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!