Q1 2025 Zymeworks Inc Earnings Call
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Speaker Change: I'll now turn the conference over to Sharon I'll end up Dark Smith director of Investor Relations. Please go ahead.
Ed.
Speaker Change: Thank you. Thank you.
Speaker Change: Everyone. Thanks for joining us.
Speaker Change: Thank you for having us conference call.
Speaker Change: Before we begin I would like to remind you that we'll be making a number.
James: Thanks James.
Really without limitation.
James: I think like any company.
James: Company policy.
James: The statements are based upon our current expectations and that assumption.
James: Risks and uncertainties.
James: As companies in our industry.
James: I'll take it.
James: For a discussion of these risks and uncertainties refer you to our SEC filings found on our website.
James: Sir.
James: And among all behind US we are in person.
Speaker Change: The Vice President and Chief Business Officer.
Speaker Change: So recent business updates along with the financial results for first quarter 2025.
Speaker Change: What do I Miss spoke to pool, our Chief Scientific officer will give an overview of our mix and R&D.
Speaker Change: Including highlights from our first two presentations at the investment sensation.
Speaker Change: Luisa.
Luisa: At the end of the cool pool.
Luisa: <unk> and Ken Galbraith, nausea, and see us will be available for Q&A.
Speaker Change: Sabine Mccann, our recently appointed senior Vice President and co development.
Speaker Change: And remind us again when the school will also be available.
Speaker Change: Today, I will now turn the call over scene.
Speaker Change: Thank you Chanel and thank you all for joining us today.
Speaker Change: I'm pleased to walk you through a corporate and operational highlights for the first quarter of 2025.
Speaker Change: I'd like to begin by emphasizing that our performance. This quarter reflects the discipline focus and resilience of our business model and a dynamic environment for innovative biotech companies, we continue to execute against our long term strategy and deliver meaningful progress across our portfolio.
Speaker Change: Our programs are moving towards clear measurable clinical milestones with near term opportunities to validate our technology platforms and meaningful patient populations globally.
Speaker Change: Throughout this period of continued progress we have demonstrated our ability to operate at a high standard and provide value to shareholders, while prudently managing our cash.
Speaker Change: We are also able to manage our cash burn going forward through active review and evaluation of our portfolio and development priorities with this in mind and as previously highlighted by a management team. We are committed to an evidence based approach to pipeline management.
Speaker Change: Decisions on investment in clinical development are tied to clear clinical and scientific validation.
Speaker Change: On the research and development front, we are honored to have our wholly owned pipeline represented at ACR annual meeting with six posters on preclinical data presented across our antibody drug conjugate and T cell engagement pipeline.
Speaker Change: Well it will be taking us through key highlights from these process later on today's call.
Speaker Change: We are also looking forward to presenting more preclinical data on our wholly owned pipeline at several upcoming medical conferences in the second quarter, including the American Thoracic Society annual meeting, where an abstract has been accepted for GW, one five to eight and novel I O for all 33 by specific.
Speaker Change: Molecule.
Speaker Change: We will also be obtaining ESCO.
Speaker Change: And as my gynecological cancer annual meetings, where we will be presenting trial in progress posters on <unk> 171, and CW 191, respectively.
Speaker Change: Similarly, our partner Jazz is also planning to present on these accepted abstracts.
Speaker Change: On three sorry.
Speaker Change: Except that abstracts at S Guy on saying the data map, including a four year follow up of the five phase III Dynamo and metastatic DEA, which will provide state of understanding of the long term outcomes and overall survival presented data that plus chemotherapy in her two positive advanced patients with met.
Speaker Change: Static gea.
Speaker Change: This progress is further reflected in the announcement from jazz in April 2025 did the EMEA committee for medicinal products for human use or <unk> has adopted a positive opinion recommending the approval of <unk> for treatment of advanced <unk>, two plus biliary tract cancer patients.
Speaker Change: A final decision is expected in the coming months importantly, if approved this would also represent an opportunity for an increase in royalty revenue for <unk> in the near future.
Speaker Change: We are also looking forward to the upcoming presentation by J&J and eschar, highlighting the phase one data for our bi specific T cell engage at engineered utilizing isometric platform targeting a novel target K L. K two in metastatic castration resistant prostate cancer.
Speaker Change: Uh huh.
Speaker Change: Some of you might have seen the preliminary data at ACR last week and we're encouraged by the early clinical activity in <unk>.
Speaker Change: Safety profile observed to date.
Speaker Change: I wouldn't say this program move forward, especially with such a difficult to treat patient population in need of novel targets.
Speaker Change: As a reminder, under the terms of the agreement in place with J&J, but this product the company remain eligible to receive development milestones of up to $86 million commercial milestone payments of up to $373 million and mid single digit royalties on commercial sales.
Speaker Change: Turning to our financial position. This afternoon assignment reported financial results for the first quarter of 2000 25000.
Speaker Change: Net loss for the three months ended March 31, 2025 was $22 6 million compared to a net loss of $31 $7 million for the same period in 2020 for.
Speaker Change: The decrease in net loss was primarily due to an increase in revenue, which was partially offset by an increase in operating expenses and increase in income tax expense and a decrease in interest income.
Speaker Change: As reported our revenue for the three months ended March 31, 2025 was $27 $1 million compared to $10 million for the same period in 2024.
Speaker Change: Revenue for the three months ended March 31, 2025 included $14 million of milestone revenue from GSK in relation to our clinical milestone under our 2016 platform technology transfer and license agreement.
Speaker Change: $3 $1 million of milestone from Daiichi Sankyo following the first patient dosed in the clinical trial related to our 2018 license agreement.
Speaker Change: Nice $6 million for the development support and.
Speaker Change: Drug supply revenue in addition to the zero point $2 million of royalty income from jazz.
Speaker Change: Zero point $2 million of drug supply revenues from Beijing.
Operator: 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. If you have a question, press star and the 1-1 on your telephone keypad.
Speaker Change: These achievements underscore the strength of our foundational partnerships and the relevance of our platform across multiple products moving into clinical development by our partners.
<unk> million dollars compared to $10 million for the same period in 2024.
Revenue for the three months ended March 31, 2025 included $14 million of milestone revenue from GSK and realized into a clinical milestone under our 2016 platform technology transfer and license agreement.
Speaker Change: We are also hopeful that continued development by our collaboration partners will provide a future source of revenues for US. These revenues also reflect growing momentum for the HERA and demonstrate the value of our partnership strategy and expanding patient reach while helping us improve our financial efficiency.
Shrinal Inamdar: I'll now turn the conference over to Shrinal Inamdar, Senior Director of Investment Relations. Shrinal, please go ahead. Thank you, Operator, and good afternoon, everyone.
$3 $1 million of milestone from Daiichi Sankyo following the first patient dosed in the clinical trial related to our 2018 license agreement.
Shrinal Inamdar: Thanks for joining our first quarter 2025 results conference call. Before we begin, I would like to remind you that we will 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. All of the containments are based upon our current expectations and various assumptions and are subject to the usual risks and uncertainties associated with companies in our industry and at our stage of development.
Speaker Change: Overall operating expenses were $52 $7 million for the three months ended March 31, 2025 compared to 47.3.
$96 million for the development support and.
Drug supply revenues. In addition to the zero point $2 million of royalty income from jazz.
Speaker Change: $3 million for the same period in 2024.
Zero point $2 million of drug supply revenue from Beijing.
Representing an increase of 10%.
These achievements underscore the strength of our foundational partnerships and the relevance of our platform across multiple products moving into clinical development by our partners.
Speaker Change: Research and development expense was $35 $7 million for the three months ended March 31 2025.
Shrinal Inamdar: For a discussion of these risks and uncertainties, we refer you to our latest SEC filings that are found on our website and as part of the SEC.
Speaker Change: This $32 million for the same period in 2024.
We are also hopeful that continued development by our collaboration partners will provide a future source of revenues for US. These revenues also reflect growing momentum for the HERA and demonstrate the value of our partnership strategy and expanding patient reach while helping us improve our financial efficiency.
Shrinal Inamdar: In a moment, I'll be handing over to Leone Patterson, our Executive Vice President and Chief in Business Officer, who will be discussing recent business updates along with the financial results for our first quarter 2025.
Speaker Change: Primarily driven by an increase in CW 251, and other preclinical research expenses.
Speaker Change: Partially offset by reductions in costs on Santa data Bad then at Databank somebody Toten, and GW 191, and GW to 'twenty two.
Shrinal Inamdar: Following this, Dr. Paul Moore, our Chief Scientific Officer, will give an overview of our recent R&D development, including highlights from our poster presentations at the American Association for Clinical Research.
Overall operating expenses were $52 $7 million for the three months ended March 31, 2025 compared to 47 point.
Speaker Change: General and administrative expenses was $17 million for the three months ended March 31, 2025, compared to $15 8 million for the same period in 2024.
Shrinal Inamdar: At the end of the call, Leone, Paul and Ken Galbraith, our Chair and CEO, will be available for Q&A, along with Dr. Sabine McCann, our recently appointed Senior Vice President of Clinical Development.
$3 million for the same period in 2024.
Speaker Change: Marilyn due to an increase in stock based compensation expense.
Representing an increase of 10%.
Speaker Change: As of March 31, 2025, we had 321 $6 million of cash resources, consisting of cash cash equivalents and marketable securities as compared to $324 $2 million as of December 31, 2024.
Research and development expense was $35 $7 million for the three months ended March 31, 2025 compared to $32 million for the same period in 2024.
Shrinal Inamdar: And a reminder, the audio and slides from this call will also be available on the Timeworks website later today. I will now turn the call over to you.
Leone Patterson: Thank you, Shrinal, and thank you all for joining us today. I'm pleased to walk you through our corporate and operational highlights for the first quarter of 2025. I'd like to begin by emphasizing that our performance this quarter reflects the discipline, focus, and resilience of our business model. In a dynamic environment for innovative biotech companies, we continue to execute against our long-term strategy and deliver meaningful progress across our portfolio. Our programs are moving towards clear, measurable clinical milestones, with near-term opportunities to validate our technology platforms in meaningful patient populations globally. Throughout this period of continued progress, we have demonstrated our ability to operate at a high standard and provide value to shareholders while prudently managing our cash burn.
Primarily driven by an increase in CW 251, and other preclinical research expenses.
Speaker Change: We remain well capitalized and based on our current operating plans, we expect our existing cash resources as of March 31, 2025, when combined with the assumed receipt of Susan anticipated regulatory milestones that will enable us to fund planned operations into the second half of 2020.
Partially offset by reductions in costs on Santa data Bad then indebted bad, but so the tungsten and GW 191, and CW to 'twenty two.
General and administrative expenses was $17 million for the three months ended March 31, 2025, compared to $15 8 million for the same period in 'twenty 'twenty four.
Speaker Change: Seven which should take us through multiple catalysts in our pipeline.
Marilyn due to an increase in stock based compensation expense.
Speaker Change: Additional details on our quarterly results I encourage you to review our earnings release and other SEC filings as available on our website at Www <unk> com.
As of March 31, 2025, we had $321.6 million of cash resources, consisting of cash cash equivalents and marketable securities as compared to $324 $2 million as of December 31, 2024.
Speaker Change: With that I'd like to hand over to our Chief Scientific officer, Dr to pull more.
Leone Patterson: We are also able to manage our cash burn going forward through active review and evaluation of our portfolio and development priorities. With this in mind, and as previously highlighted by our management team, we are committed to an evidence-based approach to pipeline management, where decisions on investment and clinical development are tied to clear clinical and scientific validation.
Speaker Change: Thanks, Lee and good afternoon, everyone.
Speaker Change: Previously mentioned, we are pleased to have attended yet another productive ECR presume works this year with six posters presented by our team.
We remain well capitalized and based on our current operating plans, we expect our existing cash resources as of March 31, 2025, when combined with the assumed receipt of Susan anticipated regulatory milestones will enable us to fund planned operations into the second half of 2020.
Speaker Change: Preclinical data presented across both our innovative multi specific antibodies and BBC programs. It was not just scientific progress.
Speaker Change: <unk> diversification of our R&D strategy.
Leone Patterson: On the research and development front, we are honored to have our wholly owned pipeline represented at AACR annual meeting, with six posters on preclinical data presented across our antibody drug conjugate and T cell engager pipeline. Paul will be taking us through key highlights from these posters later on today's call.
Speaker Change: Among the highlights we are especially encouraged by the preclinical data presented on CW to name our most recent.
Seven which should take us through multiple catalysts in our pipeline.
For additional details on our quarterly results I encourage you to review our earnings release and other SEC filings as available on our website at Www <unk> com.
Speaker Change: Recent A&D nominated oncology candidate with a plan.
Speaker Change: Submissions in the first half of 2026.
Speaker Change: VW to name as a <unk> specific T cell engagement targeting DLL three a protein expressed on the cell surface of small cell lung cancer and other aggressive neuroendocrine tumors.
Speaker Change: With that I'd like to hand over to our Chief Scientific officer, Dr to pull more.
Leone Patterson: We are also looking forward to presenting more preclinical data on our HoliLine pipeline at several upcoming medical conferences in the second quarter, including the American Thoracic Society Annual Meeting, where an abstract has been accepted for ZW1528, our novel IL-4, IL-33 bispecific molecule. We will also be attending ASCO and ESMO, Gynecological Cancer Annual Meetings, where we will be presenting trial and progress posters on ZW171 and ZW191, respectively. Similarly, our partner, Jazz, is also planning to present on these accepted abstracts.
Speaker Change: Once we owning and good afternoon, everyone as.
Speaker Change: This tri specific T cell engaging <unk> incorporate CD 20, Ecu stimulation and has shown potent antitumor activity in preclinical models, including small cell lung cancer.
Speaker Change: As previously mentioned we are pleased to have attended yet another productive ECR presume works this year with six posters presented by our team.
Speaker Change: Breath of preclinical data presented across both our innovative multi specific antibodies and DTC programs. It was not just scientific progress.
Speaker Change: These cancers are notoriously hard to treat and where there's been some success with the approval of per watts them up in small cell lung cancer and showing the benefit of a bi specific approach for solid tumors.
Speaker Change: <unk> diversification of our R&D strategy.
Speaker Change: Clear need for next generation molecules that can improve the standard of care with broader and more durable responses.
Speaker Change: Among the highlights we were especially encouraged by the preclinical data presented on CW to name. Our most recent IMD nominated oncology candidate with a planned <unk>.
Speaker Change: That's where we believe that W. Two and Einsteins.
Speaker Change: We've designed Q&A using our <unk> platform combined with our proprietary is a metric in effect technologies to activate T cells in a more controlled and effective way.
Speaker Change: <unk> submissions in the first half of 2026.
Leone Patterson: On three, sorry, accepted abstracts at ASCO on Xanadatamab, including a four-year follow-up of the five-phase two of Xanadatamab and metastatic DEA, which will provide further understanding of the long-term outcomes and overall survival for Xanadatamab plus chemotherapy in HER2-positive advanced patients with metastatic DEA. This progress is further reflected in our announcement from JAS in April 2025 that the EMEA Committee for Medicinal Products for Human Use, or CHMP, has adopted a positive opinion recommending the approval of Xanadatumab for treatment of advanced HER2 plus biliary tract cancer patients. A final decision is expected in the coming months. Importantly, if approved, this could also represent an opportunity for an increase in royalty revenue for Zymeworks in the near future.
VW to name as a <unk> specific T cell engaging targeting DLL three a protein expressed on the cell surface of small cell lung cancer and other aggressive neuroendocrine tumors.
Speaker Change: A key feature of our design is the obligate nature of CD 20 induced with Citi.
Speaker Change: 28 binding by $209 of course, only in the presence of simultaneous CDC binding.
Speaker Change: This tri specific T cell engaging <unk> incorporate CD 28, co stimulation and has shown potent antitumor activity in preclinical models, including small cell lung cancer.
Speaker Change: This is shown clearly in the top left panel where control mode.
Speaker Change: Either CDP or CD 20, CD 28 binding nor do demonstrate the CD 20 years contribution is conditional on CDP engagement.
Speaker Change: These cancers are notoriously hard to treat and where there's been some success with the approval of per watts them up in small cell lung cancer and showing the benefit of a bi specific approach for solid tumors. There is a clear need for next generation molecules that can improve the standard of care with broader and more durable responses.
Speaker Change: This will bleed co stimulation limits potential for unwanted T cell cross linking or Fructoside, an important safety and specificity advantage over <unk>.
Speaker Change: Thus far we believe that W. Two and Einsteins.
Speaker Change: The more the obligate nature of tumor engagement.
Speaker Change: We've designed <unk> using our <unk> platform combined with our proprietary is a metric in effect technologies to activate T cells in a more controlled and effective way.
Speaker Change: L. Three ensures that two nine's activity is precisely focused where it's needed.
Speaker Change: Additional data in a poster further supports the specificity.
Speaker Change: What's particularly encouraging is the strength and durability of response were seeing in preclinical models.
Speaker Change: A key feature of our design is the obligate nature of CD 20 engagement CD.
Leone Patterson: We are also looking forward to the upcoming presentation by J&J at ASCO, highlighting their Phase 1 data for a bispecific T-cell engager engineered utilizing an asymmetric platform targeting a novel target, KLK2, a metastatic castration-resistant prostate cancer. Some of you may have seen the preliminary data at AACR last week, and we're encouraged by the early clinical activity and safety profile observed to date. It's rewarding to see this program move forward, especially with such a difficult-to-treat patient population in need of novel targets. As a reminder, under the terms of the agreement in place with J&J for this product, the company remains eligible to receive development milestones of up to $86 million, commercial milestone payments of up to $373 million, and mid-single-digit royalties on commercial sales.
Speaker Change: Shown in the Middle 12 panel. The addition of CD 20 enhances T cell fitness and robustness in the presence of TLLP positive tumor cells.
Speaker Change: CD 28 binding by $2 million of course, only in the presence of simultaneous CDC binding.
Speaker Change: This is shown clearly in the top left panel where control mode, who's with either <unk> or CD 20, CD 28 binding nor do demonstrate the CD 20 years contribution is conditional on CDP engagement.
Speaker Change: Compared to control molecules locking CD 20 engagement.
Speaker Change: Versus the clinical benchmark, AMG 757 or to let them up Q&A and provides more sustained tumor cytotoxicity across repeated rounds of stimulation, which is accompanied by expansion of T cells with memory phenotype.
Speaker Change: This will bleed co stimulation limits potential for unwanted T cell cross linked to our practices and important safety and specificity advantage over <unk>.
Speaker Change: Under the more stringent conditions of low effector to target of issues. The biological impact of two names mediated T cell activation and co stimulation is reflected in the enhanced tumor cytotoxicity across a range of TLLP Express model cell lines as shown in the bottom left hand panel.
Speaker Change: Furthermore, the obligate nature of tumor engagement via DLL three ensures that two nine's activity is precisely focused where it's needed additional.
Speaker Change: Additional data in a poster further supports the specificity.
Speaker Change: What's particularly encouraging is the strength and durability of response, we're seeing in preclinical models.
Speaker Change: Year to $9 outperformed benchmark controls, including for load them up.
Speaker Change: And in the Middle Top panel. The addition of CD 20 enhances T cell fitness and robustness in the presence of TLLP positive tumor cells.
Speaker Change: T cell bi.
Specific.
Speaker Change: Those two guys CLO <unk> CD 137 try specific.
Speaker Change: Compared to control molecules locking CD 20 engagements and versus the clinical benchmark AMG 757 or to let them up Q&A and provides more sustained tumor cytotoxicity across repeated rounds of stimulation, which is accompanied by expansion of T cells with memory phenotype.
Speaker Change: <unk> studies in xenograft models of <unk> positive tumors and drafted either with human <unk>.
Leone Patterson: Turning to our financial position this afternoon, Zymeworks reported financial results for the first quarter of 2025. Zymeworks net loss for the three months ended March 31, 2025, was $22.6 million compared to a net loss of $31.7 million for the same period in 2024. The decrease in net loss was primarily due to an increase in revenue, which was partially offset by an increase in operating expenses, an increase in income tax expense, and a decrease in interest income. As reported, our revenue for the three months ended March 31, 2025, was $27.1 million, compared to $10 million for the same period in 2024.
Speaker Change: Or add mix with naive human T cells.
Speaker Change: $2 nine exhibits anti tumor activity with evidence of enhanced antitumor activity relative to a lot of them.
Speaker Change: Beyond the data shown here, our ACR poster further characterize the safety profile of Q&A incorporating results from a dedicated most model of cytokine release syndrome complementary in vitro silicon <unk> and studies conducted in non human primates.
Speaker Change: Under the more stringent condition of low effector to targa issues. The biological impact of two names mediated T cell activation and co stimulation is reflected in the enhanced tumor cytotoxicity across a range of DLL three expressing model cell lines as shown in the bottom left hand panel.
Speaker Change: In the non human Primate studies repeat dosing of <unk> was well tolerated and tuna and demonstrated an antibody like pharmacokinetic profile.
Speaker Change: Year to $9 outperformed benchmark controls, including for load them up.
Speaker Change: Characteristics that can be associated with more predictable behavior in clinical settings.
Speaker Change: T cell bi specific.
Speaker Change: Those two guys CLO <unk> CD 137 try specific.
Speaker Change: Taken together these data reinforce the significance of the CD 20 arm and driving deeper and more durable T cell responses, while maintaining stringent control and safety to blicket engagement with T cells, and CLO <unk> expressing tumor cells.
Leone Patterson: Revenue for the three months ended March 31, 2025 included $14 million of milestone revenue from GSK in relation to a clinical milestone under our 2016 Platform Technology Transfer and License Agreement. $3.1 million of milestone revenue from Daiichi Sankyo following the first patient dose and the clinical trial related to our 2018 license agreement. $9.6 million for the development support and Drug supply revenue in addition to the $0.2 million of royalty income from JAS and $0.2 million of drug supply revenue from Beijing. These achievements underscore the strength of our foundational partnerships and the relevance of our platform across multiple products moving into clinical development by our partners.
Speaker Change: Efficacy studies in xenograft models of <unk> positive tumors and drafted either with human <unk>.
Speaker Change: Our admixed with naive human T cells.
Speaker Change: Cited about the trajectory of <unk> as we work towards IND submission in the first half of 2026.
Speaker Change: $2 nine exhibits anti tumor activity with evidence of enhanced antitumor activity relative to a lot of them.
Speaker Change: And our early R&D programs, we continue to focus on novel targets and customized modalities that we believe offer meaningful opportunities for therapeutic innovation.
Speaker Change: Beyond the data shown here, our ACR poster further characterize the safety profile of <unk> incorporating results from a dedicated most model of cytokine release syndrome.
Speaker Change: Two of these EDC programs revealed the ECR focus on <unk> and PTK seven both tumor associated antigens with limited expression in normal tissues, and broad relevance across difficult to treat solid tumors.
Speaker Change: Upon entry in vitro silicon <unk> and studies conducted in non human primates.
Speaker Change: In the non human Primate studies repeat dosing of <unk> was well tolerated and tuna and demonstrate an antibody like pharmacokinetic profile.
Speaker Change: Victor risks that can be associated with more predictable behavior in clinical settings.
Speaker Change: Well, we havent provided guidance on AMD timelines for these programs. We continue to explore opportunities on hold went to advance these programs either internally or through social collaborations.
Speaker Change: Taken together these data reinforce the significance of the CD 20 arm and driving deeper and more durable T cell responses, while maintaining stringent control and safety.
Leone Patterson: We are also hopeful that continued development by our collaboration partners will provide a future source of revenues for us. These revenues also reflect growing momentum for ZAHERA and demonstrate the value of our partnership strategy in expanding patient reach while helping us improve our financial efficiency. Overall, operating expenses were $52.7 million for the three months ended March 31, 2025, compared to $47.3 million for the same period in 2024, representing increase of 10%. Research and development expense was $35.7 million for the three months ended March 31, 2025, compared to $32 million for the same period in 2024.
Speaker Change: For those of you less familiar <unk> is over expressed in multiple indications of high unmet need including non small cell lung cancer triple negative breast cancer.
Speaker Change: Engagement of both T cells, and CLO <unk> expressing tumor cells.
Speaker Change: We're excited about the trajectory of <unk> as we work towards IND submission in the first half of 2026.
Speaker Change: Net cancer and Gi cancers.
Speaker Change: Notably licensee as expressed in the majority of patient samples across these indications.
Speaker Change: And our early R&D programs, we continue to focus on novel targets and customized modalities that we believe offer meaningful opportunities for therapeutic innovation.
Speaker Change: Suggesting a potential for broad applicability, while maintaining target specificity.
Speaker Change: Clinical validation of licensee Anthony the target has been reported by clinical stage Brent benchmark.
Speaker Change: Two of these EDC programs revealed the ECR focus on <unk> and PTK seven both tumor associated antigens with limited expression in normal tissues, and broad relevance across difficult to treat solid tumors.
Speaker Change: L Y E $59 53, and <unk> dollars four based EDC from genetic.
Speaker Change: Breast cancer, and non small cell lung cancer.
Speaker Change: We havent provided guidance on IMD timelines for these programs, we continue to explore opportunities on hold went to advance these programs either internally or through social collaborations.
Speaker Change: <unk> hundred seven which targets <unk> <unk> utilizes <unk> novel.
Speaker Change: <unk> hundred 90, <unk> with a drug antibody ratio of eight which.
Speaker Change: For those of you less familiar <unk> is over expressed in multiple indications of high unmet need including non small cell lung cancer triple negative breast cancer head and neck.
Speaker Change: Which enables strong cytotoxicity.
Leone Patterson: primarily driven by an increase in ZW251 and other preclinical research expenses. Partially offset by reductions in costs on Xenodatabab, Xenodatabab Servototin, NGW-191, NGW-221. General and administrative expenses was $17 million for the three months ended March 31, 2025, compared to $15.8 million for the same period in 2024, primarily due to an increase in stock-based compensation expense. As of March 31, 2025, we had $321.6 million of cash resources consisting of cash, cash equivalents, and marketable securities, as compared to $324.2 million as of December 31, 2024.
Speaker Change: A range of solid tumor indications.
Speaker Change: Consistent with our general approach to ADC designed and care also in selection of antibodies targeting arm.
Speaker Change: Cancer and Gi cancers.
Speaker Change: Notably licensee as expressed in the majority of patient samples across these indications.
Speaker Change: 3% to seven utilizes a novel humanized IGT, one antibody, which exhibits markedly superior licensee binding internalization and spirit penetration relative to the ICT six antibody and corporate in the prior clinical stage program.
Speaker Change: Suggesting a potential for broad applicability, while maintaining target specificity.
Speaker Change: Clinical validation of <unk>, Anthony VC target has been reported by clinical stage Brent benchmark.
Speaker Change: L Y E $59 53, and <unk> dollars four based EDC from genetic.
Speaker Change: As shown on the right three to seven has demonstrated consistent and beetroot target specificity specific set of toxicities across multiple cancer types.
Speaker Change: Breast cancer, and non small cell lung cancer.
Speaker Change: This activity is observed in these broad range of indications and is consistently superior to the benchmark with a likewise improvement also observed in xenograft models in vivo.
Speaker Change: <unk> hundred seven which targets FY <unk> utilizes <unk> novel.
Speaker Change: $650 <unk> with a drug antibody ratio of eight.
Speaker Change: These findings underscore the potential of <unk> to deliver more consistent and deeper response, and <unk> expressing cancers, regardless of baseline expression levels and important consideration given the heterogeneity often seen in tumors.
Which enables strong side of toxicity.
Speaker Change: Cross a range of solid tumor indications.
Speaker Change: Consistent with our general approach to ADC designed and care also in selection of antibodies targeting arm.
Leone Patterson: We remain well capitalized, and based on our current operating plans, we expect our existing cash resources as of March 31, 2025, when combined with the assumed receipt of certain anticipated revenue milestones, will enable us to fund planned operations in the second half of 2027, which should take us through multiple catalysts in our pipeline.
Speaker Change: 3% to seven utilizes a novel humanized IGT, one antibody, which exhibits markedly superior licensee binding internalization and spirit penetration relative to the ICT six antibody and corporate in the prior clinical stage program.
Speaker Change: On the safety side.
Speaker Change: Two seven was well tolerated in a non GOP tox study in nonhuman primate exposure levels.
Speaker Change: Exceeded those projected to be efficacious and the maximum tolerated dose was established out of <unk>.
Speaker Change: Or above 60 mix per kg.
Speaker Change: As shown on the right three to seven has demonstrated consistent in vitro targeted specificity specific set of toxicity across multiple cancer types.
Speaker Change: Observe clinical effects.
Speaker Change: We're limited to transit reductions in body weight and food intake post dosing for few serious adverse events.
Leone Patterson: For additional details on our quarterly results, I encourage you to review our earnings release and other SEC filings as available on our website at www.zymeworks.com.
Speaker Change: This activity is observed in these broad range of indications and is consistently superior to the benchmark with a likewise improvement also observed in xenograft models in vivo.
Speaker Change: Altogether. These data build a compelling case for <unk> seven is a differentiated therapeutic candidate targeting <unk> and a first in class opportunity for <unk>.
Paul Moore: With that, I'd like to hand over to our Chief Scientific Officer, Dr. Paul Moore. Thanks, Leone, and good afternoon, everyone. As previously mentioned, we are pleased to have attended yet another productive AACR for Zymeworks this year, with six posters presented by our team. The breadth of preclinical data presented across both our innovative multi-specific antibodies and DVC programs highlights not just scientific progress, but the thoughtful diversification of our R&D strategy. Among the highlights, we're especially encouraged by the preclinical data presented on ZW209, our most recent IND-nominated oncology candidate with a planned IND submission in the first half of 2026.
Speaker Change: Moving onto slide 12, PTK seven is a transmembrane protein that is over expressed in a range of solid tumors, including non small cell lung triple negative breast ovarian esophageal colorectal head and neck and cervical cancers.
Speaker Change: These findings underscore the potential of 3% to 7% to deliver more consistent and deeper response, and <unk> expressing cancers, regardless of baseline expression levels and important consideration given the heterogeneity often seen in tumors.
Speaker Change: Previous clinical data with <unk> seven targeting ADC.
Speaker Change: On the safety side 327 was well tolerated in a non GOP tox study in non human primate exposure levels exceeded exceeded those projected to be efficacious and the maximum tolerated dose was established that are at or above 60 mix per kg.
Speaker Change: A demonstrated evidence of anti.
Speaker Change: Tumor activity, albeit limited and several of these indications reinforcing <unk> seven is a validated <unk> ADC target.
Speaker Change: Structurally <unk> seven offers a large multi domain extrasolar region that enables the development of antibodies against distinct non <unk> epitopes and the opportunity to develop <unk> as a solution to enhance payload delivery.
Speaker Change: Observe clinical effects.
Speaker Change: We're limited to transit reductions in body weight and food intake post dosing with no serious adverse events.
Speaker Change: Altogether. These data build a compelling case for <unk> hundred seven is a differentiated therapeutic candidate targeting <unk> and a first in class opportunity for <unk>.
Speaker Change: Depending on the target antigen modal power topic, Pdc's may not deliver as much payload into cancer cells <unk> <unk>.
Paul Moore: ZW209 is a trispecific T cell engager targeting DLL3, a protein expressed on the cell surface of small cell lung cancer and other aggressive neuroendocrine tumors. This trispecific T cell engager incorporates CD28 co-stimulation and has shown potent anti-tumor activity in preclinical models, including small cell lung cancer. These cancers are notoriously hard to treat, and while there's been some success with the approval of perlatumab in small cell lung cancer, ensuring the benefit of a bi-specific approach for solid tumors, there is a clear need for next generation molecules that can improve the standard of care with broader and more durable responses.
Speaker Change: Moving onto slide 12, PTK seven is a transmembrane protein that is over expressed in a range of solid tumors, including non small cell lung triple negative breast ovarian esophageal colorectal head and neck and cervical cancers.
Speaker Change: This may have contributed to the modest activity.
Speaker Change: Previous PTK seven targeting ADC.
Speaker Change: Thus opening the door to byproduct shopping formats and other modular based approaches including next generation ADC targeting <unk> seven.
Speaker Change: <unk> clinical data with <unk> seven targeting ADC.
Speaker Change: Byproduct topic antibodies over several advantages over traditional mono mono power topic designs, but.
Speaker Change: <unk> demonstrated evidence of anti.
Speaker Change: Tumor activity, albeit limited and several of these indications reinforcing <unk> seven is a validated <unk> ADC target.
Speaker Change: Binding two distinct sales in the same antigen that can enhance receptor clustering increased cell surface retention and prove internalization, but those that are particularly important in EDC design. These.
Speaker Change: Structurally <unk> seven offers a large multi domain extrasolar region that enables the development of antibodies against distinct non op are lapping epitopes and the opportunity to develop by power topic Bdcs as a solution to enhance payload delivery.
Paul Moore: That's where we believe ZW209 stands out. We've designed 209 using our Tri-TCE CoStim platform, combined with our proprietary asymmetric and effect technologies to activate T-cells in a more controlled and effective way. A key feature of our design is the obligate nature of CD28 engagement. CD28 binding by 209 occurs only in the presence of simultaneous CD3 binding. This is shown clearly in the top left panel for control molecules with either CD3 or CD28 binding knocked out, demonstrate that CD28's contribution is conditional on CD3 engagement. This obligate co-stimulation limits potential for unwanted T cell cross-linking or fracticide, an important safety and specificity advantage of our tri-TCE platform.
Speaker Change: These properties could translate to more efficient pillow delivery increased cytotoxicity and increased cytotoxicity in tumor cells.
Speaker Change: Importantly, he brings deep experience in designing developing and advancing byproducts apprehensive voice.
Speaker Change: Depending on the target antigen modal power topic, Pdc's may not deliver as much payload into cancer cells as bipolar topic Adcs and this may have contributed to the modest activity seen with previous PTK seven targeting ADC.
Speaker Change: Work was done a data hub.
Speaker Change: On a date him up a bipolar topic her two targeting antibody has demonstrated meaningful clinical activity and valid validated the potential.
Speaker Change: Thus opening the door to byproduct shopping formats and other modular based approaches including next generation ADC targeting <unk> seven.
Speaker Change: Bipolar topic approaches as well as providing clinical validation for our proprietary user metric platform not just from a biological standpoint, but also in terms of manufacture ability.
Speaker Change: Byproduct topic antibodies offer several advantages over traditional mono mono power topic designs.
Speaker Change: This gives us confidence that our bipolar topic <unk> <unk> PVC program <unk>.
Speaker Change: Can benefit from both proven mechanistic advantages and our deep experience and utilizing our established scalable platform.
Speaker Change: Binding two distinct sites and the same antigen that can enhance receptor clustering increased cell surface retention and prove internalization, but those that are particularly important in EDC design.
Speaker Change: In preclinical studies, we've observed improved antibody binding and higher internalization and PTK seven expressing sell lengths compared to conventional formats. This enhanced uptake has resulted in greater payload delivery and corresponding cytotoxicity activity supporting the value of byproduct topic targeting in this context.
Paul Moore: Furthermore, the obligate nature of tumor engagement via DLL-3 ensures that 209's activity is precisely focused where it's needed. What's particularly encouraging is the strength and durability of the response we're seeing in preclinical models. As shown in the middle top panel, the addition of CD28 enhances T cell fitness and robustness in the presence of DLL3-positive tumor cells. Compared to control molecules lacking CD28 engagement and versus the clinical benchmark, AMG757, or teladimab, 209 provides more sustained tumor cytotoxicity across repeated rounds of stimulation, which is accompanied by expansion of T cells with memory phenotypes. Under the more stringent condition of low effector-to-target ratios, the biological impact of 209's mediated T cell activation and co-stimulation is reflected in the enhanced tumor cytotoxicity across a range of DLL3-expressing model cell lines, as shown in the bottom left-hand path.
Speaker Change: These properties can translate to more efficient payload delivery increased cytotoxicity and increased cytotoxicity in tumor cells.
Speaker Change: Importantly, he brings deep experience in designing developing and advancing byproducts apprehensive voice through our <unk>.
Speaker Change: Work was done in <unk>.
Speaker Change: <unk> a bipolar topic her two targeting antibody has demonstrated meaningful clinical activity and valid validated the potential of bipolar topic approaches as well as providing clinical validation for our proprietary <unk> metric platform not just from a biological standpoint, but also in terms of manufacture ability.
Speaker Change: From a pharmacokinetic and Tolerability standpoint, the theater are also compelling and non human primates are <unk> seven byproducts Arthur <unk> was well tolerated at doses up to 60 mix per gig no mortality or adverse clinical signs were observed in.
Speaker Change: And any change in hematology or chemistry were minor in transit.
Speaker Change: I'll make the effects were consistent with expected classifieds and not considered dose limited.
Speaker Change: This gives us confidence of our byproducts of a <unk> seven CVC program <unk>.
Speaker Change: Can benefit from both proven mechanistic advantages and our deep experience in utilizing our established scalable platform.
Speaker Change: These findings suggest that our bipolar topic ADC may offer a differentiated profile, particularly in tumors, where <unk> is broadly expressed where internalization has historically been a limiting factor. We look forward to continued optimization work and evaluating this approach across relevant clinical model preclinical models.
Speaker Change: In preclinical studies, we've observed improved antibody binding and higher internalization and PTK seven expressing sell lengths compared to conventional formats. This enhanced uptake has resulted in greater payload delivery and corresponding cytotoxicity activity supporting the value of byproduct topic targeting in this context.
Speaker Change: Lastly, moving onto a poster presentation on.
Speaker Change: GW 171, amuses Fulin targeting T cell <unk>, demonstrating enhanced safety and antitumor activity in a range of music <unk> expressing cancers as.
Paul Moore: Here, 209 outperformed benchmark controls, including Trolatomab, BIT-Cell, Bi-Specific. Roast two guys, DLL3CD3CD137, tri- Efficacy studies in xenograft models of DLL3-positive tumors engrafted either with human PBMCs or admixed with naive human T-cells. 209 exhibits anti-tumor activity with evidence of enhanced anti-tumor activity relative to erlatum. Beyond the data shown here, our AACR poster further characterizes safety profile of 209, incorporating results from a dedicated mouse model of cytokine release syndrome, complementary and in vitro cytokine release assays, and studies conducted in non-human primates. In the non-human primate studies, repeat dosing at 10 mg per kg was well tolerated, and 209 demonstrated an antibody-like pharmacokinetic profile, a characteristic that can be associated with more predictable behavior in clinical settings.
Speaker Change: From a pharmacokinetic and Tolerability standpoint, the theater are also compelling and non human primates are <unk> seven byproducts Arthur <unk> was well tolerated at doses up to 60 mix per gig no mortality or adverse clinical signs were observed in any change in hematology or chemistry were minor in transit.
Speaker Change: As you know we have reported the first patient dosed in October 'twenty 'twenty four for our first in human Phase one trial, which is continuing to accrue across sites in the U S UK and South Korea, and I'll touch on the ongoing trial and a couple of slides.
Speaker Change: Wake effects were consistent with expected classified and not considered dose limited.
Speaker Change: 171 is engineered with a lower affinity CD three binding arm, which is designed to reduce the likelihood of indiscriminate T cell activation and cytokine release.
Speaker Change: These findings suggest our byproducts, helping ADC may offer a differentiated profile, particularly in tumors, where <unk> is broadly expressed where internalization has historically been a limiting factor. We look forward to continued optimization work and evaluating this approach across relevant clinical model preclinical models.
Speaker Change: Especially in the absence of high <unk> expression.
Speaker Change: Many T cell engages with high CD three affinity like earlier generation, one plus one formats of triggered systemic crs because they activate T cells, even when target engagement. This week are off tumor.
Speaker Change: Lastly, moving onto a poster presentation on.
Speaker Change: In head to head preclinical comparisons when southern one has demonstrated superior cytotoxicity versus other next generation mesothelin targeting by specifics.
Speaker Change: GW 171, amuses Fulin targeting T cell engagement, demonstrating enhanced safety and antitumor activity in a range of music <unk> expressing cancers. As you know we have reported the first patient dosed in October 'twenty 'twenty four for our first in human Phase one trial, which is continuing to accrue across sites in the U S UK and South Korea.
Speaker Change: Importantly, this enhanced tumor cell, killing comes with improved selectivity.
Paul Moore: Taken together, these data reinforce the significance of the CD28 arm in driving deeper and more durable T cell responses, while maintaining stringent control and safety through obligate engagement of both T cells and DLL3-expressing tumors. We're excited about the trajectory of 209 as we work towards IND submission in the first half of 2026.
Speaker Change: Observe reduced non specific T cell binding relative to other programs. In this space are features that may contribute to a more favorable safety profile.
Speaker Change: Touch on the ongoing trial and a couple of slides.
Speaker Change: In the Middle column, you can see the 171 exhibits selective and high affinity binding to tumor cells expressing high.
Speaker Change: 171 is engineered with a lower affinity CD three binding arm, which is designed to reduce the likelihood of indiscriminate T cell activation and cytokine release, especially in the absence of high <unk> expression.
Speaker Change: Levels of Mesothelin, while showing minimal binding to cells with Louisa field expression.
Paul Moore: In our earlier R&D programs, we continue to focus on novel targets and customized modalities that we believe offer meaningful opportunities for therapeutic innovation. Two of these ADC programs revealed at AACR focus on Y6E and PTK7, both tumor-associated antigens with limited expression in normal tissues and broad relevance across difficult-to-treat solid tumors. While we haven't provided guidance on I&D timelines for these programs, we continue to explore opportunities on how and when to advance these programs, either internally or through thoughtful collaboration. For those of you less familiar, Ly6C is overexpressed in multiple indications of high unmet need, including non-small cell lung cancer, triple negative breast cancer, head and neck cancer, and GI cancer.
Speaker Change: Importantly, 171 maintains liquidity for CDP, which is a deliberate design choice to reduce off target T cell activation improve safety.
Speaker Change: Many T cell engages with high CD three affinity like earlier generation, one plus one formats of triggered systemic crs because they activate T cells, even when target engagement. This week are off tumor and.
Speaker Change: This profile underscores <unk> ability to preferentially target tumors, while sparing normal tissues with minimal use of stealing expression.
Speaker Change: Moving to the cytotoxicity data on the right 171 continues to demonstrate potent and selective tumor cell, killing and hi, <unk>, hi settings, but not in low <unk> expressing cells compared to benchmark molecules, including <unk>.
Speaker Change: In head to head preclinical comparisons when southern one has demonstrated superior cytotoxicity versus other next generation mesothelin targeting by specifics.
Speaker Change: Importantly, this enhanced tumor cell, killing comes with improved selectivity.
Speaker Change: Observe reduced non specific T cell binding relative to other programs. In this space are features that may contribute to a more favorable safety profile.
<unk> hundred five Cte 95, and the June G by specific competitor.
Speaker Change: W. 171 hundred 71 consistently shows equal or superior cytotoxicity across a panel of tumor selling with varying levels of music feeling expression, particularly at low effector to target ratios, which more reflects more closely reflects conditions in the tumor microenvironment.
Speaker Change: In the Middle column, you can see the 171 exhibits selective and high affinity binding to tumor cells expressing high <unk>.
Speaker Change: Levels of Mesothelin or showing minimal binding to cells with Louisa field expression.
Paul Moore: Notably, Lysak-C is expressed in the majority of patient samples across these indications. Suggesting a potential for broad applicability while maintaining target specific. Clinical validation of Y6C and an ADC target has been recorded by clinical stage benchmark DLYE5953A and MMAEE-STAR4-based ADC from Genentech in breast cancer and non-small cell lung cancer. 327, which targets Y6E, utilizes Zymeworks' novel 6519 payload with a drug-antibody ratio of 8, which enables strong cytosolicity across a range of solid tumor indicators. Consistent with our general approach to ADC design, and care also in selection of the antibody targeting arm, 327 utilizes a novel humanized IgG1 antibody, which exhibits markedly superior Lysic-C binding, internalization, and spheroid penetration relative to the Lysic-6 antibody incorporated in the prior clinical stage program.
Speaker Change: Importantly, 171 maintains liquidity for CDP, which is a deliberate design choice to reduce off target T cell activation improve safety.
Speaker Change: As you can see on the left hand side of this slide and the last panel of tumor cell lines, including those that shed soluble mesothelin 171, mid teen strong anti tumor potency.
Speaker Change: This profile underscores <unk> ability to preferentially target tumors, while sparing normal tissues with minimal resist doing expression.
Speaker Change: Moving to the cytotoxicity data on the right 171 continues to demonstrate potent and selective tumor cell, killing and hi, <unk>, hi settings, but not in law mesothelin expressing cells compared to benchmark molecules, including <unk>.
Speaker Change: Notably no correlation was observed between the amount of shared Mesothelin and 170, <unk> efficacy underscoring the robustness of its mechanism of action. These findings support our hypothesis that our two plus one design. So since activity in the presence of shared mesothelin through ability dependent mesothelin binding when high expressing tumor cells.
Speaker Change: AMG 305, Cte 95, and the June <unk> by specific competitor.
Speaker Change: What also stands out as depicted in the graph on the right hand side of the slide is the 171 also demonstrated cytotoxicity T cell activation and silicon beliefs, and more complex translational relevant patient derived xenograft models, continuing endogenous tumor infiltrating lymphocytes as well as in vivo xenograft models.
Speaker Change: DSW 170, 171 consistently shows equal or superior cytotoxicity across a panel of tumor cell lines with varying levels of music feeling expression, particularly at low effector to target ratios, which more reflects more closely reflects conditions in the tumor microenvironment.
Speaker Change: These data support further the potential of 170 <unk> to drive meaningful responses and music feeling expressed in tumors.
Speaker Change: As you can see on the left hand side of this late in a large panel of tumor cell lines, including those that shed soluble mesothelin 171 maintained strong antitumor potency.
Speaker Change: Too early and challenging tumor microenvironment.
Speaker Change: Together these data reinforce our confidence in 170 ones potential to deliver meaningful therapeutic benefit while demonstrating a favorable tolerability profile.
Paul Moore: As shown on the right, T27 has demonstrated consistent in vitro target-specific cytotoxicity across multiple cancer types. This activity is observed in these broad range of applications and is consistently superior to the benchmark, with a likewise improvement also observed in xenograft models in vivo. These findings underscore the potential of 327 to deliver more consistent and deeper response in Lys-Xe expressing cancers, regardless of baseline expression levels, an important consideration given the heterogeneity often seen in tumors. On the safety side, 327 was well tolerated in a non-GLP tox study in non-human primates, exposure levels exceeded those projected to be efficacious, and the maximum tolerated dose was established at or above 60 mg per kg.
Speaker Change: Notably no correlation was observed between the amount of shared Mesothelin and 170, <unk> efficacy underscoring the robustness of its mechanism of action. These findings support our hypothesis that our two plus one design sustained activity in the presence of shared mesothelin through avidity dependent mesothelin binding when high <unk> expressing tumor cells.
Speaker Change: With a phase one clinical trials in mind, both studies for 171, and 191 remain on track and are recruiting well across sites. This slide highlights the breakdown of currently activating clinical sites by geographic region. Our global clinical trial footprint is a key component of our strategy to move efficiently through early development.
Speaker Change: What also stands out as depicted in the graph on the right hand side of the slide is the 171 also demonstrated cytotoxicity T cell activation and silicon beliefs and more complex translation the relevant patient derived xenograft models, continuing endogenous tumor infiltrating lymphocytes as well as in vivo xenograft models.
Speaker Change: By engaging sites across multiple geographies within and outside the United States, we're able to maintain momentum and enrollment while optimizing the use of clinical supply and supporting streamlined operational execution.
Speaker Change: These data support further the potential of 170 <unk> to drive meaningful responses and music feeling expressing tumors.
Leone: Looking ahead, we do plan to present trial in progress posters for both <unk>, one and one name one at upcoming peer reviewed medical conferences in the second quarter as Leone mentioned earlier.
Speaker Change: Too early and challenging tumor microenvironment.
Speaker Change: Together these data reinforce our confidence in 170 ones potential to deliver meaningful therapeutic benefit while demonstrating a favorable tolerability profile.
Paul Moore: Observe clinical effects. We're limited to transient reductions in body weight and food intake post-dosing for food-serious adversity. Altogether, these data built a compelling case for P27 as a differentiated therapeutic candidate targeting Y-succeed and a first-in-class opportunity for Zymeworks.
Leone: And with that I will hand over to <unk> to conclude conclude todays call and open up the call for Q&A.
Speaker Change: With a phase one clinical trials in mind, both studies for 171, and 191 remain on track and are recruiting well across sites. This slide highlights the breakdown of currently activated clinical sites by geographic region. Our global clinical trial footprint is a key component of our strategy to move efficiently through early development.
Leone: Thank you Paul and good afternoon, everyone.
Speaker Change: We hope our markman on today's call. It is very clear that our R&D organization continues to deliver on our core mandate.
Paul Moore: Moving on to slide 12, PTK7 is a transmembrane protein that is overexpressed in a range of solid tumors, including non-small cell lung, triple negative breast, ovarian, esophageal, colorectal, head and neck, and cervical cancer. Previous clinical data with PTK7 targeting ADCs have demonstrated evidence of anti-tumor activity, albeit limited, in several of these indications, reinforcing PTK7 as a validated ADC target. Structurally, PTK7 offers a large multi-domain extracellular region that enables the development of antibodies against distinct non-overlapping epitopes and the opportunity to develop biparatopic ADCs as a solution to enhance payload delivery. Depending on the target antigen, monoparatopic ADCs may not deliver as much payload into cancer cells as biparatopic ADCs, and this may have contributed to the modest activity seen with previous PTK7-targeting ADCs, thus opening the door to biparatopic formats and other modular-based approaches, including next-generation ADCs targeting PTK7.
Speaker Change: The pipeline route into translational science and focused on meaningful clinical outcome, while providing multiple near term catalysts for potential shareholder value creation.
Speaker Change: By engaging sites across multiple geographies within and outside the United States, we're able to maintain momentum and enrollment while optimizing the use of clinical supply and supporting streamlined operational execution.
Speaker Change: The second poster presentations at ACR. This year reflect the depth of that work spanning early and mid stage candidates across multiple modalities. This includes our multi specific on ADC platforms, which are enabling us to target a diverse set of tumor antigen with increasingly refined approaches.
Speaker Change: Looking ahead, we do plan to present trial in progress posters for both <unk>, one and 191 at upcoming peer reviewed medical conferences in the second quarter as Leone mentioned earlier.
Speaker Change: We remain on track to submit our IND for TWC 51 by mid 2005 and important milestone for that program and for our broader strategy of building a portfolio with a potential to address unmet needs across the quality and immunology.
Speaker Change: And with that I will hand over to Ken to conclude conclude todays call and open up the call for Q&A.
Speaker Change: Our focus on execution also central leadership.
Ken: Thank you Paul and good afternoon, everyone.
Speaker Change: We welcome doctors to be Mccann, as our senior Vice President clinical development.
Ken: We hope our markman on today's call is very clear that our R&D organization continues to deliver on our core mandate.
Speaker Change: Her experience across hematology oncology in both academic and industry studies with Gilead, Daiichi Sankyo, and Bristol Myers Squibb.
Ken: Our pipeline route into translational clients and focus on meaningful clinical outcome, while providing multiple near term catalysts for potential shareholder value creation.
Speaker Change: We will support our clinical stage count and help shape, our global development and regulatory strategy.
Ken: The second poster presentations at ACR. This year reflect the depth of that work spanning early and mid stage candidates across multiple modalities. This includes our multi specific on ADC platforms, which are enabling us to target a diverse set of tumor antigen with increasingly refined approaches.
Speaker Change: After adjustments to join the Nymex in 2023 will continue to serve as executive VP.
Paul Moore: Biparatopic antibodies offer several advantages over traditional monoparatopic designs. By binding two distinct sites in the same antigen, they can enhance receptor clustering, increase cell surface retention, improve internalization, factors that are particularly important in ADC design. These properties can translate to more efficient payload delivery, increased cytotoxicity, and increased cytotoxicity in tumors. Importantly, we bring deep experience in designing, developing, and advancing biparatopic antibodies through our work with ZanaDataMap. ZanaDataMap, a biparatopic HER2 target antibody, has demonstrated meaningful clinical activity and validated the potential of biparatopic approaches, as well as providing clinical validation for our proprietary isometric platform, not just from a biological standpoint, but also in the terms of manufacturability.
Speaker Change: Ammo or at least our emerging R&D portfolio, and autoimmune and inflammatory diseases as well as our global clinical development operations.
Barbara Schafer: In addition, Barbara Schafer, who joined <unk> in 2004 has been promoted to senior Vice President of clinical development operations.
Ken: We remain on track to submit our IND for TWC 51 by mid 2005 and important milestone for that program and for our broader strategy of building a portfolio with a potential to address unmet needs across oncology and immunology.
Barbara Schafer: Gather they will play a pivotal role in shaping the clinical development strategy for our portfolio to support our advancing pipeline.
Ken: Our focus on execution also extended our leadership in April we welcomed Dr. Sabine Mccann as our senior Vice President clinical development.
Barbara Schafer: Financially, we remain well capitalized with $321 6 million in cash and equivalents at the end of the first quarter and projected runway into the second half of 2027, when our existing path versus the combined was assumed receipt of certain anticipated regulatory milestones.
Ken: Our experienced across hematology oncology in both academic and industry studies with Gilead, Daiichi Sankyo, and Bristol Myers Squibb.
Barbara Schafer: Our lower cash operating burn for the first quarter was aided by clinical progress made by our partner.
Ken: We will support our clinical stage count and help shape, our global development and regulatory strategy.
Barbara Schafer: Platform partnerships are a core part of our strategy to broaden patient impact while maintaining capital efficiency and we are encouraged by the momentum our partners generate.
Ken: Dr. Jeff Smith, who joined <unk> in 2023, while continuing to serve as executive VP and CMO, where he leads our emerging R&D portfolio and autoimmune and inflammatory diseases as well as our global clinical development operations and.
Paul Moore: This gives us confidence that our biparatopic PTK7 ADC program can benefit from both proven mechanistic advantages and our deep experience in utilizing our established scalable platform. In preclinical studies, we've observed improved antibody binding and higher internalization in PTK7-expressing cell lines compared to conventional formats. This enhanced uptake has resulted in greater payload delivery and corresponding cytotoxicity activity, supporting the value of biparatopic targeting in this context. From a pharmacokinetic and tolerability standpoint, the data are also compelling. In non-human primates, our PTK7-bipyretrophic ADC was well-tolerated at doses up to 60 mg per kg. No mortality or adverse clinical signs were observed, and any change in hepatology or chemistry were minor and transient.
Barbara Schafer: Overall, we executed steadily on our long term strategy.
Ken: In addition, Barbara Schafer, who joined <unk> in 2004 has been promoted to senior Vice President of clinical development operations.
Barbara Schafer: Advancing a diverse pipeline of adcs in T cell engagement, staying disciplined financially and positioning the organization for meaningful progress in the years ahead.
Speaker Change: Gather they will finance of overall in shaping our clinical development strategy for our portfolio to support our advancing pipeline.
Barbara Schafer: On this slide we've highlighted multiple near term catalysts events in 2025, most notably with the phase III top line data readout presented in a map in the horizon <unk>.
Speaker Change: Financially, we remain well capitalized with $321 6 million in cash and equivalents at.
Barbara Schafer: As you know an eventual approval in this indication with rigor a significant cash milestone payment from <unk> as.
Speaker Change: The first quarter and projected runway into the second half of 247 on our existing capital versus the combined was assumed receipt of certain anticipated regulatory milestones.
Barbara Schafer: As well as contribution to the increase in ongoing royalty revenue, which is tiered up to 20% of net sales from Jeff.
Speaker Change: Our lower cash operating burn for the first order was aided by clinical progress made by our partner.
Barbara Schafer: Before I conclude I want to leave you with a few final thoughts.
Speaker Change: Platform partnerships are a core part of our strategy to broaden patient impact while maintaining capital efficiency and we are encouraged by the momentum our partners generate.
Barbara Schafer: In today's environment, where the biotech industry is undergoing a healthy reset we believe the company will create long term value for shareholders or those that deliver real clinical progress on meaningfully new medicines make disciplined capital decisions and maintain our focus on operational execution.
Paul Moore: I make effects were consistent with expected class effects and not considered those limited. These findings suggest that our bipartitoic ADC may offer a differentiated profile, particularly in chambers where PTK7 is broadly expressed or where internalization has historically been a limiting factor. We look forward to continued optimization work in evaluating this approach across relevant preclinical models.
Speaker Change: Overall, we executed steadily on our long term strategy.
Speaker Change: Advancing a diverse pipeline of adcs, <unk>, staying disciplined financially and positioning the organization for meaningful progress in the years ahead.
Barbara Schafer: That is the approach we've taken since 2022, when I took over as chair and CEO and implemented fundamental strategic changes at Zimmer.
Speaker Change: On this slide we've highlighted multiple near term catalyst events in 2025, most notably with the phase III top line data readout presented in a map in the horizon <unk>.
Barbara Schafer: During the remainder of 2025 and into 2026, we look forward to seeing the results of our chosen strategic direction and updating you on our progress along the way we.
Paul Moore: Lastly, moving on to our poster presentation on ZW171, a mesothelon-targeting T cell engager, demonstrating enhanced safety, anti-tumor activity in a range of mesothelon-expressing cancers. As you know, we have reported the first patient dose in October 2024 for our first in-human Phase 1 trial, which is continuing to recruit across sites in the U.S., U.K., and South Korea, and I'll touch on the ongoing trial in a couple of slides. 171 is engineered with a lower affinity CD3 binding arm, which is designed to reduce the likelihood of indiscriminate T cell activation and cytokine release, especially in the absence of high mesothelin expression.
Speaker Change: As you know an eventual approval in this indication, which trigger a significant cash milestone payment from <unk> as.
Barbara Schafer: We are advancing multiple differentiator program based on strong biology, and meaningful patient need and we have clear near term milestones that we believe will continue to validate our scientific platform and our operating strategy.
Speaker Change: As well as contribution to the increase in ongoing royalty revenue, which is tiered up to 20% of net sales from Jeff.
Speaker Change: Before I conclude I want to leave you with a few final thoughts.
Based on our current operating plans, we made funded through key catalysts.
Speaker Change: In today's environment, where the biotech industry is undergoing a healthy reset we believe that companies will create long term value for shareholders or those that deliver real clinical progress on meaningfully new medicines make disciplined capital decisions and maintain our focus on operational execution.
Barbara Schafer: On our wholly owned pipeline as well as partnerships with leading pharmaceutical organization and we are prioritizing investments towards programs that have the highest potential to drive value creation and impact patient block.
Barbara Schafer: Governance and operational operational discipline remains central to everything we do.
Paul Moore: Many T-cell engages with high CD3 affinity, like earlier generation 1 plus 1 formats, have triggered systemic CRS because they activate T-cells even when target engagement is weak or off tumor. In head-to-head preclinical comparisons, 171 has demonstrated superior cytotoxicity versus other next-generation mesothelioma targeting bispecifics. Importantly, this enhanced tumor cell killing comes with improved selectivity. We've observed reduced nonspecific T cell binding relative to other programs in this space, a feature that may contribute to a more favorable safety. In the middle column, you can see that 171 exhibits selective and high affinity binding to tumor cells expressing high- levels of mesotheliin while showing minimal binding to cells with low mesotheliin expression.
Speaker Change: That is the approach we've taken since 2022, when I took over as chair and CEO and implemented fundamental strategic changes at Zimmer.
Barbara Schafer: Our board brings diverse independent perspective, with deep expertise in drug development in biotech value creation.
Speaker Change: During the remainder of 2025 and into 2026, we look forward to seeing the results of our chosen strategic direction and updating you on our progress along the way we.
Barbara Schafer: Together, we hold ourselves accountable for delivering against clear data driven goal and then making difficult decisions when necessary.
Speaker Change: We are advancing multiple differentiated program based on strong biology, and meaningful patient need and we have clear near term milestones that we believe will continue to validate both our scientific platform and our operating strategy.
Barbara Schafer: As we move forward, our focus is on execution efficiency and clinical validation and we look forward to showing continued progress in the quarters ahead.
Barbara Schafer: Thank you and I'd now like to turn the call over to the operator to begin the question and answer session offer.
Speaker Change: Based on our current operating plans remains funded through key catalysts.
Speaker Change: On our wholly owned pipeline as well as partnerships with leading pharmaceutical organization and we are prioritizing investments worth program that have the highest potential to drive value creation and impact patients lives.
Barbara Schafer: We'll now begin the question and answer session.
Barbara Schafer: To join the queue you May Press Star then one on your telephone keypad.
Paul Moore: Importantly, 171 maintains low affinity for CD3, which is a deliberate design choice to reduce off-target T-cell activation and improve safety. Its profile underscores its ability to preferentially target tumors while sparing normal tissues with minimal mesothelial expression. Moving to the cytotoxicity data on the right, 171 continues to demonstrate potent and selective tumor cell killing in high mesothelial and high settings, but not in low mesothelial-expressing cells, compared to benchmark molecules, including AMG305, CT95, and the GNG-bispecific comparator. ZW171 consistently shows equal or superior cytophysicity across a panel of tumor cell lines with varying levels of mesothelin expression, particularly at low effector-to-target ratios, which more closely reflects conditions in the tumor microenvironment.
Barbara Schafer: Here at totaling 19 your request.
Speaker Change: Governance and hop rental operational discipline remains central to everything we do.
Barbara Schafer: If you are using a speakerphone please pick up your handset before pressing any keys to it.
Speaker Change: Our board brings diverse independent perspective, with deep expertise in drug development in biotech value creation.
Barbara Schafer: Your question. Please press star one again.
Barbara Schafer: We will pause for a moment as callers join the queue.
Speaker Change: Together, we hold ourselves accountable for delivering against clear data driven gold and then making difficult decisions when necessary.
Charles: And our first question comes from the line of Charles <unk> of ISI Capital. Your line is now open.
Speaker Change: As we move forward, our focus is on execution efficiency and clinical validation and we look forward to showing continued progress in the quarters ahead.
Speaker Change: Hello, everyone. Thanks for the call the uptake and for the questions great to hear the emphasis the continued emphasis on cash burn discipline. Maybe my first question here on as you look towards prioritizing assets and indications for development across your broad preclinical and early clinical.
Speaker Change: Thank you and I'd now like to turn the call over to the operator to begin the question and answer session.
Speaker Change: Sure.
Speaker Change: Well now begin the question and answer session to join the queue. You May Press Star then one on your telephone keypad.
Charles: Pipeline.
Charles: Perhaps what is it.
Some of your base case assumptions with respect to backend milestone royalty revenues that you may receive from assets with.
Speaker Change: You'll hear it totaling 19 your request.
Speaker Change: If you are using a speakerphone please pick up your handset before pressing any Keith.
Paul Moore: As you can see on the left-hand side of this slide, in a large panel of tumor cell lines, including those that shed soluble mesothelin, 171 maintains strong anti-tumor. Notably, no correlation was observed between the amount of shed mesothelin and 171's efficacy, underscoring the robustness of its mechanism of action. These findings support our hypothesis that our 2 plus 1 design sustains activity in the presence of shed mesothelin through a viridity-dependent mesothelin binding on high med-expressing tumors. What also stands out, as depicted in the graphs on the right-hand side of the slide, is that 171 also demonstrated cytotoxicity, T-cell activation, and cytokine release in more complex, translationally relevant patient-derived xenograft models containing endogenous tumor-infiltrating lymphocytes, as well as in vivo xenograft models.
Charles: Let's call it a possible wide range of outcomes like that debt amount across some of these into key patients.
Speaker Change: To withdraw your question. Please press star one again.
Speaker Change: We will pause for a moment as callers join the queue.
Charles: At <unk> partners and how do they factor into your into your prioritization in terms of like scenario levels. Thank you.
Speaker Change: And our first question comes from the line of Charles <unk> of ISI Capital. Your line is now open.
Speaker Change: Yes, Thanks for the question Charles and I guess.
Speaker Change: Hello, everyone. Thanks for the call the updates and for the questions great to hear the emphasis to continued emphasis on cash burn discipline, maybe my first question here.
Speaker Change: As I said in my closing remarks, I think capital allocation is an important market build out going along with clinical execution and great science, and we will practice appropriate capital allocation with our board.
Speaker Change: As you look towards prioritizing assets and indications for development across your broad preclinical and early clinical pipeline.
Speaker Change: As we put ourselves in position to receive.
Speaker Change: Additional capital and whether it's milestones are from from any other source obviously.
Speaker Change: What are some of your base case assumptions with respect to back end milestone and royalty revenues that you may receive from assets with.
Speaker Change: We're quite excited about the progress being made by jazz envisioning.
Paul Moore: These data support further the potential of 171 to drive meaningful responses in mesothelial expression tumors, particularly in challenging tumor microenvironments. Together, these data reinforce our confidence in 171's potential to deliver meaningful therapeutic benefit, while demonstrating a favorable tolerability profile. With our phase one clinical trials in mind, both studies for 171 and 191 remain on track and are recruiting well across sites. This slide highlights the breakdown of currently activated clinical sites by geographic region. Our global clinical trial footprint is a key component of our strategy to move efficiently through early development. By engaging sites across multiple geographies within and outside the United States, we're able to maintain momentum in enrollment while optimizing the use of clinical supply and supporting streamlined operation.
Speaker Change: Whereas anxious and excited to see the horizon one data.
Speaker Change: Let's call it a possible wide range of outcomes like any debt that amount across some of these into key patients.
Speaker Change: Later, this year as well as continuing to see the progress on the additional clinical studies that Jive the Beijing.
Speaker Change: At <unk> partners and how do they factor into your into your prioritization in terms of like scenario levels. Thank you.
Speaker Change: Underway and certainly.
Speaker Change: There'll be a financial important an important financial piece for us in that progress and I think we will have to act with capital allocation.
Charles: Yes, Thanks for the question Charles and I guess.
Charles: As I said in my closing remarks, I think capital allocation is an important market build out going along with clinical execution and great science, and we will practice appropriate capital allocation with our board.
Speaker Change: Properly along the way with our board as I said in addition to that we're now seeing some of the technology partnership that we started many years ago.
Speaker Change: Starting to push forward really interesting.
Speaker Change: <unk>.
Speaker Change: Assets, obviously, we're really looking forward to the actual presentation by Johnson <unk> Johnson the other Cascade to CD three you saw engage her in prostate cancer, which which again was made with in collaboration with our priority of domestic platform and so therefore, we have a financial interest in the ultimate success of that.
Charles: As we put ourselves in position to receive.
Charles: Additional capital and whether it's milestones are from from any other source obviously.
Charles: We're quite excited about the progress being made by jazz envisioning.
Charles: Whereas anxious and excited to see the horizon <unk> one data.
Paul Moore: Looking ahead, we do plan to present trial-in-progress posters for both 171 and 191 at upcoming peer-reviewed medical conferences in the second quarter, as Leone mentioned earlier.
Charles: Later this year.
Speaker Change: That product as well as helping it makes a big leap forward for patients and so I think I can do to think about that money that may come in at a later stage well make the appropriate decisions.
Charles: As well as continuing to see the progress on the additional clinical studies that jazz in Beijing.
Charles: Underway and certainly.
Charles: There'll be a financial important an important financial piece for us in that progress and I think we will have to act with capital allocation.
Speaker Change: To allocate capital to continue to build our R&D portfolio, where it deserves it.
Ken Galbraith: And with that, I will hand over to Ken to conclude today's call and open up the call for Q&A. Thank you, Paul, and good afternoon, everyone. We hope that from the remarks made on today's call, it's very clear that our R&D organization continues to deliver on its core mandate. Advancing a pipeline rooted in translational science and focused on meaningful clinical outcomes, while providing multiple near-term catalysts for potential share of a diet. The six poster presentations at AACR this year reflect the depth of that work, spanning early and mid-stage candidates across multiple modalities. This includes our multi-specific NADC platforms, which are enabling us to target a diverse set of tumor antigens with increasingly refined approaches.
Speaker Change: Mobile data easily sort that out as.
Charles: Properly along the way with our board as I said in addition to that we're now seeing some of the technology partnerships that we started many years ago.
Speaker Change: As well as make the right decisions as we did last year about returning capital to shareholders, where we found ourselves in a position to do that and believe that that will boost our total shareholder return so.
Charles: Starting to push forward really interesting.
Speaker Change: I think we're well suited as a way to right now with the board that I have the internal discipline inside the company to make those appropriate capital allocation decisions as they are necessary and I think we've already shown the ability to do that with our capital allocation last year back to shareholders as well as.
Charles: Assets, obviously, we're really looking forward to the actual presentation by Johnson <unk> Johnson, the other cascade to CD three Keystone engage her in prostate cancer, which which again was made with in collaboration with ancillary as a metric platform and so therefore, we have a financial interest in the ultimate success of that of that.
Speaker Change: Some of the changes we've made in R&D priorities, even given last quarter. So I feel very comfortable we'll make those appropriate decision for shareholders.
Charles: Products as well as helping it makes a big leap forward for patients and so I think I continue to think about that funding that may come in at a later stage well make the appropriate decisions.
Ken Galbraith: We remain on track to submit our IND for ZW251 by mid-2025, an important milestone for that program and for our broader strategy of building a portfolio with the potential to address unmet needs across oncology and immunology. Our focus on execution also extends to leadership.
Speaker Change: Third.
Speaker Change: Got it great great to hear thanks for that and my second question on much much narrower in scope, but Paul. Thank you very much for walking us through each of those preclinical assets may be very quick ones <unk> nine the DLL three T cell engagement that you guys have.
Charles: To allocate capital to continue to.
Charles: To build our R&D portfolio, where we're at.
Charles: Reserves at global data easily sort that out.
Ken Galbraith: In April, we welcome Dr. Sabine McCann as our Senior Vice President of Clinical Development. Her experience across hematology and oncology in both academic and industry settings, with Gilead, Daiichi Senkyo, and Bristol Myers Squibb, will support our clinical case candidates and help shape our global development and regulatory strategy. Dr. Jeff Smith, who joined Zymeworks in 2023, will continue to serve as Executive VP and CMO, where he leads our Emerging R&D Portfolio in Autoimmune and Inflammatory Diseases, as well as our Global Clinical Development Operations.
Charles: As well as make the right decisions as we did last year about returning capital to shareholders, where we found ourselves in a position to do that and believe that that would boost our total shareholder return. So I think we're well suited situated right now with the board that I have the internal discipline inside the company to make those appropriate capital allocation decisions as they are necessary I think we've already shown the.
Speaker Change: As like Todd talked about continuing to move into earlier and earlier lines of small cell lung cancer and we all know the profile of talk from a lot of that could you also remind us about some of the cytokine induction data that you've bought.
Charles: Ability to to do that with our capital allocation last share back to shareholders as well.
Speaker Change: I guess produced with your DLL three and what are some of the implications there with things like cytokine release syndrome. Thank you yes.
Charles: Some of the changes we've made in R&D priorities, even even last quarter.
Speaker Change: Yes, Thanks Charles.
Charles: I feel very comfortable we'll make those appropriate decision for shareholders.
Speaker Change: So whats what we've done just.
Ken Galbraith: In addition, Barbara Schaeffler, who joined Zymeworks in 2024, has been promoted to Senior Vice President of Clinical Development Operations. Together, they will play a pivotal role in shaping the clinical development strategy for our portfolio to support our advancing pipeline.
Charles: Sure.
Speaker Change: As a remainder is.
Speaker Change: Got it great great to hear thanks for that and my second question on much much narrower in scope, but Paul. Thank you very much for walking us through each of those are preclinical assets, maybe very quickly on <unk> nine.
Speaker Change: Designed a molecule that can engage CD.
Speaker Change: And <unk> and DLL three and.
Speaker Change: And the engagement of CD 20, it only happens when you have engaged <unk> III. So we think that profile is a very favorable profile compared to other approaches where you would combine.
Ken Galbraith: Financially, we remain well capitalized, with $321.6 million in cash and equivalents at the end of the first quarter and projected runway into the second half of 2027, when our existing cash resources are combined with assumed receipt of certain anticipated regulatory models. Our lower cash operating burn for the first quarter was aided by clinical progress made by our partners. These platform partnerships are a core part of our strategy to broaden patient impact while maintaining capital efficiency, and we're encouraged by the momentum our partners are generating.
Speaker Change: DLL three T cell engagement that you guys have now, especially as athletes like Tom talked about continuing to move into earlier and earlier lines of small cell lung cancer and we all know the profile of a lot of that could you also remind us about some of the cytokine induction data that you've bought.
Speaker Change: 28 by specific see what the CDC by specific where there you may have to be more.
Speaker Change: Broad and your CD 20 activation more T cells, which can actually then trigger more broad cytokine profile, okay across across a broader number of T cells. What we're doing is really only engaging.
Speaker Change: I guess to produce west of your DLL, three and what are some of the implications there with things like cytokine release syndrome. Thank you yes.
Speaker Change: The CD three CD 28, when you've engaged CD CD three so a more limited T cell will be activated when you've engaged DLL three and we think that that generates a cytokine response that will incorporate crew stimulation, which will be addition to what you get with just simply CDC activation that will be more.
Ken Galbraith: Overall, we've executed steadily on our long-term strategy. advancing a diverse pipeline of ADCs and TESOL engagers, staying disciplined financially, and positioning the organization for meaningful progress in the years ahead.
Speaker Change: Thanks, Charles Yes, so whats.
Speaker Change: What we've done just.
Speaker Change: As a remainder is.
Speaker Change: <unk> designed the molecule that can engage CD.
Speaker Change: And CD 28 on <unk> III and.
Ken Galbraith: On this slide, we've highlighted multiple near-term catalyst events in 2025, most notably with the Phase III top-line data readout for XanaDataMath in the HORIZON-GEA01 study. As you know, an eventual approval and vindication would trigger a significant cash milestone payment for Zymeworks, as well as contributions to an increase in ongoing royalty revenue, which is tiered up to 20% of net sales from JET.
Speaker Change: And the engagement of CD 20, it only happens when you have engaged <unk> III. So we think that profile is a very favorable profile compared to other approaches where you would combine.
Speaker Change: Localized activation of T cells, and we think the benefit of the therapeutic benefit.
Speaker Change: <unk> really play out well in increasing the therapeutic index that we see with the balanced.
Speaker Change: 28 by specific to see what the CDC by specific where there you may have to be more.
Speaker Change: Limited localized impact on T cells, and that's going to reflected then in our nonhuman Primate studies, we've done various studies and we've also done studies and will fully humanized mice that are used as models for CD 20 activation and we really see a limited.
Speaker Change: Broad and your CD 20 activation more T cells, which can actually then trigger more broad cytokine profile, okay across the across a broader number of T cells. What we're doing is really only engaging.
Ken Galbraith: Before we conclude, I want to leave you with a few final thoughts. In today's environment, where the biotech industry is undergoing a healthy reset, we believe that companies will create long-term value for shareholders, are those that deliver real clinical progress on meaningfully new medicines, make disciplined capital decisions, and maintain a focus on operational execution. That is the approach we've taken since 2022 when I took over as chair and CEO and implemented fundamental strategic changes at Zymeworks.
Speaker Change: Of target profile there so.
Speaker Change: The CD three CD 28, when you have <unk> III. So a more limited T cell will be activated when you've engaged DLL three and we think that that generates a cytokine response that will incorporate co stimulation, which will be addition to what you get with just simply CDC activation that will be a more.
Speaker Change: That's kind of a give.
Speaker Change: Important thing to bear in mind, when you think about our molecule is quite different than say other approaches others have used.
Speaker Change: And we definitely are thinking about limiting that cytokine release.
Speaker Change: To where it's needed and.
Speaker Change: A.
Ken Galbraith: During the remainder of 2025 and into 2026, we look forward to seeing the results of our chosen student direction and updating you on our progress along the way. We are advancing multiple differentiator programs based on strong biology and meaningful patient needs, and we have clear near-term milestones that we believe will continue to validate both our scientific platform and our operating strategy. Based on our current operating plans, we remain funded through key catalysts. on our wholly owned pipeline, as well as partnerships with leading pharmaceutical organizations, and we are prioritizing investments towards programs that have the highest potential to drive value creation and impact patients' lives.
Speaker Change: Yes.
Speaker Change: Localized activation of T cells, and we think the benefit of that therapeutic benefit will actually really play out well in increasing the therapeutic index that we see with the balanced.
Speaker Change: Great. Thanks for taking the questions and congrats again on all the progress.
Speaker Change: Thanks.
Speaker Change: Thank you one moment for our next question.
Speaker Change: Limited localized impact on T cells, and that's going to reflect a gain in our nonhuman Primate studies, we've done various studies and we've also done studies in <unk>.
Speaker Change: And our next question comes from the line of Pine Cheng of Jay.
Speaker Change: Your line is now open.
Speaker Change: Hey, guys.
Speaker Change: Fully humanized mice that are used as models for CD 20 activation and we really see a limited.
Speaker Change: Thanks for taking our questions. This afternoon.
Speaker Change: Maybe first just on quickly on Fannie data map.
Speaker Change: Of target profile there. So that's that's kind of a give.
Speaker Change: We glean from the subset analysis of keynote <unk>, one that focused on.
Speaker Change: The important thing to bear in mind, when you think about our molecule is quite different than say other approaches others have used.
Speaker Change: Asia versus non Asia and efficacy.
Ken Galbraith: Governance and operational discipline remain central to everything we do. Our board brings diverse, independent perspectives with deep expertise in drug development and biotech value creation. Together, we hold ourselves accountable to delivering against clear, data-driven goals and to making difficult decisions when necessary. As we move forward, our focus is on execution, efficiency, and clinical validation, and we look forward to sharing continued progress in the quarters ahead.
Speaker Change: I was just curious what your thoughts are on how ex U S patients in the phase III horizon Gea.
Speaker Change: And we definitely are thinking about limiting that cytokine release.
Speaker Change: To where it's needed and.
Speaker Change: Could impact the powering and the outcome on PFS and OS.
Speaker Change: <unk>.
Speaker Change: Yes.
Speaker Change: Do you think the trial is de risked.
Speaker Change: Great. Thanks for taking the questions and congrats again on all the progress.
Speaker Change: On both endpoints and I have a quick follow up thank you.
Speaker Change: Thanks.
Speaker Change: Thank you one moment for our next question.
Brian: Yes, Thanks, Brian I think.
Speaker Change: One of our Kols address it.
Brian: Even at our R&D day in December.
Moderator: And our next question comes from the line of Pine Cheng.
Brian: For this with.
Brian: With Kols from the time that we start of that study.
Speaker Change: Your line is now open.
Brian: I think in general.
Operator: Thank you, and I'd now like to turn the call over to the operator to begin the question and answer session. Operator?
Pine Cheng: Hey, guys.
Brian: And across multiple studies is that the may not really a significant difference.
Speaker Change: Thanks for taking our questions. This afternoon.
Speaker Change: Maybe first just on quickly on Fannie has got a map.
Brian: And.
Operator: We'll now begin the question and answer session. To join the queue, you now may press star and then 1-1 on your telephone keypad. You will hear a tone acknowledging your request.
Speaker Change: We glean from the subset analysis of keynote <unk>, one that focused on.
Brian: Efficacy across ethnicities patients.
Brian: Patients overall.
Brian: No as we are starting to the additional comp analysis from the 211 study not a day that could produce some of that data for various pricing and reimbursement purposes.
Speaker Change: Asia versus non Asia and efficacy.
Speaker Change: I was just curious what your thoughts are on how ex U S patients in the phase III horizon Gea.
Operator: If you are using a speakerphone, please pick up your handset before pressing any keys. To withdraw your question, please press star 11 again. We will pause for a moment as callers join the queue.
Speaker Change: Could impact the powering and the outcome on PFS and OS.
Brian: There is a there is a slight difference in that.
Speaker Change: Do you think the trial is de risked.
Brian: Asia and non agency.
Brian: If you look at it I think on the <unk>.
Speaker Change: On both endpoints and I have a quick follow up thank you.
Brian: Components of the ICD, which is about 200 patients.
Charles Yue: And our first question comes from the line of Charles Yue of Lightside Capital. Your line is now open. Hello, everyone. Thanks for the call, the updates and for the questions. Great to hear the emphasis, the continued emphasis on cash burden discipline.
Speaker Change: Yes, Thanks, Brian I think.
Brian: We saw Asia subject do better on both arms of the study has been nominated as of yet.
Speaker Change: One of our Kols address it.
Speaker Change: Even at our R&D day in December.
Speaker Change: Part of this with with Kols from the time that we start of that study and I think in general what they see.
Speaker Change: I'm not sure we know what to make of that.
Brian: Size of the population.
Speaker Change: And across multiple studies isn't the main not really a significant difference.
Brian: At 200, or other normalize I'm not I'm not sure.
Charles Yue: Maybe my first question here, as you look towards prioritizing assets and indications for development across your broad preclinical and early clinical pipeline, perhaps what are some of your base case assumptions with respect to back-end milestones and royalty revenues that you may receive from assets with, let's call it, a possible wide range of outcomes like ZanyDat, Datamap, across some of these indications at overarching partners, and how do they factor into your prioritizations in terms of scenario analysis? Yeah, thank you for the question, Charles. And I guess, you know, as I said in my closing remarks, you know, I think capital allocation is an important biotech skill to have going along with clinical execution and great science.
Brian: But it is a little unusual.
Speaker Change: And.
Speaker Change: Efficacy across ethnicity.
Brian: I think if you look at all of the other study and look at them on a combined basis.
Speaker Change: Patients overall.
Brian: Arc.
Speaker Change: No as we are starting to see additional sub analysis from the 211 study the other day.
Brian: Really be much different than an efficacy across a wide.
Speaker Change: You have to produce some of that data for various pricing and reimbursement purposes.
Brian: Patients obviously horizon.
Brian: While more than 300 come across a very diverse globally very diverse.
Speaker Change: There is a there is a slight difference in that in that.
Speaker Change: Treat Asian, and non Asian subjects.
Brian: Standpoint.
Brian: Prevalence of tears.
Speaker Change: If you look at it I think on the aging of the components of the ICD, which is about 200 patients.
Brian: Much higher.
Speaker Change: Eastern market or we will have risen in those markets as well, but I'm not sure what to make of the sub populations that we didn't do that study and we don't have enough detail to really understand.
Speaker Change: We saw Asia subject on that study do better on both arms of the study then nominated in the sub debt.
Speaker Change: Why is it better on both arms of that study.
Speaker Change: Not sure we know what to make of that.
Speaker Change: On a size of that population at 200 or other anomalies I'm not I'm not sure.
Speaker Change: Comparison or not.
Speaker Change: Throughout March.
Ken Galbraith: And we will practice appropriate capital allocation with our board as we put ourselves in position to receive additional capital in, whether it's milestones or from any other source. Obviously, down at AMAB, we're quite excited about the progress being made by JAS and Beijing. We're as anxious and excited to see the Horizon GA1 data results later this year, as well as continuing to see the progress on the additional clinical studies that JAS and Beijing have underway. And certainly, there'll be an important financial piece for us in that progress. And I think we'll have to act with capital allocation properly along the way with our board, as I said.
Speaker Change: How does that.
Speaker Change: But it is a little unusual.
Speaker Change: Some of that data at a later date.
Speaker Change: Got it and maybe just one quick follow up.
Speaker Change: I think if you look at all of the other studies and look at them on a combined basis.
Just going back to the J&J assets.
Speaker Change: Art.
Speaker Change: Really be much different in the end.
Speaker Change: Okay, Okay to buy specific with 83.
Speaker Change: And efficacy across a wide.
Speaker Change: Expectation on the prostate update at <unk>.
Speaker Change: Patients obviously horizon.
Speaker Change: Recall that there is a plan to move forward into later stage study can.
Speaker Change: While more than 300 come across very diverse globally very diverse.
Can you maybe remind us how the partnership works from from a dollar perspective. Thank you.
Speaker Change: These standpoint.
Speaker Change: The prevalence of tears.
Speaker Change: Much higher.
Speaker Change: Yes, Arthur Conan partnership with J&J outline publicly again it wasn't our target.
Speaker Change: Asian market, we will have risen in those markets as well, but I'm not sure what the megabit subpopulations liquidity of 11, we didnt.
Speaker Change: Hey.
Speaker Change: And we don't have enough detail to really understand.
Speaker Change: Brought back to our platform because it didn't have a way to build a bias against.
Ken Galbraith: In addition to that, you know, we're now seeing some of the technology partnerships that we started many years ago starting to push forward really interesting clinical stage assets. Obviously, we're really looking forward to the actual presentation by Johnson & Johnson, the other KLK2, CD3 T-cell engager in prostate cancer, which, again, was made in collaboration with us with our endometric platform, and so therefore, we have a financial interest in the ultimate success of that product. As well as hoping it makes a big leap forward for patients.
Speaker Change: Why is it better on both arms of that study.
Speaker Change: We did not using asymmetric with obviously the same.
Speaker Change: Comparison or not.
Speaker Change: We use design and a map.
Speaker Change: Yes.
Speaker Change: The payroll through August.
This is Tom <unk>.
Speaker Change: And some of that data at a later date.
Speaker Change: And that from what I saw.
Speaker Change: Got it.
Speaker Change: You are.
Speaker Change: Just one quick follow up.
Speaker Change: It looks quite interesting Emerald reports that data are there financial assistant this program as we are.
Speaker Change: Just going back to the J&J assets the cap.
Speaker Change: Okay to buy specific with <unk>.
Speaker Change: And patterns of either milestone based on production development.
Speaker Change: What's the expectation on the prostate update at <unk>.
Speaker Change: Right.
Speaker Change: And I recall that there is a plan to move far into a later stage study.
Speaker Change: What happens beyond the phase one data at all.
Speaker Change: Can you maybe remind us how the partnership works from from a dollar perspective. Thank you.
Speaker Change: And what their intentions are and we will look into that and in addition, we have a mid single digit royalty on sales of <unk>.
Ken Galbraith: And so, I think as we continue to think about that funding that may come in at a later stage, we'll make the appropriate decisions to allocate capital to continue to build our R&D portfolio where it deserves it, when clinical data usually sorts that out, as well as make the right decisions, as we did last year about returning capital to shareholders, where we found ourselves in a position to do that and believe that that would boost total shareholder returns. So, I think we're well-situated right now with the board that I have and the internal discipline inside the company to make those appropriate capital allocation decisions as they're necessary, and I think we've already shown the ability to do that with our capital allocation last year back to shareholders, as well as some of the changes we've made in R&D priorities even last quarter.
Speaker Change: Yes.
Speaker Change: On the partnership with J&J outline publicly again it wasn't our target.
Speaker Change: Three.
Speaker Change: With positive data.
Speaker Change: Hey.
Speaker Change: Im very encouraged from the other comments has been from J&J that this could be a very soon again.
Speaker Change: Brought back to our platform because it didn't have a way to build a bias against it so.
Speaker Change: So we did not using asymmetric with obviously the same platform.
Speaker Change: Product for them.
Speaker Change: Vince.
Speaker Change: We use design.
Speaker Change: Improvement in center care for patients.
Speaker Change: <unk> and <unk>.
Speaker Change: We'll follow that very closely.
Speaker Change: And that from what I saw.
Speaker Change: Obviously, the value of the remaining royalties and milestones.
Speaker Change: You are.
Speaker Change: It looks quite interesting MRO going forward to that data.
Speaker Change: Would be very interesting.
Speaker Change: Are there financial assistance program as we are entitled to other milestones based on production development.
Speaker Change: For us as this program progresses beyond the phase one.
Speaker Change: Great. Thank you Ken.
Speaker Change: Thank you one moment for our next question.
Charles Yue: So, I feel very comfortable we'll make those appropriate decisions for shareholders as they're necessary. Got it. Great, great to hear. Thanks for that.
Speaker Change: What happens beyond the phase one data.
Speaker Change: No.
Speaker Change: Our next question comes from the line of Stephen Willey of Stifel. Your line is now open.
Speaker Change: And what their intentions are and we're looking for that in addition, we have.
Speaker Change: Mid single digit royalty on sales of <unk>, a <unk> three.
Charles Yue: And my second question on much, much narrower in scope, but Paul, thank you very much for walking us through each of those preclinical assets. Maybe very quickly on ZW209, the DLL3 T cell engager that you guys have, you know, especially as acts like TAR-Tarmotimab continue to move into earlier and earlier lines of small cell lung cancer. We all know the profile of TAR-Tarmotimab.
Speaker Change: Yes, good afternoon, thanks for taking the questions.
Speaker Change: I know you've been a little bit hesitant to give guidance around when we might see 171 and one of them. Neither one data.
Speaker Change: <unk>.
Speaker Change: With positive data.
Speaker Change: Very encouraged from the other comments has been from J&J that this could be a very soon again.
Speaker Change: It is not included in the list of catalysts that you guys have itemized on the slide and I understand that you guys have.
Speaker Change: Product for them.
Speaker Change: <unk>.
Speaker Change: Improvement in standard of care for patients.
Speaker Change: Kind of pointed to a desire to present.
Speaker Change: We'll follow that very closely.
Speaker Change: More fulsome data peer reviewed settings.
Speaker Change: Obviously, the value of the remaining royalties and milestones.
Paul Moore: Could you also remind us about some of the cytokine induction data that you've, I guess, produced with your DLL3 and what are some of the implications there with things like cytokine release syndrome? Thank you. Yeah, I know. Thanks, Charles. Yeah, so what we've done just as a reminder is we've designed a molecule that can engage CD3 and CD28 and DLL3 and the engagement of CD28 only happens when you've engaged CD3. So we think that profile is a very favorable profile compared to other approaches where you would combine a CD28 bispecific, say with a CD3 bispecific, where there you may have to be more broad in your CD28 activation, hit more T cells, which can actually then trigger, you know, more broad cytokine profile, okay, across a broader number of T cells.
Speaker Change: But just curious if.
Speaker Change: Would be very.
Speaker Change: You are intending to provide some level of communication with respect to reaching certain dose escalation or dose expansion milestones. So I guess I asked the question because theres a lot of interest around.
Speaker Change: Training.
Speaker Change: For us as this program progresses beyond the phase one.
Speaker Change: Great. Thank you Ken.
Speaker Change: Thank you one moment for our next question.
Speaker Change: The progress being made on 191, just giving the same novel linker payload is being leveraged across a variety of different wholly owned programs.
Speaker Change: Our next question comes from the line of Stephen Willey of Stifel. Your line is now open.
Stephen Willey: Yes, good afternoon, thanks for taking the questions.
Stephen Willey: I know you've been a little bit hesitant to give guidance around when we might see $1 seven water and water by the <unk> data I know it's not included in the list of catalysts that you guys have itemized on the slide and I understand that you guys have.
Speaker Change: Yes. Thanks.
Speaker Change: We're hesitant to provide guidance.
Speaker Change: <unk>.
Speaker Change: It's appropriate at this stage, obviously, we are still early.
Speaker Change: We're very encouraged so far by the speed of our phase one study we had this idea of having a larger.
Stephen Willey: Kind of pointed to a desire to present more fulsome data at peer reviewed settings.
Speaker Change: Globally diversified footprint.
Speaker Change: So that we could all of the patients quickly.
Stephen Willey: But just curious if.
Stephen Willey: You are intending to provide some level of communication with respect to reaching certain dose escalation or dose expansion milestones. So I guess I asked the question because theres a lot of interest around.
Speaker Change: And so far that's working as.
Speaker Change: As well as we could have ever hoped.
Paul Moore: What we're doing is really only engaging The CD28, when you've engaged CD3, so a more limited T cell will be activated when you've engaged DLL3. And we think that while that generates a cytokine response that will incorporate co-stimulation, which will be addition to what you get with just simply CDC activation, that will be a more localized activation of T cells. And we think the benefit of the therapeutic benefit will actually really play out well in increasing the therapeutic index that we see with the balanced, limited, localized impact on T cells. And that's going to reflect it then in our non-human primate studies, where we've done various studies, and we've also done studies in fully humanized mice that are used as models for CD28 activation, and we really see a limited off-target profile there.
Speaker Change: Do I think we're encouraged by the early data we've seen it's early.
Speaker Change: So far we've had no surprises in your translation from our preclinical hypothesis.
Stephen Willey: The progress being made on 191, just giving the same novel linker payload is being leveraged across a variety of different wholly owned programs.
Speaker Change: That being said, it's still early in that process I think we do want to make sure that.
Speaker Change: As we prepare or peer reviewed data.
Speaker Change: Yes, it's not that we're hesitant to provide guidance.
Speaker Change: A peer reviewed forum.
Speaker Change: Finally, we can make some conclusions that are important.
Speaker Change: Yes.
Speaker Change: It's appropriate at this stage, obviously, we affirm is still early.
To share and I think you guys need before it's somewhat all that thing.
Speaker Change: We're very encouraged so far by the speed of our phase one study we had this idea of helping out larger.
Speaker Change: So as we think thats appropriate we'll file for an abstract will be presented at the meeting and once that abstract that was made public that will be the guidance on Peru give more than that but I think thats. It.
Speaker Change: Globally diversified footprint.
Speaker Change: We define quality patients quickly.
Speaker Change: The appropriate thing to do.
Speaker Change: Wanted.
Speaker Change: And so far that's working.
Speaker Change: Do that as an IR events or prevent the pick the peer group absolutely do that but again don't think that we're in.
Speaker Change: Well as we could have ever hoped perdue I think we're encouraged by the early data we've seen it's early.
Operator: So that's kind of an important thing to bear in mind when you think about our molecule. It's quite different than, say, other approaches others have used. And we definitely are thinking about limiting that cytokine release to where it's needed. Great. Thanks for taking the questions and congrats again on all the progress. Thanks. Thank you. One moment for our next question.
Speaker Change: Not really encouraged by our progress to date.
Speaker Change: So far we've had no surprises in euro translation from our preclinical hypothesis.
Speaker Change: Our pace.
Speaker Change: Again after the changes we made on control dot Gov, and those possessors, you'll be able to have these are as a management trial.
Speaker Change: That being said, it's still early in that process I think we do want to make sure that when.
Speaker Change: And the guidance would give us look forward to an abstract that will be appropriate timeframe was accepted and then mark happy to talk about.
Speaker Change: As we prepare or peer reviewed.
Speaker Change: Given that our peer reviewed forum.
Speaker Change: And at the appropriate time, and we can make some conclusions that are important.
Speaker Change: And at that point, but until then.
Speaker Change: Don.
Speaker Change: To share and I think the guidance, we had before it's somewhat pools I think that's it.
Speaker Change: Is that the company think it.
Speaker Change: Appropriate to get too far ahead of yourself in an early.
Speaker Change: We think that's appropriate.
Speaker Change: Early phase one studies in cellular separately.
Speaker Change: While our abstract will be presented at a meeting and we want that abstract that was made public that will be the guidance on Peru give more than that but I think that's the appropriate thing to do.
Speaker Change: Anytime a guidance or timing.
Brian Cheng: And our next question comes from the line of Brian Cheng of JPM. Your line is now open. Hey guys, thanks for taking our questions this afternoon.
For that.
Speaker Change: Okay, that's fair.
Speaker Change: Then just I know you've talked about having.
Speaker Change: Wanted.
Speaker Change: To do that as an IR events or prevent that takes a period of investment.
Speaker Change: Finite amount of clinical development capacity in house for the wholly owned programs.
Brian Cheng: Maybe first, just quickly on Fannie's data map, as we glean from the subset analysis of Kino 811 that focused on Asian versus non-Asian efficacy, we're just curious what your thoughts are on how ex-U.S. patients in the Phase III Horizon GEA could impact the powering and the outcome on PFS and OS. Do you think the trial is the risk on both ends? And I have a quick follow-up.
Speaker Change: Is that.
Speaker Change: Again.
Speaker Change: I think that we're not really encouraged by our progress to date.
Speaker Change: And that kind of forces you to.
Speaker Change: <unk>.
Speaker Change: Out of this.
Certain capital allocation and strategic decisions with respect to each of these programs but.
Speaker Change: Great.
Speaker Change: Again adverse changes to be made on control Doc government was presented if you will be able to see those as a management trial.
Speaker Change: Is the clinical development infrastructure or capacity is that something that you're willing to flex outwards, depending upon the.
Speaker Change: And the guidance would be from a forward two and.
Speaker Change: An abstract how would be appropriate timeframe was accepted and then mark happy to talk about.
Speaker Change: The <unk>.
Speaker Change: Success of <unk> and the triggering of specific milestones from jazz is there a situation where you are.
Speaker Change: And at that point, but until then.
Speaker Change: Don.
Speaker Change: Is that the company think.
Speaker Change: Broker to get too far ahead of yourself in an early.
Speaker Change: <unk> with your wholly owned portfolio beyond the capacity that you have in.
Ken Galbraith: Yeah, thanks, Brian. I think one of our KOLs addressed this even at our R&D day in December, and we've continued to explore this with KOLs from the time that we started that study. And I think, in general, what they've seen across multiple studies is, in the main, not really a significant difference in efficacy across ethnicities of patients overall. I know, as we're starting to see additional sub-analysis from the Kino Data 11 study, now that they do have to produce some of that data for various pricing and reimbursement purposes, there is a slight difference in that study between Asian and non-Asian subjects.
Speaker Change: Early phase one studies and so you'll just have to wait.
Speaker Change: For anytime a guidance or timing.
Speaker Change: Some of those additional funds Ken.
Speaker Change: For that.
Speaker Change: Trigger an expansion of that infrastructure to accommodate the growing pipeline. Thanks.
Speaker Change: Okay, that's fair.
Speaker Change: Then just I know you've talked about having.
Speaker Change: Finite amount of clinical development capacity in house for the wholly owned programs.
Speaker Change: Yes, no. Good question I mean, right now, we're really happy with what we've rebuilt.
Speaker Change: And that kind of forces you to.
Speaker Change: As the networks.
Speaker Change: <unk>.
Speaker Change: <unk>.
Speaker Change: The phase one program.
Speaker Change: Certain capital allocation and strategic decisions with respect to each of these programs but.
Speaker Change: So far they are growing as quickly as the pump.
Speaker Change: Really encouraged with the way that we decided to do that we've built out a new frontier.
Speaker Change: Is the clinical development infrastructure or capacity is that something that you're willing to flex outwards depending upon.
Speaker Change: Our slide deck, a pretty large number of clinical sites in a number of countries.
Speaker Change: The <unk>.
Speaker Change: Alright dose escalation, but just to allow us to move equipment consolidated.
Speaker Change: Success of <unk> and the triggering of specific milestones from jazz is there a situation where.
Ken Galbraith: If you look at it, I think on the Asian subject components of the ITP, which is about 200 patients, we saw Asian subjects on that study do better on both arms of the study than non-Asian subjects. I'm not sure we know what to make of that, whether that's the smaller size of that subpopulation at 200 or other anomalies. I'm not sure. But it is a little unusual to see that. I think if you look at all the other studies and look at them on a combined basis, our KOLs have suggested there shouldn't really be much difference in the end in efficacy across a wide set of patients.
Speaker Change: So the next step.
Speaker Change: For one time on one nine months those programs are moving very quickly and we want to make sure that we have resources available to move quickly to all data.
Speaker Change: You are.
Speaker Change: Enamored with your wholly owned portfolio beyond the capacity that you have in <unk>.
Speaker Change: Where it helps us to go and I think we're well situated to do that.
Speaker Change: Some of those additional funds Ken.
Speaker Change: We're obviously paying 251.
Speaker Change: Trigger an expansion of.
Speaker Change: Into the clinic coming up here pretty shortly and I feel comfortable with our ability to execute that program in the same.
Speaker Change: Of that infrastructure to accommodate the growing pipeline. Thanks.
Speaker Change: Yes, no. Good question I mean, right now, we're really happy with what we've rebuilt.
Speaker Change: Fast way with good quality of investigators and a large footprint the way we have a once every one to one.
Speaker Change: As the networks to execute.
Speaker Change: Nine months so far.
Speaker Change: The phase one program for park, they're growing as quickly as it.
Speaker Change: <unk>.
Speaker Change: Non issue.
Speaker Change: Our execution has been really good operationally.
Speaker Change: Really encouraged with the way that we decided to do that we felt that issue.
Speaker Change: My question is is an important skill of off the cuff.
Ken Galbraith: Obviously, Verizon has well more than 300 clinical trial sites, very diverse globally, very diverse from an ethnicity standpoint, although prevalence of GA, as you know, is much higher in Asian markets, so we will have inclusion in those markets as well. But I'm not sure what to make of the subpopulation. We didn't execute that study, and we don't have enough details to really understand why Asian subjects did better on both arms of that study compared to non-Asian subjects. So we'll have to let the KOLs who published that study explain to me some of that data later.
Speaker Change: In our slide deck, a pretty large number of clinical sites in a number of countries.
Speaker Change: Not right now.
Speaker Change: Not enough too much about terms of diluting calendar change in the way that we're doing that but I think as we.
Speaker Change: I know this escalation, but just to allow us to move quickly with holiday.
Speaker Change: Have other agents with drilling.
Speaker Change: So the next step.
Speaker Change: There'll be a limiting factor right now the way that we design.
Speaker Change: Thanks for once a month nine months those programs are moving very quickly and we want to make sure that would be up resources available to move quickly consolidator.
Speaker Change: Designers.
Speaker Change: So I feel really comfortable with the capital we're putting against that the resources, we have against the speed we have.
Speaker Change: Greg houses to go I think we're well situated to do that.
Speaker Change: The clarity on our ability to move quickly to the next.
Speaker Change: We're obviously going to 51.
Speaker Change: Stage.
Speaker Change: Into the clinic coming up here pretty shortly and I feel comfortable with our ability to execute that program in the same.
Speaker Change: And clinical data from those programs.
Speaker Change: The data suggests to us this time.
Speaker Change: So so far I don't need more capital to do that if we needed that we will make appropriate policies is driven around.
Speaker Change: Fast way with good quality of investigators and a large footprint. The way we have won several 119 months so far that's not.
Brian Cheng: Got it.
Brian Cheng: And maybe just one quick follow-up. You know, just going back to the J&J assets, the KLK-2 bispecific with CD3, what's the expectation on the prostate update at ASCO? And I recall that there is a plan to move forward into a later stage study. Can you maybe remind us how, you know, the partnership works from, you know, from a dial-up perspective? Thank you. Yeah, I mean, our technology partnership with J&J, I think, is outlined publicly. Again, it wasn't our target, but they brought that to our asymmetric platform because they didn't have a way to build a device specific against KLK2.
Speaker Change: Investment criteria.
Speaker Change: That's not an issue I think our execution has been really good operationally.
Speaker Change: Right Alex.
Speaker Change: <unk> provides and we're really happy about where we are.
Speaker Change: She is an important skill of Opex I think we have that right now.
Speaker Change: And our execution.
Speaker Change: The year to be able to do that for years on capital at risk that drove a bigger okay great.
Speaker Change: Don't want enough too much of that in terms of diluting calendar change in the way that we're doing that but I think as we have.
Alright, thanks for taking questions.
Speaker Change: Other agents with drilling over there.
Speaker Change: I don't think it'll be a limiting factor right now in the way that we do.
Speaker Change: Thank you for our next question.
Speaker Change: Okay.
Speaker Change: <unk> designed it.
Speaker Change: And our next question comes from the line of Jonathan Miller of Evercore ISI. Your line is now open.
Speaker Change: So I feel really comfortable with the capital we're putting against the resources, we have against the speed we have.
Speaker Change: The clarity on our ability to move quickly to the next.
Jonathan Miller: Great. Thanks, so much for taking the question guys and congrats on the progress maybe just building on that previous question a little bit obviously, you've got.
Speaker Change: Page.
Speaker Change: And the clinical development of those programs.
Speaker Change: The data suggests to us this time.
Speaker Change: So so far I don't need more capital to do that if we needed that one moment.
Jonathan Miller: A large internal pipeline and as we as we earn more about at ACR and against that.
Speaker Change: Our policy is driven around.
Jonathan Miller: A lot of potential programs that you could add to either development collaborations or are your internal pipeline, if and when the time comes how many.
Speaker Change: Investment criteria of a private company.
Speaker Change: Alex.
Speaker Change: <unk> proprietary we're really happy about where we are.
Speaker Change: Our execution and we will continue to be able to do that for years on capital at risk and build a bigger okay great.
Jonathan Miller: I know we've discussed this obliquely and the Patrick how many programs can you support early development for it internally and what is the gating factor on external collaborations and I know those take work for <unk> as well.
Speaker Change: Okay. Thanks for taking the question.
Speaker Change: Okay.
Speaker Change: Thank you Amit for next question.
Speaker Change: Okay.
Speaker Change: How many how many molecules could you have across the portfolio, whether they're internal and external trying to get a sense for when those things we heard about at ACR could become more relevant to the story.
Speaker Change: And our next question comes from the line of Jonathan Miller of Evercore ISI. Your line is now open.
Jonathan Miller: Great. Thanks, so much for taking the question guys and congrats on the progress maybe just building on that previous question a little bit obviously, you've got a.
Jonathan Miller: Yes, great question.
Jonathan Miller: I think in building out our clinical infrastructure, we built out in a way that we believe that we can handle with the existing rolled out we have now probably around five internal programs ourselves a big one.
Ken Galbraith: And so, we'll follow that very closely. Obviously, the value of the remaining royalties and milestones would be very interesting for us as this program progresses beyond the Phase 1.
Speaker Change: A large internal pipeline and as we as we earn more about at ACR and against day.
Speaker Change: A lot of potential programs that you could add to either development collaborations or their internal pipeline, if and when the time comes how many.
Jonathan Miller: So we're kind of within that bandwidth now with the current we've declared.
Jonathan Miller: Got it and I think on a preclinical basis, if you look at us translating molecules.
Operator: Great, thank you, Ken. Yeah. Thank you. One moment for our next question.
Speaker Change: I know we've discussed this obliquely and Patrick how many programs can you support early development for it internally and what is the gating factor on external collaborations and I know those take work for us and works as well.
Jonathan Miller: Probably handle the.
Jonathan Miller: And at any one time improvement.
Stephen Wiley: Our next question comes from the line of Stephen Wiley of Steve Wo, your line is now open. Yeah, good afternoon. Thanks for taking the questions. I know you've been a little bit hesitant to give guidance around when we might see 171 and 191 data. I know it's not included in the list of catalysts that you guys have itemized in the slide, and I understand that you guys have. kind of pointed to a desire to present more fulsome data at peer-reviewed settings, but just curious if you're intending to provide some level of communication with respect to reaching certain dose escalation or dose expansion milestones.
Jonathan Miller: Yes.
Jonathan Miller: Thats pretty reasonable.
Jonathan Miller: With to handle the portfolio, we obviously have.
Speaker Change: How many how many molecules could you have across the portfolio, whether they're internal and external trying to get a sense for when those things we heard about at ACR could become more relevant to the story.
Jonathan Miller: A substantial amount of substrate and our preclinical programs really interesting molecule and we think are all different and we just we make the choices, which should help improve the quality of the clinical portfolio that we have.
Speaker Change: Yes, great Great question John.
Speaker Change: I think in building out our clinical infrastructure, we built out in a way that we believe that we can handle with the existing build out we have now probably around five internal programs ourselves for phase one.
Jonathan Miller: To date, we've been doing this on our own.
Jonathan Miller: In keeping all of our assets unencumbered.
Jonathan Miller: We do evaluate partner just on a regular basis and look at work from operations might allow us.
Speaker Change: So we're kind of within that bandwidth now with the current lead required.
Jonathan Miller: To go more quickly provide some funding provide some resources, which means we don't have.
Speaker Change: And I think on a preclinical basis, if you look at us translating molecules.
Jonathan Miller: To utilize our resources and we'll keep making those.
Jonathan Miller: Decisions. So I think for some of those newer disclosure to make we're evaluating whether we could do that internally, we're evaluating whether a collaborative approach might allow us to do that so far we have not had attrition in our in our portfolio that would cause you to be just wanted to make sure we werent.
Stephen Wiley: And I guess I ask the question because there's a lot of interest around. The progress being made on 191, just giving the same novel linker payload, is being leveraged across a variety of different Holy Gnomes. Yeah, thank you. It's not that we're hesitant to provide guidance. We just don't think it's appropriate at this stage. Obviously, these programs are still early. You know, we're very encouraged so far by the speed of our Phase I studies. We had this idea of building a larger, globally diversified footprint of clinical sites so that we could find quality patients quickly in the dose-test patient stage.
Speaker Change: Probably handle about.
Speaker Change: And at any one time improvement.
Speaker Change: Got it.
Speaker Change: So thats pretty reasonable and with the portfolio, we obviously have.
Speaker Change: A substantial amount of substrate and our preclinical programs are really interesting molecule. We think are all different and we just we make the choices, which would help improve the quality of our clinical portfolio that we have.
Jonathan Miller: Two months.
Jonathan Miller: So I think right now you are comfortable with the pace of our of our clinical development nomination.
Speaker Change: To date, we've been doing this on our own.
Jonathan Miller: Something that we can add on.
Speaker Change: In keeping all of our doctors unencumbered.
Jonathan Miller: In a proper way and we're doing that in alpha one step more than nine months two five months ago.
Speaker Change: We do evaluate partner just on a regular basis and look at work from operations might allow us.
The transition to the clinic.
Jonathan Miller: And we will evaluate them cooperative opportunities.
Speaker Change: To grow more quickly provide some funding provided some clinical resources.
Ken Galbraith: And so far, that's working as well as we could have ever hoped to do. I think we're encouraged by the early data. We've seen it's early. So far, we've had no surprises in translation from our preclinical hypothesis in clinical studies. That being said, it's still early in that process. I think we do want to make sure that when, as we prepare for some peer-reviewed, some data to be presented in peer-reviewed forums, that it's the appropriate time and we can make some conclusions that are important to share. And I think the guidance we gave before is still what holds.
Jonathan Miller: That's going to be able to adapt some of those other programs without requiring capital investment for us at all and without acquiring taking up some of the time of our regardless of the think forward either R&D or <unk>.
Speaker Change: <unk> utilized our referral resources.
Speaker Change: Making note.
Speaker Change: Decisions. So I think for some of those newer disclosure to make we're evaluating.
Speaker Change: Whether we could do that internally, we are evaluating whether a collaborative approach might allow us to do that so far we have not had attrition in our in our portfolio that would cause you to be just wanted to make sure we werent.
Jonathan Miller: In early clinical studies is that the thing we evaluate on a regular on.
Jonathan Miller: On a regular basis and as we make decisions about collaboration and public before.
Jonathan Miller: More about that.
Jonathan Miller: Okay.
Speaker Change: Two months.
Jonathan Miller: Hope that answered your question.
Speaker Change: So I think right now youre comfortable with the pace of our of our clinical development nomination.
Jonathan Miller: Yes, sure absolutely. Thanks, so much.
Ken Galbraith: I think as soon as we think that's appropriate, we'll file for an abstract to be presented at a meeting. And once that abstract file is made public, that will be the guidance. And I'm sure we'll get more than that. But I think that's just the appropriate thing to do. We don't want to do that at an IR event or a corporate event. We think the peer-reviewed section is the way to do that. But again, don't let that think that we're not really encouraged by our progress to date, excited that it's going apace. Again, as there's changes to be made on clintrials.gov in those progress, you'll be able to see those as they're made in ClinTrials.
Speaker Change: Thank you one moment for our next question.
Speaker Change: Something that we can add on.
Speaker Change: In a proper way and we're doing that alpha 171191 unexpected.
Jonathan Miller: Yeah.
Speaker Change: I wanted to go.
Speaker Change: And our next question comes from the line of Andrew Berens of Leerink Partners. Your line is now open.
Speaker Change: Transition to the clinic.
Speaker Change: We'll evaluate from cooperative opportunities that might present position.
Jonathan Miller: Hi, everyone. This is Amanda on for Andy Mary Thanks for taking our question.
Speaker Change: We're able to add that some of those other programs without requiring capital investment for us at all and without acquiring.
Speaker Change: Maybe just one from us at ACR, you had a poster on our relatively new ADC target the ally.
Speaker Change: Some of the time of our regards to think forward either through Iot or.
Speaker Change: Looks like at least one other ADC target has had initial phase one data publicly disclose I just wanted to get a little bit more color on what gives you confidence in this target and your offset over the others out there. Thanks.
Speaker Change: And early clinical studies that the thing we evaluate on a regular.
Speaker Change: On a regular basis and as we make decisions about collaborations and became public before.
Stephen Wiley: And the guidance we'll give is just to look forward to an abstract title with the appropriate timeframe when it's accepted. And then we're happy to talk about it at that point. But until then, we just don't, inside the company, think it's appropriate to get too far ahead of yourself in early Phase 1 studies. And so you'll just have to wait for any time with guidance or timing for that. Okay, that's fair.
Speaker Change: More about that.
Speaker Change: Yes no.
Speaker Change: Thanks for asking that question.
Speaker Change: Okay.
Speaker Change: Yes.
Speaker Change: I hope that answered your question.
Speaker Change: Youre absolutely right there had been a prior <unk>.
Speaker Change: <unk> against that target.
Speaker Change: Yes, sure absolutely. Thanks, so much.
Speaker Change: And that clinical data had been reported against licensee there.
Speaker Change: Okay.
Speaker Change: Thank you one moment for our next question.
Speaker Change: The PLO was different.
Speaker Change: Yes.
Speaker Change: On the <unk>.
Speaker Change: Antibody was very different so one of the things that we realized that our team realized with target was.
Speaker Change: And our next question comes from the line of Andrew Burns of Leerink Partners. Your line is now open.
Stephen Wiley: And then just, I know you've talked about having finite amount of clinical development capacity in-house for the wholly-owned program. And that kind of forces you to, you know, make certain capital allocation and strategic decisions with respect to each of these programs. Is the clinical development infrastructure or capacity, is that something that you're willing to flex outwards depending upon the success of ZANI and the triggering of specific milestones from jazz? Is there a situation where, you know, you're enamored with your wholly owned portfolio beyond. The capacity that you have and some of those additional funds can.
Speaker Change: Hi, everyone. This is Amanda Entre Andy Bang, Thanks for taking our question.
Speaker Change: The opportunity to really optimize both.
Speaker Change: Antibody and appeal and so what we're deploying on the <unk> side is a different payload it's approval payload.
Speaker Change: Maybe just one from us at ACR, you had a poster on <unk> ADC target license.
Speaker Change: In the field that has kind of <unk>.
Speaker Change: It looks like at least one other ADC with a target for that initial phase one data publicly disclose I just wanted to get a little bit more color on what gives you confidence in this target and your offset over the others out there. Thanks.
Speaker Change: Gained a lot of momentum and we think that that is the of this target and the expression profile about target, we think theres room, there for a <unk> molecule.
Speaker Change: Yes.
Speaker Change: Of course, we have our payload that we've got that's been <unk>.
Speaker Change: Thanks for asking that question.
Speaker Change: Yes.
Speaker Change: Selected for optimal.
Speaker Change: Absolutely right there had been a prior <unk>.
Speaker Change: Properties that we believe are needed.
Speaker Change: Program against that target.
Speaker Change: And then equally important for this target the antibody selectivity and getting an antibody we spend a lot of time of our team and it was focused on getting an antibody that's really.
Speaker Change: And that clinical data had been reported against <unk>.
Speaker Change: The PLO was different.
Speaker Change: On the <unk>.
Speaker Change: Antibody with very different so one of the things that we realize our team realized with target was.
Ken Galbraith: trigger an expansion of that infrastructure to accommodate the growing pipeline. Thanks. Yeah, no, good question. I mean, right now, we're, you know, really happy with what we rebuilt at Zymeworks to execute these Phase I programs. And so far, they're going as quickly as they possibly could, and really encouraged with the way that we decided to do this. We built out, as you saw in our slide deck, a pretty large number of clinical sites in a significant number of countries before it goes to escalation. But that's just to allow us then to move quickly and follow data to the next So, the next step, and I think for 171 and 191, those programs are moving very quickly, and we want to make sure that we have resources available to move quickly to follow data where it tells us to go, and I think we're well-situated to do that.
Speaker Change: Significantly better at <unk> delivering.
Speaker Change: The opportunity to really optimize both.
Speaker Change: And internalization.
Speaker Change: That was kind of describing the ports so not benchmarked against that prior molecule. So we think that will give us.
Speaker Change: Antibody under period, and so what we're deploying on the <unk> side is a different payload is approvable payload.
Speaker Change: An advantage on this performance.
Speaker Change: In the field that has kind of <unk>.
Speaker Change: What was encouraging news from the original pre clinically there was it was evidenced with clinical responses.
Speaker Change: And a lot of momentum and we think that that is the target and the expression profile of the target, we think theres room, there for a <unk> molecule.
Speaker Change: Optimal.
Speaker Change: But also the targets seem to be relatively.
Speaker Change: Of course, we have our <unk> that we've got that's been <unk>.
Speaker Change: Safe target for an ADC.
Speaker Change: Selected for optimal properties that we believe are needed.
Speaker Change: With our enhanced antibody and with our prepared payload when we've modeled items and homologous monkeys. We also see a very favorable tolerability profile with that kind of thing.
Speaker Change: And then equally important for this target the antibody selectivity and getting an antibody we spend a lot of time of our team and it was.
Speaker Change: Together with the efficacy that.
Speaker Change: Focused on getting an antibody that's really.
Speaker Change: Significantly better than the Tolerability, we just think is.
Ken Galbraith: We're obviously putting 251 into the clinic coming up here pretty shortly, and I feel comfortable with our ability to execute that program in the same fast way with good-quality investigators in a large footprint the way we have with 171 and 191. So, so far, that's not an issue. I think our execution has been really good operationally, and that clinical execution is an important skill of ours to have, and I think we have that right now. I don't want to mess too much with that in terms of diluting talent or changing the way that we're doing that, but I think as we have other agents which are able to move in the clinic, I don't think it'll be a limiting factor right now the way that we've designed it.
Speaker Change: Nice recipe for a real game changer best in class molecule against this target.
Speaker Change: Significantly better at pizza delivery.
Speaker Change: And internalization.
Speaker Change: That was kind of describing the pools, so not benchmarked against that prior molecule. So we think that will give us.
Speaker Change: Got it thanks, so much.
Speaker Change: Thank you one moment for our next question.
Speaker Change: An advantage on this performance.
Speaker Change: Yes.
And our next question comes from the line of our cost of borrowing of Jefferies. Your line is now open.
Speaker Change: And what was encouraging more from the original pre clinically there was it was evidence of clinical responses.
Speaker Change: Hi, This is Steven on for cost in your preclinical models with Chartwell Adcs, you're able to get to Max doses with term meaningfully higher than what you've seen with <unk> is there any concern that youre toxins could potentially not be potent enough.
Speaker Change: Optimal.
Speaker Change: But also the targets seem to be relatively.
Speaker Change: Safe target for an ADC.
Speaker Change: With our enhanced antibody and with our preferred payload will mute modal dotting cinema August because we also see a very favorable tolerability profile with that too.
Speaker Change: And Additionally, if you could provide any color on what your go forward doses are afraid TWD 191, and 251 that'd be great.
Ken Galbraith: So I feel really comfortable with the capital we're putting against it, the resources we have against it, the speed we have, the clarity in our ability to move quickly to the next stage in clinical development for those programs when the data suggests to us that it's time to do that. So, far, I don't need more capital to do that. If we needed that, then we'll make the appropriate capital allocations around the investment criteria. I'm really happy where we are in our execution and we'll continue to do that without putting any more capital at risk to build a bigger company.
Speaker Change: Together with the efficacy.
Speaker Change: Sure, Yes, I know.
Speaker Change: Significantly better than the Tolerability, we just think is.
Speaker Change: Good question and we've actually done a lot of benchmarking of our appeal with.
Speaker Change: A nice recipe for a real game changer best in class molecule against this target.
Speaker Change: Then <unk> or <unk>, we see actually in preclinical models very comparable efficacy profile along.
Speaker Change: Got it thanks, so much.
Speaker Change: Thank you one moment for our next question.
Speaker Change: Along with a lot of in vitro data and then also in in vivo models. So I think we're very confident based on.
Speaker Change: Yes.
Speaker Change: And our next question comes from the line of <unk> <unk> of Jefferies. Your line is now open.
Speaker Change: The preclinical models that we have the necessary efficacy.
Speaker Change: Hi, This is Steven on for cost in your preclinical models with Turbo Adcs, you're able to get to Max doses with terminal for higher than what you've seen with <unk> is there any concern that youre toxins could potentially not be permanent.
Speaker Change: It's in the same ranges <unk> payloads.
Speaker Change: <unk>.
Ken Galbraith: All right, thanks for taking the questions. Thank you.
Speaker Change: What was the second question.
Speaker Change: Any color on go forward doses alright.
Operator: We'll move it for our next question.
Speaker Change: And Additionally, if you could provide any color on what your go forward doses are afraid TWD 191 and 251.
Speaker Change: Yes, yes, yes, no we cant.
Jonathan Miller: And our next question comes from the line of Jonathan Miller of Evercore SI. Your line is now open. Great. Thanks so much for taking the question, guys, and congrats on the progress. Maybe just building on that previous question a little bit, obviously, you've got a large internal pipeline, and as we heard more about at ACR and again today, a lot of potential programs that you could add to either development collaborations or your internal pipeline, even when the time comes.
Speaker Change: Specify those but as you.
Speaker Change: Alluded to the fact that we have this very high tolerability dose.
Speaker Change: Sure, Yes, I know.
Speaker Change: Good question and we've actually done a lot of benchmarking of our appeal.
Speaker Change: Non human primates that enables us to guide or start with a higher starting dose in patients.
Speaker Change: Then <unk>, we see actually in preclinical models very comparable efficacy profile both along.
Speaker Change: But that would be the typical approach anyone developing ADC withdrew Edinburgh.
Speaker Change: Along with a lot of in vitro data and and also in in vivo models.
Speaker Change: And assume that we would be consistent with that.
Speaker Change: Got it thank you thanks.
Speaker Change: I think we're very confident based on.
Speaker Change: Thank you one moment for our next question.
Speaker Change: The preclinical models that we have the necessary efficacy.
Jonathan Miller: How many, you know, I know we've discussed this obliquely in the past, but how many programs can you support early development for internally, and what is the gating factor on external collaborations? And I know those take work for Zymeworks as well. How many molecules could you have across the portfolio, whether they're internal and external? Trying to get a sense for when those things we heard about at ACR could become more relevant to the story. Yeah, no, great, great question. You know, I think in building out our clinical infrastructure, you know, we built it in a way that we, you know, we believe we could, we could handle with the existing build out we have now probably around five internal programs ourselves through phase one.
Speaker Change: It's in the same ranges <unk> payloads.
Speaker Change: Our next question comes from the line of Nausea, Mohit <unk> of Citigroup. Your line is now open.
Speaker Change: <unk>.
Speaker Change: What was the second question.
Mohit: Yes, hi, thank you.
Speaker Change: Paul I see you did the comp analysis versus the Amgen molecule for the for your DLL. Three did you also look at.
Speaker Change: Any color on that go forward, Joe says alright, well at nine 1%.
Speaker Change: Yes, yes, yes, no we cant.
Speaker Change: Specify those but as you can.
Speaker Change: 209 performs against some of the DLL three adcs out there of which there are few.
Speaker Change: Alluded to the fact that we have this very high tolerability dose.
Speaker Change: Nonhuman primates that enables us to guide or start with a higher starting dose in patients.
Speaker Change: Yes, we haven't we haven't done that the models are a little bit different provide.
Speaker Change: But that would be the typical approach anyone developing ADC with threw it in there.
Speaker Change: So.
Speaker Change: In this case, we tend to compare against similar modalities.
Speaker Change: And assume that we would be consistent with that.
Speaker Change: We certainly are aware of.
Ken Galbraith: So that, you know, we're, we're kind of within that bandwidth now with the currently declared.
Speaker Change: Got it thank you thanks.
Speaker Change: The attraction of ADC approach is also for you.
Speaker Change: Thank you one moment for our next question.
Speaker Change: Procurements open so thats why were doing adcs.
Ken Galbraith: So, let's do a quick overview of the candidates. I think on a preclinical basis, if you look at us translating molecules to the clinic, we could probably handle about ten at any one time, including the clinical candidates. So, we've got a pretty reasonable bandwidth to handle the portfolio. We obviously have a substantial amount of substrate in our preclinical programs of really interesting molecules that we think are all different. And we just, you know, we make the choices which we hope improves the quality of the clinical portfolio that we have. To date, we've been doing this all on our own and keeping all of those assets unencumbered.
Speaker Change: There we are aware of what the competitive spaces is there in this case for small cell lung cancer, we felt on the bikes.
Aegon: Our next question comes from the line of Aegon in Ocho Mohit <unk> of Citigroup. Your line is now open.
Aegon Mohit: Yes, hi, thank you.
Speaker Change: We encourage the data from Amgen and the ability to get these more durable responses that really was an attraction here for us focusing on the T cell engaging approach.
Speaker Change: All I see you did the comp analysis versus the Amgen molecule for the for your DLL. Three did you also look at.
Speaker Change: 200, <unk> performs against some of the DLL three adcs out there of which there are few.
Speaker Change: But we certainly keep people ourselves aware of the ADC approaches there too.
Speaker Change: But doing a head to head comparisons it's not so easy to do those in the same models different kind of models.
Yes, we haven't we haven't done that I mean, the models are a little bit different provider.
Speaker Change: Okay, what's your sort of more general view, though in terms of the strategy of the T cell engagement versus the ADC.
Speaker Change: So.
Ken Galbraith: We do evaluate partnerships on a regular basis and look at where collaborations might allow us to go more quickly, provide some funding, provide some clinical resources, which means we don't have to utilize the virtual resources, and we'll keep making those. So, I think for some of those newer disclosures we're going to make, we're evaluating whether we could do that internally. We're evaluating whether a collaborative approach might allow us to do that. So far, we've not had a cushion in our portfolio that would cause BW220 at IND, just to make sure we weren't taking on too much.
Speaker Change: In this case, we tend to compare against similar modalities.
Speaker Change: For this particular target.
Speaker Change: We certainly are aware of that.
Speaker Change: Yes, I think you are in this particular target we really like this is the target too.
Speaker Change: The attraction of ADC approach is also for procurement so thats why were doing adcs.
To evaluate with our <unk> platform.
Speaker Change: We are aware of what the competitive spaces is there in this case for small cell lung cancer, we felt on the backs of.
Speaker Change: And so we have the <unk>.
Speaker Change: Onset for T cell engagement. So that was partly why we we went there with a T cell approach, we certainly have.
Speaker Change: We encourage the data from Amgen and the ability to get these more durable responses that really was an attraction here for us focusing on the T cell engaging approach.
Speaker Change: We could've done ADC, but in this case, we felt lets take a tumor type in this target.
Speaker Change: But we certainly keep or sell.
Speaker Change: The way the data was more made more sense to move the T cell approach and then of course we.
Speaker Change: I was aware of the ADC approaches there too.
Speaker Change: <unk>.
Speaker Change: We tried we did our preclinical studies and the data that we've seen with the preclinical data studies, just really encourages us to continue on that path towards the clinic. So that was that was.
Speaker Change: And that.
Speaker Change: Doing a head to head comparisons it's not so easy to do those in the same models different kind of models.
Speaker Change: Okay, what's your sort of more general view, though in terms of the strategy of the T cell engagement versus the ADC.
Speaker Change: The driver there is certainly when we think about a therapeutic indication we will evaluate both in ADC and the T cell engagement.
Ken Galbraith: And we'll evaluate some collaborative opportunities that might put us in a position to be able to advance some of those other programs without requiring capital investment for ourselves and without acquiring, taking up some of the time of our informal resources to move things forward, either to IND or in early clinical studies. That's the thing we evaluate on a regular basis, and as we make decisions about collaborations that become public, I think we'll be able to discuss more about that. Hope that answers your question. Yeah, sure, absolutely, thanks so much. Thank you. One moment for our next question.
Speaker Change: This particular target.
And we will we do see benefit perhaps some things of having both approaches available.
Speaker Change: Yes, I think Youre in this particular chart that we really like this is the target to.
Speaker Change: To evaluate with our <unk> platform.
Speaker Change: We think in this case for DLL three this was.
Speaker Change: And so we have the <unk> proof of concept for T cell engagement. So that was partly why we we went there with a T cell approach, we certainly have we.
Very obvious targets due to the T cell engagement with the CD 20 Ecu stimulation.
Speaker Change: Okay. Thank you.
Margaret: Thank you Margaret for next question.
Speaker Change: We could've done ADC, but in this case, we felt lets take a tumor type in this target.
Margaret: And our next question comes from the line of Eric <unk> of Wells Fargo. Your line is now open.
Speaker Change: The weighted data was more it made more sense to go with a T cell approach and then of course we.
Speaker Change: We tried we did our preclinical studies and the data that we've seen with the preclinical data studies, just really encourages us to continue on that path towards the clinic. So that was that was the driver. There is certainly when we think about a therapeutic indication we will evaluate both in ADC and the T cell engagement.
Margaret: Hi, This is <unk> on for Derik. Thanks for taking our question a quick one from US. So are there any learnings from 171 or 191 development that could be applied to optimize our expedite the development of your other ADC or T cell engage with candidates.
Andrew Behrens: And our next question comes from the line of Andrew Behrens of Living Partners.
Phoebe Tan: Your line is now open. Hi, everyone.
Speaker Change: And we will we do see benefit perhaps some things are having.
Speaker Change: Yes go ahead Paul.
Paul Moore: This is Amanda Entree-Andy Barron. Thanks for taking our question. Maybe just one from us. At AACR, you had a poster on a relatively new ADC target, the LY6E, and it looks like at least one other ADC with this target has had initial phase one data publicly disclosed. I just wanted to get a little bit more color on what gives you confidence in this target and in your asset over the others out there. Thank you. Yeah, no, thanks for asking that question. Yeah, you're absolutely right. There had been a prior program against that target, and that clinical data had been reported against Y6C.
Speaker Change: Both approaches available but.
Paul: Yes, no definitely for sure I mean, I think we've put a lot of learnings.
Speaker Change: But we think in this case for DLL. Three this was this is a.
Paul: Clinical design, we're able to leverage learnings from other ADC is another T cell engages and certainly as we move forward other adcs in T cell engages we'll learn from what we've done ourselves.
Speaker Change: A very obvious targets due to the T cell engagement with the CD 20 Ecu simulation.
Speaker Change: Okay. Thank you.
Margaret: Thank you Margaret for next question.
Paul: So we're always leering and not.
Speaker Change: And our next question comes from the line of Eric <unk>.
Paul: And knowledge base there.
Paul: So reveal more in the trials in progress poster.
Eric: <unk> of Wells Fargo. Your line is now open.
Posters. This year that are already scheduled to be presented and you'll see there. We can give you a little bit more color on that and you can then maybe see from that how we may also.
Speaker Change: Hi, This is <unk> on for Derik. Thanks for taking our question a quick one from US. So are there any learnings from 171 or 191 development that could be applied.
Paul Moore: There, you know, the payload was different, and the antibody was very different. So one of the things that we realized, or our team realized with that target, was the opportunity to really optimize both antibody and the payload. And so what we're deploying on the payload side is a different payload. It's a topo payload. You know, in the field, that has kind of gained a lot of momentum, and we think that that is a, for this target and the expression profile of that target, we think there's room there for a topo payload module. And of course, we have our payload that we've got that's been selected for optimal, you know, properties that we believe are needed.
Paul: Continue that these types of strategies and other coupons, but can't really see much more than that.
Speaker Change: Optimize our expedite the development of your other ADC or T cell engaged candidates.
Paul: Great. Thanks.
Speaker Change: Yeah.
Paul: Yes go ahead Paul.
Speaker Change: Thank you one moment for our next question.
Paul: Yes, no definitely for sure I mean, I think we've put a lot of learnings back into the clinical design, we're able to leverage learnings from other adcs and other T cell engaging and certainly as we.
As a reminder to ask a question you will need to press star one on one or your telephone keypad.
Speaker Change: And our next question comes from the line of Robert Burns of AC Wainwright. Your line is now open.
Paul: We'll move forward other adcs in T cell engages we'll learn from what we've done ourselves.
Robert Burns: Guys. Thanks for taking my thanks for taking my questions and congrats on the data that you presented at ACR just two for me if I may.
Paul: So we're always leering and not.
Paul: The knowledge base there.
Paul: We will reveal more in the trials in progress post.
Speaker Change: Given the repeat challenge assay data.
Paul: Posters this year that are there.
Speaker Change: For 209 as well as the in vivo data.
Paul: <unk> already scheduled to be presented and Youll see there. We can give you a little bit more color on that and you can then maybe see from that how we may also.
Paul Moore: And then, equally important for this target, the antibody selectivity and getting an antibody, we spent a lot of time, or our team kind of was focused on getting an antibody that's really, you know, a lot, you know, significantly better at payload delivery and internalization. And that was kind of described in the poster, and that's benchmarked against that prior molecule. So we think that will give us, you know, an advantage on its performance. And what was encouraging, though, from the original preclinical data was that it was evidence of clinical responses. You know, they weren't optimal. But also, the targets seem to be relatively, you know, safe target for an ADC.
Speaker Change: Factor alone I am vouchers.
Speaker Change: Moving from the front line.
Speaker Change: <unk> indicated frontline setting for SCLC.
Paul: Continue that these pics or strategies and other programs, but can really see much more than that.
Speaker Change: Combination with Astrazeneca Kinsey I was curious to get your thoughts as to how you see the impact of earlier utilization of ultra.
Paul: Great. Thanks.
Speaker Change: Thank you one moment for our next question.
Speaker Change: On the efficacy of <unk> nine in a later phase <unk>.
Speaker Change: Again as a reminder to ask a question you will need to press star one on one or your telephone keypad.
Speaker Change: Scenario.
Speaker Change: Okay.
Speaker Change: Yes, yes, no I think <unk>.
Speaker Change: Yes.
Speaker Change: Would we be thinking about the design of our molecules, obviously, obviously, we need to stage of clinical testing, but we.
Speaker Change: And our next question comes from the line of Robert Burns of HC Wainwright. Your line is now open.
Speaker Change: We do see the ability of a T cell engagement strategy to really move the needle in in small cell lung cancer and <unk>.
Speaker Change: Hey, guys. Thanks for taking my thanks for taking my questions and congrats on the data that you presented at ACR just two for me if I may given the repeat challenge assay data.
Operator: And with our enhanced antibody and with our, you know, preferred payload, when we've modeled that in Sinomog as monkeys, we also see a very favorable tolerability profile. So that kind of, together with the efficacy that's, you know, significantly better and the tolerability, we just think is, you know, a nice recipe for a real team changer, best-in-class molecule against the target. Got it. Thanks so much. Thank you. One moment for our next question.
Speaker Change: For 209 as well as the in vivo data.
Speaker Change: We think that the Amgen data the <unk> data bodes well.
Speaker Change: Factor alone I am vouchers.
Speaker Change: But I think that in the design of the molecule. If you can enhance the efficacy and constant durability of response.
Speaker Change: Moving from the front line.
Speaker Change: Scott indicated frontline setting for SCLC.
Speaker Change: We broadened the response rate that.
Speaker Change: In combination with Astrazeneca Kenzie I was curious to get your thoughts as to how you see the impact of earlier utilization of ultra.
Speaker Change: That's what that's what you can do with this next generation molecule that we've developed and I think that as well as the efficacy. We are very careful and tolerability <unk> seen that in our ADC approach I think you've seen that in our 171 approach and Thats also reflected into <unk>, where we really think about tolerability. So that we can.
Speaker Change: On the efficacy of <unk> nine in a later phase.
Speaker Change: Scenario.
Speaker Change: Yes, yes, no I think that.
Akash Javari: And our next question comes from the line of Akash Javari of Jeffrey's Airlines Now.
Speaker Change: Definitely when we've been thinking about the design of our molecules, obviously, obviously, we need to stage of clinical testing, but we.
Speaker Change: Ultimately combine it with potentially under care once you establish the monotherapy data so heading towards that getting the best benefit for patients.
Phoebe Tan: Hi, this is Phoebe Ankurakosh. In your preclinical models with your tropical ADCs, you're able to get to max doses, which are meaningfully higher than what we've seen with in HER2. Is there any concern that your toxins could potentially not be potent enough? And additionally, if you could provide any color on what your go forward doses are for ZW191 and ZW251 diabetes. No, sure. Yeah, no. Good question. And we've we've actually done a lot of benchmarking of our payload with the INHER-2 payload or the Roxa T-CAN, and we see actually in preclinical models very comparable efficacy profile, both along a lot of in vitro data and then also in in vivo xenograft models.
Speaker Change: We do see the ability of a T cell engagement strategy to really move the needle in in small cell lung cancer, and we think that the amgen data the <unk> data bodes well.
Speaker Change: 10, a wired into into our thinking on the design of all our R. R.
Speaker Change: Both of them.
Speaker Change: Awesome. Thank you for that and one more question. So the PTK seven targeted agent. Obviously, we saw the comparator in vivo data that you presented I was one of those compounds that comparator preclinical compounds one of the ones that Whitehall therapeutics is advancing and if not how do you view that competitive agents that competitor agents.
Speaker Change: But I think that in the design of the molecule. If you can enhance the efficacy and constant durability of response.
Speaker Change: <unk> broadened the response rate.
Speaker Change: That's what that's what Youre kind of do with this next generation molecule that we've developed and I think that as well as the efficacy. We are very careful and tolerability <unk> seen that in our ADC approach I think <unk> seen that in our 171 approach and Thats also reflected in <unk>.
Speaker Change: <unk> to your PTK seven targeted ADC. Thank you.
Speaker Change: Yes.
Speaker Change: Use coker <unk> as the comparator that was the product clinical benchmarking.
Speaker Change: <unk> hundred <unk>, where we really think about tolerability. So that we can ultimately combine it with potentially under care. Once you establish the monotherapy data so heading towards that getting the best benefit for patients.
Paul Moore: So I think we're very confident, you know, based on the preclinical models that we have the necessary efficacy that's in the same range as the Roxa T-CAN payloads. What was the second question, then? Any color on go-forward doses for 1, 9, 1, and 2, 5? Yeah, yeah, yeah, yeah, no, we can't really specify those, but as you, you know, alluded to the fact that we have this very high tolerability dose in non-human primates, that enables us to guide or start with a higher starting dose in patients, and, you know, that would be the typical approach anyone developing ADC would do, and we're, you know, assume that we would be consistent about that.
Speaker Change: What we were really trying to demonstrate was the improvement you can get with a byproduct topic. We also had our own leaf.
Speaker Change: <unk> our model Paratrophic antibody, we also benchmark, but whenever we've seen.
Speaker Change: With tenant wired into into our thinking on the design of all our R. R.
Speaker Change: In this for this particular target, we really think <unk> can push things for other targets is not always the case, but in this case.
Speaker Change: Both of them.
Speaker Change: Awesome. Thank you for that and one more question. So the <unk> targeted agents. Obviously, we saw the comparator in vivo data that you presented I was one of those compounds that comparator preclinical compounds one of the ones that Whitehall therapeutics is advancing and if not how do you view that competitive agent that can penetrate agent.
Speaker Change: Ever model Paratrophic antibody, we've looked at either we've developed or.
Benchmark clinical that we hired available we outperform so that to us.
Speaker Change: Bodes well, we think we're really doing something different to byproducts, obviously can't be achieved.
Speaker Change: Relative to your PTK seven targeted ADC. Thank you.
Speaker Change: We will continue to monitor that.
Speaker Change: Yes.
Speaker Change: As other competitor molecules come across but a real drive here was really to see what we could do with a byproduct.
Speaker Change: Use <unk> as the comparator that was the prior clinical benchmarking.
Paul Moore: Got it.
Operator: Thank you. One moment for our next question.
Speaker Change: We can leverage that capability, obviously, we did it for <unk> and it really moved the needle there in this case.
Speaker Change: What we were really trying to demonstrate was the improvement you can get with a byproduct topic. We also had our own Lee.
Yigal Nochomovitz: Our next question comes from the line of Yigal Nochomovitz of Citigroup. Your line is now open. Yeah, hi. Thank you. Paul, I see you did the comp analysis versus the Amgen molecule for your DLL-3. Did you also look at how 209 performs against some of the DLL-3 ADCs out there, of which there are a few? Yeah, we haven't, we haven't done that. I mean, the models are a little bit different for that. So, in this case, for that, we tend to compare against similar modalities. We certainly are aware of the attraction of ADC approaches also for, you know, for tumors, so that's why we're doing ADCs.
Speaker Change: <unk> our model Paratrophic antibody, we also benchmark, but whenever we've seen.
Speaker Change: Tying it to see what we can do on <unk> seven target. It seems applicable for this type of approach.
Speaker Change: And we will continue to monitor that as we're doing our preclinical work.
Speaker Change: And this for this particular target, we really think byproducts off it can push things for other targets is not always the case, but in this case.
Speaker Change: And consider benchmarks as appropriate.
Speaker Change: Awesome. Thank you guys.
Speaker Change: Whatever model pirates, helping antibody we've looked at either we've developed or the bedroom.
Speaker Change: Thank you Robert.
Speaker Change: I'm showing no further questions at this time I'll now turn it back to Ken <unk> for closing remarks.
Speaker Change: Benchmark clinical that we hired available we outperformed so that to us.
Speaker Change: Thank you operator, thank you everyone for your time listening to US we're always available for questions. Afterwards, if you didn't get a chance to ask additional questions our.
Speaker Change: Bodes well, we think we're really doing something different the byproducts that can't be achieved but we will continue to monitor that.
Speaker Change: As other competitor molecules come across but a real driver here was really to see what we could do with the byproducts of cooking and we can leverage that capability. Obviously, we did it for zani and it really move the needle there in this case we're apply.
Speaker Change: Or something else and in the meantime, please stay tune further developments and we thank our shareholders for their continued support thank you.
Speaker Change: Thank you for your participation in today's conference. This does conclude the program you may now disconnect.
Paul Moore: And, you know, there, you know, we are aware of what the competitive space is there. In this case, for small cell lung cancer, we felt, you know, on the backs of, you know, the encourage, you know, the data from Amgen and the ability to get these more durable responses, that really was an attraction here for us focusing on the T cell engager approach. But we certainly keep ourselves aware of the ADC approaches there, too. And that, you know, but, you know, doing the head-to-head comparisons, it's not so easy to do those in the same models, different kind of models.
Speaker Change: Applying it to see what we can do on <unk> seven target. It seems applicable for this type of approach.
Speaker Change: We'll continue to monitor that as we're doing our preclinical work.
Speaker Change: And consider benchmarks as appropriate.
Speaker Change: Awesome. Thank you guys.
Speaker Change: Thank you Robert.
Speaker Change: Thank you I'm showing no further questions at this time I'll now turn it back to Ken <unk> for closing remarks, yes.
Speaker Change: Yes. Thank you operator, thank you everyone for your time listening to US we're always available for questions. Afterwards, if you didn't get a chance to ask additional questions or.
Paul Moore: Well, okay, well, what's your sort of more general view, though, in terms of the strategy of the T cell engager versus the ADC for this particular target? Yeah, I think here in this particular target, we really like this as a target to... to evaluate with our co-stim platform. And so, you know, we have the Tarlatomab sort of proof of concept for T-cell engager. So that was partly why we went there with a T-cell approach. We certainly have, we could have done ADC, but in this case, we felt this type of tumor type and this target, you know, the way the data was more, made more sense to go with a T-cell approach.
Speaker Change: Or something else.
Speaker Change: In the meantime, please stay tuned for further developments and we thank our shareholders for their continued support thank you.
Speaker Change: Thank you for your participation in today's conference. This does conclude the program you may now disconnect.
Speaker Change: Yes.
Speaker Change: [music].
Paul Moore: And then, of course, we tried, you know, we did our preclinical studies and the data that we've seen with the preclinical data studies just really encourages us to continue on that path forward. So that was a driver there. Certainly, when we think about a therapeutic indication, we will evaluate both an ADC and a T-cell engager, and we do see benefit, perhaps, sometimes in having both approaches available, but we think, in this case, for DLL3, this is a very obvious target to do with a T-cell engager with the CD28 co-stimulation. Okay, thank you.
Speaker Change: Okay.
Speaker Change: [music].
Speaker Change: Yeah.
Speaker Change: Yes.
Speaker Change: [music].
Operator: Thank you. One moment for our next question.
Speaker Change: Yes.
Derek Archila: And our next question comes from a line of Derek Archila of Wells Fargo, your line is now open. Hi, this is Yvonne for Derek. Thanks for taking our question. A quick one from us.
Yvonne: So are there any learnings from 171 or 191 development that could be applied to optimize or expedite the development of your other ADC or TESOL Engager candidates? Yeah, no, definitely for sure. I mean, I think we put a lot of learning into the clinical design. We are able to leverage learnings from other ADCs and other T-cell engagers. And certainly, as we move forward, other ADCs and T-cell engagers will learn from what we've done ourselves. So we're always layering in that knowledge base. We'll sort of reveal more in the trials in progress posters this year that are already scheduled to be presented.
Paul Moore: And you'll see there, we can give you a little bit more color on that. And you can then maybe see from that how we might also continue these types of strategies in other programs. But I can't really say much more than that. Thanks.
Operator: Thank you, one moment, for our next question. Again, as a reminder to ask a question, you'll need to press star 1-1 or your telephone keypad.
Robert Burns: And our next question comes from the line of Robert Burns of AC Wainwright. Your line is now open. Hey guys, thanks for taking my questions and congrats on the data that you presented at AACR. Just two for me, if I may.
Robert Burns: Given the repeat challenge assay data for 209, as well as the in vivo data, and factoring in IM-DELTA's move into the frontline setting for SCLC in combination with AstraZeneca's and Finzi, I was curious to get your thoughts as to how you see the impact of earlier utilization of IM-DELTA on the efficacy of 209 in the later phase scenario. Yeah, yeah, no, I think definitely when we've been thinking about the design of our molecules, obviously, obviously, we need to stage our clinical testing. But we, you know, we, we do see the ability of a T cell engager strategy to really move the needle in, in small cell lung cancer.
Paul Moore: And we think that the Amgen data, the tarlatum map data, you know, goes well. But I think then in the design of your molecule, if you can enhance the efficacy, enhance the durability of response, you know, potentially broaden the response rate, that, that's what you're, that's what you're kind of do with this next generation molecule that we've developed. And I think that, you know, as well as the efficacy, we are very careful on tolerability. You've seen that in our ADC approach. I think you've seen that in our 171 approach. And that's also reflected in 209, where we really think about tolerability so that we can ultimately combine it with, you know, potentially standard care once you've established the monotherapy data.
Paul Moore: So heading towards that, getting the best benefit for patients is, you know, it's kind of wired into, into our thinking on the design of all our, our, our, our molecules. Awesome. Thank you for that.
Paul Moore: And one more question. So the PTK7 targeted agent, obviously, you know, we saw the comparator in vivo data that you presented, was one of those compounds, one of the comparative preclinical compounds, one of the ones that Whitehawk Therapeutics is advancing. And if not, how do you view that competitive agent, that competitor agent, relative to your PTK7 targeted ADC? Yeah, we use cocatuzumab as the comparator. You know, that was the prior clinical benchmark. And you know, we, there, what we were really trying to demonstrate was the improvement you can get with a biparatopic. We also had our own lead monoclonal antibody or monoparatopic antibody we also benchmarked.
Paul Moore: But whatever we've seen, in this, for this particular target, we really think biparatopic can push things. For other targets, it's not always the case. But in this case, whatever monoparatopic antibody we've looked at, either we've developed, or the sort of benchmark clinical that we had available, we outperformed. So that, to us, you We're really doing something different with the biparatopic that can't be achieved, but we will continue to monitor that as other competitor molecules come across. But our real drive here was really to see what we could do with the bipartotopic. And we can leverage that capability.
Operator: Obviously, we did it for Xani, and it really moved the needle there. In this case, we're applying it to see what we can do on PTK7, a target that seems applicable for this type of approach. And we'll continue to monitor that as we're doing our preclinical work and consider benchmarks as appropriate. Awesome. Thank you, guys. Thank you, Robert. Thank you. I'm showing no further questions at this time.
Ken Galbraith: I'll now turn it back to Ken Galbraith for closing remarks. Yeah, thank you, operator. Thank you, everyone, for your time listening to it.
Ken Galbraith: We're always available for questions afterwards if you didn't get a chance to ask additional questions or something else, and in the meantime, please stay tuned for further developments, and we thank our shareholders for their continued support. Thank you. Thank you for your participation in today's conference.
Operator: This does conclude the program. You may now disconnect.