Core Insights - Zymeworks Inc. has outlined its strategic priorities and key milestones for 2026, focusing on maximizing value creation for patients, partners, and shareholders following significant progress in 2025 [1][2] 2025 Accomplishments - The company achieved positive Phase 3 results for Ziihera in treating HER2-positive gastroesophageal adenocarcinoma, with potential milestone payments of up to $440 million related to regulatory approvals in multiple regions [3][4] - Zymeworks reported cash resources of approximately $270.6 million as of December 31, 2025, which, along with anticipated milestone payments, is expected to provide a cash runway beyond 2028 [3][16][17] - A share repurchase plan of $125 million was announced to reduce share count and enhance shareholder value [3][12] Strategic Focus for 2026 - The company aims to integrate royalty growth, strategic acquisitions, and internal R&D innovation to drive long-term value creation [5][6] - Zymeworks plans to pursue partnerships and acquisitions based on strategic fit rather than immediate cash needs, emphasizing a disciplined approach to capital allocation [5][6] Clinical Development and Pipeline - Ongoing clinical studies for ZW191 and ZW251 are set to continue in 2026, with plans for future IND filings for multispecific programs [9][10] - The company anticipates presenting additional data from its clinical trials at major medical meetings in 2026 [13] Leadership and Governance - Zymeworks strengthened its leadership team and board of directors by adding experienced biotech executives [2][8] Financial Guidance - The company has outlined a disciplined framework for adjusted gross operating expenditures of approximately $300 million over three years, with a focus on cost discipline and capital allocation [15]

Summary of Zymeworks FY Conference Call (December 02, 2025) Company Overview - **Company**: Zymeworks (NasdaqGS: ZYME) - **Industry**: Biotechnology Key Points and Arguments 1. **Strategic Evolution**: Zymeworks has evolved its strategy since 2022, focusing on extracting value from its IP assets without needing to build a traditional commercial entity [2][3][4] 2. **HERIZON-GEA-01 Data Impact**: The top-line data from HERIZON-GEA-01 was a significant factor in the company's strategic planning, indicating a future of excess capital and the need for thoughtful capital allocation [4][5] 3. **Integration of R&D and Royalty Portfolio**: Zymeworks aims to maintain both R&D and royalty streams within the same entity, believing that synergies exist between the two, which can drive shareholder value [5][6][10][17] 4. **Partnerships and Licensing**: The company has successfully partnered with Jazz, retaining royalties and milestones, which has proven beneficial as the market conditions improved [8][9][21] 5. **Focus on Internal Development**: Zymeworks has built a wholly owned portfolio of R&D assets, allowing for optionality in future partnerships and capital allocation [9][25] 6. **Competitive Advantage**: Zymeworks differentiates itself from traditional royalty players by having both R&D capabilities and a royalty portfolio, allowing for unique strategic maneuvers [15][17] 7. **Future Asset Development**: The company is exploring external assets for potential integration into its portfolio, leveraging its experience in capital allocation and strategy [12][13][25] 8. **Market Positioning**: Zymeworks believes it can achieve outsized returns by effectively managing its dual role as an R&D entity and a royalty organization [18][19] 9. **Potential of Rybrevant**: Rybrevant is projected to have peak sales potential between $1 billion and $5 billion, reflecting the company's confidence in its assets [22][23] 10. **ADC Development**: Zymeworks is advancing its ADC (Antibody-Drug Conjugate) assets, including ZW191, which shows promise in early data and may lead to strategic partnerships [26][28][30] Additional Important Content - **Market Perception**: The company has shifted market perception regarding its assets, particularly in gastric cancer, which was undervalued previously [21] - **Tolerability and Efficacy**: Zymeworks is focused on ensuring tolerability and efficacy in its ADCs, particularly for fragile patient populations like those with HCC (Hepatocellular Carcinoma) [34][36] - **Combination Strategies**: The company recognizes the importance of combination therapies and is open to partnerships that can enhance its competitive positioning in the market [30][31] This summary encapsulates the strategic direction, market positioning, and future plans of Zymeworks as discussed in the conference call, highlighting the company's focus on innovation and value creation in the biotechnology sector.

Business Strategy & Financial Performance - Zymeworks is transitioning to a revenue-generating organization with in-house R&D capabilities, focusing on royalty streams and strategic capital allocation for shareholder returns[6] - The company reported $103 million in revenues for 2025 as of September 30, 2025[31] - Zymeworks anticipates up to $440 million in near-term milestones from global GEA approvals for Ziihera[20, 31] - A $125 million share repurchase plan has been announced[4, 31] - Existing cash resources are expected to fund operations beyond 2028, assuming full execution of the share repurchase plan and anticipated regulatory milestone payments[2, 31, 82] Pipeline & Partnerships - Zymeworks received a $25 million regulatory milestone payment from Jazz for FDA approval of Ziihera for HER2+ (IHC 3+) BTC[4] - The company also received a $20 million milestone payment from BeOne for NMPA conditional approval of Ziihera for BTC[4] - Zymeworks recognized $25.2 million in partnership milestone payments[4] - Zymeworks has potential future milestone payments of up to $434 million from one partner and up to $1.1 billion from another, plus tiered royalties[22] Clinical Development - Initial clinical data from the Phase 1 trial of ZW191 showed a 64% overall response rate in gynecological cancers at doses ≥6.4mg/kg[42, 49] - ZW251, an ADC targeting GPC3, is in Phase 1 clinical trials for hepatocellular carcinoma (HCC)[4, 55]

Financial Data and Key Metrics Changes - Total revenue for Q3 2025 was $27.6 million, up from $16 million in Q3 2024, primarily due to a $25 million milestone from Janssen and $1 million in royalties from Jazz Pharmaceuticals and BeiGene [9][10]. - Overall operating expenses decreased slightly to $49.7 million in Q3 2025 from $50.2 million in Q3 2024, a reduction of 1% [10]. - Net loss improved to $19.6 million in Q3 2025 compared to a net loss of $29.9 million in Q3 2024, attributed to increased revenue [10][11]. - Cash, cash equivalents, and marketable securities totaled $299.4 million as of September 30, 2025, down from $324.2 million at the end of 2024 [11]. Business Line Data and Key Metrics Changes - The company recognized a $25 million development milestone from Jazz Pharmaceuticals related to the clinical progress of pacritimab, contributing significantly to revenue [6][9]. - Royalty revenues of $1 million were earned based on Ziihera net product sales by Jazz and BeiGene [8]. Market Data and Key Metrics Changes - The company continues to see strong momentum in its partnered programs, with Jazz presenting positive trial data at ESMO [5][6]. - The first patient has been dosed in the phase one clinical trial of ZW251, targeting GPC3 in hepatocellular carcinoma, indicating ongoing clinical development [4][17]. Company Strategy and Development Direction - The company aims to leverage partnerships to accelerate development and maintain control over R&D innovations while de-risking clinical developments [25][27]. - The focus remains on advancing programs with clear differentiation and strong scientific rationale, utilizing partnerships to offset development risks [27]. - The company is committed to disciplined capital allocation to drive sustainable long-term returns [9][25]. Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the company's outlook, citing the strength of the pipeline and the successful execution of clinical trials [8][11]. - The company anticipates that existing cash resources, combined with expected regulatory milestones, will fund operations into the second half of 2027 [11]. Other Important Information - The company completed share repurchases of $22.7 million under its previously authorized program, reflecting confidence in its outlook [8]. - The decision to discontinue the development of ZW171 was made to prioritize programs with clearer paths to patient benefit [20][21]. Q&A Session Summary Question: Thoughts on the update in the PFS analysis for Horizon GEA 01 - Management aligned with Jazz's regulatory strategy regarding the readout of Horizon GEA 01 and did not provide additional comments [30]. Question: Implications of ZW191 data for GPC3 and potential development strategies - Management expressed intrigue regarding the GPC3 construct and emphasized the importance of safety in the hepatocellular carcinoma population [31][33]. Question: Insights on GPC3 payload and preclinical efficacy expectations - Management noted that while topo1 is not standard for liver cancer, there is precedent for its use, and they believe their ADC can deliver effective treatment [38][44]. Question: Confidence in GPC3 activity in the post-IO setting - Management indicated that GPC3 expression levels are not expected to be modulated by IO treatment, supporting their development plan [60][62]. Question: Expectations on durability for ZW191 and potential for partnerships - Management found early data from ZW191 encouraging and indicated ongoing discussions with potential partners [70][71]. Question: Correlation between H-score and PS2 plus scoring methodologies - Management confirmed that H-score is a validated method for evaluating expression levels and correlates well with PS2 plus scores [81][84].

3Q 2025 Results Conference Call and Webcast November 6, 2025 Nasdaq: ZYME | zymeworks.com Legal Disclaimer This presentation and the accompanying oral commentary include "forward-looking statements" or information within the meaning of the applicable securities legislation, including Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. Forward-looking statements in this presentation and the accompanying oral commentary include, but are no ...

Core Insights - Zymeworks Inc. reported financial results for Q3 and nine months ended September 30, 2025, highlighting progress in clinical trials and financial performance [1][13]. Clinical Highlights - Initial Phase 1 clinical data for ZW191, an antibody-drug conjugate (ADC) targeting folate receptor-α, showed promising results, with objective response rates of 53% overall and 64% for gynecological cancers [3][8]. - The Phase 1 trial for ZW251, targeting GPC3 for hepatocellular carcinoma, has commenced with the first patient dosed [5][7]. - Dose optimization for ZW191 is set to begin in Q4 2025, focusing on safety and efficacy at doses of 6.4 mg/kg and 9.6 mg/kg [4]. Business Updates - The company achieved a $25 million development milestone from Johnson & Johnson in Q3 2025, reflecting ongoing clinical progress [9]. - Zymeworks earned $1 million in royalties from Ziihera® net product sales during Q3 2025 [7][9]. - As of September 30, 2025, Zymeworks had cash resources of $299.4 million, down from $324.2 million at the end of 2024, providing a cash runway into the second half of 2027 [14]. Financial Performance - Total revenue for Q3 2025 was $27.6 million, up from $16 million in Q3 2024, primarily due to higher milestone revenue [13]. - Research and development expenses were $35.6 million in Q3 2025, slightly down from $36.4 million in Q3 2024 [13]. - The net loss for Q3 2025 was $19.6 million, an improvement from a net loss of $29.9 million in Q3 2024 [13][19]. Leadership and Strategic Initiatives - Zymeworks appointed Dr. Adam Schayowitz as Acting Chief Development Officer to enhance R&D and business development efforts [11]. - The company completed $22.7 million in share repurchases as part of its strategic program, aimed at enhancing shareholder value [12][13].

Core Insights - The conference call discusses preliminary results from the Phase I trial of ZW191, presented at the AACR-NCI-EORTC Conference in Boston [1][3] - The presentation includes a review of the design rationale and scientific principles behind ZW191's development [2] - Initial Phase I clinical data highlights will be summarized by Dr. Patricia LoRusso from Yale Cancer Center [3] Company Development - Zymeworks is focusing on the development path forward for ZW191 following the initial trial results [3] - The call will conclude with a Q&A session involving Dr. LoRusso and the Senior Vice President of Clinical Development [3]

Summary of Zymeworks Conference Call on ZW191 Phase One Trial Results Company and Industry - **Company**: Zymeworks - **Industry**: Biotechnology, specifically focused on antibody-drug conjugates (ADCs) for cancer treatment Key Points and Arguments Overview of ZW191 - ZW191 is an antibody-drug conjugate designed to target folate receptor alpha, utilizing a novel IgG monoclonal antibody conjugated to a topoisomerase I inhibitor, ZD-06519, with a drug-to-antibody ratio of eight [4][5] - The design aims to enhance tumor penetration and deliver high payload levels, particularly in tumors with low folate receptor alpha expression [5] Phase One Trial Design - The trial focuses on three primary tumor types: platinum-resistant epithelial ovarian cancer, serous or endometrial cancer, and adenocarcinoma non-small cell lung cancer [8] - Patients had a performance status of zero or one and were heavily pretreated, with a median of three prior treatments [10][11] Patient Demographics - 41 patients were treated, with approximately 70% having metastatic platinum-resistant ovarian cancer, 20% endometrial cancer, and 10% non-small cell lung cancer [10] - The patient population included a mix of Asian and Caucasian participants, with a significant number being heavily pretreated [9][10] Safety Profile - The trial reported minimal grade 3 or greater treatment-related adverse events, with only seven patients experiencing such events [12] - No serious treatment-related adverse events or deaths were reported, indicating a favorable safety profile [12][18] Efficacy Results - Preliminary data showed significant anti-tumor activity, with a 50% partial response rate in patients with gynecological cancers at doses between 6.4 mg/kg and 9.6 mg/kg [16][18] - Notably, ZW191 demonstrated efficacy in patients with low or negative folate receptor alpha expression, contrasting with other ADCs that require high expression for efficacy [14][15][16] Next Steps in Development - The maximum tolerated dose was determined to be 11.2 mg/kg, with plans to proceed with dose optimization at 6.4 mg/kg and 9.6 mg/kg [20] - Enrollment for the next phase of the study is expected to begin soon, focusing on refining the balance between efficacy and safety [20][21] Strategic Partnerships and Future Plans - Zymeworks aims to explore strategic partnerships to accelerate development and expand global reach, particularly for ZW191 and other pipeline ADCs [21][22] - The company is also considering combination therapies with existing treatments, such as bevacizumab, to enhance efficacy in earlier lines of treatment [71][86] Additional Insights - The design of ZW191 allows for a broader therapeutic window, supporting further investigation in advanced solid tumors [19] - The company is also looking into other preclinical candidates targeting novel antigens, indicating a robust pipeline beyond ZW191 [22][91] Important but Overlooked Content - The trial's design allows for the inclusion of patients regardless of prior mirvetuximab treatment, which may increase enrollment as the drug gains approval globally [25][26] - The efficacy observed in patients with low folate receptor alpha expression highlights a significant advantage of ZW191 over existing therapies, potentially expanding the treatment landscape for these patients [28][31] - The discussion around the mechanism of resistance for folate receptor alpha-based ADCs suggests that the payload's stability and the linker chemistry play crucial roles in the observed safety and efficacy [65][66] This summary encapsulates the critical aspects of the conference call, focusing on the development and potential of ZW191 in the oncology landscape.

Core Insights - Zymeworks Inc. announced preliminary results from a Phase 1 study of ZW191, an antibody-drug conjugate targeting folate receptor-alpha, at the AACR-NCI-EORTC Conference [1][2] Study Results - The Phase 1 study enrolled 41 patients with heavily pretreated platinum-resistant ovarian cancer, metastatic endometrial cancer, and metastatic non-small cell lung cancer, with 85% of patients remaining on treatment [3] - The maximum tolerated dose was determined to be 11.2 mg/kg, with dose optimization planned for 6.4 mg/kg and 9.6 mg/kg, involving approximately 30 patients in each cohort [4] Efficacy and Safety - ZW191 demonstrated a 44% overall response rate (ORR) across all response-evaluable participants and a 53% ORR for doses between 6.4 mg/kg and 9.6 mg/kg [6] - In gynecological cancer participants, the ORR was 50% overall and 64% for doses ≥6.4 mg/kg, with responses observed starting at 3.2 mg/kg [6] - The safety profile was manageable, with low rates of dose modifications and no serious treatment-related adverse events reported [6] Technology and Mechanism - ZW191 is designed to target folate receptor-alpha, which is present in approximately 75% of high-grade serous ovarian carcinomas and 70% of lung adenocarcinomas, utilizing a proprietary payload to kill tumor cells [8] Company Overview - Zymeworks is a clinical-stage biotechnology company focused on developing novel biotherapeutics for difficult-to-treat diseases, including cancer and autoimmune diseases, with a robust pipeline and strategic partnerships [9]

Core Viewpoint - Zymeworks Inc. is set to report its third quarter 2025 financial results on November 6, 2025, followed by a conference call and webcast to discuss the results and provide a corporate update [1][2]. Company Overview - Zymeworks Inc. is a clinical-stage biotechnology company focused on developing novel, multifunctional biotherapeutics aimed at improving treatment for difficult-to-treat diseases such as cancer, inflammation, and autoimmune diseases [3]. - The company utilizes its proprietary Azymetric™ technology to engineer and develop zanidatamab, a HER2-targeted bispecific antibody, which has received accelerated approval from the U.S. FDA and conditional approvals in China and Europe for treating specific types of cancer [3]. - Zymeworks is advancing a robust pipeline of product candidates, including ZW191, which is currently in a Phase 1 study, and ZW251, expected to enter clinical trials in 2025 [3]. - The company has established strategic partnerships with global biopharmaceutical companies to leverage its therapeutic platforms [3].