Thank you for standing by. This is the conference operator. Welcome to Zymeworks Second Quarter 2025 Results Conference Call and Webcast. As a reminder, all participants are in listen-only mode and the conference is being recorded. After the presentation, there will be an opportunity to ask questions. To ask a question, please press Star one one on your telephone keypad. 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. Thank you for joining our second quarter 2025 results conference call. Before we begin, I'd like to remind you that we'll 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 at our stage of 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 Financial Officer. We 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. Our second Topo ADC candidate, ZW251. At the end of the call, Leone, Sabeen, Paul and Kenneth Galbraith, our Chair and CEO, will be available for Q&A. As a reminder, the audio and slides on this call will also be available on Zymeworks' website later today. I'll now hand the call over to. Leone Thank you, Chanel, 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 in 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 hepatocellular carcinoma. 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 IL4Rα/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 physician's 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 Horizon GEA pivotal study data readout. We look forward to the top-line progression-free survival data from the Horizon GEA1 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 aims to increase pathological complete response rates, improve long-term outcomes, and reduce 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, Johnson & Johnson Innovative Medicines reported phase I trial results for pasiridamab, a first-in-class T cell engaging bispecific antibody targeting human kallikrein 2 or KLK2 expressed on the surface of prostate cancer cells. Pasiridamab 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. Pasiridamab 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 pasiridamab across four phase I trials to explore dosing regimens both as monotherapy and in combination with a range of agents including checkpoint inhibitors, taxanes, and antigen 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 DS2243, 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 the 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 Pharmaceuticals and BeiGene, meaning that we are anticipating an increase in royalty revenues at Zymeworks for the remainder of 2025 and beyond. Also under the terms of our agreement with BeiGene, the NMPA approval in China resulted in a $20 million milestone payment which we recognize 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 BeiGene 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 BeiGene 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 also recognized $7.5 million option exercise payments in relation to our 2014 licensing agreement and collaboration agreement with Bristol Myers Squibb. As a reminder, we remain eligible to receive up to $313 million in development and commercial milestones from the Bristol Myers Squibb 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 non-refundable milestone from BeiGene 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 Bristol Myers Squibb due to the exercise of the commercial license option and $0.6 million of royalty revenues from Jazz Pharmaceuticals and BeiGene. These revenues were partially offset by reduction in development support and drug supply revenue from Jazz Pharmaceuticals and other non-recurring milestones achieved in the second quarter of 2024. Overall operating expenses were $49.4 million for the three 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 non-cash impairment charge recognized in 2024 related to zanidatamab, ZW49, and reduction in costs for zanidatamab, ZW49, and ZW220. These were partially offset by an increase in ZW171, ZW191, and other preclinical research expenses for ZW209 and ZW251. Net income was $2.3 million for the three 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 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 combined with the assumed reset 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 Clinical Development by our partners. For additional details on our quarterly results, I encourage you to review our earnings release and other SEC filings available on our website at www.zymeworks.com. I would now like to hand the call over to the SVP, Clinical Development, Dr. Sabeen Mekan, to run through progress on our clinical development programs. Thanks Leone and good afternoon everyone. We're pleased to have presented trial in progress postings 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 multispecific 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 one, eight, and 15 of each 21-day cycle. The starting dose level is based on a quantitative systems pharmacology-guided minimal anticipated biological effect level approach and includes sequential doses of 4.2 μg cycle one day one, 12.6 μg cycle one day eight, and 38 μg cycle one day 15. Dose level two and above are determined by the data from prior dose 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 will be thoughtful and decisive about next steps in line with o bservations on its tolerability and pharmacologic activity. Moving on to the design for ZW191 as presented at the ESMO Gynaecological Cancers Congress. The study is designed in two 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 one is a dose escalation phase where we are evaluating the safety profile of ZW191 and determining the maximum tolerated dose. The starting dose or dose level one is 1.6 mg/kg administered once every three 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 would have enabled. Given that this is the first time we are dosing our 519 payload in humans, we plan to evaluate approximately six 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 two 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 the 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 anti-tumor 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 selections for this program, but also provide data that would potentially accelerate and de-risk the future development of ZW251 and other pipeline ADCs utilizing our Z519 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. 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 I 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 precedents set from our previous wave of 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 pleased to share updates from our R&D pipeline where we continue to see strong momentum, particularly with the IND clearance of ZW251 as Sabeen touched on. We are encouraged by the clinical progress observed to date with our lead ADC candidate ZW191, which demonstrates early signs of translational alignment between preclinical predictions and clinical outcomes. We believe these early data from ZW191 provide a strong foundation and confirm our confidence in the therapeutic potential of our proprietary topoisomerase 1 inhibitor payload ZD06519. This alignment has reinforced our decision to advance ZW251 into the clinic. ZW251 incorporates the same foundational elements as ZW191, including our topoisomerase 1 inhibitor payload and an optimized antibody framework, but it's specifically engineered to address hepatocellular carcinoma, a disease with high unmet medical need and few effective targeted therapies. What we think makes GPC3 particularly attractive from a therapeutic standpoint is its expression profile. It is highly expressed in the majority of HCC tumors while exhibiting minimal expression in normal adult tissues. This tumor-selective expression reduces the risk of off-target effects and supports a favorable therapeutic index for GPC3-targeted therapies. As you can see from the panel on the left-hand side of this slide, GPC3 is overexpressed in more than 75% of HCC tumors while showing limited expression on normal tissues, confirming it as a compelling candidate for selective ADC targeting. Importantly, GPC3 is expressed during fetal development but is largely silenced in healthy adult tissue. This oncofetal expression pattern provides a unique window for tumor targeting without disrupting normal adult physiology. Prior studies have demonstrated the successful accumulation of anti-GPC3 antibodies in patient tumors, validating GPC3's accessibility and relevance as a therapeutic target. While GPC3 has attracted attention across the industry, it's important to note that most of the exploration to date has been in the context of other therapeutic modalities. We are among the first to systematically advance GPC3 as a target for antibody-drug conjugates with ZW251. We've taken a thoughtful, translationally grounded approach to unlocking the potential of this target using our proprietary ADC platform. Now, turning your attention to the panel in the middle of this slide. As mentioned previously, ZW251 incorporates a moderately potent bystander active topoisomerase 1 inhibitor payload, ZD06519, enabling us to deliver higher protein doses compared to those employing more potent camptothecin derivatives such as ixatecan-based ADCs. This, we believe, facilitates enhanced target engagement and tumor penetration, especially important in tumors with lower, heterogeneous GPC3 expression, an important consideration for achieving therapeutic impact across a wider patient population. At its core, ZW251 consists of a humanized IgG1 monoclonal antibody that binds GPC3 with high specificity and affinity. Importantly, this antibody demonstrates the desired cross-reactivity in both human and non-human primate models, which is critical for translational relevance and safety assessments. Preclinical studies have demonstrated that once bound, the antibody is internalized into GPC3-expressing tumor cells, initiating intracellular delivery of the cytotoxic payload. Our goal was to optimize the balance between safety and efficacy in a patient population often complicated by liver dysfunction. As you can see on the panel on the far right of this slide, preclinical studies have demonstrated that ZW251 at DAR 4 delivers compelling breadth of antitumor activity across diverse HCC models compared to a DAR 8 ADC control. This activity is also observed in models with variable glypican-3 or GPC3 expression. Importantly, this lower DAR will potentially provide additional flexibility in clinical dosing, which I had mentioned is critical in HCC where liver impairment can significantly impact treatment tolerability. I'd like to also briefly touch on the preclinical and safety PK and PK data we've generated for ZW251, which strongly supports our clinical development plan. In our non-human primate studies, ZW251 exhibited dose-proportional pharmacokinetics as measured by total antibody levels. This is an important indicator of predictable drug behavior, which helps inform both dose selection and exposure modeling as we move toward first-in-human studies. From a safety standpoint, ZW251 was well tolerated across all dose groups, including doses up to 1,120 m. We observed no mortality, no adverse clinical signs, and no significant effects on body weight or food consumption throughout the study period. Taken together, these results support a compelling tolerability profile and suggest that ZW251 may be suitable for higher dosing levels in humans and potentially higher levels than we've been able to achieve with ZW191, which is designed at a DAR 8. These findings give us strong confidence as we prepare for clinical entry and believe ZW251 is well positioned to offer differentiated safety efficacy balance compared to other ADCs in development. Looking ahead, we believe growing data sets supporting our ADC platform could accelerate time to clinic for new assets like ZW251 and also maximize the broader therapeutic impact of our technology across tumor types. We would like to remind you that ZW220, our NAPI2B targeted ADC in Darfor bomb format utilizing our 519 payload, remains IND ready. We remain committed to advancing both ZW191 and ZW251 with scientific rigor and we look forward to sharing additional data at peer-reviewed medical conferences in the future. Moving on now to 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 IL4 receptor alpha and IL33 for the treatment of respiratory diseases including chronic obstructive pulmonary disease and asthma. Our initial therapeutic focus for ZW1528 is COPD, a difficult to treat condition that remains poorly controlled in a large proportion of patients despite existing therapies. The high prevalence of uncontrolled disease and recurrent exacerbations underscores the need for more effective mechanism-based approaches. Chronic inflammation plays a key role in driving COPD disease pathology, characterized by dysregulation of both type 2 and non-type 2 immune responses in the lung, leading to chronic airway injury, inflammation, and tissue remodeling. The design of ZW1528 is grounded in the biology of these pathways and informed by the limitations of current treatments. As shown on the middle panel of the slide, ZW1528 is designed to simultaneously block key inflammatory pathways, specifically targeting IL33 and IL4 and IL13. These cytokines are known to play central roles in airway inflammation and disease progression. IL33 is a pro-inflammatory cytokine closely linked to epithelial stress, immune activation, and structural lung damage. Meanwhile, IL4 receptor alpha signaling is the primary driver of type 2 inflammation, which perpetuates disease activity in exacerbations in a substantial portion of patients on the right-hand side of the slide. In preclinical studies, ZW1528 is shown to reduce lung inflammation in a murine model of type 2 inflammation with activity comparable to dupilumab. Specifically, mice with humanized IL4 and IL4 receptor alpha challenged with house dust mite to induce type 2 lung inflammation were treated with ZW1528, resulting in a marked decrease in lung tissue pathology, including alveolar wall thickening, bronchial hyperplasia, and inflammatory cell infiltration. Flow cytometry analysis of lung immune cells revealed reduced eosinophilic infiltration and a rebalancing of alveolar macrophage populations, which was also associated with reduced serum IgE levels as well as reduced expression of key type 2 cytokines IL4 and IL5 in lung tissue, confirming the molecule's blockade of type 2 inflammatory responses matching the activity of the dupilumab replica that was also tested in the same experiment. The ability of ZW1528 to also block non-type 2 responses by virtue of the anti-IL33 specificity is then evident from the ex vivo analysis of COPD patient PBMCs, as shown by reducing IFN-gamma positive NK cells. This reduction in cytokine response is comparable, if not greater, to that achieved by an analog, abitapicamab, a benchmark clinical anti-IL33 mAb. Not surprisingly, dupilumab had no effect in blocking this type 1 response. Mechanically and by design, ZW1528 demonstrates robust inhibition of both IL4 receptor alpha and IL33-mediated signaling. To evaluate the ability of ZW1528 to block both pathways simultaneously, in vitro studies using human epithelial cells responsive to both the IL4 receptor and IL33 pathway activation were performed and showed ZW1528 potently blocked IL4 and IL33 combination-induced CCL2 gene expression, outperforming the results achievable with monoclonal benchmark therapies and their combination. These findings validate the rationale for our design of ZW1528 and support its therapeutic potential across a range of airway inflammatory conditions. By targeting two non-redundant upstream pathways with a single molecule, ZW1528 offers a potentially comprehensive approach to disease modulation, something single pathway or combination approaches have struggled to achieve. Before I conclude, I wanted to touch on recent high-profile readouts from peers which have renewed focus on the role of IL33 in COPD. While some recent competitor trials did not meet their primary endpoint in both of their two randomized registration studies, we believe it's important to contextualize these results carefully. The consistency of IL33 targeting across multiple large studies supports its biological relevance in COPD. The mechanism remains valid, but there are critical questions around trial design, patient selection, and the observed lower than expected exacerbation rates across the broader population that remain to be answered. We look forward to seeing the full data sets, which will be key in understanding which particular subpopulations did in fact derive benefit, something that could guide future trial strategies. Also, unlike these programs that solely target IL33, ZW1528 blocks both IL4, IL13 via IL4 receptor alpha, and the alarmin cytokine IL33. We believe this simultaneous co-localized blockade allows us to modulate both type 2 inflammation and epithelial-driven immune activation, offering potentially broader and more durable disease control in COPD as well as other inflammatory indications such as asthma. The evolving competitive landscape, including recent trial readouts, continues to inform our thinking around patient selection, trial design, and biological targeting, and we're incorporating these insights as we advance ZW1528 towards an expected non-U.S. regulatory filing submission in the second half of 2026. We look forward to presenting more data on ZW1528 at the European Respiratory Society Conference in September. To wrap up, we remain focused on innovation and disciplined execution across our R&D pipeline, and we're committed to meeting our ultimate goal of improving the standard of care for patients with serious unmet medical needs. With that, I will hand it over to Ken to conclude today's call and open up the call 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 that'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 Pharmaceuticals. 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 strengths of our proprietary technology platforms such as Azymetric with targeted partnerships to fully unlock asset value and deliver durable returns for shareholders. Azymetric technology 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 successes in zanidatamab as well as multiple high-value licensing partnerships with some of the industry's most respected pharmaceutical companies. As Leone's 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 they're already seeing materialize through the first half of 2025. Our evolving strategy is building on our successful track record of discovering and developing highly differentiated assets and executing strategic partnerships to maximize our value through upfront and milestone payments and continued royalty rights. Together, we believe our platform 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 multiple antibodies spanning both clinical and preclinical stages in solid tumors, chemo, 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 would 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 for 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 inflow as well as de-risk category developments through partnership 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 three and a half years, we've been able to accrete growing value from Ziihera, our partnership 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 and risk of late stage development to our collaborators, providing us with the opportunity to reinvest certain levels of non-diluted 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 unrelenting commitment to science and 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 fields 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 to position us as thought leaders and collaborators of choice for companies seeking cutting-edge solutions for patients with high unmet medical needs. 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 in the forefront of oncology and autoimmune inflammation innovation for years to come. Here, 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 zanidatamab 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 zanidatamab could be supplemented over time by additional potential revenues from existing partnerships such as our collaboration with Johnson & Johnson Innovative Medicines with Ziihera, as well as new partnerships and collaborations formed from our wholly owned R&D pipeline or accessed externally. As the zanidatamab 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 flow 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 review the anticipated revenues as strategic long-dated cash flows and we plan to preserve them. As such, we're not planning on automatically scaling our operations in response to cash inflows and our R&D and must remain disciplined and tightly aligned to programs where we have both scientific conviction and a clear path to long-term value through partnerships and collaboration. 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 where leadership such as monetization, acquisitions, or selective return of capital will enhance that value, as we've done in the past for 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 partner, 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. I hope today's call provided 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 taxable stream from the HER2 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. 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. Operator. We will now begin the question and answer session. To join the question queue, you may press Star one one on your telephone keypad. You would then hear a tone acknowledging your request. If you are using a speakerphone, please pick up your handset before pressing any keys. To withdraw your question, please press Star one one a gain, we will pause a moment as callers join the queue. Our first question comes from Andrewe Behrens from Leerink Partners. Please go ahead. Hi, this is Emily on for Andy. With the Horizon GEA readout coming up, I'm wondering if PD-L1 status will be broken out for the triplet for arm C in the top line, or will this come later on? I'm also curious if you could provide any color on how much of the $525 million regulatory milestone is weighted towards GEA versus other indications. Thank you. Yeah, thanks Emily for both questions. I think you know what data is included in a top line press release is going to be up to both Jazz and BeiGene since they're the sponsor and co-sponsor of the study. We'll leave that for them to decide what might come in a top line release versus what might be, say, for a conference proceeding. For the second question, we have, you know, $500 million left in development milestones in our agreement with Jazz, having received $25 million to the approval of BTC, and we've not provided any guidance around when that, what that $500 million will be allocated to. I think as we earn those payments, you'll obviously find out the magnitude of those around each of the GEA milestones as well as the other indications. Thank you. Our next question comes from Charles Zhu from LifeSci Capital. Please go ahead. Hello everyone. Congrats on the broad progress and fully understand we're heavily anticipating the faith in Horizon GEA study results coming up shortly. I had two 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 and similar indications like CDH6 for you to continue the development of this program? The second one, Paul, I picked up some of your comments on, you know, 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 in patients, beyond where some of our more potent options have focused on whether it's like, you know, Child two, class B or even potentially class C patients. How are you thinking about those? Thank you. Yeah, let me take the first one, Charles, and I'll pass it on to Paul for the second one. I think when we look at ZW191, we learned a lot from development of our first medicines and zanidatamab, which has gone from us discovering it right through to approval and now launch. You remember in the HER2 space with NAV developed, there were established brands with Herceptin and Perjeta and Kadcyla, there were other entrants which were looking to move the innovation needle like us, including T-DXd and other ADC formats. We really focus 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. Obviously, there we learned a lot about having good activity but also having a tolerability profile that allowed 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. I think if you look at where zanidatamab's ended up with it 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. Big deal for us. We learn a lot about that with ZW191. We think there's room to move innovation further when we look at gynecological and non-small cell lung cancer. That's really interesting for us to think about in ZW191 as well, as there are some broader expression profiles there. We obviously took a different approach with how we built our ADC and what we think will benefit from that differential design with a monofunctional payload, the strongly internalizing antibody. Being able to get to a higher dose with the antibody dose is important and additional targeting is important. The tolerability profile we engineered in that molecule, which hopefully will make it more amenable to combinations. We'll need to see the data to confirm that, but 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. I think as we start to see the initial data and understand it, we'll be testing our thesis about, you know, a completely different ADC than others to develop and looking at the clinical responses for the differentiated mechanism to understand where we might have an opportunity to move innovation even further than you've seen with agents today in folate receptor or more broadly in targets, but in the same therapeutic area, some of the ones you mentioned. Right now we're very encouraged with the positioning for ZW191 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. I'll let Paul talk about 251. Yep. Yep. Thanks, Charles. As I indicated and as you're aware, we have to think carefully with diseases like hepatocellular carcinoma and liver capacity. In our design thinking of the molecule and the payload, we really have spent a lot of time thinking about tolerability in general for our ADCs. That's then reflected in the real high tolerability in the preclinical models I mentioned. In particular for ZW251, we have a maximum tolerated dose of 120 mg per kg primate. That gives you one lens into the tolerability. We think what that then provides us is bandwidth as we take that molecule into the clinic. I can't say too much about ZW191, but so far that's holding, our hypothesis is holding. I think when we go into HCC, we will be systematic in our study. We'll push forward in a disease subset of patients that we think are the most appropriate. As we get the data, we'll analyze and see how far we can go within that patient population and also think about the ability to move up in line in combination. That's also very much in our thinking as we think about a particular disease indication and applicability of a molecule. Certainly, we're encouraged by the tolerability profile while not impacting the efficacy as I showed in the preclinical profile in various HCC models. Got it. Great. Thank you so much. Congrats again on the progress. Thanks, Charles. Thank you. Our next question comes from Yaron Werber from TD Cowen. Please go ahead. Yiran, thanks for taking our question. Congrats on the quarter. A couple from me want to follow up on ZW191. Generally, when can we start to think about data from the phase I trial? I see that in your trial design you have an expansion cohort also in non-small cell. What do you know about the expression of IL4Rα in non-small cell lung cancer and how to characterize the opportunity? Thanks so much. Yeah, I'll take the first one. I'll let Paul take the expression question. We're nine to ten months into the start of the dose escalation studies for both ZW191 and ZW171. With an ADC you can tend to get an easier read on where you're going. We've gone very well so far. I think we will look for opportunities to present that data once we think we have something interesting to share. Once we have our investigators agreeing with us on that and as we find an opportunity to submit and have an abstract accepted in a peer review meeting, we're still looking for those potential possibilities which could be in 2025 and if not in 2026. We said before that any data we present will be at a peer reviewed meeting. You have the right format. That means timing is related to having an abstract accepted for that basis. We won't provide further guidance around that until you see an abstract title accepted or a late breaking abstract published for a presentation. You'll just have to wait on that. We're intrigued with ZW191. With the first nine months of dosing there's more to explore. We'll look for an appropriate opportunity with our investigators to share data, at least initial data along the way. Paul, you want to add this? I think we're actually precious. Yeah, yeah. 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. That encourages us to move forward in that indication. 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 amongst 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 it also has bystander activity that we think also helps overcome tumor heterogeneity, expression target expression that's heterogeneous. With that profile, we feel that non-small cell lung cancer is underserved and could benefit from us evaluating ZW191 there. So much. Thank you. Our next question comes from Stephen Willey from Stifel. Please go ahead. Good afternoon. Thanks for taking the questions. Not sure if Paul, Sabeen, or Ken w ant to take this? Wondering if you'd be willing to offer your thoughts on the zanidatamab data that was presented at ASCO. You know, obviously very well tolerated, not a whole lot of CRS, a good median rPFS at the recommended phase II dose. The PSA 50 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. She's just kind of curious as to w hat do 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, thanks. Yeah, sure. Thank you. I'll let Paul provide a little comment. J & J Innovative Medicines molecule. You know, we obviously were involved in the program and have a financial interest. We follow very closely and we're really excited about what they've been able to build there with our Azymetric platform, the same way we build our own agents. I'll let Paul talk a little bit about his observations around it. Yeah, no, yep. Stephen. I mean we were aware of what was being published and what's presented, and J & J did publish their observations as well. From our perspective, or from my perspective, I think the selection of the target is really important there. I think that target seems to be able to support a much better therapeutic window and tolerability profile. We know from T cell engagers the challenges with targets that are expressed in the tumor but also have some expression elsewhere. I think that finding that target is, you know, there's challenges with that, and I think the KLK2 seems to have that profile. The tolerability is quite remarkable, like the dose that they've gone up to with their molecule. I think that then supports this exciting profile where they have a very manageable drug that they then see as the opportunity and combine with other therapies to really push forward the efficacy profile. We see that as exciting. It's kind of somewhat not that surprising if you think about it in the selection of that target. You may need some additional—let's see how the data prove that. This is just pure personal commentary. Let's see how that develops. You can see that they're quite excited about the combination with different modalities. I think that's what a T cell engager offers you, is that ability to then combine with other complementary mechanisms to really get an even better response profile. Is there any overlap with respect. To the CD3 variant that's used in that molecule and the one that's used on ZW171 just in terms of affinity? Yeah, I'm not sure I can say too much about that, Stephen. Certainly, we thought about the affinities for different targets, and I think we went with a low affinity CD3 in the case of mesothelin. We felt that that was the right play. For other targets, you could consider different affinity CD3s because they have a different normal tissue profile. I think that affords you that opportunity. I think that's really it. The biology can really drive your selection there rather than just assuming what works for one target works for another target. The affinity on the CD3 on that trispecific is different than ZW171 Understood. Yeah, thanks for taking the question. Thank you. Our next question comes from Brian Chang from JP Morgan. Please go ahead. Hey guys, thanks for taking our question this afternoon. We were just looking at the details of the dose escalation for ZW171. How your methylphelin program. Can you give us a better sense? Of just how the dose escalation schedule is determined? You know, specifically, you know, when we look at the dose level one it seems that you have characterized 4.2 mg and also 38 mg in a dose level one. Should we assume that 4.2 mg as the dose level one, the low end of the dose range, and then 38 mg as the high end of the dosing range? Thanks. Yeah, thanks Brian. I'll let Paul answer that. Yeah, I can answer that. Sabeen can feel free to add as well. No, when we talk about, when we look at that, Brian, what we mean by dose level, it's really the target dose is 38μg. When we think of dose level one, we're stepping up to that target dose, so we can more think that the target dose of dose level one is 38 μg. Does that clarify? Yes, thank you. Thank you. Our next question comes from Akash Tewari from Jefferies, please go ahead. Hi, this is Stevie on for Akash, we were wondering about your view on the Horizon GAO1 readout being delayed to Q4 2025 and how it affects your confidence on the data and what could be reasons behind the delay. Thank you. Noah. Noah. Thank you for the question. Again, it's a cost using the word delay twice again as you did this conference. We don't see this as a delay. I think the prior guidance from Jazz Pharmaceuticals was given as their best estimate, second half of 2025, and now they've given where we are in August, they've re-guided that to give a guidance of Q4 2025, which is still within the bounds of the second half. I think as explained before, design lay, 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 until we're ready to unblind the study after the specific number of events that are necessary to do that. We don't see any of those delays in that. The study's been recruited some time ago, but it's fully recruited and being followed. As soon as the number of events that are required to trigger the data readout are done, then that will occur. That's still happening within the second half of 2025. It'll happen in Q4 according to the guidance given by Jazz Pharmaceuticals two days ago and repeated by V1 yesterday. Thank you. Our next question comes from Yigal Nochomovitz from Citigroup. Please go ahead. Yeah, hi Ken and team. Two questions on relevant topics, one on supply chain and one on drug development using new technology 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. 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? 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. Thank you. Yeah, thanks for the question. With respect to zanidatamab commercially, both Jazz Pharmaceuticals and BeiGene have direct responsibility now for supply of zanidatamab. With respect to this, obviously BeiGene has that already with respect to U.S. market supply. We feel very comfortable with the steps they've taken to protect the current commercial efforts and hopefully an upcoming launch for GEA in the U.S. We are very comfortable with the steps they've taken to protect the supply chain and be able to supplement it where necessary with a domestic manufacturer if required. I'm not concerned there and you can talk to Jazz Pharmaceuticals or BeiGene directly about that. The second compounds obviously are very early in clinical development or late in preclinical development. There are lots of opportunities for us to understand how to deal with any new regulations which might be in place as those approach commercialization. We are still very comfortable where we are with zanidatamab. With respect to AI, obviously Vammark started the computational platform and a computational biology company. We've been doing AI long before it was ever called AI and the way we think about engineering and developing complex biologics. I'll let Paul talk a little bit more about that. Yeah, no, thanks for asking that question. As Ken mentioned, it's kind of in the roots of putting engineering at Zymeworks, and we still have that kind of theme that's based in our design and our thinking about molecules—how do you make the best molecule, how do you get to that sort of needle in a haystack sometimes that you need to get to to get the right, the really thing that you want to develop. Whether that's from target binding or giving it a diversity, we have the luxury of then being able to screen different molecules through the screening capacity of Azymetric. We do use that. I mean, we apply it, and we're keeping aware of the capability externally as well that we can tap into those and collaborations. It is very much in our forethought as we tackle particularly in the multispecifics, and we think about how best to combine different binders or the ultimate sort of profile or biophysical properties that you want that can really lend itself to AI strategies. Thank you. Thank you. Our next question comes from John Miller from Evercore. Please go ahead. Hello guys. Congrats on the print and thanks for taking our question. This is JP for John. I have two questions on ZW1528. Recent posters show longer half-life, and today you're showing better inhibition. How do you expect the differentiating profound humans be driven between bispecific design versus long half-life? On ZW251, how do you expect to proceed on dosing? Are you going to start with very conservative dosing, or do you think you can get more aggressively to higher doses to show signs of efficacy? Yeah, I'll let Paul take the ZW1528 question and ask Sabeen to talk about ZW251 dosing. Yeah, I think well spotted. You know, we didn't mention the half-life extension that we incorporated into ZW1528 today. That is definitely a feature that we think is important as we think about dosing strategy, and we will evaluate that in the clinic. We'll have various pharmacodynamic readouts that will allow us to support our thinking on the half-life. That is a good point to highlight that we have incorporated YTE mutation. I think then on the biology, we see really that the desire, that the thinking here is that there's mixed immune contributions in COPD. IL4 is obviously clinically validated. IL33 also clinically validated to a degree. What we believe is by covering both of those pathways, we can get benefit that's beyond what you can achieve by just one. Our preclinical data suggests that we have that feature. In some of the actual models, what we're looking at is that we can also recapitulate, we can see that in COPD patient samples ex vivo. We do those types of studies to sort of confirm the contribution and the design of the molecule works. Also, we've got some encouraging data to suggest that maybe we're going to get activity beyond what you can get with combinations. That suggests that mechanistically we're doing something different with our molecule, either how we anchor on IL4 or how we wholly inhibit IL4 receptor and IL33. That's giving us an additional mechanistic advantage that we'll then see how that plays out when we go into the clinic. Yeah, can you talk about the second part? Obviously we just cleared our IND, so we've had a chance to have discussion with regulators on this. Now, Sabeen, anything you want to add on the ZW251 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 very confident about the safety of this molecule from a preclinical perspective. We also now have experience with this linker payload, 519, based on the data that we're seeing from ZW191. We can afford to be a little less conservative with our starting dose. 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. 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 carcinoma. Okay, this is very helpful. Thank you very much, guys, and congrats again. Thank you. Our next question comes from Derek Archila from Wells Fargo. Please go ahead. Hi, this is Simone on for Derek. Congrats on the progress. Just one question. Do you expect ZW1528 to move as quickly as ZW171, ZW191, and ZW251, and if you do choose to partner any of your in-house programs, is there a specific one that you prioritize partnering on first? Thank you. Yeah, I think right now what we've shown for ZW171 and ZW191, and we're going to start to show that again, I think with ZW251, is the ability to work quickly on ideas that we have preclinically and translate them quickly into clinical studies and to be able to execute these phase I programs at a very fast pace. We would expect that ZW1528 would be no different than that. With respect to partnering prioritization, obviously we have six compounds with six different products that we've nominated, including ZW220, which is IND ready. We would expect that in order to be competitive with any of those agents and to bring further clinical development to the market, we would need progress to come along with us, join us along the way somewhere. We have open partnering discussions on all six 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 tox, 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. Both of those are attractive, and I think we won't try and set prioritization 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 six and the advanced portfolio. Thank you. As a reminder to ask a question, you need to press Star one one on your telephone and wait for your name to be announced. Our next question comes from Mayank Amtani from B. Riley Securities. Please go ahead. Hi. Thanks for taking a question and congrats on the progress. This isSoundarya 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, of the six dose levels you have planned to evaluate, do you expect to have accumulated at the cut-off point? Thank you. No, thanks for the question. 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 on our initial phase I study. I think we'll be talking to our investigators about the appropriate time to do that. Obviously, we said we'll do it at peer review medical meetings. I think as soon as we've 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 review format, then we'll take the appropriate steps to submit and hopefully get accepted in abstract, either regular or 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 after presented. We'll have to wait. I'd just rather do that than any specific pictograms. You have to wait for that that's occurred. We're certainly at a stage in ZW191 where we found what we're doing very interesting. It's so early. We're still exploring continued patient enrolment, but it is possible that we'll have some data to share in 2025, and if not, an early opportunity in 2026 is possible. Okay. Thank you. Yeah, you're welcome. I am showing no further questions at this time. I will now turn it back to Kenneth 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 four 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. We're anticipating the outcome of Horizon GEA-1 as much as our investors are, and we look forward to being able to present those results with our partner Jazz Pharmaceuticals and BeiGene on a top-line basis in Q4 2025 as guided. In the meantime, we'll make more progress with the portfolio and look forward to reporting on that in the months ahead with you. 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.