Bicara Therapeutics Q4 2025 Earnings Report

Bicara Therapeutics EPS Results

• Actual EPS: -$0.68
• Consensus EPS: -$0.72
• Beat/Miss: Beat by +$0.04
• One Year Ago EPS: N/A

Bicara Therapeutics Revenue Results

• Actual Revenue: N/A
• Expected Revenue: N/A
• Beat/Miss: N/A
• YoY Revenue Growth: N/A

Bicara Therapeutics Announcement Details

• Quarter: Q4 2025
• Date: 3/30/2026
• Time: Before Market Opens
• Conference Call Date: Monday, March 30, 2026
• Conference Call Time: 8:30AM ET

Bicara Therapeutics (NASDAQ:BCAX) is a clinical-stage biopharmaceutical company dedicated to developing novel neurohormone-based therapies for psychiatric and neurological disorders. The company’s research focuses on harnessing endogenous signaling pathways in the brain, with the goal of offering new treatment options for conditions that remain inadequately addressed by existing medications. Bicara applies proprietary peptide engineering and intranasal delivery platforms to optimize central nervous system uptake and therapeutic effect.

The company’s lead candidates include PST-001, an intranasal vasopressin-1A receptor antagonist in development for postpartum depression, and PST-002, an oxytocin receptor modulator being investigated for social anxiety and autism spectrum disorder. Both programs are supported by preclinical validation and early-stage clinical data demonstrating target engagement and potential improvements in mood and social functioning. Bicara’s pipeline leverages translational biomarkers to guide dose selection and patient stratification in ongoing studies.

Founded in 2020 and headquartered in Cambridge, Massachusetts, Bicara Therapeutics completed its initial public offering on the Nasdaq in 2021. The company’s management team brings together experienced leaders from neuroscience, endocrinology and pharmaceutical development. Bicara also collaborates with academic centers and contract research organizations to accelerate its clinical programs and expand the understanding of neurohormone mechanisms in human disease.

Looking ahead, Bicara plans to advance its lead candidates through proof-of-concept studies while exploring additional neurohormone targets for depression, anxiety and other central nervous system indications. By combining peptide chemistry with intranasal formulations, the company aims to address significant unmet needs in mental health and to establish a new class of therapeutics with improved efficacy and tolerability profiles.

Bicara Therapeutics Q4 2025 Earnings Call Transcript

Key Takeaways

• Positive Sentiment: Management announced that ficerafusp alfa in combination with pembrolizumab received Breakthrough Therapy Designation for first‑line metastatic/unresectable HPV‑negative head and neck cancer, signaling potential regulatory acceleration.
• Positive Sentiment: Bicara selected 1,500 mg weekly as the optimal biological dose and has advanced into the phase III FORTIFY‑HN01 pivotal study with a planned interim analysis in mid‑2027 toward a possible accelerated approval strategy.
• Positive Sentiment: Management highlighted Phase Ib data across ~90 patients showing deep, durable responses—reported median duration of response of 21.7 months and median overall survival of 21.3 months—which they position as a key clinical differentiator for HPV‑negative disease.
• Positive Sentiment: The company completed an oversubscribed public offering (net proceeds ~$161.8M) and entered 2026 with $414.8M, stating a cash runway into the first half of 2029 to fund the pivotal program, alternative dosing study, manufacturing, and pre‑launch activities.
• Negative Sentiment: Bicara cautioned that operating expenses rose in 2025 and are expected to increase further in 2026 as it ramps clinical operations, manufacturing and early commercial/medical build, implying higher near‑term cash burn despite the recent financing.

Presentation

[Operator]

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

[Rachel Frank, Senior Director and Head of Investor Relations and Corporate Communications at Bicara Therapeutics]

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

[Rachel Frank, Senior Director and Head of Investor Relations and Corporate Communications at Bicara Therapeutics]

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

[Claire Mazumdar, CEO at Bicara Therapeutics]

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.

[Claire Mazumdar, CEO at Bicara Therapeutics]

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, improve safety, and enhance durability directly at the tumor site. Ficerafusp alfa 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.

[Claire Mazumdar, CEO at Bicara Therapeutics]

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

[Claire Mazumdar, CEO at Bicara Therapeutics]

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

[Claire Mazumdar, CEO at Bicara Therapeutics]

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

[Ryan Cohlhepp, President and COO at Bicara Therapeutics]

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

[Ryan Cohlhepp, President and COO at Bicara Therapeutics]

In December 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 biological dose for our ongoing pivotal phase III FORTIFY-HN01 trial. Just last month at the Multidisciplinary Head and Neck Cancers Symposium, we presented data from a higher but less frequent dose of ficerafusp alfa in combination with pembrolizumab, 2,000 milligrams every two weeks, from which we announced our plan to develop a less frequent loading and maintenance dosing option. Our aim is to gain alignment with the FDA on this approach and initiate that study in parallel to the pivotal study to allow to have data from that regimen in hand upon potential U.S. approval. Clinically, tumor shrinkage is seen at all doses. It trends deeper with higher exposure.

[Ryan Cohlhepp, President and COO at Bicara Therapeutics]

1,500 milligram cohort showed deeper median depth of response versus 750 milligrams, and the exploratory 2,000 milligram every two-week cohort produced consistently high proportions of deep responders with greater than 80% shrinkage and complete response rates. Our translational data shows consistent TGF-beta inhibition across all ficerafusp alfa 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 ficerafusp alfa 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 inhibition where deeper, more durable responses are urgently needed for patients.

[Ryan Cohlhepp, President and COO at Bicara Therapeutics]

We remain confident that this biology will continue to translate into clinically differentiated long-term outcomes for these patients. Importantly, ficerafusp alfa's deep responses are paired with sustained durability without any trade-off. The median duration of response approaches 22 months, more than three times longer than the 6.7 months median duration of response reported with pembrolizumab plus chemotherapy. Our 2,000 mg every two-week cohort similarly delivered multiple deep responses persisting beyond 20 months, underscoring the consistency of benefit across dosing schedules.

[Ryan Cohlhepp, President and COO at Bicara Therapeutics]

Crucially for patients, providers and payers, ficerafusp alfa maintains this level of durability even with less frequent dosing. This positions ficerafusp alfa favorably in a market moving toward treatment regimens that reduce clinic burden, improve quality of life and support long-term adherence. We believe this performance reflects ficerafusp alfa's tumor-penetrating mechanism, enabling depth and durability that translate into meaningful long-term outcomes while supporting a more flexible patient-centric dosing paradigm.

[Ryan Cohlhepp, President and COO at Bicara Therapeutics]

We're often asked whether deep depth of response translates to long-term outcomes. As we first showed at ASCO last year, there's a clear distinction in duration of response, progression-free survival and overall survival among HPV negative head and neck cancer patients who have had deep responses versus those that do not. This data is what drives our belief that deep responses that are the hallmark of ficerafusp alfa's clinical profile drive outsized durability and long-term benefit.

[Ryan Cohlhepp, President and COO at Bicara Therapeutics]

Importantly, other investigational agents also need to demonstrate the deep and durable responses to meaningfully improve long-term clinical outcomes. As our recent financing highlights, we have strong conviction in ficerafusp alfa's clinical data and its differentiated profile compared to other investigational agents in the head and neck cancer space, and we are continuing to bolster our commercial and medical investment in preparation for a potential U.S. launch, including hiring of the Chief Commercial Officer this year.

[Ryan Cohlhepp, President and COO at Bicara Therapeutics]

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 front-line recurrent metastatic setting. An 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 ficerafusp alfa, we have the potential to significantly expand an already significant HPV-negative head and neck cancer market. Ficerafusp alfa's clinical data show us that we further expand that market in 2 ways.

[Ryan Cohlhepp, President and COO at Bicara Therapeutics]

First, by growing the number of patients who are responding to therapy, as seen with the fact that ficerafusp alfa provides a 2-3 times greater overall response rate. Second, by growing the duration of response as seen by ficerafusp alfa's 2- 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.

[Ryan Cohlhepp, President and COO at Bicara Therapeutics]

With this knowledge in hand, we are eager to further invest in our pre-launch activities across commercial and medical, including additional evidence generation strategies that may further expand the market opportunity beyond that being studied in our pivotal trial. Recent competitive updates have only strengthened our conviction that ficerafusp alfa may have the best chemo-sparing regimen that actually addresses both the EGFR and TGF-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.

[Ryan Cohlhepp, President and COO at Bicara Therapeutics]

As we head into the Q2, we look forward to providing long-term follow-up data from across our phase Ib studies of ficerafusp alfa in combination with pembrolizumab in frontline recurrent metastatic HPV-negative head and neck cancer. The phase Ib 1500 mg every week data presented at ASCO 2025 were mature, with a median duration of response of 21.7 months and a median overall survival of 21.3 months. In this update, we are looking for a better understanding of that IO tail at extended duration of follow-up, as well as the additional maturity on key endpoints from the 750 mg every week and the 2000 mg every two weeks data sets.

[Ryan Cohlhepp, President and COO at Bicara Therapeutics]

No other investigational agent targeting EGFR in the head and neck cancer space have shown durability of outcomes out this far, a key differentiating factor for ficerafusp alfa that resonates deeply with clinicians. With that, I'll turn it to Ivan to review the financials.

[Ivan Hyep, CFO at Bicara Therapeutics]

Thanks, Ryan. Earlier this morning, we reported detailed Q4 and full year 2025 financial results in our press release, and I'll summarize a few highlights here. Our total operating expenses for 2025 increased compared to the Q4 and full year 2024, driven by clinical operations and development expenses, including increased manufacturing and process development costs associated with our ongoing pivotal FORTIFY-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.

[Ivan Hyep, CFO at Bicara Therapeutics]

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

[Ivan Hyep, CFO at Bicara Therapeutics]

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

[Operator]

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

[Tyler Van Buren, Managing Director and Senior Biotechnology Equity Research Analyst at TD Cowen]

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

[Claire Mazumdar, CEO at Bicara Therapeutics]

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

[Claire Mazumdar, CEO at Bicara Therapeutics]

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-to-1 randomization of 1,500 milligrams weekly, randomized 2-to-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.

[Claire Mazumdar, CEO at Bicara Therapeutics]

I will pass it over to Tanya to give additional details to the FORTIFY-HN01 momentum.

[Tanya Green, Chief Development Officer at Bicara Therapeutics]

Hi, thanks. This is Tanya Green, Chief Development Officer. Yeah, as Claire said, we have really strong momentum for the 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.

[Operator]

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

[Eric Schmidt, Analyst at Cantor Fitzgerald]

Well, good morning and thanks for taking the question and congrats on all the recent progress. Questions on the colorectal cancer update that we might see in 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, you know, in particular, what type of benchmarks you think you'd hope to be able to provide in order to demonstrate proof of concept? Thank you.

[Ryan Cohlhepp, President and COO at Bicara Therapeutics]

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

[Ryan Cohlhepp, President and COO at Bicara Therapeutics]

You know, the two cohorts that we are currently exploring, seeking signals in are third line. You know, as you know, that's a highly challenging population. Again, we've got both a cohort in monotherapy as well as one in combination with pembrolizumab at the 1,500 mg weekly dose. Again, you know, I think we continue to look at that data, you know, for signal-seeking purposes and determine whether there's a path forward in CRC, particularly as we look to see about, you know, the opportunity to move into earlier lines of therapy in colorectal cancer, using those signals to determine whether there's, you know, something there to invest further.

[Eric Schmidt, Analyst at Cantor Fitzgerald]

Thank you.

[Operator]

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

[Stephen Willey, Managing Director at Stifel]

Yeah, good morning. Thanks for taking the questions. I guess with the understanding that you're gonna be providing the kind of pooled expansion cohort data at ASCO in a few months, just curious if the patients in the 750 mg once weekly cohort were given the opportunity to uptitrate to the 1500 mg dose, just given the, I guess, the relative deficiency in depth of response.

[Claire Mazumdar, CEO at Bicara Therapeutics]

Great question, Steve. What we'll be presenting at ASCO is likely an update from three separate cohorts. The 3-year follow-up median follow-up for the 1500 mg dose weekly, the 750 mg weekly dose, it was about a 30-patient cohort with at least 18 months of follow-up, and same for the 2000 mg every two-week cohort, an additional 30 patients with about 18 months of follow-up. In that particular cohort, to your question, the 750, we did not increase the dose afterwards. These were patients that were maintained at the 750 mg dose throughout their course of treatment, 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.

[Claire Mazumdar, CEO at Bicara Therapeutics]

If your question regarding the pivotal study in FORTIFY-HN01, I do believe that we were able to cross over the patients enrolled at this lower dose. If they remained on treatment, they did cross over to the 1500 mg dose in the pivotal study. Thank you for your question.

[Stephen Willey, Managing Director at Stifel]

Maybe just a quick follow-up. I know there's been kinda some background discussion about having interest in the pre-metastatic setting, whether it's neoadjuvant and adjuvant, and just wondering kinda where you are on that now? Does the pursuit of this new loading maintenance strategy and the need to generate maybe 200 patients worth of data, change perhaps the plans to pursue biotherapeutics in the pre-metastatic setting? Thanks.

[Claire Mazumdar, CEO at Bicara Therapeutics]

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

[Ryan Cohlhepp, President and COO at Bicara Therapeutics]

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

[Operator]

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

[Judah Frommer, Equity Analyst at Morgan Stanley]

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

[Claire Mazumdar, CEO at Bicara Therapeutics]

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

[Tanya Green, Chief Development Officer at Bicara Therapeutics]

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

[Ivan Hyep, CFO at Bicara Therapeutics]

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

[Judah Frommer, Equity Analyst at Morgan Stanley]

Thanks.

[Operator]

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

[Kelsey Goodwin, Senior Research Analyst at Piper Sandler]

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

[Ryan Cohlhepp, President and COO at Bicara Therapeutics]

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

[Operator]

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

[Reni Benjamin, Equity Research Analyst at Citizens JMP Securities]

Hey, great. Guys, thanks for taking the questions, and congrats on the progress. Just sticking with FORTIFY, can you maybe just help quantify a little bit as to what you mean by substantial enrollment? 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 you know 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 ficerafusp alfa? Thank you.

[Claire Mazumdar, CEO at Bicara Therapeutics]

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

[Claire Mazumdar, CEO at Bicara Therapeutics]

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. Thank you for your question.

[Reni Benjamin, Equity Research Analyst at Citizens JMP Securities]

Great. Thanks for taking the questions.

[Operator]

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

[Jeet Mukherjee, Biotechnology Analyst at BTIG]

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

[Ryan Cohlhepp, President and COO at Bicara Therapeutics]

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

[Ryan Cohlhepp, President and COO at Bicara Therapeutics]

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. That gives us the confidence and why we wanna initiate with a weekly dosing phase and then be able to transition to extend that interval out to every 3 weeks. Again, what we'll look to do is to match the pharmacokinetic profile from both an exposure as well as a C trough perspective to the 750 mg weekly, which again, we know as you saw on that data set that we presented last year, you see really good response rates. You see really good activity even at the 750.

[Ryan Cohlhepp, President and COO at Bicara Therapeutics]

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

[Ryan Cohlhepp, President and COO at Bicara Therapeutics]

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

[Operator]

Thank you. One moment for our next question. Our next question comes from Eva Fortea with Wells Fargo. Your line is open.

[Eva Fortea, VP, Equity Research at Wells Fargo]

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

[Claire Mazumdar, CEO at Bicara Therapeutics]

Great question, Eva. 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 1-19. In fact, it's in this patient population that pembro has worse response rates across the board. Seeing very strong response rates in the CPS 1-19 really speaks to the underlying biology of being able to target both EGFR and TGF-beta, which is why we believe we're able to target these very immunosuppressive tumors.

[Claire Mazumdar, CEO at Bicara Therapeutics]

In fact, we do think that it's always going to be a differentiating aspect of our molecule compared to other EGFR inhibitors that are currently being tested that have not seen the outsized impact in the CPS low. In fact, we do believe that especially given we are going after a chemo-sparing regimen, being able to go after these 1-19 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.

[Eva Fortea, VP, Equity Research at Wells Fargo]

Got it. Thanks.

[Operator]

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

[Lana Usmanova, Research Associate at Goldman Sachs]

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

[Claire Mazumdar, CEO at Bicara Therapeutics]

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

[Operator]

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

[Claire Mazumdar, CEO at Bicara Therapeutics]

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.

[Operator]

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

Participants

Executives

• Claire Mazumdar, CEO
• Ivan Hyep, CFO
• Rachel Frank, Senior Director and Head of Investor Relations and Corporate Communications
• Ryan Cohlhepp, President and COO
• Tanya Green, Chief Development Officer

Analysts

• Eric Schmidt, Analyst at Cantor Fitzgerald
• Eva Fortea, VP, Equity Research at Wells Fargo
• Jeet Mukherjee, Biotechnology Analyst at BTIG
• Judah Frommer, Equity Analyst at Morgan Stanley
• Kelsey Goodwin, Senior Research Analyst at Piper Sandler
• Lana Usmanova, Research Associate at Goldman Sachs
• Reni Benjamin, Equity Research Analyst at Citizens JMP Securities
• Stephen Willey, Managing Director at Stifel
• Tyler Van Buren, Managing Director and Senior Biotechnology Equity Research Analyst at TD Cowen