BCAX

Good day, and thank you for standing by. Welcome to the Bicara Therapeutics first quarter 2026 earnings conference call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question-and-answer session. To ask a question during the session, you will need to press star one one on your telephone. You will hear an automated message advising your hand is raised. To withdraw your question, please press star one one again. Please be advised that today's conference is being recorded. I would now like to hand the conference over to your first speaker today, Rachel Frank, Vice President of Investor Relations and Corporate Communications. Please go ahead.

Thank you, and good morning, everyone. It's a pleasure to welcome you to Bicara Therapeutics' first quarter 2026 earnings call. Earlier this morning, we issued a press release highlighting results from the quarter in 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 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.

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

Good morning, thank you for joining us today. The 1st quarter of 2026 set a strong foundation for the year ahead. We made measurable progress on the strategy we outlined earlier this year, with continued momentum behind our lead asset, ficerafusp alfa or FICERA, which we believe is a potentially best and first-in-class bifunctional EGFR-directed antibody combined with a TGF-beta ligand trap for the treatment of HPV negative first-line head and neck cancer. Our priorities remain focused on executing a strategic development plan for FICERA, preparing for commercial success by laying the foundation to capture a large and growing global market in head and neck cancer, and expanding FICERA's potential beyond our lead indication while maintaining financial discipline. To deliver on those priorities, we are building the team to match our ambitions as we transition from a clinical stage to a commercial stage organization.

With that in mind, I want to share a few updates this morning. After several years as our Chief Medical Officer, David Raben has transitioned to a Senior Executive Advisor role, and Bill Schelman, previously Executive Vice President of Clinical Development, has stepped into the CMO role. David has been instrumental in shaping Bicara into the company it is today, guiding FICERA into pivotal phase III development and building the foundation of our clinical and medical organization. We are deeply grateful for his contributions and look forward to his continued partnership in his advisory capacity. Bill is well-positioned to build on that foundation. He joined us last fall as an experienced development and commercial stage leader and has quickly made an impact across our development programs. As we build toward commercial launch, we are thrilled to have brought on a proven leader to guide that work.

Alex Kharazi joined last week as our Chief Commercial Officer, bringing extensive oncology, commercialization, and leadership experience. Alex will continue building out the team with additional hires across market access and commercial operations in the months ahead. In addition, we made a number of key updates in the first quarter. First, our continued execution has us on track to achieve substantial enrollment in FORTIFY-HN01 by the end of the year, positioning us for an interim analysis in mid-2027 for potential accelerated approval. With that progress, our belief in Ficera's potential to be both best and first-in-class in frontline recurrent and metastatic HPV-negative head and neck cancer has only strengthened. That conviction is grounded in Ficera's differentiated mechanism, the depth and durability of response we have observed in our development approach. Recent developments in the competitive landscape are reinforcing this view.

While the market has at times viewed peer timelines as ahead of ours, that picture is changing, driven by our own continued progress as well as the significant upsizing of a peer's pivotal trial. Together, these dynamics support our potential path to first-in-class. They also validate the strategic choice we made to develop Ficera specifically for HPV-negative patients, where the science, the unmet need, and the commercial opportunity align. Second, and Bill will speak to this in more detail, based on discussions with the FDA, we plan to initiate a study that will evaluate Ficera in combination with pembrolizumab as a loading and every 3-week maintenance dosing regimen. This is an advancement that we believe has the potential to expand optionality for patients and providers and enhances the long-term commercial profile of Ficera.

Just last Friday, a peer-reviewed manuscript was published in the Journal of Clinical Oncology detailing results from our phase I-B expansion cohort evaluating 1,500 milligrams of FICERA weekly in combination with pembrolizumab in frontline recurrent and metastatic head and neck cancer, data most recently presented at ASCO 2025. This publication is an important milestone that validates and adds to the growing body of scientific evidence supporting FICERA's differentiated mechanism of action and clinical benefit. It also provides the broader oncology community with a peer-reviewed view of the data underpinning our pivotal program. Lastly, with the completion of an oversubscribed public offering in February, built on an already strong cash position, we are well-positioned to invest in the opportunities ahead of us.

As we look ahead to the next quarter and the remainder of the year, we're excited to share meaningful long-term follow-up data at ASCO in a few weeks. The data will further characterize FICERA's safety profile, along with the depth and durability of response driven by TGF-beta inhibition. These data span all 3 clinical doses tested in expansion cohorts, including the dose we're advancing in our pivotal trial. We are also continuing to enroll multiple Phase I-b expansion cohorts to identify early proof of concept signals and inform FICERA's development strategy, both within head and neck cancer and across solid tumors. With that, I'll turn it to Bill to walk through our recent clinical updates and what to expect from us at ASCO this year.

Thanks, Claire, and good morning, everyone. We have taken a deliberate and thoughtful approach to evaluating FICERA in patient populations with high unmet need and with the strongest biological rationale. This has included development in head and neck cancer, as well as other solid tumors, including metastatic colorectal cancer, cutaneous squamous cell carcinoma, and anal cancer. In that context, our recent disclosures have focused on clinical data from approximately 90 patients across 3 cohorts from our phase I-B study evaluating FICERA in combination with pembrolizumab in front-line recurrent or metastatic HPV-negative head and neck cancer. This patient population has particularly poor outcomes with limited treatment options and represents the vast majority of patients in this setting.

The 1,500 milligram weekly plus pembrolizumab cohort, which is the dose we are currently evaluating in the Phase III portion of the FORTIFY-HN01 pivotal trial, was presented at ASCO last year and represents our most mature data set. With two years of follow-up, deep and durable responses were observed with a median duration of response of 21.7 months and a median overall survival of 21.3 months, more than doubling the overall survival observed with the standard of care pembrolizumab in HPV-negative patients. The 750 milligram weekly plus pembrolizumab cohort supported the evaluation of the optimal biological dose of FICERA in the Phase II portion of our ongoing FORTIFY trial and helped to inform selection of the 1,500 milligram weekly as the OBD that is currently being evaluated in the Phase III portion of the study.

The data from these cohorts also reinforces our confidence in the interim analysis of overall response rate as the foundation for pursuing accelerated approval. The cohort evaluating 2,000 milligrams of the every other week plus pembrolizumab demonstrated that even at a less frequent dose, we see rapid and deep responses that are the hallmark of the FICERA clinical profile. The data from this cohort also helped inform our alternative dosing regimen study. Across all 3 phase I-B cohorts, the depth and durability of response observed underscore the central role of TGF-beta inhibition in FICERA's mechanism. By enabling tumor penetration, TGF-beta inhibition drives the kind of deep and durable responses that translate to long-term survival benefit.

Taken together, the data presented to date affirm that FICERA has the potential to be a well-tolerated chemotherapy-free treatment option across the spectrum of disease burden, including in patients with large, bulky tumors and low CPS scores, where rapid and deep responses are particularly critical. As we look towards ASCO 2026, we will be presenting updated data across all 3 of these cohorts from the phase I-B study. We will provide 3-year follow-up data from the 1,500 milligram cohort, which will allow us to characterize the long-term efficacy from this dose compared to the standard of care. We will also share long-term endpoints from the 750 milligram weekly and the 2,000 milligram every other week data sets.

These data will provide the most comprehensive look at FICERA in front-line recurrent and metastatic HPV-negative head and neck cancer to date, including durability of outcomes not seen with other investigational agents targeting EGFR in this setting, a key differentiator and a signal of FICERA's best-in-class potential. Additionally, the strength and consistency of these results across cohorts further de-risk our pivotal FORTIFY-HN01 trial. Another key aspect of our ASCO update is that we'll further characterize the role of TGF-beta in head and neck cancer. TGF-beta inhibition is the defining feature of FICERA and what sets it apart from other EGFR-directed therapies. Our translational data has shown consistent TGF-beta inhibition across all FICERA doses, confirming the mechanism behind tumor penetration and immune activation, with the strongest inhibition at the 1,500 mg weekly dose and the 2,000 mg every other week dose.

We'll also look to show how tumor penetration driven by TGF-beta inhibition translates into depth and durability of response that leads to long-term outcomes for patients. Alongside the clinical story we'll continue to build at ASCO, we're also focused on optimizing how FICERA is delivered to patients. As previously mentioned, based on discussions with the FDA, we plan to initiate an alternative dosing study in the third quarter of this year. This study will enroll approximately 150 to 200 patients and will evaluate the efficacy of FICERA on a 12-week loading phase, followed by an every 3-week maintenance phase regimen.

All patients will receive 1,500 milligrams weekly of FICERA plus pembrolizumab for 12 weeks and will then be randomized to either continue 1,500 milligrams weekly of FICERA plus pembrolizumab or transition to 2,250 milligrams every 3 weeks plus pembrolizumab. The primary endpoint will evaluate progression-free survival. In designing an alternative dosing regimen, our priority is to preserve FICERA's potential best-in-class profile while creating practical options for patients and providers. We expect to seek accelerated approval for FICERA with the 1,500 milligram weekly dose from the FORTIFY-HN01 study, running this randomized study in parallel will allow us to potentially have results from this study in time for a potential approval, creating a compelling path for early adoption of this streamlined regimen.

Additionally, this addresses an important need for patients, providers, and payers, specifically by providing treatment options that will reduce clinic burden, improve quality of life, and support long-term adherence. Critically, this dosing strategy is shaping how we are thinking about life cycle management and FICERA's opportunity beyond frontline, recurrent, or metastatic head and neck cancer. With that, I'll turn it over to Ryan to discuss the potential market opportunity and what's ahead for the rest of the year.

Thank you, Bill. Turning to the broader opportunity, we have strong conviction in the differentiated profile FICERA has shown across our clinical program compared to other investigational agents in head and neck, and the development strategy we built around that profile is designed to deliver against the full opportunity at head. Head and neck cancer is a significant and fast-growing global market projected to reach more than $5 billion in global sales into the 2030s. HPV-negative patients represent a large majority of patients in the frontline recurrent metastatic setting, and HPV status is known at the time of diagnosis, which means that HPV testing is not a barrier to care. Across major markets, there are roughly 50,000 annually incident patients, including approximately 18,000 in the U.S., where we plan to launch initially.

The unmet need in this population for a therapy that drives deep, durable, and clinically significant benefit while sparing chemotherapy and improving quality of life is what makes the rigor of our clinical data and the discipline of our development strategy matter. It is also why we continue to invest in the medical and commercial infrastructure required to deliver FICERA to patients. This includes the commercial leadership team we have been building, with Alex Kharazi now leading our commercial efforts, including the pre-launch evidence generation and field readiness work required for a successful oncology launch, and we look forward to having him on the road with us at ASCO and beyond. While the frontline recurrent metastatic setting is our initial focus, the opportunity for FICERA in head and neck cancer is much larger.

Given our conviction in FICERA's potential to be both first and best in class, we see clear space to own and lead a broader segment of the head and neck cancer landscape. The locally advanced setting, in particular, represents another large market with clear biologic rationale for FICERA and a meaningful opportunity for expansion. As we think about that opportunity, we have initiated 2 investigator-initiated sponsored studies in the locally advanced setting and continue to enroll additional cohorts that will inform our expansion strategy, including a cohort of patients in frontline recurrent metastatic HPV negative head and neck cancer with CPS less than or equal to 1, as well as a cohort of patients with frontline recurrent metastatic HPV positive head and neck cancer with heavy history of smoking.

Beyond head and neck, we believe there is a strong biologic rationale to expand FICERA's pipeline and the potential into a solid tumor types with significant unmet need. We have already shown proof of concept in indications such as cutaneous squamous cell carcinoma and anal canal cancer, reinforcing our conviction in FICERA's broad applicability across TGF-beta driven tumors. Building on that foundation, we are currently enrolling patients in a phase I-B expansion cohort evaluating FICERA both as a monotherapy and in combination with pembrolizumab in patients with third line plus metastatic colorectal cancer. TGF-beta is implicated in metastatic disease and resistance to current treatments, providing a biologic rationale for evaluating FICERA in this setting. This is also a challenging setting. Patients are very sick, often progressing rapidly through prior lines of therapy.

With the treatment landscape and CRC continuing to evolve, we are taking a measured approach with a high bar for what would warrant further investment. As the data mature across these cohorts, we will continue to make thoughtful decisions about where FICERA can deliver the most differentiated value and how we allocate our resources accordingly. With that, I'll turn it to Ivan to review the financials.

Thanks, Ryan. Earlier this morning, we reported detailed first quarter 2026 financial results in our press release. I'll summarize a few highlights here. Our total operating expenses for the first quarter of 2026 increased compared to our first quarter of 2025, driven by clinical operations and development expenses associated with our ongoing pivotal FORTIFY-HN01 study, including increased manufacturing and development costs. We also saw an increase in personnel-related costs, including stock-based compensation, as we have grown our workforce primarily in support of clinical operations and development functions.

Consistent with the first quarter, we anticipate continued increases in operating expenses for 2026, reflecting increased investment in our clinical operations, particularly for the pivotal FORTIFY-HN01 study with the interim analysis expected in mid-2027 and parallel study, as well as an increase in SG&A as we invest in early commercial and medical infrastructure to support the potential launch of FICERA. We ended the first quarter of 2026 with $539.8 million in cash equivalents, and marketable securities.

Bolstered by an oversubscribed public offering in February that generated $161.8 million net proceeds and meaningfully strengthened our balance sheet, which provides cash runway into the first half of 2029 and allows us to invest thoughtfully in areas we believe will deliver future clinical and commercial success. With that, I'll now turn the call back over to the operator for questions. Operator?

Thank you. 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. In the interest of time, we do ask that you please limit yourself to 1 question. Please stand by while we compile the Q&A roster. Our first question comes from Eric Schmidt of Cantor. Your line is open.

Good morning. Thanks for taking my question. Maybe one in terms of what to expect at ASCO in a couple of weeks' time. Can you provide us with any benchmarks for 3-year outcomes data, landmark data in HPV negative head and neck? Then you mentioned looking at the role of TGF-beta as well. Does that mean that we're gonna see some correlations between PD and response rates? Thank you.

Thank you for your question, Eric. The question was relating to a preview of the ASCO 2026 datasets. As we highlighted during the call, there are two separate abstracts that were accepted as behalf of ASCO. One is focused on long-term follow-up in terms of the 3 expansion cohorts in frontline recurrent and metastatic HPV negative head and neck, with the most mature dataset being the 1,500 milligram one you were alluding to, which will have 3 years' worth of median follow-up. In that one, we really hope to speak to the so-called immunotherapy tail driven by the TGF-beta durability.

In there, if you look at prior precedents, pembrolizumab in all comers delivers about a 20%-25% 3-year overall survival, while it's believed to be about 15%-20% in the HPV negative subset from real-world datasets. The other abstract is focused on looking at depth and durability of response but from the TGF-beta inhibition. We'll continue to speak to what we believe is FICERA's defining hallmark, that TGF-beta inhibition is driving this depth of response that's ultimately leading to far superior durability than other investigational agents and leading to outsized overall survival benefit. Thank you.

Thank you very much.

Thank you. Our next question comes from Tyler Van Buren of TD Cowen. Your line is open.

Hey, guys. Good morning. Congrats on the progress. Thanks for taking the question. Just wanted to ask a quick follow-up before my question, if you don't mind. A follow-up on Eric's question related to the ASCO data. I guess it's clear that we'll have 3 years of follow-up with the 1,500 mg dose, but since investors are asking, it would be helpful if you could just clarify how much follow-up we should expect with the 2,750 dose cohorts. We can obviously guess, but just clarity there would be helpful. Then, I guess my main question is related to the alternate dosing regimen of the 1,500 mg induction with the 2,250 mg maintenance.

Do you think it's possible that that regimen could have improved durability than either 1,500 or 2,250 alone based upon exposure and the data you've produced to date?

Thanks for your questions, Tyler. I'll answer the first question first, which is a question around the other 2 cohorts being presented at ASCO, which are the 750 milligram weekly cohort as well as the 2,000 milligram every 2 week cohort. Both of those have approximately 12 to 18 months' worth of median follow-up. We do plan to share longer-term follow-up datasets for both of those at ASCO in a few weeks. To help answer your question around durability of response in the maintenance setting, I'll pass that question over to Ryan.

Thanks, Tyler, for the question. You know, in terms of the regimen, you know, again, the overall approach that we are taking there, as you mentioned, is we're initiating with the 1,500 milligrams weekly and then transitioning to a maintenance phase at 2,250. A couple, I think, key tenets of that approach. One, you know, as you recognize from the data that we've presented thus far, you know, we see deep, rapid responses which are enabled by the 1,500 milligram dose. You know, really being able to get a depth of response, you know, more than 80% of our patients are getting depth of response of 80% or greater, which we really believe is contributing to that durability.

One of the things that the 2,250 every 3 weeks enables is an exposure profile that allows us to, I think, maintain that durability after we've received or achieved very meaningful reductions in tumor reductions. You know, keeping patients on from a tolerability perspective, you know, I think being able to bring people into clinic every 3 weeks rather than every week while maintaining exposures that maintain that durable response, we absolutely believe that, you know, this regimen potentially enables both a more durable as well as a better, a more tolerable profile.

Thank you. Our next question comes from Stephen Willey of Stifel. Your line is open.

Yeah, good morning. Thanks for taking the questions. Maybe just some color around the use of PFS as a primary endpoint in the dose optimization trial, just given that this is obviously an adventure of an endpoint, there's no control arm. Is there a formal non-inferiority margin that you need to hit? I guess just any color you can provide around kind of this formal notion of comparability would be helpful. Thanks.

Thanks for your question, Stephen Willey. I'll actually answer the second part of your question first, around non-inferiority. This is actually not designed as a non-inferiority study. We got positive feedback from the FDA based off of our discussions. Based off of the sizing of the study, which we alluded to being, approximately 150 to 200 patients, it would have required far more patients as a non-inferiority study. The other focus, again, going back to Tyler Van Buren's question, the other focus of looking at this dosing regimen is really, again, to ensure that we're maintaining the efficacy profile focused on depth and durability of response with the induction into maintenance dosing. The focus of the PFS endpoint was really to look at that, ensuring the durability is consistent between the two arms.

The FDA was comfortable with PFS being that endpoint for that reason.

Great. Thanks.

Thank you. Our next question comes from Kelsey Goodwin of Piper Sandler. Your line is open.

Hey, good morning. Thanks for taking my questions. I think you alluded to it in the prepared remarks, but for your competitor's frontline trial where they increased target enrollment by about 200 patients, I just first wanted to confirm, is there any read-through to Fortify in its trial size? Secondly, how do you think about the gap in timing now between FICERA and Pido? Thanks so much.

Thank you for your that question, Kelsey. Just to highlight, we were alluding to the LiGeR-HN1 study, and you may have not seen on ClinicalTrials.gov that the page was updated to reflect enrollment of 700 patients, up from the original 500 in an all-comer study. I think that's consistent with feedback we've been hearing from investigators that they were planning to add additional HPV-negative patients. From what we have heard today is that, you know, there was potentially an imbalance in terms of HPV-positive versus HPV-negative patients in that particular study, given that there are no other HPV-positive studies in phase III. We haven't seen any read-through other than the fact that, you know, it continues to highlight what we've always highlighted, that FICERA has the potential to be both best and first in class.

We've seen very strong execution of the FORTIFY-HN01 study, and those dynamics continue to speak to what we believe is a significant narrowing of the perception around FICERA and FORTIFY being second to market. In fact, we continue to believe in our potential first in class.

That's great. Thank you so much.

Thank you. Our next question comes from Bradley Canino of Guggenheim. Your line is open.

Hey, good morning. Thanks, team. It's nice to be on the call. At ASCO, maybe just to drill into one of the doses, the lower 750 mg, which wasn't selected for the phase III. How do you look at that as really being able to support the TGF-beta hypothesis, given the exposure and coverage that it provides? Will that view only be in a subset of patients such as the responders? Just a quick second, given we're talking about the competitor trial and the upsize, where do you sit with expected timing of OS analysis for your phase III study today? Thank you.

Thanks, Bradley Canino, for your question. Welcome to the team. To the first question around the 750 mg dose. That was, as you highlighted, a dose that we did not take forward in the pivotal phase III study. However, we do see significant TGF-beta inhibition. We know that from an EGFR receptor occupancy, we are fully saturating the EGFR locus. We've always thought of it as still superior than EGFR monoclonal antibody while showing slightly less TGF-beta inhibition.

What you will continue to see at ASCO is that even in this patient population, the hypothesis that TGF-beta inhibition is driving improved depth and durability, will continue to speak to another strong data set that will reinforce the notion now in a total of 90 patients, that we have strong depth and durability data that will speak to outside overall survival benefit. Your second question was related

Timing of OS analysis for your study.

The timing for OS. Yes, I apologize. Timing of OS analysis. As we continue to guide to the interim analysis for potential accelerated approval, is slated for mid 2027, which is a look at overall response rates with 6 months of durability and likely a look at qualitative overall survival at that time. We do anticipate being focused on HPV negative patients only, that our event rates will happen more rapidly than those of our peers, and that the OS endpoint will come again more rapidly than anticipated.

Great. Thank you.

Thank you. Our next question comes from Judah Frommer of Morgan Stanley. Your line is open.

Yeah. Hi, good morning. Thanks for taking the questions, guys. Maybe just broadening out the competitor conversation a bit. We saw some data from an OX40 targeting asset this morning, but I believe in CPS greater than 20. Maybe can you just remind us of kind of the breakdown of the epidemiology by CPS score and kind of, you know, what the advantages of a broader targeting asset in FICERA could be, and again, what timelines could look like versus this asset? Thanks.

Thanks for your question, Judah. I do believe you're referring to an ENHERTU presentation that actually I believe is happening at the same time as our call. While we haven't had a chance to significantly look at the dataset, I can speak at a high level to those results. As you alluded to, the dataset from I believe a randomized phase II is focused on CPS greater than or equal to 20. These are considered the CPS high patients who typically do respond to pembro monotherapy. What we do know is that FICERA is being in the FORTIFY study, is being looked at in the CPS greater than or equal to 1.

As well, we have shown some strong results from our late line patients in CPS 0 and are currently looking at an open label CPS 0 cohort. In the CPS 1-19 category, we see strong response rates across all 3 of our cohorts between 50%-70%, really speaking to the TGF-beta inhibition going after the more immune, so-called immunosuppressive patients who are the CPS low. From an epidemiological standpoint, it's believed to be about 50/50 CPS 1-19 versus CPS 20 to greater, and 15% of the frontline market being the CPS 0. I think your other question was around just the competitive threat.

What we believe we're hearing is that they're slating to start enrollment in the pivotal study later this year, with full enrollment scheduled to be 2029, so significantly later than our interim analysis for potential accelerated approval coming mid-2027. We do not-

Thanks

See this as a competitive threat in terms of timing.

Thanks.

Thank you. Our next question comes from Randy Benjamin of Citizens. Your line is open.

Hey, great. Thanks for taking the questions, and congrats on the progress. As my question is mainly focused around the phase I-B expansion cohorts and the early proof of concept signals, can you just maybe provide more color on each of those expansion cohorts, kind of why we're going after CPS less than 1 and those patients with heavy smoking? Same thing with the CRC. What is that high bar that you're hoping to achieve when those results come out in the second half? Thank you.

Thank you for the question. You know, I'll start with the other cohorts. You know, you'd mentioned CPS less than 1 and also the, the heavy smokers. You know, I think what we had saw in dose escalation is we actually saw some pretty significant responses in those patients who had CPS 0. In fact, 1 patient in particular had a complete response there. As you go back to kind of the fundamental biology of our molecule of EGFR and TGF-beta, you know, there's a lot of biological support for the synergy associated with those 2 mechanisms being given together and also in combination with a, with a PD-1. That was, you know, biology that we wanted to probe and again, exploring a population.

You know, as Claire had alluded to in the last response, in terms of an epidemiological perspective, about 15% of patients are CPS less than 1, so it's a meaningful population, and again, a biology that's supported by our molecule. In the heavy smokers, you know, I think it goes back to our view when we looked at our dose escalation data retrospectively, there was a responder population with an HPV positive. All of those patients who responded were heavy smokers. In that case, you know, we saw people who had a history of smoking of 20 pack years or greater who responded. Again, of our 3 responders there, 2 out of the 3 of them were complete responses.

Our view is that, you know, there's likely a component of smoking that's driving the biology there, even more so than the HPV-positive infection. Again, an area that we wanted to probe as we think about those expansion opportunities within the head and neck population. CRC, you know, I think honestly, it's an evolving, you know, target. You know, we continue to look at the landscape. We've seen datasets out from other agents of recent. I think the other thing, not only is it relative to the competitive landscape, but also our own internal. You know, we had mentioned activity in cutaneous, anal canal. There's good opportunities for this molecule in the locally advanced setting of head and neck.

As we evaluate the various opportunities, you know, there are, I think, are ample opportunities to develop, FICERA across a range of different tumors and more broadly in head and neck cancer. That really is the bar, is, you know, where we think we're gonna have the most meaningful impact, and that's where we're gonna end up, you know, investing our capital.

Can I just follow up with, you know, when we might see some of the data for We know when the CRC data's coming out, but maybe from these other cohorts, when might we see those data?

Again, we've not provided specific guidance on that. Again, we'll provide, you know, greater clarity in terms of timing for that in future updates.

Great. Thank you very much for taking the questions.

Thank you. Our next question comes from Jeet Mukherjee of BTIG. Your line is open.

Great. Thanks for taking the question. Just looking ahead to your loading and maintenance regimen, just as you talk to your investigators, how do they think about a 12-week weekly regimen followed by once every 3 weeks versus just a pure once every 2-week regimen from Pido there? Is there any preference that they have generally between one or the other? Obviously, safety and efficacy being, you know, the primary point there, but just was curious if there's any preference there between the 2 regimens. Then just coming back to ASCO, are we looking to have updated data be a part of the abstracts, or will they be reserved for the conference presentation? Thank you.

I'll take your first question there. You know, as we have talked with investigators and the broader, you know, community, I think there's a real focus on that initial therapy and the rapidity and the depth of, you know, that initial therapy. I think even if you look at, you know, the historical treatment paradigm, we continue to see a fair amount of chemotherapy used, and that is largely being driven by the desire to have very rapid responses. In terms of that trade-off of, you know, being able to go to every two weeks at the outset versus being able to get rapid deep responses, the preference continues to be that rapid deep response which the weekly regimen gives.

Again, you know, I think, you know, as you think about the overall administration schedule and transitioning to every 3 weeks at the 12-week mark, I think the view there is a willingness to get faster, better efficacy quick, and then be able to go to a more convenient maintenance regimen over time.

To your second question, Jeet, which I believe was about whether the data presentation will have more mature data than the abstracts, that is correct. There will be more data provided during our presentation than what was provided in the abstracts. Thank you for your question.

Thank you. Our next question comes from Boris Peaker of Jones Trading. Your line is open.

Great. Thanks for squeezing me in. Just to follow up on a prior question when we're talking about every 2-week dosing, every 3-week maintenance dosing. In addition to potentially satisfying FDA's Project Optimus requirements, how important do you see this dosing from the commercial perspective, and kind of competitive perspective?

I'll answer your first question around Project Optimus and then pass it over to Ryan. Just to highlight, Boris, we have satisfied Project Optimus by choosing the 1,500 milligram dose weekly as opposed to the 750 milligram dose weekly within the FORTIFY-HN01 study. This is a separate parallel clinical study that is looking at moving this new alternative dosing regimen into a potential ultimate label. To your second question around the commercial uptake, I'll pass it over to Ryan.

Yeah. In terms of, you know, from a differentiation perspective, you know, efficacy remains the key parameter for differentiation, you know, consistent, I think, with most oncology molecules. Again, that's why, you know, we continue to initiate with 12 weeks of weekly therapy to maximize efficacy, deep, durable, rapid responses. And again, we think that that will be the key that's gonna drive differentiation and the initial, you know, share uptake between ourselves and competitor molecules.

Being able to also maximize and optimize for schedule once you get out to that 12-week maintenance phase, we, you know, believe that we'll be creating a regimen that has the ability to not only compete, but to differentiate and be best in class from an efficacy, tolerability, and from a convenience perspective, really, you know, being able to, you know, fully optimize the profile across all three dimensions.

Great. Thanks for taking my question.

Thank you. Our next question comes from Joseph Catanzaro of Mizuho. Your line is open.

Hey, everybody. Thanks so much for taking my questions. I actually had one as well on this maintenance trial that you've sort of, I think, touched on. Wondering if you could speak to the quantitative difference in exposure at steady state, if any, between 1,500 weekly and 2,250 every three weeks. You know, it sounds like you need those longer-term efficacy metrics, but wondering if the argument could be made on sort of equivalent PK and safety between those two regimens. Thanks.

I mean, again, from an overall exposure perspective, what we are looking to accomplish there, the 2250, essentially, we're looking for exposures that are comparable to what you've seen at 750. Again, why we look across the various datasets to really get to, I think the regimen that we have gotten to. We're looking at the strength of the data across all of our various cohorts. Again, I mean, I think the key here is starting at the 1500 milligrams, getting that rapid deep response, and then being able to maintain those exposure levels to maintain the durability of response.

Okay, great. Thanks so much.

Thank you. Our next question comes from Richard Law of Goldman Sachs. Your line is open.

Hey, guys. Good morning. Based on that accelerated approval timeline, I believe you mentioned in the past that only a small clinical team will be unblinded to review the interim phase III results and management will still be blinded. When will management team become unblinded, and when should we expect to see the data as well? Does it mean that the unblinded clinical team will file the BLA without management seeing what's in there initially when filed?

Richard, I think you're Just to understand your question, the study is a blinded study. We have an interim for potential accelerated approval in mid 2027 that will be based on response rates with 6 months' worth of follow-up as well as qualitative overall survival. Like any company, there will be, you know, the data cut will be done, the data lock will be done, and then, our team within Bicara will submit the BLA. There are no oddities to that process.

There's no separate unblinding with a different team and then where I thought that was the case before.

No. There is an IDMC, like in many cases, that will allow us to submit, and then we will move to the Bicara team.

Okay, thanks.

Thank you. I'm showing no further questions at this time. I'd like to turn it back to Claire Mazumdar for closing remarks.

Thank you for joining us today and for your continued support of Bicara. We're focused on the work ahead for the program and, most importantly, for the patients we're working to serve. We look forward to seeing many of you at ASCO in a couple of weeks.

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

Good day, and thank you for standing by. Welcome to the Bicara Therapeutics Fourth Quarter and Full Year 2025 Earnings Call. [Operator Instructions] 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.

Thank you, and good morning, everyone. It's a pleasure to welcome you to Bicara Therapeutics Fourth Quarter 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 Investors 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. 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.

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. 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 FICERA, a potentially first-in-class bifunctional EGFR-directed antibody combined with the TGF-beta 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, improved safety and enhanced durability directly at the tumor site. FICERA 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. 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. Our recent clinical data and regulatory progress clearly position FICERA as a 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 FICERA toward a pivotal study interim analysis in the middle of next year. First, FICERA 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. 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 2 additional Phase Ib clinical data sets across clinically active doses of FICERA that demonstrated consistent overall response rates, further validating FICERA's unique dual mechanism targeting both EGFR and TGF-beta and derisking the OR endpoint in our pivotal study interim analysis. Third, building on this robust data set, we selected 1,500 milligrams as our optimal biological dose and have successfully moved into the Phase III portion of our pivotal FORTIFI-HN01 study, for which we expect an interim analysis in the middle of next year. 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 FICERA with a loading and every 3-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 FICERA. 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.

Thank you, Claire, and good morning, everyone. We've now reported clinical experience in approximately 90 patients across 3 Phase Ib cohorts evaluating FICERA in combination with pembrolizumab in frontline recurrent metastatic HPV-negative head and neck squamous cell carcinoma. Our 1,500-milligram 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 of pembrolizumab in HPV-negative patients. Late last year and just last month, we presented 2 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 III FORTIFI-HN01 trial. And just last month, at the Multidisciplinary Head and Neck Cancer Symposium, we presented data from a higher but less frequent dose of FICERA in combination with pembrolizumab, 2,000 milligrams every 2 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 U.S. approval. Clinically, tumor shrinkage is seen at all doses that trends deeper with higher exposure. The 1,500-milligram cohort showed deeper median depth of response versus 750 milligrams, and the exploratory 2,000-milligram every 2-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 FICERA doses, confirming the mechanism that drives tumor penetration and immune activation. Importantly, inhibition is strongest with the 1,500-milligram weekly dose and less frequent 2,000-milligram regimen. We believe this TGF-beta-driven depth of response is the defining hallmark of FICERA and a clear differentiator versus EGFR-directed therapies, which do not target TGF-beta. 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. Importantly, FICERA's deep responses are paired with sustained durability without any trade-off. The median duration of response approaches 22 months, more than 3x longer than the 6.7 months median duration of response reported with pembrolizumab plus chemotherapy. Our 2,000-milligram every 2-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, FICERA maintains this level of durability even with less frequent dosing. This positions FICERA 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 FICERA'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. As we first showed at ASCO last year, there is 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 FICERA'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 FICERA's clinical data and its differentiated profile compared to other investigational agents in the head and neck space. 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. 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. There are roughly 50,000 annually incident patients across major markets, including approximately 18,000 in the U.S. where we plan our initial launch. With FICERA, we have the potential to significantly expand an already significant HPV-negative head and neck cancer market. FICERA's clinical data show us that we further expand that market in 2 ways: first, by growing the number of patients who are responding to therapy as seen with the fact that FICERA provides a 2 to 3x greater overall response rate; and second, by growing the duration of response as seen by FICERA's two to threefold 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 prelaunch 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. Recent competitive updates have only strengthened our conviction that FICERA may have the best chemo-sparing regimen that actually addresses both the EGFR and TGF-beta 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 the second quarter, we look forward to providing long-term follow-up data from across our Phase Ib studies of FICERA in combination with pembrolizumab in frontline recurrent metastatic HPV-negative head and neck cancer. The Phase Ib 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. 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 2-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 FICERA that resonates deeply with clinicians. With that, I'll turn it to Ivan to review the financials.

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. 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 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. 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-'27 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 FICERA. 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. This additional capital will allow us to support a planned regulatory filing for FICERA, further invest and build in our medical and commercial infrastructure ahead of a potential U.S. approval and launch. Further accelerate the development of FICERA in head and neck cancer, including a less frequent dosing schedule, fund manufacturing costs for FICERA for ongoing and anticipated drug development efforts, fund early signal finding activities to support further indication expansion for FICERA 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 FICERA as we enter a period of disciplined 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?

[Operator Instructions] Our first question comes from Tyler Van Buren with TD Cowen.

Can you provide more color on the patient demand and willingness to participate in pivotal FORTIFI study that you're seeing in both the U.S. 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 a separate study of the less frequent dosing regimen to achieve registration?

Thank you for your question, Tyler. So there are two questions. One was around 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 -- the second one first and speak to the fact that we are looking for regulatory alignment, and we'll provide far more clarity to the study in more detail once we have that regulatory alignment. But the approximate size is anywhere between 150 to 200 patients is our current estimate. The first question was around enrollment of the FORTIFI study. 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 II to the Phase III portion and going now to the 2:1 randomization of 1,500 milligrams weekly, randomized 2:1 to pembro monotherapy. We've seen great momentum also ex U.S., in particular, in European sites, Asian 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.

This is Tanya Green, Chief Development Officer. So yes, as Claire said, we're -- we have really strong momentum for the Phase III study in terms of enrollment. As is 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.

Our next question comes from Eric Schmidt with Cantor Fitzgerald.

Congrats on all the recent progress. Questions on the colorectal cancer update that we might see in the second half of the year. 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?

Eric, thank you for the question. In terms of our CRC update, as we've indicated, we look to have data in the second half of this year on those cohorts. 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. 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. 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.

Our next question comes from Stephen Willey with Stifel.

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.

Great question, Steve. So what we'll be presenting at ASCO is likely an update from 3 separate cohorts. The 3-year follow-up -- median follow-up for the 1,500-milligram dose weekly. The 750-milligram weekly dose was about a 30-patient cohort with at least 18 months of follow-up and same for the 2,000-milligram every 2-week cohort, an additional 30 patients with about 18 months of follow-up. 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. 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. 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. And so they were -- if they remained on treatment, they did cross over to the 1,500-milligram dose in the pivotal study. Thank you for your question.

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 and 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 of hundred patients worth of data change perhaps the plans to pursue [indiscernible] in the pre-metastatic...

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 is a strong biology to move into earlier lines of head and neck cancer. And we do believe it is also becoming a more competitive landscape as well. So we have begun initial signal-seeking studies in those areas and hope to provide updates as we move forward in more detail. But we do think it is a very important opportunity that could potentially triple the market opportunity compared to recurrent and metastatic setting.

Yes. 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. 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.

Our next question comes from Judah Frommer with Morgan Stanley.

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 FICERA in the case of an approval? And 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 will eat up some of the cash that was raised to maintain that guidance?

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

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.

And Judah, thanks for the question. In terms of use of proceeds for this recent financing, we are heavily focused on the alternative dosing, prelaunch activities and investment in both commercial and regulatory. 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.

Our next question comes from Kelsey Goodwin with PSC.

Maybe again just on FORTIFI and the enrollment. How should we think about the ultimate split of enrollment across geographies? 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?

Great, Kelsey, thank you for the question. In terms of geographical distribution on the trial, I'd say what we anticipated is it will be very similar to some of the recent trials, KEYNOTE-048 in particular, 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 mentioned, we intend to get regulatory input on that trial and do expect to be able to provide greater clarity later this year.

Our next question comes from Reni Benjamin of Citizens.

Congrats on the progress. Just sticking with FORTIFI, can you maybe just help quantify a little bit as to what you mean by substantial enrollment? 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? 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 FICERA?

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 II/III 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. So substantial is a key objective 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. The study will continue for full confirmatory approval on an overall survival endpoint. Today, we believe that ex U.S., a full overall survival endpoint is needed to predicate a global approval.

Our next question comes from Jeet Mukherjee with BTIG.

Great. Two for me. Could you speak to the rationale and reasons for confidence on the loading and once every 3-week maintenance strategy when it was a 2,000 mg once every 2-week regimen that showed a notable response and depth of response? And the second question was just related to the colorectal cancer update. Could you confirm if the patient enrollment criteria allows for liver mets?

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 weekly and then the 2,000 every 2 weeks has given us the ability to do extensive exposure response modeling across those data sets. 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 Ib data is that 1,500-milligram weekly dose, we're getting very rapid responses 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. 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 3 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 to the 750-milligram weekly, which, again, we know, as you saw in that data set that we presented last year, you see really good response rates. You see really good activity even at the 750. I think one of the things to remember here, if you recall our data, that depth of response, we're seeing more than 80% of our patients get an 80% or greater reduction in their tumor. 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 a 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. And in fact, the anal canal data that we have presented previously really shows our ability and FICERA's ability to resolve liver metastases in that population. So it is something that we think could be a unique differentiating perspective of our molecule, and so we did allow liver mets.

Our next question comes from Eva Fortea with Wells Fargo.

A quick one from us. We've seen now in the 3 different dose cohorts with FICERA plus pembro, a similar response rate or even higher in some cohorts with CPS 1-19 compared to CPS 20 or higher. And so is there anything about the biology that could explain this? And if this holds in the Phase III, could you comment on the potential implications from a commercial standpoint?

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 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. And in fact, it's in this patient population that pembro 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. In fact, we do think that it's 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 flow. 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 0 cohort that we plan to disclose at a later time point that also speaks to this underlying biology.

Our next question comes from Richard Law with Goldman Sachs.

This is [indiscernible] on for Rich. 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 rate?

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 prespecified 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. But as management, we will not be unblinded to the data. Thank you for your question.

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

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.

Well, ladies and gentlemen, this does conclude today's presentation. We thank you for your participation. You may now disconnect, and have a wonderful day.