Bicara (BCAX) Q3 2026 Earnings Call Transcript

DATE

Monday, Nov. 9, 2026

CALL PARTICIPANTS

• Vice President of Investor Relations - Rachel Frank
• Interim Chief Executive Officer - Ryan Cohlhepp
• Chief Medical Officer - Bill Schelman
• Chief Commercial Officer - Chris Sarchi
• Chief Financial Officer - Jen Larson
• Chief Development Officer - Tanya Green

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TAKEAWAYS

• Cash, Cash Equivalents and Marketable Securities -- $442.3 million as of Sept. 30, 2026, which management expects will fund operations into the first half of 2029.
• Research and Development Expenses -- $56.5 million, an increase from $33 million due to costs associated with the FORTIFI-HN01 and FORTIFI-FLEX trials and personnel additions.
• General and Administrative Expenses -- $19.2 million, up from $7.7 million reflecting professional fees and personnel costs for commercialization preparation.
• Net Loss -- $71.2 million for the third quarter, compared to a net loss of $36.3 million.
• Net Loss Per Share -- $1.04, compared to $0.67.
• Interim Analysis Timeline -- Substantial enrollment in the FORTIFI-HN01 pivotal study enables top-line results from an interim analysis expected in mid-2027.
• Trial Enrollment Size -- Approximately 650 patients in an human papillomavirus (HPV)-negative only population, designed to provide statistical optionality for interim analyses.
• Head and Neck Cancer Market -- Projected to exceed $5 billion globally by 2030, driven by an estimated 50,000 new HPV-negative diagnoses annually in major markets.
• Phase 1b Confirmed ORR -- 54% at the 1,500-milligram weekly dose, with 80% of responders showing tumor shrinkage of 80% or more.
• Phase 1b Complete Response Rate -- 25% for patients receiving the pivotal dose, representing the depth of response from the bifunctional agent.
• Phase 1b Median Duration of Response -- Nearly 22 months, with responses observed at a median of approximately 6 weeks.
• Phase 1b Median Progression-Free Survival -- 9.9 months, which management stated is roughly three times the rate reported for pembrolizumab monotherapy.
• Phase 1b Median Overall Survival -- Over 21 months, with 1 in 3 patients alive at the 3-year mark.
• FORTIFI-FLEX Study -- Evaluation of a 2,250-milligram every 3-week dosing regimen as a potential maintenance option following a 12-week loading dose.
• Colorectal Cancer Data -- Results from a Phase 1b cohort in patients with third-line or later metastatic colorectal cancer are expected in January 2027.
• Interim Analysis Scope -- Management confirmed the addition of an interim overall survival analysis to the FORTIFI-HN01 study protocol.
• Preclinical Data Presentation -- Preclinical results evaluating tumor-targeted TGF-beta neutralization on fibrosis are scheduled for presentation in December 2026.
• Commercial Infrastructure -- A leadership team with experience across 50 new product launches is in place to support a potential U.S. launch.
• HPV-Negative Population -- Represents 80% to 90% of global head and neck squamous cell carcinoma cases and carries a worse prognosis than HPV-positive disease.

SUMMARY

Bicara Therapeutics Inc. (NASDAQ:BCAX) reported financial results for the third quarter of 2026 and provided updates on its clinical pipeline, primarily focused on the development of ficerafusp alfa for human papillomavirus (HPV)-negative head and neck cancer. Management reported that the pivotal FORTIFI-HN01 study has reached substantial enrollment to support an interim analysis, which will now include overall survival data. The company stated that its current cash position provides a runway into the first half of 2029, covering the completion of pivotal studies and initial commercial infrastructure investments. The company indicated that Phase 1b data continue to support the drug's mechanism of action, which targets both EGFR and TGF-beta to address the distinct biology of HPV-negative tumors.

• Interim CEO Cohlhepp stated, "Our conviction in FICERA's clinical profile in frontline recurrent metastatic HPV-negative head and neck cancer and our path forward grounded in the role of TGF-beta in our early clinical experience is only strengthened by that news."
• Management confirmed the inclusion of an overall survival analysis at the interim stage of the FORTIFI-HN01 trial to optimize the speed to market and the commercial profile.
• CMO Schelman noted that HPV-negative tumors overexpress EGFR and are rich in TGF-beta, which suppresses the immune response and drives resistance to therapy.
• The company plans to present third-line metastatic colorectal cancer data in January 2027 to evaluate safety and efficacy signals for potential movement into earlier lines of treatment.
• CCO Sarchi indicated that oncologists increasingly view HPV-negative head and neck cancer as a distinct population that warrants a targeted approach.
• The FORTIFI-FLEX study is evaluating a less frequent dosing option of 2,250 milligrams every 3 weeks, which physicians requested to enhance the profile of ficerafusp alfa.

INDUSTRY GLOSSARY

• Ficerafusp alfa (FICERA): A bifunctional antibody designed to simultaneously target EGFR and bind to human TGF-beta.
• HNSCC: Head and neck squamous cell carcinoma.
• HPV-negative: A subtype of head and neck cancer not associated with human papillomavirus, typically characterized by worse clinical outcomes.
• EGFR: Epidermal growth factor receptor, a protein that promotes cancer cell growth when overexpressed.
• TGF-beta: Transforming growth factor beta, a cytokine in the tumor microenvironment that suppresses immune responses.
• FORTIFI-HN01: The company's pivotal Phase 3 clinical trial for ficerafusp alfa in frontline recurrent or metastatic HPV-negative head and neck cancer.
• CPS: Combined Positive Score, a measurement used to determine PD-L1 expression levels in tumor samples.
• BLA: Biologics License Application, a request for permission to introduce a biologic product into interstate commerce.

Full Conference Call Transcript

Operator: Good day, and thank you for standing by. Welcome to the Bicara Therapeutics Third Quarter 2026 Earnings Conference Call. [Operator Instructions] Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker today, Rachel Frank, Vice President of Investor Relations. Ma'am, please go ahead.

Rachel Frank: Thank you, and good morning, everyone. It's a pleasure to welcome you to Bicara Therapeutics Third Quarter 2026 Earnings Call. Earlier this morning, we issued a press release highlighting the results from the quarter and provided a business update. You can access the press release, as well as the slides that we'll be reviewing today by going to the Investors section of the 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 Ryan Cohlhepp, Interim Chief Executive Officer; Bill Schelman, Chief Medical Officer; Chris Sarchi, Chief Commercial Officer; and Jen Larson, Chief Financial Officer. Tanya Green, Chief Development Officer, is also on the line and available for Q&A. I'll now turn the call over to Ryan.

Ryan Cohlhepp: Thank you, Rachel, and good morning, everyone. Since stepping into the interim CEO role earlier this fall, I've spent a lot of time on the road with clinicians, investors and hardworking [ Bicarians ] that make our work possible. My conversations have reaffirmed my belief in the potential practice-changing benefit of Ficerafusp alfa, known as FICERA, which continues to drive strong enrollment momentum in our ongoing pivotal FORTIFI-HN01 study of FICERA in combination with pembrolizumab for the treatment of frontline recurrent metastatic HPV-negative head and neck cancer.

Our research and insights reinforce that the health care providers respond positively to the depth and durability of response that has become a hallmark of FICERA's clinical profile, the chemo-sparing nature of its regimen and the potential for every 3-week dosing regimen in the future. Recurrent metastatic head and neck remains a disease of serious unmet need, particularly for patients with HPV-negative disease who continue to face limited treatment options for long-term outcomes and a significant impact on quality of life. We are proud to be part of the field that is pushing what's possible for these patients, and we welcome progress from others working to change outcomes in this disease.

Ultimately, what is good for patients is good for all of us. With that in mind, I want to acknowledge the top line results recently announced by one of our peers in the space, which provided a very encouraging update for patients. Our conviction in FICERA's clinical profile in frontline recurrent metastatic HPV-negative head and neck cancer and our path forward grounded in the role of TGF-beta in our early clinical experience is only strengthened by that news. We still have much to learn about how those results may shape the treatment landscape for patients with HPV-negative disease, including how outcomes differ by HPV status and how mature the survival data are.

What they do show is further validation for this new class of EGFR-targeted therapies in head and neck cancer, including FICERA and they sharpen our focus as we evaluate our strategy to bring the greatest value to patients with HPV-negative disease. FICERA has breakthrough therapy designation, specifically for the treatment of HPV-negative head and neck cancer based on a differentiated clinical data, which facilitates our ongoing interactions with the FDA. Today, we remain focused on executing on enrollment, conducting an interim analysis that provides meaningful clarity to physicians, patients and shareholders on FICERA's differentiated clinical profile and filing a BLA that optimizes both our speed to a potential U.S. approval and our goal of a maximally competitive commercial profile.

Today, we announced that FORTIFI-HN01 has achieved substantial enrollment to enable top line interim analysis, which we continue to expect in the middle of next year. And with the aim of maximizing speed to market in a competitively differentiated way, we can confirm that we are planning for an interim overall survival analysis, something we've been evaluating for some time, and we'll share more on timing and scope, as we believe is appropriate in the context of a fluid and competitive environment. Reaching substantial enrollment in FORTIFI-HN01 marks an important step forward for Ficara this quarter.

Alongside it, we advanced FORTIFI-FLEX to evaluate a more flexible dosing regimen, and we continue building the commercial and medical organization that will support a potential launch. Together, this progress positions us for our next phase of growth as we pursue our first approval in head and neck cancer, a large and growing market projected to reach more than $5 billion globally by 2030. Before I turn it over to Bill, I want to reinforce that our absolute priority at Bicara is clear, the successful development, approval and commercialization of FICERA in frontline recurrent metastatic HPV-negative head and neck cancer. Beyond head and neck, there's also clear biologic rationale for FICERA in other solid tumors.

In our Phase Ib expansion study in third-line MSS RAS, BRAF wild-type metastatic colorectal cancer, evaluating FICERA both as a monotherapy and in combination with pembrolizumab, we're seeing encouraging early safety and efficacy signals in this late-line population. What we're looking for is an efficacy signal paired with a safety profile that supports combination since earlier lines are where we see the greatest potential for clinical benefit. We now plan to present these data at a relevant forum in January.

As we near our top line interim analysis and our first potential regulatory filing, we continue to evaluate how we can take an evidence-based approach to the next pillars of growth for FICERA beyond head and neck cancer, while being disciplined stewards of our financial resources. With that, I'll turn it over to Bill.

Bill Schelman: Thanks, Ryan, and good morning, everyone. HPV-negative head and neck cancer is biologically distinct from HPV-positive disease. These tumors overexpress EGFR and are rich in TGF-beta, which suppresses the immune response and drives resistance to therapy. FICERA was designed to inhibit both EGFR and TGF-beta and to work synergistically with immunotherapy, overcoming barriers in the tumor microenvironment so that the drug and immune cells can penetrate the tumor. When I speak with treating physicians, what they tell me matters most for their patients is depth and durability of response as they believe these yield the greatest long-term outcomes like overall survival.

By pursuing that clear mechanistic biologic fit, we believe FICERA has the potential to redefine the standard of care in first-line recurrent or metastatic HPV-negative head and neck cancer, which represents roughly 80% to 90% of cases globally. I want to take a few minutes to revisit the long-term Phase Ib data we presented at ASCO this year because while FORTIFI-HN01 remains blinded and ongoing, they are the clearest window we have into FICERA's clinical profile. As these data mature, we believe they continue to derisk the pivotal study on the endpoints that matter most, response rate, complete response rate, as a measure of depth and most importantly, duration of response, progression-free survival and overall survival.

At the 1,500-milligram weekly pivotal dose with a median follow-up of 3 years, FICERA plus pembrolizumab achieved a confirmed objective response rate of 54% and a complete response rate of 25%. As a clinician, what stands out to me is the depth of those responses. Specifically, 80% of responders had tumor shrinkage of 80% or more. Responses came quickly at a median of about 6 weeks, and they were durable with a median duration of response of nearly 22 months. Median progression-free survival was 9.9 months, roughly 3x what has been reported for pembrolizumab alone and median overall survival was just over 21 months. Most importantly, about 1 in 3 patients was alive at 3 years.

That's roughly double what real-world data would lead us to expect with pembrolizumab alone in HPV-negative patients. We continue to believe that these clinical results are driven by TGF-beta and the role it plays in remodeling the tumor microenvironment to allow for greater depth of response. When we pool patients across all 3 dose cohorts in our Phase Ib study, 750 milligrams weekly, 1,500 milligrams weekly and 2,000 milligrams every 2 weeks, those with deep responses remained in response for a median of more than 2.5 years, and they went nearly 3 years without progression. We haven't yet reached median overall survival in that group.

Our paired biopsy showed reduced TGF-beta signaling in the tumor and greater CD8 T cell infiltration. We believe that immune cell penetration potentiates immunotherapy translating into more durable responses. With new data emerging in head and neck cancer, including recent results reported across both HPV-positive and HPV-negative patients, I think it's important to look at the context behind our data. In these patients, tumor characteristics matter as much as the efficacy numbers themselves. First, HPV status. Every patient in our Phase Ib data set was HPV negative, and it's the only population we are enrolling in FORTIFI-HN01. These patients have the worst prognosis in head and neck cancer.

So every number you've heard from me today comes from the hardest-to-treat patients. It's also why results broken out by HPV status are essential to interpreting any data set in this disease. Second, site of disease. Most patients at our pivotal dose had local regional disease, either alone or resistant metastases. Local regional recurrence is typically harder to treat because previously irradiated tissue can limit how well a drug reaches the tumor. Third, PD-L1 expression. Half of our patients in the Phase Ib study had a CPS below 20, where checkpoint inhibitors have historically been least effective, yet responses with FICERA plus pembrolizumab were essentially the same regardless of CPS. And fourth, tumor burden.

Nearly half of patients had large bulky tumors where rapid and deep responses matter most. In these patients, clinicians have historically added chemotherapy. FICERA has shown rapid responses and tumor debulking and offers the potential for a chemotherapy-sparing regimen in this setting. Taken together, our data come from a more symptomatic, harder-to-treat population, often with worse outcomes and a significant impact on quality of life. With up to 3 years of follow-up, that makes the depth and durability we have observed and their potential to translate into overall survival, all the more notable. We remain confident in FICERA's potential to deliver meaningful outcomes for patients living with HPV-negative head and neck cancer and to change clinical practice.

Ultimately, we believe the Phase III data will define how this treatment landscape evolves, and we look forward to sharing our pivotal results. With that, I'll turn it over to Chris to talk about the commercial opportunity.

Christopher Sarchi: Thanks, Bill. As Ryan mentioned earlier, head and neck squamous cell carcinoma is a large and growing market. Each year, roughly 50,000 patients across the U.S., EU5 and Japan are newly diagnosed with HPV-negative disease, about 18,000 of them here in the U.S. And today's options for these patients offer limited response rates and limited durability. FICERA was specifically designed for this population and has the potential to grow the market by increasing both response rates and duration of therapy. As Bill described, what sets FICERA apart is how deeply and how durably patients responded, not just how many responded. The depth and durability are exactly what this market lacks today and FORTIFI-HN01 is designed to confirm this benefit.

Our market research over the past year suggests a meaningful shift in how physicians view FICERA. Oncologists increasingly see HPV-negative disease as a distinct population that warrants a targeted approach. Complete responses, historically in the single digits with standard of care regimens are now cited alongside durability as key drivers of treatment choice, and we believe our mechanism is increasingly understood as a reason for the depth and durability we've seen to date. We're also optimizing FICERA's dosing for flexibility and convenience. FORTIFI-FLEX is evaluating a less frequent dosing option, which physicians have asked for with the potential to further enhance FICERA's profile.

Behind all of this, our commercial leadership team with more than 50 collective new product launches is now in place and our go-to-market strategy, disease education, payer and access strategy and data and analytics infrastructure are all underway. As the landscape evolves, we recognize that being first to market can bring certain advantages. But as we've seen in many oncology launches and based on discussions we've had with HCPs, the first entrant doesn't necessarily translate to sustained market leadership. Over time, physicians choose the therapy with the most compelling clinical profile and the strongest label for their patients.

That's why our focus is twofold: moving with speed and aiming to deliver a differentiated BLA submission that we believe can support the strongest label. Beyond the regulatory considerations, our aim is for FICERA to enter the market with a competitive profile that gives physicians, patients and payers a clear reason to choose it with a label that reflects its depth and durability of response and ultimately survival in HPV-negative patients. But let me close with what this means for patients. First-line head and neck cancer is a market that's large enough to sustain many entrants.

We intend to successfully compete in this market while aiming to provide an important new option and a new sense of hope for these patients and the providers. With that said, I'll now turn the call over to Jen to discuss our financials.

Jennifer Larson: Thanks, Chris. Earlier this morning, we reported detailed third quarter 2026 financial results in our press release, and I'll summarize a few highlights here. Research and development expenses were $56.5 million for the third quarter of 2026 as compared to $33 million for the third quarter of 2025. The increase was primarily due to costs associated with the ongoing FORTIFI-HN01 pivotal trial, FORTIFI-FLEX trial as well as the company's ongoing Phase I/Ib dose expansion cohorts and increase in personnel costs. General and administrative expenses were $19.2 million for the third quarter of 2026 as compared to $7.7 million for the third quarter of 2025.

The increase was primarily due to additional personnel costs and professional fees associated with expanding the organization as the company advances its pivotal trial and prepares for potential commercialization. We anticipate that our overall operating expenses through year-end will remain consistent with our most recent quarterly results as we continue with the development of FICERA and continue to prepare for a potential U.S. launch. We ended the third quarter of 2026 with approximately $442.3 million in cash, cash equivalents and marketable securities, which provides cash runway into the first half of 2029.

As a reminder, that runway includes advancing pivotal FORTIFI-HN01 study of FICERA in frontline recurrent metastatic head and neck cancer through to a final overall survival analysis, supporting a planned regulatory filing for FICERA, providing initial investment into medical and commercial infrastructure ahead of a potential U.S. approval and launch, clinical development costs for FORTIFI-FLEX, funding manufacturing costs for FICERA for existing drug development efforts and other general corporate purposes. With that, I'll now turn the call back over to the operator for questions. Operator?

Operator: [Operator Instructions] Our first question will come from the line of Tyler Van Buren with TD Cowen.

Tyler Van Buren: I know you discussed it to some extent, but maybe you could just elaborate on why HPV status is so central to FICERA's strategy in the context of recent developments. And given the open questions around recent data in the space, why do HPV subgroups and survival maturity matter? And what should investors be looking for at the full data presentation?

Ryan Cohlhepp: Thanks, Tyler, for the question. So definitely, this has been a key area in terms of our approach and what we believe is a differentiated approach to our clinical development plan. If you look at the historical data with EGFR monoclonal antibodies, I think you consistently see a real clear distinction between the activity seen with an EGFR monoclonal and the positive versus negative based upon the biology and what is driving that. In our own data, we saw similar results, which is why we chose to develop the drug in HPV-negative only in our pivotal trial. I think of recent, we also saw data from the OrigAMI cohort.

And in that particular cohort, what they demonstrated with AMI was about a 29% response rate from an HPV positive perspective. So I think, again, that data also was continued reinforcement of the historical data we've seen. As we think about the subsets from a survival perspective, I think it also plays forward. One of the things that is known is the HPV-positive patients historically have lived longer than HPV negative. The overall -- I think overall ability to -- for those patients to live longer is just greater.

So I think there is a clear distinction both from a response rate as well as a survival outcome that can meaningfully influence the outcomes by subset of both response rate and overall survival. So understanding that, understanding, especially when you're looking at different points in the Kaplan-Meier's survival curve, understanding the influence of different subsets is important and an area that investors could -- should continue to focus on as they evaluate the data sets.

Operator: And one moment for our next question. Our next question is going to be from the line of Eric Schmidt with Cantor.

Eric Schmidt: Congrats on the progress on execution of FORTIFI. I was curious about the comment that you can now confirm an interim overall survival analysis in that frontline study. Could that analysis happen as early as mid-2027? And what are your plans for sort of statistical utilization around that analysis?

Ryan Cohlhepp: Yes. Thanks for the question, Eric. So we definitely are at a point where we can confirm that we will incorporate an OS analysis at an interim. We've not yet guided to when that will be. And certainly, we'll continue to provide greater clarity as we -- I think finalize that. I think one of the things, I think all along in the conduct of this trial, our plans were to closely evaluate emerging survival data, both for our own program as well as the class and the overall space as a whole and taking that relevant information that is accruing over time to incorporate it into our own planning.

And so again, we're not at a point now where we're providing more clarity on that top line guidance middle of next year, but certainly will as we continue to work towards that point and refining guidance.

Operator: And our next question is going to come from the line of Tazeen Ahmad with Bank of America.

Tazeen Ahmad: I'm sorry if I missed this in your prepared remarks, but Ryan, do you know if you need to upsize the study in order to be able to include OS as part of that interim next year? And then given that investors have assumed that there's now, I guess, basically a bogey that you need to be close to, can you just share what your thoughts are about what OS benefit is going to be needed to be seen in order to be competitive just based with maybe any initial discussions you've had with physicians and also how important the hazard ratio becomes at that point as well?

Ryan Cohlhepp: Again, thank you for the question, Tazeen. So we actually did not speak to overall trial size. What I can say is we're confident in the size as currently. Again, the overall size of our trial is around 650 patients in an HPV-negative only population. So by comparison, again, the other studies that have recently read out, I think, are now at 700 in a mixed population. Early on in the design of our trial, we did so with that size, reflecting that it was a negative only population and was going to be adequately sized not only for a final analysis, but also to give us optionality as we think about incorporating an interim analysis.

So I would say that we thought about that prospectively and are not in a position where we are going to need to upsize. In terms of what's going to be competitive, I think to some degree, again, that will be influenced based upon historical standard of care, 3 to 4-month improvement over that standard of care would have been seen as meaningful. We were targeting for an overall effect that exceeded that based upon what we had seen in our early Phase I experience. I do think that it's an evolving in terms of what that level of competitiveness is going to need to be.

And I think in the absence of further information, I think it's hard to speculate. But again, if you look at our Phase I experience, we have a high degree of confidence in our ability to meaningfully show survival well ahead of what is clinically meaningful in today's standard of care.

Operator: And one moment for our next question. Our next question will come from the line of Stephen Willey with Stifel.

Stephen Willey: Apologies if I missed this earlier. But -- I'm sure that you're projecting the number of death events that you hope to have accrued at the time of the response rate interim. So just curious what that projection suggests about the statistical power that you might have at that point to similarly detect an OS benefit at the interim. And then also, maybe I think there's -- just curious as to if your expectations around kind of what a disclosure framework might look like when you announce the interim data, have those expectations at all kind of changed in light of how Genmab chose to disclose their top line data?

Ryan Cohlhepp: Yes. So your first question, I'll start with and then I'll ask Bill to add to it as well. Again, I think one of the things, as you know, the key difference in our trial versus the LiGeR trial is that it's a blinded trial. So in terms of the data that we have with our own trial, which will be used to, I think, answer your key question, I think that's a key difference. But we'll ask Bill to also speak to what we are able to see and as we think about our interim, the power we'll have there.

Bill Schelman: Yes. Thanks, Ryan. So at the interim, we are anticipating reporting the response characteristics. As we've discussed depth and durability are definitely underpin the prediction to overall survival. And so with the design we have, we definitely are looking to show the -- not only the response characteristics, but the depth and durability and then how they translate into overall survival. With the current study design we have, we have already contemplated those factors and then are looking to the number of events that will support an overall survival benefit.

Ryan Cohlhepp: And then to your second question, again, we certainly saw the approach taken with the most recent data set. I think we'll, I think, continue the one thing that I think both ourselves and that particular company can agree on is that it's an increasingly competitive space and want to make sure that we put ourselves in a position and our data in a position both from a regulatory perspective and an overall competitive perspective to be best positioned. That being said, we also have a philosophy here of there are many stakeholders, including the investor community.

So finding that right balance of transparency at our data disclosure, while also making sure that we maintain the right posture from a competitive perspective will be what guides the way we do that disclosure.

Operator: And our next question is going to come from the line of Kelsey Goodwin with Piper Sandler.

Kelsey Goodwin: Maybe shifting a bit to CRC. In terms of the third-line data set coming in January, maybe first, what kind of led to getting pushed into 2027? And then in terms of how we should think about that data set, given it's late line and the plan is to kind of move forward into earlier lines. How should we think about how to translate that third-line data, how to think about the path to frontline and how far behind J&J and Genmab you might be, how you might be able to catch up? Just trying to kind of wrap our heads around that.

Ryan Cohlhepp: Yes, absolutely. So in terms of timing, again, historically, we have always presented at medical congresses and prefer to be able to do that and not just any conference. We want to be able to put it in a venue that is relevant for the audience. And that really guided our view in terms of where the data should sit and look to be able to provide more clarity in terms of when January and that we'll be presenting that data.

In terms of the read-through, again, I think the most relevant data sets with the data that we have coming out, again, as a reminder, it's a third line plus data set, both in monotherapy and then a cohort in combination with pembro is I think some of the more recent data sets, what we've seen from petosemtamab in that same population is around a 10% response rate. We saw Incyte with their TGF-beta PD-1 showing about a 15% in that population. So I would say those are the relevant benchmarks based on the most recent data.

I think that being said, at the most recent ESMO, we saw what that can translate to as you move into earlier lines in the first and second line, which is much stronger and also very consistent with the way EGFR monoclonals have operated and behaved. So I'd say the read-through from a third line into front line, I think in a lot of ways, even in terms of the wealth of data that exists with EGFR monoclonal antibodies would suggest that these are going to be highly active compounds, FICERA included as you move into that earlier line.

So one of the things that is also was an important piece for us in the third-line setting is understanding whether there was a consistent tolerability profile in CRC to what we have seen in head and neck cancer. So I would say some degree of activity consistent with what has been seen historically as well as a consistent safety profile are important read-throughs as we present that data in January.

Operator: And one moment for our next question. Our next question will come from the line of David Lebowitz with BMO Capital Markets.

Xi Chen: This is [ Theo ] on for David. So a quick one from us regarding -- so we see the amivantamab has recently been approved for head and neck and later line. Just kind of curious about your thoughts over if patients in the FORTIFI, who progressed can receive amivantamab? And how should we think about the impact on the shape of the OS curve at both interim and also for the follow analysis?

Ryan Cohlhepp: Yes. So in terms of the most recent approval, again, if you look at the -- what's approved within that label is for patients who have progressed on PD-1 plus chemotherapy. As a reminder of the design of our trial, the active arm is FICERA plus pembro and the control arm is pembro monotherapy. So strictly within the label that has recently been approved. Neither one of those arms is within the label of Ami. That being said, we know in the U.S. that there can be off-label use. We've not yet seen that trend. Rybrevant has been available.

So in many cases, you would have seen that off label use even in the absence of an approval, which we've not yet seen. I think the other important element, again, is the fact that we have a blinded trial. So not only are those patients not within label for Ami. It's also not clear to physicians because of the blinded nature of the trial and their ability to -- whether they're EGFR naive or not. So I think we think there is very limited exposure based upon that approval. And again, there's -- a lot of our enrollment sits outside of the U.S. where, again, that approval doesn't exist.

In terms of, I think your question on survival curve, we'll ask Bill to speak to that.

Bill Schelman: Yes. Thanks, Ryan. So as Ryan commented, the study is a blinded study. And so with that, the clinicians won't have a sense of whether or not they received EGFR prior EGFR therapies or not. This is again something that we've been thinking about and planning for and ensuring that post discontinuation therapies are contemplated. And we also have some statistical analyses to look at this and to understand the potential impact of post discontinuation therapies further.

Ryan Cohlhepp: And I think in terms of the relevance and as you think about the shape of the OS curve, I think the data that we presented out at 3 years, where you saw twice as many patients are alive at the 3-year mark on FICERA plus pembro versus standard of care. We believe that, that is likely to represent the tail end of the curve even in the FORTIFI trial.

Operator: And one moment for our next question. Our next question will be from the line of Sean Laaman with Morgan Stanley.

Sean Laaman: A couple of questions just on the commercial positioning. And how has petosemtamab changed your launch assumptions, if at all? And if it is approved in 2027 and establishes a few years of prescribing experience before FICERA gets approved, where do you think Bicara can realistically win first? Is it HPV-negative stresses, deeper responders, patients avoiding chemo, that type of thing? And what evidence do you believe would justify premium pricing for FICERA? Would superior CR and durability be sufficient? Or do you think payers will require demonstrated OS differentiation?

Ryan Cohlhepp: Great. So I'll start and then ask Chris to speak to your various questions. I mean I think one thing that I'd like to point out is timing. Again, I think a key view that we continue to hold is that timing sits at less than a year between ourselves and petosemtamab, which we know based on historical analogs is a key driver of ultimate peak share uptake when you've got a competitive space with multiple agents. So I think that's one area that is really important to clarify. We have not shifted our view in terms of where we sit relative to the approval of petosemtamab.

And Chris, if you'd like to speak to the broader competitive dynamic and how we think about the uptake of ourselves versus peto.

Christopher Sarchi: Yes. Thanks for the question, Sean. So as Ryan said, we view peto as an important competitor. And we also think that the recent Phase III results are further validation of the significant unmet need and the opportunity that exists in first-line metastatic head and neck cancer. And so as this market evolves, being first to market, we recognize can bring certain advantages. But as we've also seen many times, first mover doesn't necessarily translate into sustained market leadership. And so our goal, as you've heard, is moving with speed and a differentiated BLA to establish a competitive profile that gives physicians, patients and payers a reason to choose FICERA.

In regards to your question around pricing, we're going to be pricing relative to the value that we believe FICERA will bring to the market, but we're excited about the opportunity.

Ryan Cohlhepp: The other thing that I would add, as we think about the launch dynamic is, I think prior to last week, I think we've gone in with an assumption that both drugs were going to have an initial accelerated approval label on a basis of response rate, where the longer-term endpoints like overall survival would going to be part of that initial label. I think what our view has shifted is it's more likely that both initial labels will have a component of overall survival. Again, we haven't yet had regulatory interactions.

We don't know, frankly, whether -- even though we had a clear hazard ratio coming from the petosemtamab trial, ultimately, whether that data will be mature enough and representative enough to be incorporated into the label, their initial label. So there's still a lot to be answered there from a regulatory perspective with an assumption that both agents get out with an OS label. I do think we continue to believe that the depth and durability will drive differentiated overall survival for our program. And the data that we saw last week doesn't do anything to reduce our confidence in our agents' ability to meaningfully differentiate based upon the depth and durability that we've demonstrated.

And we'll probably now be in a position with our early stage of the launch, where you're actually able to compete on the endpoint we think we'll have an ability to meaningfully differentiate on.

Operator: And one moment for our next question. Our next question will come from the line of Jeet Mukherjee with US BTIG.

Blake Gitler: This is Blake on for Jeet. Quick one on the FLEX trial. Can you just give any update on enrollment progress there? And does the FDA commentary from last quarter still stand that you're okay with 150 to 200 patients in the trial?

Ryan Cohlhepp: Yes. So consistent with what we've communicated on enrollment progress with FORTIFI, we don't speak to specifics on that. What we have guided to is that we anticipate having that data prior to our first approval. That remains unchanged. And the overall design of the trial also has remained unchanged.

Operator: One moment for our next question. Our next question comes from the line of Reni Benjamin with Citizens Bank.

Reni Benjamin: I guess, Ryan, I'd like to maybe expand a little bit more on your regulatory strategy. You commented a little bit to a prior question. But if peto and pembro get approved before FICERA, how are you thinking in terms of best and worst-case scenarios, full approval versus accelerated approval? And how do you address those different scenarios?

Ryan Cohlhepp: Yes. Again, we don't speak to specifics in terms of regulatory strategy. But what we did say today is that we plan to incorporate an interim analysis for overall survival. I do think that in the absence of specific regulatory interactions or guidance, we have always recognized that overall survival is a key endpoint and ultimately the endpoint that the FDA is looking for -- for a final analysis. So I don't want to, I think, speculate or to, I think, say much more than that other than the fact that we will continue to engage with the FDA and other regulatory bodies. We've got the pathway to do that on a real-time basis with breakthrough designation.

And I think that will be a nature of the discussion. What I had said earlier is while we saw a top hazard ratio number last week, we don't yet have clarity even in terms of their regulatory path. And so I think there's still a lot of unknowns, and we will continue to update our own plan and guide to that based upon when there's relevant changes and interactions that we've had with regulators and information and new information that we gather over time.

Reni Benjamin: And just when do you think you will have those interactions with the regulators? Will it be after you have data? Or do you plan on having that beforehand?

Ryan Cohlhepp: Again, we don't speak to specifics in terms of our regulatory strategy. But throughout any clinical trial and BLA process, there are different natural time points to engage with the FDA and other regulators. And again, I won't speak to the specifics of that, but we have an ongoing dialogue with the FDA, as we move through this process.

Operator: And I would now like to hand the conference back over to Ryan Cohlhepp for closing remarks.

Ryan Cohlhepp: Thank you very much to everyone for joining today. As is very clear, this is an incredibly important moment for our field and for Bicara. We remain focused on execution and speed and on bringing FICERA to patients with HPV-negative head and neck cancer. We look forward to updating you, as we progress through the end of this year and into 2027. Thank you, everyone.

Operator: [Audio Gap] disconnect. Everyone, have a great day.

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