Earnings call transcript: Zymeworks sees revenue surge in Q2 2025

Zymeworks Inc. reported a significant increase in revenue for the second quarter of 2025, achieving $48.7 million compared to $19.2 million in the same period last year. This growth was driven by key milestone payments and deferred revenue recognition. The company’s stock, however, saw a decline of 2.01% in aftermarket trading, closing at $12.16. Zymeworks also announced a positive net income of $2.3 million, a turnaround from a net loss of $37.7 million in Q2 2024. According to InvestingPro data, the company maintains a "GOOD" overall Financial Health score, with analyst price targets ranging from $12 to $30, suggesting potential upside.

Key Takeaways

• Revenue jumped to $48.7 million in Q2 2025, a significant increase from $19.2 million in Q2 2024.
• Net income reached $2.3 million, reversing a loss from the previous year.
• Stock price fell by 2.01% in aftermarket trading.
• Cash resources increased to $333.4 million, with a runway expected to last into 2027.
• Zymeworks is advancing multiple product candidates, with several in clinical development stages.

Company Performance

Zymeworks showcased robust financial performance in the second quarter, marked by substantial revenue growth and a shift to profitability. The company’s strategic partnerships and milestone payments significantly contributed to its top-line results, with revenue growing 85% over the last twelve months. InvestingPro analysis reveals the company holds more cash than debt on its balance sheet, with a healthy current ratio of 4.71, indicating strong liquidity. Zymeworks is actively progressing its clinical pipeline, with several candidates in Phase I studies, which positions it well in the oncology and autoimmune inflammatory disease markets.

Financial Highlights

• Revenue: $48.7 million in Q2 2025, up from $19.2 million in Q2 2024.
• Net income: $2.3 million, compared to a net loss of $37.7 million in the previous year.
• Cash resources: $333.4 million as of June 30, 2025, up from $124.2 million at the end of 2024.

Outlook & Guidance

Zymeworks has outlined an optimistic outlook, with expectations for increased royalty revenues from international approvals of zanadatumab. The company anticipates top-line data from the Horizon GEA-1 study in the fourth quarter of 2025 and is preparing for potential regulatory filings in 2026. The guidance for future quarters includes EPS forecasts ranging from -0.29 to -0.52 USD and revenue projections between $18.1 million and $30.81 million. InvestingPro reports that two analysts have recently revised their earnings upwards for the upcoming period, though the consensus indicates the company may not achieve profitability this year. For detailed analysis and additional insights, investors can access the comprehensive Pro Research Report, available for Zymeworks and 1,400+ other US stocks.

Executive Commentary

CEO Ken Galbraith expressed confidence in the company’s strategic collaborations, stating, "We believe these collaborations validate our science, and they position us well for meaningful milestones and royalty revenue opportunities." Chief Scientific Officer Paul Moore highlighted the potential of ZW1528, stating, "By targeting two non-redundant upstream pathways with a single molecule, fifteen twenty eight offers a potentially comprehensive approach to disease modulation."

Risks and Challenges

• Competitive pressures in the ADC and bispecific technologies market.
• Potential delays in regulatory approvals for pipeline products.
• Dependence on strategic partnerships for milestone payments and revenue.
• Macroeconomic factors that could impact funding and investment.

Zymeworks remains focused on maintaining disciplined R&D investments while exploring further partnership opportunities to mitigate development risks. The company’s strategic positioning in high unmet medical need areas, such as HER2+ cancers and COPD, underscores its commitment to advancing its clinical pipeline and achieving long-term growth.

Full transcript - Zymeworks Inc (ZYME) Q2 2025:

Conference Operator: Thank you for standing by. This is the conference operator. Welcome to XymeWorks second quarter two thousand twenty five 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. Would now like to turn the conference over to Trinelle N. Amdur, Senior Director of Investor Relations. Please go ahead.

Trinelle N. Amdur, Senior Director of Investor Relations, Zymeworks: Thank you, operator, and good afternoon, everyone. Thanks for joining our second quarter twenty twenty five 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 stage of development. A discussion of these risks and uncertainties will refer to the latest SEC filings as found on our website and as filed with the SEC.

In a moment, I will hand over to Ione Paterson, our Executive Vice President and Chief Business and Financial Officer, who will provide an overview of our recent business and partnership updates along with financial results for our second quarter twenty twenty five. Following this, Doctor Sabine McCann, our Senior Vice President of Clinical Development will provide progress updates on our Phase one program CW171 and CW191. We will then pass the call over to Doctor. Paul Moore, our Chief Scientific Officer, who will give an overview of recent R and D development as well as an update on IND clearance for our second topo ADC candidate, CW251. At the end of the call, Leonie, Sabine, Paul and Kan Gelbrough, our Chair and CEO, will be available for Q and A.

As a reminder, the audio and slides from this call will also be available on Zymos’ website later today. I will now hand the call over to Leonie.

Ken Galbraith, Chair and CEO, Zymeworks: Thank you, Chanel, and thank you all for joining us today. I’ll first walk you through our highlights for the 2025. On our clinical programs, we presented trial and progress posters for ZW-one hundred seventy one and ZW-one hundred ninety one, which are both progressing in their respective Phase I studies. Sabine 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 TOPO-one inhibitor payload ADC, ZW251,

Ken Galbraith, Chair and CEO, Zymeworks: for

Ken Galbraith, Chair and CEO, Zymeworks: 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 and D programs and long term business strategy.

On our preclinical pipeline, we are pleased to have presented inaugural data on our novel IL-four, IL-thirty three 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, zanadatumab continues to progress through the presentation of updated long term survival data at ASCO, highlighting that among forty one GEA patients with centrally confirmed HER2 positive tumors, treatment with zanadatumab in combination with physician’s choice of chemotherapy resulted in a median progression free survival of fifteen point two months and a median overall survival of thirty six point five months. We believe these data reflect the durability and tolerability of zanadatumab and support our thesis of patients staying on treatment longer. This builds on the meaningful efficacy and tolerability profile seen to date with zanadatumab and provides further confidence for the highly anticipated Horizon DEA pivotal study data readout.

We look forward to the top line progression free survival data from the Horizon GEA-one study expected late in the 2025, as Jazz announced this week. Jazz also recently announced the initiation of a phase two trial studying zanodiazepam as increase pathological complete response rates, improve long term outcomes, and reduce overall toxicity. Lastly, conditional regulatory approvals for zanadatumab 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 Zymworks. Beyond this, our platform partnerships also continue to produce at the ASCO annual meeting.

J and J Innovative Medicines reported phase one trial results for pasaritamab, a first in class T cell engaging bispecific antibody targeting human Kallikrein two, or KLK2, expressed on the surface of prostate cancer cells. Paxoritomig demonstrates Paxoritomig’s anti tumor, I’m sorry, pulmonary anti tumor 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 and J. Fasiridomig also demonstrates a favorable safety profile with very low rates of cytokine release syndrome and could be safely administered in an outpatient setting. J and J has registered trials to evaluate pasaritamab across four phase one 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 and J on the advancement of this program.

We view this development as a strong signal of both scientific conviction and continued investment in the KRKT program. Also at the ASCO Annual Congress, our partner, Daichi Sankyo, presented a trial in progress poster for a Phase I first in human study of DS-two 243, a bispecific T cell engager in patients with advanced tumors, 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 and 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 Zanademab in China and Europe obtained by our partners Jazz in Beijing, meaning that we are anticipating an increase in royalty revenues in ZymWorks for the remainder of 2025 and beyond. Also, under the terms of our agreement with B1 Medicines, the NMPA approval in China resulted in a $20,000,000 milestone payment, which we recognize as revenue this quarter, along with $18,300,000 of deferred revenue recognized in connection with reaching this milestone. While the initial royalties being reported from B1 this quarter are modest, They represent the first tangible signal of near term revenue growth from zanadatumab’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 B1 territories, increasing to up to 20% when cumulative amounts foregone as a result of a royalty reduction of 0.5 reaches a cap in the low double digit millions of dollars. Similarly, quarter, we also recognized $7,500,000 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 three thirteen million dollars 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 $48,700,000 in the 2025 compared to $19,200,000 for the 2024. The increase was primarily due to a $20,000,000 nonrefundable milestone from B1 upon conditional approval of the BLA for danadatumab for second line treatment of HER2 plus BTC by the NMPA in China, plus the recognition of $80,300,000 deferred revenue in relation to the achievement of that milestone. Dollars 7,500,000.0 from BMS due to the exercise of the commercial license option and $600,000 of royalty revenues from Jazz and B1. These revenues were partially offset by a reduction in development support and drug supply revenue from Jazz and other nonrecurring milestones achieved in the 2024.

Overall, expenses were $49,400,000 for the three months ended 06/30/2025, compared to $62,100,000 for the same period in 2024, representing a decrease of 20%. The decrease in operating expenses was primarily due to the $17,300,000 non cash impairment charge recognized in 2024 related to zanadatumab, zovodotin, and reduction in costs for zanadatumab, zovodotin, and ZW220. These were partially offset by an increase in 100 71, 191 and other preclinical research expenses for ZW 02/2009 and February. Net income was 2,300,000 for the three months ended 06/30/2025, compared to a net loss of $37,700,000 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 17,300,000.0 on intangible assets in the 2024, partially offset by a decrease in interest income.

As of 06/30/2025, we had $333,400,000 of cash resources consisting of cash, cash equivalents and marketable securities, which is an increase in cash resources compared to $124,200,000 as of 12/31/2024. We remain well capitalized and based on our current operating plans, we expect our existing cash resources as of 06/30/2025 when complied with the assumed receipt of certain anticipated regulatory milestones will enable us to fund planned operations into the 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 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. Well, I’d like to hand the call over to SVP Clinical Development Doctor.

Sabine McCahn to run through progress on our clinical development programs.

Trinelle N. Amdur, Senior Director of Investor Relations, Zymeworks: Thanks, Leone, and We’re good afternoon, pleased to have presented trial in progress for both ZW171 and ZW191 at recent peer reviewed medical conferences, highlighting the translation from Pre, clinical 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 and 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 fifteen of each twenty one day cycle.

The starting dose level is based on quantitative systems, pharmacology, guided minimal anticipated biological effect level, label approach and includes sequential doses of four point two micrograms cycle one day, one. Twelve point six micrograms cycle one day, eight and thirty eight micrograms cycle one day, fifteen. Those level two and above are determined by the data from prior dose. Based on pre specified 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 one trial of CW one hundred seventy one as it continues to progress and will be thoughtful and decisive about next steps in line with observations on its tolerability and pharmacologic activity. Moving on to the design for ZW, one hundred ninety one as presented at the ESMO gynecological 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 a variant cancer and a mutual cancer and non small cell lung cancer. Part one is the dose escalation phase where we are evaluating the safety profile of CW one hundred ninety one and determining the maximum tolerated dose. The starting dose or dose level one is one point six milligrams per kilogram 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 one trial of VW one hundred ninety one compared to what our preclinical studies would have enabled. Given that this is the first time we are dosing our five nineteen 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 two, 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 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, identifying optimal biological dose, and explore the potential of our ADC platform to utilize our proprietary payload and linker across expressing tumors. That being said, ZW-one hundred ninety one is also providing important translational insights that not only inform those selections of this program, but also provide data that could potentially accelerate and derisk the future development of DW251 and other pipeline ADCs utilizing our five nineteen payload.

As with ZW-one 171, we will continue to monitor early data from the Phase I trial of ZW-one 191 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 inhuman tolerability and efficacy profile of our novel payload ZD06519, we are confident in advancing ZW251, our second turboisomers one inhibitor ADC towards Phase one 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 waves on 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.

Paul Moore, Chief Scientific Officer, Zymeworks: Thank you, Sabine. I’m pleased to share updates from our R and D pipeline, where we continue to see strong momentum, particularly with the IND clearance of ZW251. As Sabine 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 the ZW191 provide a strong foundation and confirms our confidence in the therapeutic potential of our proprietary topoisomerase one inhibitor payload ZD06519. This alignment has reinforced our decision to advance ZW251 into the clinic.

Two fifty one incorporates the same foundational elements as one hundred ninety one, including our topoisomerase one inhibitor payload and 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 the slide, GPC3 is overexpressed in more than seventy five percent of HCC tumors, while showing limited expression in normal tissues, confirming as a compelling candidate for selective EDC targeting.

Importantly, GPC3 is expressed during fetal development, but is largely silenced in healthy adult tissue. This fetal, 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 glypogen three or GPC3 has attracted attention across the industry, it’s important to know that most of their exploration today has been in 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 the slide, as mentioned previously, two fifty one incorporates a moderately potent bystander active topoisomerase one inhibitor payload, ZD06519, enabling us to deliver higher protein doses compared to those employing more potent amphetecin derivatives such as exatecan 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, two fifty one 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 nonhuman 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 two fifty one at DAR4 delivers compelling breadth of antitumor activity across diverse HCC models compared to a Dar8 ADC control. This activity is also observed in models with variable glycogen three 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 data we’ve generated for February, which strongly supports our clinical development plan. In our nonhuman primate studies, two fifty one 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, two fifty one was well tolerated across all dose groups, including doses up to one hundred and twenty mg per kg. We observed no mortality, no adverse clinical signs, 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 two fifty one may be suitable for higher dosing levels in humans and potentially higher levels than we’ve been able to achieve with one hundred ninety one, which is designed as a DAR8. These findings give us strong confidence as we prepare for clinical entry. We believe two fifty one is well positioned to offer differentiated safety efficacy balance compared to other ADCs in development. Looking ahead, we believe growing datasets supporting our ADC platform could accelerate time to clinic for new assets like two fifty one, and also maximize the broader therapeutic impact of our technology across tumor types. And we’d like to remind you that CW220, our NaPi2b targeted ADC in DARF format utilizing our five nineteen payload remains IND ready.

We remain committed to advancing both 01/1991 and two fifty one with scientific rigor. 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 and D Day, fifteen twenty eight is our first nominated product candidate from our autoimmune and inflammatory pipeline, a bispecific targeting an antibody targeting IL-four receptor alpha and IL-thirty three for the treatment of respiratory diseases, including chronic obstructive pulmonary disease and asthma. Our initial therapeutic focus for 1528 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 deriving COPD disease pathology characterized by dysregulation of both type two and non type two immune responses in the lung, leading to chronic airway injury, inflammation and tissue remodeling. The design of fifteen twenty eight is grounded in the biology of these pathways and informed by the limitations of current treatments. As shown on the middle panel of

Ken Galbraith, Chair and CEO, Zymeworks: the

Paul Moore, Chief Scientific Officer, Zymeworks: slide, ZW1528 is designed to simultaneously block key inflammatory pathways, specifically targeting IL-thirty three and IL-four and IL-thirteen. These cytokines are known to play central roles in airway inflammation and disease progression. IL-thirty three is a pro inflammatory cytokine, closely linked to epithelial stress, immune activation, and structural lung damage. Meanwhile, IL-four receptor alpha signaling is a primary driver of type two inflammation, which perpetuates disease activity and 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 mu ring model of type two inflammation with activity comparable to topilimab.

Specifically mice with humanized IL4 receptor alpha, challenged with house dust mite to induce type two 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 two cytokines IL-four and IL-five in lung tissue confirming the molecules blockade of type two inflammatory responses, matching the activity of the dupilumab BRCA that was also tested in the same experiment. The ability of fifteen twenty eight to also block non type two responses by virtue of the anti IL-thirty three specificity is then evident from the ex vivo analysis of COPD patient PBMC as shown by reducing a furan gamma positive NK cells. This reduction in cytokine response is comparable, if not greater, to that achieved by an analog of betapicamab, a benchmark clinical anti IL-thirty three map. Not surprisingly, dupilumab had no effect in blocking this type one response.

Mechanistically and by design, CW1528 demonstrates robust inhibition of both IL-four receptor alpha and IL-thirty three mediated signaling. To evaluate the ability of fifteen twenty eight to block both pathways simultaneously, in vitro studies using human epithelial cells responsive to both the IL-four receptor and IL-thirty three pathway activation were performed and showed fifteen twenty eight potently blocked IL-four, IL-thirty three combination induced CCL2 gene expression, outperforming the reversible achievable with monoclonal benchmark therapies in 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, fifteen twenty eight 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 IL-thirty three 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 IL-thirty three targeting across multiple large studies supports its biological relevance in COPD. The mechanism remains valid, but there are critical questions that are in 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 datasets, 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 IL-thirty three, fifteen twenty eight blocks both IL-four, IL-thirteen via IL-four receptor alpha and the alarm cytokine IL-thirty three.

We believe this simultaneous co localized blockade allows us to modulate both type two 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 involving 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 US regulatory filing submission in the 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 and D pipeline, and we’re committed to meeting our ultimate goal, 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 and A.

Ken Galbraith, Chair and CEO, Zymeworks: Thank you, Paul. As we move through the remainder of 2025, there’s no question that Capital Markets continues 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 and B1, 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 Asymmetric with targeted partnerships to fully unlock asset value and deliver durable returns for shareholders.

The Azimetric 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 successes in a data map, as well as multiple high value licensing partnerships with some of the industry’s most respected pharmaceutical companies, as Leonis 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 being materialized through the 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 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 and D candidates, especially in our advanced portfolio, makes us focus on value growth a long term sustainable business model. We’re currently advancing a wholly owned pipeline of differentiated antibody drug conjugates and multi specific antibodies spanning both clinical and preclinical stages in solid tumors, hemonc 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 partnering programs like Zahira 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 de risk 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 three and a half years, we’ve been able to accrete growing value from Zahira, 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 from risk of late stage development to our collaborators, providing us with the opportunity to reinvest certain levels of non dilutive capital, such as upfront payments and early milestone payments, back in a productive R and D organization, while also continuing to consider allowing excess capital back to shareholders as appropriate, thereby helping us to keep our innovative R and D cycle moving while preserving capital efficiency. By retaining royalty rates and long term economics on partner programs, we aim to give shareholders continued exposure to the upside of innovative R and D efforts as they progress their commercialization, but with lower risk than capital exposure. It’s important to highlight that at our core, Zynerich is a science first company, and our evolving strategy is not changing that. Our unwavering commitment to scientific excellence is what built the asymetric platform, resulted in the discovery and development of Zahira, and what continues to differentiate us today in the highly competitive fields of antibody drug conjugates and multi specific antibody therapeutics. As innovation in competition in oncology and autoimmune inflammatory disease becomes increasingly complex, our ability to seek out tough biological problems helps us to business 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 we’re seeking to build a business that’s not only financially sound, but one that keeps Steinmetz at the forefront of oncology and autoimmune inflammation for years to come. Given the strong potential we see for peak sales of zanadanumab, we believe we have a compelling opportunity to anchor our future strategy around anticipated royalty and milestone streams from Zahira 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 Dahira could be supplemented over time by additional potential revenues from existing partnerships, such as our collaboration with J and J Innovative Medicines with Vazrutinib, as well as new partnerships and collaborations formed from our wholly owned R and D pipeline or accessed externally. As the year of revenue grows with continued financial discipline applied to ongoing R and D investment, we intend to continue evaluating opportunities to allocate excess cash for shareholder returns. Excess cash may allow for opportunistic investments to bolster our royalty driven cash flows or additional investment in innovative R and 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 and 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, would 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 on 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 call provided clarity on how Zimmerx intends to continue operating with a very clear and disciplined mindset, or more specifically, as intentional capital allocators. A positive study outcome for Horizon GA-one 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 Zahira and other assets, combined with continued investment in R and 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 health care assets, and deliver meaningful returns for 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. Operator?

Conference Operator: We will now begin the question and answer session. To join the question queue, you may press 11 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 11 again.

We will pause a moment as callers join the queue. Our first question comes from Andrew Barron from Leerink Partners. Please go ahead.

Emily, Analyst, Leerink Partners: Hi. This is Emily on for Andy. With the horizon read out coming up. I’m wondering if PDL one status will 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 ZANI $525,000,000 regulatory milestone is weighted towards GEA versus other indications.

Thank you.

Ken Galbraith, Chair and CEO, Zymeworks: Yeah, thanks, Emily, both questions. I think what data is included in a top line press release is going to be up to both JAS and B1 since they’re the sponsor and co sponsor of the studies. So 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 $500,000,000 left in development milestones in our agreement with Jazz, having received $25,000,000 for the approval of BTC, and we’ve not provided any guidance around what that $500,000,000 will be allocated to. But I think as we earn those payments, you’ll obviously find out the magnitude of those around each of the GEA milestone as well as the other indications.

Conference Operator: Thank you. Our next question comes from Charles Zhu from LifeSci Capital. Please go ahead.

Charles Zhu, Analyst, LifeSci Capital: Hello, everyone. Congrats on the broad progress and, you know, fully understand we’re heavily anticipating the Phase III Horizon GEA study results coming up shortly. But I had two questions on some of your in house pipeline assets, you don’t mind. Maybe the first one is from a clinical positioning and capital allocation perspective, how similar or better does ZW-one hundred ninety one 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, 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, you know, beyond in patients beyond where some of our more potent options have focused on, whether it’s like, you know, Child Pugh Class B or even potentially Class C patients? How are you thinking about those? Thank you.

Ken Galbraith, Chair and CEO, Zymeworks: Yeah, let me take the first one, Charles, and I’ll pass it on to Paul for the second one. You know, I think when we look at DW-one hundred ninety one, we learned a lot from development of our first medicines, enjatumab, which has gone from us discovering it right through to approval and now launch. And again, remember that Hercoot Space was enjatumab most 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 with TDXC 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 SanidataMap, 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 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. But I think if you look at where zanitatumab 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 peak sales per year.

So we learn a lot about that. With GW-one hundred ninety one, we think there’s room to move innovation further when we look at ADC, both with gynecological and non small cell lung cancer. And so that’s really interesting for us to think about in DW-one hundred ninety one, as well as there are some broader expression 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 some 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’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 ZanatataMap 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 you’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 01/1991, and we’re excited to continue exploring with additional data sets around that to see if we can have a differentiated approach, will benefit the patient population more than others have in the innovation that’s been done elsewhere.

And I’ll let Paul talk about February.

Paul Moore, Chief Scientific Officer, Zymeworks: Yep, thanks Charles. Yeah, 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. So in particular for two fifty one, we have maximum tolerated dose of one hundred and twenty mgs per kg in primates.

So that sort of gives you one lens into the tolerability. And we think what that then provides us is bandwidth as we take that molecule into the clinic. We can’t say too much about 191, but so far that’s holding, our hypothesis is holding. So I think when we go into HCC, we’ll be systematic in our study. We’ll push forward in a disease subset of patients that we think are the most appropriate.

And then as we get the data, we’ll analyze and see how far we can go within that patient population. And then also think about the ability to move up in line in combination. So that’s also very much in our thinking as we think about a particular disease indication and applicability of a molecule. But certainly we’re encouraged by the tolerability profile, while not impacting the efficacy as I showed in preclinical profile in various HCC models.

Charles Zhu, Analyst, LifeSci Capital: Got it. Great. Thank you so much and congrats again on the progress.

Ken Galbraith, Chair and CEO, Zymeworks: Thanks, Charles.

Conference Operator: Thank you. Our next question comes from Yaron Weber from TD Cowen. Please go ahead.

Yaron Weber, Analyst, TD Cowen: Good morning, Yaron. Thanks for taking our question and congrats on the quarter. A couple for me. One to follow-up on, one nine one. Generally.

When can we start to think about data from the phase one trial? And then I see that in your product line, you have expansion cohorts also in non small cell. What do you know about the expression of alpha in non small cell lung cancer? And how would you characterize the opportunity? Thanks so much.

Ken Galbraith, Chair and CEO, Zymeworks: Yeah, I’ll take the first one. I’ll let Paul take the expression question, but, you know, obviously we’re nine to ten months into the start of the dose escalation studies for both one hundred ninety one and one hundred seventy one, and obviously with AEC you can tend to get an easier read on where you’re going. So, you know, 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, then we’re still looking for those potential possibilities, which could be in 2025 and if not in 2026. We’ve said before that any data we present will be at a peer review meeting, so we have to get to the right format.

And also that obviously that means timings related to having an abstract accepted for that basis. And 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 obviously intrigued with 191 with the first nine months of dosing. There’s more to explore, but again, we’ll look for an appropriate opportunity with our investigators to share data, at least initial data along the way. Paul, you want answer the second question?

Paul Moore, Chief Scientific Officer, Zymeworks: Yeah, 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 BOLT receptor expression. So, you know, that encourages us to move forward in that indication. And I think, you know, well, when you think about the design of our molecule, we were careful to pick an antibody, it was very efficient internalization. We think that will aid in therapeutic profile and potential of the molecule. It was amongst the strongest at payload delivery.

And then also, we alluded to the selection of our payload and it was very important that we designed that and selected that payload that it also has bystander activity that we think also helps overcome tumor target expression that’s heterogeneous. So with that profile, we feel that non small cell lung cancer is underserved and could benefit from us evaluating 191 there.

Yaron Weber, Analyst, TD Cowen: Thank so much.

Conference Operator: Thank you. Our next question comes from Steven Willey from Stifel. Please go ahead.

Steven Willey, Analyst, Stifel: Yeah. Good afternoon. Thanks for taking the questions. I’m not sure if Paul, Sabine or Ken want to take this, but I was just wondering if you’d be willing to offer your thoughts on the hazardous to make 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 liver mets. 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. Thanks.

Ken Galbraith, Chair and CEO, Zymeworks: Yeah. Sure. Thank you. I’ll let Paul provide a little comment. Even though J and J is innovative medicines molecule, know, we obviously we’re involved in the program and have a financial interest.

So we follow very closely, and we’re really excited about what they’ve been able to build there with our asymmetric platform the same way we build our own agents. But I’ll let Paul talk a little bit about these observations around the data.

Paul Moore, Chief Scientific Officer, Zymeworks: Yeah, Yep, Steven, mean, we’re aware of what was being published and what’s presented and J and J did publish their observations as well. So 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. And I think that, there’s not, finding that target is, there’s challenges with that.

And I think the KLK2 seems to have that profile. So the tolerability is quite remarkable, the dose that they’ve gone up to with their molecule. And I think that then supports then this exciting profile where they have a very manageable drug that they then see as the opportunity to combine with other therapies to really push forward the efficacy profile. So we see that as exciting. It’s kind of somewhat not that surprising if you think about it in the selection of that target, but then you may need some additional, let’s see how the data provide.

This is just pure personal commentary. Let’s see how that develops. But you can see that they’re quite excited within the combination with different modalities. And I think that’s what a T cell engager offers you is that ability to then combine with other complimentary mechanisms to really get an even better response profile.

Steven Willey, Analyst, Stifel: 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?

Paul Moore, Chief Scientific Officer, Zymeworks: Yeah, I’m not sure I can say too much about that, Steven. Know, 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. But for other targets that, you know, you could consider different affinity CD3s because they have a different normal tissue profile, I think that affords you that opportunity. So I wouldn’t, I think that’s really the biology can really drive your selection there rather than just assuming what works for one target works for another target.

Ken Galbraith, Chair and CEO, Zymeworks: If you think about DW2A9 is the all three targets, affinity on the CD three on that is different than one seven one. Understood.

Paul Moore, Chief Scientific Officer, Zymeworks: Yeah. Thanks for

Conference Operator: taking the question.

Ken Galbraith, Chair and CEO, Zymeworks: Yeah. No. Thank you.

Conference Operator: Our next question comes from Brian Shane from JPMorgan. Please go ahead.

Brian Shane, Analyst, JPMorgan: Hey, guys. Thanks for taking our question this afternoon. Maybe just looking at the details of the dose escalation for one hundred seventy one, 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 one, it seems that you have characterized four point two mg and also thirty eight mg dose level one. So should we assume that four point two mg as the dose level one, the low end of the dose range and then thirty eight mg as the high end of the dosing range?

Thanks.

Ken Galbraith, Chair and CEO, Zymeworks: Yeah, thanks, Brian. I’ll let Paul answer that.

Paul Moore, Chief Scientific Officer, Zymeworks: I can answer that and Sabine can feel free to add as well. But no, when we talk about, when we look at that, Brian, what we mean by dose level, it’s really the target dose is thirty eight microgram. So when we think of dose level one, you know, we’re stepping up to that target dose. So we can more think that the target dose of dose level one is thirty eight micrograms. Does that clarify?

Brian Shane, Analyst, JPMorgan: Yes. Yes. Thank you.

Conference Operator: Thank you. Our next question comes from Akash Tewari from Jefferies. Please go ahead.

Emily, Analyst, Leerink Partners: Hi. This is Phoebe on for Akash. We were wondering about your view on the Horizon GEA01 readout being delayed to Q4 twenty five and how it affects your confidence on the data and what could be reasons behind the delay? Thank you.

Ken Galbraith, Chair and CEO, Zymeworks: No, thank you for the question. Again, Akash using the word delay twice again at this conference. We don’t see it as a delay. I think the prior guidance from Jazz was given as their best estimate was 2025, and then they’ve given where we are in August, they’ve re guided that to give the guidance of Q4 twenty twenty five, which is still within the bounds of the second half. Think as we explained before, there’s an LA, it’s obviously an event driven trial, and they’re trying to give guidance around blinded event data, which they have access to.

It’s an open label study, so it’s important to protect the integrity 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 of the delays in that basis. Obviously, the studies were recruited some time ago, so they’re 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 2025.

It’ll happen in Q4 according to the guidance given by Janice yesterday and repeated by the sorry, two days ago and repeated by v one yesterday.

Conference Operator: Thank you. Our next question comes from Yigal Nochomovitz from Citigroup. Please go ahead.

Trinelle N. Amdur, Senior Director of Investor Relations, Zymeworks0: Yeah. Hi, Ken and team. 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? Thank you.

Ken Galbraith, Chair and CEO, Zymeworks: Yeah, thanks for the question, Yael. With respect to zanadatumab, commercially, both Jazz and B1 have direct responsibility now for supply of zanadatumab. With respect to Tisley, obviously, Beijing has that already with respect to US 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 US. So we feel very comfortable with the steps they’ve taken to protect the supply chain and be able to supplement it where necessary with the domestic manufacturer if required.

So I’m not concerned there, and you can talk to the hazard of Beijing directly about that. The second 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’re still very comfortable where we are with zanadatumab. With respect to AI, obviously Zymerk started as a computational platform and a computational biology company, so we’ve been doing AI long before it was ever called. AI and the way we think about engineering and developing complex biologics.

But I’ll let Paul talk a little bit more about that.

Paul Moore, Chief Scientific Officer, Zymeworks: Yeah, thanks for asking that question. And as Ken mentioned, it’s kind of in the roots of protein engineering at Zymeworks and we still have that kind of theme that’s based in our design and our thinking about molecules that 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 and whether that’s from target binding or giving you the diversity, we can then, we have the luxury of them being able to screen different molecules through the screening capacity of asymmetric. So 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.

So it is very much in our forethought as we tackle particularly in the multi specifics. And we think about how best to combine different binders or the ultimate sort of profiler biophysical properties that you want, that can really lend itself to AI strategies.

Ken Galbraith, Chair and CEO, Zymeworks: Thank you.

Conference Operator: Thank you. Our next question comes from John Miller from Evercore. Please go ahead.

Trinelle N. Amdur, Senior Director of Investor Relations, Zymeworks1: Hello, guys. Congrats on the print, and thanks for taking our question. This is JP for John. Two questions. On 1528, recent poster show longer half life and today you’re showing better inhibition.

So how do you expect the differentiating profile in humans be driven between bispecific design versus long half life? And then on February, how do you expect to proceed on dosing? Are you going to start with very conservative dosing, or you think you can get more aggressively to higher doses to show signs of efficacy?

Ken Galbraith, Chair and CEO, Zymeworks: Yeah, take the 1528 question and then ask Sabine to talk about February dosing. Yeah,

Paul Moore, Chief Scientific Officer, Zymeworks: so, yep, I think well spotted. We didn’t mention the half life extension that we incorporated into 1528 today, but that is definitely a feature that we think is important as we think about dosing strategy and we evaluate that in the clinic. We’ll have various pharmacodynamic readouts that will allow us to support our thinking on the half life. But that is a good point to highlight that we have incorporated YTE mutation. I think then on the biology, I mean, we see really the thinking here is that, you know, there’s mixed immune contributions in COPD with, you know, IL-four is obviously clinically validated, IL-thirty three also clinically valid to do re.

What we believe is by covering both of those pathways that we can get benefit that’s beyond what you can achieve by just one. And that there, our preclinical data suggests that we have that feature. And then in some of the actual models, what we’re looking at is that we can also recapitulate, we can see that in COPD patients, samples ex vivo. So we do those types of studies to sort of confirm the contribution and the design of the molecule works. And then also we put 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 an IL-four or how we inhibit IL-four receptor and IL-thirty three, that’s giving us an additional mechanistic advantage that we’ll then see how that plays out when we go into the clinic.

Ken Galbraith, Chair and CEO, Zymeworks: Yeah, maybe Suneet, 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. Suneet, anything you want add on the two fifty one dosing approach?

Trinelle N. Amdur, Senior Director of Investor Relations, Zymeworks: Absolutely. First, we’re excited to get our second ADC two fifty one into the clinic. With regards to its first in human dosing, as Paul pointed out earlier, we are very confident about safety of this molecule from a preclinical perspective. And also now we have experience with this linker payload five nineteen based on the data that we’re seeing from 191. So we can afford to be a little less conservative 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 two fifty one 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.

Trinelle N. Amdur, Senior Director of Investor Relations, Zymeworks1: Okay. This is very helpful. Thank you very much, guys, and congrats again.

Ken Galbraith, Chair and CEO, Zymeworks: Thank you.

Conference Operator: Our next question comes from Derek Archila from Wells Fargo. Please go ahead.

Emily, Analyst, Leerink Partners: Hi. This is Simone on for Dara. Congrats on the progress. Just one question. Do you expect 1528 to move as quickly as January, January, and February?

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.

Ken Galbraith, Chair and CEO, Zymeworks: Yeah. I think right now, I think what we’ve shown for 01/1971 and 01/1991, and we’re going to start to show that again, I think with February, is the ability to work quickly on ideas that we have preclinically and to transition quickly into clinical studies and to be able to execute these Phase one programs at a very fast pace. And so we would expect that 1528 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 VW220, 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 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 top six, 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 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 in all of those efforts in the top six and the advanced portfolio.

Conference Operator: 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 Umtani from B. Riley Securities. Please go ahead.

Emily, Analyst, Leerink Partners: Hi. Thanks for taking our question, and congrats on the progress. This is Kaurav on for Mayank. Regarding your ADC candidate VW one nine one, do we expect any data at any upcoming fall conferences like ESMO? And how much of the dose escalation data believe of the six dose level you plan to evaluate, you expect to have accumulated at the cutoff point?

Thank you.

Ken Galbraith, Chair and CEO, Zymeworks: No, thanks for the question. I think I tried to answer this earlier. We’re very excited where we are with EW one hundred ninety one, and I think we’re looking for opportunity to share what we’ve learned so far in our initial phase one 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 that at peer reviewed medical meetings. So 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 reviewed format, then we’ll take the appropriate steps to submit and hopefully get accepted in abstract as a regular late breaking for a conference.

We won’t indicate when that might be or won’t give any guidance for that until you see a title announced orally, pick, or abstract presented. So we’ll have to

Emily, Analyst, Leerink Partners: wait. Okay.

Ken Galbraith, Chair and CEO, Zymeworks: Just rather do that than any specific oral exams. You have to wait for that. That’s to occur, but we’re certainly at a stage in one on one where we find what we’re doing very interesting. It’s so 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 is possible.

Emily, Analyst, Leerink Partners: Okay. Thank you.

Ken Galbraith, Chair and CEO, Zymeworks: Yep. You’re welcome.

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

Ken Galbraith, Chair and CEO, Zymeworks: 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 and A session. Obviously, it’s about four years ago that we started working seriously on moving zanatumab 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 Horizon G01 as much as our investors are, and we look forward to being able to present those results with our partner Jazz and B1 in a top line basis in Q4 twenty twenty five as guided.

In the meantime, we’ll make more progress to 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.

Conference Operator: Thank you for your participation in today’s conference. This does conclude the program. You may now disconnect.

This article was generated with the support of AI and reviewed by an editor. For more information see our T&C.