Q1 2026 CytomX Therapeutics Inc Earnings Call

May 7, 2026

Speaker #1: Good afternoon, everyone. Thank you for standing by. Welcome to the CytomX Therapeutics first-quarter 2026 financial results call. Please be advised that today's conference is being recorded.

Operator: Good afternoon, everyone. Thank you for standing by. Welcome to the CytomX Therapeutics Q1 2026 Financial Results Call. Please be advised that today's conference is being recorded. I would now like to hand the call over to your host for today, Chris Ogden, CytomX Chief Financial Officer. Please go ahead.

Speaker #1: I would now like to hand the call over to your host for today, Chris Ogden, CytomX Chief Financial Officer. Please go ahead.

Speaker #2: Thank you. Good afternoon, and thank you for joining us. Before we begin, I would like to remind everyone that during this call, we will be making forward-looking statements.

Chris Ogden: Thank you. Good afternoon, and thank you for joining us. Before we begin, I would like to remind everyone that during this call we'll be making forward-looking statements. Because forward-looking statements relate to the future, they're subject to inherent uncertainties and risks that are difficult to predict, and many of which are outside of our control. Important risks and uncertainties are set forth in our most recent public filings with the SEC at sec.gov. We undertake no obligation to update any forward-looking statements, whether as a result of new information, future developments, or otherwise. Earlier this afternoon, we issued a press release that includes a summary of our Q1 2026 financial results and highlights recent progress at CytomX. We encourage everyone to read today's press release and the associated materials which have been filed with the SEC.

Speaker #2: Because forward-looking statements relate to the future, they are subject to inherent uncertainties and risks that are difficult to predict and many of which are outside of our control.

Speaker #2: Important risks and uncertainties are set forth in our most recent public filings with the SEC at sec.gov. We undertake no obligation to update any forward-looking statements, whether as a result of new information, future developments, or otherwise.

Speaker #2: Earlier this afternoon, we issued a press release that includes a summary of our first quarter 2026 financial results and highlights recent progress at CytomX.

Speaker #2: We encourage everyone to read today's press release and the associated materials which have been filed with the SEC. Additionally, the press release recording of this call and our SEC filings can be found under the Investors and News section of our website.

Chris Ogden: The press release, recording of this call, and our SEC filings can be found under the Investors and News section of our website. With me on the call today is Dr. Sean McCarthy, CytomX's Chief Executive Officer and Chairman. Sean will provide an update on our pipeline and company progress before I cover the financials for the quarter. We will conclude with a Q&A session. With that, I'll now turn the call over to Sean.

Speaker #2: With me on the call today is Dr. Sean McCarthy, CytomX's Chief Executive Officer and Chairman. Sean will provide an update on our pipeline and company progress before I cover the financials for the quarter.

Speaker #2: We will then conclude with a Q&A session. With that, I'll turn the call over to Sean.

Speaker #3: Thanks, Chris, and good afternoon, everyone. We're very pleased to be here today to provide an update on our first quarter developments and guidance for what's continuing to be a transformational year for CytomX.

Sean McCarthy: Thanks, Chris. Good afternoon, everyone. We're very pleased to be here today to provide an update on our Q1 developments and guidance for what's continuing to be a transformational year for CytomX. 2026 is off to a very exciting start, driven by our excellent clinical progress with Varseta-M in late-line colorectal cancer. Varseta-M is a first-in-class EpCAM targeting antibody-drug conjugate, or ADC, that was uniquely designed and enabled by our proprietary PROBODY therapeutic masking platform. Varseta-M is the only EpCAM-directed ADC in clinical development to our knowledge, affording us a strong lead and a powerful competitive advantage. EpCAM is one of the most abundant solid tumor surface antigens, and CytomX's breakthrough in unlocking EpCAM as an ADC target positions Varseta-M as a company-building asset over the near and long term.

Speaker #3: 2026 is off to a very exciting start, driven by our excellent clinical progress with Varsita M in late-line colorectal cancer. Varsita M is the first-in-class ATCAM-targeting antibody-drug conjugate, or ADC, that was uniquely designed and enabled by our proprietary pro-body therapeutic masking platform.

Speaker #3: Varsita M is the only ATCAM-directed ADC in clinical developments to our knowledge, affording us a strong lead and a powerful competitive advantage. ATCAM is one of the most abundant solid tumor surface antigens and CytomX breakthrough in unlocking ATCAM as an ADC target positions Varsita M as a company-building asset over the near and long term.

Speaker #3: We see multiple layers of value creation potential for CytomX through the advancement of Varsita M. In colorectal cancer, which I'll now refer to as CRC, our goal is for Varsita to become a core component of the standard of care including in earlier-line therapy.

Sean McCarthy: We see multiple layers of value creation potential for CytomX through the advancement of Varseta-M. In colorectal cancer, which I'll now refer to as CRC, our goal is for Varseta to become a core component of the standard of care, including in earlier line therapy. Metastatic CRC remains one of the largest areas of unmet need in oncology today, which really underscores the urgency we feel at CytomX to progress Varseta-M towards the market as rapidly as possible. Commercially, in the late line setting alone, this represents a multi-billion dollar market. In addition to the very substantial opportunity in CRC, we also plan to capitalize on our leadership in EpCAM targeting by developing Varseta-M in other cancers and ultimately as a pan-tumor therapy.

Speaker #3: Metastatic CRC remains one of the largest areas of unmet need in oncology today, which really underscores the urgency we feel at CytomX to progress Varsita M towards the market as rapidly as possible.

Speaker #3: Commercially, in the late-line setting alone, this represents a multibillion-dollar market. In addition to the very substantial opportunity in CRC, we also plan to capitalize on our leadership in ATCAM targeting by developing Varsita M in other cancers and ultimately as a pan-tumor therapy.

Speaker #3: Varsita has the long-term potential to positively impact the lives of so many people with cancer, and we are focused on executing with urgency to rapidly progress this potential therapy to regulatory approval.

Sean McCarthy: Varseta-M has the long-term potential to positively impact the lives of so many people with cancer, and we are focused on executing with urgency to rapidly progress this potential therapy to regulatory approval. CytomX has made a very strong start in the clinic with Varseta-M. In our most recent phase I data update in March this year, we shared updated efficacy data in late-line metastatic CRC, showing a confirmed overall response rate between 20% and 32% and approximately 7 months of median progression-free survival. These data position Varseta-M as a potentially transformative step forward in the treatment of metastatic CRC, where currently available therapies offer overall response rates only in the low single digits and just a few months of PFS. Varseta-M is working exactly as designed and is unlocking the true potential of EpCAM for the first time.

Speaker #3: CytomX has made a very strong start in the clinic with Varsita M. In our most recent phase one data update in March this year, we shared updated efficacy data in late-line metastatic CRC showing a confirmed overall response rate between 20 and 32 percent.

Speaker #3: And approximately seven months of median progression-free survival. These data position Varsita as a potentially transformative step forward in the treatment of metastatic CRC, where currently available therapies offer overall response rates only in the low single digits and just a few months of PFS.

Speaker #3: Varsita M is working exactly as designed, and it's unlocking the true potential of ATCAM for the first time. With Varsita, CytomX is bringing the power of the ADC class to colorectal cancer.

Sean McCarthy: With Varseta-M, CytomX is bringing the power of the ADC class to colorectal cancer. I want to really underscore here that we've achieved something very significant with our PROBODY platform technology. In our view, and based on our preclinical data and efforts of others over many years, we believe we can say with confidence that a conventional unmasked ADC targeting EpCAM would have no chance of achieving dose levels that deliver meaningful anticancer activity due to severe on-target toxicities. In contrast, with Varseta-M, we have achieved remarkable anticancer activity in one of the hardest to treat cancer types. We firmly believe we have done the hardest experiment first by focusing initially in CRC and that the best is yet to come.

Speaker #3: I want to really underscore here that we've achieved something very significant with our pro-body platform technology. In our view, and based on our preclinical data, and efforts of others over many years, we believe we can say with confidence that a conventional, unmasked ADC targeting ATCAM would have no chance of achieving those levels that deliver meaningful anti-cancer activity due to severe on-target toxicities.

Speaker #3: In contrast with Varsita M, we have achieved remarkable anti-cancer activity in one of the hardest-to-treat cancer types. We firmly believe we have done the hardest experiment first by focusing initially in CRC and that the best is yet to come.

Speaker #3: In terms of key near-term objectives for Varsita M, we are currently in dose optimization with the goal of advancing into a registrational study in late-line CRC in the first half of 2027.

Sean McCarthy: In terms of key near-term objectives for Varseta-M, we are currently in dose optimization with the goal of advancing into a registrational study in late-line CRC in H1 2027. Today, we're very pleased to share that we have completed enrollment in the ongoing dose optimization cohorts with 40 total patients now enrolled across the 8.6 and 10 mg/kg doses, taking total enrollment across the phase I study to 113 patients. We remain well on track for an update before the end of this year as we work towards prioritizing one of these two doses of this highly active drug candidate for our first pivotal study.

Speaker #3: Today, we're very pleased to share that we have completed enrollment in the ongoing dose optimization cohorts with 40 total patients now enrolled across the 8.6 and 10 milligram-per-kilogram doses, taking total enrollment across the phase one study to 113 patients.

Speaker #3: We remain well on track for an update before the end of this year as we work towards prioritizing one of these two doses of this highly active drug candidate for our first pivotal study.

Speaker #3: In evaluating the potential registrational study dose, we're focused on optimizing the risk-benefit of Varsita M, building on the significant learnings in the dose escalation, expansion, and optimization phases.

Sean McCarthy: In evaluating the potential registrational study dose, we're focused on optimizing the risk-benefit of Varseta-M, building on the significant learnings in the dose escalation, expansion, and optimization phases. Regarding Varseta-M safety, we have been highly encouraged by the preliminary results we shared in March from dose optimization that show that updated patient management strategies have the potential to substantially reduce the rate of high-grade diarrhea we saw earlier in phase I development. This is the principal adverse event of interest with Varseta, and it's something we feel confident we can get an increasingly well-developed understanding of as we move forward through the optimization cohorts and beyond. Typically, patients respond very well to management, and our overall discontinuation rates are low, accounting for the impressive progression-free survival data we have shared to date.

Speaker #3: Regarding Varsita M safety, we have been highly encouraged by the preliminary results we shared in March from dose optimization that show that updated patient management strategies have the potential to substantially reduce the rate of high-grade diarrhea we saw earlier in phase one development.

Speaker #3: This is the principal adverse event of interest with Varsita, and it's something we feel confident we can get an increasingly well-developed understanding of as we move forward through the optimization cohorts and beyond.

Speaker #3: Typically, patients respond very well to management and our overall discontinuation rates are low, accounting for the impressive progression-free survival data we have shared to date.

Speaker #3: In terms of our next clinical communication, we expect to provide an overall Phase 1 data update, including safety and efficacy from the monotherapy dose optimization, in the second half of this year.

Sean McCarthy: In terms of our next clinical communication, we expect to provide an overall phase I data update, including safety and efficacy from the monotherapy dose optimization in H2 of this year. We expect these data, along with FDA interactions in 2026, to inform Varseta-M monotherapy dose selection and the first registrational study design. Our primary goal with Varseta-M is initially to develop in the late line, where we see this drug candidate as highly differentiated and frankly, as offering a highly impactful new option for CRC patients. Over time, our vision for Varseta in CRC is to replace systemic irinotecan in the treatment paradigm and potentially to displace chemotherapy entirely. Accordingly, and in parallel to its development as a monotherapy in CRC, we are aggressively advancing Varseta-M into combination studies to enable earlier line utilization. Strategically, we see an enormous opportunity for Varseta in early-line CRC.

Speaker #3: We expect these data along with FDA interactions in 2026 to inform Varsita M monotherapy dose selection and the first registrational study design. Our primary goal with Varsita M is initially to develop in the late line where we see this drug candidate as highly differentiated and, frankly, as offering a highly impactful new option for CRC patients.

Speaker #3: Over time, our vision for Varsita in CRC is to replace systemic arenatecan in the treatment paradigm and potentially to displace chemotherapy entirely. Accordingly and in parallel to its development as a monotherapy in CRC, we are aggressively advancing Varsita M into combination studies to enable earlier-line utilization.

Speaker #3: Strategically, we see an enormous opportunity for Varsita in early-line CRC to access this opportunity we have initiated a combination with bevacizumab as a first step to moving Varsita into earlier-line therapy.

Sean McCarthy: To access this opportunity, we have initiated a combination with bevacizumab as a first step to moving Varseta-M into earlier line therapy. Anti-VEGF antibodies, including bevacizumab, are extensively utilized in early and late-line CRC treatment, so this will be a foundational combination. Varseta-M doses assessed in combination with bevacizumab will include both every 2 weeks and every 4 weeks schedules to align dosing with the approved 5 mg per kg every 2 week schedule standardly used in the clinic today. We expect initial clinical data for this combination by H1 2027. We're also accelerating plans to study Varseta-M in combination with chemotherapy, and we plan to begin a phase I/II chemotherapy combination study in H2 2026, evaluating Varseta-M in combination with bevacizumab, fluorouracil, and leucovorin, with the potential to advance into the first and second lines.

Speaker #3: Anti-VEGF antibodies, including bevacizumab, are extensively utilized in early and late-line CRC treatment, so this will be a foundational combination. Varsita M doses assessed in combination with bevacizumab will include both every two weeks and every four weeks schedules to align dosing with the approved 5 mg/kg every two weeks schedule standardly used in the clinic today.

Speaker #3: We expect initial clinical data for this combination by the first half of 2027. We're also accelerating plans to study Varsita in combination with chemotherapy, and we plan to begin a phase one, two chemotherapy combination study in the second half of 2026, evaluating Varsita in combination with bevacizumab via fluorouracil and leucovorin with the potential to advance into the first and second lines.

Speaker #3: In addition to our work in colorectal cancer, we are on track to begin phase one expansion cohorts in additional ATCAM expressing indications in the second half of 2026.

Sean McCarthy: In addition to our work in colorectal cancer, we are on track to begin phase I expansion cohorts in additional EpCAM expressing indications in the second half of 2026. We look forward to providing an update on the initial non-CRC indications later this year with the goal of generating clinical data supporting Varseta's ultimate pan-tumor potential. Turning now to CX-801, our masked interferon alpha-2b program, which is currently in phase I development for advanced checkpoint refractory melanoma. Our vision here is for CX-801 to become a new centerpiece for combination cancer immunotherapy as we harness and redirect the power of this cytokine to reprogram and activate antitumor immunity. We initially see CX-801 as well-positioned to address the high unmet need in PD-1 refractory melanoma, where response rates to approved standard of care remain in the single-digit percentages with limited treatment options available or in clinical development.

Speaker #3: We look forward to providing an update on the initial non-CRC indications later this year with the goal of generating clinical data supporting Varsita's ultimate pan-tumor potential.

Speaker #3: Turning now to CX801, our masked interferon alpha-2b program, which is currently in Phase 1 development for advanced checkpoint-refractory melanoma. Our vision here is for CX801 to become a new centerpiece for combination cancer immunotherapy as we harness and redirect the power of this cytokine to reprogram and activate anti-tumor immunity.

Speaker #3: We initially see CX801 as well positioned to address the high unmet need in PD-1 refractory melanoma, where response rates to approved standard of care remain in the single-digit percentages, with limited treatment options available or in clinical development.

Speaker #3: Interferon alpha-2b is a potent cytokine that has validated clinical activity in melanoma and other cancers and our initial translational data from phase one suggests that CX801's mechanism of action is working as designed in the tumor microenvironment.

Sean McCarthy: interferon alpha-2b is a potent cytokine that has validated clinical activity in melanoma and other cancers, and our initial translational data from phase I suggests that CX-801's mechanism of action is working as designed in the tumor microenvironment. Importantly, our data shared at SITC in 2025 are highly supportive of our strategy for combining with the checkpoint inhibitor KEYTRUDA. Our ongoing CX-801 phase I monotherapy dose escalation study has advanced to the 4th dose level, which exceeds the approved clinical dose of unmasked interferon alpha-2b. CX-801 has been well-tolerated to date, suggesting that our masking strategy is broadening the therapeutic window as designed. Combination dose escalation with KEYTRUDA is also progressing very well and is now actively enrolling in the 3rd dose level.

Speaker #3: Importantly, our data shared at CITCI in 2025 are highly supportive of our strategy for combining with the checkpoint inhibitor Keytruda. Our ongoing CX801 phase one monotherapy dose escalation study has advanced to the fourth dose level, which exceeds the approved clinical dose of unmasked interferon alpha-2b CX801 has been well tolerated to date suggesting that our masking strategy is broadening the therapeutic window as designed.

Speaker #3: Combination dose escalation with Keytruda is also progressing very well and is now actively enrolling in the third dose level. Overall, we view CX801 as very well positioned to address a significant unmet need in advanced melanoma and we look forward to sharing initial clinical data by the end of this year.

Sean McCarthy: Overall, we view CX-801 as very well-positioned to address a significant unmet need in advanced melanoma, and we look forward to sharing initial clinical data by the end of this year. With that, I'll now transition back to Chris.

Speaker #3: With that, I'll now transition back to Chris.

Speaker #1: Thank you, Sean. Reinforcing Sean's earlier sentiment, we kicked off 2026 from a position of strength, not only with Varsita M's encouraging data but with the financing completed in March a strong balance sheet that enables us to continue to execute against the significant value creation potential of Varsita and the pro-body platform.

Chris Ogden: Thank you, Sean. Reinforcing Sean's earlier sentiment, we kicked off 2026 from a position of strength, not only with Varseta-M's encouraging data, but with the financing completed in March, a strong balance sheet that enables us to continue to execute against the significant value creation potential of Varseta and the PROBODY platform. CytomX is in a strong financial position with projected cash runway to at least H2 2028 and the potential to achieve multiple milestones. Of note, our runway guidance does not include any supplemental milestones from existing collaborations or any new business development. Importantly, we expect our current cash position will enable us to advance Varseta-M into a registrational study in late-line CRC. Deliver safety and efficacy data for Varseta-M in combination with bevacizumab, as well as Varseta-M data in combination with chemotherapy. Deliver initial clinical data for Varseta-M in indications beyond CRC.

Speaker #1: CytomX is in a strong financial position with projected cash runway to at least the second half of 2028 and the potential to achieve multiple milestones.

Speaker #1: Of note, our runway guidance does not include any supplemental milestones from existing collaborations or any new business development. Importantly, we expect our current cash position will enable us to advance Varsita M into a registrational study in late line CRC, also deliver safety and efficacy data for Varsita M in combination with bevacizumab, as well as Varsita M data in combination with chemotherapy, and deliver initial clinical data for Varsita M in indications beyond CRC.

Speaker #1: Based on these opportunities, which have the potential to yield significant long-term commercial potential, we expect our capital allocation to be highly focused on Varsita M over the near to medium term.

Chris Ogden: Based on these opportunities, which have the potential to yield significant long-term commercial potential, we expect our capital allocation to be highly focused on Varseta-M over the near to medium term. With that, I'll now walk through our Q1 financial results. As of 31 March 2026, we ended the quarter with $346.7 million in cash equivalents, and investments versus $137.1 million in cash as of 31 December 2025. Looking at revenue and operating expenses for the quarter, total revenue was $10.3 million compared to $50.9 million in Q1 2025. The decrease in revenue was primarily attributed to the completion of obligations in 2025 under collaborations with Bristol Myers Squibb and Amgen.

Speaker #1: With that, I'll now walk through our first quarter financial results. As of March 31, 2026, we ended the quarter with $346.7 million in cash, cash equivalents, and investments versus $137.1 million in cash as of December 31, 2025.

Speaker #1: Looking at revenue and operating expenses for the quarter, total revenue was $10.3 million, compared to $50.9 million in the first quarter of 2025. The decrease in revenue was primarily attributed to the completion of obligations in 2025 under collaborations with Bristol-Myers Squibb and Amgen.

Speaker #1: Operating expenses for the first quarter were $29.8 million, compared to $28.3 million in the first quarter of 2025. R&D expenses were $19.2 million during the first quarter, representing an increase of 0.4 million versus the first quarter of 2025, primarily due to increased manufacturing activities for Varsita M, partially offset by $1.8 million in restructuring expense incurred in the first quarter of 2025.

Chris Ogden: Operating expenses for Q1 were $29.8 million compared to $28.3 million in Q1 2025. R&D expenses were $19.2 million during Q1, representing an increase of $0.4 million versus Q1 2025, primarily due to increased manufacturing activities for Varseta-M, partially offset by $1.8 million in restructuring expense incurred in Q1 2025. G&A expenses increased by $1.1 million during the 3 months ended 31 March 2026 to $10.6 million, compared to $9.4 million for the corresponding period in 2025, which included $1.1 million of one-time restructuring expenses.

Speaker #1: G&A expenses increased by $1.1 million during the three months ended March 31, 2026, to $10.6 million, compared to $9.4 million for the corresponding period in 2025, which included $1.1 million of one-time restructuring expenses.

Speaker #1: As we move throughout the remainder of 2026, we will continue to be disciplined in our capital allocation and advancing the highest Varsita M priorities for patients and CytomX stakeholders.

Chris Ogden: As we move throughout the remainder of 2026, we will continue to be disciplined in our capital allocation and advancing the highest Varseta-M priorities for patients and CytomX stakeholders. With that, I'll turn the call back to Sean for closing remarks.

Speaker #1: With that, I'll turn the call back to Sean for closing remarks.

Speaker #2: Thanks, Chris, and thanks, everyone, for joining us today. We're very proud of the remarkable progress we've made with Varsita M and we're now in the privileged position of bringing the transformative potential of an EpCam-directed antibody-drug conjugate to colorectal cancer patients.

Sean McCarthy: Thanks, Chris. Thanks everyone for joining us today. We're very proud of the remarkable progress we've made with Varseta-M. We're now in the privileged position of bringing the transformative potential of an EpCAM-directed antibody drug conjugate to colorectal cancer patients. We look forward to providing additional updates as the year progresses and as the development program for Varseta-M broadens substantially. We also remain focused on the advancement of the clinical program for CX-801, with the initial goal of delivering a more effective treatment option for patients with advanced melanoma. Before I conclude today's call, I want to sincerely thank and recognize the patients who join our studies, their families, our clinical investigators, and our dedicated CytomX team. With that, operator, let's go ahead and open up the call for Q&A.

Speaker #2: We look forward to providing additional updates as the year progresses and as the development program for Varsita M broadens substantially. We also remain focused on the advancement of the clinical program for CX801, with the initial goal of delivering a more effective treatment option for patients with advanced melanoma.

Speaker #2: Before I conclude today's call, I want to sincerely thank and recognize the patients who join our studies: their families, our clinical investigators, and our dedicated CytomX team.

Speaker #2: With that, operator, let's go ahead and open up the call for Q&A.

Speaker #3: Certainly. As a reminder to ask a question, please press star 11 on your telephone and wait for your name to be announced. To withdraw your question, please press star 11 again and please stand by while we compile our Q&A roster.

Operator: Certainly. As a reminder, to ask a question, please press star one one on your telephone and wait for your name to be announced. To withdraw your question, please press star one one again. Please stand by while we compile our Q&A roster. Our first question will come from Paul Jeng of Guggenheim. Your line is open, Paul.

Speaker #3: And our first question will come from Paul Jing of Guggenheim. Your line is open, Paul.

Speaker #4: Hi, thanks for taking the question. So for Varsita M, can you just talk a little bit about the scope of the clinical update you'll have in the second half?

Paul Jeng: Hi. Thanks for taking the question. For Varseta-M, can you just talk a little bit about the scope of the clinical update you'll have in H2? You know, will some or most of the dose optimization cohort patients have sufficient follow-up for PFS? Do you plan to break down responses by subgroup such as, you know, third line versus fourth line plus a therapy? How are you thinking about initial disclosures of overall survival from the study? Thanks very much.

Speaker #4: Will some or most of the dose optimization cohort patients have sufficient follow-up for PFS? Do you plan to break down responses by subgroups such as third line versus fourth line plus of therapy?

Speaker #4: And then how are you thinking about initial disclosures of overall survival from the study? Thanks very much.

Speaker #2: Yeah, thanks, Paul. For the questions, so we are expecting that the update in the second half will be fairly substantial as we've mentioned today.

Sean McCarthy: Thanks, Paul, for the questions. We are expecting that the update in H2 will be fairly substantial. As we've mentioned today, we've now enrolled 113 patients across the dose escalation, expansion and now optimization phases of the study. This is a very rich data set that is emerging for our first evaluation of Varseta-M in CRC patients. In terms of the update, it will be across the entire study. It will include data from the full 40-patient optimization phase. We expect to have, you know, reasonable follow-up in terms of safety and efficacy for the optimization patients, including I would think an initial estimate of PFS.

Speaker #2: We've now enrolled 113 patients across the dose escalation expansion and now optimization phases of the study. So this is a very rich data set that is emerging for our first evaluation of Varsita in CRC patients.

Speaker #2: So in terms of the update, it will be across the entire study. It will include data from the full 40-patient optimization phase. And yeah, we expect to have reasonable follow-up in terms of safety and efficacy for the optimization patients.

Speaker #2: Including, I would think, an initial estimate of PFS. As you'll recall, last year, our guidance as we came through the second half of 2025 was that we wanted to communicate data this year when it was mature and meaningful, and that continues to be the case.

Sean McCarthy: As you'll recall, last year our guidance as we came through H2 2025 was that we wanted to communicate data this year when it was mature and meaningful, and that continues to be the case and continues to be our philosophy. In terms of subgroups, yeah, we'll certainly communicate the demographics of the patient population that we're enrolling. We do expect it to look quite similar to the patient population that we enrolled in the escalation and expansion phases. I wanna emphasize that one of the really differentiating and distinguishing features of Varseta-M as a drug for colorectal cancer is that we can treat every patient. We're not selecting patients. We don't need to select patients.

Speaker #2: It continues to be our philosophy. In terms of subgroups, yeah, we'll certainly communicate the demographics of the patient population that we're enrolling. We do expect it to look quite similar to the patient population that we enrolled in the escalation and expansion phases.

Speaker #2: And I want to emphasize that one of the really differentiating and distinguishing features of Varsita M as a drug for colorectal cancer is that we can treat every patient.

Speaker #2: We're not selecting patients. We don't need to select patients. This really is a drug for all-comer late-line CRC. And we see this as potentially a huge competitive advantage as we move to drug toward the market.

Sean McCarthy: This really is a drug for all comers late-line CRC, and we see this as potentially a huge competitive advantage as we move the drug toward the market. In terms of the third component of your question and overall survival, yes, we absolutely anticipate having or providing, if you like, a first look at OS in this update in H2 of the year.

Speaker #2: In terms of the third component of your question and overall survival, yes, we absolutely anticipate having or providing, if you like, a first look at OS in this update in the second half of the year.

Speaker #4: Great. Thank you very much.

Paul Jeng: Great. Thank you very much.

Speaker #3: Thank you. And our next question will be coming from the line of Edward Tintoff of Piper Sandler. Your line is open, Edward.

Operator: Thank you. Our next question will be coming from the line of Edward Tenthoff of Piper Sandler. Your line is open, Edward.

Chris Ogden: Great. Thank you very much and, really excited for more data looking in H2. I just had 1 quick clarification question on the 1-2 chemo combo. Will that be triplet?

Edward Tenthoff: Great. Thank you very much and, really excited for more data looking in H2. I just had 1 quick clarification question on the 1-2 chemo combo. Will that be triplet of what you have Of that, or I guess quadruple, with the two chemos. Will that include Avastin? Do you need any of the Avastin combo data to start that, you know, chemo combo trial? I just wanna make sure I understand that correctly.

Speaker #5: Great. Thank you very much. And I'm really excited for more data looking in the back half. I just had one quick clarification question on the one to chemo combo.

Speaker #5: Will that be triplets? So will you have a vast or I guess quadruple with the two chemos? And will that include Avastin? And do you need any of the Avastin combo data to start that chemo combo trial?

Edward Tenthoff: Of that, or I guess quadruple, with the two chemos. Will that include Avastin? Do you need any of the Avastin combo data to start that, you know, chemo combo trial? I just wanna make sure I understand that correctly.

Speaker #5: I just want to make sure I understand that correctly.

Speaker #2: Yeah, hi, Ted. Thanks for the question. Taking the first question. First, in terms of the nature of the combination, yeah, we absolutely will want to evaluate the Varsita M plus chemo plus Bev combination.

Sean McCarthy: Yeah. Hi, Ted. Thanks for the question.

Sean McCarthy: Yeah. Hi, Ted. Thanks for the question. Taking the first question first, in terms of the nature of the combination. Yeah, we absolutely will want to evaluate the Varseta-M plus chemo plus Bev combination. We will want to look at that. Right now, we don't see the data from the ongoing, sorry, Varseta-M plus Bev, as gating necessarily to starting that work in the H2.

Edward Tenthoff: Hi, Ted. Thanks for the question.

Sean McCarthy: Taking the first question first, in terms of the nature of the combination. Yeah, we absolutely will want to evaluate the Varseta-M plus chemo plus Bev.

Edward Tenthoff: Yeah

Edward Tenthoff: combination. We will want to look at that. Right now, we don't see the data from the ongoing, sorry, Varseta-M plus Bev, as gating necessarily to starting that work in the H2.

Speaker #2: We will want to look at that. Right now, we don't see the data from the ongoing Varsita M plus Bev as gating necessarily to starting that work in the second half.

Edward Tenthoff: Yeah.

Edward Tenthoff: We do of course see that Bev combination work. The Varseta-M Bev combination is going to be really important to further down the road considering from a registrational study perspective, the design of that study, if indeed we do at some future point decide to compare Varseta-M plus Bev against other comparator arms. We do plan to look at that triplet in the chemo combination later this year.

Speaker #2: We do, of course, see that Bev combination work. The Varsita M Bev combination is going to be really important to further down the road considering from a registrational study perspective.

Sean McCarthy: We do of course see that Bev combination work. The Varseta-M Bev combination is going to be really important to further down the road considering from a registrational study perspective, the design of that study, if indeed we do at some future point decide to compare Varseta-M plus Bev against other comparator arms. We do plan to look at that triplet in the chemo combination later this year.

Speaker #2: The design of that study, if indeed we do at some future point decide to compare Varsita M plus Bev against other comparator arms, but we do plan to look at that triplet in the chemo combination.

Speaker #2: Later this year.

Speaker #5: Yeah. And then that's really helpful. And then when it comes to the new Epcam positive tumors, I'm really excited to hear what you're thinking is.

Edward Tenthoff: Yeah. That's really helpful. When it comes to the new EpCAM-positive tumors, I'm really excited to hear what your thinking is. Maybe you can share with us now kind of what goes into some of that prioritization, 'cause there's a lot of different places you could go, I think.

Speaker #5: Maybe you can share with us now kind of what goes into some of that prioritization. Because there's a lot of different places you could go.

Speaker #5: Thanks.

Speaker #2: Yes, there are so many places we could go because Epcam is such a broadly expressed cancer target on so many solid tumors. So we do have a lot of opportunities to work through and prioritize.

Sean McCarthy: Yes, there are so many places we could go because EpCAM is such a broadly expressed cancer target on so many solid tumors. We do have a lot of opportunities to work through and prioritize. It's not lost on us, of course, or really anybody else that there are some, there's quite a number of, if you like, adjacent GI tumors.

Speaker #2: It's not lost on us, of course, or really anybody else that there are some there's quite a number of, if you like, adjacent GI tumors that can make a lot of sense to evaluate.

Edward Tenthoff: Yeah

Edward Tenthoff: That could make a lot of sense to evaluate with Varseta-M. There are also many others. Something that we continue to work through and prioritize, and we will communicate more specificity on exactly what we're planning to do in H2.

Sean McCarthy: That could make a lot of sense to evaluate with Varseta-M. There are also many others. Something that we continue to work through and prioritize, and we will communicate more specificity on exactly what we're planning to do in H2.

Speaker #2: With Varsita M, there are also many others. So, something that we continue to work through and prioritize, and we will communicate more specificity on exactly what we're planning to do in the second half.

Speaker #5: Great. I'm looking forward to it. And more data. Keep up the great work.

Edward Tenthoff: Great. I am looking forward to it and more data. Keep up the great work.

Speaker #2: Thanks, Ted.

Sean McCarthy: Thanks, Ted.

Speaker #3: Fine. Of Anupam Rama of JPMorgan. Your line is open.

Operator: Of Anupam Rama of J.P. Morgan, your line is open.

Operator: Of Anupam Rama of JPMorgan, your line is open.

Joy: Hey, guys, this is Joy on for Anupam. Thanks so much for taking our question. I think previously you had said you were targeting midyear FDA interactions to start discussing the pivotal trial design. To what extent is reaching alignment on the trial design ultimately gated on seeing your dose optimization update later this year? I assume you can start having those conversations with FDA now with your initial data in hand. Just how should we think about the update later this year in terms of solidifying your registrational strategy? Thanks.

Joy So: Hey, guys, this is Joy on for Anupam. Thanks so much for taking our question. I think previously you had said you were targeting midyear FDA interactions to start discussing the pivotal trial design. To what extent is reaching alignment on the trial design ultimately gated on seeing your dose optimization update later this year? I assume you can start having those conversations with FDA now with your initial data in hand. Just how should we think about the update later this year in terms of solidifying your registrational strategy? Thanks.

Speaker #6: Hey, guys. This is Joyce on for Anupam. Thanks so much for taking our question. I think previously you had said you were targeting mid-year FDA interactions to start discussing the pivotal trial design.

Speaker #6: To what extent is reaching alignment on the trial design ultimately gated on seeing your dose optimization update later this year? I assume you can start having those conversations with FDA now with your initial data in hand.

Speaker #6: But just how should we think about the update later this year in terms of solidifying your registrational strategy? Thanks.

Speaker #2: Yeah, thanks. Great question. Really important question. And I'll start by saying that we're just really excited to have this dialogue with FDA as we progress through the year.

Sean McCarthy: Yeah, thanks. Great question. Really important question. I'll start by saying that we're just really excited to have this dialogue with FDA. As we progress through the year, we anticipate multiple interactions, and we do expect that the data from the optimization cohorts will be central to those conversations in relation to dose selection for the first pivotal study. That's, of course, a large part of the reason we're doing these additional 2 N equals 20 cohorts at the 8.6 and 10 mg per kg doses is to generate data to satisfy Project Optimus and have as highly productive a conversation with FDA as we can.

Speaker #2: We anticipate multiple interactions and we do expect that the data from the optimization cohorts will be central to those conversations. In relation to dose selection, for the first pivotal study, that's, of course, a large part of the reason we're doing these additional two N equals 20 cohorts at the 8.6 and 10 microcute doses is to generate data to satisfy Project Optimus and have as highly productive a conversation with FDA as we can.

Speaker #2: So yes, that data will be important. And that's why we're guiding that really towards the end of the year, or by the end of the year, the next comprehensive update that we plan to provide will not only include of course data across the 130 patient phase one study, but will also include guidance as to where we're going next in terms of design of the first pivotal study, what the patient population is, what the comparator arm is, and of course, what the dose is.

Sean McCarthy: Yes, that data will be important, and that's why we're guiding that, really towards the end of the year or by the end of the year. The next comprehensive update that we plan to provide will not only include, of course, data across the 133 patient phase I study but will also include guidance as to where we're going next in terms of design of the first pivotal study, what the patient population is, what the comparator arm is, and of course, what the dose is.

Operator: Our next question will be coming from the line of Roger Song of Jefferies. Your line is open, Roger.

Speaker #3: And our next question will be coming from the line of Roger Song of Jefferies. Your line is open, Roger.

Operator: Our next question will be coming from the line of Roger Song of Jefferies. Your line is open, Roger.

Speaker #4: Hey, thank you, team, for taking our questions. Congrats on the progress. This is Nabil on for Roger. Maybe one from me first. So just on the 8.6 versus 10 meg per cu, just a little bit curious if you could maybe give some color on the dose decision logic.

Nabil: Hey, thank you, team, for taking our questions. Congrats on the progress. This is Nabil on for Roger. Maybe, one from me first. Just on the 8.6 versus 10 mg per kg, just a little bit curious if you could maybe give some color on the dose decision logic. Because we saw the headline ORR, 32% versus 20%. What is the framework that you guys would apply to finally lock in on a dose? Is it related to tolerability at this point? Because we noticed in the exposure response model, it looks like there's pretty similar efficacy. Are you weighing depth and durability? Are you weighing safety more? Thank you.

Nabil Elouahabi: Hey, thank you, team, for taking our questions. Congrats on the progress. This is Nabeel on for Roger. Maybe, one from me first. Just on the 8.6 versus 10 mg per kg, just a little bit curious if you could maybe give some color on the dose decision logic. Because we saw the headline ORR, 32% versus 20%. What is the framework that you guys would apply to finally lock in on a dose? Is it related to tolerability at this point? Because we noticed in the exposure response model, it looks like there's pretty similar efficacy. Are you weighing depth and durability? Are you weighing safety more? Thank you.

Speaker #4: Because we saw the headline OR 32% versus 20%. But what is the framework that you guys would apply to finally lock in on a dose?

Speaker #4: Is it related to tolerability at this point? Because we noticed in the exposure response model, it looks like there's pretty similar efficacy. So are you weighing depth and durability?

Speaker #4: Are you weighing safety more? Thank you.

Speaker #2: Yeah, thanks, Nabil. That's obviously there's a lot in that question. In terms of the work that we are doing in real time, and we'll be continuing to do as we move through the year to lock in on the go-forward dose.

Sean McCarthy: Thanks, Nabil. There's a lot in that question in terms of the work that we are doing in real time and will be continuing to do as we move through the year to lock in on the go-forward dose. You know, first thing I'll say is we think we've got two, you know, two great choices here in terms of the 8.6 and 10 mg per kg doses, both of which, as you'll recall, we're currently evaluating on an adjusted ideal body weight basis in the context of the dose optimization cohort. We're gonna learn a lot as the year goes by as to the performance of these two doses, of course, in terms of efficacy, also in terms of safety.

Sean McCarthy: Thanks, Nabeel. There's a lot in that question in terms of the work that we are doing in real time and will be continuing to do as we move through the year to lock in on the go-forward dose. You know, first thing I'll say is we think we've got two, you know, two great choices here in terms of the 8.6 and 10 mg per kg doses, both of which, as you'll recall, we're currently evaluating on an adjusted ideal body weight basis in the context of the dose optimization cohort. We're gonna learn a lot as the year goes by as to the performance of these two doses, of course, in terms of efficacy, also in terms of safety.

Speaker #2: And first thing I'll say is we think we've got two great choices here. In terms of the 8.6 and 10 microcute doses, both of which, as you'll recall, we're currently evaluating on an adjusted ideal body weight basis.

Speaker #2: In the context of the dose optimization cohort. So we're going to learn a lot as the year goes by as to the performance of these two doses.

Speaker #2: Of course, in terms of efficacy, also in terms of safety. And on efficacy specifically, as we've been discussing for quite some time now, we do anticipate that at least our base case for our first registrational study, we do anticipate the overall survival will be our primary endpoint.

Sean McCarthy: On efficacy specifically, as we've been discussing, you know, for quite some time now, we do anticipate that at least our base case for our first registrational study, we do anticipate that OS will be our primary endpoint. That of course means that ORR is really an important metric here for how the drug's performing, and this drug is performing extraordinarily well. As you said, 20% ORR at 8.6, 32% at 10 MPK. That is remarkable activity. We also have remarkable PFS of 7 months as reported on 16 March. We are very keen to see how that translates into OS as the data matures.

Speaker #2: And that, of course, means that ORR is really an important metric here for how the drug's performing. And this drug is performing extraordinarily well.

Speaker #2: As you said, 20% ORR, 8.6, 32% at 10 MPK. That is remarkable activity. But we also have remarkable progression-free survival. Of seven months as reported on March 16th.

Speaker #2: And we are very keen to see how that translates into OS as the data matures. With OS, of course, as I just mentioned, being our primary in most likely primary in the go-forward pivotal study.

Sean McCarthy: With OS, of course, as I just mentioned, being our primary, most likely primary in the go-forward pivotal study. You know, we'll see. We'll see how these two doses deliver in terms of all of these different metrics, and we'll choose accordingly.

Speaker #2: So we'll see. We'll see how these two doses deliver in terms of all of these different metrics. And we'll choose accordingly.

Nabil: Excited to see that as well. Thank you.

Nabil Elouahabi: Excited to see that as well. Thank you.

Speaker #5: Excited to see that as well. Thank you.

Speaker #2: You're welcome.

Sean McCarthy: You're welcome.

Speaker #3: And our next question will come from the line of Olivia Brayer of Cantor Fitzgerald. Your line is open, Olivia.

Operator: Our next question will come from the line of Olivia Brayer of Cantor Fitzgerald. Your line is open, Olivia.

Speaker #7: Hi, good afternoon. Thank you for the questions. For that second-half data disclosure, can I just clarify that you guys plan to break out tolerability and efficacy for those 40 patients specifically in the optimization cohort?

Olivia Brayer: Hi, good afternoon. Thank you for the questions. For that H2 data disclosure, can I just clarify that you guys plan to break out tolerability and efficacy for those 40 patients specifically in the optimization cohort? If so, will we still get PFS and potentially even an early look at some OS data from those patients specifically? From a timing perspective, top line H2 of this year, does that mean you'll likely follow it up with a presentation at a medical conference sometime in early 2027? I've got one quick follow-up on the new formulation with Bev.

Speaker #7: And if so, will we still get PFS and potentially even an early look at some OS data from those patients specifically? And then from a timing perspective, top line, second half of this year, does that mean you'll likely follow it up with a presentation at a medical conference sometime in early 2027?

Speaker #7: And then I've got one quick follow-up on the new formulation with Bev.

Speaker #2: Yeah, thanks, Olivia. So yeah, obviously, the 40 patient optimization cohorts is of high interest to us. And others. And so we absolutely plan to report the full safety picture, which we gave an early look at in the March 16th disclosure.

Sean McCarthy: Thanks, Olivia. Yeah, obviously the 40-patient optimization cohort is of high interest to us and others. We absolutely plan to report the full safety picture, which we gave an early look at in the March 16 disclosure. We gave an early look at the first 2 months of experience, which was being, you know, very encouraging. We plan to give a similar look for the full 40 patients by the end of the year together with efficacy. As I've already mentioned, you know, PFS would certainly be a goal there to have PFS for those 40 patients. I think OS is gonna be too early.

Speaker #2: We gave an early look at the first two months of experience, which was very encouraging. So we plan to give a similar look for the full 40 patients by the end of the year.

Speaker #2: Together with efficacy. And as I've already mentioned, PFS would certainly be a goal there to have PFS. For those 40 patients. I think OS is going to be too early.

Sean McCarthy: You know, we're just, as we reported today, we've completed enrollment, that's been relatively recent. I think OS is gonna be immature. We do anticipate having OS from the escalation and expansion phases, which I think will be particularly telling, because remember that in those, in those patients, those first, escalation ops, and expansion patients, we had not optimized our adverse event management plan. We were still able to deliver 7 months of PFS, and we're optimistic that we'll have an encouraging OS number as we get to report that later in the year. In terms of, you know, venue for data updates, you know, we do, we do think a medical meeting this year is on the cards.

Speaker #2: We're just as we've reported today, we've completed enrollment, but that's been relatively recent. So I think OS is going to be immature. But we do anticipate having OS from the escalation and expansion phases, which I think will be particularly telling.

Speaker #2: Because remember that in those patients, those first escalation and expansion patients, we had not optimized our adverse event management plan. But we were still able to deliver seven months of PFS.

Speaker #2: And we're optimistic that we'll have an encouraging OS number as we get to report that later in the year. In terms of venue for data updates, we do think a medical meeting this year is on the cards.

Sean McCarthy: Certainly as we move into 2027, additional medical meetings, we're of course, keeping our options open.

Speaker #2: Certainly, as we move into 2027, additional medical meetings. We're of course keeping our options open.

Sean McCarthy: Certainly as we move into 2027, additional medical meetings, we're of course, keeping our options open.

Speaker #7: Okay, very helpful. And then for the combination with Bev, is there anything you guys can tell us at this point about the formulation work that you've done to get Varsetta M administered as an every two and four-week dosing schedule instead of every three weeks?

Olivia Brayer: Okay. Very helpful. For the combination with Bev, is there anything you guys can tell us at this point about the formulation work that you've done to get Varseta-M administered as an every 2 and 4 week dosing schedule instead of every 3 weeks? Is there any data that you'll be sharing there at some point?

Speaker #7: Or is there any data that you'll be sharing there at some point?

Speaker #2: Well, there's no real formulation work that needs to be done. It's simply an adjustment of the schedule from Q3 to Q2. And then accordingly to Q4.

Sean McCarthy: Well, there's no real formulation work that needs to be done. It's simply an adjustment of the schedule from Q3 to Q2, and then accordingly to Q4. That's to match as I just mentioned on the call, that's to match the established clinical use of Bev in the FOLFOX, FOLFIRI setting on a 2-week schedule. There's no additional formulation. It's simply a question of adjusting the frequency of dosing to match the use of bevacizumab in the marketplace today.

Speaker #2: And that's to match the, as I just mentioned on the call, that's to match the established clinical use of Bev in the FOLFOX, FOLFIRI setting on a two-week schedule.

Speaker #2: So there's no additional formulation. It's simply a question of adjusting the frequency of dosing. To match the use of Bevacizumab in the marketplace today.

Speaker #7: Okay, thanks, Sean. Appreciate it.

Olivia Brayer: Okay. Thanks, Sean. Appreciate it.

Speaker #2: You're welcome.

Sean McCarthy: You're welcome.

Speaker #3: And our next question will come from the line of Matt Biegler of OPCO. Your line is open, Matt.

Operator: Our next question will come from the line of Matt Biegler of OpCo. Your line is open, Matt.

Speaker #4: Hey guys, thanks for the question. Just kind of curious how you're seeing the emerging competitive profile here of Varsetta M versus the other ADCs that are also in development, Presem TCT being one of them.

Matt Biegler: Hey, guys. Thanks for the question. Just kinda curious how you're seeing the emerging competitive profile here of Varseta-M versus the other ADCs that are also in development, Presuntictum, being one of them. Then I guess more importantly, do you think this is like a winner-takes-all, zero-sum game here with the topo 1 base ADCs? Or do you think different patients might get different ADCs depending on, you know, certain health status, et cetera? Thanks.

Speaker #4: And then I guess more importantly, do you think this is a winner-takes-all zero-sum game here with the topo one base ADCs? Or do you think different patients might get different ADCs depending on certain health status?

Speaker #4: Etc. Thanks.

Speaker #2: Thanks, Matt. Well, we certainly don't see this as winner-takes-all by any means. And I think that would be a very unusual scenario for an oncology drug in this class in an area of unmet need.

Sean McCarthy: Thanks, Matt. Well, we certainly don't see this as winner takes all by any means, and I think that would be a very unusual scenario for an oncology drug in this class in an area of unmet need like this. I mean, our thinking is very different on that question. First of all, with regards to Varseta-M, we have a first-in-class anti-EpCAM antibody drug conjugate. I, again, I really can't emphasize how important it is to realize that we've done something really, really special with our technology to unlock the potential of EpCAM for the first time with our PROBODY therapeutic platform. Secondly, we really do believe that Varseta-M has the potential to be the best-in-class ADC for colorectal cancer.

Speaker #2: Like this. I mean, our thinking is very different on that question. So first of all, with regards to Varsetta M, we have a first-in-class anti-Epcam, antibody-drug conjugate.

Speaker #2: And again, I really can't emphasize how important it is to realize that we've done something really, really I'll use the word special with our technology to unlock the potential of Epcam for the first time with our pro-body therapeutic platform.

Speaker #2: Secondly, we really do believe that Varsetta M has the potential to be the best-in-class ADC for colorectal cancer. This drug is highly active. It's highly active in terms of its response rate.

Sean McCarthy: This drug is highly active. It's highly active in terms of its response rate. It's highly active in terms of its progression-free survival, and we'll see what it can deliver in terms of overall survival as we move forward. This is a very active drug, and we believe does have the potential to be best in class. We're going all out with this drug to get it to the market as quickly as we can. We think it's highly competitive and, we think there's a ton of value to build in our company with this drug, most importantly, an enormous amount of benefit to bring to these patients.

Speaker #2: It's highly active in terms of its progression-free survival. And we'll see what it can deliver in terms of overall survival as we move forward.

Speaker #2: This is a very active drug. And we believe does have the potential to be best-in-class. So we're going all out with this drug to get it to the market as quickly as we can.

Speaker #2: We think it's highly competitive. And we think there's a ton of value to build in our company with this drug. Most importantly, an enormous amount of benefit to bring to these patients.

Speaker #4: Thanks.

Matt Biegler: Thanks.

Speaker #3: As a reminder to ask a question, please press star 11 on your telephone and wait for your name to be announced. Our next question will be coming from the line of Mitchell Kapoor of HC Wainwright.

Operator: As a reminder, to ask a question, please press star one one on your telephone and wait for your name to be announced. Our next question will be coming from the line of Mitchell Kapoor of H.C. Wainwright. Your line is open, Mitchell.

Speaker #3: Your line is open, Mitchell.

Speaker #5: Hi, thank you for taking my question. This is Yan Z sitting in for Mitchell. I was wondering, could you break so actually, with the enrollment now completed in the 40 patient dose optimization cohort, can you give any update on whether grade three or higher diarrhea in the optimized adjusted ideal body weight plus prophylaxis population is still tracking closer to that initial 10% rate that was seen in the first 20 patients?

Jan Zi: Hi. Thank you for taking my question. This is Jan Zi sitting in for Mitchell. Actually, with the enrollment now complete in the 40-patient dose optimization cohort, can you give any update on whether grade 3 or higher diarrhea in the optimized, adjusted ideal body weight plus prophylaxis population is still tracking closer to that initial 10% rate that was seen in the first 20 patients? Or whether it's moved closer to something like the historical 25% to 30% range at the 8.6 and 10 mgs per kg as follow-up has occurred?

Speaker #5: Or whether it's moved closer to something like the historical 25 to 30 percent range at the 8.6 and 10 mg/kg as follow-up has recurred?

Speaker #2: Well, no new data today. That data will be coming. We're obviously highly encouraged by the initial data we presented on March 16th from the first couple of months of follow-up of the first 20 patients enrolled.

Sean McCarthy: Well, no new data today. That data will be coming. We obviously were highly encouraged by the initial data we presented on 16 March from the first couple months of follow-up of the first 20 patients enrolled into the optimization cohorts with a rate of grade 3 diarrhea of 10%. I think we commented at the time, and we've been very consistent about this over the last few months, that, you know, our objective is, of course, to manage the rate of grade 3 to the best of our ability with this updated AE management strategy that includes upfront use of loperamide and budesonide. It appears to be performing very well as of that first data update, and we're encouraged to see additional data now from the full 40 patients.

Speaker #2: Into the optimization cohorts, with a rate of grade three diarrhea of 10%. I think we commented at the time and I think we've been very consistent about this over the last few months that our objective is, of course, to manage the rate of grade three to the best of our ability with this updated AE management strategy that includes upfront use of loperamide and budesonide.

Speaker #2: It appears to be performing very well as of that first data update. And we're encouraged to see additional data now from the full 40 patients.

Speaker #2: That data will be shared later in the year. Our goal overall is to manage the grade threes into the 10% to 20% range.

Sean McCarthy: That data will be shared later in the year. Our goal overall is to manage the grade 3s into the 10% to 20% range. You know, that we think is really the target, and that's based on our own research. It's based on a lot of conversations we've had, and quite honestly, a lot of work has been published and presented by others over the last, you know, six or so months. We're very much on track, as I said in my prepared remarks, to get a strong handle on that particular aspect of the Varseta-M program.

Speaker #2: That we think is really the target. And that's based on our own research. It's based on a lot of conversations we've had. And quite honestly, a lot of work that's been published and presented by others over the last six or so months.

Speaker #2: So we're we feel we're very much on track, as I said in my prepared remarks, to get a strong handle on that particular aspect of the Varsetta M program.

Speaker #5: I see. Thanks. Curious also, if so, for an optimized regimen, how standardized is prophylaxis practice? Do you see any implementation friction that could matter in a community oncology setting if, for example, Varsetta M moves earlier in late-line CRC?

Jan Zi: I see. Thanks. Curious also if, for an optimized regimen, how standardized is prophylaxis in practice? Do you see any implementation friction that could matter in a community oncology setting if, for example, Varseta-M moves earlier in late-line CRC?

Sean McCarthy: We really don't. The, you know, the upfront work that we're doing right now with these optimization cohorts is absolutely intended to, you know, to pin down a prophylaxis strategy that will be readily translated into the community setting as we move into our first pivotal study and, of course, as we bring the drug to the market. It's a good question. It's an important question, and it's one that we've asked ourselves, and that is, again, just to restate a big part of why we're doing this upfront optimization work right now. Right now we don't see any challenges with the translation, if you like, of this updated AE management plan into a larger number of sites and ultimately into the commercial marketplace.

Speaker #2: We really don't. The upfront work that we're doing right now with these optimization cohorts is absolutely intended to pin down a prophylaxis strategy that will be readily translated into the community setting.

Speaker #2: As we move into our first pivotal study and, of course, as we bring the drug to the market. So it's a good question. It's an important question.

Speaker #2: And it's one that we've asked ourselves. And that is, again, just to restate, a big part of why we're doing this upfront optimization work right now.

Speaker #2: But right now, we don't see any challenges with the translation, if you like, of this updated AE management plan into a larger number of sites and ultimately into the commercial marketplace.

Speaker #5: Thank you so much. I'm looking forward to the next update.

Jan Zi: Thank you so much. I'm looking forward to the next update.

Speaker #3: Thank you.

Operator: Thank you.

Speaker #2: You're welcome.

Sean McCarthy: You're welcome.

Speaker #3: I'm not showing any further questions in the queue. I would now like to turn the call back to Dr. Sean McCarthy, chairman and CEO for closing remarks.

Operator: I'm not showing any further questions in the queue. I would now like to turn the call back to Dr. Sean McCarthy, Chairman and CEO, for closing remarks.

Speaker #2: Thank you. And again, I'd just like to thank everyone for joining us today. We're very excited about our progress here. I hope that comes across and we really look forward to providing additional updates as the year progresses.

Sean McCarthy: Thank you. Again, I'd just like to thank everyone for joining us today. We're very excited about our progress here. I hope that comes across. We really look forward to providing additional updates as the year as the year progresses.

Operator: And this concludes today's program. Thank you for participating. You may now disconnect.