Bicara Therapeutics Inc. ($BCAX)

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 in 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 built a global team of over 100 employees headquartered in Boston, with a clear focus on advancing our lead asset by [ SerafisAlpha ] 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 two modulation, where one arm localizes to the tumor, while the other serves as the modulator designed to deliver superior efficacy, improve safety and enhance durability directly at the tumor site. Bicara specifically addresses a key challenge 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 positioned FICERA as the potential best and first-in-class asset with differentiated clinical profile on those 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 inflect 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 stignation 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 Ib clinical data sets across clinically active doses of FICERA that demonstrate 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 and have successfully moved into the Phase III portion of our pivotal FORTIFI-HN01, 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 in every 3-week maintenance dose. A strategic commercial decision based on updated clinical, translational and pharmacokinetic data that we believe will enable additional optionality for patients and providers choosing treatments with FICERA. Lastly, to support the 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 three 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 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 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 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. 1,500-milligram [ cohort ] show 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 home 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 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 positioned 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 demonstrate the deep and [ 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 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 U.S. where we plan our initial launch. With FICERA, we have the potential to significantly expand an already significant HPV-negative head and [ cancer ] market. FICERA's clinical data show us that we further expand that market in two ways. First, by growing the number of patients who are responding to therapy as seen with the [ pack ] of 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 or 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. The FICERA may have the best [ chemospharian ] regimen that actually addresses both the EGFR and TGF 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. The opportunity to set the tone for what the therapeutic borrower 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 and frontline recurrent metastatic HPV-negative head and neck cancer. The Phase Ib 300-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, an extended duration of follow-up as well as the additional maturity on key endpoints from the 750-milligram [ a ] week and a 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 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 [ a ] 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 offer, which further strengthens our balance sheet, and we maintain cash runway guidance into the first half 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 cost 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 [ intent ] 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 [ lines ] to participate in pivotal 4 to 5 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're looking for regulatory alignment and we'll provide far more clarity to the study in the detail once we have that regulatory alignment. But the approximate size is anywhere between 150 to 200 patients are current estimates. 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 through designation as well as moving from the Phase II to the Phase III portion and going up 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 in 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 have really strong momentum for Phase III study in terms of enrollment 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.

Our next question comes from Eric Schmidt with Cantor Fitzgerald.

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 [ stop ] with 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?

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 planned 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 a way no less than 20 patients per cohort. Yes. I think 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 2 cohorts that we are currently exploring seeking signals in our third line. As you know, that a highly challenging population. And again, we've got both the 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 ASCO in a few months. Just curious if the patients in the 750 mg once weekly cohort were given the opportunity to up the high trade to the 150 mg dose, just given the -- I guess, the relative efficiency in depth of response.

Great question, Steve. So we'll be presenting at ASCO is likely an update from three separate cohorts. The 3-year follow-up, a 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 and 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 the lower dose. And so they were -- if they remained on treatment, they did cross over the 1,500 milligram dose in the pivotal study.

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 [ bites ] on the premium static?

No. I think to that question, I 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 believe it is also becoming 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 in more detail, but we do think it is a very important opportunity that could potentially triple the market opportunity compared to recurrent [ metastaxi ]?

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 then 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 Pitosemtimab trials and kind of what that does from a potential market share capture perspective for you the likelihood to [ 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.

Great. And so I'll pass over the first part of the question to Tanya Green, Development Officer, to speak to the sites and the study and then to Ivan Hyep, our CFO, for forecast [ guarding ].

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 that 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 heavily focused on 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? It is this similar to other trials in this setting? And then second, in terms of the ridging 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 number of patients required for the ORR interim versus kind of the final OS? Can you give us a sense as to as to how that might look? And then just 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 dialing 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 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 as 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 the 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 from me. Could you speak to the rationale and reasons for confidence on the loading in once every 3-week maintenance strategy when it was a 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?

Yes. 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, a point for months that we're getting responses. The vast majority of patients will have achieved the response within 12 weeks. And at that same time, the -- most of them will have hit their maximum 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 death response, we're seeing more than 80% of our patients get an 80% or greater reduction in their tumor, so you think of that 12-week mark, you've got significantly less tumor in the patients with the [ Previc ] 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 delivery metastases. And in fact, the [ Anacona ] 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 livermets.

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 Tara plus pembro, a similar response rate or even higher in some cohorts with CPS-119 compared to CPS20 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 is 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 hemosparing regimen being able to go after these 1 to 19 will allow us to have a dominant share and what accounts for approximately 50% of the total head and neck market, but slightly so 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] just one from us. How are you thinking about on blind beside for the interim analysis for accelerated approval? Will that 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.

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