Financial Data and Key Metrics Changes - The company reported a net loss of $438 million for 2025, an improvement from a net loss of $522 million in 2024, reflecting a reduction in losses [44] - R&D expenses decreased to $456 million in 2025 from $507 million in 2024, a reduction of 10% [44] - SG&A expenses decreased to $92 million in 2025 from $119 million in 2024, representing a 23% decrease [44] - The company started 2026 with approximately $782 million in cash, cash equivalents, and investments, not including the upfront cash and equity from the Astellas collaboration [45] Business Line Data and Key Metrics Changes - The collaboration with Astellas is expected to accelerate the development of VIR-5500, a T-cell engager for prostate cancer, which is the company's most advanced immuno-oncology asset [7][8] - The financial terms of the collaboration include a total potential of $1.7 billion in combined upfront and milestone payments, with a 50/50 profit-sharing arrangement in the U.S. [14][41] Market Data and Key Metrics Changes - Prostate cancer remains a significant global health burden, with one in eight men diagnosed in their lifetime and a five-year survival rate of only 30% for patients with metastatic castration-resistant prostate cancer (mCRPC) [9] - There are approximately 100,000 mCRPC patients in the U.S. and Europe, indicating a substantial and growing unmet need for novel solutions [9] Company Strategy and Development Direction - The strategic collaboration with Astellas aims to advance the global development and commercialization of VIR-5500, unlocking significant market opportunities while de-risking the pipeline of cancer immunotherapies [7][8] - The company plans to initiate dose expansion cohorts in late-line mCRPC monotherapy and combination therapies in the second quarter of 2026, with a focus on addressing high unmet needs in metastatic prostate cancer [39][62] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the potential of VIR-5500, citing favorable safety and efficacy signals from the phase I clinical data [18][39] - The collaboration with Astellas is seen as a key enabler for rapid advancement and broader patient access to VIR-5500, enhancing the company's position in immuno-oncology [46][47] Other Important Information - The PRO-XTEN platform, which powers VIR-5500, is expected to unlock opportunities for developing next-generation T-cell engagers in solid tumors [8] - The company has developed seven preclinical programs and plans to progress to development candidate selection by early 2027 [46] Q&A Session Summary Question: Can you comment on the range of PSA responses seen by prior line of therapies, particularly with regard to prior radiotherapy? - Management noted strong PSA responses, particularly at higher doses, with one patient showing promising results post-radioligand treatment [54][55] Question: What are the next steps before moving to phase III with Astellas? - The company plans to enter expansion cohorts in Q2 2026, focusing on late-line mCRPC as monotherapy and combinations with enzalutamide [61][62] Question: How does the larger cohort of patients evaluated on VIR-5500 evolve the thinking about its positioning within the treatment paradigm? - Management indicated plans to address a broad range of patients, including late-line mCRPC and early-line combinations, highlighting the high unmet need in these populations [68] Question: Can you provide more information on the go-forward dose for VIR-5500? - The go-forward dose is expected to be in the range of 3,000 to 3,500 micrograms per kg, with no grade 3 CRS observed at these doses [79][80]

Financial Data and Key Metrics Changes - The company has approximately $500 million left in regulatory milestones and about $860 million in commercial milestones, with royalties ranging from 10% to 20% based on net sales [10][11][12] Business Line Data and Key Metrics Changes - The zanidatamab program is a significant focus, with upcoming Phase 3 study readouts expected in Q4, which could drive value for the company [6][10] - ZW171 has been discontinued due to on-target, off-tumor toxicity, reflecting the company's disciplined approach to capital allocation [14][16][17] Market Data and Key Metrics Changes - The competitive landscape for zanidatamab includes potential opportunities in breast cancer, with Jazz Pharmaceuticals exploring this area [11][12] - ZW191 is positioned as a strong contender in the folate receptor alpha ADC space, with a focus on differentiating its product through superior internalization and potency [20][21][22] Company Strategy and Development Direction - The company emphasizes a disciplined approach to capital allocation and decision-making regarding its pipeline programs, focusing on those with the highest potential for patient benefit [14][16] - The strategy includes exploring partnerships for various programs, particularly ZW191, to enhance development and market reach [30][39] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism about the upcoming data readouts and the potential for zanidatamab to capture significant market value, estimating a valuation of over $2 billion [12][13][45] - The company is preparing for multiple catalysts over the next 12 to 18 months, including clinical studies for ZW251 and ZW209 [45] Other Important Information - The ZW209 program, utilizing a tri-TCE platform, is expected to enter clinical trials in the first half of 2026, showcasing the company's commitment to advancing its innovative pipeline [34][45] - The company is also exploring early-stage pipeline opportunities, including novel targets and ADCs, to leverage its protein engineering capabilities [33][34] Q&A Session Summary Question: What is the significance of the upcoming zanidatamab readout? - The readout is expected to provide clarity on the differentiation of zanidatamab in the competitive landscape, particularly in gastroesophageal adenocarcinoma [6][7] Question: What are the financial implications of the zanidatamab program? - The company has significant regulatory and commercial milestones associated with zanidatamab, which could lead to substantial revenue through royalties and milestone payments [10][11] Question: What led to the discontinuation of ZW171? - The decision was based on a lack of efficacy and on-target, off-tumor toxicity, demonstrating the company's commitment to prudent capital allocation [14][16][17] Question: How does Zymeworks differentiate its ADCs? - The company focuses on the holistic design of ADCs, ensuring that the antibody is optimized for internalization and payload delivery, which sets it apart from competitors [20][21][22] Question: What are the next steps for ZW191? - The company is considering partnerships for ZW191 and exploring various tumor types for clinical trials, including ovarian and endometrial cancers [30][39]