA, 2020: Became the first ° DEC authorized vaccine in the world to combat COVID-19 and began vaccine distribution, According to the CDC, by December 23, 2020, more than 1.8 million doses of the Pfizer/BioNTech vaccine had been administered in the United States with an additional 200 million doses expected to be distributed in US by July 31, 2021 with the global total in that period surpassing a billion doses.

VACCINE AND TREATMENT DEVELOPMENT

A key part of that distribution effort is centered in Portage, MI where Pfizer’s largest manufacturing facility is located. At more than 1300 acres and 2,400 people strong, the facility is a cornerstone to one of the most thriving life science corridors in the nation.

Vaccine manufacturing begins with raw materials production in St. Louis, followed by drug purification in Andover, MA, and then combining with other raw materials at the Portage facility. The bulk vaccine is then transferred to an aseptic filling line where it is filled into a sterilized vial and capped, inspected, and transferred to packaging lines.

From there, it is distributed — with widespread availability in the United States expected in the next six months.

The Pfizer-BioNTech vaccine is an mRNA-based vaccine. Traditional vaccines rely on weakened versions of a virus to elicit an immune response in the vaccine recipient. This vaccine relies instead on a section of COVID-19

mRNA that codes for a specific protein that enables the virus to bond with other cells and multiply. Pfizer and BioNTech were able to isolate that section of mRNA, wrap it in a protective covering of lipid nanoparticles and inject it into healthy muscle tissue. The effect is that the existing cells take in the mRNA and begin to produce the COVID-19 protein they are coded for — but only the protein, not the whole virus.

The body is then able to recognize the protein as an intruder and mounts an appropriate immune response.

The net effect of both types of vaccines is the same — the vaccine recipient develops an immunity to the virus, but a key factor in the speed with which the Pfizer-BioNTech vaccine was able to be developed and manufactured is the fact that it is mRNA-based. The process for isolating the mRNA molecule is simpler and more efficient than what is required to grow and hybridize the living vaccine to make it safe for vaccine use.

This is a first-of-it-kind vaccine, demonstrating the effect of collaboration and innovation in life science development.

“I couldn’t be prouder of my fellow Pfizer colleagues and partners at BioNTech,” Dr. Bourla said in a video statement. “Their historic science-driven effort has delivered a vaccine with the potential to bring an end to the most devastating pandemic in a century.”

PFIZER.COM

BIOMATTERS ® | COVID -19 SPECIAL EDITION

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VACCINE AND TREATMENT DEVELOPMENT

ENDO PHARMACEUTICAL

Par Sterile Fights COVID-19 Through Innovative and Collaborative Manufacturing

BY ENDO PHARMACEUTICAL AND MICHBIO STAFF

By now, we’ve all heard inspiring stories of companies that responded to COVID-19 with empathy, a shared sense of community and a hefty dose of old-fashioned grit.

Ford and GM pivoted to medical equipment, Carhartt redirected its workwear production to medical gowns and masks, and breweries and distilleries around the country pumped out sanitizer.

Among the corporations contributing to the fight: Endo, through its subsidiary Par Sterile Products, LLC (Par Sterile), with a manufacturing facility in Rochester, Michigan.

How the company made a difference: boosting supplies of medically necessary drugs for COVID-19 patients, agreeing to provide fill-finish manufacturing services to Novavax in support of its COVID-19 vaccine candidate, NVX-CoV2373, and donating millions (in cash and medicines) to organizations helping people survive, both medically and economically.

As an Endo subsidiary, Par Sterile Products specializes in aseptic injectable products that help improve patient quality of life. Its manufacturing facility in Rochester, Michigan has an excellent regulatory compliance record and a reputation for high-quality products.

ENDO AND PAR STERILE BACKGROUND Endo is a specialty pharmaceutical company committed to helping everyone it serves live their best life through the delivery of quality, life-enhancing therapies. In its constant pursuit to address the many needs of patients, Endo has a long history of evolving and developing businesses that provide diverse products.

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“Rosie the Riveter Moment” Like virtually every other company in the world, Endo faced challenges in 2020 as it moved employees who could work outside of the office to remote work, modified schedules and processes to meet new safety protocols for those working at manufacturing facilities, and supported its thousands of team members around the world, for starters.

Knowing that patients and their healthcare providers depend on Endo, the company turned its energy to an emerging need: meeting the rapidly increasing demand for two of its products for critical COVID-19 patients.

“It was a Rosie the Riveter moment for us,” said Michael Randolph, the company’s Senior Vice President, Commercial Operations and General Manager of the Rochester facility, when describing the increased shipments—ranging from five to 10 times normal rates—in the early days of the pandemic.

As emergency rooms were packed with patients, there wasn’t much that one individual could do to help outside of a hospital setting. Remember the meme making its rounds at the time: “Your grandparents were called to war. You're being called to sit on your couch.”

The Par Sterile team had a different calling.

“We thought, ‘What can we do to fight COVID?’” recalled Randolph. “Our solution: Stay healthy, come to work every day and make these very critical products that serve patients in need.”

Never Worked Harder Once the team had its mission, everything changed. “We threw the schedule out the window.”

Increasing supply of two medically necessary drugs became the top priority, and everything else had to fall in line.

“Say the word ‘COVID,’ and people are willing to do just about anything,” said Randolph. “We had vendors rushing shipments, showing up to provide maintenance and helping us troubleshoot our processes. They were part of the team.”

Amid the organized chaos, Randolph focused on Endo’s guiding priorities: Keep people safe, and keep producing needed medication.

Though the pressure to produce had never been greater, the safety of every team member was non-negotiable. On top of wanting to keep individuals healthy, an outbreak could prove disastrous in continuing drug supply for both COVID-19 and other critical care patients.

The company implemented safety measures such as modified work schedules, increased social distancing, restricted site access and enhanced screening protocols. That made life a little more complicated at the site, but the team persevered to get the job done.

“Everyone said it. No one worked harder in their lives.”

And while the manufacturing team on the ground rallied around their new mission, Endo team members from across the globe lent support however they could—handling logistics, helping to reimagine operations and fast-tracking any request out of the Rochester facility.

“We needed new packaging because we were increasing the supply in each package, and anyone who knows pharma will tell you that this isn’t a simple change,” said Randolph. “But the team moved at lightning speed to get us what we—and ultimately, hospitals and patients—needed. The importance wasn’t lost on anybody.”

COVID-19 Vaccine Production Support As the Par Sterile team cranked out the two drugs at an unprecedented pace, parent company Endo asked the government what else they could do.

“We had proven that we could step up when needed,” said Blaise Coleman, president and CEO of Endo. “We offered our assistance to the federal government to put us to work where needed for the country.”

VACCINE AND TREATMENT DEVELOPMENT

That meant temporarily halting production of other drugs to free up space and workers, adding shifts, bringing in new equipment to produce more batches, and working with vendors and suppliers to enable increased production.

The answer came when Endo and fellow pharmaceutical company Novavax announced that the Rochester facility agreed to provide fill-finish manufacturing services to Novavax for its COVID-19 vaccine candidate for both Phase 3 clinical trials and, if approved, for commercial distribution in the United States.

At the time of the announcement, Novavax president and CEO Stanley C. Erck credited Endo’s partnership and expertise for enabling rapid delivery of the vaccine for clinical testing.

To Endo’s president and CEO, the role made sense. “Our Rochester, Michigan facility has a long history of manufacturing critical vaccines and sterile injectable products,” said Coleman. “This critical initiative embodies the collaboration and innovation necessary to fight this deadly virus. Those two traits describe our Rochester team perfectly.”

Note: NVX-CoV2373 is in Phase 3 trials at the time of publication, including PREVENT-19, a large pivotal trial in the U.S. and Mexico that is recruiting participants.

Donations for Organizations on the Front Lines In addition to Endo’s commitment to maintaining the continuous supply of its critical care products and agreeing to provide manufacturing support for a vaccine candidate, the company showed its commitment in a tried-and-true move: cash and medicine donations.

Endo gave over $5 million in product and monetary support to Americares and the Red Cross—organizations doing the vital work of helping people impacted by COVID-19 and the economic fallout as a result of the pandemic.

Some of the money came from an employee match program, as team members clamored to help in their own personal ways. For medically trained team members, Endo provided leaves of absence and any other accommodations necessary to enable them to join the call for additional staff around the world.

“Our company has responded in big and small ways,” said Coleman. “What we’ve done—what we’re still doing—exemplifies the shared mission of pharmaceutical companies, and it’s a testament to the shared humanity of everyone living through this crisis and helping their communities survive.”

ENDO.COM

BIOMATTERS ® | COVID -19 SPECIAL EDITION

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VACCINE AND TREATMENT DEVELOPMENT

G R A N D R I V E R A S E P T I C M A N U FA C T U R I N G

West Michigan CDMO Partners on the Manufacture of COVID-19 Vaccine Candidate

BY GRAND RIVER ASEPTIC MANUFACTURING

2020 was bound to be a memorable year for Grand River Aseptic Manufacturing (“GRAM”), as the West Michigan company would be celebrating its 10th year in business and opening the doors to its new, state-of-the-art large-scale fill/finish facility in the heart of Grand Rapids.

What GRAM — and the entire world — could not have predicted was how urgently the pharmaceutical supply chain, and the company, would be called on in 2020, or how important the Michigan life sciences industry would be to the United States’ response to COVID-19.

To accommodate increasing client demands prior to the COVID-19 pandemic, GRAM — which was founded in 2010 and has experienced tremendous growth during the past decade thanks to leadership from President and CEO Tom Ross, an exemplary track record with the Food and Drug Administration and support from local economic development organizations — invested over $60 million initially, and more since, in a world class new facility that broke ground in 2018. At just over 60,000 sq. ft., the facility was built with a modern design and advanced technology on an expedited timeline to begin good manufacturing practice (GMP) by Fall 2020. Construction was completed on budget and on time — which would prove to be critical for the sake of the nation.

With its West Michigan location being a differentiator from others within the pharmaceutical industry, the GRAM team leverages its location as a strength and is immensely proud to call Grand Rapids home.

Ribbon Cutting Ceremony June 2020: Grand Rapids Mayor Rosalynn Bliss (right) with GRAM CEO Tom Ross (left) at GRAM’s ribbon cutting ceremony

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GRAM employees encompass five facilities in downtown Grand Rapids — with three being manufacturing facilities at nearly 100,000 sq. ft. all within one mile — making a small campus of their own downtown. The company’s growth and success in “Beer City” has led GRAM to earn recognition in Inc. Magazine’s Inc. 5000 list for the past four years and to receive a spot on West Michigan’s Best and Brightest Companies To Work For® list in 2017 and 2020. At the grand opening of the new facility in June 2020, Grand Rapids Mayor Rosalynn Bliss highlighted the company’s growth and contributions within the community — recognition GRAM takes to heart. Recent growth skyrocketed the company to being a national leader during a truly unprecedented year.

In August 2020, just two months after doors to the new facility opened, the United States Federal Government selected GRAM to expand fill/finish capacity under Operation Warp Speed, with the ultimate goal of helping to combat COVID-19. As the race to manufacture a vaccine was underway, GRAM rapidly became part of the solution — due in large part to its recently completed pharmaceutical manufacturing facility. Nimble decision-making processes, strong communication across GRAM’s 200+ employees, and unrelenting grit to take on any challenge led the GRAM

VACCINE AND TREATMENT DEVELOPMENT TOP: GRAM Large Scale Filling Exterior 2020: Grand River Aseptic Manufacturing’s new large-scale fill/finish facility officially opened in June 2020, just in time to support Operation Warp Speed’s response BOTTOM: Bausch + Strobel Vial Filler with Capper: GRAM was tapped to support the fill and finish manufacture of Johnson & Johnson’s SARS-CoV-2 vaccine candidate

team quickly to the next phase of equipment qualification.

From there, media fills were expedited to ensure the new equipment and technology were prepared for manufacturing a COVID-19 vaccine candidate.

With the Operation Warp Speed partnership underway, GRAM was called on by leading pharmaceutical giant Johnson & Johnson to support the manufacture of its SARS-CoV-2 vaccine candidate.

In September 2020, GMP production of Johnson & Johnson’s vaccine candidate began at GRAM’s new facility. By providing the capacity to perform advanced aseptic fill and finish services — the last two steps in the manufacturing process for vaccines and/or therapeutics — GRAM is helping to ensure that the country has sufficient domestic supply upon regulatory approval of the SARS-CoV-2 vaccine developed

by Janssen Pharmaceuticals, Inc., one of the Janssen Pharmaceutical Companies of Johnson & Johnson.

As the partnerships with Operation Warp Speed and Johnson & Johnson were formed, GRAM quickly shifted from qualifying the new facility to recruiting and onboarding new employees that fit within the company’s culture

of togetherness — both inside and outside the facility walls. GRAM is incredibly fortunate to have access to the high-quality talent pool as well as the robust life sciences ecosystem in West Michigan. With GRAM’s location being an extension of Grand Rapids’ “Medical Mile” — the blossoming health and life sciences corridor of prestigious medical, research and education institutions in the city’s downtown area — GRAM is proud that its work is part of the many innovations coming out of West Michigan to keep our region and nation healthy.

As GRAM looked forward to a milestone year, the company could have never imagined the opportunities that 2020 would bring — forming important partnerships that have led to tremendous growth in a short amount of time and more so, serving the U.S. population and combating a pandemic that has shattered lives. It is an extraordinary privilege to be part of a solution for the American people, and GRAM commends its team, and the many others across the state of Michigan, who have stepped up to the challenge with enthusiasm and determination.

GRANDRIVERASEPTICMFG.COM

BIOMATTERS ® | COVID -19 SPECIAL EDITION

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VACCINE AND TREATMENT DEVELOPMENT

NEOGEN®

Offering Critical Support During COVID-19

BY NEOGEN COMMUNICATIONS STAFF

For the past 39 years, NEOGEN has been doing its part to help keep the world safe by providing the products and services needed to protect the food supply.

The current COVID-19 pandemic has significantly impacted businesses and sent economic shockwaves to each industry.

In this rapidly changing environment, NEOGEN has passionately worked to provide an array of biosecurity solutions to industry partners, so they can do their part to protect the global food supply chain as well

Committed to Deliver NEOGEN has always taken its employees’ health and safety very seriously. As the world experienced a shortage of biosecurity solutions (disinfectants, hand sanitizer, masks, etc.), the company was fortunate to supply employees with COMPANION™ Hand Sanitizer and Disinfectant Wipes, as well as other supplies, to help keep them and their families safe.

NEOGEN has been continuously adapting to the changing state of public health and the State of Michigan’s Executive Orders by establishing a remote work option, updating travel procedures, and canceling in-person events. NEOGEN’s continued success is credited to its dedicated employees who resiliently adapt to the ever-changing world to ensure the company delivers on its promise to keep the global food supply safe.

“During the COVID-19 pandemic, our global teams have displayed incredible resilience and dedication to their work as our industry partners depend on us to deliver the products and services they need. It’s because of our employees’ adaptability and commitment that NEOGEN has persevered and grown during these unprecedented times.”

— John Adent, President & CEO of NEOGEN®

LEARN MORE ABOUT THE COMPANION PRODUCT LINE AT NEOGEN.COM/SOLUTIONS/CLEANERS-DISINFECTANTS, OR CALL 800.234.5333.

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Support for Industry Partners Another priority of NEOGEN’s has been industry partners — both local and global. During 2020, NEOGEN’s executives diligently monitored the company’s business support services from all angles, asking: How can NEOGEN help fellow industries?

As NEOGEN continuously modified its business needs to better support partners, the company made giant leaps to make its COMPANION disinfectant solutions accessible to everyone. The campaign to promote and distribute COMPANION reached research facilities, food manufacturers, dairy producers, cattle farmers, and colleges — to name just a few.

As COVID-19 continues to spread throughout the globe, NEOGEN employees realize we aren’t out of the woods yet.

The company would like to recognize and thank all of its dedicated employees who tirelessly help supply partners with the critical solutions they need.

Assisting with the Vaccine As Michigan moves into Phase 1B of the vaccine distribution, NEOGEN has stepped up and offered its refrigeration and freezer site for additional COVID-19 vaccine storage. The company’s sites have both -20 and -70°C freezers and standard refrigerated cold storage to ensure solutions aren’t compromised. In addition to cold storage, since many of NEOGEN’s solutions require cold shipment, the company naturally contain the necessary materials — coolers, ice bricks, and wraps — to assist in proper transportation.

Stay Healthy & Safe

VACCINE AND TREATMENT DEVELOPMENT

HOW DO VACCINES AND VIRUSES WORK? An Explanation for Non-Scientists

HOW DOES A VIRUS WORK? If you think of an individual cell in the body as a factory, where the nucleus provides the power, the cell’s DNA provides the schematics, and the various cell parts provide the machinery required for construction, then you have the necessary foundation to understand how a virus works once it enters the body.

For everyday functions — like repairing damaged muscle cells after an intense workout — the cells in the body use their internal DNA to activate their machinery to produce new cells. However, in the presence of a virus, that machinery gets hijacked and the cell begins to create copies of the virus that are subsequently released into the body to go take over more cells.

HOW DOES THE VIRUS DO THAT? Individual virus cells contain their own DNA — their own building schematics — but lack the power and the machinery necessary to produce their own copies. When they enter the body, they use a spike on the outside of their structure as a key to gain entry to the body’s existing cells.

At the point that the virus gains entry to the body cell, it disperses its own DNA and reprograms the cell to produce copies of the virus.

HOW DOES A VIRUS GET A KEY TO A BODY CELL? When a virus becomes a threat to humans, it essentially means that it has mutated to a point that the spike on the outside of the virus will work effectively as a key to unlock human cells — before such a time, the virus cells could enter the body but would not be able to multiply and would be no threat. But as it encounters the human body — as it would with any other species — it takes a look around and could, in a later version, make a subtle mutation that suddenly unlocks the body cells.

This is a part of what people mean when they say a virus has “made the jump” from animals to humans — it means the virus has developed the right key to be able to access the machinery in a human cell when it was unable to before.

BIOMATTERS ® | COVID -19 SPECIAL EDITION

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VACCINE AND TREATMENT DEVELOPMENT

HOW DOES THE BODY COPE WITH THE VIRUS? As the virus multiplies, its newly created cells are released into the body with the purpose of invading other healthy cells. Sometimes, instead of a regular healthy cell, the virus comes into contact with cells involved in immunity. Those cells immediately recognize the virus as an invader and begin building an immune response, that, at the very basic level, takes on a couple of forms.

One form is the creation of antibodies. One of the cells involved in immunity is the B-cell which is programmed to identify the “key” a virus is using to gain access to the body’s cells and create a matching “cap” (i.e. antibody) for that key so that

the virus cell is neutralized and can be flushed out of the system. The other major aspect of immune response is targeting and eliminating the infected the cells so that they stop producing the virus — that is the job of the T-cell.

Together, the B and T-cells prevent new virus cells from being created and destroy the ones that were taken over before the immune system was able to mount its response. In the future, when that virus enters the body again, the immune system remembers the specific key the virus uses and reacts quickly to prevent much — or all — of the noticeable symptoms.

WHERE DO VACCINES PLAY INTO THIS PROCESS? In the case of vaccines, what has historically been done is to inject a weakened — or dead — version of the virus into the body. Those weakened cells don’t have the capacity to enter the body’s cells |but they do still have the same spikes on the outside — the same key — as the live virus. The immune system is then able to mount a response to those cells without the virus being able to multiply and create symptoms in the meantime.

In the event the live virus enters the body at a later time, the immune system is already prepared and can intervene to prevent the infection in the same way it would if it had first encountered the live virus rather than the weakened vaccine version.

DO THE EXISTING COVID -19 VACCINES WORK IN THE SAME WAY? Short answer — kind of, the result is the same, but the method is different. In the case of the Johnson & Johnson vaccine, it is what is called a “viral vector vaccine.” Different from the traditional vaccine that uses a dead version of the virus it seeks to prevent, a viral vector vaccine uses another virus’ cell as a transport vehicle for DNA from the virus the vaccine is preventing.

Specifically, J&J took a weakened adenovirus — a virus that typically causes a common cold — and injected the cells of that adenovirus with DNA from COVID-19. When the adenovirus enters a human cell, it disperses its own DNA and the portion of the COVID-19 DNA that was added so that when

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the cell begins to produce copies of the virus, they are common cold cells that are dressed up to look like COVID-19. This method means that neither the adenovirus or COVID-19 is capable of causing an infection, but the cells are recognized as intruders and trigger an immune response.

But - that is not the only vaccine approach taken for COVID-19, in fact, the Pfizer and BioNTech, and Moderna vaccines use an entirely different approach in first-of-their-kind mRNA vaccines.

VACCINE AND TREATMENT DEVELOPMENT

WHAT IS AN mRNA VACCINE? If we back up to when the virus cell enters the body’s cell and disperses its genetic material — its DNA — we could look very closely and find a specific section of that DNA - a messenger whose job is to carry the instructions for the virus to the appropriate machines within the cell; that messenger is called mRNA. Virus DNA

A specific section of that DNA — mRNA

One section of mRNA carries the design for the spike protein to the surface of the body cell.

In the case of COVID-19, one section of mRNA carries the design for the protein required to produce the spikes on the outside of the cell — or, to keep with the analogy, it carries the diagram of the key the virus uses to enter the body cells.

Researchers at Pfizer and BioNTech, and Moderna were able to isolate that specific messenger and insert it into a body. Once its inserted, it tells body cells to produce the spikes — and only the

Antibody

The really interesting part is that the mRNA that is injected is broken down and flushed out of the body leaving no trace of the vaccine but having already created a memory of the virus in the immune system. In fact, the mRNA alone is too fragile to live long enough to enter a body cell, so the vaccine surrounds the mRNA with lipid nanoparticles (think oil or fat) to protect it until it has a chance to set off the process of developing immunity.

WHY NOT JUST USE THE SAME TYPE OF VACCINE THAT HAS BEEN USED IN THE PAST? The mRNA type of vaccine has some definite advantages to the traditional weakened virus variety, including:

The body immediately recognizes them as intruders and mounts an immune response

spikes — of the virus cell. Some of those spikes travel to the surface of the body cell. When they do, the body immediately recognizes them as intruders and mounts an immune response in the same way it would if it encountered the live virus, or the J&J “virus in disguise”.

An mRNA vaccine can be produced more quickly than a traditional vaccine because an mRNA molecule is far simpler to create than a hybrid — weakened — virus cell used in a traditional vaccine,

The vaccine uses the body’s own machinery to produce the relevant virus parts rather than needing to externally produce full virus cells for injection,

There is no risk of infection from the virus because the body is only given instructions for a small part of the virus cell,

The vaccine has the potential to remain effective against new strains of the virus because most mutations alter aspects other than the directions for the spike protein.

That being said, there are some logistical drawbacks of the mRNA vaccine — specifically the mRNA is so fragile that it will quickly degrade at room temperature and requires extreme cold for transportation and storage to remain viable. So, while the vaccine technology has significant potential applications, it will work best as part of a fleet of vaccines including the J&J DNA-based vaccine.

The J&J vaccine, since it uses a full adenovirus cell to carry the COVID-19 DNA into the body, it has the advantage of being far more stable than an mRNA vaccine. That means it can be stored at regular fridge temperature rather than extreme cold. That easier storage, coupled with the fact that the J&J vaccine requires only dose to produce a sufficient immune response, makes it an ideal candidate for use in developing countries, in rural areas where access to extreme cold storage is scarce, and for people who are mobility or transportation impaired, or have a fear of needles, which would make a second shot difficult to manage.

Together, these vaccines create a powerful arsenal in the effort to stop the spread of COVID-19 and save lives.

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Disease Management

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Managing COVID-19: Saving Lives and Reducing Infection Rates has Been a Shared Burden KEYSTONE SOLUTIONS GROUP

TEKNA

MICHIGAN TECHNOLOGICAL UNIVERSITY

GENEMARKERS RAPIDBIO

LYNX DX

VELESCO PHARMA

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State of the Art Testing Solutions Support Rapid Scale-Up of COVID-19 Diagnostics

NEUMODX MOLECULAR

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Ensuring Products are Safe for Consumers, Even During a Pandemic

IMPACT ANALYTICAL

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Overshadowed by Ventilator Shortage Headlines, Home Oxygen Therapy is Critical to COVID-19 Patient Recovery OXUS AMERICA

Local ECMO Company Delivering Lifesaving Therapy for COVID-19 Patients Who Fail Traditional Lung Protective Ventilation MC3 CARDIOPULMONARY

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MANAGING COVID-19 :

Saving Lives and Reducing Infection Rates has Been a Shared Burden

BY ALISHA BROWN, MARKETING AND COMMUNICATIONS DIRECTOR, MICHBIO

COVID-19 was spreading exponentially, the sick were being hospitalized in numbers that overwhelmed the health care system, and proven effective treatments and vaccines were months away.

That was the situation in early 2020 as COVID-19 spread around the globe. In the absence of treatments and vaccines, managing the strain on healthcare systems and saving lives relied on reducing and then controlling disease spread while providing urgent care to those in need — not a small task. In fact, managing COVID-19 has proven to be an industry-wide effort with substantial collaboration with funding and regulatory organizations, and decision-makers at both the state and federal level.

Management Through Prevention Preventing illness prior to the development of a vaccine is accomplished by minimizing avenues for virus transmission - meaning reduced personal interactions, usage of appropriate personal protective equipment, and widespread decontamination of surfaces.

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In Michigan, as in many other states, drastic lockdown measures were taken that decreased the frequency and duration of personal interactions which provided an opportunity for the establishment of crucial supply chains and partnerships, and the ramp-up of manufacturing of essential products. For example, Keystone Solutions Group (opposite) was able to begin production of face shields in record time and provide protection for essential workers, healthcare professionals, and others, while ramping up packaging production to minimize supply chain disruptions for essential products.

Similarly, lockdown periods gave organizations like Tekna (opposite) the opportunity to formulate plans to support workers when they would eventually return to the office. The company re-envisioned a UVC disinfection product typically used in healthcare settings for broader use in offices to help remote workers transition back to the office safely.

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Critical Product Need is Met with Expert Solutions from Keystone

By Jim Medsker, President, Keystone Solutions Group

As the COVID-19 pandemic rose quickly on the radar on early 2020, the team at Keystone Solutions Group held true to their name and provided much needed solutions to some of the most critical product needs. Initially, there were several requests for face shields and sample collection swabs. The demand then expanded to sample collection vials and complete kits. To meet immediate demands as quickly as possible, the Keystone team mobilized and leveraged its partnerships with key suppliers. Within a few weeks, Keystone was producing face shields. Within six weeks, Keystone was providing sterile packaged sample collection swabs to local healthcare facilities as well as New York City. Shortly thereafter, vials and complete kits were in production and being distributed to those in need.

As of today, production continues, as well as infrastructure improvements to ensure the increasing demand is met. Shortly after launching face shield production, Keystone partnered with Goodwill Industries of Southwest Michigan to increase production capacity.

Additionally, the company is currently constructing an additional clean room and has acquired specialized, high-speed packaging equipment to help ensure uninterrupted supply of these key products.

Sterile medical devices often take several months from start to launch and the Keystone team has been able to accomplish that mission in a manner of weeks with several essential products to be able to swiftly provide critical solutions in the COVID-19 response effort. It has been a challenging and fulfilling mission and the team is honored and blessed to be able to help make a dent in the pandemic.

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Tekna Helps Make Offices Safer Submitted by Bryce Porter, Industrial Design Manager, Tekna

Since the beginning of the pandemic, Tekna continues to find ways to pivot its design and manufacturing business in response to needs in our community and beyond. Born out of necessity through the pandemic to quickly disinfect tools and equipment, Tekna adopted UVC light technology used in the healthcare setting to a new line of products that will be commercially available by the end of the year. Currently in pilot testing with WMU, surgical centers, and other diverse businesses, the need to disinfect commonly used tools and technology in an efficient matter resonates with many looking for ways to normalize in-person work, education and provide additional layers of safety, comfort and confidence

to staff and customers. Through the help and collaboration of its Michigan-based supply chain, Tekna looks to mitigate future disruption to supply by keeping its partnerships local — a win, win for the people and businesses of Michigan.

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At the same time, Michigan Technological University (below) launched its Mobile Thermal Utility Sanitizer capable of disinfecting up to 10,000 PPE units every two hours to support healthcare professionals contending with a shortage of face masks and other essential protective equipment.

Of course, support for the COVID-19 effort was not limited to the bio-industry — for example, distilleries around the State began to produce hand sanitizers to meet surging demand. In turn, that shift in operations created an increased need for product safety testing — such as that provided by Impact Analytical (pg 40) - to ensure that even rapidly produced and urgently needed products were safe to use.

Throughout, preventing illness has been a major focus of state and national legislators, bio-industry organizations, and those outside of the industry who were capable of pivoting their business models to respond to the urgent need for protective products. Even with this collaborative effort, prevention was only a small part of the entire disease management equation.

Management Through Tracing Infections

MTU Sanitizer Disinfects PPE Submitted by Allison Mills, Associate Director of Research News, Michigan Technological University

A refrigerated shipping container. Commercial-grade baking sheets. A modified oven. A prototype that uses heat to sanitize personal protective equipment (PPE).

That’s what an engineering team from Michigan Technological University tested in a campus parking lot — a refrigerated shipping container turned into a giant oven. They call it the Mobile Thermal Utility (MTU) Sanitizer.

The MTU Sanitizer can disinfect PPE between 140-170 degrees Fahrenheit temperatures, hot enough to break up coronaviruses, within a large trailer made with local, off-the-shelf parts that are easy to get and put together.

The unit can clean 5,000 to 10,000 PPE units every two hours and can run continuously.

Inside, the refrigeration unit is swapped for a generator-run heating unit and is lined with stainless steel racks and trays holding PPE. The Michigan National Guard currently has the MTU Sanitizer and the design is waiting on emergency use approval.

MTU.EDU/NEWS/STORIES/2020/APRIL/MTU-ENGINEERSBUILD-MOBILE-UNIT-TO-CLEAN-COVID19-PPE.HTML Images by Andrew Barnard/Michigan Tech Caption: The National Guard is using their truck and trailer to haul the MTU Sanitizer to downstate Michigan.

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Understanding community-wide infection rates, and tracing spread is only possible with significant diagnostic testing.

However, reaching the critical mass of testing that is required to control infection, presented a unique challenge.

Even for organizations with the lab space, equipment, and expertise required to quickly scale-up testing, the administrative and logistical burden of managing the collection, tracking, processing, and results communication for a large number of tests was an insurmountable barrier for many labs. Coupled with the lack of infrastructure — testing locations, community education and support, logistical and transportation services, and more — approved test kits, and supply chains for test manufacturing, the barriers to entry meant a slow ramp-up of testing capacity.

That is why, at the outset of the pandemic, testing was reserved for diagnosing symptomatic patients and it was only after the infrastructure caught up to, and surpassed, the capacity required for urgent care-related diagnosis, that communities could map their relative infection density and employ tracing and isolation policies that could mitigate transmission.

Many organizations stepped into the testing space to fill the urgent need, such as Genemarkers (opposite) who transitioned aspects of their existing lab space to service diagnostic tests for COVID-19, and RapidBio (opposite) who was founded for the purpose of providing COVID-19 diagnostic testing services.

Submitted by Ashley Choker, Clinical Services Account Manager, Genemarkers, LLC

Genemarkers, a clinical testing company located in downtown Kalamazoo, was grateful to receive a grant from the Pure Michigan Business Connect program to support a quick pivot from its traditional services to COVID-19 diagnostic testing. Having performed PCRbased testing since 2008, the technicians and laboratory leadership were eager to step up and do their part to help stop the spread of the disease. With only 8 staff, the Genemarkers team pulled together and began testing in June 2020. Genemarkers leveraged partnerships with local pharmacies to provide test collection services and is currently working with six pharmacies throughout southwest Michigan. Genemarkers is also supporting many skilled nursing facilities and assisted living communities whom this pandemic has hit the hardest. The Company now has over 50 employees and has run over 200,000 patient tests.

GENEMARKERSLLC.COM

RapidBio Real Time PCR Testing Submitted by John Cunningham, CEO, RapidBio

RapidBio is a molecular diagnostics laboratory dedicated exclusively to providing high throughput SARS-CoV-2 diagnostic services using real time PCR methods. Located in the Michigan Life Science Innovation Center, in Plymouth, MI, the company features a 5,000 sf lab facility, utilizes fully automated robotic instrumentation for sample handling, and currently has a team of 30 people, with a capacity to run up to 6,000 samples/day.

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Genemarkers Pivots to COVID Testing

Testing became an impactful part of the COVID-19 management puzzle as the ability to monitor infection rates more broadly was established.

One critical organization in that effort is Lynx DX (pg 36) who transitioned their lab space and logistical and administrative capabilities from prostate cancer screenings to community-wide COVID-19 testing, became one of the largest testing organizations in the state and is the go-to testing provider for the University of Michigan as they manage asymptomatic spread on their campus.

At an even broader scale, high-throughput test processing was urgently needed to keep pace with the growing demand. Michigan’s NeuMoDx Molecular (pg 38) developed a COVID-19 diagnostic test, which was granted an Emergency Use Authorization, that is processed on the company’s proprietary, sample-to-result lab equipment capable of providing results in approximately 80 minutes continuously.

Of course, ramping-up testing would be impossible without the simultaneous increase of test kit production and assembly by countless organizations around the state — including Velesco Pharmaceutical Services (pg 36) who immediately took up the call for contract manufacturing of test kits.

Testing has now transitioned to both diagnostic and serology (antibody) testing and continues to be an important part of disease management requiring collaboration among suppliers, manufacturers, labs, support services, and others at record speed.

RapidBio has partnered with Wayne Health, an affiliate of Wayne State University to support community collections, a major medical center, local schools, and partners across the country. The company is launching a drive through sample collection facility at the USA Hockey facility on Beck Road.

Additional testing planned will include a complete respiratory panel, UTI, wound, and other molecular diagnostic testing services.

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Velesco Pharma Provides Essential Contract Services

By Alisha Brown, Marketing and Communications Director, MichBio

The COVID-19 pandemic has generated significant demand in all areas of pharmaceutical development, as well as, a demand for diagnostic testing services that aid in the management of the disease in the period of time between initial discovery, and vaccine and treatment development.

Velesco Pharmaceutical Services - a Wixom-based company that provides contract research and manufacturing to the pharmaceutical industry with specific expertise in early phase drug development - has been involved in both supporting the development of drug therapies and the assembly of diagnostic test kits.

The company’s GMP clinical manufacturing facility is working with pharmaceutical companies that are developing potential COVID-19 treatments to manufacture investigational drugs in support of early phase clinical trials. Early phase trials are used to determine if an investigational new drug is safe to use and efficacious — they involve a smaller number of study participants who are monitored closely for potential side effects. Reliable investigational new drug manufacturing

is essential to the success of early phase clinical trials; Velesco Pharmaceutical Services has decades of experiences aiding companies as they develop study protocols and work through the early drug development process.

In addition to investigational new drug manufacturing, Velesco is assembling diagnostic COVID-19 testing kits that are sent to diagnostic laboratories to process COVID-19 swabs.

The State-wide effort to increase the number of diagnostic tests conducted each day has meant a steady demand for manufacturers like Velesco.

VELESCOPHARMA.COM

Lynx Dx Becomes Trusted Testing Partner for Michigan For the State of Michigan, one key component in the scaleup of diagnostic testing in response to COVID-19 is Lynx Dx — a University of Michigan spinout working on entering the prostate screening space at the beginning of 2020. When it became clear that prostate screening rates were dramatically reduced and likely to remain that way for some time, Lynx had a decision to make — ride out the slow period or transition their existing commercial lab and testing expertise to COVID-19 — they chose the latter.

In the time since making that decision, Lynx Dx has become an essential testing partner for Michigan working with the Washtenaw County Health Department and State of Michigan Department of Health and Human Services to provide broad community testing that enables disease tracking and management, and supports decisionmakers in their efforts to isolate the sources of spread for intervention.

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Currently, Lynx operates a large drive-through testing site in Ann Arbor in partnership with the Washtenaw Country Health Department and 2/42 Community Church, provides testing for homeless shelters and around 40 nursing homes. Lynx is also the official asymptomatic testing provider for the University of Michigan enabling the institution to regain control of infection on campus. Lynx went from an emerging prostate screening lab to the 4th largest COVID-19 testing facility in Michigan and grew from 4 employees to over 80 in the effort to keep up with testing demand.

LYNXDX.COM

At the same time as organizations were ramping up production of personal protective equipment and disinfectants, and laying the groundwork for communitywide diagnostic testing, others coalesced around the need for essential medical equipment for treating the sick.

Most patients do not get critically sick and many of those that do respond well to traditional intervention, but there are some who do not. For those patients, one of the only remaining options for oxygenation therapy is ECMO — a lung-bypass that provides external oxygenation of a patient’s blood — provided by companies like MC3 Cardiopulmonary (pg 42).

In the early days of the pandemic, healthcare professionals relied on their experience with other respiratory illnesses and used ventilators to provide breathing support for the sickest patients. Ventilators were such an essential part of that early treatment that they quickly became scarce.

While some organizations worked to increase ventilator manufacturing, others innovated to expand the usage of the available equipment. For example, MakeMedical (below) who developed a ventilator splitter that enabled care professionals to treat two patients with a single machine.

The combined effort of these organizations to provide the necessary equipment to treat COVID-19 patients is a small part of the monumental task that faced health systems and the industry at the outset of the pandemic. While the understanding of the disease and best practices for treatment have evolved and the need to specific supplies, like ventilators, has leveled off, they are replaced with the need for new or different tools for patient care and the bioindustry has continuously responded.

Even as the need for ventilators was matched with supply, organizations like Oxus America (pg 41) that provide equipment for supplemental oxygen therapy - such as that provided in a patient’s home as they recover from a severe respiratory illness - scrambled to increase new equipment and refurbish any and all existing machines to meet the surging demand. For many patients who experience even modest COVID-19 symptoms, home oxygen therapy is required to make a full recovery.

While the end goal has always been the development of effective treatments and vaccines, the collaborative effort of industry organizations, paired with the willingness of millions of individual people to follow the guidelines laid out by public health experts and decision makers, and the dedication of healthcare workers the world over, has reduced the number of lives lost and patients infected significantly.

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Management Through Treating Infections

3D Printing and Rapid Prototyping Provide an Innovative Solution to the Ventilator Shortage

By Owen Tien, MakeMedical

MakeMedical’s contribution to the fight against COVID-19 was the rapid development and prototyping of a new type of ventsplitting device, the VentMI™ (Ventilate Multiple Individuals).

Faced with potential ventilator shortages, the MakeMedical team, consisting of practicing surgeons and additive manufacturing professionals, worked to develop ways to increase ventilatory capacity in a way that could quickly be brought to bear where needed. The concept of the device was developed in early March, and through the use of 3D Printing and CAD driven design they were able to prototype multiple iterations of the device daily. By early April MakeMedical had moved to a machined and ready for large-scale production device that was subsequently approved for use through an Emergency Use Authorization (EUA) by the FDA. While splitting a ventilator should only be done in an emergency and isn’t a novel concept, the VentMI™ allows healthcare professionals to retain certain individualized controls over each patient on a split ventilator. A simple splitter requires that each patient be on the exact same settings with

the ventilator controlling both patients’ breathing. VentMI™ has an internal novel pressure valve system that snaps shut and open when specific pressure parameters are met for one patient, while the ventilator controls the other patient’s settings. The addition of custom machined PEEP valves allows for a system that reduces the downsides of ventilator splitting.

The system is 1/20th the cost of an additional ventilator and can be rapidly deployed by a trained medical professional.

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NEUMODX MOLECUL AR

State of the Art Testing Solutions Support Rapid Scale-Up of COVID-19 Diagnostics

BY ALISHA BROWN, DIRECTOR OF MARKETING AND COMMUNICATIONS, MICHBIO SOURCE MATERIALS PROVIDED BY NEUMODX MOLECULAR

For the past twenty-five years, the bio-industry has been evolving. Industry infrastructure, with sophisticated labs appearing at major institutions and companies around the globe, coupled with the ability to measure and analyze the expression of the entire genome, has put an emphasis on speed and accuracy in diagnostic testing.

Add a global pandemic where the ability to track and trace disease spread is essential to preventing infection and saving lives, and the importance of high-throughput, highly efficient, diagnostic testing has never been more evident.

NeuMoDx Molecular, an Ann Arbor-based company led

by Sundu Brahmasandra, PhD, has been working in the diagnostic testing space since 2012 and has developed a family of scalable molecular testing platforms that fully integrate the entire molecular diagnostic process from “sample to result” to give laboratory professionals the tools they need to operate efficiently and cost-effectively — an ability that has proven to be invaluable during the COVID-19 pandemic.

In March of 2020, NeuMoDx developed a rapid, automated in vitro real-time RT-PCR diagnostic test for the detection of SARS-CoV-2 RNA that works in the NeuMoDx Molecular Systems. The company was granted an Emergency Use Authorization and aided in the rapid scale-up of COVID-19 testing that was required to trace, study, and manage the growing pandemic.

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“Our industry-leading equipment can be loaded with an assay and run with little or no intervention by lab workers,” said Dr. Brahmasandra. “In clinical settings, this enables lab personnel to maximize utilization of their resources, while at the same time significantly improving patient care by reporting accurate diagnostic results in a rapid manner.

In the case of COVID-19 diagnostics, such efficiency and accuracy of testing can be a powerful tool in significantly slowing the spread of the disease.”

When used with the NeuMoDx SARS-CoV-2 ready-to-use reagents, the NeuMoDx Molecular Systems require only three steps to reach a result of a SARS-CoV-2 test and can test approximately 660 patient specimens in a 24-hour period while occupying less than two square meters of lab space.

“In normal operation,” continued Dr. Brahmasandra, “when the machine is loaded with COVID-19 samples, the first results come back in approximately 80 minutes, with additional results every few minutes continuously until all loaded samples are tested. In a hospital or emergency setting when lab workers are likely conducting multiple diagnostic tests at the same time, the STAT mode can be used and testing for COVID-19 can be done without disrupting any other tests currently loaded. This allows for 80-minute test results without requiring a dedicated machine that may sit idle between patients.”

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NeuMoDx Molecular assay kits and testing systems have been used to process millions of COVID-19 diagnostic tests around the globe.

In September of 2020, NeuMoDx was acquired by Qiagen, the leading global provider of sample to insight solutions that ties together sample and assay technology with bioinformatics and automation to isolate, analyze, and interpret testing data seamlessly and cost-effectively. NeuMoDx’s industry-leading devices have the fastest fully automated turnaround time allowing laboratories to process ever-larger volumes and deliver ever-faster insights into many infectious diseases making them an ideal fit for QIAGEN and an important piece of its global testing portfolio.

In addition to COVID-19 testing, NeuMoDx has received FDA 510(k) clearance for its NeuMoDx GBS Assay for the detection of Group B Streptococcus (GBA) DNA in antepartum pregnant women and will continue development of tests to detect and monitor sexually transmitted and infectious diseases.

“At NeuMoDx,” continued Dr. Brahmasandra, “improving clinical molecular diagnostic workflow is all we do and our 200+ employees are solely focused on developing, producing, and supporting the world’s most advanced systems for automated, high throughput clinical molecular diagnostics.”

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I M PA C T A N A LY T I C A L

Ensuring Products are Safe for Consumers, Even During a Pandemic

BY ALISHA BROWN, MARKETING AND COMMUNICATIONS DIRECTOR, MICHBIO, BASED ON SOURCE MATERIALS PROVIDED BY IMPACT ANALYTICAL

The urgency with which organizations developed products essential to the COVID-19 effort left many decision-makers, and the general public, with one important question — are the products safe?

That is where organizations like Impact Analytical, a full-service contract lab providing comprehensive testing solutions for the pharmaceutical, bioanalytical, plastics, medical device, consumer products, and chemical industries, come in - analytical testing can ensure that a product meets regulatory requirements for safety.

The Midland-based company quickly assessed the urgent need for increased testing and invested both in equipment and people to address the needs of the industry. Impact conducted extractable and leachable studies for single use medical devices — such as those used to administer vaccines — to ensure that the product being developed would not cause the devices it was in contact with to leach substances that could have potentially adverse effects on the product itself or consumers using it.

“I am proud of the lengths our employees went to, to make sure we could provide this important service — they worked many long days and weekends to ensure that potentially life-saving drugs could be shipped to Europe at the very start of the pandemic.” Stated Neil Chapman, President of Impact Analytical.

In addition, Impact was called upon to test hand sanitizer products quickly developed and brought to market — in many cases by companies outside of the life science industry or without any prior experience in sanitizer manufacturing — to ensure they met FDA safety requirements.

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“For the average end-user, ethanol, methanol, and propanol all sound the same,” continued Chapman, “but they have very different effects on the body. If a sanitizer contains methanol as an ethanol substitute it can lead to methanol poisoning and give the user headaches, blurred vision, nausea and more — and the average consumer would never know to look for it. Testing like ours ensures the products are safe.”

Impact recently expanded its team to include experts in bioanalytical sales and testing, as well as investing over $1M in new equipment that enabled the company to quickly develop processes and protocols, and provide testing results in a timely manner to help clients avoid delays to market.

This new hardware, along with industry recognized experts, has allowed Impact to enter new markets providing analytical support to the bioanalytical industry. Bioanalytical testing gives a quantitative measure of the amount of an API/NCE that is contained in a sample.

While the contract testing services made a significant impact to the State’s ability to respond to COVID-19, Impact also contributed in the area of production company lab support.

With many organizations in company-mandated shutdowns, there was a sizeable backlog of testing across all business sectors — that Impact, as an essential business, was able to take on and ensure those clients were able to continue their production. Throughout, analytical testing service companies, like Impact Analytical, have served varying functions all with the same goal — make sure any product that makes it to market is safe to use.

IMPACTANALYTICAL.COM

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OXUS AMERICA

Overshadowed by Ventilator Shortage Headlines, Home Oxygen Therapy is Critical to COVID-19 Patient Recovery

BY TIM HATT, SR., DIRECTOR OF SALES AND MARKETING, OXUS AMERICA

In late February 2020 newscasts were consumed by the now familiar litany of COVID-19 related infections, deaths, hospitalization rates, PPE shortages and the call for ventilators — COVID-19 was front-and-center in mainstream American thought. At the same time, companies providing home medical equipment were all too aware of what it meant for their industry. Although nightly news reports raised the alarm regarding the shortage of ventilators, industry professionals knew that supplemental oxygen delivery was a much more frequently used therapy and the related equipment was about to become the most sought after equipment in COVID-19 patient recovery.

require maintenance, and Oxus provides the key service components to allow them to operate at peak efficiency.

By early April 2020, Oxus had heard from all of the leading home medical equipment providers about the severe shortage of parts in the industry. Oxus accelerated the expansion of its manufacturing footprint - hiring new staff and investing in equipment and tooling to meet the overwhelming demand. Oxus’ mission was clear: manufacture quality oxygen concentrator service parts to enable the local and national oxygen providers to expand and maintain their oxygen concentrator fleets and meet the needs of an unfortunately growing patient population.

In 1965, the Medicare Act authorized a benefit known as DMEPOS (Durable Medical Equipment, Prosthetics, Orthotics and Supplies). This benefit paid for medical treatment in the home setting, including long-term oxygen therapy. At first, at-home oxygen therapy was used infrequently because it required large and difficult to use oxygen tanks. However, the advent of the oxygen concentrator — a medical device used for separating ambient room air and producing a 94% concentration of oxygen - in the late 1970’s paved the way for the widespread use of inhome oxygen therapy seen today.

Oxus America’s team, with a long history rooted in Michigan’s automotive manufacturing sector and over 15 years dedicated to medical devices, was uniquely suited to the challenge. Led by its engineers, Oxus collaborated with its supply chain, local employment agencies, and state and county governments to marshal the required resources and implement an aggressive plan. The work done by Oxus, oxygen concentrator OEMs, and home medical equipment providers throughout the nation has allowed for the delivery of the critical home oxygen therapy that severely affected COVID-19 patients require for a successful recovery.

What those in the industry knew in back in February, was that while ventilators were needed for hospitalized patients, COVID-19 would lead directly to a sharp increase in demand for long-term in-home oxygen therapy for recovering patients. To satisfy that the spike in demand, every Home Medical Equipment provider was both trying to purchase as many new oxygen concentrators as possible, but also, was scouring every warehouse and storage facility they had to bring out of retirement any repairable oxygen concentrators they could find.

The country is facing yet another wave of COVID. While the nation’s newscasts are dominated once more with reports of hospitalizations, PPE shortages and infection rates, and news of a vaccine; the medical device industry and its suppliers, like Oxus, are stepping up to support other needs of the health care system, like home-based long-term oxygen therapy.

Enter Oxus America, an ISO 13485 Certified OEM manufacturer of oxygen concentrator service parts located in Auburn Hills MI. Oxygen concentrators

OXUSAMERICA.COM

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DISEASE MANAGEMENT

MC3 CARDIOPULMONARY

Local ECMO Company Delivering Lifesaving Therapy for COVID-19 Patients Who Fail Traditional Lung Protective Ventilation

BY RIO FOSTER, VP SALES AND MARKETING, MC3 CARDIOPULMONARY

MC3 Cardiopulmonary, located in Dexter, was founded in 1991 by Robert Bartlett, M.D., a pioneering University of Michigan surgeon, and Scott Merz, to develop Extracorporeal Membrane Oxygenation (ECMO) technology for patients who would otherwise succumb to heart and lung disease.

In 2013, Robert Foster, a successful medical device businessman, acquired MC3 with a laser focus on manufacturing best-in-class ECMO products.

The standard of care in the intensive care unit (ICU) for the sickest respiratory patients is mechanical ventilation. While this technology is very effective in many patients, for some, it simply does not work. ECMO works as an artificial lung by delivering oxygen to the patient when the lungs or heart are unable to do so. For respiratory failure, a catheter is placed in the central vein near the heart and is connected to a blood pump, similar to that found in a heart-lung machine.

Deoxygenated blood passes through a gas exchange module or “oxygenator,” and freshly oxygenated blood is returned to the patient. For patients with cardiac failure, blood is drained from the vein and returned to the system.

ECMO requires safe access the patient’s central circulatory system, which is why MC3’s first ECMO product was focused on vascular access. The CRESCENT™ Dual Lumen catheter, cleared in 2018 as the first device indicated by FDA for long-term ECMO, quickly became a market success.

MC3 is heavily invested in improving ECMO access catheters for a broad range of clinical applications and patient characteristics.

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“There is an underserved population suffering with lung failure, and the introduction of our Crescent catheter means new options for clinicians and their patients,” said Scott Merz, CEO of MC3 Cardiopulmonary.

Dr. Errol L. Bush, Surgical Director, Advanced Lung Disease and Lung Transplant Program, Johns Hopkins University, said the following during his moderation of the ECMO and COVID-19 session at the 2021 Society of Thoracic Surgery conference:

“COVID-19 forced us to be innovative in our utilization of ECMO and more thoughtful about criteria for patients to be considered ECMO candidates because of the intense amount of resources ECMO would require in the setting of heavily strained resources caused by the pandemic.

Due to the advancements in ECMO technology over the last decade, we are finally able to manage these patients more safely and with better outcomes than previously thought.

Our experience backs up previous reports regarding the successful use of Dual Lumen Catheter for VV ECMO, and our preference for their use has really built our ECMO program and enabled safe deployment and successful outcomes with our new multidisciplinary bedside model.”

MC3 has also innovated the designs of artificial lungs or oxygenators used in ECMO. Just before COVID-19, MC3 launched its second game-changing ECMO therapy solution— the NAUTILUS™ Smart ECMO Module—first in Europe and

DISEASE MANAGEMENT

then in the United States. Blood enters Nautilus and passes through both a heat exchange membrane—where temperature is adjusted—and a gas transfer membrane—where oxygen is added, and carbon dioxide is removed. The device contains integrated sensors with an electronic touch screen display and a status bar that enables vital, at-a-glance monitoring of hemodynamic device health parameters. These features are enabling clinicians to support patients suffering from COVID-19 who are failing traditional support modalities.

“Launching a new medical device during the global pandemic has been a gratifying yet challenging endeavor on so many levels. We have worked hard to stay safe and keep production running while attempting to aggressively ramp up manufacturing to meet the product demands of our global distributor, Medtronic,” said Scott Merz.

New Evidence to Support ECMO and Covid-19 A recent study in The Lancet (October 10, 2020) reported the broad international experience with ECMO in COVID-19 patients, which are captured in the Extracorporeal Life Support Organization (ELSO) Registry. ELSO is an Ann Arbor-based organization founded by Dr. Bartlett, with the mission to provide continuing education, guideline development, and maintenance of a comprehensive patient registry of the use of ECMO. The Lancet article reported the outcomes of 1,035 ECMO-supported COVID-19 patients treated between January 1 and May 1, 2020, within 213 hospitals across 36 countries.

Research showed the mortality rate within this patient group was 37.4% and concluded that experienced ECMO centers should consider the use of ECMO in refractory COVID-19related respiratory failure.

“We continue to track outcomes of ECMO use in COVID-19 patients,” said Christine Stead, CEO, ELSO. “ELSO’s global live dashboard shares patient outcomes in as close to real time as data entry allows. We believe that ECMO can be an effective treatment option for COVID-19 patients.”

In a study of early intervention with ECMO in COVID-19 patients, a research letter published in the August 2020 JAMA issue presented the outcomes of 40 consecutive COVID-19 cases, showing survival was 85%.

Interest and adoption of ECMO as a life-saving technology has increased since the start of the pandemic. Michigan has played a central role in the advancement of ECMO therapies, both in the clinical work done by Dr. Bartlett, and now in the devices made by MC3 in Dexter and helping patients worldwide.

MC3CORP.COM

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Public Health Management

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Public Health Management: From Supply Chain Coordination to Mobile Health Care, Essential Services Aid in the Pandemic Effort

IN2BEING

LAWRENCE TECHNOLOGICAL UNIVERSITY

UNIVERSITY OF MICHIGAN

50 |

Leveraging Michigan’s Arsenal of Innovation in the Fight Against COVID-19

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Confronting Covid-19

MICHIGAN’S UNIVERSITY RESEARCH CORRIDOR

52 |

Importance of Operationalizing Public Health Strategies

NSF INTERNATIONAL

53 |

Navigating the Rapidly Changing COVID Regulatory Climate Takes a Seasoned Expert

EMMA INTERNATIONAL

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Animal Housing Area Becomes FDA Authorized Decontamination System

MICHIGAN STATE UNIVERSITY

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Innovation Built on Collaboration

MICHIGAN ECONOMIC DEVELOPMENT CORPORATION

WAYNE STATE UNIVERSITY AND WAYNE HEALTH’S MOBILE TESTING PROGRAM

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PUBLIC HEALTH MANAGEMENT:

From Supply Chain Coordination to Mobile Health Care, Essential Services Aid in the Pandemic Effort

BY ALISHA BROWN, MARKETING AND COMMUNICATIONS DIRECTOR, MICHBIO

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With so many organizations involved in COVID-19 work, there has been significant demand for high-level coordination, management of supply chains, funding support and operationalizing of recommended strategies. These roles are easily overlooked when compared to the highly publicized vaccine development and direct patient care but are no less important to the success of the pandemic effort.

For the Michigan Economic Development Corporation (MEDC) it meant mobilizing the existing Pure Michigan Business Connect (pg 50) platform to serve as a state-level clearinghouse for COVID-19 information and resources, as well as a place where supply chain requests could be made, funding opportunities disclosed, and national programs accessed. And for the University Research Corridor (URC) (pg 51) it meant monitoring, collecting, and distilling of research occurring at the state’s higher education institutions to aid in rapid information exchange.

With new information, best practices, and studies emerging almost daily, it quickly became clear that there was an urgent need for groups that could “connect the dots” — share supply with demand and serve as conduits for information, funding opportunities, and other essentials. For in2being (opposite) that took the form of weekly virtual gatherings, dubbed COVID Connect, that began as a place for those looking for resources to connect with suppliers and morphed into a go-to source for the latest information on research from around the state and the nation.

Included in the research conducted at higher ed institutions were studies on the impact the of specific lockdown measures on mortality and the economy from the University of Michigan Department of Mathematics (opposite), disease spread modeling from Lawrence Technological University Mathematics faculty (pg 48), and examination of existing drug compounds that could be produced more quickly and combined to make essential medicines even with disrupted supply chains from the University of Michigan synthetic chemistry faculty (pg 48). These studies, and many others, provided vital information to decision-makers on how best to proceed with management of public behavior, balancing economic and public health concerns, and more.

MICHBIO | michbio.org

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Start-up Experts at in2being Provide Essential Supply Chain Support

By Gene Parunak, Managing Director, in2being & Metric Marketing

in2being responded to the COVID-19 pandemic in good faith as did many other Michigan companies. As an initial effort, team members with expertise in textiles began making face masks for local hospitals, which were well received. It became apparent, however, that without significant supply chain infrastructure, mask making by hand would not make a dent in the true need. in2being’s core expertise is working with startups to develop and clear medical devices through the FDA. Leveraging this know-how, in2being created a weekly webinar series called COVID Connect to provide insights and updates on FDA emergency use authorizations (EUA’s) and a point of connection for companies looking to partner with each other.

Ecosystem partners like MichBio, the University of Michigan, Keystone Solutions Group, and others helped put out the call, and 230 live callers tuned in to the first episode.

These webinars have created a strong platform for dialogue. Many connections have been made, including an unprecedented amount of ongoing communication and partnering between East and West Michigan.

The community is what makes MedTech Crossroads. Without the participation by many in the community, including MichBio, MedTech Crossroads could not have become what it is today.

Join Medtech Crossroads every Friday @ 2pm ET.

After 11 weeks, COVID fatigue set in for many. To stay ahead of this, in2being transitioned the webinar series into a multifaceted program called Medtech Crossroads. These episodes focus on different aspects the medtech ecosystem (investment, development, entrepreneurship, manufacturing) while coming back to COVID as needed.

IN2BEING.COM

The Key to Ending Lockdown is Found in Socially-Dependent Behaviors

By Alisha Brown, Director of Marketing and Communications, MichBio based on source materials provided by the University of Michigan

The COVID-19 pandemic and subsequent lockdowns have highlighted the complex relationship between a country’s public health and its economic health. Models that can calculate the impacts of disease outbreak — both to the population and the economy — can be useful tools for decisionmakers attempting to balance the immediate and long-term impact to both.

A team of researchers at the University of Michigan including April Nellis, a doctoral candidate in the U-M Department of Mathematics, developed an SIR (susceptible-infectedremoved) model that considers herd immunity, behaviordependent transmission rates, remote workers, and indirect externalities of lockdown to predict a timeline for exiting lockdown when herd immunity, either through natural disease spread or vaccine deployment, is achieved.

The underlying SIR epidemiology model predicts the spread of disease by taking into consideration the number of susceptible individuals, the number of infectious individuals and the number of removed individuals—whether by death, recovery or resistance — and includes unique lockdown scenarios for two different populations — low and high-risk

adults. The model also includes a number of other factors, including recovery rate, base mortality rate of COVID-19, rate of ICU admittance, interaction level between groups, timeline for a vaccine or cure and proportion of workforce that can work remotely, among other parameters.

Using this model, the team demonstrated that a lockdown which ends with the arrival of herd-immunity, coupled with social-dependent behaviors such as increased mask usage and social caution when infection rates are high, can shorten the duration of lockdown periods while decreasing mortality to one-third of no-lockdown levels and mitigating loss to economic output.

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Mathematical Models Shed Light on Social Behaviors in Disease Spread Submitted by Matthew Johnson and Bruce Pell, Assistant Professors, Department of Mathematics & Computer Science, Lawrence Technological University

A significant challenge in forecasting the spread of infectious diseases such as COVID-19 is understanding how the disease’s spread influences social behavior, and how behavioral changes in turn alter the spread of the disease.

Understanding this relationship is especially important for novel diseases such as COVID-19 since containment has necessarily focused on social behaviors such as social distancing, face mask utilization, and restricted travel.

a susceptible class, an infectious class, and a removed class, and the course of the disease spread is predicted through interactions of these classes. The models developed by Johnston and Pell additionally incorporate social perceptions such as fear of infection, which depends upon the population’s infection level, and social frustration, which depends on the level of disruption caused by social distancing.

Assistant professors of mathematics Matthew Johnston and Bruce Pell of Lawrence Technological University have used the power of mathematics to face these challenges headon. Together with a team of undergraduate students, they have been developing sophisticated mathematical models which explicitly incorporate the effects of social distancing on the spread of COVID-19, and track the progression of the pandemic over time.

By fitting their models to data, Johnston and Pell hope to create forecasts of the spread of the disease that will guide public policy and predict the timing and scale of secondary waves of infection.

The models used are extensions of the classical SIR differential equations model. In these classes of models, a population is divided into distinct compartments, such as

LTU.EDU

Researchers Use AI to Support the Pharmaceutical Supply Chain

By Alisha Brown, Director of Marketing and Communications, MichBio based on source material provided by the University of Michigan

With the race on to develop safe and effective vaccines and treatments for COVID-19, synthetic chemists at the University of Michigan, including researcher Tim Cernak, an assistant professor of medicinal chemistry and chemistry, began to examine an overwhelming problem — how can the industry possibly produce enough doses of any of the approved treatments to meet the urgent and growing demand with the existing supply chain of pharmaceutical building blocks?

Every drug has a defined molecular structure, but there are many ways to assemble that structure using varying commercially available building blocks. If the team could identify alternate building blocks that were more readily available, or could be produced in advance of drug approval, the industry could avoid significant delays in production.

Using artificial intelligence, crowdsourced information on patented synthetic routes, and the available building blocks, the team was able to examine 12 drugs in development for the treatment of COVID-19. The AI was able to create different recipes for each of the drugs which the team was able to examine and winnow down to those that were simpler that the existing synthetic routes and used building blocks not already in the supply chain to develop avenues to productions that were both more cost-effective and would reduce the strain on the supply chain.

LSA.UMICH.EDU/MATH

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PUBLIC HE ALT H MANAGEMEN T The Industrial Sewing and Innovation Center in Detroit sewing isolation gowns in a 12,000 square foot third floor of the work apparel outfitter Carhartt Inc.'s Midtown Detroit building, rather than the T-shirts and other apparel initially planned to launch the site.

When those decision-makers developed guidelines, such as workplace safety and return to work requirements, groups like NSF International (pg 52) stepped in to fill the gap between those guidelines and actual operations with education, documentation of progress, and more. Together, the combination of funding research, distilling findings, and operationalizing the subsequent recommendations served a major role in managing COVID-19.

In addition, regulatory changes for COVID-19-related products had to be both communicated and navigated to ensure products were able to come to market and get to care professionals. EMMA International (pg 53), among others, took on that role in Michigan and aided organizations with regulatory filings in both the United States and the EU. Large scale projects in the state that were built on crosssector collaboration and partnerships demonstrate how effective this combined high-level coordination and management can be. For example, at Michigan State University (pg 54) a team of experts from higher ed, industry, healthcare systems and more came together to transform a large animal facility on the MSU campus to a major mask decontamination site serving multiple counties, health systems and organizations throughout the state while developing a “playbook” for future mobilization of similar coordinated efforts.

But perhaps the best example is the work being done at Wayne State University (pg 56) to bring together community partners and bio-industry resources to directly address health disparities in the state by mapping underserved areas, deploying appropriate mobile health centers, and connecting affected communities and individuals with not only COVID-19 testing, care, and vaccinations, but also with social services to aid in community well-being. While this focused effort to understand and tackle health disparities was born out of the urgent need to address the pandemic, it will continue into the future and have a lasting impact on healthcare within the state — and it would not be possible without the high-level coordination of available services, supplies, and expertise.

While this form of public health management does not get the same media attention as vaccine research or patient care, every other piece of the COVID-19 effort relies on the work done to connect the dots in the supply chain, share information, provide operational support, and distribute funding to the right places at the right time.

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M I C H I G A N E C O N O M I C D E V E L O P M E N T C O R P O R AT I O N

Leveraging Michigan’s Arsenal of Innovation in the Fight Against COVID-19

BY BOBBY CHASNIS, DIRECTOR OF PURE MICHIGAN BUSINESS CONNECT AT THE MICHIGAN ECONOMIC DEVELOPMENT CORPORATION

It has been almost a year since the novel coronavirus disrupted nearly every part of life. The pandemic has closed schools and businesses, disrupted supply chains and production, and forced states and individuals to adapt and navigate COVID-19 safety restrictions while filling the gap of personal protective equipment (PPE).

In Michigan, manufacturing and life sciences became essential services along with first responders and frontline workers. The high demand for PPE reflected a skyrocketing number of cases developing across the state. In response, the Michigan Economic Development Corporation (MEDC) turned to its Pure Michigan Business Connect (PMBC) program to develop and deploy the COVID-19 Emergency Access and Retooling Grants program that awarded a total of $1 million to 12 small businesses and nonprofits who retooled production lines to produce critical health and human service supplies in response to the outbreak.

The state’s deep manufacturing knowledge was transformed, and our skilled workforce transitioned — providing for critical resources and helping companies stay viable during economic uncertainty. For example, Traverse City-based TentCraft received $75,000 in grant funds to pivot from creating custom prints and tents for event booths and sports arenas to producing medical tents for drive-through testing and pop-up mobile infirmaries. With no previous experience manufacturing products for the health care or medical industry, TentCraft was able to quickly shift its operations to not only support local instillations but grew nationally with orders being delivered to hospital systems in Texas, Massachusetts, Illinois and Pennsylvania. In total, the 12 businesses that received retooling grants produced 2.5 million units of PPE right here in Michigan in a matter of months, while generating $27 million in new sales supporting their workforce and continued operations in the state.

However, procurement needs during the pandemic extend beyond PPE, and COVID-19 has presented a unique set of challenges for the traditional supplier and buyer relationship. To fill this gap, PMBC responded with a free, 50

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virtual procurement and donation assistance platform. The platform helps facilitate introductions between Michigan businesses and organizations capable of providing human services and health resources, such as face shields, masks, cleaning equipment, or medical devices to assist businesses in need of supplies to keep employees and customers safe. Since Michigan’s phased approach to the economy reopening in June, this platform transitioned to support businesses — and even schools and municipalities — in need of non-medical PPE, with more than 4,125 businesses or organizations with PPE needs accessing the portal to connect with 420 Michigan suppliers to date.

In all corners of the state and across all industries, Michiganders have joined together to find innovative ways to use every resource available. That includes leveraging the MEDC Tech Startup Stabilization Fund that allowed start-ups to continue vital advanced high-tech research and provide economic relief to companies such as Bedestrain, providing robotic delivery services within and around health care facilities. And the COVID-19 Mobility Solutions Grant that provided startups with funding to aid in the development and deployment of solutions to address the mobility challenges presented by COVID-19 in Michigan. In total, the MEDC has supported 18,500 companies and small businesses statewide, helping to retain more than 146,900 jobs across all 83 counties through 20 different COVID-19 relief programs and initiatives.

And, just like businesses have altered their operations amid the COVID-19 pandemic, PMBC has also done the same. That shift started with leveraging Michigan’s manufacturing roots, life science know-how and deep talent pool to support vital response efforts and continues with dedication to providing economic relief to workers, small and mid-sized businesses and communities.

MICHIGANBUSINESS.ORG

MICHIGAN’S UNIVERSITY RESEARCH CORRIDOR

PUBLIC HE ALT H MANAGEMEN T

CONFRONTING COVID-19 Michigan’s top three research universities — Michigan State University, the University of Michigan and Wayne State University — are collaboratively working to solve the many challenges COVID-19 has brought to medicine, education, the economy, and everyday life.

2,468

medical professionals graduated from URC universities in 2018 – more than any peer university research clusters in the nation

500+

COVID-19-related research projects are occurring at the URC universities

100+

clinical trials, medical device and COVID-19 testing protocols being developed by URC universities

42% the share of doctors practicing in Michigan (nearly 19,000 doctors) who graduated from a URC medical school

65+

@URCMICH

URCMICH.ORG

New technologies available for license from MSU, U-M and WSU, spanning from new models for PPE to testing assays to antiviral therapeutics

@RESEARCHCORRIDOR BIOMATTERS ® | COVID -19 SPECIAL EDITION

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N S F I N T E R N AT I O N A L

Importance of Operationalizing Public Health Strategies

BY RYAN DALY, PERFORMANCE MARKETING MANAGER, NSF INTERNATIONAL

With the scientific understanding of the COVID-19 virus rapidly changing, constant improvement is critical. Businesses are swimming in guidance, but they need help applying and operationalizing the guidance to their own unique situations.

Public health experts at NSF International, a not-forprofit, non-governmental public health organization, are continuously reviewing and evolving protocols and guidance, both through direct work with businesses, as well as with states and municipalities.

As COVID-19 cases surge and businesses struggle, the State of Michigan is approaching workplace safety in an unprecedented way — by partnering with NSF to educate and collaborate with small businesses that need help complying with the State’s COVID-19 safety requirements. As part of the MIOSHA Ambassador program, Ambassadors work with Michigan businesses to help them understand and follow workplace safety regulations. They offer free education and one-on-one support to help businesses apply safety directives to their individual situations.

For any COVID-19 preventive program to be effective, businesses must introduce new processes and create new habits, from rigorous sanitation protocols and social distancing practices, to controls for shielding employees and customers from unnecessary interaction, limiting indoor capacity and increasing air ventilation.

WHEN OPERATING DURING THE PANDEMIC, IT’S IMPORTANT TO: PLAN: Ensure you have the right program in place from the start. An independent verification of COVID-19 preventive measures can help business owners build confidence to open and operate with continuity.

REMAIN AGILE: To defend against complacency, it’s imperative that any COVID-19 mitigation program contains rigor and is constantly evolving to reflect the changing nature of the pandemic.

SYSTEMATIC APPROACH: What works on day 1 may not work on day 20 or day 200. As the situation evolves, so must the protocols and procedures. To provide the greatest level of protection, businesses must establish new habits and behaviors, which takes time and consistency.

As a global public health organization, NSF International is dedicated to doing its part to reduce the spread of COVID-19, providing resources and expertise from a team of microbiologists, Ph.D.s, medical doctors, former regulators, engineers, chemists and other professionals specializing in public health and the environment.

NSF.ORG/CONSULTING/OPERATING-DURING-COVID-19

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E M M A I N T E R N AT I O N A L

Navigating the Rapidly Changing COVID Regulatory Climate Takes a Seasoned Expert

BY NIKITA ANGANE, MS, LEAD QUALITY ENGINEER, EMMA INTERNATIONAL

Whenever there is a public health emergency, such as the Zika virus in 2016 or the current novel coronavirus, there is a rush to get diagnostic tests and other medical products to detect and treat the emergency available quickly.

Often, companies forget the quality and regulatory work required to bring their products to the market. EMMA International has been supporting its clients by keeping the dreadful compliance headache away while they work on innovations that support public health amidst the COVID-19 pandemic.

During the COVID 19 pandemic, when most of the states in the US declared a ‘state of emergency,’ foreign/international travel restrictions were put in place, and the FDA released a series of advisories and statements to keep the public informed of the situation. The FDA also authorized the emergency use of certain devices and drugs and released temporary policies to help mitigate the supply shortages of COVID essential products.

EMMA International is helping companies in the pharmaceutical, diagnostic, and medical device industries comply with the temporary policies and ensure that safe and effective medical products are being brought into the US market during these tough times.

The EMMA team has helped companies producing hand sanitizers, face masks, gloves, ventilators, and test-kits to submit emergency use authorization (EUA) applications.

This authorization is intended to maximize the number of medical devices on the market and hopefully meet the demand of the health care system.

Additionally, with the change in the economic environment, and the decisions by some state officials to declare emergencies in their regions leading to a temporary shutdown of non-essential activities, many companies transitioned to the manufacturing of COVID essential products. EMMA International has helped such companies

pivot from their existing manufacturing operations and support new activities to ramp up production that can meet the surge in demand.

These tough times also brought forward a new era of working from home. To increase the production of medical devices, quality and regulatory work could not stop, which meant that it needed to adapt to the new challenges. EMMA International’s OQA program ensured that our team of internal experts, with the experience and credentials suited for any quality or regulatory needs, were available when and where needed.

Furthermore, on March 10, 2020 the FDA released a statement that all inspections outside of the U.S would be postponed, and FDA inspections resumed in July 2020.

Under such circumstances, it was more important than ever to ensure that the products being introduced into the market were safe for their use and effective for their purpose.

While the FDA is working with U.S. government partners including the Centers for Disease Control and Prevention (CDC), medical product manufacturers, and international partners to control the situation surrounding the COVID 19 outbreak, EMMA International is here for its clients to help them navigate the regulatory world and bring their innovative products into the hands of the consumers.

EMMAINTERNATIONAL.COM

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M I C H I G A N S TAT E U N I V E R S I T Y

Animal Housing Area Becomes FDA Authorized Decontamination System

BY ALISHA BROWN, MARKETING AND COMMUNICATIONS DIRECTOR, MICHBIO, BASED ON SOURCE MATERIALS PROVIDED BY MICHIGAN STATE UNIVERSITY

If you tuned into the news in March 2020, you would find stories on the urgent need for personal protective equipment (PPE) for healthcare and emergency service providers, front-line workers, and others.

The exponential rise in demand for such products pushed the supply chain beyond its capacity and forced health care workers to extend the life of specific pieces of PPE — notably N95 respirators — beyond the typical one-time use. The ability to decontaminate PPE rapidly, and at the required scale, became essential for the continued functioning of the healthcare system and treatment of COVID-19 patients. A solution came from an unlikely place — the Michigan State University Campus Animal Resources department — the group that oversees the care, facilities, and treatment of all biomedical animals in the MSU system.

“We had this idea,” says Claire Hankenson, DVM, MS, DACLAM, Director and Attending Veterinarian, Campus Animal Resources & Professor, Pathobiology and Diagnostic Investigation, CVM, “that we could repurpose a 10-room building used for large animal housing, that happened to be sitting empty, as a large-scale N95 respirator decontamination center.”

Dr. Hankenson became part of a team including experts in environmental health and safety, and supply chains, as well as, partners from Sparrow Health System, that began the long process to design the center, manage the conversion, develop the logistic infrastructure necessary for transparency, efficiency, and communication, seek FDA authorization, and, finally, open the center to clients.

“One of the interesting things that happened,” continued Hankenson, “was the realization that our initial plan to decontaminate masks up to 20 times was far above what was actually capable of gaining FDA approval.”

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The group went through an iterative process to eventually settle on the maximum of three decontaminations per mask — that were carefully documented to ensure no masks exceeded 3 cleanings and that all masks were returned to their original owner - that was granted FDA Emergency Use Authorization in July.

Following the authorization, the team partnered with statewide clinics and healthcare sites to ensure that the needs of State Hospitals, the National Guard, and drive-through testing sites were addressed as critical infrastructure in the overall State response to the pandemic.

“Because we had the benefit of supply chain experts and healthcare partners on our team,” continued Hankenson, “we were able to develop a plan that provided more than just general supply chain support, and target critical elements of the State’s monitoring and response efforts.”

The MSU Decontamination System uses vaporized hydrogen peroxide (VHP) — an EPA-proven product effective against multiple bacterial species, viral agents, fungi, and priors — to fog batches of N95 respirators with a capacity of approximately 45,000 per week.

“While we do expect to convert the building back to animal housing in the future,” continued Hankenson, “we plan to have the system operational for at least 6-months while demand is high. What’s more — we’ve gone through this process now and have an instruction manual for how to set up the system again should the need arise.”

For more information: An article titled “Vaporized Hydrogen Peroxide Decontamination of N95 Respirators in a Dedicated Animal Research Facility for Reuse During a Novel Coronavirus Pandemic” detailing the project was published in the Journal of ABSA International, 2020, Vol. 25(3).

CANR.MSU.EDU

MICHIGAN STATE UNIVERSITY

INN VATION CENTER

The MSU Innovation Center provides a variety of integrated services to the BioTech sector.

Imagine the possibilities: • • • •

Access to more than 5,000 researchers Nearly $600 million in annual R&D expenditures 500-plus research and instructional buildings Advanced facilities, pilot plants and lab spaces

Connect your business to MSU today.

We offer a world-class network for entrepreneurs, investors and inventors who are looking for everything — all in one place: Business-CONNECT Links the right people and resources to develop an idea.

MSU Technologies Offers the best MSU ideas ready for commercial licensing.

Spartan Innovations Creates investment-ready businesses from MSU ideas.

innovationcenter.msu.edu

@msuinnovation

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W AY N E S TAT E U N I V E R S I T Y A N D W AY N E H E A LT H ’ S M O B I L E T E S T I N G P R O G R A M

Innovation Built on Collaboration

BY PHILLIP LEVY, MD, M.P.H, PROFESSOR & ASSOCIATE CHAIR FOR RESEARCH IN THE DEPARTMENT OF EMERGENCY MEDICINE, WAYNE STATE UNIVERSITY

Within days of the first COVID-19 cases in Michigan, Wayne State University (WSU) and Wayne Health (WH), in partnership with ACCESS, launched Southeast Michigan’s first, high-throughput, drive-through COVID-19 testing program.

Within 3 weeks, nearly 3000 individuals were tested.

Soon thereafter, WSU and WH, rolled out their innovative mobile testing program which has since gone on to provide COVID-19 testing to more than 32,000 people statewide (https://www.waynehealthcares.org/mobile-health-unit/).

In addition to COVID-19 testing, the WSU and WH mobile units provide blood pressure, diabetes, cholesterol, and kidney function screening, as well as HIV testing and on-site referrals for public benefits like Medicaid and cash assistance, unemployment assistance, emergency food and shelter services, and other vital linkages to care. Now with a fleet of 5 fully upfitted vehicles that include temperatureregulated medical-grade refrigeration, the mobile units are being deployed in support of community-wide COVID-19 vaccine administration.

Designed to bring services to those in greatest need, the mobile health program reflects WSU and WH’s longstanding dedication to improving care for vulnerable and highrisk communities across metropolitan Detroit. That it has achieved success reflects the willingness of regional, Michigan based partners to collaborate and work towards a common goal. Because of such collaboration, de novo development of a HIPAA compliant, text message-based intake and result reporting software program with Patient

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Education Genius, establishment of a highly reliable testing supply chain solution that incorporates multiple biomedical industry partners including Garcia Laboratory, NxGen MDx, World Wide Health & Safety and RapidBio, and creation of a completely new vehicle concept for the mobile health program with the Ford X team, were possible. Because of such collaboration, lives were undoubtedly saved.

However, it took more than industry partnerships to enable this work. The philanthropic community within Michigan and beyond was critical with a tremendous outpouring of support from individual donors and non-profit organization including United Way, the Community Foundation of Southeast Michigan/Detroit Medical Center Foundation, the Ralph Wilson Foundation, Community Organized Relief Effort (CORE), DTE Energy Foundation, Blue Cross Blue Shield of MI, and the Cielo Foundation. Their generosity allowed for community-wide testing for COVID-19, both viral (PCR) and antibody (IgG), free of charge with no prescription or appointment needed, through the first and second waves of the pandemic, while also planting the seeds for broader health outreach efforts. It also drew visibility to the program and directly led to the inclusion of mobile health infrastructure expansion as one of the strategic initiatives proposed by the Michigan Coronavirus Racial Disparities Task Force.

Endorsement of the mobile health program by the Task Force brought a collaboration with the Michigan Department of Health and Human Services (MDHHS) and funding to support further growth of the model and extension of services. Included among the latter was the

addition of on-site patient health navigators who provide linkage to care for anyone requesting assistance with medical or social service needs. Developed and delivered in partnership with the Detroit Parent Network (DPN), the navigator program has fielded more than 1800 requests for assistance since October 2020. Through a separate, CDC funded program with the MDHHS Heart Disease and Stroke Prevention unit, cardiometabolic risk factors screenings are also offered and ensure that patients who need medical follow up for management of related conditions including hypertension, diabetes, and hyperlipidemia, receive appointments before leaving the test site.

While all of this is necessary for success, it is definitely not sufficient - without community trust in the process, failure is assured. Cognizant of this, since initiation of the mobile testing program in April 2020, the mobile health program has partnered with more than 200 different organizations, many of them faith-based, all of whom serve as an inlet to their community for WSU and mobile health services. Collaborating at all stages from event planning to execution ensures that delivery aligns with expectations and that partners are engaged throughout, helping to drive participation. To amplify the message, the program has also worked closely with iHeart Media to develop a radio and social media campaign, aimed at reaching a younger audience.

As transition in made to the vaccine phase of the pandemic, testing still has an important role to play, as does the mobile outreach model. Throughout, data has been to target communities at greatest risk to suffer from COVID-19 and the program will continue to deploy resources in an effort to reach those in greatest need.

As work is done to ensure equitable distribution of the vaccine, new collaborations will arise but the mission will remain the same – to battle in unison against COVID-19, the most important enemy of our time.

WAYNE.EDU

NEW MICHBIO

MEMBER SPOTLIGHT

C

urrently, 80% of clinical trial failures are due to studies not meeting their enrollment goals, and there is an unmet need for technologies that reduce friction and improve the pace and predictability of the recruitment process.

Ripple Science aims to reduce clinical trial failures by 50% by adapting sales and marketing automation to accelerate participant recruitment and boost retention. Additional benefits come from leveraging recruitment and retention data in Ripple to measure what matters and provide actionable insights powered by data science.

The mission at Ripple Science is to empower clinical research investigators and their study teams by replacing disconnected spreadsheets, databases, calendars, email accounts, text services, etc. with an integrated platform. The company is leading this essential phase of technology adoption in the clinical trial space by automating and assisting the participant journey workflow. With fewer gaps in communication and a customer service-oriented approach, Ripple users have reported accelerated recruitment and higher retention rates for their studies.

Ripple is the market-leading SaaS platform used by public and private clinical research organizations across more than 485 studies with over 1 million participant events tracked. Ripple is currently used by research investigators at more than 100 academic and research centers around the world, including Johns Hopkins University, Stanford University, the Brain Research Foundation Canada, Uptown Research Institute, and Lakeside Life Sciences.

Ripple Science is a Michigan-based company founded by Dr. Nestor Lopez-Duran, a Professor of Clinical Psychology at The University of Michigan. Peter Falzon, President and CEO at Ripple Science, is a Michigan native who returned to the state after a 20year career leading life science companies in Silicon Valley.

RIPPLESCIENCE.COM

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MICHBIO

BY THE NUMBERS

14

LARGEST BIOSCIENCE STATE

10

LARGEST MEDICAL DEVICE STATE

th

MICHIGAN BIO-INDUSTRY QUICK FACTS

38,981*

1,877

*

BiOSCIENCE JOBS

144,184*

th

TOTAL EMPLOYMENT IMPACT

BIOSCIENCE ESTABLISHMENTS

$92,717

*

AVERAGE BIOSCIENCE SALARY

$28

>

BILLION

BIOSCIENCE PERFORMANCE METRICS* BIOSCIENCE R&D (FY 2018)

$1.536 billion* VENTURE CAPITAL INVESTMENT (2016-2019)

$557.6 million* PATENTS (2014-2017)

2,563* † Summated from Battelle/AdvaMed The Economic Impact of the U.S. Advanced Medical Technology Industry. PhRMA Biopharmaceuticals Sector Impact on Michigan’s Economy, 2016. * TEConomy/BIO, the Biosciences Economy: Propelling Life-Saving Treatments, Supporting State and local Communities, 2020

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ECONOMIC IMPACT †

MICHBIO: BY THE NUMBERS

1.9%

DISTRIBUTION OF MICHIGAN BIOSCIENCES INDUSTRY

18%

48%

ESTABLISHMENTS

6.1%

Agri-Biosciences Medical Device

31%

31% EMPLOYMENT

1.8%

13.6%

22.6%

26%

Pharma R&D/Testing Logistics

BIOMATTERS ® | COVID -19 SPECIAL EDITION

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AFTER THE

ELEVATOR PITCH Lactocore, Inc. is a biopharmaceutical company at the preclinical stage that develops a pipeline of novel peptidebased therapeutics for CNS disorders starting with a proprietary computer-aided discovery engine. The leading candidate LCGA-17 is targeted against depression, anxiety and related disorders. These indications represent a huge unmet medical need as currently approved therapies are often ineffective and have a variety of medically significant side effects. There are close to 4 million patients in the US alone who simply do not respond to existing therapies for depression, and millions more who do not respond to, or cannot tolerate, existing therapies for anxiety.

Headquartered in Plymouth, MI, Lactocore is a privately-funded, semi-virtual company, with discovery group in Moscow, Russia and development efforts centered in the US and implemented via global CROs. The core team of scientists has combined expertise in silico drug discovery, peptide drug development and behavioral neuroscience.

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Lactocore’s leading candidate LCGA-17 is a novel inhibitor of VGCC (voltage-gated calcium channel), a versatile clinically relevant target for CNS indications including anxiety. LCGA-17 is a rapid-acting short peptide targeted for intranasal delivery, with long-lasting robust antidepressant and anxiolytic activity demonstrated in multiple animal behavioral models. LCGA-17 revealed no side effects typical to marketed VGCC inhibitors (gabapentinoids) such as sedation, addiction potential.

The compound is undergoing IND-enabling studies and is projected to reach clinical trials in Q4 2021.

Other drug candidates in Lactocore’s pipeline include novel peptide modulators of mGluR5, TrkB, NTSR1, and NOP1 receptors, with potential in a variety of indications including mood disorders, ADHD, dyskinesias, schizophrenia, and pain.

LACTOCORE.COM

Michigan continues to be a leader in advancing biosciences research and commercialization, thanks to its rich pipeline of intellectual property. A whole new crop of startups are germinating in the state, which is good news for the regional cluster of established companies that are focused on innovation in therapeutics, medical devices, healthcare technologies, clinical diagnostics and agri-/industrial biotechnology. Renewal is crucial to sustaining and growing an innovation cluster. All the way around, Michigan bioscience businesses are truly improving the quality of life for patients and consumers.

Many of us know a family member, a colleague or are ourselves someone who has battled cancer. The sickening chemotherapy treatments that usually must be endured as a result are all too familiar. Chemo is very effective at killing cancer cells, but without a means to target only the tumor, toxic chemo drugs damage healthy tissues as they travel throughout the body. To the patient the treatment can feel worse than the disease.

(CIPN), characterized by numbness, burning, and tingling sensations in the extremities, plus weakness and loss of dexterity, plagues many chemotherapies. Survival is diminished when CIPN demands treatment cutback.

Moreover, unlike other effects, CIPN persists for months to years, degrading quality of life in survivorship. The capacity of PALM to target chemotherapy to tumors without risk of CIPN is ground-breaking.

Imagine the impact a drug delivery technology will have that is able to increase the effectiveness of chemotherapy drugs while diminishing side effects. This is what Peptinovo aims to do.

Ovarian cancer patients and their standard treatment with paclitaxel, a particularly neurotoxic chemo drug, are the initial focus for PALM. With few other options, more than 60% of patients experience CIPN due to paclitaxel. PALM will provide a major improvement in tolerance and survival.

Approval of paclitaxel-loaded PALM for other cancers and use of the PALM platform for other chemo drugs will follow.

Peptinovo Biopharma Inc., headquartered in Ann Arbor, has created a truly innovative drug-delivery platform, named a Peptide-Amphiphile Lipid Micelle (PALM), that delivers higher doses of chemotherapy drugs to tumors for greater effect, while avoiding damage to nerves. Chemotherapy-induced peripheral neuropathy

PEPTIVOVO.COM

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