Zymeworks Inc. Price & Performance (ZYME)

Thank you for joining our fourth quarter and year end twenty twenty four results conference call. Before we begin, I would 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 usual risks and uncertainties associated with companies in our industry and at our stage of development For a discussion of these risks and uncertainties, we refer you to our latest SEC filings as found on our website and as filed with the SEC. In a moment, I will hand over to Leonie Patterson, our Head of and and Chief Business and Financial Officer, Liane will be discussing recent corporate updates, along with financial results for our fourth quarter and year ended 2024. Following this, Doctor. Paul Moore, our Chief Scientific Officer will talk about key highlights from our fourth quarter including our expanded focus on autoimmune inflammatory diseases as well as hematological oncology.

At the end of the call, Leonie, Paul and Ken Galbraith, our Chair and CEO, will be available for Q and A. As a reminder, the audio and slides from this call will be available on the Zymeworks website later today I will now hand the call over to Yoni.

Over to you. Thank you, Chanel, and thank you all for joining us today.

We're pleased to be reporting on another successful quarter marked by the approval of zanadatumab and continued progress on our clinical development strategy. In December was a great opportunity for us about just how far we've come, not only with the development of our holding on pipeline over the past two years, but also the larger impact we have been able to make through our global Over the last decade, we have built a strong track record of successful partnerships with some of the world's leading pharmaceutical companies And this timeline slide highlights this commitment to scientific innovation and collaboration. During this time, our cutting edge platforms such as Effect, and Azimetric have driven multiple partnerships across oncology and beyond with industry leaders including Bristol Myers Squibb, Daiichi Sankyo, Janssen, Merck, GSK, Jazz and Beijing. One of the key aspects that we believe makes us a preferred partner is our ability to rapidly evolve our platforms to address emerging therapeutic challenges. By peratopic engineering or the development of TOPO-one platform for ADCs we strive to continuously push the boundaries of biologics and multifunctional therapeutics. Looking ahead, we remain focused on advancing our next generation of wholly owned therapeutic Our expansion into autoimmune and inflammatory diseases as well as hematologic indications reflects our commitment to stay at the forefront of innovation value creation.

For our partners, this means continued access to potential best in class Biologics a derisked approach to development and a shared vision for bringing transformative therapies to patients. Over the past year, there has been significant progress in our partnered programs achieving multiple key milestones that reflect the strength of our collaborations and the commercial potential of our pipeline. In total, we have earned over $45,000,000 over the past twelve months from our partnerships. Which I will outline in more detail in the following slides. More recently, in January 2025, we achieved a $14,000,000 research milestone from GSK, under our 2016 license agreement related to a clinical milestone which we believe is a testament to the potential long term value of our innovative [indiscernible] As part of this agreement with GSK, we remain eligible for further research, development and commercialization milestones. Underscoring the potential for continued value creation. In relation to our partnership with Jazz, Jihira achieved net product sales of 1,100,000.0 in Q4 twenty twenty four following the product launch in December 2024 and FDA approval in November 2024, Our royalties from net sales by Jazz have been reflected in our income statement in Q4 twenty twenty four. These recent achievements reflect the strength of our partnerships and the ability of our innovative platforms to drive additional clinical and commercial success.

We remain committed to advancing breakthrough therapies, expanding our collaborations and unlocking new opportunities for growth. With this foundation of trust, proven execution and differentiated technology, we are well positioned to continue exploring the potential for partnerships unlocking new opportunities together Our goal is to advance our broad and diverse pipeline towards clinical trials as we continue to evaluate and pursue [indiscernible] global and regional business development opportunities leveraging Zymeworks' experience as a trusted and preferred strategic partner. Now turning to our financial position. This afternoon, Signworks reported financial results for the fourth quarter of twenty twenty four. Zoneworks net loss for the year ended December 31, 2024 was $122,700,000 or $1.62 per diluted share. Compared to a net loss of $118,700,000 in 2023. The increase in net loss was primarily due to a $17,300,000 non cash impairment charge recognized in 2024 related to zanadetumab, Zovadota and an increase in income tax expense. Which was partially offset by lower research and development and general and administrative expenses. As reported, our revenue for the year ended December 31, 2024 was $76,300,000 compared to $76,000,000 for the same period in 2023. Revenue for 2024 included $25,000,000 of milestone revenue from Jazz in relation to the FDA approval of ZEIRA for the treatment of HER2 positive BTC.

Dollars 37,500,000.0 for development support and drug supply revenue from Jazz dollars 8,000,000 of milestone revenue from Beijing in relation to the of the NPA in China of the BLA for Zenitamab for second line treatment of HER2 positive BTC. Dollars 2,500,000.0 of milestone revenue from GSK relation to the sequence pen nomination under the 2016 license agreement, dollars 3,000,000 from Beijing for drug supply and research support payments and $200,000 from other partners for research support and other payments.

Revenue in 2023 included $71,500,000 for development support and drug supply from JES. Dollars 1,600,000.0 from Beijing for drug supply and other research support payments and $2,900,000 from our other partners to research support and other payments. Overall, operating expenses were $213,400,000 the year ended 12/31/2024, compared to $214,100,000 in 2023. Representing a slight increase of 0.3% year over year. This slight increase is overall and overall operating expense. Has resulted in from a decrease in both research and development expenses and general administrative expenses. This was offset by a non cash impairment charge of $17,300,000 as a result of the company's decision to discontinue the Zanadetamab's overdose in clinical development program which utilized the technology represented by acquired and processed research and development assets. The decrease in research and development expenses year over year was primarily due to a decrease in expenses from Datadamab As a result of the transfer of responsibility for this program to JAS, and a decrease in expenses for ZW-one hundred and seventy one and ZW-one hundred and ninety one as the majority of manufacturing and IND enabling studies were completed in 2023. Prior to filing of the IND application in 2024. This decrease was partially offset by an increase in manufacturing and ID enabling supporting activities for ZW-two twenty and ZW-two fifty one.

Along with other preclinical and research activities. Stock based compensation expense increased primarily due to new grants during 2024 and a lower expense in 2023 as a result of the cancellations and modifications of awards in respect of employees transferred to Jazz. Turning to G and A. The decrease in G and A expense was primarily due to a decrease in external consulting expenses, information technology, legal fees and other expenses for advisory services. Insurance and depreciation and amortization expenses, compared to 2023. This was partially offset by costs incurred due to the termination of our long term facility lease in Seattle in 2024 and an increase in stock based compensation expense over 2023 primarily due to new grants during 2024 and reversal of compensation expense for option cancellations and modifications in 2023. Other income net was $20,500,000 for the year ended 12/31/2024 compared to $18,800,000 for the same period in 2023. Other income net for 2024 included $19,900,000 of interest income and $800,000 of foreign gains partially offset by other miscellaneous charges, Other income net for 2023 included $19,700,000 of interest income and $300,000 of miscellaneous income partially offset by $1,200,000 of foreign exchange losses. Currently, we have approximately 69,600,000.0 shares of common stock outstanding and approximately 5,100,000.0 shares of common stock this year ago under pre funded warrants.

As of 12/31/2024, we had $324,200,000 of cash resources consisting of cash, cash equivalents and marketable securities as compared to $456,300,000 as of 12/31/2023. For additional details on our quarterly and year end results, I encourage you to review our earnings release and other SEC filings as available on our website at www.zywerks.com. Based on current operating plans, our strong financial position, of $324,200,000 and cash resources as of 12/31/2024 together with certain anticipated regulatory milestone payments continues to provide an expected cash runway into the second half of twenty twenty seven.

Just a reminder that we may also be able to extend this runway or fund an expanded R and D scope through potential additional regulatory approval milestone payments in connection with our existing partnerships, most notably with Jazz and Beijing and potentially new partnerships and collaborations which we may choose to form In addition, pending applicable regulatory approvals, we we are eligible to receive commercial milestone payments based on annual sales of the Sahara and also tiered royalties between 1020% on Jazz's annual net sales.

Between 1019.5% on Beijing sales. We began earning royalty revenue from our Jazz partnership associated with BTC approval in Q4 twenty twenty four. With that, I'd like to hand over to our Chief Scientific Officer, Doctor. Paul Moore, who will provide an overview of key highlights from our R and D Day. Which took place in December 2024 as well as provide updates on our Phase one clinical trials for DW-one hundred and seventy one and ZW-one hundred and ninety one. Thanks, Lee, and good afternoon, everyone. And thank you to those of you who joined us in New York for our R and D Day back in December. We hope you found it to be an informative event. As a refresher for those who attended and also for those of you who were not able to attend, I wanted to spend a few minutes now to briefly provide an overview of progress we reported. First of all, this slide provides a visual remainder of the tumor types we're prioritizing. But all fall within the blue sphere and comprise cancers with poor survival rates those where three or five year survival remain [indiscernible] Together with a threshold level [indiscernible] In blue font are the molecules we've already developed [indiscernible] or RR developing?

The five by five. And the tumor types we cover within this framework. As you can see, our work to date aligns closely with our strategic focus on solid tumors specifically [indiscernible] Gynecological and digestive tract cancers, which reinforce our commitment to tackling the most challenging cancers while also identifying opportunities for additional development. In purple font, of the oncology areas, we are pursuing with our advanced portfolio these are areas where we believe our next generation molecules can make the biggest NPI. In addition to thoracic and digestive tract cancers where we already have We see opportunity also for hematological malignancies malignancies such as multiple myeloma, DLBCL and acute myeloid leukemia. As you can see here, Xyngular's current oncology pipeline is designed to address unmet needs across lung, gynecological and digestive tract cancers. Leveraging either multi specific T cell engagers or ADC therapeutic modalities to build a diverse and derisk portfolio At R and D Day, we were excited to announce a nomination of ZW-two zero nine, a next generation T cell engager incorporating conditional CD28 co stimulation. And potentially first in class molecules designed to enhance the precision and durability of T cell responses against DLL3 expressing cancers.

This nomination highlights the continued innovation in our approach of developing next generation T cell engagers beyond CD3 activation. Our evolution from designing CW-one 71 will leverage a trivalent finding approach to our current leading preclinical candidate [indiscernible] our commitment to driving innovation. With ZW-two zero nine, we have refined our platform to help optimize T cell activation through addition to costimulatory mechanisms. With the goal of enhanced specificity, and potent antitumor responses.

We believe this innovative strategy not only maximizes the therapeutic potential of T cells, but also aims to deliver durable target efficacy against cancer. By leveraging public T cell binding, conditional CD28 engagements in the design of two zero nine, This novel approach is specifically designed to prevent potential unintended T cell activation Well, I'll need needling targeted tumor cytotoxicity, In preclinical studies, this candidate has demonstrated differentiated long term cytotoxicity in vitro even at low effective to target ratios. We've also observed enhanced T cell proliferation and survival which could significantly improve the durability of responses for patients. Together, our T cell engager programs such as 171 targeting mesothelin and two zero nine targeting DLL fleet with a novel CV-twenty eight stimulatory mechanism aim to enhance immune activation and tumor selectivity potentially improving response durability and safety. Our antibody drug conjugate or EDC candidates including one hundred and ninety one two twenty and two fifty one, utilize our innovative linker payload to optimize tumor, panther and therapeutic index. These assets target well validated tumor antigens antigens such as follicular receptor alpha, [indiscernible] [indiscernible] [indiscernible] positioning them for potential best in class differentiation. As outlined in line with our press release this afternoon, we have prioritized resources to advance two fifty one with an IND application now planned for mid [indiscernible] Hepaticella carcinoma remains anaerial high unmet medical need and we believe two fifty one represents a compelling opportunity to help [indiscernible] By accelerating this program, we are positioning ourselves to potentially bring that transformative therapy to patients sooner.

The encouraging preclinical results and well defined clinical and regulatory path for two fifty one meeting our clear choice for prioritization. As part of this strategic prioritization, we have paused preparations for the commencement of Phase one studies for 20 at this time. It is important to note that two twenty remains a highly differentiated IND ready ADC with strong potential in ovarian cancer and non small cell lung cancer. We remain confident in the asset's potential we'll continue to evaluate the optimal timing its clinical development. Including potential partnership opportunities. We look forward to providing future updates on the development for 2020 the near future. Our decision to focus on two fifty one aligns with our broader strategy advancing programs with the highest near term impact while ensuring prudent financial management. We continue to study advanced and non small cell lung cancer patients with our ongoing 71 and ZW-one 91 Phase one studies, which may provide VAL-one sites applicable to CW220's future development Together, taken together, our balanced portfolio employing diverse modalities in selected line criteria we believe will also enable the potential for multiple combination strategies whether with standard of care therapies or within our own pool. Or within our own portfolio.

And both for induction and maintenance setting. As we continue advancing our pipeline, this strategic approach provides multiple shots in goal. Helping to mitigate risk while maximizing potential value creation in our solid tumor oncology portfolio. During our R and D Day, we also unveiled our ability to utilize Zymeworks Zymeworks and experience for autoimmune and inflammatory disease. With the nomination of ZW-fifteen 28. As you know, often in oncology, the immune system is underactive and the goal is to amplify immune responses such as we do through employment of T cell engager approach approaches [indiscernible] In autoimmune, it's the opposite. You essentially have a hyperactive immune system that needs to be controlled. This contrast opens up overlapping pathways for the same molecular mechanisms to activate the immune system in cancer, can be reprogrammed to suppress it autoimmune disease. Many of the tools and models that we use in the development of our oncology pipeline can therefore be adapted to autoimmune and inflammatory disease which we believe allows for a seamless transition of expertise. In Seignworth, we're well positioned to take advantage of this overlap Our Chief Medical Officer, Doctor. Jeffrey Smith, and myself have worked on the development of autoimmune therapies in the past giving us the knowledge and experience to advance our molecules through preclinical development IND and into the clinic.

We see an opportunity to be selective in how we apply our technology focusing on autoimmune inflammatory diseases, where we can make meaningful impact. Regarding application of Zymeworks expertise in plant and antibody engineering and to autoimmune and inflammatory disease or AIID two initial categories of opportunity. First, in the context of inflammatory disorders, from multiple cytokine drive disease progression, and blocking a single pathway may not be enough by developing bispecific antibodies that can block multiple segments, we have the potential to improve outcomes beyond traditional therapy. In this context, our previous work with LEO Pharma helped establish a panel panels for antibody specificity which we leveraged to evaluate preclinically, a series of therapeutic candidates. Our first candidate nominated for is ZW1528. It's an IL-four receptor [indiscernible] by IL-thirty three bispecific. We believe to be beneficial [indiscernible] [indiscernible] such as mixed type chronic ops obstructive pulmonary disease or CEGO PETE. By blocking multiple cytokines in a single module is supported by our preclinical studies. Second, within autoimmune diseases for self reactive or auto reactive lymphocytes, Sight disease targeting, modulating or even depleting these populations can lead to therapeutic benefit. This applies to diseases like lupus, rheumatoid arthritis, type one diabetes.

Approaches such as immune cell depletion, immune cell reprogram can be highly affected With our understanding of immune modulation and experimental systems, together with proven expertise in biologics and platform technologies, such as our next generation multi specific PECL engages were well positioned to apply these capabilities to select Moving on now to our Candidates and Clinical Development. As you know, have initiated two global Phase one clinical trials in twenty twenty twenty four, for both one hundred and seventy one and one hundred and ninety one which are currently enrolling participants in North America Asia Pacific Europe, and are both in the dose escalation phase. Since our last earnings call, we have continued to advance the clinical development 171? From North America to having clinical sites activated and patient recruitment ongoing across multiple regions including Germany, South Korea and The UK. These updates reflect steady progress in our global development strategy with continued focus on advancing 1,701 across key markets. Similarly, since our last earnings calls, we have continued to advance the global clinical development including the important milestone of dosing our first patient in November 2024. Since then, we have broadened development beyond The United States with clinical sites activated and patient recruitment ongoing in Japan, South Korea, Australia and Singapore These developments reflect solid progress in expanding 190 one's clinical across key regions positioning us for continued momentum coming quarters.

For both of these products, we have the advantage of very tolerable molecules based on preclinical data which allows us to implement a higher starting dose than you may have seen with other agents in similar classes. This of course, provides an advantage to try to go more quickly to an active range while studying the tolerability profile. We look forward to sharing trial and progress posters for these Phase one clinical trials at an upcoming medical conference we also expect to have strong presence at the EECR Annual Meeting in Chicago in April and look forward to our scientific presentations at that period end.

I'd like to now hand over to Ken for some closing remarks. Thank you, Paul. We hope the continued progress we've made with our Phase one trials demonstrates our ability to translate innovation into clinical progress.

And this year, we're continuing to make significant strides in advancing another promising ADC CW-two 51 toward IND submission and Phase one clinical trials. The prioritization acceleration of the IND for ZW-two 51 reflects our disciplined approach to pipeline resource allocation ensuring we focus on the programs with the highest potential impact. We do look forward to providing an update on the continued development of ZW-two 20 as we continue to have a strong belief in this differentiated ADC with our five nineteen payload. As we advance our R and D portfolio, we intend to actively manage our emerging by continuing to evaluate our development priorities based on emerging data, the competitive landscape and strategic opportunities to maximize near term value creation. We're very excited about exploring the potential of VW251 in clinical studies. Targeting GPC3 with an ADC introduces an innovative approach for hepatocellular carcinoma an area where new treatment options are urgently needed. With potentially best in class designs and differentiated mechanisms of action, our pipeline offers meaningful opportunities for strategic partnerships and long term value creation. Before we move on to Q and A, I'd like to acknowledge the appointment of [indiscernible] New addition to the Board over the past two years.

Bringing the total number of representative board seats for FR1 to two out of the current 11 board members. Oleks' appointment reflects the continued growth of EQR1's shareholding underscoring their confidence in the potential of Zymeworks and this decision follows years of constructive and ongoing discussions with Ecuador One. The Board remains well governed and this balance structure ensures robust and independent oversight while also benefiting from Oleg's years of experience in the biotech sector. We're very confident in Oleg's experience and insights in driving value creation across the global biogas sector will be invaluable as we continue to execute on our strategic priorities and have a positive contribution to long term value for all shareholders. So in conclusion, today's update, I believe we're well positioned to deliver growth and meaningful shareholder value starting with commercial activities from our partner Jazz and the resulting initial royalties from Zahira in [indiscernible] Along with our wholly owned pipeline catalyst, this is going to be an exciting year for us.

With top line PFS data from the Horizon GO GA-one study, of zenodatumumab in combination with chemotherapy now expected in the second half of twenty twenty five. As well as continued progress by Jazz in Beijing, in broadening the commercial reach for Zohira and in evaluating other indications, through ongoing investigational trials, for zanatata meth. We look forward to presenting multiple poster presentations at upcoming medical meetings including the American Association for Cancer Research Annual Meeting in Chicago the American Thoracic Society International Conference in San Francisco, and others during 2025. With that, I'd like to thank everyone for listening to our call, and I'd like to turn the call over to the operator to begin the question and answer session. [indiscernible] We'll now begin the question and answer session. Our first question comes from the line of Stephen Willey with Stifel.

Yes, good afternoon. Thanks for taking the questions. On February, I think you've made some commentary in the past, maybe have even reiterated today a desire to get into combination cohorts as quickly as possible. So should we think about the way that you will evaluate this drug in dose expansion as being any different from either one hundred and seventy one or one hundred and ninety one and should we expect that there'll be an urgency to initiate combination cohorts here maybe a bit quicker than for the other compounds?

Yes. Thanks, Steve. I think we have the same strategy for the entire portfolio. I think we're interested early on to seeing some some interesting signs of tumor activity. But we firmly believe that both ADCs and T cell engagers being used in combination with standard of care in the earliest patient setting possible might be the greatest possibility or probability of creating a sustainable response.

And so we're extremely interested in that in the entire portfolio.

Specifically with ZW-two 51 and HCC obviously, we all know the poor prognosis for patients. And the lack of a long term overall survival for that patient population So we'll study it in a dose escalation, understand the drug [indiscernible] tolerability profile, some differentiated mechanism and some initial activity And then we will be interested in studying the drug beyond that in expansion cohorts both its own, but also with the greatest possibility of a stronger outcome in an earlier treatment setting in combination as you suggested. So I think we think this way throughout the portfolio. For February itself given the patient population that's something that we're going to look forward to as quickly as we As we can.

Okay. And then maybe just on On NAPITOVI, I think you certainly characterize this as being IND ready for the middle part of this year. You fairly optimistic about the target, the biology, the commercial rationale. Can you maybe just expand a little bit on perhaps what either internally or externally kind of prompted this prioritization of two fifty one over over Over to you, Donnie.

Yes. I think we've as we said, we've talked before that we do intend to actively manage our emerging and developing portfolio. And that means making very specific decisions about resource allocation because every biotech has a amount of time focus and resources. We're very excited about CW-two 51 and we've been able to find a way to accelerate the timing to get into clinical studies. And we'd like to continue that momentum to make sure that we can accelerate that program as quickly as possible in Phase one studies. Without losing also the momentum we currently have in our dose escalation recruitment in ZUV-one hundred and seventy one and N-one 91. Which is going very well. We want to make sure we don't lose momentum there as well. So given our excitement about two fifty one and our ability to accelerate that in the clinic, we decided to make that decision. ZW220 remains a very interesting ADC for us. It is highly differentiated based on the data we presented. We've taken it right up to IND ready state It would not take us long to initiate that program when we decide to to do that. But this is primarily about our excitement about prioritizing two fifty one given the excitement we have around looking what impact this agent could have on that patient population, which again is a little different patient population than the gynecological and thoracic indications, which were mostly in ZW ZW-one hundred and seventy one one hundred and ninety one and two twenty clinical study plans So I think we're still very interested in ZW-two twenty.

But I think our excitement for February, the ability to accelerate into clinical studies and make sure we can do that continuing in Phase one Just made us make that resource allocation decision and we're going to actively manage the portfolio. So it's not the last resource allocation decision we'll make to move things around when we see an opportunity and a real unmet need and we think that we can go quickly to pursue that opportunity and something that could have a very high impact on that patient population and a very high impact on our portfolio as well. All right.

For taking the questions.

Thank you.

Our next question comes from the line of Akash Tewari with Jefferies.

This is Manoj on for Agash.

Thanks for taking our questions. On the Horizon DTA trial, we are seeing from the original two thousand and eight trial design paper that you assumed a relatively aggressive enrollment compared to the historical trials like Togazia, about GinoT-eleven. Do you attribute the current delay in readout timing to slower than initially expected enrollment? Or can we actually say it's more related to slower event rate accumulation in drug or control arms? And just one more what are your expectations on the percentage of patients in the PD-one high status in the Horizon GA trial? Given this is an open label trial, is there a risk in geographies where KEYNOTE-one is approved that PD-one high patients plan patients are randomized to a clinical Dropout So the overall trial is more tilted towards low, really low population. Just wondering, how you consider that possibility?

No, thanks. On the second question, I just we just can't speculate. Well, the clinical data will be here this year and so we'll wait to see that clinical data. I think Jazz gave pretty good update last week on their earnings call about the guidance the change in guidance for the outcome and the rationale for that. I think they addressed that in their press release and remarks plus their Q and A. So want to go beyond the guidance they've already provided. So I'll just refer you back to that guidance. I'll refer you back to Jazz for that question.

Thanks.

Yes.

Our next question comes from Yigal Nikomovitz with Citigroup Yes. Hi, thanks.

So a follow on Steve's question around the February.

One. Was there something specific that you saw that was really sort of as a standout experiment or standout results in preclinical work with February that made you take this decision And was this a fairly recent decision or was this something that has been brewing for some time? Thanks.

No, thanks. I can get Paul to answer the first part of your question. I think the second part, we're always looking for ways to accelerate getting our programs into clinical studies and ensure we've got really good momentum in Phase one clinical studies and we did that last year with ZW-one hundred and seventy one and one hundred and ninety one and those are going well. And with two fifty one, we have been looking for opportunities to accelerate the timing to get into the clinic and we've been able to find that. And I think they have a really good pathway to generating clinical data for that agent. And so that's why we're excited and that's why we prioritize it some resource allocation. But Paul, I don't know if you want to mention anything else about preclinical data of interest around the decision.

Yes, no. Yes, absolutely. I mean, I think we've signaled some of the exciting data that we've had on on February in prior presentations, but the data has continued very exciting I think our profile in therapeutic control of HCC models, PDX models that data has continued to to mature and support our decision. So with that, From that aspect, we always felt that the opportunities to break into a new therapeutic area was exciting. There's such an unmet medical need there. So I think the rationale for moving that that forward as quickly as we can is solid. Obviously, as we're doing our IND enabling studies as well, but [indiscernible] [indiscernible] we can We can interpret that data as it comes out. It was something so you need to navigate that. And that's all been navigated so far as best as we can see. So it gives us [indiscernible] confidence in to accelerate the timeline. On that one. So it's really Just always been exciting molecule and we've been able to, as Ken and Noted. Able to accelerate it. So we want to get that to patients as soon as possible.

Okay. And then for two twenty for the NAPI-2b, is the base case assumption that if you were to bring that one back online that it would be through a partnership or through your own efforts? Or is that unclear or to be determined?

Yes. We haven't given any guidance on when we might initiate that because I think we need to make wait to make that decision. But obviously, we've continued to invest in it to get it to an IND ready state. So we've completed everything that we believe we'd need to take that in clinical studies, including the pre IND consultation, the GLP talks and the clinical supply. So that program could be initiated pretty quickly in the clinical studies. And I think as soon as we have guidance on being able to do that, we'll we'll provide that guidance to you. Okay. Thanks, Ken and Paul. Thank you.

Our next question comes from Brian Cheng with JPMorgan.

Hey, guys. Thanks for taking my questions. Good afternoon. Maybe just going back to the pause on 02/20, what's the [indiscernible] preclinical work or the perception of NAB2B in general among investors And then as we think about the rest of the portfolio, is there any ability for you to now pull forward asset like two zero nine Yes.

Thanks, Brian. We haven't changed our guidance on two zero nine, but obviously we've shown with DW-two 51, we can find ways to accelerate those programs. I think the decision we took to prioritize resource allocation on two fifty one was simply because of the excitement we have for that. Nothing else about CW220 at all. I think we want to accelerate two fifty one in the clinic. We want to make sure we have good momentum. In Phase one studies. And we don't want to lose momentum that we have currently now and our ongoing dose escalation studies for ZW-one hundred and seventy one and one hundred and ninety one And I think we're just trying to be very careful not to take on too much to make sure we focus and allocate our resources where we think can have the highest impact so I think that's the decision that we're talking about. And I think it's a very disciplined [indiscernible] And we look forward to moving 51 into the clinic and starting those Phase one studies continue to prosecute the dose escalation studies that are ongoing for one one hundred and seventy one and one hundred and ninety one and the good momentum we have there.

Okay. Thank you, Ken. Yes. Thank you, Ryan.

Our next question comes from Jonathan Miller with Evercore ISI. [indiscernible] topic. Obviously, you haven't made final decisions here, but I noticed it's still in your pipeline slide. You're still talking about an IP2b as a target, but obviously it seems a little bit in limbo. Should I still think of this as part of the initial slate of targets that really matter to you that 5x5 slate or should I be thinking more about promoting some of those autoimmune or inflammatory programs into those 5x5 slots just in terms of the whole pipeline development where is NAPI-two B ranking? Now compared to the six or seven programs that you've talked about explicitly? Yes.

It's Image two twenty is still a very high interest molecule us. And I think you saw from the preclinical data we've we presented before including Enon last year, It is highly differentiated and we're interested exploring that. I think this decision is more about our excitement for two fifty one and being able to accelerate that into the clinic and get good momentum in the Phase one studies as well as not lose momentum from the dose escalations we have going on now for one hundred and seventy one and one hundred and ninety one. So you'll see it's in our pipeline. It's of high interest. We've taken it right up to the to the point of IND filing and it would not take us much time or effort to initiate those clinical studies, but we'll just decide to do that at the right time just to make sure that for the portfolio itself, we can follow the areas of high impact and two fifty one is definitely that and make sure we can move momentum throughout the entire portfolio as it as it grows. It's nothing other than that.

Okay. I won't call it attrition. No, no.

Can I then ask On Zanny, obviously, you still got material regulatory milestones left? That I was very excited about. And I'm sure you can't speak with any detail on what is going to enable those, although I think we can all sort of guess. Can you just say how many indications and geographies are the remaining milestones split between? Is there one is there an expectation that one is really driving the bulk of that remaining $500,000,000 or should I expect that to be [indiscernible] Yes. We're not we're unfortunately not able to guide on the future milestones. You obviously saw the milestone we got for the BTC approval and you obviously saw the milestones we received from Beijing in their territory. And as those events continue to happen, we'll report what those milestones are. And you'll just have to wait until that that occurs. We're really excited that Sahir has launched And The U. S. And BTC, we're really excited about potential for that to be broadened. To both China and Europe where there's regulatory matters pending. Obviously really excited to see the results of the top line RISE in GA-one study in the second half.

As well as excited by the progress that Jazz and Beijing are making on the other registration studies for expansion purposes that they have ongoing. And then I think we're extremely excited about the partnerships and I think our share of Royalties and milestones will report as they come along and then we'll be able to add it up after the fact.

All right. Makes sense. I guess then finally, can you give us an update on your current expectations for data disclosure on the internal programs? I mean, obviously, you're still relatively early for 01/1971, 01/1991 in the escalation phase. But how are you thinking about when you might disclose data? How much data you'd want to have in hand before you start sharing that publicly?

Yes. We'll continue to evaluate that as data comes in. I think those studies are progressing very nicely. For us. And I think we want to make sure that continues even though we're accelerating two fifty one into clinical studies.

And have that go as well as the first two have. I think we've been very clear that We intend to provide updates on our clinical programs on a regular basis. We'll We'll do that at a peer reviewed medical or scientific meeting. And I think we have said before, we won't give any guidance until we've decided we have an update that's meaningful to present.

In that peer reviewed format. And once we've done that and submitted it and have an abstract accepted and talk about the title, then we'll we'll guide that you'll see data at that point. And we just with that guidance at all. The studies are progressing well, but as you say relatively early. We want to make sure that we have something meaningful to put in front of that peer reviewed audience about the the status of the work that we're doing and what's going to come next. So you'll just have to wait for for that guidance to occur.

All right. Thanks so much. [indiscernible] Our next question comes from Jay Olson with Oppenheimer.

Hey, congrats on the progress, including the addition of Oleg to your Board. And thanks for We have two questions. First, on autoimmune and inflammatory diseases. Can you talk about the gating factors for filing the IND for 1528 and could that be accelerated based on read across from competitors programs like Regeneron's IL-thirty three readout and COPD? Yes, thanks. I can let Paul talk about Zymeworks that will take us up to IND. And obviously, from our experience at 01/1971, 191 last year and now at two fifty one, we always look for opportunities for programs of the highest possible impact in our portfolio to find ways to accelerate those. So we'll continue to do that. For this program as well.

But Paul, do you want to talk about Paul about what work we need to get done to get to IND or the nature of that work. [indiscernible] Yes, sure. Yes, I know, I mean, obviously, we shared some data at the R and D Day on that. So we're very excited about preclinical profile. We have some pilot NHP study some pilot PK. So That's checking a lot of boxes for us. So now we have to do the The IND enabling activities, think about the toxide plans, have the materials for that, have the materials to support filings. So that pretty much takes a standard amount of time. And as Ken alluded to and we've shown with the other programs, there are some some places where we can [indiscernible] But we prefer to give realistic guidance as best we can to That's why we're seeing second half of twenty twenty six.

I mean, I think you mentioned that there are other readouts coming from Regeneron and we know also AstraZeneca and other companies have IL-thirty [indiscernible] Certainly, that will we'll be keeping an eye on that, but we're very confident in the design of our molecule and how we've designed that and how it adds benefit to to blocking both of those pathways that we will be focused on our molecule. But certainly, we realize that that could add additional clinical validation to our strategy.

And we do expect [indiscernible] Continue to report on some of that preclinical data as we progress towards IND, the same way we did for for our other agents one hundred and seventy one and one hundred and ninety one and and others. So expect to see additional data as we make our way towards IND. Okay, great. Thank you. That's super helpful.

And then secondly, in cancer, can you just share your thoughts on payload ADCs and is that something that you might be interested in? Go ahead, Paul.

Absolutely. Certainly, we think a lot about payloads. We're We're investigating additional payloads that we could build [indiscernible] capabilities we have in house just now I think there, it's really important to think about the The challenge or the therapeutic rationale for for making such molecules. We see so we do think about that. But it has to really provide a benefit in design for us. Thinking about that. So Seth, certainly, we're aware that We've really invested significantly on January, what we believe will be our best in class TOFO platform but behind that saw about other payloads and then how you could combine that either with topo or with themselves is certainly on our radar. But a lot of will come back to the biology, the target [indiscernible] And the need for do you need that or is that the right solution? For what you develop.

Great. Thank you so much for taking the questions. Thanks, Jay.

Our next question comes from Justin Zaland with BTIG.

Congrats on the progress.

For February, can you speak to your desired target product profile an efficacy, safety and or dosing a differentiated profile from the competitive landscape. And I have a follow-up on 01/1991.

Yes. Paul, do you have any comments you want to make about February. I don't think we have so specific about our target product profile, but Paul is there any to add about two fifty one from what we see in preclinical data that we think we'd like to try and accomplish.

Yes. No, I think there we know what the benchmarks are in those therapeutic areas and we feel that will be what we'll be striving for to demonstrate in the clinical studies separately from preclinical data, the efficacy that we see across a broad range of I mean, I mentioned a broad range of hepatocellular PDX models is [indiscernible] [indiscernible] [indiscernible] we are big believers in the importance of the target. When we're designing our molecules. The penetrance of GPC3 It looks It looks bright. Will we need to enrich? We will find out. So that may also be a factor in our final target product profile. But as of now, based on the data that we see from the preclinical studies, we seem to be able to have broad range of [indiscernible] [indiscernible] and that translates into the clinic we feel this could be really impactful for patients that are [indiscernible] in big need for additional options of lines of therapy.

Makes sense to me. And regarding 191, can you talk to how stable your linker is relative to competitor technologies? And that is to say, do you expect the tough 91 to be similar to free arino Tecan or Tredelvy for instance I can take the first stab. I mean, our linked stability is what we would consider a traditional linkeder stability. What we have avoided here is using highly stable winkers We're more in the realm of what others have used for approved ADCs. So that's more traditional anchor stability. Regarding the profile of safety profile, I think the tolerability, that's been something that we've really focused in on when we've been developing our ADC, our TOPO I think one of the Howard questions was on combination strategies and And we really that was really cornerstone that we had a tolerable profile A, so that we could get the dose up in patients so that we could get to a certain threshold level that we think is important that you get to to get maximal anti tumor activity. As well as the ability then to do combinations where you've got a more tolerable profile. Obviously, we need the efficacy We can't lose that.

But by being able to dose higher, we think we can get a more efficacious response as well having a more profile that's more compatible with other standard of care. So that's really our thinking there. And our preclinical data supports that. In the tolerability that we've seen for 01/1991 where we've been able to to dose up to sixty mgs per kg with a DARI eight and have a Clean Mill Health. So That's really our philosophy and thinking on the design.

Excellent. Well, thanks again for taking my questions.

No, thank you.

We're showing no further questions in queue at this time. I'd like to turn the call back to Ken Galbraith for closing remarks.

That's great. Thank you, operator. Well, thank you everyone for listening to our progress on the call today and look forward to reporting continued progress at Zymeworks on the portfolio in the months ahead. So thank you very much.

This concludes today's conference call. Thank you for participating. You may now disconnect.