Full Year 2025 Bicara Therapeutics Inc Earnings Call

March 30, 2026

Operator: Good day, and thank you for standing by. Welcome to the Bicara Therapeutics Q4 and full year 2025 earnings call. At this time, all participants are on a listen-only mode. After the speaker's presentation, there'll be a question-and-answer session. To ask a question during the session, you'll need to press star one one on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star one one again. Please be advised today's conference is being recorded. I would now like to hand the conference over to your speaker today, Rachel Frank. Please go ahead.

Speaker #1: After the speaker's presentation, there'll be a question-and-answer session. To ask a question during the session, you'll need to press star one one on your telephone.

Speaker #1: You will then hear an automated message advising your hand is raised. To withdraw your question, please press star 1 1 again. Please be advised today's conference is being recorded.

Speaker #1: I would like to hand the conference over to your speaker today, Rachel Frank. Please go ahead. Thank you, and good morning, everyone. It's a pleasure to welcome you to Bicara Therapeutics' fourth quarter and full year 2025 earnings call.

Rachel Frank: Thank you, and good morning, everyone. It's a pleasure to welcome you to Bicara Therapeutics' Q4 and full year 2025 earnings call. Earlier this morning, we issued a press release highlighting results from the quarter and recent business progress. You can access the press release as well as the slides that we'll be reviewing today by going to the investor section of our company website. Before we begin, please note that this call will include forward-looking statements under the Safe Harbor Provisions of the Private Securities Litigation Reform Act of 1995. Please refer to our most recent SEC filings for important risk factors that could cause our actual performance and results to materially differ from those expressed or implied in these forward-looking statements. Any forward-looking statement made on this call represents our views only as of today, and we disclaim any obligation to update any forward-looking statements.

Speaker #1: Earlier this morning, we issued a press release highlighting results from the quarter and recent business progress. You can access the press release, as well as the slides that we will be reviewing today, by going to the investor section of our company website.

Speaker #1: Before we begin, please note that this call will include forward-looking statements under the Safe Harbor provisions of the Private Securities Litigation Reform Act of 1995.

Speaker #1: Please refer to our most recent SEC filings for important risk factors that could cause our actual performance and results to materially differ from those expressed or implied in these forward-looking statements.

Speaker #1: Any forward-looking statement made on this call represents our views only as of today, and we disclaim any obligation to update any forward-looking statements. Joining us on the call today are Claire Mazumdar, Chief Executive Officer; Brian Kolke, President and Chief Operating Officer; and Ivan Hayek, Chief Financial Officer.

Rachel Frank: Joining us on the call today are Claire Mazumdar, Chief Executive Officer, Ryan Cohlhepp, President and Chief Operating Officer, and Ivan Hyep, Chief Financial Officer. I'll now turn the call over to Claire.

Claire Mazumdar: Good morning, and welcome to Bicara Therapeutics' inaugural quarterly earnings call. I'm Claire Mazumdar, Chief Executive Officer. Today marks an important milestone for our company as we begin this tradition of regular communication with investors, analysts, and stakeholders to provide transparent updates on our business progress and strategic direction via the quarterly earnings call process. We're implementing these quarterly calls as part of our commitment to maintain an open dialogue with the Street and ensuring you have consistent visibility into our execution against key milestones and strategic objectives. Before I jump into our Q4 2025 highlights and recent progress, let me provide a brief background for those who are newer to our story. Bicara Therapeutics is a clinical-stage biotech company pioneering bifunctional antibodies for targeted tumor modulation.

Speaker #1: I'll now turn the call over to Claire.

Speaker #2: Good morning and welcome to Bicara Therapeutics' inaugural quarterly earnings call. I'm Claire Mazumdar, Chief Executive Officer. Today marks an important milestone for our company as we begin this tradition of regular communication with investors, analysts, and stakeholders to provide transparent updates on our business progress and strategic direction via the quarterly earnings call process.

Speaker #2: We're implementing these quarterly calls as part of our commitment to maintain an open dialogue with the Street and ensuring you have consistent visibility into our execution against key milestones and strategic objectives.

Speaker #2: Before I jump into our Q4 2025 highlights and recent progress, let me provide a brief background for those who are newer to our story.

Speaker #2: Bicara Therapeutics is a clinical stage biotech company pioneering bifunctional antibodies for targeted tumor modulation. Founded in 2020, we've built a global team of over 100 employees headquartered in Boston with a clear focus on advancing our lead asset by Sarah Fisk Alpha or Phicera, a potentially first-in-class bifunctional EGFR-directed antibody combined with a TGF beta ligand trap.

Claire Mazumdar: Founded in 2020, we've built a global team of over 100 employees headquartered in Boston with a clear focus on advancing our lead asset, ficerafusp alfa or BCA101, a potentially first-in-class bifunctional EGFR-directed antibody combined with the TGF-β ligand trap. Our innovative approach combines tumor targeting with tumor modulation, where one arm localizes to the tumor while the other serves as a modulator designed to deliver superior efficacy, improve safety, and enhance durability directly at the tumor site. BCA101 specifically addresses a key challenge in solid tumor treatment by enabling immune cell penetration into tumors, reducing fibrosis and immunosuppression while reversing TGF-β-driven resistance mechanisms, ultimately designed to drive the deep, durable responses that may translate into better outcomes and survival for patients. Over the past several months, there have been significant shifts in how the competitive landscape in frontline recurrent and metastatic head and neck cancer is evolving.

Speaker #2: Our innovative approach combines tumor targeting with tumor modulation, where one arm localizes to the tumor while the other serves as a modulator, designed to deliver superior efficacy, improve safety, and enhance durability directly at the tumor site.

Speaker #2: Phicera specifically addresses a key challenge in solid tumor treatment by enabling immune cell penetration into tumors, reducing fibrosis and immunosuppression, while reversing TGF-beta-driven resistance mechanisms.

Speaker #2: Ultimately designed to drive the deep, durable responses that may translate into better outcomes and survival for patients. Over the past several months, there have been significant shifts in how the competitive landscape and frontline recurrent and metastatic head and neck cancer is evolving.

Claire Mazumdar: Our recent clinical data and regulatory progress clearly position Bicara as the potential best and first-in-class asset with a differentiated clinical profile on both long-term outcomes and tolerability. Looking back at the progress we've made since October 2025, I'm energized by the exceptional momentum we've built across our pipeline and operations. Over the past several months, we've achieved multiple critical inflection points that fundamentally strengthen our position as we advance Bicara toward a pivotal study interim analysis in the middle of next year. First, Bicara received Breakthrough Therapy Designation, or BTD, in combination with pembrolizumab for the first-line treatment of patients with metastatic or unresectable HPV-negative recurrent head and neck squamous cell carcinoma.

Speaker #2: Our recent clinical data and regulatory progress clearly position Phicera as a potential best- and first-in-class asset, with a differentiated clinical profile on both long-term outcomes and tolerability.

Speaker #2: Looking back at the progress we've made since October 2025, I'm energized by the exceptional momentum we've built across our pipeline and operations. Over the past several months, we've achieved multiple critical inflection points that fundamentally strengthen our position as we advance Phicera toward a pivotal, steady interim analysis in the middle of next year.

Speaker #2: First, Phicera received breakthrough therapy designation, or BTD, in combination with pembrolizumab for the first-line treatment of patients with metastatic or with unresectable HPV-negative, recurrent head and neck squamous cell carcinoma.

Claire Mazumdar: This designation from the FDA underscores the growing recognition of HPV-negative head and neck cancer as a distinct clinical indication within head and neck cancer, one with particularly poor outcomes, limited therapeutic options, and that represents the vast majority of patients. Second, we presented two additional Phase 1b clinical datasets across clinically active doses of ficerafusp alfa that demonstrated consistent overall response rates, further validating ficerafusp alfa's unique dual mechanism targeting both EGFR and TGF-β and de-risking the ORR endpoint in our pivotal study interim analysis. Third, building on this robust data set, we selected 1,500mg as our optimal biological dose and have successfully moved into the Phase 3 portion of our pivotal FORTIFI-HN01 study, for which we expect an interim analysis in the middle of next year.

Speaker #2: This designation from the FDA underscores the growing recognition of HPV-negative head and neck cancer as a distinct clinical indication within head and neck cancer—one with particularly poor outcomes, limited therapeutic options, and that represents the vast majority of patients.

Speaker #2: Second, we presented two additional Phase 1b clinical datasets across clinically active doses of Phicera that demonstrated consistent overall response rates, further validating Phicera's unique dual mechanism targeting both EGFR and TGF-beta, and de-risking the OR endpoint in our pivotal study interim analysis.

Speaker #2: Third, building on this robust dataset, we selected 1,500 milligrams as our optimal biological dose and have successfully moved into the Phase 3 portion of our pivotal Fortify HN01 study, for which we expect an interim analysis in the middle of next year.

Claire Mazumdar: This represents a major strategic advancement that brings us significantly closer to our goal of delivering a potential best and first-in-class treatment option for patients living with HPV-negative head and neck cancer. Fourth, we recently announced plans to develop ficerafusp alfa with a loading and every three-week maintenance dose, a strategic commercial decision based upon updated clinical, translational, and pharmacokinetic data that we believe will enable additional optionality for patients and providers choosing treatment with ficerafusp alfa. Lastly, to support this accelerated trajectory and pull forward investments in our early commercial and medical build, we successfully completed an oversubscribed public offering, strengthening our balance sheet and providing the capital foundation necessary to execute this next chapter of our business with confidence. With that, I'll turn it to Ryan to provide a bit more detail on our recent clinical updates and business progress.

Speaker #2: This represents a major strategic advancement that brings us significantly closer to our goal of delivering a potential best- and first-in-class treatment option for patients living with HPV-negative head and neck cancer.

Speaker #2: Fourth, we recently announced plans to develop Phicera with a loading and every-three-week maintenance dose, a strategic commercial decision based upon updated clinical, translational, and pharmacokinetic data that we believe will enable additional optionality for patients and providers choosing treatment with Phicera.

Speaker #2: Lastly, to support this accelerated trajectory and pull forward investment in our early commercial and medical build, we successfully completed an over-subscribed public offering, strengthening our balance sheet and providing the capital foundation necessary to execute this next chapter of our business with confidence.

Speaker #2: With that, I'll turn it to Ryan to provide a bit more detail on our recent clinical updates and business progress.

Ryan Cohlhepp: Thank you, Claire, and good morning, everyone. We've now reported clinical experience in approximately 90 patients across three phase 1b cohorts evaluating ficerafusp alfa in combination with pembrolizumab in frontline recurrent metastatic HPV-negative head and neck squamous cell carcinoma. Our 1,500mg every week data is the most mature with 2 years of follow-up and demonstrates deep durable responses that lead to median duration of response and median overall survival of 21.7 and 21.3 months, respectively, nearly tripling the median overall survival observed with the standard of care pembrolizumab in HPV-negative patients. Late last year and just last month, we presented two additional cohorts.

Speaker #3: Thank you, Claire. And good morning, everyone. We've now reported clinical experience in approximately 90 patients across three Phase 1b cohorts evaluating Phicera in combination with pembrolizumab in frontline, recurrent, metastatic, HPV-negative head and neck squamous cell carcinoma.

Speaker #3: Our 1,500-milligram-every-week data is the most mature, with two years of follow-up, and demonstrates deep, durable responses that lead to a median duration of response and median overall survival of 21.7 and 21.3 months, respectively.

Speaker #3: Nearly tripling the median overall survival observed with the standard of care pembrolizumab and HPV-negative patients. Late last year, and just last month, we presented two additional cohorts: in December of 2025 at Esmo Asia, we presented data from our 750 milligram every week cohort, which helped to ultimately inform 1,500 milligrams every week as the optimal biologic dose for our ongoing pivotal Phase 3 Fortify HN01 trial.

Ryan Cohlhepp: In December 2025 at ESMO Asia, we presented data from our 750 mg every week cohort, which helped to ultimately inform 1,500 mg every week as the optimal biological dose for our ongoing pivotal Phase 3 FORTIFI-HN01 trial. Just last month at the Multidisciplinary Head and Neck Cancers Symposium, we presented data from a higher but less frequent dose of ficerafusp alfa in combination with pembrolizumab, 2,000 mg every two weeks, from which we announced our plan to develop a less frequent loading and maintenance dosing option. Our aim is to gain alignment with the FDA on this approach and initiate that study in parallel to the pivotal study to allow to have data from that regimen in hand upon potential US approval. Clinically, tumor shrinkage is seen at all doses. It trends deeper with higher exposure.

Speaker #3: And just last month, at the Multidisciplinary Head and Neck Cancer Symposium, we presented data from a higher but less frequent dose of Phicera in combination with pembrolizumab—2,000 milligrams every two weeks.

Speaker #3: From which we announced our plan to develop a less frequent loading and maintenance dosing option. Our aim is to gain alignment with the FDA on this approach and initiate that study in parallel to the pivotal study to allow us to have data from that regimen in hand upon potential U.S. approval.

Speaker #3: Approval. Clinically, tumor shrinkage is seen at all doses, but trends deeper with higher exposure. The 1,500 milligram cohort showed a deeper median depth of response versus 750 milligrams.

Ryan Cohlhepp: 1500 mg cohort showed deeper median depth of response versus 750 mg, and the exploratory 2000 mg every two weeks cohort produced consistently high proportions of deep responders with greater than 80% shrinkage and complete response rates. Our translational data shows consistent TGF-β inhibition across all ficerafusp doses, confirming the mechanism that drives tumor penetration and immune activation. Importantly, inhibition is strongest with the 1500 mg weekly dose and less frequent 2000 mg regimen. We believe this TGF-β-driven depth of response is the defining hallmark of ficerafusp and a clear differentiator versus EGFR-directed therapies, which do not target TGF-β. This mechanism is especially meaningful in HPV-negative disease, a setting with poor outcomes and limited innovation, where deeper, more durable responses are urgently needed for patients. We remain confident that this biology will continue to translate into clinically differentiated long-term outcomes for these patients.

Speaker #3: And the exploratory 2,000-milligram every-two-week cohort produced consistently high proportions of deep responders, with greater than 80% shrinkage and complete response rates. Our translational data shows consistent TGF-beta inhibition across all Phicera doses.

Speaker #3: Confirming the mechanism that drives tumor penetration and immune activation. Importantly, inhibition is strongest with the 1,500-milligram weekly dose and the less frequent 2,000-milligram regimen.

Speaker #3: We believe this TGF-beta-driven depth of response is the defining hallmark of Phicera and the clear differentiator versus EGFR-directed therapies, which do not target TGF-beta.

Speaker #3: This mechanism is especially meaningful in HPV-negative disease, a setting with poor outcomes and limited innovation, where deeper, more durable responses are urgently needed for patients.

Speaker #3: We remain confident that this biology will continue to translate into clinically differentiated, long-term outcomes for these patients. Importantly, Phicera's deep responses are paired with sustained durability without any trade-off.

Ryan Cohlhepp: Importantly, ficerafusp alfa's deep responses are paired with sustained durability without any trade-off. The median duration of response approaches 22 months, more than three times longer than the 6.7 months median duration of response reported with pembrolizumab plus chemotherapy. Our 2000 mg every two-week cohort similarly delivered multiple deep responses persisting beyond 20 months, underscoring the consistency of benefit across dosing schedules. Crucially for patients, providers, and payers, ficerafusp alfa maintains this level of durability even with less frequent dosing. This positions ficerafusp alfa favorably in a market moving toward treatment regimens that reduce clinic burden, improve quality of life, and support long-term adherence. We believe this performance reflects ficerafusp alfa's tumor-penetrating mechanism, enabling depth and durability that translate into meaningful long-term outcomes while supporting a more flexible, patient-centric dosing paradigm. We're often asked whether deep depth of response translates to long-term outcomes.

Speaker #3: The median duration of response approaches 22 months, more than three times longer than the 6.7-month median duration of response reported with pembrolizumab plus chemotherapy.

Speaker #3: Our 2,000-milligram every-two-week cohort similarly delivered multiple deep responses persisting beyond 20 months, underscoring the consistency of benefit across dosing schedules. Crucially for patients, providers, and payers, Phicera maintains this level of durability even with less frequent dosing.

Speaker #3: This positions Phicera favorably in a market moving toward treatment regimens that reduce clinic burden, improve quality of life, and support long-term adherence. We believe this performance reflects Phicera's tumor-penetrating mechanism, enabling depth and durability that translate into meaningful long-term outcomes while supporting a more flexible, patient-centric dosing paradigm.

Speaker #3: We're often asked whether deep depth of response translates to long-term outcomes. As we first showed at ASCO last year, there's a clear distinction in duration of response, progression-free survival, and overall survival among HPV-negative head and neck cancer patients who have had deep responses versus those that do not.

Ryan Cohlhepp: As we first showed at ASCO last year, there's a clear distinction in duration of response, progression-free survival, and overall survival among HPV negative head and neck cancer patients who have had deep responses versus those that do not. This data is what drives our belief that deep responses that are the hallmark of ficerafusp alfa's clinical profile drive outsized durability and long-term benefit. Importantly, other investigational agents also need to demonstrate the deep and durable responses to meaningfully improve long-term clinical outcomes. As our recent financing highlights, we have strong conviction in ficerafusp alfa's clinical data and its differentiated profile compared to other investigational agents in the head and neck cancer space, and we are continuing to bolster our commercial and medical investment in preparation for a potential US launch, including hiring of the Chief Commercial Officer this year.

Speaker #3: This data is what drives our belief that deep responses, which are the hallmark of Phicera's clinical profile, drive outsized durability and long-term benefit. Importantly, other investigational agents also need to demonstrate deep and durable responses to meaningfully improve long-term clinical outcomes.

Speaker #3: As our recent financing highlights, we have strong conviction in Phicera's clinical data and its differentiated profile compared to other investigational agents in the head and neck space.

Speaker #3: And we are continuing to bolster our commercial and medical investment, in preparation for a potential U.S. launch, including hiring of the Chief Commercial Officer this year.

Ryan Cohlhepp: Head and neck cancer is a significant and fast-growing global market, projected to reach more than $5 billion in global sales in the 2030s. HPV negative patients represent the heavy majority of patients in the frontline recurrent metastatic setting, and HPV status is known by the time the disease recurs or metastasizes, which means that HPV testing will not be a barrier to care. There are roughly 50,000 annually incident patients across major markets, including approximately 18,000 in the US, where we plan our initial launch. With ficerafusp alfa, we have the potential to significantly expand an already significant HPV negative head and neck cancer market. Ficerafusp alfa's clinical data show us that we further expand that market in two ways.

Speaker #3: Head and neck cancer is a significant and fast-growing global market, projected to reach more than $5 billion in global sales in the 2030s. HPV-negative patients represent the heavy majority of patients in the frontline recurrent metastatic setting, and HPV status is known by the time the disease recurs or metastasizes, which means the HPV testing will not be a barrier to care.

Speaker #3: There are roughly 50,000 incident patients annually across major markets, including approximately 18,000 in the U.S., where we plan our initial launch. With Phicera, we have the potential to significantly expand an already significant HPV-negative head and neck cancer market.

Speaker #3: Phicera’s clinical data show us that we can further expand that market in two ways. First, by growing the number of patients who are responding to therapy, as seen with the fact that Phicera provides a two to three times greater overall response rate. Second, by growing the duration of response, as seen by Phicera’s two- to three-fold improvement over standard-of-care median duration of response.

Ryan Cohlhepp: First, by growing the number of patients who are responding to therapy, as seen with the fact that ficerafusp alfa provides a 2 to 3 times greater overall response rate, and second, by growing the duration of response, as seen by ficerafusp alfa's 2- to 3-fold improvement over standard of care median duration of response. We are pioneering a new treatment paradigm for HPV-negative head and neck cancer with a tailored therapy engineered to overcome the unique biology of this disease and achieve deep, durable, and clinically significant benefit while sparing the use of chemotherapy to further improve quality of life for patients. With this knowledge in hand, we are eager to further invest in our pre-launch activities across commercial and medical, including additional evidence generation strategies that may further expand the market opportunity beyond that being studied in our pivotal trial.

Speaker #3: We are pioneering a new treatment paradigm for HPV-negative head and neck cancer, with a tailored therapy engineered to overcome the unique biology of this disease and achieve deep, durable, and clinically significant benefit, while sparing the use of chemotherapy to further improve quality of life for patients.

Speaker #3: With this knowledge in hand, we are eager to further invest in our pre-launch activities across commercial and medical, including additional evidence generation strategies that may further expand the market opportunity beyond that being studied in our pivotal trial.

Ryan Cohlhepp: Recent competitive updates have only strengthened our conviction that ficerafusp alfa may have the best chemo-sparing regimen that actually addresses both the EGFR and TGF-β inhibition underlying biology of HPV negative head and neck cancer to improve long-term outcomes for patients. We are preparing to launch in an environment where, based upon evolving regulatory and clinical development commentary across our competitor set, we have the opportunity to set the tone for what the therapeutic bar looks like for significantly improving unmet medical need in this space. As we head into Q2, we look forward to providing long-term follow-up data from across our phase 1b studies of ficerafusp alfa in combination with pembrolizumab in front line recurrent metastatic HPV negative head and neck cancer.

Speaker #3: Recent competitive updates have only strengthened our conviction that Phicera may have the best chemosparing regimen that actually addresses both the EGFR and TGF-beta inhibition underlying the biology of HPV-negative head and neck cancer to improve long-term outcomes for patients.

Speaker #3: We are preparing to launch in an environment where, based upon evolving regulatory and clinical development commentary across our competitor set, we have the opportunity to set the tone for what the therapeutic bar looks like for significantly improving unmet medical need in this space.

Speaker #3: As we head into the second quarter, we look forward to providing long-term follow-up data from across our Phase 1b studies of Phicera in combination with pembrolizumab and frontline recurrent metastatic HPV-negative head and neck cancer.

Ryan Cohlhepp: The Phase 1b 1,500 mg every week data presented at ASCO 2025 were mature with a median duration of response of 21.7 months and a median overall survival of 21.3 months. In this update, we are looking for a better understanding of that IO tail at extended duration of follow-up, as well as the additional maturity on key endpoints from the 750 mg every week and the 2,000 mg every two-week data sets. No other investigational agent targeting EGFR in the head and neck cancer space have shown durability of outcomes out this far, a key differentiating factor for ficerafusp alfa that resonates deeply with clinicians. With that, I'll turn it to Ivan to review the financials.

Speaker #3: The Phase 1B 1,500-milligram every week data presented at ASCO 2025 were mature, with a median duration of response of 21.7 months and a median overall survival of 21.3 months.

Speaker #3: In this update, we are looking for a better understanding of that IO tail at extended duration of follow-up, as well as the additional maturity on key endpoints from the 750-milligram every-week and the 2,000-milligram every-two-week data sets.

Speaker #3: No other investigational agent targeting EGFR in the head and neck cancer space has shown durability of outcomes out this far. A key differentiating factor for Phicera that resonates deeply with clinicians.

Speaker #3: With that, I'll turn it to Ivan to review the financials.

Ivan Hyep: Thanks, Ryan. Earlier this morning, we reported detailed Q4 and full year 2025 financial results in our press release, and I'll summarize a few highlights here. Our total operating expenses for 2025 increased compared to the Q4 and full year 2024, driven by clinical operations and development expenses, including increased manufacturing and process development costs associated with our ongoing pivotal FORTIFI-HN01 study. We also saw an increase in personnel-related costs, including stock-based compensation, as we grew our workforce throughout the year, primarily in support of clinical operations and development functions.

Speaker #2: Thanks, Ryan. Earlier this morning, we reported detailed fourth quarter and full-year 2025 financial results in our press release, and I'll summarize a few highlights here.

Speaker #2: Our total operating expenses for 2025 increased compared to the fourth quarter and full year 2024, driven by clinical operations and development expenses, including increased manufacturing and process development costs associated with our ongoing pivotal Fortify HN01 study.

Speaker #2: We also saw an increase in personnel-related costs, including stock-based compensation, as we grew our workforce throughout the year, primarily in support of clinical operations and development functions.

Ivan Hyep: We anticipate an increase in operating expenses for 2026, driven by increased investment in clinical operations, particularly for the pivotal FORTIFI-HN01 study, the interim analysis for which is expected in mid-2027, as well as an increase in SG&A and headcount expenditures as we invest in early commercial and medical infrastructure to support the potential launch of ficerafusp alfa. We entered 2026 with $414.8 million in cash equivalents, and marketable securities. In Q1, we raised an additional $161.8 million in net proceeds via an oversubscribed public offering, which further strengthens our balance sheet, and we maintain cash runway guidance into H1 2029.

Speaker #2: We anticipate an increase in operating expenses for 2026, driven by increased investment in clinical operations—particularly for the pivotal Fortify HN01 study, the interim analysis for which is expected in mid-2027—as well as an increase in SG&A in head and neck expenditures, as we invest in early commercial and medical infrastructure to support the potential launch of Phicera.

Speaker #2: We entered 2026 with $414.8 million in cash, cash equivalents, and marketable securities. In the first quarter, we raised an additional $161.8 million in net proceeds via an oversubscribed public offering, which further strengthens our balance sheet, and we maintain cash runway guidance into the first half of 2029.

Ivan Hyep: This additional capital will allow us to support a planned regulatory filing for ficerafusp alfa, further invest and build in our medical and commercial infrastructure ahead of a potential US approval and launch, further accelerate the development of ficerafusp alfa in head and neck cancer, including a less frequent dosing schedule, fund manufacturing costs for ficerafusp alfa for ongoing and anticipated drug development efforts, fund early signal finding activities to support further indication expansion for ficerafusp alfa, and fund other general corporate purposes. Our existing cash as of year-end and this additional recent cash infusion puts us in a position to be able to drive smart growth for ficerafusp alfa as we enter a period of discipline but increased investment to drive future clinical and commercial success. With that, I'll now turn the call back over to the operator for questions. Operator?

Speaker #2: This additional capital will allow us to support a planned regulatory filing for Phicera, and further invest in and build our medical and commercial infrastructure ahead of a potential U.S.

Speaker #2: Approval and launch. Further accelerate the development of Phicera in head and neck cancer, including a less frequent dosing schedule; fund manufacturing costs for Phicera for ongoing and anticipated drug development efforts; fund early signal-finding activities to support further indication expansion for Phicera; and fund other general corporate purposes.

Speaker #2: Our existing cash as of year-end, and this additional recent cash infusion, put us in a position to be able to drive smart growth for Phicera as we enter a period of disciplined but increased investment to drive future clinical and commercial success.

Speaker #2: With that, I'll now turn the call back over to the operator for questions. Operator?

Operator: Thank you, ladies and gentlemen. If you have a question or a comment at this time, please press star one one on your telephone. If your question has been answered or you wish to move yourself from the queue, please press star one one again. We will pause for a moment while we compile our Q&A roster. Our first question comes from Tyler Van Buren with TD Cowen. Your line is open.

Speaker #3: Thank you, ladies and gentlemen. If you have a question or a comment at this time, please press *11 on your telephone. If your question has been answered or you wish to remove yourself from the queue, please press *11 again.

Speaker #3: We will pause for a moment while we compile our Q&A roster. Our first question comes from Tyler Van Buren with TD Cowen. Your line is open.

Tyler Van Buren: Hey, guys. Good morning. Thanks for taking the questions. Can you provide more color on the patient demand and willingness to participate in pivotal FORTIFI-HN01 that you're seeing in both the US and in ex-US sites? As a follow-up, kind of related question, do you have a sense of how many patients you might need to enroll in the separate study of the less frequent dosing regimen to achieve registration?

Speaker #4: Hey, guys. Good morning. Thanks for taking the questions. Can you provide more color on the patient demand and willingness to participate in the pivotal Fortify study that you're seeing in both the U.S.?

Speaker #4: And in ex-U.S. sites? And as a follow-up, or kind of related question, do you have a sense of how many patients you might need to enroll in the separate study of the less frequent dosing regimen to achieve registration?

Claire Mazumdar: Thank you for your question, Tyler. There are two questions. One was around, you know, momentum around patient enrollment in the FORTIFI-HN01 study, and then the other was approximately how many patients do we plan to enroll in the parallel bridging study for the loading and maintenance dose. I'll answer the first one or the second one first, and speak to the fact that we're looking for regulatory alignment and we'll provide far more clarity to the study in more detail once we have that regulatory alignment. The approximate size is anywhere between 150 to 200 patients is our current estimate. The first question was around enrollment of the FORTIFI-HN01 study.

Speaker #5: Thank you for your question, Tyler. So, there are two questions. One was around momentum around patient enrollment in the Fortify HN01 study, and then the other was approximately how many patients do we plan to enroll in the parallel bridging study for the loading and maintenance dose.

Speaker #5: I'll answer the first one or the second one first, and speak to the fact that we're looking for regulatory alignment. We'll provide far more clarity to the study in more detail once we have that regulatory alignment.

Speaker #5: But the approximate size is anywhere between 150 to 200 patients, which is our current estimate. The first question was around enrollment of the Fortify study.

Claire Mazumdar: What I can say is that we continue to build significant momentum in that study as we have both received breakthrough designation as well as moving from the phase 2 to the phase 3 portion and going now to the 2-to-1 randomization of 1,500 milligrams weekly, randomized 2 to 1 to pembro monotherapy. We've seen great momentum also ex-US, in particular in European sites, Asia Pacific sites, as well as South America, with a significant momentum in areas where we know that there's a high prevalence of smoking. I will pass it over to Tanya to give additional details to the FORTIFI-HN01 momentum. Hi. Thanks. This is Tanya Green, Chief Development Officer. So yeah, as Claire said, we have really strong momentum for the phase 3 study in terms of enrollment.

Speaker #5: What I can say is that we continue to build significant momentum in that study, as we have both received breakthrough designation, as well as moved from the Phase 2 to the Phase 3 portion, and are now going to the 2-to-1 randomization of 1,500 milligrams weekly, randomized 2-to-1 to pembrol monotherapy.

Speaker #5: We've seen great momentum also ex-U.S., in particular in European sites, Asia-Pacific sites, as well as South America, with significant momentum in areas where we know that there's a high prevalence of smoking.

Speaker #5: I will pass it over to Tonya to give additional details to the Fortify HN01 momentum.

Tanya Green: Hi. Thanks. This is Tanya Green, Chief Development Officer. So yeah, as Claire said, we have really strong momentum for the phase 3 study in terms of enrollment.

Speaker #6: Hi, thanks. This is Tonya Green, Chief Development Officer. So, yeah, as Claire said, we have really strong momentum for the Phase 3 study in terms of enrollment, as publicly available.

Tanya Green: As publicly available, we have 129 active sites right now, and this team remains highly focused in executing the study, to achieve substantial enrollment by the end of this year, which will keep us on track to have our interim analysis by mid-2027.

Speaker #6: We have 129 active sites right now, and this team remains highly focused on executing the study to achieve substantial enrollment by the end of this year, which will keep us on track to have our interim analysis by mid-2027.

Operator: Thank you. One moment for our next question. Our next question comes from Eric Schmidt with Cantor Fitzgerald. Your line is open.

Speaker #3: Thank you. One moment for our next question. Our next question comes from Eric Schmidt with Cancer Fitzgerald. Your line is open.

Eric Schmidt: Oh, good morning, and thanks for taking the question and congrats on all the recent progress. Questions on the colorectal cancer update that we might see in H2. Could you just give us a sense for the scope of that update in terms of patients dosing and, you know, in particular, what type of benchmarks you think you'd hope to be able to provide in order to demonstrate proof of concept? Thank you.

Speaker #4: Hello. Good morning, and thanks for taking the question. Congrats on all the recent progress. I have questions on the colorectal cancer update that we might see in the second half of the year.

Speaker #4: Could you just give us a sense for the scope of that update in terms of patients, dosing, and, in particular, what type of benchmarks you think you'd hope to be able to provide in order to demonstrate proof of concept?

Speaker #4: Thank you.

Ryan Cohlhepp: Hi, Eric. Thank you for the question. You know, in terms of our CRC update, you know, as we've indicated, you know, we look to have data in H2 this year on those cohorts. You know, in terms of the total number of patients that we plan to present, I think that's still somewhat variable based upon enrollment. Consistent with our previous updates, you know, we're always looking for datasets, probably, you know, no less than 20 patients per cohort. You know, I think that, you know, certainly, you know, even as recently, we've seen the treatment landscape evolve and we're mindful of that with recent data that's been out. You know, I'd say what we're...

Speaker #3: Hi, Eric. Thank you for the question. In terms of our CRC update, as we've indicated, we expect to have data in the second half of this year on those cohorts.

Speaker #3: In terms of the total number of patients that we plan to present, I think that's still somewhat variable based upon enrollment. But consistent with our previous updates, we're always looking for data sets, probably no less than 20 patients per cohort.

Speaker #3: I think that certainly, even as recent, we've seen the treatment landscape evolve, and we're mindful of that with recent data that's been out. I'd say what we're—the two cohorts that we are currently exploring and seeking signals in are third line. As you know, that's a highly challenging population.

Ryan Cohlhepp: You know, the two cohorts that we are currently exploring, seeking signals in are third-line. You know, as you know, that's a highly challenging population. Again, we've got both a cohort in monotherapy as well as one in combination with pembrolizumab at the 1500mg weekly dose. Again, you know, I think we continue to look at that data, you know, for signal-seeking purposes and determine whether there's a path forward in CRC, particularly as we look to see about, you know, the opportunity to move into earlier lines of therapy in colorectal cancer using those signals to determine whether there's, you know, something there to invest further.

Speaker #3: And again, we've got both a cohort in monotherapy as well as one in combination with pembrolizumab at the 1,500-milligram weekly dose. So, again, I think we continue to look at that data for signal-seeking purposes and determine whether there's a path forward in CRC, particularly as we look to see about the opportunity to move into earlier lines of therapy in colorectal cancer—using those signals to determine whether there's something there to invest further.

Eric Schmidt: Thank you.

Operator: One moment for our next question. Our next question comes from Stephen Riley with Stifel. Your line is open.

Speaker #4: Thank you.

Speaker #3: One moment for our next question. Our next question comes from Stephen Wiley with Stifel. Your line is open.

Stephen Riley: Yeah, good morning. Thanks for taking the questions. I guess with the understanding that you're gonna be providing the kind of pooled expansion cohort data ASCO in a few months, just curious if the patients in the 750 mg once weekly cohort were given the opportunity to uptitrate to the 1,500 mg dose, just given the, I guess, the relative deficiency in depth of response. Great question, Stephen. What we'll be presenting at ASCO is likely an update from three separate cohorts. The 3-year follow-up, median follow-up for the 1,500 mg dose weekly, the 750 mg weekly dose, it was about a 30-patient cohort with at least 18 months of follow-up. Same for the 2,000 mg every two-week cohort, an additional 30 patients with about 18 months of follow-up.

Stephen Willey: Yeah, good morning. Thanks for taking the questions. I guess with the understanding that you're gonna be providing the kind of pooled expansion cohort data ASCO in a few months, just curious if the patients in the 750 mg once weekly cohort were given the opportunity to uptitrate to the 1,500 mg dose, just given the, I guess, the relative deficiency in depth of response. Great question, Stephen. What we'll be presenting at ASCO is likely an update from three separate cohorts. The 3-year follow-up, median follow-up for the 1,500 mg dose weekly, the 750 mg weekly dose, it was about a 30-patient cohort with at least 18 months of follow-up. Same for the 2,000 mg every two-week cohort, an additional 30 patients with about 18 months of follow-up.

Speaker #7: Yeah, good morning. Thanks for taking the questions. I guess, with the understanding that you're going to be providing the kind of pooled expansion cohort data at ASCO in a few months, just curious if the patients in the 750 mg once-weekly cohort were given the opportunity to up-titrate to the 1,500 mg dose, just given the, I guess, the relative deficiency in depth of response.

Speaker #5: Great question, Steve. So, what we'll be presenting at ASCO is likely an update from three separate cohorts: the three-year follow-up, median follow-up, for the 1,500 milligram dose weekly.

Speaker #5: The 750-milligram weekly dose—it was about a 30-patient cohort with at least 18 months of follow-up. And same for the 2,000-milligram every two-week cohort, an additional 30 patients with about an 18-month follow-up.

Claire Mazumdar: In that particular cohort, to your question, the 750, we did not increase the dose afterwards. These were patients that were maintained at the 750 mg dose throughout their course of treatment. We will be providing an update to PFS and duration of response from those cohorts that will continue to speak to the depth and durability profile that we see across our cohorts. If your question regarding the pivotal study in FORTIFI-HN01, I do believe that we were able to cross over the patients enrolled at this lower dose. If they remained on treatment, they did cross over to the 1,500 mg dose in the pivotal study. Thank you for your question. Maybe just a quick follow-up.

Speaker #5: So, in that particular cohort, to your question, the 750, we did not increase the dose afterwards. These were patients that were maintained at the 750-milligram dose throughout their course of treatment.

Speaker #5: And we will be providing an update to PFS and duration of response from those cohorts that will continue to speak to the depth and durability profile that we see across our cohorts.

Speaker #5: If your question regarding the pivotal study in FORTIFY HN01, I do believe that we were able to cross over the patients enrolled at the lower dose, and so, if they remained on treatment, they did cross over to the 1,500 milligram dose in the pivotal study.

Speaker #5: Thank you for your question.

Stephen Riley: I know there's been kind of some background discussion about having interest in the pre-metastatic setting, whether it's neoadjuvant and adjuvant, and just wondering kind of where you are on that now, and does the pursuit of this

Speaker #7: And then maybe just a quick follow-up. I know there's been kind of some background discussion about having interest in the pre-metastatic setting, whether it's neoadjuvant, in adjuvant, and just wondering kind of where you are on that now, and does the pursuit of this new loading maintenance strategy and the need to generate maybe a couple hundred patients' worth of data change, perhaps, the plans to pursue Bicara therapies in the pre-metastatic setting?

Stephen Willey: I know there's been kind of some background discussion about having interest in the pre-metastatic setting, whether it's neoadjuvant and adjuvant, and just wondering kind of where you are on that now, and does the pursuit of this

Stephen Riley: New loading maintenance strategy and the need to generate maybe a couple hundred patients' worth of data change perhaps the plans to pursue bifunctional therapies in the pre-metastatic setting? Thanks.

Stephen Willey: New loading maintenance strategy and the need to generate maybe a couple hundred patients' worth of data change perhaps the plans to pursue bifunctional therapies in the pre-metastatic setting? Thanks.

Claire Mazumdar: No, I think to that question, we do believe that the locally advanced setting of head and neck has always been a large opportunity. Given the signal we've seen in the recurrent and metastatic setting, there's a strong biology to move into earlier lines of head and neck cancer. We do believe it is also becoming a more competitive landscape as well. We have begun initial signal sequence studies in those areas and hope to provide updates as we move forward in more detail. We do think it is a very important opportunity that could potentially triple the market opportunity compared to recurrent and metastatic setting.

Speaker #7: Thanks.

Speaker #5: No, I think to that question, we do believe that the locally advanced setting of head and neck has always been a large opportunity, and given the signal we've seen in the recurrent and metastatic setting, there's a strong biology to move into earlier lines of head and neck cancer.

Speaker #5: And we do believe it has also become a more competitive landscape as well. So we have begun initial signal-sequence studies in those areas and hope to provide updates as we move forward.

Speaker #5: In more detail, but we do think it is a very important opportunity. That could potentially triple the market opportunity compared to the recurrent and metastatic setting.

Ryan Cohlhepp: Yeah, Steve, you know, I'd say that in fact, you know, our evolution of the dosing paradigm, I think, you know, further supports and reinforces our ability to go into those earlier lines in head and neck cancer. You know, from a overall operational execution perspective, you know, part of, you know, the key driver of our last financing was to be able to fund that alternative dosing schedule as well as, you know, continued investment in earlier areas of head and neck cancer.

Speaker #3: Yeah, Steve, I'd say that, in fact, our evolution of the dosing paradigm, I think, further supports and reinforces our ability to go into those earlier lines in head and neck cancer.

Speaker #3: And from an overall operational execution perspective, part of the key driver of our last financing was to be able to fund that alternative dosing schedule, as well as continued investment in earlier areas of head and neck cancer.

[Analyst]: Very helpful. Thanks for taking the questions.

Stephen Willey: Very helpful. Thanks for taking the questions.

Speaker #7: Very helpful. Thanks for taking the questions.

Operator: One moment for our next question. Our next question comes from Judah Frommer with Morgan Stanley. Your line is open.

Speaker #3: One moment for our next question. Our next question comes from Judah Frommer with Morgan Stanley. Your line is open.

Judah Frommer: Yeah. Hi, guys. Thanks for taking the questions. Maybe just can you help us with an update on how many centers you're in with FORTIFI-HN01, what overlaps are with petosemtamab trials and kind of what that does from a potential market share capture perspective for you, the likelihood based on investigator response for investigators at your centers to stick with ficerafusp alfa in the case of an approval. Then just secondarily, maybe just help us with that cash runway guidance being maintained despite the raise. What was not contemplated in the previous guide that is in there now that'll eat up some of the cash that was raised to maintain that guidance? Thanks.

Speaker #8: Yeah, hi, guys. Thanks for taking the questions. Maybe just—can you help us with an update on how many centers you're in with Fortify HN01, what overlaps there are with pedosentimab trials, and kind of what that does from a potential market share capture perspective for you?

Speaker #8: The likelihood, based on investigator response, for investigators at your centers to stick with Fyzera in the case of an approval. And then, just secondarily, maybe just help us with that cash runway guidance being maintained despite the raise.

Speaker #8: What was not contemplated in the previous guide that is in there now, that'll eat up some of the cash that was raised to maintain that guidance?

Claire Mazumdar: Sounds great. I'll pass over the first part of the question to Tanya Green, our Development Officer, to speak to the sites and the study, and then to Ivan Hyep, our CFO, for cash guidance.

Speaker #8: Thanks.

Speaker #5: Sounds great. And so I'll pass over the first part of the question to Tanya Green, our Development Officer, to speak to the sites and the study.

Speaker #5: And then to Ivan High, our CFO. Forecast guidance.

Tanya Green: Hi, yes. Thanks for the question. In terms of sites, we have 129 sites that are open globally. In terms of the competitive overlap with the other studies, we do believe that there are some sites that overlap, but we have seen great, you know, momentum at all of our sites in terms of patients, so that we don't see that being a consideration.

Speaker #6: Hi. Yes, thanks for the question. So in terms of sites, we have 129 sites that are open globally. And in terms of the competitive overlap with the other studies, we do believe that there are some sites that overlap, but we have seen great momentum at all of our sites in terms of patients, so we don't see that being a consideration.

Ivan Hyep: Judah, thanks for the question. In terms of use of proceeds for this recent financing, we heavily focused on alternative dosing, pre-launch activities, and investment in both commercial and regulatory. For us, we didn't feel that we needed to change guidance there, as it allows us to kind of build up instead of just extending runway.

Speaker #7: And Judah, thanks for the question. In terms of use of proceeds for this recent financing, we heavily focused on the alternative dosing pre-launch activities and investment in both commercial and regulatory.

Speaker #7: And so for us, we didn't feel that we needed to change guidance there, as it allows us to kind of build up instead of just extending runway.

Judah Frommer: Thanks.

Operator: One moment for our next question. Our next question comes from Kelsey Goodwin with Piper Sandler. Your line is open.

Speaker #8: Thanks.

Speaker #3: One moment for our next question. Our next question comes from Kelsey Goodwin with PSC. Your line is open.

Kelsey Goodwin: Oh, hey, good morning. Thanks for taking my question. Maybe again, just on FORTIFI-HN01 and the enrollment. How should we think about the ultimate split of enrollment across geographies? Is this similar to other trials in this setting? Second, in terms of the bridging trial design, I guess, do you have a sense of when you might be able to provide more color for the street? Thanks so much.

Speaker #6: Oh, hey. Good morning. Thanks for taking my question. Maybe again, just on Fortify and the enrollment, how should we think about the ultimate split of enrollment across geographies?

Speaker #6: And is this similar to other trials in the setting? And then, second, in terms of the bridging trial design, I guess, do you have a sense of when you might be able to provide more color for the Street?

Ryan Cohlhepp: Great, Kelsey. Thank you for the question. You know, in terms of geographical distribution on a trial, I'd say what we anticipated is this will be very similar a lot, you know, some of the recent trials, you know, KEYNOTE-048 in particular. You know, I think what we had anticipated and continue to see in our own enrollment is very consistent with some of those historical trials. In terms of the alternative dosing, you know, again, as Claire had mentioned, you know, we intend to get regulatory input on that trial and do expect to be able to provide greater clarity later this year.

Speaker #6: Thanks so much.

Speaker #3: Great, Kelsey. Thank you for the question. In terms of geographical distribution on a trial, I’d say what we anticipated is it’ll be very similar to a lot—some of the recent trials, Keynote-48 in particular.

Speaker #3: And I think what we had anticipated and continue to see in our own enrollment is very consistent with some of those historical trials. In terms of the alternative dosing, again, as Claire had mentioned, we intend to get regulatory input on that trial.

Speaker #3: And do expect to be able to provide greater clarity later this year.

Operator: Thank you. One moment for our next question. Our next question comes from Reni Benjamin of Citizens. Your line is open.

Speaker #7: Thank you. One moment for our next question. Our next question comes from Renny Benjamin of Citizens. Your line is open.

Reni Benjamin: Hey, great. You guys, thanks for taking the questions, and congrats on the progress. Just sticking with FORTIFI-HN01, can you maybe just help quantify a little bit as to what you mean by substantial enrollment? As we think about the number of patients required for the ORR interim versus kind of the final OS, can you give us a sense as to, you know, how that might look? Then just kinda related, since this would be used for accelerated approval, can you give us some thoughts on how you're thinking about more of a global filing as well for ficerafusp alfa? Thank you.

Speaker #9: Hey Greg, you guys, thanks for taking the questions and congrats on the progress. Just sticking with Fortify, can you maybe just help quantify a little bit as to what you mean by substantial enrollment?

Speaker #9: And as we think about the number of patients required for the ORR interim versus kind of the final OS, can you give us a sense as to how that might look?

Speaker #9: And then just kind of related, since this would be used for accelerated approval, can you give us some thoughts on how you're thinking about more of a global filing as well for Fyzera?

Claire Mazumdar: Great question. To your question around substantial enrollment, that is really predicated on what the FDA is looking at the time in terms of a seamless Phase 2/3 design. What the FDA wants to ensure is that we are close to fully enrolled in the total confirmatory study so as not to introduce bias at the time of granting an accelerated approval. Substantial is a key adjective for, you know, very meaningful enrollment to ensure we're not introducing additional bias into the confirmatory study. To that question, we do believe that in the United States, with the FDA, we are on a path to potential accelerated approval predicated on a response rate endpoint from an interim analysis that will also look at durability of response as well as qualitative overall survival.

Speaker #9: Thank you.

Speaker #5: Great question. So, to your question around substantial enrollment, that is really predicated on what the FDA is looking for at the time in terms of a seamless Phase 2/3 design.

Speaker #5: What the FDA wants to ensure is that we are close to fully enrolled in the total confirmatory study, so as not to introduce bias at the time of granting an accelerated approval.

Speaker #5: So, 'substantial' is a key adjective for very meaningful enrollment to ensure we're not introducing additional bias into the confirmatory study. To that question, we do believe that in the United States, with the FDA, we are on a path to potential accelerated approval predicated on a response rate endpoint from an interim analysis that will also look at durability of response, as well as qualitative overall survival.

Claire Mazumdar: The study will continue for full confirmatory approval on an overall survival endpoint. Today, we believe that ex-US, a full overall survival endpoint is needed to predicate a global approval. Thank you for your question. Great. Thanks for taking the questions.

Speaker #5: The study will continue for full confirmatory approval on an overall survival endpoint. Today, we believe that XUS, a full overall survival endpoint, is needed to predicate a global approval.

Speaker #5: Thank you for your question.

Operator: One moment for our next question. Our next question comes from Jeet Mukherjee with BTIG. Your line is open.

Speaker #9: Thanks for taking the questions.

Speaker #3: One moment for our next question. Our next question comes from Jeet Mukherjee with BTIG. Your line is open.

Jeet Mukherjee: Great. Thanks for taking the question. Two from me. Could you speak to the rationale and reasons for confidence on the loading and once every three-week maintenance strategy when it was a 2000 mg once every two-week regimen that showed a notable response and depth of response? The second question was just related to the colorectal cancer update. Could you confirm if the patient enrollment criteria allows for liver mets? Thank you.

Speaker #10: Great, thanks for taking the question. Two from me. Could you speak to the rationale and reasons for confidence on the loading and once-every-three-week maintenance strategy, when it was a 2,000 mg once-every-two-week regimen that showed a notable response and depth of response?

Speaker #10: And the second question was just related to the colorectal cancer update. Could you confirm if the patient enrollment criteria allows for liver mets?

Ryan Cohlhepp: Yeah. Thanks for the question. So on the alternative dosing, you know, we have gotten comfortable with our proposed, you know, strategy there. Looking at the compilation of all of our data sets, you know, I think this is where really having the 750mg weekly, the 1500 weekly, and then the 2000 every two weeks has given us the ability to do extensive exposure response modeling across those data sets. You know, I think a couple of key notes in terms of the data, you know, one of the things that we know when we look at the patients in our 1b data is that 1500mg weekly dose, we're getting very rapid responses. You know, at 1.4 months, we're getting responses.

Speaker #10: Thank you.

Speaker #8: Yeah, thanks for the question. So, on the alternative dosing, we have gotten comfortable with our proposed strategy there. Looking at the compilation of all of our data sets, I think this is where really having the 750 milligram weekly, the 1,500 milligram weekly, and then the 2,000 milligram every two weeks has given us the ability to do extensive exposure-response modeling across those data sets.

Speaker #8: I think a couple of key notes in terms of the data. One of the things that we know when we look at the patients in our 1B data is that with the 1,500 milligram weekly dose, we're getting very rapid responses.

Speaker #8: At 1.4 months that we're getting responses, the vast majority of patients will have achieved the response within 12 weeks. And at that same time, most of them will have hit their maximal depth of response by the 12-week time.

Ryan Cohlhepp: The vast majority of patients will have achieved the response within 12 weeks. At that same time, most of them will have hit their maximal depth of response by the 12-week time. That gives us the confidence in why we wanna initiate with a weekly dosing phase and then be able to transition to extend that interval out to every 3 weeks. Again, what we'll look to do is to match the pharmacokinetic profile from both an exposure as well as a Ctrough perspective to the 750 mg weekly, which again, we know as you saw on that data set that we presented last year, you see really good response rates. You see really good activity, even at the 750.

Speaker #8: And so that gives us the confidence in why we want to initiate with a weekly dosing phase, and then be able to transition to extend that interval out to every three weeks. Again, what we'll look to do is to match the pharmacokinetic profile from both an exposure as well as a C-trough perspective.

Speaker #8: To the 750 milligram weekly, which again, we know—as you saw on that data set that we presented last year—you see really good response rates.

Speaker #8: You see really good activity, even for the 750. I think one of the things to remember here, if you recall our data, is that depth of response—we’re seeing more than 80% of our patients get an 80% or greater reduction in their tumor.

Ryan Cohlhepp: I think one of the things to remember here, if you recall our data, you know, that depth of response, we're seeing more than 80% of our patients get an 80% or greater reduction in their tumor. You think they're at that 12-week mark, you've got significantly less tumor in the patients at the 12-week mark, which gives us confidence in our ability to extend out that interval, maintain very durable response, and give the patients the ability to have a more convenient administration schedule. For your CRC question, the inclusion criteria does allow for liver metastases. In fact, the anal canal data that we have presented previously really shows our ability and Bicara's ability to resolve liver metastases in that population.

Speaker #8: So, you think they're at that 12-week mark—you've got significantly less tumor in the patients at the 12-week mark—which gives us confidence in our ability to extend out that interval, maintain very durable response, and give the patients the ability to have a more convenient administration schedule.

Speaker #8: For your CRC question, the inclusion criteria does allow for liver metastases, and in fact, the anal canal data that we have presented previously really shows our ability—and Fyzera's ability—to resolve liver metastases in that population.

Ryan Cohlhepp: It is something that we think could be a unique differentiating perspective of our molecule, and so we did allow liver mets.

Speaker #8: So it is something that we think could be a unique, differentiating perspective of our molecule. And so we did allow a liver mets.

Operator: Thank you. One moment for our next question. Our next question comes from Ava Fordyce with Wells Fargo. Your line is open.

Speaker #7: Thank you. One moment for our next question. Our next question comes from Eva Fordio with Wells Fargo. Your line is open.

Ava Fordyce: Good morning. Thanks for taking our question. Quick one from us. We've seen now the 3 different dose cohorts with ficerafusp alfa plus pembro, a similar response rate or even higher in some cohorts with CPS 1-19 compared to CPS 20 or higher. Is there anything about the biology that could explain this? If this holds in the phase 3, could you comment on the potential implications from a commercial standpoint? Thanks.

Speaker #5: Good morning. Thanks for taking our question. Quick one from us. We've seen now in the three different dose cohorts with Fyzera plus Pembrol, a similar response rate or even higher in some cohorts with CPS 1–19 compared to CPS 20 or higher.

Speaker #5: And so, is there anything about the biology that could explain this? And if this holds in the Phase 3, could you comment on the potential implications from a commercial standpoint?

Claire Mazumdar: Great question, Ava. To your question, it is known that in particular in HPV negative head and neck cancer, there are both higher levels of EGFR and TGF beta that makes these tumors typically more immunosuppressive or treatment resistant than their HPV positive counterparts. In particular, in fact, HPV negative tumors tend to have a slight skewing for CPS low or the CPS 1 to 19. In fact, it's in this patient population that pembro has worse response rates across the board. Seeing very strong response rates in the CPS 1 to 19 really speaks to the underlying biology of being able to target both EGFR and TGF beta, which is why we believe we're able to target these very immunosuppressive tumors.

Speaker #5: Thanks.

Speaker #4: Great question, Eva. So, to your question, it is known that, in particular, in HPV-negative head and neck cancer, there are both higher levels of EGFR and TGF-beta.

Speaker #4: That makes these tumors typically more immunosuppressive or treatment resistant than their HPV-positive counterparts. In particular, in fact, HPV-negative tumors tend to have a slight skewing for CPS low, or the CPS 1 to 19.

Speaker #4: And in fact, it's in this patient population that Pembrol has worse response rates across the board. And so seeing very strong response rates in the CPS 1 to 19 really speaks to the underlying biology of being able to target both EGFR and TGF-beta, which is why we believe we're able to target these very immunosuppressive tumors.

Claire Mazumdar: In fact, we do think that it's always going to be a differentiating aspect of our molecule compared to other EGFR inhibitors that are currently being tested that have not seen the outsized impact in the CPS low. In fact, we do believe that especially given we are going after a chemo-sparing regimen, being able to go after these 1 to 19 will allow us to have a dominant share in what accounts for approximately 50% of the total, head and neck market, but slightly skewed even higher in the, in the HPV negative. In fact, to your question, you may remember that we also have a cohort open in the CPS 0 cohort that we plan to disclose at a later time point that also speaks to this underlying biology.

Speaker #4: In fact, we do think that has always going to be a differentiating aspect for our molecule compared to other EGFR inhibitors that are currently being tested, that have not seen the outsized impact in the CPS low.

Speaker #4: And, in fact, we do believe that—especially given we are going after a chemo-sparing regimen—being able to go after these 1 to 19 will allow us to have a dominant share in what accounts for approximately 50% of the total head and neck market, but slightly skewed even higher in the HPV-negative. In fact, to your question, you may remember that we also have a cohort open in the CPS zero cohort that we plan to disclose at a later time point that also speaks to this underlying biology.

Ava Fordyce: Got it. Thanks.

Operator: One moment for our next question. Our next question comes from Richard Law with Goldman Sachs. Your line is open.

Speaker #5: Got it. Thanks.

Speaker #7: One moment for our next question. Our next question comes from Richard Law with Goldman Sachs. Your line is open.

Lana Usman: Hi, everyone. This is Lana Usman on for Rich Law. Thanks for taking our question. Just one from us. How are you thinking about when to unblind the study for the interim analysis for accelerated approval? Will it be based on an overall survival event rate?

Speaker #9: Hi, everyone. This is Juan Usman on for Rich. Thanks for taking our question. Just one from us. How are you thinking about, on blind, the site for the instrument analysis for accelerator approval?

Claire Mazumdar: To your question, this is a fully double-blinded study. We will not be unblinding the study as it needs to continue for overall survival. At the time of our pre-specified statistical analysis, based off of the number of patients for overall response rates, durability, and qualitative overall survival, the IDMC will look at that data. As management, we will not be unblinded to the data. Thank you for your question.

Speaker #9: Will it be based on an overall survival event rate?

Speaker #4: To your question, this is a fully double-blinded study. We will not be unblinding the study, as it needs to continue for overall survival. At the time of our pre-specified statistical analysis, based off a number of patients for overall response rates, durability, and qualitative overall survival, the IDMC will look at that data.

Speaker #4: But as management, we will not be unblinded to the data. Thank you for your question.

Operator: I'm not showing any further questions. Tom, I'd like to turn the call back over to Claire.

Claire Mazumdar: Thanks, everyone, for joining us for our first quarterly earnings call and for your support of Bicara Therapeutics. There's never been a better time to be following our story, and we look forward to speaking with you all again soon. Thank you, and have a good day.

Speaker #7: And I'm not showing any further questions at this time. I'd like to turn the call back over to Claire.

Speaker #4: Thanks, everyone, for joining us for our first quarterly earnings call and for your support of Bicara Therapeutics. There's never been a better time to be following our story, and we look forward to speaking with you all again soon.

Operator: Ladies and gentlemen, this concludes today's presentation. We thank you for your participation. You may now disconnect and have a wonderful day.

Speaker #4: Thank you, and have a good day.

Full Year 2025 Bicara Therapeutics Inc Earnings Call

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