Financial Data and Key Metrics Changes - Total revenue increased to $48.7 million in Q2 2025 from $19.2 million in Q2 2024, primarily due to a $20 million milestone from B1 and recognition of $80.3 million in deferred revenue [15][16] - Operating expenses decreased by 20% to $49.4 million in Q2 2025 from $62.1 million in Q2 2024, mainly due to a prior year impairment charge [17] - Net income was $2.3 million for Q2 2025, compared to a net loss of $37.7 million in Q2 2024 [17][18] - Cash resources increased to $333.4 million as of June 30, 2025, from $124.2 million at the end of 2024 [18] Business Line Data and Key Metrics Changes - The company has three product candidates in active Phase I trials in 2025, with two additional candidates expected to enter the clinic in 2026 [7][8] - Zanadatumab showed a median progression-free survival of 15.2 months and overall survival of 36.5 months in a study involving HER2 positive tumors [9][10] - The company recognized a $7.5 million option exercise payment related to a licensing agreement with BMS [14] Market Data and Key Metrics Changes - Conditional regulatory approvals for zanadatumab in China and Europe are expected to increase international patient access and potential future royalties [10][13] - The company anticipates an increase in royalty revenues from zanadatumab's international approvals for biliary tract cancer [13] Company Strategy and Development Direction - The company aims to leverage its proprietary technology platforms and strategic partnerships to enhance asset value and deliver long-term returns for shareholders [44][46] - The focus is on advancing a wholly owned pipeline of differentiated antibody drug conjugates and multi-specific antibodies across various therapeutic areas [46][48] - The company is committed to maintaining a science-first approach while exploring partnerships to share risk and resources [48][49] Management's Comments on Operating Environment and Future Outlook - Management emphasized the importance of capital discipline and clarity in strategy to drive long-term value [44][51] - The company is focused on maximizing cash flow streams from royalties and other healthcare assets while maintaining flexibility in operations [51][52] - Anticipated growth in royalty and milestone income is not expected to trigger an automatic increase in operational expenditures [51] Other Important Information - The company presented data on its novel IL-4, IL-33 bispecific antibody for COPD at a recent conference, highlighting its potential in treating respiratory diseases [36][38] - The IND clearance for ZW251, targeting hepatocellular carcinoma, is seen as a significant advancement in the company's pipeline [28][29] Q&A Session Summary Question: Will PDL1 status be broken out for the triplet for arm C in the top line? - The inclusion of data in a top line press release will be determined by Jazz and B1, the sponsors of the studies [56][57] Question: How much of the ZANI $525 million regulatory milestone is weighted towards GEA versus other indications? - There is $500 million left in development milestones with Jazz, but no specific guidance on allocation has been provided [57] Question: How does ZW191 compare to other topoisomerase-based ADCs? - The company aims to create a differentiated asset with a novel mechanism and tolerability profile, which could allow for combinations with other treatments [60][63] Question: What is the approach for evaluating ZW251 in liver cancer patients? - The company will systematically study the tolerability and efficacy of ZW251 in appropriate patient subsets, considering liver impairment [68][69] Question: When can data from the Phase I trial of ZW191 be expected? - Initial data is anticipated to be shared at peer-reviewed meetings in 2025 or 2026, depending on abstract acceptance [74] Question: What is known about the expression of alpha in non-small cell lung cancer? - Analysis shows a subset of non-small cell lung cancer patients with BOLT receptor expression, encouraging further evaluation in this indication [78]

Financial Performance & Partnerships - Recognized approximately $75 million in 2025, including around $45 million from partnership-related cash milestones and option exercise fees, which significantly reduced net operating cash burn in the first half of 2025 compared to the first half of 2024[12] - Milestone, option exercise, and related deferred revenue of $45.8 million recognized in 2Q 2025 from BeOne and BMS[16, 17] - Potential future milestone payments from existing partnerships could reach up to $6.1278 billion, with royalty rates varying from low single-digit percentages to 20% depending on the partner and therapeutic indication[13] - Cash, cash equivalents, and marketable securities totaled $324.2 million in 2Q 2025, an increase of $9.2 million year-to-date, benefiting from milestone revenues and favorable working capital movements[16, 17] Clinical Development Updates - Investigational New Drug (IND) application cleared for ZW251, with first-in-human studies planned to start in 2025[11, 12, 47] - Phase 2 trial initiated to evaluate zanidatamab in HER2+ neoadjuvant and adjuvant breast cancer[12] - Bristol Myers Squibb collaboration progresses with a $7.5 million option exercise payment to Zymeworks[12] - ZW171: Global Phase 1 study in MSLN-Expressing Solid Tumors (NCT06523803) is an open-label, FIH, dose-escalation study (N~160)[19] - ZW191: Global Phase 1 Study in FRα-Expressing Solid Tumors (NCT06555744) is an open-label, FIH, dose-escalation study (N~145)[24] Zanidatamab Regulatory & Clinical Progress - NMPA granted BeOne conditional approval of zanidatamab in China for BTC, resulting in a $20 million payment to Zymeworks[12] - EMA granted conditional marketing approval of zanidatamab in Europe for BTC, expanding patient access and potential future royalties payable to Zymeworks[12, 47] - Jazz presented encouraging overall survival (OS) data for zanidatamab in 1L HER2+ GEA at the ASCO Annual Congress, showing a median OS of 36.5 months[12]

Core Insights - Zymeworks Inc. reported financial results for Q2 2025, highlighting significant revenue growth and advancements in its clinical pipeline, particularly with its lead product zanidatamab [1][16]. Financial Performance - Total revenue for Q2 2025 was $48.7 million, a substantial increase from $19.2 million in Q2 2024, driven by milestone payments and deferred revenue recognition [16]. - Research and Development (R&D) expenses rose to $34.4 million in Q2 2025 from $29.2 million in Q2 2024, reflecting increased investment in various clinical programs [16]. - The company achieved a net income of $2.3 million in Q2 2025, a significant turnaround from a net loss of $37.7 million in Q2 2024 [16][21]. Clinical Developments - Zymeworks has three product candidates expected to enter active Phase 1 trials in the second half of 2025, with two additional candidates on track for 2026 [2]. - The IND application for ZW251 was cleared by the FDA, with first-in-human studies planned for 2025 [3][7]. - Zanidatamab has shown promising results in clinical trials, with a median progression-free survival of 15.2 months and overall survival of 36.5 months in patients with HER2-positive gastroesophageal adenocarcinoma [9][10]. Strategic Partnerships - The company has established strategic partnerships that have validated its Azymetric platform, generating meaningful revenue and supporting clinical development [2]. - Zymeworks recognized $20 million in milestone revenue from BeOne Medicines related to the conditional approval of zanidatamab in China [10]. - The collaboration with Jazz Pharmaceuticals for zanidatamab is expected to enhance future royalties, with the European Commission granting conditional marketing authorization for the treatment of HER2-positive biliary tract cancer [11]. Cash Position - As of June 30, 2025, Zymeworks had cash resources of $333.4 million, providing a projected cash runway into the second half of 2027 [3][16].

Core Viewpoint - Zymeworks Inc. is advancing its clinical-stage pipeline with the presentation of new preclinical data for ZW1528, a bispecific molecule targeting IL-4Rα and IL-33, aimed at treating respiratory inflammation, particularly chronic obstructive pulmonary disease (COPD) [1][2]. Group 1: Product Development - ZW1528 demonstrates high affinity binding to IL-4Rα and IL-33, effectively blocking IL-4, IL-13, and IL-33 signaling pathways, which are critical in respiratory inflammation [5][6]. - The bispecific design of ZW1528 shows promising manufacturability and stability, supporting high dosing concentrations and subcutaneous administration [5][7]. - Zymeworks is also developing ZW1572, another bispecific inhibitor targeting IL-4Rα and IL-31 for atopic dermatitis, as part of its expanding IL-4Rα program portfolio [3][5]. Group 2: Preclinical Data and Findings - Preclinical data presented at the ATS conference indicate that ZW1528 can suppress both Type 2 and non-Type 2 immune responses in primary human immune cells from COPD patients [6][7]. - In vivo studies in murine models of lung inflammation show efficacy for ZW1528, with extended pharmacokinetics observed in rodent and non-human primate models [6][7]. - The bispecific antibody's blockade of cytokine-driven activation in human epithelial cells is superior to that achieved with monoclonal antibodies targeting either IL-4Rα or IL-33 [7]. Group 3: Company Overview - Zymeworks is a global biotechnology company focused on developing multifunctional biotherapeutics for difficult-to-treat conditions, including cancer and autoimmune diseases [8]. - The company has a robust pipeline of product candidates and has entered into strategic partnerships to enhance its therapeutic platforms [8].

Core Insights - Zymeworks Inc. reported financial results for Q1 2025, highlighting a significant increase in revenue and ongoing advancements in its clinical pipeline [1][15][20] Recent Developments - The appointment of Dr. Sabeen Mekan as Senior Vice President of Clinical Development is expected to enhance Zymeworks' oncology portfolio and regulatory strategy [3] - Six posters were presented at the AACR annual meeting, showcasing progress in the company's T cell engager and antibody-drug conjugate platforms [4][5] Financial Performance - Revenue for Q1 2025 was $27.1 million, a substantial increase from $10.0 million in Q1 2024, driven by milestone revenues from GSK and Daiichi Sankyo [15] - Research and development expenses rose to $35.7 million in Q1 2025 from $32.0 million in Q1 2024, primarily due to increased activities related to ZW251 and ZW209 [16] - The net loss for Q1 2025 was $22.6 million, down from $31.7 million in the same period last year, attributed to higher revenues [20] Cash Position - As of March 31, 2025, Zymeworks had $321.6 million in cash resources, expected to fund operations into the second half of 2027 [21] Pipeline and Collaborations - Zymeworks is advancing multiple clinical candidates, including ZW171 and ZW191, with an investigational new drug application for ZW251 planned by mid-2025 [22] - The company has strategic partnerships with BeiGene and Jazz Pharmaceuticals for the development and commercialization of zanidatamab [22][8]

Financial Data and Key Metrics Changes - Zymeworks reported a net loss of $122.7 million for the year ended December 31, 2024, compared to a net loss of $118.7 million in 2023, primarily due to a $17.3 million noncash impairment charge [14][16] - Revenue for 2024 was $76.3 million, slightly up from $76 million in 2023, including $25 million of milestone revenue from Jazz related to the FDA approval of Ziihera [14][15] - Operating expenses were $213.4 million for 2024, a slight decrease from $214.1 million in 2023, reflecting lower research and development expenses [15][16] Business Line Data and Key Metrics Changes - The company earned over $45 million from partnerships in the past year, with significant contributions from Jazz and BeiGene [10][12] - Ziihera achieved net product sales of $1.1 million in Q4 2024 following its launch, contributing to the company's revenue [11] Market Data and Key Metrics Changes - Zymeworks had approximately $324.2 million in cash resources as of December 31, 2024, down from $456.3 million in 2023, providing a cash runway into the second half of 2027 [21][22] Company Strategy and Development Direction - The company is focused on advancing its next-generation therapeutics, particularly in autoimmune and inflammatory diseases, as well as hematological oncology [9][12] - Zymeworks aims to leverage its innovative platforms to address emerging therapeutic challenges and expand its collaborations [8][12] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the potential of ZW251 for hepatocellular carcinoma and emphasized the importance of accelerating its clinical studies [46][47] - The company anticipates significant milestones in 2025, including top-line data from the HERIZON-GEA-01 study of zanidatamab [50] Other Important Information - The appointment of Oleg Nodelman to the Board reflects the growth of EcoR1's shareholding and confidence in Zymeworks' potential [48] - The company is exploring the potential of multi-payload ADCs and is investigating additional payloads for its products [120] Q&A Session Summary Question: On ZW251, will there be urgency to initiate combination cohorts? - Management confirmed that they are interested in early signs of tumor activity and will study ZW251 in both dose escalation and expansion cohorts [54][56] Question: What prompted the prioritization of ZW251 over ZW220? - The decision was based on excitement for ZW251 and the ability to accelerate its clinical studies, while still maintaining momentum for ZW171 and ZW191 [58][60] Question: What are the gating factors for filing the IND for ZW1528? - The company is focused on completing IND enabling activities and expects to provide realistic guidance for filing in the second half of 2026 [115][116] Question: Can you share thoughts on multi-payload ADCs? - Management indicated that they are investigating additional payloads and consider the therapeutic rationale important for developing such molecules [120] Question: What is the desired target product profile for ZW251? - The company aims to demonstrate efficacy across a broad range of hepatocellular carcinoma models and believes in the importance of the target in their design [128][129]