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 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]