Thank you for standing by. This is the conference operator. Welcome to Zymeworks Second Quarter 2025 Results Conference Call and Webcast. The conference is being recorded. I would now like to turn the conference over to Shrinal Inamdar, Senior Director of Investor Relations. Please go ahead.

Thank you, operator, and good afternoon, everyone. Thanks for joining our second quarter 2025 results conference call. Before we begin, I'd like to remind you that we will be making a number of forward-looking statements during this call, including, without limitation, those forward-looking statements identified in our slides and the accompanying oral commentary. Forward-looking statements are based upon our current expectations and various assumptions and are subject to the usual risks and uncertainties associated with companies in our industry and our stated development. For discussion of these risks and uncertainties, we refer you to the latest SEC filings as found on our website and as filed with the SEC. In a moment, I will hand over to Leone Patterson, our Executive Vice President and Chief Business and Financial Officer, who will provide an overview of our recent business and partnership update along with financial results for our second quarter 2025. Following this, Dr. Sabeen Mekan, our Senior Vice President of Clinical Development, will provide progress updates on our Phase I program, ZW171 and ZW191. We will then pass the call over to Dr. Paul Moore, our Chief Scientific Officer, who will give an overview of recent R&D development as well as an update on IND clearance for our second Topo ADC candidates, ZW251. At the end of the call, Leone, Sabeen, Paul and Ken Galbraith, our Chair and CEO, will be available for Q&A. As a reminder, the audio and slides from this call will also be available on the Zymeworks website later today. I will now hand the call over to Leone.

Thank you, Shrinal, and thank you all for joining us today. I'll first walk you through our highlights for the second quarter of 2025. On our clinical programs, we presented trial and progress posters for ZW171 and ZW191, which are both progressing in their respective Phase I studies. Sabeen will provide more color on the dosing regimen and study design for each of these trials later in the call. We are also pleased to have announced the IND clearance of our second TOPO1 inhibitor payload ADC, ZW251 for the treatment of HCC. Based on our observations of ZW191 in the clinic to date, we are excited to get the study up and running. With this development, ZW251 would be our third product candidate in active Phase I trials in 2025. Two additional product candidates are on track to enter the clinic in 2026, while ZW220 remains IND-ready. Together, these developments demonstrate consistent execution across our R&D programs and long-term business strategy. On our preclinical pipeline, we are pleased to have presented inaugural data on our novel IL-4, IL-33 bispecific in development for COPD at the American Thoracic Society International Conference. Paul will talk more about the preclinical data presented later in the call and how we see ZW1528 positioned in the competitive landscape. Meanwhile, zanidatamab continues to progress through the presentation of updated long-term survival data at ASCO, highlighting that among 41 GEA patients with centrally confirmed HER2-positive tumors. Treatment with zanidatamab in combination with physicians' choice of chemotherapy resulted in a median progression-free survival of 15.2 months and a median overall survival of 36.5 months. We believe these data reflect the durability and tolerability of zanidatamab and support our thesis of patients staying on treatment longer. This builds on the meaningful efficacy and tolerability profile seen to date with zanidatamab and provides further confidence for the highly anticipated HERIZON-GEA pivotal study data readout. We look forward to the top line progression-free survival data from the HERIZON-GEA-01 study expected late in the fourth quarter of 2025 as Jazz announced this week. Jazz also recently announced the initiation of a Phase II trial studying zanidatamab as it increases pathological complete response rates, improves long-term outcomes and reduces overall toxicity. Lastly, conditional regulatory approvals for zanidatamab in China and Europe for second-line HER2-positive biliary tract cancer this quarter also expand international patient access and potential future royalties payable to Zymeworks. Beyond this, our platform partnerships also continue to produce at the ASCO Annual Meeting, J&J Innovative Medicines reported Phase I trial results for pasritamig, a first-in-class T-cell engaging bispecific antibody targeting human kallikrein 2 or KLK2 expressed on the surface of prostate cancer cells. Pasritamig demonstrates preliminary antitumor activity in prostate cancer patients to establish a proof of concept for KLK2 as a target in prostate cancer and to warrant further development by J&J. Pasritamig also demonstrates a favorable safety profile with very low rates of cytokine release syndrome and could be safely administered in an outpatient setting. J&J has registered trials to evaluate pasritamig across 4 Phase I trials to explore dosing regimens, both as monotherapy and in combination with a range of agents, including checkpoint inhibitors, taxanes, androgen receptor pathway inhibitors. We look forward to learning more from J&J on the advancement of this program. We view this development as a strong signal of both scientific conviction and continued investment in the KLK2 program. Also at the ASCO Annual Congress, our partner, Daiichi Sankyo, presented a trial in progress poster for a Phase I first-in-human study of DS-2243, a bispecific T-cell engager in patients with advanced solid tumors. Similarly, we look forward to following Daiichi's progress in this program. Continuing on to the topic of partnerships. This quarter, progress continues across our strategic partnerships, further validating the strength and versatility of our platform as well as our strategic partnering model, which enables broad and accelerated clinical development with the right collaborators. The achievement of key development milestones from these partnerships generated meaningful revenue, helping us to offset our measured R&D cash burn. As you can see on this slide, we have a strong network of leading pharmaceutical partners whose complementary capabilities could serve as meaningful future catalysts alongside our own with the potential to enhance our enterprise value and competitive advantage long-term. Let me walk you through a few examples of that. The recent conditional approval of zanidatamab in China and Europe obtained by our partners Jazz and BeiGene means that we are anticipating an increase in royalty revenues for Zymeworks for the remainder of 2025 and beyond. Also, under the terms of our agreement with BeOne Medicines, the NMPA approval in China resulted in a $20 million milestone payment, which we recognized as revenue this quarter, along with $18.3 million of deferred revenue recognized in connection with reaching this milestone. While the initial royalties being reported from BeOne this quarter are modest, they represent the first tangible signal of near-term revenue growth from zanidatamab's international approvals in biliary tract cancer. As a reminder, we are eligible to receive tiered royalties of up to 19.5% of net sales in BeOne territories, increasing to up to 20% when cumulative amounts forgone as a result of a royalty reduction of 0.5% reaches a cap in the low double-digit millions of dollars. Similarly, this quarter, we recognized $7.5 million option exercise payment in relation to our 2014 licensing agreement and collaboration agreement with BMS. As a reminder, we remain eligible to receive up to $313 million in development and commercial milestones from the BMS collaboration in addition to potential tiered royalties on global product sales. As we look forward to the second half of this year, our partner programs are expected to continue advancing. And with that, we anticipate the potential of additional near-term development milestones to be achieved. These events are tied to meaningful clinical progress from our partners. And while the timing is driven externally, we see clear potential for additional non-dilutive cash inflows to materialize. Now turning to our financial results. Total revenue was $48.7 million in the second quarter of 2025 compared to $19.2 million for the second quarter of 2024. The increase was primarily due to a $20 million nonrefundable milestone from BeOne upon conditional approval of the BLA for zanidatamab for second-line treatment of HER2+ BTC by the NMPA in China, plus the recognition of $18.3 million deferred revenue in relation to the achievement of that milestone. $7.5 million from BMS due to the exercise of the commercial license option and $0.6 million of royalty revenues from Jazz and BeOne. These revenues were partially offset by a reduction in development support and drug supply revenue from Jazz and other nonrecurring milestones achieved in the second quarter of 2024. Overall, operating expenses were $49.4 million for the 3 months ended June 30, 2025, compared to $62.1 million for the same period in 2024, representing a decrease of 20%. The decrease in operating expenses was primarily due to the $17.3 million noncash impairment charge recognized in 2024 related to zanidatamab zovodotin and reduction in costs for zanidatamab zovodotin and ZW220. These were partially offset by an increase in ZW171, 191 and other preclinical research expenses for ZW209 and 251. Net income was $2.3 million for the 3 months ended June 30, 2025, compared to a net loss of $37.7 million for the same period in 2024. This was partially due to an increase in revenue and a decrease in operating expenses, which included an impairment charge of $17.3 million on intangible assets in the second quarter of 2024, partially offset by a decrease in interest income. As of June 30, 2025, we had $333.4 million of cash resources consisting of cash, cash equivalents and marketable securities, which is an increase in cash resources compared to $324.2 million as of December 31, 2024. We remain well capitalized and based on our current operating plans, we expect our existing cash resources as of June 30, 2025, when complied with the assumed receipt of certain anticipated regulatory milestones, will enable us to fund planned operations into the second half of 2027, which is anticipated to take us through multiple catalyst events on our pipeline. These achievements underscore the strength of our foundational partnerships and the relevance of our platform across multiple products moving into the clinic. For additional details on our quarterly results, I encourage you to review our earnings release and other SEC filings as available on our website at www.zymeworks.com. Now I'd like to hand the call over to SVP Clinical Development, Dr. Sabeen Mekan, to run through progress on our clinical development programs.

Thanks, Leone, and good afternoon, everyone. We are pleased to have presented trial in progress posters for both ZW171 and ZW191 at recent peer-reviewed medical conferences, highlighting the translation from preclinical tolerability profiles to clinical starting doses for each program. In some cases, these updates also provide insights and learnings for the safety and tolerability profiles we could see for earlier-stage product candidates within our ADC and multi-specific T-cell engager portfolios. Firstly, in June 2025, we presented a trial in progress poster for ZW171 at the American Society of Clinical Oncology Annual Meeting. The study employs a subcutaneous step-up dosing regimen on days 1, 8 and 15 of each 21-day cycle. The starting dose level is based on a quantitative systems pharmacology-guided minimal anticipated biological effect level, MABEL approach, and includes sequential doses of 4.2 micrograms Cycle 1 Day 1; 12.6 micrograms Cycle 1 Day 8; and 38 micrograms Cycle 1 Day 15. Dose level 2 and above are determined by the data from prior doses based on prespecified rules within the protocol. The modified toxicity probability interval (mTPI) design is being used to establish the maximum tolerated dose and recommended dose for expansion. We will continue to monitor early data from the Phase I trial of ZW171 as it continues to progress, and we will be thoughtful and decisive about next steps in line with observations on its tolerability and pharmacologic activity. Moving on to the design for ZW191 as presented at the ESMO Gynecological Cancers Congress. The study is designed in 2 parts with the primary objectives of evaluating safety, tolerability and identifying the recommended dose for expansion in patients with ovarian cancer, endometrial cancer and non-small cell lung cancer. Part 1 is the dose escalation phase, where we are evaluating the safety profile of ZW191 and determining the maximum tolerated dose. The starting dose or dose level 1 is 1.6 milligrams per kilogram administered once every 3 weeks by intravenous infusion. We felt it was important to take a conservative approach with the starting dose for the Phase I trial of ZW191 compared to what our preclinical studies could have enabled, given that this is the first time we are dosing our 519 payload in humans. We plan to evaluate approximately 6 dose levels with escalation guided by safety and tolerability using a modified toxicity probability interval design. This adaptive design allows us to identify the optimal dose range with both statistical rigor and operational flexibility. Following successful dose escalation, we would plan to move into Part 2, which consists of 2 components. Part 2a focuses on dose optimization in ovarian cancer, enabling us to refine the dosing strategy based on safety, exposure and preliminary activity signals. Part 2b is a dose expansion phase in patients with FR alpha expressing endometrial cancer or non-squamous non-small cell lung cancer. This part of the study allows us to further characterize safety and explore antitumor activity in biomarker-enriched populations. Our goal with the study is to establish a strong foundation for ZW191's clinical profile, identify an optimal biological dose and explore the potential of our ADC platform to utilize our proprietary payload and linker across FR alpha expressing tumors. That being said, ZW191 is also providing important translational insights that not only inform dose selection for this program, but also provide data that could potentially accelerate and derisk the future development of ZW251 and other pipeline ADCs utilizing our 519 payload. As with ZW171, we will continue to monitor early data from the Phase I trial of ZW191 as it continues to progress and take an adaptive approach with any necessary protocol amendments to optimize the trial design. Based on the clinical and translational data we are seeing to date and leveraging our growing understanding of the in-human tolerability and efficacy profile of our novel payload, ZD06519, we are confident in advancing ZW251, our second topoisomerase 1 inhibitor ADC towards Phase I clinical development. Enrollment for ZW191 and ZW171 is proceeding as planned, and we are meeting our internal timelines for both programs, which reflects the strong coordination across our clinical and operational teams. We look forward to sharing initial clinical data at appropriate future medical conferences as the ZW191 and ZW171 studies progress. I will now hand over to Paul, who will talk more about ZW251, which has recently received IND clearance in the U.S. Following precedent set from our previous Phase I programs, we also plan to initiate clinical sites for ZW251 globally, and I look forward to updating you on our progress and study design considerations on a future call.

Thank you, Sabeen. I'm excited to provide updates on our R&D pipeline, where we are experiencing strong momentum, especially with the IND clearance of ZW251. As mentioned by Sabeen, we are optimistic about the clinical progress made so far with our lead ADC candidate, ZW191, which shows early signs of alignment between preclinical predictions and clinical results. We believe the initial data from ZW191 offer a solid foundation and reaffirm our confidence in the therapeutic potential of our proprietary topoisomerase 1 inhibitor payload, ZD06519. This alignment has strengthened our decision to advance ZW251 into clinical trials. ZW251 shares the fundamental components of ZW191, including our topoisomerase 1 inhibitor payload and an optimized antibody framework, but is specifically designed to target hepatocellular carcinoma, a disease that has a significant unmet medical need and few effective targeted therapies. We find GPC3 particularly appealing from a therapeutic perspective due to its expression profile. It is highly expressed in most HCC tumors while showing limited expression in normal adult tissues, which minimizes the risk of off-target effects and supports a favorable therapeutic index for GPC3-targeted therapies. As illustrated in the panel on the left, GPC3 is overexpressed in over 75% of HCC tumors while displaying limited expression in normal tissues, making it a strong candidate for selective ADC targeting. Notably, GPC3 is expressed during fetal development but is largely silenced in healthy adult tissues, providing a unique opportunity for targeting tumors without affecting normal adult physiology. Previous studies have validated GPC3's accessibility and significance as a therapeutic target through successful accumulation of anti-GPC3 antibodies in patient tumors. While glypican-3 (GPC3) has gained attention in the industry, much of the exploration so far has focused on other therapeutic modalities. We are among the pioneers systematically advancing GPC3 as a target for antibody-drug conjugates. With ZW251, we have taken a carefully considered approach to harnessing the potential of this target using our proprietary ADC platform. Regarding the panel in the middle of the slide, ZW251 features a moderately potent bystander-active topoisomerase 1 inhibitor payload, ZD06519, which enables us to deliver higher protein doses compared to those that use more potent camptothecin derivatives like exatecan-based ADCs. We believe this enhances target engagement and tumor penetration, especially critical in tumors with lower heterogeneous GPC3 expression, which is essential for achieving therapeutic impact across a broader patient population. ZW251 consists of a humanized IgG1 monoclonal antibody that binds GPC3 with high specificity and affinity. This antibody also exhibits desirable cross-reactivity in both human and nonhuman primate models, which is crucial for translational relevance and safety evaluations. Preclinical studies have shown that once bound, the antibody is internalized into GPC3-expressing tumor cells, leading to intracellular delivery of the cytotoxic payload. Our objective was to optimize the balance between safety and efficacy in a patient population often complicated by liver dysfunction. The panel on the far right shows that preclinical studies demonstrate that ZW251, with a drug-antibody ratio (DAR) of 4, displays significant antitumor activity across various HCC models compared to a DAR8 ADC control. This activity is also evident in models with varying GPC3 expression. Importantly, this lower DAR may offer greater flexibility in clinical dosing, which is vital in HCC where liver impairment can greatly affect treatment tolerability. I also want to touch briefly on the preclinical safety and pharmacokinetics data we've generated for ZW251, which strongly supports our clinical development plan. In our nonhuman primate studies, ZW251 showed dose-proportional pharmacokinetics indicated by total antibody levels. This predictability of drug behavior is an essential factor for both dose selection and exposure modeling as we prepare for first-in-human studies. From a safety perspective, ZW251 was well tolerated at all dose levels, including doses up to 120 mg per kg, with no fatalities or adverse clinical signs, and no significant effects on body weight or food consumption during the study. Overall, these results indicate a favorable tolerability profile and suggest that ZW251 could be suited for higher doses in humans compared to ZW191, which is designed at a DAR8. We are confident as we prepare for clinical entry. We believe ZW251 is well positioned to provide a differentiated safety and efficacy balance compared to other ADCs in the pipeline. Looking ahead, we believe the growing data sets supporting our ADC platform could reduce the time to clinic for new assets like ZW251 and maximize the broader therapeutic impact of our technology across various tumor types. Additionally, ZW220, our NaPi2b targeted ADC with our 519 payload, remains IND-ready. We are committed to advancing both ZW191 and ZW251 with scientific rigor and look forward to sharing more data at peer-reviewed medical conferences in the future. Now, I'd like to discuss another potential first-in-class candidate from our preclinical pipeline, ZW1528. As you may recall from our R&D Day, ZW1528 is our first nominated product candidate from our autoimmune and inflammatory pipeline, a bispecific antibody targeting IL-4 receptor alpha and IL-33 for treating respiratory diseases such as chronic obstructive pulmonary disease and asthma. Our initial therapeutic focus for ZW1528 is COPD, a challenging condition that remains poorly managed for many patients despite existing treatments. The high prevalence of uncontrolled diseases and frequent exacerbations highlights the need for more effective mechanism-based approaches. Chronic inflammation plays a key role in COPD pathology, characterized by dysregulation of both type 2 and non-type 2 immune responses in the lung, resulting in persistent airway injury, inflammation, and tissue remodeling. ZW1528’s design is based on the biology of these pathways and informed by the limitations of current therapies. As shown in the middle panel, ZW1528 is engineered to simultaneously block critical inflammatory pathways by targeting IL-33 and IL-4 as well as IL-13. These cytokines are fundamental to early inflammation and disease progression. IL-33 is a pro-inflammatory cytokine closely linked to epithelial stress, immune activation, and structural lung damage. Meanwhile, IL-4 receptor alpha signaling is a primary driver of type 2 inflammation, which perpetuates disease activity and exacerbations in many patients. In preclinical studies, ZW1528 reduced lung inflammation in a murine model of type 2 inflammation, showing activity comparable to dupilumab. Mice with a humanized IL-4 receptor alpha challenged with house dust mite to induce type 2 lung inflammation were treated with ZW1528, leading to a significant reduction in lung tissue pathology, including alveolar wall thickening and bronchial hyperplasia. Flow cytometry analysis revealed reduced eosinophilic infiltration and a rebalancing of alveolar macrophage populations, which corresponded with decreased serum IgE levels and lower expression of key type 2 cytokines in lung tissue, confirming the molecule's inhibition of type 2 inflammatory responses, matching the effectiveness of dupilumab in the same experiment. ZW1528’s capability to also block non-type 2 responses through its anti-IL-33 specificity is shown in ex vivo analysis of COPD patient PBMC, where reduced interferon-gamma positive NK cells were observed. This reduction in cytokine response is comparable, if not superior to that achieved by an anti-IL-33 mAb analog. Importantly, dupilumab did not block this type 1 response. Mechanistically, ZW1528 demonstrates strong inhibition of both IL-4 receptor alpha and IL-33-mediated signaling. To assess ZW1528's ability to block both pathways, in vitro studies using human epithelial cells responsive to both IL-4 receptor and IL-33 activation were conducted, showing ZW1528 effectively blocked IL-4/IL-33 combination-induced CCL2 gene expression, outperforming monoclonal benchmark therapies in their combinations. These findings validate our design rationale for ZW1528 and support its therapeutic potential across various airway inflammatory conditions. By targeting two nonredundant upstream pathways with a single agent, ZW1528 offers a potentially comprehensive approach to disease modulation, which has been a challenge for single pathway or combination therapies. Before concluding, I want to mention recent prominent readouts from peers that have renewed attention to IL-33's role in COPD. While some recent competitor trials did not meet their primary endpoint in both randomized registration studies, it is crucial to carefully contextualize these results. The consistent targeting of IL-33 across multiple large studies supports its biological relevance in COPD, and critical questions remain regarding trial design and patient selection, especially given the observed lower-than-expected exacerbation rates across the wider population. We eagerly await the complete data set, which will be vital in understanding which specific subpopulations benefitted, potentially guiding future trial strategies. Unlike these programs that focus solely on IL-33, ZW1528 blocks both IL-4 and IL-13 via IL-4 receptor alpha and the alarmin cytokine IL-33. This simultaneous targeting may allow us to regulate both type 2 inflammation and epithelial-driven immune activation, providing broader and more durable disease control in COPD and other inflammatory conditions like asthma. The evolving competitive landscape, including recent trial results, continues to shape our strategies for patient selection and biological targeting, and we are applying these insights as we develop ZW1528, aiming for a non-U.S. regulatory filing submission in the latter half of 2026. We anticipate presenting more data on ZW1528 at the European Respiratory Society Conference in September. In conclusion, we remain dedicated to innovation and meticulous execution across our R&D pipeline, committed to our ultimate goal of improving the standard of care for patients with significant unmet medical needs. Now, I'll pass it over to Ken to wrap up today's call and open the floor for Q&A.

Thank you, Paul. As we move through the remainder of 2025, there's no question that capital markets continue to reward clarity, capital discipline and real progress towards durable value. That's how we've designed our strategy and it's how we're evolving our business model to optimize both long-term value for shareholders while making a meaningful difference in patient outcomes. As demonstrated by our partnerships with Jazz and BeOne, we believe that long-term success in biotech lies at the intersection of platform-driven innovation and strategic execution. That belief now forms the backbone of our strategy, combining the strength of our proprietary technology platforms such as Azymetric with targeted partnerships to fully unlock asset value and deliver durable returns for shareholders. The Azymetric platform has proven itself to be a differentiated antibody platform that allows for precise control over geometry and valency, essential features for engineering next-generation biologics with superior selectivity and function. This has already been validated through clinical and regulatory success with zanidatamab as well as multiple high-value licensing partnerships with some of the industry's most respected pharmaceutical companies, as Leone has walked through earlier. We believe these collaborations validate our science and they position us well for meaningful milestones and royalty revenue opportunities in the years ahead as we've already seen materialize through the first half of 2025. Our evolving strategy is both building on our successful track record of discovering and developing highly differentiated assets and executing strategic partnerships to maximize their value through upfront and milestone payments and continued royalty rights. Together, we believe our platform and pipeline creates a business model that offers investors exposure to a rich diversified portfolio anchored by the potential for product-linked cash flows. We believe that our ability to partner assets currently under development as well as future R&D candidates, especially in our advanced portfolio, makes this focus on value growth a long-term sustainable business model. We're currently advancing a wholly owned pipeline of differentiated antibody-drug conjugates and multispecific antibodies spanning both clinical and preclinical stages in solid tumors, hem/onc and autoimmune inflammatory disease. Since 2022, we've been building this portfolio of clinical-stage and preclinical product candidates using our own capital and resources, thus maintaining 100% of the commercial rights of the portfolio. Now we're focused on integrating new partnerships and collaborations into our portfolio development to help share risk, capital and resources while maintaining a certain level of independent research. Our preferred partnership model will allow for broad and accelerated clinical development of these assets with the right partners who bring deep capabilities, global scale and commercial reach. This would enable partner programs like Ziihera has done to advance faster and broader than we could alone, maximizing future commercial potential through royalties and other payments while helping to manage clinical execution risk and stabilize internal cash burn. We believe our model is differentiated, scalable and offers immense growth potential for years to come. We believe that the stability of anticipated cash inflows as well as derisked candidate development through partnerships is attractive in the current competitive landscape and helps provide us with potential alternative funding opportunities to traditional equity financing. Since we've not completed a meaningful public equity offering in 3.5 years, we've been able to accrete growing value from Ziihera, our partnerships and wholly owned portfolio to our stockholders with minimal dilution. And we've also been able to return capital to shareholders through repurchase and retirement of common shares as we did last year. Importantly, partnerships would enable us to transfer the cost risk of late-stage development to our collaborators, providing us with the opportunity to reinvest certain levels of nondilutive capital, such as upfront payments and early milestone payments back in a productive R&D organization, while also continuing to consider allowing excess capital back to shareholders as appropriate, thereby helping us to keep our innovative R&D cycle moving while preserving capital efficiency. By retaining royalty rights and long-term economics on partner programs, we aim to give shareholders continued exposure to the upside of innovative R&D efforts as they progress to commercialization, but with lower risk and capital exposure. It's important to highlight that at our core, Zymeworks is a science-first company, and our evolving strategy is not changing that. Our unwavering commitment to scientific excellence is what built the Azymetric platform, resulted in the discovery and development of Ziihera and what continues to differentiate us today in the highly competitive field of antibody-drug conjugates and multispecific antibody therapeutics. As innovation and competition in oncology and autoimmune inflammatory disease becomes increasingly complex, our ability to seek out tough biological problems helps us position us as thought leaders and collaborators of choice for companies seeking cutting-edge solutions for patients with high unmet medical need. By leading with science, leveraging our platform and structuring partnerships thoughtfully, we're seeking to build a business that's not only financially sound, but one that keeps Zymeworks at the forefront of oncology and autoimmune inflammation innovation for years to come. Given the strong potential we see for peak sales of zanidatamab, we believe we have a compelling opportunity to anchor our future strategy around anticipated royalty and milestone streams from Ziihera in biliary tract cancer, GEA and other potential future indications, which we believe could provide a predictable long-term source of substantial and durable positive cash flows. These core royalty revenues from Ziihera can be supplemented over time by additional potential revenues from existing partnerships such as our collaboration with J&J Innovative Medicines with pasritamig as well as new partnerships and collaborations formed from our wholly owned R&D pipeline or accessed externally. As the year of revenue grows and with continued financial discipline applied to ongoing R&D investment, we intend to continue evaluating opportunities to allocate excess cash for shareholder returns. Excess cash may allow for opportunistic investment to bolster our royalty-driven cash flows or additional investment in innovative R&D programs with future potential for partnership formation on attractive terms. I just want to emphasize this point: expected growth in royalty and milestone income does not necessarily trigger an increase in operational expenditures. We would view these anticipated revenues as strategic long-dated cash flows, and we plan to treat them as such. We're not planning on automatically scaling our operations in response to cash inflows and our R&D investment remains disciplined and tightly aligned to programs where we have both scientific conviction and a clear path to long-term value through partnerships and collaborations. What this means in practice is that while we expect to be well positioned as visibility on royalty revenue streams increases, we're prioritizing the protection of our current cash runway and keeping flexibility intact. We're evolving our strategy and believe that utilizing this income to fund focused, high-return initiatives is the best path to maximizing long-term shareholder value. That said, we regularly evaluate whether a shift such as monetization, acquisitions or selective return of capital will enhance that value as we've done in the past through our share repurchase program. Every dollar we deploy must pass a high bar for return and risk profile. And where we see opportunities to scale with the right partners, we will pursue those selectively. We believe shareholders are looking for a high return on invested capital as well as growth from continued innovation. And in biotech, we believe that we must improve returns on invested capital to earn the right to grow. All today's calls provide clarity on how Zymeworks intends to continue operating with a very clear and disciplined mindset or more specifically as intentional capital allocators. A positive study outcome for HERIZON-GEA-01 expected in the fourth quarter this year should bolster our ability to execute against a broader long-term strategy anchored around a growing cash flow stream from Ziihera and other assets, combined with continued investment in R&D programs with a series of partnerships and collaborations to share future risk, capital and resources. In summary, our goal is to build shareholder value over the long term by thoughtfully deploying capital in ways that reinforce our scientific leadership, expand our reach through external partnerships, enhance future cash flow streams from royalties and other healthcare assets and deliver meaningful returns to our shareholders. And we thank you again for your continued support. With that, I'd like to thank everyone for listening, and I'll turn the call over to the operator to begin the question-and-answer session.

Our first question comes from Andrew Berens from Leerink Partners.

This is Emily on for Andy. With the HERIZON-GEA readout coming up, I'm wondering if PD-L1 status be broken out for the triplet for arm C in the top line? Or will this come later on? And then I'm also curious if you could provide any color on how much of the Zyme $525 million regulatory milestone is weighted towards GEA versus other indications?

Yes, thanks, Emily, for both questions. I think what data is included in the top line press release is going to be up to both Jazz and BeOne since they're the sponsor and cosponsor of the study. So we'll leave that for them to decide what might come in a top line release versus what might be safe for a conference proceeding. For the second question, we have $500 million left in development milestones in our agreement with Jazz, having received $25 million for the approval of BTC. And we've not provided any guidance around what that $500 million will be allocated to. But I think as we earn those payments, we'll obviously find out the magnitude of those around each of the GEA milestones as well as the other indications.

Our next question comes from Charles Zhu from LifeSci Capital.

On the broad progress and I fully understand we're heavily anticipating the Phase III HERIZON-GEA study results coming up shortly. But I had 2 questions on some of your in-house pipeline assets, if you don't mind. Maybe the first one is from a clinical positioning and capital allocation perspective, how similar or better does ZW191 need to be relative to other topoisomerase-based ADCs targeting FR alpha or other potentially overlapping targets in similar indications like CDH6 for you to continue the development of this program? And maybe the second one, Paul, I picked up some of your comments on really being mindful of liver impairment and tolerability for ZW251 in liver cancer patients. I guess, along that vein, to what degree are you looking to also evaluate this asset beyond where some of our more potent options have focused on, whether it's like Child-Pugh class B or even potentially class C patients? How are you thinking about those?

Yes, let me take the first one, Charles, and I'll pass on to Paul for the second one. I think when we look at ZW191, we learned a lot from the development of our first medicine, zanidatamab, which has gone from us discovering it right through to approval and now launch. And again, remember in the HER2 space with zanidatamab developed, there were established brands with Herceptin and Perjeta and Kadcyla. There were other entrants which are looking to move the innovation needle like us, including with T-DXd and other ADC formats. We really focused on trying to do something that was a very novel mechanism, create a novel biological approach, which we certainly did with zanidatamab, which is still the only approved bispecific approach in the HER2 space and really the only one that's been validated in any sense by any clinical data. And obviously, there, we learned a lot about having good activity, but also having a tolerability profile that allows combinations to occur more readily and looking at the benefit of those combinations. We didn't expect to have the whole market ourselves. We didn't expect to be first or the primary choice in every indication in a broad set of potential tumor types. But I think if you look at where zanidatamab ended up with competing with established brands, other competitors entering the market before you, other innovators coming along, we're still going to be able to create what we think is a differentiated asset, which has a commercial potential of several billion dollars in peak sales per year. So we learned a lot about that. With ZW191, we think there's room to move innovation further when we look at ADCs, both in gynecological and non-small cell lung cancer. And so that's really interesting for us to think about in ZW191 as well as there are some broader spectrum profiles there. And we obviously took a different approach with how we built our ADC and what we think will benefit from that differential design with the modestly potent payload, the strongly internalizing antibody, being able to get to a higher dose; we think antibody dose is important and additional targeting is important. But the tolerability profile we engineered in that molecule, which hopefully will make it more amenable to combinations. And we need to see the data to confirm that; that's certainly a place in the future that we could go with ADCs. It certainly was a big deal for zanidatamab to be able to do that. So I think as we start to see the initial data and understand it, we'll be testing our thesis about a completely different ADC than others have developed and looking at the clinical responses for that differentiated mechanism to understand where we might have an opportunity to move innovation even further than we've seen with agents to date in folate receptor or more broadly in targets in those same therapeutic areas, some of the ones you mentioned. And right now, we're very encouraged with the positioning for 191, and we're excited to continue exploring with additional data sets around that to see if we can have a differentiated approach, which will benefit the patient population more than others have and the innovation that's been done elsewhere. And I'll let Paul talk about 251.

Thank you, Charles. As I mentioned, we need to carefully consider diseases like hepatocellular carcinoma and liver capacity. In designing the molecule and its payload, we've dedicated a significant amount of time to ensuring tolerability for our ADCs, which is reflected in the high tolerability observed in our preclinical models. Specifically, for ZW251, we have established a maximum tolerated dose of 120 mg per kg in primates, providing insight into its tolerability. We believe this allows us the necessary bandwidth as we move into clinical trials. While I can't disclose much about 191, our hypothesis remains intact. As we approach HCC, we will conduct systematic studies, targeting a specific subset of patients we find most suitable. We will analyze the data to determine how we may progress within this patient population and consider the possibility of combining treatments. This aspect is very much part of our strategy as we evaluate the relevance of the molecule for particular disease indications. Overall, we are optimistic about the tolerability profile without compromising efficacy, as shown in various HCC models in our preclinical data.

Congrats again on the progress.

Thanks, Charles.

Our next question comes from Yaron Werber from TD Cowen.

Congrats on the quarter. A couple from me. I want to follow up on 191. Generally, when can we start to think about data from the Phase I trial? And then I see that in your product design, you have expansion cohorts also in non-small cell. What do you know about the expression of FR alpha in non-small cell lung cancer? And how would you characterize that opportunity?

I will answer the first question, and then I'll let Paul address the question on expression. We are currently about 9 to 10 months into the dose escalation studies for both ZW191 and ZW171. With AC, it's typically easier to assess the direction of our progress. So far, we are performing well. We plan to present the data when we have something noteworthy to share, once we have agreement from our investigators. We are looking for opportunities to submit and have an abstract accepted at a peer-reviewed meeting, which could happen in 2025 or possibly 2026. As mentioned earlier, any data we present will be at a peer-reviewed meeting, and it must be in the correct format, which is dependent on the timing of abstract acceptance. We won't provide further updates until there is an accepted abstract title or a late-breaking abstract published for presentation. For now, you'll need to wait for that information. However, we're quite interested in the first 9 months of dosing of 191, and there remains more to explore. We will seek the right opportunity with our investigators to share at least some initial data along the way. Paul, would you like to answer the second question regarding expression?

Yes, yes. So the question about expression in non-small cell lung cancer. And we've done analysis ourselves of looking at that by IHC and consistent with what's been published, we do see a subset of patients in non-small cell lung cancer with folate receptor expression. So that encourages us to move forward in that indication. And I think as well, when you think about the design of our molecule, we were careful to pick an antibody that was very efficient at internalization. We think that will aid in the therapeutic profile and potential of the molecule. It was among the strongest payload delivery. And then also, we alluded to the selection of our payload and it was very important the way we designed that and selected that payload that also has bystander activity that we think also helps overcome tumor expression target expression is heterogeneous. So with that profile, we feel that non-small cell lung cancer is underserved and could benefit from us evaluating ZW191 there.

Our next question comes from Stephen Willey from Stifel.

I'm not sure if Paul, Sabeen or Ken want to take this. But I was just wondering if you'd be willing to offer your thoughts on the pasritamig data that was presented at ASCO. Obviously, very well tolerated, not a whole lot of CRS, a good median rPFS at the recommended Phase II dose. But the PSA50 rates, I guess, are lower relative to what we've seen with other PSMA targeting bispecifics. I think the patient population appeared to be a bit curated with respect to visceral and liver met. So just kind of curious as to what you think is happening here and kind of what's driving the uniqueness of this molecule? Is it the format? Is it the target? I guess any thoughts would be helpful.

Yes, of course. Thank you. I'll allow Paul to share some comments. Although we are directly involved in Johnson & Johnson's innovative medicines program and have a financial stake in it, we closely monitor their progress and are truly excited about what they have developed using our Azymetric platform, similar to how we create our own agents. I'll turn it over to Paul to discuss his insights regarding the data.

We are aware of the published information and the observations shared by J&J. From my perspective, the selection of the target is crucial. This target appears to provide a better therapeutic window and tolerability profile. We understand the difficulties with targets that are found in tumors but also expressed elsewhere. Finding the right target presents its challenges, but KLK2 displays a promising profile. The tolerability of the dosage they have achieved is impressive, supporting an exciting profile for a manageable drug that they view as an opportunity to combine with other therapies to enhance efficacy. This is an exciting development and one that makes sense considering the target selection, although we will need to see how the data unfolds. They seem enthusiastic about combining with various modalities. A T-cell engager allows for combined approaches with other mechanisms to achieve an even better response profile.

And is there any overlap with respect to the CD3 variant that's used in that molecule and the one that's used on 171 just in terms of affinity?

Yes. I'm not sure I can say too much about that, Stephen. Certainly, we considered the affinities for different targets. We opted for a low affinity CD3 in the case of mesothelin because we believed it was the right choice. However, for other targets, different affinity CD3s could be considered due to their varying normal tissue profiles. This presents an opportunity. Therefore, I think the biology should really guide your selection instead of assuming that what works for one target will work for another.

If you think about ZW209, the targets. The affinity on the CD3 on that for IHC is different than 171.

Our next question comes from Brian Cheng from JPMorgan.

Maybe just looking at the details of the dose escalation for 171, your mesothelin program. Can you give us a better sense of just how the dose escalation schedule is determined? Specifically, when we look at the dose level 1, it seems that you have characterized 4.2 mg and also 38 mg in dose level 1. So should we assume that 4.2 mg as the dose level 1, the low end of the dose range and then 38 mg as the high end of the dosing range?

Yes, thanks, Brian. I'll let Paul answer that.

Yes, I can answer that, and Sabeen can feel free to add as well. When we talk about the dose level, our target dose is 38 micrograms. So when we refer to dose level 1, we are referring to stepping up to that target dose. Therefore, we consider the target dose of dose level 1 to be 38 micrograms. Does that clarify?

Yes, yes.

Our next question comes from Akash Tewari from Jefferies.

This is Phoebe on for Akash. We were wondering about your view on the HERIZON-GEA-01 readout being delayed to Q4 '25 and how it affects your confidence on the data? And what could be reasons behind the delay?

No, thanks for the question. Again, Akash using the word delay twice again as you did this conference. We don't see it as a delay. I think the prior guidance from Jazz was given as their best estimate for the second half of 2025. And now they've re-guided that to give the guidance of Q4 2025, which is still within the balance of the second half. I think as we explained before, we don't see it as a delay; it's obviously an events-driven trial, and they're trying to give guidance around blind event data, which they have access to. It's an open-label study. So it's important to protect the integrity of the data set, obviously, until we're ready to unblind the study after the specific number of events that are necessary to do that. So we don't see any delay in that basis. Obviously, the study has been recruited some time ago, but it's fully recruited and being followed and as soon as the number of events that are required to trigger the data readout are done, then that will occur and it's still happening within the second half of 2025, but it will happen in Q4 according to the guidance given by Jazz yesterday and repeated by BeOne yesterday.

Our next question comes from Yigal Nochomovitz from Citigroup.

Two questions on relevant topics, one on supply chain and one on drug development using new technologies such as AI. I know you have a long lead time to get to market for the new wave of products, which puts you in a fortunate position in terms of being able to plan. So what can you say about how you're doing scenario planning on the supply chain to potentially address some of the questions around domestic manufacturing that are obviously important? And then on the topic of AI, I'm curious how much is going on at the early discovery for yet-to-be launched programs where you're doing AI for protein design and things of that nature?

Yes, thanks for the question, Yigal. With respect to zanidatamab commercially, both Jazz and BeOne have direct responsibility now for supply of zanidatamab. And with respect to tislei, obviously, BeiGene has that already with respect to U.S. commercial supply. So we feel very comfortable with the steps they've taken to protect the current commercial efforts and obviously, hopefully, an upcoming launch for GEA in the U.S. So we feel very comfortable with the steps we've taken to protect the supply chain and be able to supplement it where necessary with domestic manufacturers if required. So I'm not concerned there, and you can talk to Jazz and BeiGene directly about that. With respect to our other compounds, obviously, we're very early in clinical development or late in preclinical development. So lots of opportunities for us to understand how to deal with any new regulations which might be in place as those approach commercialization. So we feel very comfortable where we are with zanidatamab. With respect to AI, obviously, Zymeworks started as a computational platform and a computational biology company. So we've been doing AI long before anyone ever called it AI and the way we think about engineering and developing complex biologics. But I'll let Paul talk a little bit more about that.

Yes, thank you for that question. As Ken mentioned, this is rooted in protein engineering at Zymeworks, and we continue to focus on how to create the best molecule. Our goal is to find that effective solution, whether it involves target binding or providing diversity. We have the advantage of screening different molecules through Azymetric’s capabilities, and we also keep in mind external resources we can collaborate with. This focus is especially important as we work on multispecifics and consider the best ways to combine different binders to achieve desired profiles and biophysical properties, which can significantly benefit from AI strategies.

Our next question comes from Jon Miller from Evercore.

Congrats on the print. This is J.P. for Jon. I have 2 questions. On 1528, recent posters show longer half-life and today, you're showing better inhibition. So how do you expect the differentiation in profound humans be driven between bispecific design versus long half-life? And then on 251, how do you expect to proceed on dosing? Are you going to start a very conservative dosing? Or do you think you can get more aggressively to higher doses to show signs of efficacy?

Yes, I'll let Paul take the 1528 question and then ask Sabeen to talk about 251 dosing.

Yes, you made a good observation. We didn't mention the half-life extension we included in 1528 today. However, we believe this is an important aspect to consider when thinking about dosing strategy, and we will assess it in the clinic. We will have various pharmacodynamic readouts to support our insights on the half-life. It's worth noting that we have incorporated the YTE mutation. Regarding the biology, our aim is to address the mixed immune contributions in COPD. IL-4 has been clinically validated, as has IL-33 to some extent. We believe that by targeting both pathways, we can achieve benefits greater than what one alone would provide. Our preclinical data indicates we possess this capability, and in some models, we observe similar effects in samples from COPD patients. We conduct these studies to confirm the contributions and ensure the design of the molecule is effective. Additionally, we have promising data suggesting that our approach may yield activity beyond what combinations can offer. This indicates that we are doing something uniquely effective with our molecule, whether in how we interact with IL-4 or how we inhibit the IL-4 receptor and IL-33, providing us with a mechanistic advantage that we will further investigate in the clinic.

And maybe, Sabeen can you talk about the second part? Obviously, we've just cleared our IND, so we've had a chance to have discussion with regulators on this. But I don't know, Sabeen, anything you want to add on the 251 dosing approach?

Absolutely. First, we're excited to get our second ADC ZW251 into the clinic. With regards to its first-in-human dosing, as Paul pointed out earlier, we are confident about the safety of this molecule from a preclinical perspective. And also now we have experience with this linker payload 519 based on the data that we're seeing from ZW191. So we can afford to be a little less conservative with our starting dose. Obviously, we will reveal the exact doses later as we reveal more information about the trial. But we're confident in proceeding with being somewhat less conservative with ZW251 as we proceed into the clinic. And we're excited to show good safety given its preclinical safety profile and tolerability and the effect that we've seen in patients with hepatocellular cancer.

Our next question comes from Derek Archila from Wells Fargo.

This is Simone on for Derek. Congrats on the progress. Just one question. Do you expect 1528 to move as quickly as 171, 191 and 251? And if you do choose to partner any of your in-house programs, is there a specific one that you prioritize partnering on first?

Yes, I think right now, I think what we've shown for 171 and 191, and we're going to start to show that again, I think with 251 is the ability to work quickly on ideas that we have preclinically and it translates in quickly in the clinical studies and to be able to execute these Phase I programs at a very fast pace. And so we would expect the 1528 would be no different than that. With respect to partnering prioritization, obviously, we have 6 compounds with 6 different products that we nominated, including ZW220, which is IND-ready. We would expect that in order to be competitive with any of those agents and to take them through further clinical development to market, we would need partners to come along with us, join us along the way somewhere. So we have open partnering discussions on all 6 of those molecules. In addition to that, we're building our next wave of compounds through advance. And rather than moving all of that into clinical studies ourselves as we did with the top 6, we're certainly interested in having discussions around partners joining us at a very early stage to build maybe a number of molecules with us in a broader collaboration. And both of those are attractive. And I think we won't try to prioritize around those. We're open to discussions around the entire portfolio, and we'll see at what point partners would like to join us along the way in all of those efforts in the top 6 and the advanced portfolio.

Our next question comes from Mayank Mamtani from B. Riley Securities.

Congrats on the progress. This is Gaurav on for Mayank. Regarding your ADC candidate, ZW191, do we expect any data at any upcoming fall conferences like ESMO? And how much of the dose escalation data believe of the 6 dose levels you plan to evaluate, you expect to have accumulated at the cutoff point?

No, thanks for the question. And I think I tried to answer this earlier. We're very excited where we are with ZW191. And I think we're looking for an opportunity to share what we've learned so far in our initial Phase I study. And I think we'll be talking to our investigators about the appropriate time to do that. And obviously, we said we'll do it at a peer-reviewed medical meeting. So I think as soon as we decided with our investigators that we have enough data to present because it's of interest to us, and we want to share it in a peer-reviewed format, then we'll take the appropriate steps to submit and hopefully get accepted an abstract at a regular late-breaking for a conference. We won't indicate when that might be or won't give any guidance to that until you see a title announced or a late-breaker abstract presented. So we'll have to wait just rather to do that than any specific early guidance, so you'll have to wait for that to occur, but we're certainly at a stage in 191 where we find what we're doing very interesting. It's still early. We're still exploring continued patient enrollment, but it is possible that we'll have some data to share in 2025, if not, an early opportunity in 2026.

I am showing no further questions at this time. I will now turn it back to Ken Galbraith for closing remarks.

That's great. Thank you, operator. Thanks, everyone, for listening to our call today and for the questions that you provided to us in the Q&A session. Obviously, it's about 4 years ago that we started working seriously on moving zanidatamab into the Phase III clinical trial in GEA because we felt we had a molecule that could really help patients in this therapeutic category. And we're anticipating the outcome of HERIZON-GEA-01 as much as our investors are, and we look forward to being able to present those results with our partner, Jazz and BeOne in a top line basis in Q4 2025 as guided. In the meantime, we'll make more progress in the portfolio and look forward to reporting on that in the months ahead with you. So thank you very much for your time and attention, everyone, have a great rest of your summer. Thank you.

Thank you for your participation in today's conference. This does conclude the program. You may now disconnect.