Zymeworks (ZYME) Status Update summary

R&D Strategy and Portfolio Expansion

• Achieved five clinical-stage programs 18 months ahead of schedule, completing the 5x5 portfolio with ZW209 nomination and expanding into digestive system cancers, hematological malignancies, and autoimmune/inflammatory diseases.

• Advanced portfolio targets solid tumors, hematological cancers, and autoimmune/inflammatory diseases, leveraging multifunctional protein engineering and multispecific antibody technology.

• R&D investment is balanced across clinical and preclinical programs, with a focus on novelty, differentiation, and value addition through 2027.

• The organization is structured to manage up to six early-stage clinical programs and a robust preclinical pipeline globally.

• Portfolio management is data-driven, with clear milestones for attrition, partnering, and resource allocation, providing flexibility for future partnerships and product rights retention.

Clinical and Preclinical Program Highlights

• ZW171 (mesothelin/CD3 T-cell engager) and ZW191 (folate receptor alpha ADC) are in global Phase 1 trials for ovarian, lung, and endometrial cancers, with initial data expected in 2025.

• ZW220 (NaPi2b ADC) and ZW251 (GPC3 ADC) are advancing toward INDs in 2025, targeting gynecological, lung, and liver cancers.

• ZW209, a DLL3/CD3/CD28 tri-specific T-cell engager, is set for IND in 2026, designed for enhanced durability and safety in small cell lung cancer.

• ZW1528, a bispecific IL-4Rα/IL-33 antibody for COPD and autoimmune diseases, is in IND-enabling studies, with IND planned for 2H 2026.

• Zanidatamab, a HER2-targeted bispecific antibody, received FDA approval for HER2-positive BTC, with pivotal Phase 3 GEA data expected in 2Q25.

Technology Platforms and Innovation

• Azymetric and EFect platforms enable rapid, high-throughput engineering of multi-specific antibodies, T cell engagers, and bispecific cytokine blockers.

• AI/ML integration accelerates discovery cycles, optimizes paratope libraries, and supports novel target identification and antibody optimization.

• Conditional masking and cleavable sequences enhance tumor selectivity and safety for ADCs and T-cell engagers.

• Plug-and-play engineering allows for modular assembly of multi-specifics, supporting expansion into hematology and autoimmunity.

• ADVANCE program focuses on novel payloads, optimized antibody formats, and next-generation ADCs, with four new payload mechanisms in discovery.