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Selecting a CMO: Zymeworks’ Perspective
David Poon, Ph.D.Executive Director
External R&D and Alliances
A Clinical-Stage Biopharmaceutical Company DevelopingFit-for-Purpose, Multifunctional Therapeutics for Oncology
Complementary Next-‐Generation
PlatformsAzymetric™ ZymeLink™ EFECT™ AlbuCORE™
Marquee Strategic Partnerships
Zymeworks Wholly-Owned Therapeutics Pipeline
Zymeworks Historically is a Fully Virtual Company
• Prior to 2016/17, Zymeworks relies on an external network of partners and CROs/CMOs for all “wet-lab” work– Design and engineering performed in-house– External work ranging from gene synthesis to antibody
production to in vivo models– Experienced in managing a complex chain of vendors
• In 2017, Zymeworks opened its own lab space– Expand capabilities rather than replace existing partners/CROs– No plans to internalize manufacturing!
Manufacturing of Antibodies
Cell-Line Development
Upstream Development
Downstream Development
cGMP Manufacturing
Manufacturing of Bispecific Antibodies
Cell-Line Development
Upstream Development
Downstream Development
cGMP Manufacturing
Analytics
• Virtually identical to monoclonal antibodies with additional analytics and selections needed
ZW25: Anti-HER2 Bispecific Antibody
Unique Mechanisms of Action
• Biparatopic -‐ targets two distinct HER2 epitopes• Increased binding density• Enhanced effector-‐mediated cytotoxicity• Blocks ligand-‐dependent and -‐independent tumor growth• Enhanced HER2 down-‐regulation
Data Highlights
• Superior activity compared to Herceptin or SoC in PDX models of Breast, Gastric and Ovarian Cancer
• Orphan Drug Designation for Gastric and Ovarian Cancer
ZW25
ZW25 Manufacturing Considerations
• Achieving aggressive timelines– Early POC to IND in ~3 years– Corporate/financing considerations– Competition in the technology and disease landscape
• Avoiding failures ”at all cost”– First cGMP validation for the Azymetric™ platform– First manufacturing campaign for Zymeworks– Financial and timeline impacts
ZW25 Manufacturing Considerations
• Ensuring “partnerability” of the program– Out-licensing will likely include the RCB/MCB so need to ensure
the underlying cell line and approach is widely accepted
• Selecting the best providers for each segment• Canadian options were explored but were not viable
ZW25 Bispecific Antibody Supply Chain
Cell-Line Development(Switzerland)
Up/Downstream Development
(US)
cGMP Manufacturing
(US)
Fill/Finish(US)
2700L tank
cGMP Manufacturing
(China)
Fill/Finish(China)
2000L tank
• Timeline met• More expensive option• Back-up CMO strategy
ZW33 Bispecific Antibody Drug Conjugate Supply Chain
Cell-Line Development(Switzerland)
Fill/Finish(US)
cGMPAntibody
Manufacturing(China)
cGMPDrug-Linker
Manufacturing(China)
cGMPBio-Conjugation
(US)
Challenges Encountered
• Offshore risk– Language barriers– Time zone differences, travel required– Exposed to IP / legal / geopolitical risks
• Big name CMO does not mean guaranteed success• US office required to hire the experts in CMC / QA / Regulatory
Elements of a Canadian Solution
• Mechanism to build-up credibility– Expertise– Demonstrated successful campaigns
• Robust ecosystem with integrated supply chains for Canadian and International partners– Cell lines / manufacturing / analytics / fill-finish / chemistry– Key to have significant logistics advantage
(vs. just another pit-stop)• Competitive pricing
Thank You!
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