Q4 2024 Zymeworks Inc Earnings Call
Thank you for standing by. This is the conference operator. Welcome to Zymork's fourth quarter and year end in 2024, 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 then 1-1 on your telephone keypad.
Speaker Change: I would now like to turn the conference over to Shrinal Inamdar, C.U. Director of Investor Relations. Shrinal, let's go ahead.
Speaker Change: Thank you, Fraser. Good afternoon, everyone. Thank you for joining our fourth quarter and the year-end 2024 results conference call.
Speaker Change: Before we begin, I would like to remind you that we'll be making a number of forward listening statements during this call, including without limitation, those forward listening statements identified in our slides and the accompanying oral commentary.
Speaker Change: Forward living statements are based upon our current expectations and various assumptions, and a subject to usual risk and uncertainties associated with companies in our industry and our stage of development.
Speaker Change: For discussion of these risks and the certainties, we refer you to our latest SUT filings found on our website and as well with the SUTC.
Speaker Change: In a moment, I will hand over to the youngy Patterson, our Executive Vice President, and Chief Business and Financial Officer.
Leone Patterson: The annual debate discussing recent corporate updates along with financial results for our fourth course in the end of 2024.
Speaker Change: Following this, Dr. Paul Moore, our chief scientific officer, will talk about key highlights from our fourth quarter, including our expanded focus on auto-immune and inflammatory diseases, as well as hematological oncology.
Speaker Change: At the end of the call, Leone, Paul and Ken Galbraith, our Chair and CEO , will be available for Q&A.
Leone Patterson: And reminded the audio and title of this call will be available on Zymeworks' website later today. Oh now, hand the call, call over to Leone. Over to you.
Leone Patterson: Thank you, Shrinalin. Thank you all for joining us today. We're pleased to be reporting on another successful quarter. Marked by the approval of dinner data map and continued progress on our clinical development strategy. Thank you for joining us today.
Leone Patterson: Our R&D day in December last year was a great opportunity for us to about it, just how far we've come, not only with the development of our wholly owned pipeline over the past two years, but also the larger impact we have been able to make through our global strategic partnerships.
Leone Patterson: 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 Science of Innovation and Collaboration
Leone Patterson: 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-Miles Squibb, Daichi Sanquillo, Janssen, Merck, GSK, Jans and Beijing. [inaudible]
Leone Patterson: 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.
Speaker Change: Whether it's by paratopic engineering or the development of our Topo 1 platform for ADCs, we started to continuously push the boundaries of biologics and multi-functional therapeutics.
Speaker Change: Looking ahead, we remain focused on advancing our next generation of wholly-owned therapeutics. Our expansion into autoimmune and inflammatory diseases, as well as hematologic indications, reflects our commitment to staying at the forefront of innovation and value creation.
Speaker Change: For our partners, this means continued access to potential basin class biologics, a dearest approach to development, and a shared vision for bringing transformable therapies to patients.
Speaker Change: Over the past year, there has been significant progress in our partner programs, achieving multiple key milestones that reflect the strength of our collaborations and the commercial potential of our pipeline.
Speaker Change: In total, we have earned over $45 million over the past 12 months from our partnerships.
Speaker Change: which I will outline in more detail in the following slides.
More recently, in January 2025,
Speaker Change: We achieved a $14 million 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 approach.
Speaker Change: As part of the agreement with GSK, we remain eligible for further research, development, and commercialization milestones, underscoring the potential for continued value creation.
Speaker Change: In relation to our partnership with jazz, Seher achieved net product sales of 1.1 million and Q4 2024 following the product launch in December 2024 and FDA approval in November 2024.
Speaker Change: Al Rortis from Net South by Jazz, has been reflected in our income statement in Q4 2024.
Speaker Change: These recent achievements reflect the strength of our partnerships and the ability of our innovative platforms to drive additional clinical and commercial success.
Speaker Change: We remain committed to advancing breakthrough therapies, expand our preparations, and unlocking new opportunities for growth.
Speaker Change: With this foundation of trust, proven execution, and differentiated technology we are well positioned to continue exploring the potential for partnerships and unlocking new opportunities together.
Speaker Change: Our goal is to advance our broad and diverse pipeline towards clinical trials as we continue to evaluate net pursuit, synergistic, global, and regional business development opportunities leveraging Zymework's experience as a trusted and preferred strategic partner.
Speaker Change: Now, turning to our financial position, this afternoon, Sywerks reported financial results for the fourth quarter of 2024.
Speaker Change: Zymework's net loss for the year-end of December 31, 2024 was $122.7 million or $1.62 per diluted share, compared to a net loss of $118.7 million in 2023.
Speaker Change: The increase in net loss was primarily due to a $17.3 million non-cash and payment charge recognized in 2024, related to Xanadata Mab, Zovodota, End, and an increase in income tax expense.
Speaker Change: Which was partially offset by lower research and development and general administrative expenses.
Speaker Change: As reported, our revenue for the year-end at December 35, 2024 was $76.3 million compared to $76 million for the same period in 2023.
Speaker Change: Revenue for 2024, included $25 million of milestone revenue from jazz in relation to the FDA approval of Zhehera for the treatment of her two positive BTC.
Speaker Change: $37.5 million for the Valment Support and Drug Supply Revenue from Jazz.
Speaker Change: 8 million dollars of milestone reverting from Beijing in relation to the acceptance by the CDU of the NPA and China of the BLA for Senate data map for second-line treatment of her two positive BTC. The CDU of the BLA for second-line treatment of her two positive BTC.
Speaker Change: $2.5 million of mouse and river from GSK in relation to the sequence pen nomination under the 2016 [inaudible]
Speaker Change: $3 million from Beijing for drug supply and research support payments, and $0.2 million from other partners for research support and other payments.
Speaker Change: Revenue in 2023 includes a 71.5 million dollars to develop the support and direct supply from jazz.
Speaker Change: $1.6 million from Beijing for drug supply and other research support payments, and $2.9 million from our other partners for research support and other payments.
[inaudible]
Speaker Change: Overall, operating expenses were $213.4 million for the year ended December 31, 2024, compared to $214.1 million in 2023, representing a slight increase of 0.3% year of year.
Speaker Change: This slight increase is overall and overall operating expense, so it's resulted in from a decrease in both recession development expenses and dual administration expenses.
Speaker Change: This was all set by a non-cash and payment charge of $17.3 million as a result of the company's decision to discontinue the Zanadata Mads overdose in clinical development program, which utilizes the technology represented by a quiet and process recession development assets.
Speaker Change: The decrease in research and development expenses year-to-year was primarily due to a decrease in expenses from the data map as a result of the transfer of responsibility for this program to jazz.
Speaker Change: and a decrease in expenses for CW-171 and DW-191 as the majority of manufacturing and IND enabling studies were completed in 2023, prior to filing of the IND applications in 2024.
Speaker Change: This decrease was partial set by an increase in manufacturing and idea-nearing supporting activities for ZW-220 and ZW-251, along with other preclinical and research activities.
Speaker Change: 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' transfer to jazz.
Speaker Change: 2020's the GNA, the decrease in GNA expenses was primarily due to a decrease in external consulting expenses for information technology, legal fees and other expenses for advisory services, insurance and depreciation and amortization expenses compared to 2023.
Speaker Change: This was partially set by Carson Curgey to the termination of our long-term facility lease in Seattle in 2024 and an increase in stop-based conversation expense over 2023, primarily due to new grants during 2024 and reversal of conversation expense.
for option, cancellations and modifications of 233.
Speaker Change: Other income, net was $20.5 million for the year ended December 31, 2024, compared to $18.8 million for the same period in 2023.
Speaker Change: Other income net for 2024 included $19.9 million of interest income and $0.8 million of foreign exchange gains, partially will set by other miscellaneous charges.
Speaker Change: Other income net for 2023 included $19.7 million of interest income and $0.3 million of financial miscellaneous income, possibly a step by $1.2 million of foreign exchange losses.
Speaker Change: Currently, we have approximately 69.6 million shares of Comestock Outstanding and approximately 5.1 million shares of Comestock, Disciobo, and a pre-funded warrants.
Speaker Change: As of December 31, 2024, we had $324.2 million of cash, resources consisting of cash, cash equivalents and marketable securities, as compared to $456.3 million as of December 31, 2023.
Speaker Change: For additional details on our quarterly and year-and-results, I encourage you to review our new release and other FCC filings as available on our website at www.zylox.com.
Speaker Change: Based on current operating plans, a strong financial position of $324.2 million in cash resources as of December 31, 2024, together with Sedan and anticipated Rupertou Marathon payments, continues to provide an expected cash runway into the second half of 2027.
Speaker Change: Just a reminder that we may also be able to extend this runway or fund an expanded R&D Scope.
Speaker Change: Through potential additional regulatory approval milestone payments and connection with our existing partnerships, most notably with jazz and Beijing, and potentially new partnerships and collaborations which we may choose to form.
Speaker Change: In addition, pending applicable regulatory accruals, we are eligible to receive commercial lots of payments based on annual sales of the Hira.
Speaker Change: and also tiered royalties between 10 and 20% on Jesus' annual net sales and between 10 and 19.5% on Beijing sales.
Speaker Change: We began earning royalty revenue from our jazz partnership, a social as BTC approval in Q4 2024.
Speaker Change: With that, I'd like to hand over to our Chief Scientific Officer, Dr. Paul Moore, who will provide an overview of key highlights from our R&D day, which took place in December 2024, as well as provide updates on our Phase 1 clinical trials for ZW171 and ZW191.
Thank you for watching!
Thank you. Thank you. Thank you.
Thanks. Thanks, Leone, and good afternoon, everyone.
Speaker Change: And thank you to those of you who joined us in New York for our R&D Day, back in December . We hope you found it to be an informative event.
Speaker Change: 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 the progress we reported.
Speaker Change: First of all, this slide provides a visual remainder of the tumor types we are prioritizing that all fall within the blue sphere and comprise cancers with pure survival rates.
Speaker Change: Those were three or five-year survival remains unacceptably low, together with a threshold level of incidence.
Speaker Change: In Bluefront, for the molecules we've already developed, Yani, or are developing, the 5x5, and the tumor types to cover within this framework.
Speaker Change: As you can see, our work today aligns closely with our strategic focus on solid tumors, specifically thoracic, gynecological and digestive tract cancers, which we enforce our commitment to tackling the most challenging cancers, but also identifying opportunities for additional development.
Speaker Change: In Parkle font of the oncologist we are proceeding with our advanced portfolio. These are areas where we believe our next generation molecules can make the biggest impact.
Speaker Change: In addition to thoracic and digestive tract cancers, where we already have plants in the food hall, we see opportunities also for equipment to logical mental illnesses, malignancies such as multiple myeloma, PLVCL, and acute myeloid leukemia.
Speaker Change: As you can see here, Zymework's current oncology pipeline is designed to address unmet needs across lung, gynecological and digestive tract cancers.
Speaker Change: Leveraging either multi-specific T-cell engages, or ADC therapeutic modalities, to build a diverse and de-risk portfolio.
Speaker Change: At R&D Day, we were expected to announce the nomination of ZW-209, a next-generation T-celling edger incorporating conditional CD-28 costagulation.
Speaker Change: And potentially, first in class moments of design to enhance the precision and durability of T-cell responses against BLL-3 expressing concerns.
Disnomination Highlight. [inaudible]
Speaker Change: The continued innovation and our approach of developing next-generation T-cell engages beyond.
CD3 activation.
Speaker Change: Our evolution from designing ZW171, where we will relabrige at Tri-Vailant, mining approach to our current leading preclinical candidate, ZW209, at Tri-specific, where flags are commitment to driving innovation.
Speaker Change: With ZW209, we have refined our platform to help optimize diesel activation through addition and costimulatory mechanisms for the goal of enhanced specificity and poor anti-tumor responses.
Speaker Change: We believe that innovative strategy not only maximizes the therapeutic potential of T-cells but also aims to deliver durable target efficacy against cancer.
Speaker Change: By leveraging a obligated T-cell binding and conditional CD-28 engagement in the design of 209, this novel approaches specifically designed to prevent potential unintended T-cell activation while enabling targeted tumor-sided toxicity.
and pre-critical studies.
Speaker Change: This candidate has demonstrated differentiated long-term cytotoxicity in vitro, even at low effects of the target ratios. We've also observed enhanced T-cell proliferation and survival, which can significantly improve the durability of responses for patients.
Speaker Change: Together, our T-cell Engager programs, such as 171, Targeting Music Dealers, and 209, Targeting DLL-3 with a novel CD-28, post-simulatum mechanism aimed to enhance immune activation and tumor selectivity, potentially improving response to durability and safety.
Speaker Change: Our antibody drug conjugate or EDC candidates, including 191-220-251, utilize our innovative linker p-loads to optimize tumor, pension, and therapeutic index.
These are the tests.
Speaker Change: Target well-validated tumor antigens, antigens such as folic receptor alpha, NAPI-2B, and GPC-3, positioning for potential best-in-class differentiation.
Speaker Change: As outlined with our press release this afternoon, we have provided prioritized resources to advance the press, 251, with an A&D application note planned from mid 2025.
Speaker Change: Hepatocelular customer remains an area of high unmet medical need and we believe 251 represents a compelling opportunity to help Hepatocelular customer patients. [inaudible]
Speaker Change: By accelerating this program, we are positioning ourselves to potentially bring that transformative therapy to patients, Shrinal. The encouraging preclinical results in well-defined clinical and regulatory parts for 251 made these are clear choice for prioritization.
Speaker Change: As part of this strategic prioritization, we have paused preparations for the commencement of phase 1 studies for ZW220 at this time.
Speaker Change: However, it is important to note that 220 remains a highly differentiated INV-ready ADC with strong potential in ovarian cancer and non-small cell one cancer.
Speaker Change: We remain confident that Ashiq's potential and will continue to evaluate the optimal timing for its clinical development, including potential partnership opportunities. We look forward to providing future updates on the development for 220 in the near future.
Speaker Change: Our decision to focus on 251 aligns with our broader strategy of advancing programs with the highest near-term impact while ensuring prudent financial management.
Speaker Change: We continue to study advanced ovarian and non-smile cell lung cancer patients with an ongoing ZW171 and ZW191 faced one studies which may provide by one site applicable to ZW220's future development.
Speaker Change: Together, taking together our balanced portfolio, employing diverse personalities and select design criteria, we believe we'll also enable this attention for multiple combination strategies, whether the standards of repair therapies are within our own portfolio, and both for induction and maintenance settings.
Speaker Change: As we continue advancing our pipeline, the strategic approach provides multiple shots in goal, helping to mitigate risk for maximizing potential value creation in our solid tumor oncology portfolio.
Speaker Change: During our R&D day, we also unveiled our ability to utilize Zymework's technology and experience for autoimmune and inflammatory disease, with the nomination of ZW1528.
Speaker Change: As you know, often in oncology, the immune system is underactive, and the goal is to amplify immune responses to the flight cancer.
Speaker Change: Such as we do through employment of T-cell-engager approaches or through checkpoint inhibition. [inaudible]
Speaker Change: In auto-immunity, 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 that activate the immune system and cancer can be reprogrammed to suppress it in order to immune disease. [inaudible]
Speaker Change: 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.
Speaker Change: In Zymeworks, we're well positioned to take advantage of this overlap, our chief medical officer, Dr. Jeffrey Smith, and myself have worked on the development of autoimmune therapies in the past, giving us an knowledge and experience to advance our molecules through pre-clinical development, IND and into the clinic. [inaudible]
Speaker Change: We see an opportunity to be selected and how we apply our technology, focusing on autoimmune inflammatory diseases where we can make meaningful impact.
Speaker Change: Regarding application of Zymework's expertise in plant and antibody engineering and particular bi-specific antibodies to autoimmune and inflammatory disease or AID, we seek two initial categories of opportunity.
Speaker Change: First, in the context of inflammatory disorders, from multiple cytokines drive disease progression, and blocking a single pathway may not be enough for benefit by developing bi-specific antibodies in multiple cytokines. We have the potential to improve outcomes beyond traditional therapies.
Speaker Change: In this context, our previous work with Leo Farma helped establish a panel of anti-body specificities which means leverage to evaluate
Our first candidate nominated for GIME is ZW-1528.
Speaker Change: which is an IL-4 receptor alpha by IL-33 by specific, which we believe could be beneficial for the treatment of disparity in inflammation, such as mixed chronic obstructive pulmonary disease or CVOP. By blocking multiple cytokines in a single molecule.
It's supported by our preclinical studies.
Speaker Change: Sackin, within autoimmune diseases for self-reactive or auto-reactive lymphosex tripe disease, targeting, modulating, or even depleting these populations can lead to therapeutic benefit. [inaudible]
Speaker Change: This applies to diseases like lupus, rheumatoid arthritis, type I diabetes, where approaches such as immune cell depletion or immune cell reprogramm can be highly effective.
Speaker Change: 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 T-cell engages, we rebelled position to apply these capabilities to select autoimmune diseases.
Moving on, no to a candidate in clinical development.
Speaker Change: As you know, we have initiated two global phase one clinical trials.
in 2024.
Speaker Change: for both 1-7-1 and 1-9-1, which are currently in ruling participants in North America, Asia-specific, and Europe , and are both in a dose escalation phase.
Speaker Change: Since our last training call, we have continued to advance the clinical development of 171 from North America to having clinical sites activated in patient recruitment ongoing across multiple regions including Germany, South Korea and the UK. These updates...
Speaker Change: Reflected any progress in our global development strategy that continued focus on advancing 171 across key markets.
Speaker Change: Similarly, since our last annual calls, we have continued to advise the global clinical development of 191, including the important milestone of the producing our first patient in November 2020-24.
Speaker Change: Since then, we have gotten development beyond the United States with clinical sites activated, and patient recruitment ongoing in Japan, South Korea, Australia, and Singapore.
Speaker Change: These developments reflect solid progress in expanding 191's clinical footprint across key regions, positioning us for continuing momentum from the coming quarter.
Speaker Change: For both of these products, we have the advantage of very tolerable molecules based on pre-clinical data, which allows us to implement a higher starting dose than you may have seen with other agents in semi-classes.
Yes.
Speaker Change: Of course, provides an advantage to try to go more quickly to an active range while studying the tolerality profile. We look forward to sharing trial and progress poses for these phase-1 clinical trials and an upcoming medical conference.
Speaker Change: We also expect to have strong presence at the AECR annual meeting in Chicago in April , and look forward to our scientific presentations at that PMM.
Ken Galbraith: I'd like to now hand over to Ken for some closing remarks.
Ken Galbraith: Thank you, Paul. We hope to continue progress we've made, whether Phase 1 trials demonstrates our ability to translate innovation into clinical progress.
Speaker Change: And this year, we're continuing to make significant strides in advancing another promising ADC, CW-251 toward IND submission and phase one clinical trials.
Speaker Change: The Prioritization Acceleration of the IND for ZW-251 reflects our distals with approach to pipeline resource allocation, ensuring we focus on the programs with the highest potential impact. The Prioritization Acceleration of the IND for ZW-251
Speaker Change: We do look forward to providing an update on the continued development of ZW 220 as we continue to have a strong belief in this differentiated ADC with our 519 payload.
Speaker Change: As we advance our RD portfolio, we intend to actively manage our emerging portfolio by continuing to evaluate our development priorities based on emerging data, the competitive landscape, and strategic opportunities to maximize near-term value creation.
Speaker Change: We're very excited about exploring the potential of ZW-251 in clinical studies.
Speaker Change: Targeting GPC-3 with an ADC introduces an innovative approach for hepatocelular across NOMA, an area where new treatment options are urgently needed.
Speaker Change: With potentially best-in-class designs and differentiated mechanisms of action, our pipeline offers meaningful opportunities for strategic partnerships and long-term value creation.
Speaker Change: Before I move on to Q&A, I'd like to acknowledge the appointment of Mr. Oleg Notalman as the seventh new addition to the board over the past two years.
Speaker Change: Bringing the total number of representative board seats for ECRF R1-2 out of the current 11 board members.
Speaker Change: Oli's appointment reflects the continued growth of Echo R1 shareholding, underscoring their confidence in the potential of Zymorks, and this decision follows years of constructive and ongoing discussions with Echo R1.
Speaker Change: The border remains well governed, and this balanced structure ensures robust and independent oversight, while also benefiting from Oleg's years of experience in the biotech sector.
Speaker Change: We're very confident that Oleg's experience in insights in driving value creation across the global biopic sector will be invaluable as we continue to execute on our street priorities and have a positive contribution to long-term value for all shareholders.
Speaker Change: 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 BTC.
Speaker Change: Along with our wholly-owned pipeline catalyst, this is going to be an exciting year for us, with top-line PFF data from the Verizon GAO-01 study of Zenit Ademab in combination with chemotherapy now expected in the second half of 2025.
Speaker Change: As well as continued progress by jazz and Beijing in broadening the commercial reach for Zahira and in evaluating other indications through ongoing investigation trials for Zahida Met.
Speaker Change: We look forward to presenting multiple poster presentations that 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.
Speaker Change: 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. Operator?
Speaker Change: We'll now begin the question and answer session. To join the question, Q, you may press star, then 1-1 on your telephone keypad. You'll hear a tone acknowledging your request.
Speaker Change: If you're using a speaker phone, please pick up your handset before pressing any keys. [inaudible]
To withdraw your question, please press star 1-1 again.
We'll pause for a moment as colors join the queue. [inaudible]
Speaker Change: Our first question comes from a line of Stephen Willie Putstiefel. [inaudible]
Good afternoon, thanks for taking the questions.
on
Speaker Change: On 251, 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. Also,
Speaker Change: Should be think about the way that you will evaluate this drug in dose expansion as being any different from either 1-7-1-1-1-9-1 and should be expect that there'll be an urgency.
Speaker Change: To initiate a combination go or tear maybe a bit quicker than for the other compounds.
[inaudible]
Speaker Change: Yeah, thanks Steve. I think we have the same strategy for...
Speaker Change: The entire portfolio, I think we're interested early on to seeing some interesting signs of tumor activity, but we firmly believe that both ADCs and T-cellingagers.
being used in combination with...
Speaker Change: Standard Care, in the earliest patient setting possible, might be the greatest possibility or probability.
of creating a sustainable response, and so we're...
Speaker Change: I'm extremely interested in that in the entire portfolio, specifically with ZW-251 in HCC. Obviously, we all know the poor prognosis for patients and the lack of a long-term overall survival for that patient population. Thank you very much.
So, we'll study it...
In a dose escalation, understand the drug.
Speaker Change: Make sure we see it differentiated, acceptable tolerability profiles from differentiated.
Mechanism, and some initial activity.
Speaker Change: And then we will be interested in studying the drug beyond that in expansion cohorts, both on its own, but also with the greatest possibility of...
Speaker Change: 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 251 itself given the patient population. That's something that we're going to look forward to as quickly as we can.
Okay, and then maybe just on... [inaudible]
I'm happy to be, you know, I think. [inaudible]
Speaker Change: You certainly characterize this as being IND ready for the middle part of this year. You guys were fairly optimistic about the target, the biology, the commercial rationale.
Speaker Change: Can you maybe just expand a little bit on perhaps what, either internally or externally, kind of prompted this prioritization of 251 over, um...
Over to you, Tony.
Thanks.
Speaker Change: I think we've talked before that we do intend to actually manage our emerging and developing portfolio and that means...
Speaker Change: Making very specific decisions about resource allocation because every biotech has a limited amount of time, focus, and resources. We're very excited about the W-251 and we've been able to...
Speaker Change: 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.
Speaker Change: Without losing also the momentum we currently have in our dose escalation recruitment in ZV-171 and N-191.
Speaker Change: Which is going very well. We want to make sure we don't lose momentum there as well.
Speaker Change: So given our excitement about 251 and our village would accelerate that in the clinic.
Speaker Change: We decided to make that decision. ZW-220 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...
Speaker Change: To do that, but this is primarily about our excitement about prioritizing 251.
Speaker Change: Given the excitement we have around, looking what impact this agent could have on that patient population.
Speaker Change: Which again is a little different patient population than the gynecological and thoracic indications, which were mostly in ZW-171-191 and 220 clinical study plans.
Speaker Change: So I think we're still very interested in the W220, but I think our excitement for 21, the ability to accelerate into clinical studies and make sure we can do that continuing phase one, just made us make that resource allocation.
Speaker Change: Decision, and we're going to actively manage the portfolios that'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. Thank you very much.
Speaker Change: On that patient population, and a very high impact on portfolio as well.
Alright, thanks for taking the questions. Thank you.
Akash Tiwari: Our next question comes from a line of Akash Tawari with Jeffries.
Speaker Change: This is Mano Jones for others. Thanks for taking our questions.
Speaker Change: On the horizon G.A. trial, we are seeing from the original 22 trial the same paper that you assumed a relatively aggressive enrollment compared to the historical trials like Togha-Jekabob, Genaud and 11. 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 PD1 high status, in the horizon G.A. trial, given this.
Speaker Change: An open-level trial, is there a risk in geography where keynote data alone is approved that PD1 high patients are randomized to the clinical dropout? So, the overall trial is more tilted towards PD1 low population. Just wondering how you consider that possibility. Thanks.
Speaker Change: No, thanks. On the second question, we just can't speculate. We'll, you know, the clinical date will be here.
Speaker Change: This year, and so we'll wait to see that clinical data. I think jazz gave a pretty good update last week on their earnings call about the guidance and the changing guidance for the outcome and the rationale for that.
Speaker Change: I think they addressed that in their press release and remarks plus their Q&A, so I don't want to go beyond the guidance they've already provided. So I'll just refer you back to that guidance or refer you back to jazz for that question.
Thanks. Thanks. Yeah.
Thank you for watching!
Our next question comes from Yigal Nochomovitz with City Group. Welcome to Yigal Nochomovitz.
Yigal Nokomovitz: Yeah, hi, thanks. Just a follow-up on speech question around the 251.
Yigal Nokomovitz: There's something specific that you saw that was really sort of a standout. [inaudible]
Yigal Nokomovitz: Experiment or a standout results in pre-clinical work with 251 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.
Speaker Change: No, thanks. I can get Paul to answer the first part of your question. I think the second part, you know, we're always looking for ways to...
Speaker Change: 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 ZW171 and 1-9-1 of those are going well. And with 251, we have been looking for opportunities to accelerate the timing to get into the clinic and we've able to find that and I think we have a really...
Speaker Change: A good pathway to generating clinical data for that agent. So that's why we're excited and that's why we've prioritized it. With some meters allocation, but Paul, I don't know if you want to mention anything else about pre-clinical data of interest around the decision.
Yannod.
Yeah, absolutely.
Speaker Change: I mean, I think we've signaled some of the exciting data we've had on 251 and prior presentations, but...
Speaker Change: The data has continued to look very exciting. I think our profile in therapeutic control of HEC models, PDX models, that data has continued to mature and support our decision.
Speaker Change: It's solid. Obviously, as we're doing our indiannabling studies as well, those go at a certain case, and we can interpret that data as it comes out. It was something…
Speaker Change: So you need to navigate that, and that's all being navigated so far as best as we can see, so it gives us the sort of confidence to accelerate the timeline on that one. So it's always been...
Speaker Change: You know, an exciting molecule and we've been able to, as Ken and we've noted, been able to accelerate it so we want to get that, that to patients as soon as possible.
Speaker Change: Okay, and then for 220 for the nephew to be 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? [inaudible]
Speaker Change: Yeah, we haven't given any guidance on why we might, and they shaped 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 90 ready states, so we've completed everything that we believe we need to, to...
Speaker Change: Take that in clinical studies, including the pre-IND consultation, the GLP talks, and the clinical supplies. So that program could be initiated pretty quickly in clinical studies. And I think as soon as we have guidance on being able to do that, we'll provide that guidance to you.
Okay, thanks, Canon Paul.
Our next question comes from Bryan Chang with JP Morgan.
Hey guys, thanks for taking out questions this afternoon.
Speaker Change: Maybe just going back to the pause on 2020, what's the decision driven by what you saw in part based on the proclinical work or the perception of Navi-Tubi in general among investors? Very good.
Speaker Change: And then, as we think about the rest of the portfolio, is there any ability for you to now pull forward asset like 209?
Speaker Change: Yeah, thanks, Brian . We haven't changed our guidance on CW 209, but obviously we're shown with CW 251. We can find ways to...
Speaker Change: Accelerate those programs. I think the decision we took to prioritize resource allocation to 51 was simply because of the excitement we have for that. Nothing else about the W220.
Speaker Change: At all, I think we want to accelerate 21 into 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 are ongoing dose escalation studies for ZW171 and 191. And I think we're just trying to be very careful not to take on too much. [inaudible]
Speaker Change: To make sure we focus and allocate our resources where we think we can have the highest impact.
Speaker Change: And so I think that's the decision that we took. And I think it's a very disciplined approach. And we look forward to moving to 211 into the clinic and starting those phase 1 studies and continuing to prosecute the dose escalation studies that are ongoing for 171-191 and the good momentum we have there. And so I think it's a very disciplined approach. And so I think it's a very disciplined approach. And so I think it's a very disciplined approach.
Okay, thank you, Ken. Yeah, thank you, Roy. Thank you.
Our next question comes from Jonathan Miller with Evercore ISI.
Speaker Change: Hey guys, thanks for the question. I'll pile on Nappy 2P while we're on the topic. Obviously you haven't made final decisions here, but I notice it's still in your pipeline slides. You're still talking about Nappy 2P as a target, but obviously it seems a little bit in limbo. Should I still think of this as...
Speaker Change: Part of the initial slate of targets that really mattered to you, that five-by-five slate, or should I be thinking more about promoting some of those autoimmune or inflammatory programs into those quote-unquote five-by-five slots?
Speaker Change: Just in terms of the whole pipeline development, where is Nappy to be ranking now compared to the six or seven programs that you've talked about explicitly?
Speaker Change: Yes, it's the image of 2020 is still a very high interest molecule to us, and I think you saw from the preclinical data we presented before, including in our last year.
He is highly differentiated and...
Speaker Change: We're interested in exploring that. I think this decision is more about our excitement for 251 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...
Speaker Change: The dose escalations we have going on now for 171-191. So you'll see it's in our pipeline as a high interest. So you'll see it's in our pipeline as a high interest.
We've taken it right up to the...
Speaker Change: To the point of IMD 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 251 is definitely that.
Speaker Change: And make sure we can move momentum throughout the entire portfolio as it grows, and it's nothing other than that.
Okay, I won't call with attrition. [inaudible]
Can I, can I, can I, then ask? [inaudible]
Speaker Change: I'm on Zany. Obviously, you've still got material regulatory milestones left that it was very exciting about, and I'm sure you can't speak with any detail on what is going to...
Speaker Change: 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 million? Or should I expect that to be more split out? [inaudible]
Speaker Change: Yeah, 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...
Miles Dunes, we received from Beijing.
Speaker Change: In their territory, and as those events continue to happen, we'll report what those milestones are, and just have to wait until that occurs. We're really excited that the tears launched. [inaudible]
Speaker Change: And the US and BTC were really excited about the potential for that to be broadened to both China and Europe where there's regulatory matters pending, and obviously really excited to see the results of the...
Top Line, Ryzen GA1 Study in the second half.
Speaker Change: As well as excited by the progress that jazz and majoring are making on the other registration studies for expansion purposes that they have ongoing and then.
Speaker Change: 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 we'll be able to add it up after the fact.
Speaker Change: 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 171-191 in the escalation phase but how are you thinking about...
Speaker Change: When you might disclose data, how much data you'd want to have in hand before you start sharing that publicly.
Speaker Change: Yeah, we'll continue to evaluate that as data comes in. I think those studies are progressing very nicely for us. And I think, you know, we want to make sure that continues, even though we're accelerating 251 into clinical studies.
Speaker Change: And have that go as well as the first two have. I think we've been very clear that, you know, we intend to provide updates on our clinical programs on a regular basis. We'll do that at a peer reviewed medical or scientific meeting.
Speaker Change: And I think we have said before we won't give any guidance until we've decided we have enough data 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 guide the you'll see data at that point and we just don't want to get ahead of ourselves with.
Speaker Change: With that guidance and all, the studies are progressing well, but it is, as you say, relatively early. And 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. You just have to wait for for that guidance to occur.
All right, thanks so much. Yeah, thanks, Sean.
Our next question comes from Jay Olsen with Oppenheimer. [inaudible]
Thank you.
Speaker Change: Oh, hey, congrats on the progress, including the addition of OLED to your board. And thanks for providing this update. We have two questions.
Speaker Change: 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 competitor's programs like Regeneron's?
IL-33, Readout, and COPD. [inaudible]
Speaker Change: Yeah, thanks. I can let Paul talk about work that will take us up to IND. And obviously from our experience of 171-191 last year and now at 251, we always look for opportunities for programs of the highest possible impact in our portfolio to find ways to...
Speaker Change: We'll accelerate those, so we'll continue to do that for this program as well, but Paul, do you want to talk about Paul about? No.
What work we need to get done to get to? [inaudible]
Speaker Change: So, you know, that's checking a lot of boxes for us, so now we have to do the, you know...
Speaker Change: I'm unitling activities, you know, think about the talk study plan, have the materials for that, have the materials to support filing. So, that pretty much takes a stand on the amount of time. And, you know, as can alluded to, and we've shown with the other programs. You know, there are some...
Speaker Change: Some places where we can contract on that, but, you know, we prefer to give, you know, realistic guidance as best we can to, you know.
So that's why we're seeing second half of 2026.
Speaker Change: I mean, I think you mentioned that there are other redotes coming from Regeneron and we know also.
AstraZeneca and other companies have I-33.
We know this.
Speaker Change: Certainly, that will, we'll keep an eye on that, but we're very confident in the design of our molecule and how we've designed that and how it's benefit to blocking both of those pathways that we'll be focused on our molecule. But certainly, we realise that that could add additional clinical validation to our strategy. Thank you.
Speaker Change: And we do expect to continue to report on some of that preclinical data as we progress towards IND, the same way we did for our other agents, 1-1-1-1-9-1-1, and others so expect to see additional data as we make our way towards IND.
Speaker Change: Okay, great. Thank you. That's super helpful. And then secondly, in cancer, can you share your thoughts on multi-payload ADCs and is that something that you might be interested in?
Go ahead, Paul.
Paul Moore: Well, absolutely. Certainly we think a lot about payloads. We're investigating additional payloads. We could build multi payload molecules, even with the capabilities we have in house, just now. I think there, it's really important to think about that...
The challenger list.
The therapeutic rationale for...
Paul Moore: For making such molecules, we do think about that, but it has to really provide a benefit, you know, in design for us, and thinking about that. So, certainly, certainly, we're aware we're aware that...
You know, we've really invested.
Paul Moore: You know, significantly on January , what we believe will be a best-than-class tofu platform, but behind that we thought about other pillows and then how you could combine that either with tofu or with themselves is certainly on our radar. [inaudible]
Paul Moore: But a lot of people will come down to the biology, the target, indication, and the need for, do you need that, or is that the right solution for what you develop? [inaudible]
Great. Thank you so much for taking the questions.
Thanks.
Paul Moore: and many more. Thank you for watching. I'll see you next time.
Our next question comes from Justin Zeland with BTAG.
Justin Zeland: Thanks for taking my questions and congrats on the progress. For 251, can you speak to your desired target product profile from an efficacy safety and or dosing?
Speaker Change: Create a differentiated profile from the competitive landscape, and I have a follow-up on a 191.
[inaudible]
Paul Moore: Yeah, I think Paul, do you have any comments you want to make about?
Speaker Change: 251, I don't think we have so specific about our target product profile, but Paul's are in these to add about 251 from what we see in preclinical data that we think we'd like to try to accomplish.
Yeah, no, I think.
Speaker Change: We know what the benchmarks are in those therapeutic areas and we feel that will be what we are striving for to demonstrate in the clinical studies, certainly from the preclinical data of the efficacy that we see across a broad range of.
I mean, I mentioned a broad range of a parasoial or PDX models is, you know, it's-
Speaker Change: You get exasus, the glyphic and three target wheat. We are big believers and the importance of the target, you know, when we're designing our molecules, the penetrance of GPC-3, you know, looks, you know, looks.
Speaker Change: Broad, 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 the population and that translates into the clinic.
Speaker Change: We feel this could be really impactful for patients that are in a big need for additional options of length of therapy.
Speaker Change: Make sense to me. And regarding 1.91, can you talk to how stable your linker is relative to competitor technologies? And that is to say, do you expect the toxicity profile for 1.91 to be similar to Free Arena T-Can, or Trudelvy, for instance? Yes, thanks.
. . . . .
Speaker Change: I'll take that. I can take the first step. I mean, our linker stability is what we would consider a traditional linker stability. What we have avoided here is using highly stable linkers. We're more in the realm of what others have used for approved ADCs, so that more traditional linker stability. I'll take the first step. I'll take the first step. I'll take the first step.
Speaker Change: You know, regarding the proof file of the safety proof file, I think the tolerability that's been something that we've really...
Speaker Change: Focused, and on when we've been developing our ADC, our topo, you know, I think one of the error questions was on combination strategies and we really, that was really cornerstone that we had a tolerable profile. [inaudible]
Speaker Change: A, so that we could get the dose up in patients, so that we could get to our 7th threshold level, the we think is important that you get to, to get anti, you know, maximum anti-trumorativity.
as well as...
Speaker Change: You know, the ability that to do combinations where you've got a more colorful profile. So obviously we need to efficacy, we can't lose that, but by being able to dose higher we think we can get, you know, a more efficacious response as well having a more, a drug profile that's more compatible with other standards of care.
Speaker Change: So that's really our thinking there. Our pre-clinical data supports that. In the tolerability that we've seen for 191, where we've been able to dose up to 60 megs per keg with a DRA total and you know, have it.
Speaker Change: So that's really our philosophy in thinking on the design.
Excellent. Well, thanks again for taking my questions.
No, thank you.
Speaker Change: As a reminder to ask a question, please press star 111 on your touchtone phone.
Thank you very much.
and many more. Thank you. Thank you.
Speaker Change: I'm showing no further questions in key with this time. I'd like to turn the call back to Ken Galbraith for closing remarks.
Ken Galbraith: That's great. Thank you, operator. Well, thank 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.
Speaker Change: This concludes today's conference call. Thank you for participating. You may now disconnect.