MDC Connects 2024: Webinar 3/5

MDC Connects 2024

Unlocking the Secrets of Medicine Commercialisation

13 Feb – 12 Mar 2024 | 1-2pm (GMT)

Introduction

• A pharmacologist by training, and with over 25 years of

experience in the industry, Graeme has led drug discovery and capability enhancement projects in large pharma and start-up across many disease areas and has significant experience in instigating and leading open innovation and drug repositioning programmes.

• At MDC, Graeme is head of Virtual R&D, which supports drug discovery innovators developing scientific strategy and plans leads the healthy ageing strategy area and supports the neuroscience portfolio.

Graeme Wilkinson, Head of Virtual R&D, Medicines Discovery Catapult

© 2024 Medicines Discovery Catapult. All rights reserved.

EXCELLENCE

INTEGRITY

COMMUNITY

INNOVATION

Building the science: Accessing the Skills for Successful Drug Discovery • Understanding the need for, and accessing, the skills, knowledge, expertise, capabilities and funding required to develop a medicine • Accessing these skills virtually and the challenges of running a virtual project.

• Developing solutions to the ‘problem’ of virtual drug discovery • End to end CROs and bespoke consultancy

© 2024 Medicines Discovery Catapult. All rights reserved.

EXCELLENCE

INTEGRITY

COMMUNITY

INNOVATION

Drug Discovery is Complex, Costly and Resource Intensive

Cell models

Library design

Synth.

Chem.

Analyt.

Chem.

Med. Chem.

TI/TV

Complex web of service providers, enablers and funders is challenging to navigate

Process Chem.

Successful projects require:

Formulation Biomarkers Drug candidate

Idea Pharmacology

Hit finding

ADME

Assay generation

Comp.

Chem.

IND enabling

Safety

GL P tox

• Knowledge; Decision making advice and expertise in drug discovery • Expertise; CROs, specialist academic institutes, etc • Delivery; Experienced drug discovery project management and due diligence

PK

PD In vivo models

In vivo efficacy

Dose to man

© 2024 Medicines Discovery Catapult. All rights reserved.

EXCELLENCE

INTEGRITY

COMMUNITY

INNOVATION

Key Challenges for SMEs and Start Ups Increasing costs and difficulties accessing funding

•

Fewer resources

•

More dependent on grant and private funding

•

Partnerships are important to sustain and build their science

Access to lab space, equipment and specialist services

Skills shortages

• •

Challenges in accessing

•

Reliance on access to

sufficient skilled individuals

specialist technologies,

Especially challenging for seed

expertise and lab space

and CRO companies

•

Essential to generate evidence required to unlock future investment

© 2024 Medicines Discovery Catapult. All rights reserved.

EXCELLENCE

INTEGRITY

COMMUNITY

INNOVATION

Access to Drug Discovery Skills

© 2024 Medicines Discovery Catapult. All rights reserved.

EXCELLENCE

INTEGRITY

COMMUNITY

INNOVATION

Not Just Drug Discovery Skills…

Understand the target and the molecule

Understand the disease indication

Understand the market and regulator

• • • • • • •

Communication Teamwork Business acumen Self-motivation Adaptability Management skills Critical thinking, problem solving

Make the science investable

© 2024 Medicines Discovery Catapult. All rights reserved.

EXCELLENCE

INTEGRITY

COMMUNITY

INNOVATION

Who Needs These Skills and Why TTOs, VCs

Start Ups, Spin Outs

Drug Discovery SMEs and CROs

Access to drug discovery and disease area expertise

Development of drug discovery plans with project management

Relationships with CRO and specialist academic service providers

DELIVERABLES: Real world evaluation and data due diligence Delivery of project plans to time and cost New business opportunities for service providers New opportunities for collaborative R&D © 2024 Medicines Discovery Catapult. All rights reserved.

EXCELLENCE

INTEGRITY

COMMUNITY

INNOVATION

Line of sight

Finding the right balance across all disciplines

Right molecule

Developing a Successful Plan

See: Cook et al, 2014. “Lessons learned from the fate of AstraZeneca’s drug pipeline: a five-dimensional framework”. Nature Reviews Drug Discovery. 13; 419.

© 2024 Medicines Discovery Catapult. All rights reserved.

START HERE! EXCELLENCE

INTEGRITY

COMMUNITY

INNOVATION

Expertise Needed Execute

“Status of the Project”

Project Data Package

Project Delivery Plan

MDC

Outline

Recommendation

Project Owner

Virtual R&D network

Project Data Package

Slide courtesy of Sarah Brockbank

© 2024 Medicines Discovery Catapult. All rights reserved.

EXCELLENCE

INTEGRITY

COMMUNITY

INNOVATION

Accessing the Skills – Where to Start Innovation clusters and service providers Membership organisations

Opportunities for mentorship, networking and professional development

© 2024 Medicines Discovery Catapult. All rights reserved.

EXCELLENCE

INTEGRITY

COMMUNITY

INNOVATION

Summary • Making sense of the journey – the skill in knowing which skills you need and when • Know your science • Vary your experience • Networking is key (meet new people, access expertise) • Learn from the experts (attend meetings, webinars, etc.)

© 2024 Medicines Discovery Catapult. All rights reserved.

EXCELLENCE

INTEGRITY

COMMUNITY

INNOVATION

Q&A Speak to us or follow up with a question on email to info@md.catapult.org.uk

© 2020 Medicines Discovery Catapult. All rights reserved.

Accessing the right Laboratory at the right time

Typical wet Lab types Chemistry laboratory : Focused upon containment and protection for lab users (DSEAR Regulations should be consulted) ●

This type of lab allows any activity involving organic or inorganic chemicals or materials that have potentially harmful side effects on humans if handled incorrectly

Typical examples would be Pharmaceutical labs, Chemical manufacturing, Agro chemicals etc

Biology Laboratories: Focused on contaminant and contamination ●

Biology labs are used to study microorganisms safely, These labs provide not only protection to the lab users against infection but also help to prevent microorganisms from the user or lab environment contaminating the samples.

Other types of lab •

Analytical or Analysis Labs

•

Research, Medical or Clinical laboratories mostly found in Hospitals or Pharmaceutical companies and CROs.

•

Cleanrooms. Special environments with the focus on minimizing pollution/contamination.

Containment levels Containment Level 1 (CL1) (Comparable to Biosafety Level 1) is used for deliberate work with microorganisms and genetically modified organisms that represent a nil or negligible risk to human health or the environment.

Containment Level 2 (CL2) (Comparable to Biosafety Level 2) is used for deliberate work with micro-organisms and genetically modified organisms that could potentially cause disease in humans or harm the environment.

Containment Level 3 (CL3) (Comparable to Biosafety Level 3) is used for deliberate work with microorganisms and genetically modified organisms that could potentially cause severe disease in humans or harm the environment.

Containment Level 4 (CL4) (Comparable to Biosafety Level 4) is the highest level of containment, and is appropriate for work with extremely dangerous pathogens that could easily be aerosol-transmitted within the laboratory, and cause severe to fatal diseases for which there are no available vaccines or treatments.

Full Lab Categorisation Guide for further information

Shared Labs - Ideal for Startups Typically found within Universities or Science Park incubators, consisting of Shared lab benches, located within a communal lab environment with additional communal write up, They typically offer flexible space for you to grow and develop your research. Monthly rolling contracts Premium versions shared lab offer dedicated lab workstations, writeup desks, and communal access to lab instruments and essential services , (an example of this is the Bruntwood SciTech Open Access Lab at Alderley Park) Pros ● ● ● ● ● ● ● ● ●

Fixed monthly cost Flexible access to specialised laboratory environment Access to State of the art Laboratory equipment Support by Lab Manager/ Lab Technicians Hazardous waste dispose of by lab team Logistics supported (shipping in and out Maintenance/ repair included Collaboration opportunities Part of Science park Ecosystem

Common challenges encountered shared spaces can include: ● ● ● ● ●

●

Activities can be restricted Communication between companies Busy and sometime chaotic environment Rely upon other users to practice good housekeeping Additional SHE considerations Additional training and documentation required

Serviced Labs (Incubator Labs) - Grow Usually modular small lab spaces that provide the grown on space from a shared lab attempting to reducing the capital burden of accessing dedicated lab space Pros ●Less Capital Cost ●Dedicated Lab space ●Simpler SHE control considerations (scope for more hazardous work) ●Communal breakout space Cons ●Usually Small ●Less Access to shared lab Equipment ● More expensive than shared lab ● Less flexibility lease terms

Biology CL1, CL2 & Chemistry Labs that are ready to go designed by operator or previous customer

Pros ● Already fitted out with fixtures and fittings, ready to occupy / Cheaper than designing own lab ● Larger – than serviced labs ●Dedicated Write up ● Dedicated Lab space (secure easier to manage SHE) ●Longer leases ●Simpler SHE control considerations (scope for more hazardous work) Cons ● Limited availability ● designed and built with either generic or another customer's requirements in mind

Usually involves a compromise

Bespoke labs - Thrive Designed and built to your specifications

What to consider when designing your lab environment : 1. Current & future staff number.

2. Different functional areas. Chemistry, Biology, Cell culture, Clean room etc 3. Up-to-date equipment schedule with manufacturer’s link – important for space allocation, power outlets, plumbing.

4. Any specialist requirements – gases, equipment or materials.

5. Business critical items.

6. Regulatory changes and impact.

7. Storage requirements – consumables, waste, cold/freezer space.

8. Replicate the process for your office space requirements.

Why a Science park ?

A science park is an organisation managed by specialised professionals, whose main aim is to promote the culture of innovation • • • •

Access state-of-the-art equipment and facilities Ecosystem stimulates the sharing of knowledge Promote innovation on a commercial level Enable communication and collaboration

What does a Science park offer Beyond Labs Science park ecosystems contain dedicated teams that focus on facilitating the creation and growth of innovationbased companies through Business support, Scientific services and Accelerator programs alongside other valueadded services

Gareth.Hampton@Bruntwood.co.uk Head of Lab Services

Accessing drug discovery expertise How do I find the right CRO for my project?

MDC Connects: Building the Science 27th February 2024

Introductions Dr Angelo Pugliese

Dr Mike Piper, CCO

Assoc. Director, In Silico Discovery and Data Analysis

Biologist by training, over 15 years commercial experience at CROs, working to support biotech companies

Computational chemist with over 15 years experience working across organisations in the US and UK

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Why work with a CRO? • Flexible access to (the right) drug discovery

capabilities and expertise…

• …so you can rapidly progress your project • The right CRO will have the right team for

your project • A CRO is a people business!

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Rapidly access the expertise and skills your project needs Assay Development

Hit Generation

Comprehensive target class expertise

Target analysis & bespoke screening strategies

• Biophysical assays • Biochemical assays • Cellular assays

Hits to Leads

• HTS/MTS/fragment screening • Or

Lead Optimisation

Hypothesis – driven compound design, synthesis & testing • Medicinal chemistry

• Primary assays

• Computational chemistry

• Orthogonal assays

• Synthetic chemistry

• DMPK

• Knowledge-based approaches (computational & medicinal chemistry) • Virtual screening

Compound Management

• (In vivo studies)

Selecting the right CRO(s) What do you need?

• •

Identify capability and expertise gaps A scientific partner, or a datagenerator?

Identify potential CRO partners • • • •

MDC Consultants Recommendations Google

Initial due diligence (CDA) •

• •

You’ll know the right CRO • •

You’ll know the right group when you speak to them So speak to a few!

Make your decision • • •

Have their scientists, across the key disciplines your project needs (med chem, comp chem, biosciences…) worked on similar projects?

Relevant target class expertise Not conflicted!

Source & compare quotes

Are those the scientists who you’ll actually be working with?

Will you be sold to by the “A” team, and work with the “C” team Customer references

• • •

•

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Effort & responsiveness during the bidding process Quality and detail of scientific input during bidding process Integrity, flexibility – not just looking to sell you 5 FTEs for a year…

Price

BioAscent Discovery: highly experienced scientific team

Chemistry, Analytical Chem, In Silico Discovery

Biosciences

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Compound Management

Introductions Dr Angelo Pugliese

Dr Mike Piper, CCO

Assoc. Director, In Silico Discovery and Data Analysis

Biologist by training, over 15 years commercial experience at CROs, working to support biotech companies

Computational chemist with over 15 years experience working across organisations in the US and UK

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A Case Study in Client Needs and Delivered Solutions: Discovery of novel TRPML1 agonists • TRPML1 (Transient Receptor Potential Mucolipin 1) is an ion channel found within

lysosomes. Mutations and dysfunction of this channel are associated with several conditions.

• Research suggests TRPML1 might play a role in neurodegenerative diseases like: • Alzheimer • Amyotrophic Lateral Sclerosis (ALS) • Parkinson Arkuda Tx was interested in this target 33

An ideal fit • Arkuda needs:

• BioAscent expertise:

• Discover novel TRPML1 agonists

• High-throughput screening (testing a

large library of compounds rapidly)

• Expertise in hit-finding technologies

• A 100k diverse IP-free screening

library

• Access to specialised skills and

resources: SBDD - CADD

• Computational chemistry and SBDD to

expertise to drive optimisation • Proven track record in drug discovery

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The collaboration process • Step 1: Understanding the client's goals and the biological target (TRPML1).

• Step 2: Designing and running high-throughput screens to find potential hits.

• Step 3: Computational chemistry to design better ligands, improving their binding

affinity and properties.

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A highly successful partnership • HTS (FLIPR assay) a library of >100,000 compounds identified the substituted

tetrazole compound 1 • Selective and CNS penetrant TRPML1 agonist • Computer-aided drug design (CADD) instrumental to design conformationally locked macrocyclic analogues which further improved potency while retaining the selectivity

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Advantages for Arkuda (the client) • Accelerated the discovery process compared to in-house capabilities alone.

• Cost-effective approach using our well-established HTS platforms.

• Access to specialized computational skills and cutting-edge technologies.

• Identified promising novel TRPML1 agonists with potential for therapeutic

development.

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Questions?

www.bioascent.com mpiper@bioascent.com @BioAscent +44 (0) 1698 534002

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