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].

Core Insights - Zymeworks Inc. announced the acceptance of a poster presentation for preliminary results from a Phase 1 study of ZW191, an antibody-drug conjugate targeting folate receptor-α, at the AACR-NCI-EORTC Conference on Molecular Targets and Cancer Therapeutics [1][2] Company Overview - Zymeworks is a clinical-stage biotechnology company focused on developing novel biotherapeutics for difficult-to-treat diseases, including cancer, inflammation, and autoimmune diseases [5] - The company has a diverse pipeline, including the lead product candidate ZW191, which utilizes a proprietary payload, ZD06519, designed to target FRα, a protein found in various challenging cancers [2][4] Product Details - ZW191 targets folate receptor-α, which is expressed in approximately 75% of high-grade serous ovarian carcinomas and about 70% of lung adenocarcinomas [4] - The design of ZW191 supports its ability to internalize into FRα-expressing cells, potentially releasing the active topoisomerase-1 inhibitor to kill tumor cells [4][6] Clinical Development - The Phase 1 study of ZW191 is actively recruiting participants, with preliminary data expected to provide insights into its efficacy in treating advanced solid tumors, including ovarian cancer, endometrial cancer, and non-small cell lung cancer [6][7] - A live webcast will be held on October 23, 2025, to discuss the data presented, featuring the lead author and Zymeworks senior management [3]

Core Insights - Zymeworks Inc. has appointed Adam Schayowitz, Ph.D., MBA as Acting Chief Development Officer to enhance its R&D and business development efforts [1][2][3] Company Overview - Zymeworks is a clinical-stage biotechnology company focused on developing multifunctional biotherapeutics for challenging diseases such as cancer, inflammation, and autoimmune disorders [1][5] - The company has a diverse pipeline of product candidates, including zanidatamab, which has received multiple regulatory approvals [5][6] Leadership Appointment - Dr. Schayowitz will report to Kenneth Galbraith, the Chair & CEO, and will work closely with R&D and Business Development teams to advance the company's product candidates [2][3] - He brings nearly 20 years of experience in oncology drug development, having held leadership roles at Pfizer Oncology and other biotech firms [3][4] Strategic Focus - The company aims to strengthen partnerships and collaborations while advancing its R&D portfolio [4][5] - Recent milestones include investigational new drug clearance for ZW251 and expanded global approvals for zanidatamab, indicating a focus on execution across the development pipeline [3][5] Product Pipeline - Zymeworks is advancing a robust pipeline, with ZW191 in Phase 1 recruitment and ZW251 expected to enter clinical trials in 2025 [5][6] - Zanidatamab is the first dual HER2-targeted bispecific antibody approved for treating HER2-positive biliary tract cancer in the U.S., Europe, and China [5]