Good morning, everyone, and welcome to day one of the 44th Annual J.P. Morgan Healthcare Conference here in San Francisco. My name is Alex Kramer, and I'm a member of the JP Morgan Healthcare Investment Banking team. It is my pleasure to introduce our next presenting company, Bicara Therapeutics. I'm joined by CEO Claire Mazumdar, who will be giving the presentation today. Following Claire's remarks, there will be a time at the end for Q&A, so I ask that you hold your questions until the end. For that portion of the presentation, I will also ask President and CEO Ryan Kohlhepp to come up as well. With that said, Claire, please take it away.
Thank you, Alex, and good morning, everyone. I'm thrilled to be here today to represent Bicara Therapeutics to present our 2026 corporate outlook, our first time to do so as a public company. I'd like to thank Alex and his colleagues at JP Morgan for the invitation. Earlier this morning, we issued a press release as well as the accompanying slides I'll be walking you through today, highlighting our 2025 accomplishments as well as our corporate outlook for the year. Those slides and the press release can be found on the Investor section of our company website. I will be making forward-looking statements today. For additional information on our risk factors, please refer to our SEC filings. Bicara is a clinical-stage biotech company focused on targeted tumor modulation.
The idea is that we develop bifunctional antibodies where one arm gets you to the tumor and the other arm is some type of tumor modulator that, when delivered directly to the tumor microenvironment, should not only provide better efficacy but improve durability and safety from the localized approach. This is exemplified by our lead program, ficerafusp alfa, or ficerafusp alfa, the first and only EGFR-directed antibody bound to a TGF-β ligand trap designed to target solid tumors. Ficerafusp alfa entered the clinic in the summer of 2020, and today Bicara is a global company of about 100 employees focused on the development of ficerafusp alfa in frontline recurrent and metastatic HPV head and neck, headquartered in Boston, Massachusetts. Ficerafusp alfa, our EGFR TGF-β, was designed to drive tumor penetration.
It is well understood today that a number of solid tumors that have both a fibrotic and immunosuppressive tumor microenvironment, of which head and neck is one, that insufficient tumor penetration from targeted therapies such as cetuximab or immunotherapies such as pembrolizumab lead to lack of efficacy and the inability of immune cells to fight the tumor. Ficerafusp alfa was designed to use the EGFR arm to fight the tumor while also localizing TGF-β inhibition directly to the tumor microenvironment, thereby synergizing with the anti-PD-1s to allow the immune cells to penetrate the tumor, enabling deep, durable responses that will lead to better outcomes and better survival for our patients. We often get the question as to why did we go into HPV-negative head and neck cancer as our first indication, and it was really about following the science.
It is well understood today that there are a number of solid tumors where there's an immunosuppressive fibrotic tumor microenvironment. Head and neck is such an example, colorectal cancer as well as pancreatic cancer. I'll focus on the last two in a little bit more detail towards the end of my presentation, but head and neck is well understood today to be made up of two distinct clinical subtypes. HPV-negative makes up the vast majority of patients at 80% to 90% of the frontline recurrent and metastatic market. What's known about these patients is that they typically have high levels of both EGFR and TGF-β, and this is what makes them therapeutically resistant and makes the tumor microenvironment very fibrotic and immunosuppressive, and ficerafusp alfa, designed to drive this inherent tumor penetration, was really well suited for a subtype like HPV-negative head and neck cancer.
2025 was a momentous year for Bicara. We shared significant progress in terms of the clinical development of our lead program, ficerafusp alfa, in HPV-negative recurrent and metastatic head and neck, the first of which is that we shared two important data sets with long-term follow-up showing significant depth and durability of response and meaningful overall survival benefits compared to standard of care in that patient population. These data sets supported the granting of breakthrough designation in the HPV-negative subtype of head and neck by the FDA, a clear recognition and underscoring by the FDA and the growing head and neck community that HPV-negative head and neck is a distinct clinical subtype from its HPV-positive counterparts, marked by limited treatment options, worse outcomes, and yet makes up the vast majority of patients in the frontline setting.
We also initiated our pivotal study designed as a seamless phase II, III, FORTIFY-HNS for the potential accelerated approval of ficerafusp alfa plus pembro in the frontline setting. We are excited to be announcing today that we have selected the 1,500 milligram dose from the phase II portion of the study to move as our go-forward dose for the phase III portion of the study, something that happened earlier than we anticipated and speaks to the key momentum we're building in 2026, and so 2026 is a key year for Bicara. As I mentioned, we're building significant momentum, and we are focused on execution of our pivotal study in head and neck cancer.
I will focus on three key pillars of success today that will really build the value and the growth of this company and be important value inflection points for Bicara this year, the first of which, as I highlighted, is on executing a strategic development plan for ficerafusp alfa in frontline HPV-negative recurrent and metastatic head and neck. With the ability to select the dose earlier this morning after an FDA interaction recently, we believe that we can accelerate enrollment to enable an interim analysis by mid-2027, supporting a potential accelerated approval in the frontline setting of HPV-negative head and neck cancer. With that in mind, we are also preparing for commercial success, anticipating an early launch in early 2028. We know that HPV-negative head and neck cancer is a growing and sizable market, and this year we are focused on making key hires and laying that commercial framework.
We hope to hire a chief commercial officer to help us build that pathway, and while head and neck cancer is a beachhead indication for ficerafusp alfa, we do believe that ficerafusp alfa has potential in a number of other solid tumors where we can follow the EGFR TGF-β biological fingerprint. We are going into metastatic colorectal cancer as well as other tumor types to really explore ficerafusp alfa's pipeline and the product potential in a financially disciplined manner. I will now focus on executing a strategic development plan for ficerafusp alfa in frontline recurrent and metastatic head and neck. As we know, head and neck cancer has a significant unmet medical need and is in need for better treatment options, in particular in the HPV-negative subset of head and neck where patients tend to do far worse.
It's well understood today that the standard of care, both Pembro or Pembro in combination with chemotherapy, only delivers a 19%-36% response rate, with a median overall survival of only 12 to 13 months in the HPV all-comer population. Real-world data suggests that the vast majority of patients who are HPV-negative, typically with a history of smoking and chewing tobacco, have a worse prognosis at only a median overall survival of seven to nine months, and so there is clearly a need for better therapies, even in the frontline setting. At ASCO 2025, in an oral presentation, we shared long-term follow-up data from our 1,500 milligram in combination with Pembro frontline data set of 30 HPV-negative patients.
Not only were we able to show a more than doubling of response rate with a confirmed response rate of 54%. These responses were deep, with 80% of our responders achieving at least an 80% tumor shrinkage and a complete response rate of 21%. Not only were these responses deep, they were also rapid, occurring with a median time to response of 1.4 months. Importantly, these responses were happening irrespective of what's known as the combined PD-L1 score or CPS score. Typically, patients with a CPS of 1 to 19, considered CPS low, tend to have worse outcomes with immunotherapy. But even in this patient population, really following the mechanism of action in a more immunosuppressive tumor type, we've been able to demonstrate deep and durable responses. Additionally, these responses are happening irrespective of tumor size, happening in patients even with bulky tumors, with very aggressive tumors.
Beyond these deep responses, what we also know is that these responses are durable. As we look at head and neck cancer, there have been a number of combinations that have been studied since the approval of Pembro. Many of these combinations have showed modest improvements in response rate, but at the expense of durability, leading to minimal to no impact on overall survival. This is where ficerafusp alfa, as the first and only EGFR TGF-β and its unique mechanism to drive durability through tumor penetration, is really outshining itself. Today, we're showing a median duration of response at 21.7 months, far exceeding what we're seeing with both approved regimens in the frontline setting as well as any other combination in development. And it is these deep and durable responses that are leading to significant overall survival benefit.
In the data set we presented at ASCO, we were able to share a median overall survival of greater than 21 months, more than tripling what was seen with standard of care in the same HPV-negative population, and it is really this significant overall survival benefit that builds confidence in our pivotal study now entering the phase III portion, and so as we look at the totality of the data for ficerafusp alfa, our EGFR TGF-β, we've been not only able to demonstrate more than a tripling in response rates, these responses are deep, leading to a significant improvement in median DOR compared to the standard of care and a more than twofold increase in median overall survival, building significant confidence in, again, our pivotal study.
As we look at the safety of this molecule, ficerafusp alfa has been a well-tolerated molecule designed specifically to spare the TGF-β, a two-isoform of TGF-β, which was historically known to lead to TGF-β-related toxicities. As we look at the safety and efficacy of this molecule, we continue to also build significant responses from our investigators, hearing how this molecule is really impacting our patients. Here is an example of a patient who had a very large, bulky tumor, and after several weeks on ficerafusp alfa plus Pembro led to a significant tumor reduction that was both deep and durable. Not only are we seeing significant improvements in efficacy metrics, we're also hearing from these investigators that there are significant quality of life benefits. This particular patient was eating through a feeding tube and had significant facial disfigurement as well as multiple comorbidities.
We heard that within several weeks on therapy, he had his first cheeseburger without a feeding tube and went on his first date with the confidence he had from having the tumor regression. This is, again, speaking to a significant body of evidence that speaks to ficerafusp alfa in combination with Pembro being able to significantly change the treatment paradigm for HPV-negative patients. Earlier last month, we presented additional data at ESMO Asia at our 750 milligram dose, showing again that ficerafusp alfa in combination with Pembro demonstrated strong response rates and a consistent safety profile compared to our 1,500 milligram dose. We also shared that the 1,500 milligram dose showed not only higher TGF-β inhibition within the tumor microenvironment, but we believe is driving a greater depth of response at the higher dose.
It is, again, this totality of data that supported the dose selection and moving towards the phase III portion of our study. What we've been able to show to date is that EGFR alone is insufficient to drive deep and durable responses. In fact, TGF-β is clinically relevant to allow for these long responses, and it is that is what is leading to a significant overall survival benefit. Our pivotal study, FORTIFY-HNS, was designed as a seamless phase II, III for the potential accelerated approval of ficerafusp alfa plus Pembro in the frontline HPV-negative recurrent and metastatic setting. As I alluded to, we started the study in the phase II portion in a 1:1:1 randomization, looking at 1,500 milligrams of ficerafusp alfa in combination with Pembro versus 750 milligrams of ficerafusp alfa in combination with Pembro versus Pembro monotherapy alone.
Today, earlier, we announced that we have selected the 1,500 milligram dose as the go-forward dose for the phase III portion of the study, but given this is a seamless study, the patients enrolled at the 1,500 milligram dose during the phase II portion of the study will continue on contributing to the pivotal efficacy analysis for both overall response rates in the interim analysis and overall survival for the final analysis, and so with that significant clinical momentum and the ability to focus now on the key execution of the study to allow for substantial enrollment by the end of this year and allow for an interim analysis by mid-2027, we are also today laying the groundwork for our commercial success. HPV-negative head and neck cancer is a sizable and growing global market.
It is known that in the major markets today, there are 50,000 annual incidence cases of HPV-negative recurrent and metastatic head and neck, and the head and neck market alone is believed to be greater than $5 billion by 2030. Ficerafusp alfa can change the treatment paradigm and create a paradigm shift by really focusing on two key areas to expand the already large and sizable HPV-negative head and neck market. We believe that having seen more than a doubling of response rates, we can address a growing patient population, but also, given that our duration of response is significantly greater than every approved therapy and molecule in development, we can grow the duration of response, expanding the market in both axes and allow for substantial growth of the head and neck market opportunity.
So today, we believe that ficerafusp alfa has the potential to achieve blockbuster status in head and neck cancer as the first and only EGFR TGF-β designed to drive tumor penetration and allow for deep and durable responses that could double the median overall survival for these HPV-negative patients. This is a large and growing market, and with our focus on building the commercial foundation this year, we believe we're well suited for a launch in early 2028. And again, as I highlighted, while our focus is on head and neck as our beachhead indication, we have always believed that ficerafusp alfa's potential was far beyond head and neck alone. And we have followed the science into other tumor types where there is a strong rationale for the inhibition of both EGFR and TGF-β, given the EGFR TGF-β biological fingerprint.
The first indication we are going into beyond head and neck is in metastatic colorectal cancer, where there is a strong rationale for the inhibition of both EGFR and TGF-β. We have preclinical data speaking to the potential in pancreatic cancer, and we'll go into these additional indications with financial discipline. TGF-β is known to be a central player in three key pathways in metastatic colorectal cancer. It is known to be a key axis in the EGFR resistance mechanism known as the epithelial-to-mesenchymal transition, or EMT phenotype, and is known to play a key role in angiogenesis, which drives metastasis, as well as play a role within the immunosuppressive tumor microenvironment. Today, typical treatments in colorectal cancer focus on either targeting EGFR or targeting anti-angiogenesis.
We believe that ficerafusp alfa can combine both of these approaches in a two-in-one approach that could allow us to address a much larger patient population and follow the science. Earlier last year, we initiated two proof-of-concept cohorts, both in ficerafusp alfa monotherapy and in combination with Pembro in third-line MSS RAS wild-type metastatic colorectal cancer. These patients, unfortunately, have limited options where standard of care only delivers about a 2% to 6% response rate. We hope to have early data in these cohorts in the second half of this year. So as we look towards 2026, we are making significant progress and are building significant momentum. Here are the key milestones we'll be looking at to continue to build growth and value inflection for the company.
As I mentioned earlier today, we selected 1,500 milligrams as our go-forward dose for the phase III portion of the study, which makes us believe that we can achieve substantial enrollment for Fortify by the end of this year to enable an interim analysis by mid-2027. In addition, we're focused on our pillar of commercial success by making critical commercial hires, including our Chief Commercial Officer this year. And we'll have a number of key data sets both within head and neck cancer as well as colorectal cancer that will continue to speak to ficerafusp alfa's potential as a pipeline within a product. I'd like to thank you all for your time today. And before I take any questions, I'd like to thank my colleagues at Bicara for their tireless work in delivering ficerafusp alfa to patients as rapidly as possible.
In addition, I'd like to thank our patients, the investigators, and their supportive care for trusting us with their care and for participating in our clinical trials. With that, thank you very much for your time.
Get Ryan up here.
Thank you very much for the very informative presentation. Obviously, a lot of good things in 2025 and a lot of great things to look forward to in 2026. I guess just first starting off, given the head and neck market is an increasingly crowded space, what do you believe is the most compelling and differentiated aspects of ficerafusp's mechanism of action?
When we designed this molecule, the idea was that there had been a number of combinations that had been studied in head and neck, but none had really led to significant benefits in terms of overall survival.
The key reason for that is they were trading higher response rate, but at the expense of durability. We have always believed that TGF-β would drive durability of response, and that is why we shared some important data sets at ASCO last year, really showing that even compared to competitors in development, ficerafusp alfa in combination with Pembro is delivering almost double, if not triple, the durability of response. That is what led to our outsized overall survival benefit.
Then just from a scientific evidence perspective, what do you believe in ficerafusp alfa's pipeline and program potential? You touched on it a little bit in the presentation, but if you could just elaborate a little bit more.
Yeah. What we know today is that there are a number of squamous cell carcinomas that tend to have very high EGFR overexpression and a known role for TGF-β.
We shared last year two important data sets in anal canal cancer and cutaneous squamous cell carcinoma that have similar biologies to HPV-negative head and neck. And we know from a history of the use of the anti-EGFR Cetuximab that colorectal cancer and pancreatic cancer and other types have a strong rationale as well. So we're following the science into other tumor types.
Great. And then I know it's top of mind for all of us, just given the announcement this morning. Can you just talk about that process of dose selection and to the extent you can, just those conversations you've had recently with the FDA and what the implications are going forward for the rest of the pivotal?
Happy to. And Ryan, please don't hesitate to add. The idea in designing a seamless phase II/III study was really the phase II portion would be done to get to a selected dose and satisfy Project Optimus within the FDA. We also had two open-label data sets of which we presented mature data at the 1,500 milligram dose at ASCO last year. Then we provided an update to our lower dose cohort of 30 HPV-negative patients at ESMO Asia last month. It was really the totality of the data based off of the TGF-β inhibition we were seeing and the consistency in response rates and efficacy that led us to selecting the 1,500 milligram dose for the phase III portion of the study. We were able to have an interaction with the FDA very recently that helped support that decision. Now we can move forward and implement that dose.
I think the one thing I would add to it is, as we were granted Breakthrough Designation in October of last year, and I think that really opened up a very productive dialogue with the FDA, which has continued through the recent interactions on dose selection. I think with the data that was submitted for the Breakthrough Designation, again, I think the compelling nature of what they were seeing from a durability perspective, again, going back to your first question around one of the key kind of differentiating elements is what we've been able to demonstrate with ficerafusp alfa is a durable response. We've tripled the responder population and are showing Pembro-like duration of response. And so I think that evidence has really supported not only our dialogue with the agency, but ultimately the dose selection that we were able to declare earlier this morning.
Great. And then I guess switching gears just a little bit. And again, I know you touched on it in the presentation, but just in terms of this commercial readiness and the preparations you're planning to make this year and beyond, can you just talk a little bit more about where those stand today, what you hope to accomplish this year? I know you said chief commercial officer. So again, to the extent you can provide any more details on what the plans are, that would be great.
I think Bicara has always differentiated itself in very well understanding the head and neck market opportunity. In particular, we have strong relationships both in the U.S. and abroad with the head and neck oncologists.
And so as we think about a potential launch in early 2028, we wanted to really build that foundation to set us up for success on the other side of an interim analysis where we could fully ungate our commercial buildup.
Yeah. And I think the data that we have been able to disclose thus far, I think it really, in our view, builds a compelling case for having a best-in-class molecule. And so with that, we'll be aggressively building for commercial success and building a corresponding organization that will be able to bring this drug to the U.S. market initially, ultimately, again, on an accelerated approval on ORR and want to be able to invest there and invest for success early.
Yeah. It speaks to really our bullishness and being able to change the treatment paradigm and in our molecule.
And then just one more on that too, just on the global market. In the presentation, you had $5 billion plus, I think, for the global market for head and neck by 2030. Can you just talk a little bit more about what underpins that market size and what you need to believe in order to believe that to be the market?
I mean, I think there's actually, it's a very large market today. We're seeing that just in Pembro sales alone. As we see that growth, Pembro only delivers a 19% response rate and a pretty short duration of response. I think the median time on treatment is six months. So if you can significantly grow the addressable patient population and the duration of response, you're actually exponentially growing the head and neck market, which is already believed to be multiple billions.
So we have very strong conviction that ficerafusp alfa can achieve blockbuster status in that setting.
And then what about just the, I guess, between the U.S. versus rest of world? Again, going back to the presentation, looked like 130K or so rest of world. And then I think Europe was the second largest and the U.S. the third largest. So can you just talk about sort of how you envision the globalization of ficerafusp alfa?
Happy to. So the first focus is our accelerated approval would allow for an earlier launch in the United States by early 2028. The rest of world would likely be on an overall survival endpoint approval, which would come shortly thereafter. Our focus is really on the key markets for head and neck. We know that ex-U.S., there is, of course, a high-prevalence smoking and chewing tobacco population.
You actually do see an even larger amount of HPV-negative patients. That number goes up to 90%, if not 95% in Asia, in the frontline market opportunity. While our focus today in the short term is on really building our commercial presence in the U.S., we do believe that there is significant potential ex-U.S. as well.
Great. And then I guess, can you just talk a little bit? I know we've talked a lot about ficerafusp alfa and head and neck and, again, mentioned in the presentation. Can you just talk a little bit about and just remind folks about the preclinical data in colorectal and sort of what excites you about that opportunity in particular?
Yeah. So I mean, we've seen recent data sets that have spoken to TGF-β being an important target in metastatic colorectal cancer.
There have been really no options that have delivered improvements in response rates beyond that 2% to 6% I alluded to in third-line cancer. But we have seen some next-generation TGF-β inhibitors and checkpoint inhibitors showing improved response rates. So I think there's really a biology there to signal-seek in third-line colorectal cancer. But we also have preclinical data in KRAS mutant populations, both in colorectal cancer and pancreatic cancer, that if you can combine with the KRAS inhibitor, you can actually address many of the resistance mechanisms to those inhibitors and see improved durability in combination with ficerafusp alfa. And so that's the biology we're looking to really address.
I'd say even more importantly than the preclinical data is I think the EGFR is a well-validated mechanism in tumor types like head and neck and CRC.
One of the key elements, though, is what is the secondary component adding to these agents? And I think the clinical data that we've established in head and neck is really beginning to show the attribution of TGF-β and the clinical benefit of that. We're seeing it in duration of response. We think that'll translate into other tumor types, including CRC. And so having that to build our confidence, not only in being able to build on already validated mechanism of EGFR, but now we're bringing TGF-β and we've got a lot of clinical evidence within the head and neck population that supports our conviction in other tumor types.
And then a lot of momentum, obviously, coming from 2025, starting off the year well in 2026. I guess, what do you foresee, if anything, really, to be any sort of headwind to the sort of successes or things you have to look forward to on the horizon?
I mean, our focus is on execution of the pivotal study. We want to deliver and build upon our momentum. And being able to select dose enables us to accelerate that enrollment and allow us to get to substantial enrollment by the end of this year. And so that's the key focus. And being financially disciplined as we continue to signal-seek beyond head and neck cancer.
And the decision on dose, I think, was a key catalyst for us. I think there were questions in terms of how quickly we would be able to do it, what those regulatory interactions were going to be, what the process to getting that decision.
Again, I think it was coming off of the Breakthrough Designation in October of last year, having that dialogue, maintaining that dialogue through the Q4, and being able to get to that decision really early. I think we now are in a position where we'll be randomizing and moving to the phase III component in a two-to-one randomization. I think really continuing to reinforce where we are and where we're headed. So I think some of those headwinds we were able to actually put behind us as we look forward into the remainder of the year.
And it's only January 12th .
Exactly.
And then can you just remind us what the cash runway guidance is that you guys have put out in the past?
So I believe we reiterated our cash runway guidance in our Q3 earnings, where we highlighted we had north of $400 million to fully fund our pivotal study through its confirmatory endpoint.
And then just last one for me, and then we'll open it up to the audience. Can you just sort of reiterate? And again, a lot of this you've talked about very enthusiastically. Just reiterate what your key growth drivers are for 2026 and beyond.
Happy to. I mean, it's really focused, again, on frontline recurrent and metastatic HPV-negative head and neck, getting to that interim analysis to support an accelerated approval, building that commercial foundation, but also being able to deliver on ficerafusp alfa's pipeline in a product by sharing early data in colorectal cancer and other head and neck subsets where we think we can very much grow beyond just frontline HPV-negative head and neck.
Don't see any. No questions. So we have a shy crowd today. I guess if there's just any other closing thoughts that you have for those in the room, those online, that would be great.
We see 2026 as a key momentous year for Bicara. We're building on our significant momentum from last year, being able to start the year off strong by selecting dose and moving to the phase III portion of the study and delivering now on execution. So we're thrilled to be here today. Thank you.
Great.