Right. good afternoon everyone. Tyler Van Buren here, Senior Research Analyst at TD Cowen. Thank you very much for joining TD Cowen's 46th annual health care conference. For our next session, we have a hybrid presentation and fireside chat style Q&A with Bicara, and it's my pleasure to introduce Ryan Cohlhepp, the President and COO. Ryan, privileged to have you here. Thank you very much for joining us. feel free to get started on the presentation.
Great. Thank you, Tyler, and thank you to the Cowen team for the invitation at the meeting this year, and your continued support. I will be making forward-looking statements in my presentation today. Please refer to the SEC for our current risk factors. Bicara Therapeutics is a company focused on developing bifunctional antibodies. Our lead program, FICERA, is exemplary of this as a EGFR TGF-beta bifunctional. TGF-beta has been used and explored across a number of different studies, but the main limitation from our perspective in developing FICERA was the inability to get an adequate levels of TGF-beta to the tumor and affect the overall tumor microenvironment. We believe we have overcome this, and I will demonstrate that both with our clinical data as well as our translational data later in the presentation.
Head and neck cancer is a fibrotic immunosuppressive solid tumor, we have also, with a deep understanding of the overall biology in head and neck cancer, have been able to evaluate that HPV-negative is a distinct and compelling clinical subset of head and neck cancer. We know that HPV-negative head and neck cancer has increased levels of EGFR expression, elevated levels of TGF-beta in the serum, and a high rate of therapeutic resistance. In 2026, we plan to drive growth and value inflection, first with the execution and strategic development plan for FICERA in the frontline HPV-negative recurrent metastatic head and neck. Again, we initiated the FORTIFY trial in February of last year and continue to gain momentum in the number of sites we are activated, as well as the number of patients that are enrolling in the trial.
We are preparing for our commercial success and will be building out the leadership team of our commercial organization in 2026 and expanding FICERA's potential while maintaining financial discipline as we consider the opportunity for FICERA outside the head and neck tumor type. Last week, we had a additional capital raise, which will continue to support that commercial build and beginning to un-gate some critical hires for us in 2026, as well as initiating an alternative dosing schedule, which will allow us to get to a maintenance regimen of every three weeks. As you look at the significant unmet need in the recurrent metastatic setting of head and neck cancer, today's standard of care, either with pembro monotherapy or in combination with chemotherapy, only give somewhere between a 19% and 36% response.
What you can see is while you are able to increase the response by adding chemotherapy, the overall median overall survival continues to remain low and that unmet need remains significant. As you look at the data that we have presented historically with 1,500 mg weekly, again, as a reminder, as we initiated our trial, our pivotal trial, we were doing dose optimization of both 750 mg and 1,500 mg and have ultimately been able to align with the FDA that 1,500 mg is a go forward dose and have transitioned to the phase III component of our trial at 1,500 mg.
You see a confirmed overall response rate of 54%, deep responses with 80% of our responders achieving a depth of 80% or greater, which has given us a complete response rate of 21% and rapid response with median time to response of 1.4 months. What you also see in the figure in the lower right corner is that we are seeing response rates regardless of CPS score. We are seeing high response rates in both the CPS 1-19 as well as the CPS greater than 20 and good response rates regardless of the overall size of tumors. We're seeing good response rates in small tumors as well as those patients that have large tumors exceeding 70 mm. We also have been able to demonstrate a high duration of response.
One of the things that we have been able to deliver with this molecule is increasing our responder population meaningfully by almost 3x while at the same time maintaining immunotherapy-like duration of response. You see that FICERA with our 1,500 mg dose has been able to demonstrate a 21.7 median duration of response, again, far outpacing other EGFR therapies. The question has often been does that matter? What we've been able to demonstrate here is that in those patients exceeding or having an overall shrinkage of 80% or more, you're seeing the Kaplan-Meier curves separate for duration of response, progression-free survival, and overall survival, demonstrating that duration of response and DOR is meaningful and a predictor of outcomes, particularly as it relates to long-term outcomes like median overall survival.
Which really begins to characterize the potential that FICERA can bring to the recurrent metastatic head and neck population. Again, we've been able to triple the increase in overall response, have a 3x increase in duration of response, and have been able to double the median overall survival. From a tolerability perspective, you see on-target AEs of acneiform rash consistent with EGFR mechanism. You also see the hypothesized TGF-beta-related AEs, which include the transient grade 1-2 mucosal bleeds and epistaxis or nosebleeds, which again are both hypothesized to be on target with TGF-beta. For our pivotal trial, the FORTIFY trial, again, which was initiated last year in February and dosed our first patient February of last year and continues to gain momentum.
We initiated the trial as a three-arm trial where we explored 750 mg of FICERA plus pembro, 1,500 mg of FICERA plus pembro, and then a pembro monotherapy control arm. In January of this year, we announced that we had aligned with the FDA and are moving forward with the 1,500 mg as our weekly dose and have subsequently dropped the 750 mg arm and continue to enroll now in a 2-to-1 randomization of FICERA versus pembro monotherapy. As you look across the experience, we had presented the 1,500 mg data at ASCO of last year. The 750 mg data was published at ESMO Asia in December of last year. Just recently, a week and a half ago, we presented the 2,000 mg every two weeks. You see a consistency of response rate across all three doses.
Again, consistent mechanistically and biologically, recognizing that at doses as low as 750 mg, we have fully saturated the EGFR target and are then looking for a differential activity and the TGF-beta-related activity for those doses in excess of 750 mg. We will subsequently be updating the durability of these three cohorts at a future medical meeting, which will, again, consistently demonstrate that FICERA stands alone in being able to deliver a duration of response, again, outside of other EGFR molecules. What I want to characterize here is, again, in the left with phospho-SMAD2, these are our tumor samples and paired biopsies. And what we're able to demonstrate is the impact that you're seeing with TGF-beta. phospho-SMAD2 is a downstream marker of TGF-beta.
You see across all doses, again, a reduction in phospho-SMAD2 levels, again, being able to demonstrate the increase of activity you're getting from TGF-beta as you continue to dose escalate and the dose responsiveness that you're seeing with TGF-beta across higher doses. The totality of our phase I data across all doses and schedules, again, has built a rationale and support for our ability to extend the administration schedule. The key premise and underlying what we're looking to accomplish with our dosing here is to be able to expand our data to reinforce our established clinical differentiation. Again, we have announced on our corporate call last week that we will have a loading phase where we will load with 1,500 mg weekly for a period of time.
Then we'll transition to a maintenance phase where we will be able to extend the interval at an every three-week dosing, which allows us to synchronize with the dosing of KEYTRUDA or pembrolizumab. This will position us to have best-in-class from an efficacy perspective. We will be able to have a preferential tolerability profile while at the same time having a best-in-class administration schedule in our maintenance phase. As we think about the potential for FICERA, we have the ability with the response rates that we've seen as well as the durability of response that we've seen to grow this market substantially by both increasing the duration of response and the overall response rate, seeing a meaningful increase in the overall market potential for an EGFR therapy in the head and neck category. Beyond head and neck, we continue to explore this molecule in other indications.
We have ongoing cohorts that we're enrolling in in colorectal cancer and anticipate being able to disclose that data in the second half of this year. There is also a strong mechanistic rationale to consider this molecule in PDAC and we'll be looking at signal-seeking studies in PDAC in the future. In 2026, it will be a pivotal and critical year for Bicara. We have already accomplished our alignment with the FDA as it relates to dose selection for the pivotal trial. We have presented our 2,000 mg data at the head and neck meeting a week and a half ago, again, building a future plan for less frequent dosing. Again, later this year, we will have our CRC data in the second half of this year. The trial will be substantially enrolled, which will enable us to have top-line data mid-2027.
We will, again, be building critical infrastructure for our commercial launch, again, that we plan in 2028. With that, I'll transition to the fireside and look forward to further questions.
Great. Thank you very much for the presentation, Ryan. Naturally we'll start off obviously with head and neck and phase II/III ongoing FORTIFI-HN01 trial. Question, you obviously get quite frequently, but how is enrollment progressing, and when could we get to completion of enrollment, and when should we expect to potentially see that accelerated, overall response rate data from pivotal?
You know, enrollment's going incredibly well. You know, again, we, you know, in late last year we were able to open Europe, that also is a meaningful catalyst. Again, the number of sites that are able to come on board once you have activated Europe. We also will be opening Asia Pac as well as South America. Again, I think the momentum and overall pace of enrollment is increasing dramatically. Earlier this year, we guided to the fact that we would have top line data for response rates mid-2027. You know, again, I think that sets us up for a 2028 approval with that data.
Do you guys have any initial indication as to what the split of enrollment between U.S. and ex-U.S. might look like or?
Yeah. I mean, again, you know, I think the. You know, as you look at the overall recruitment footprint, I think consistent with a lot of trials, you know, we would expect probably around 60% of overall enrollment to be outside the U.S. Again, I think we're tracking to that with our enrollment as we are bringing other geographies on board.
Great. As we think about that accelerated interim overall response rate.
Mm.
Endpoint or readout, what do you believe you guys need to show on that in order to file for Accelerated Approval?
I mean, we've had a number of interactions with the FDA, consistently what the FDA has guided to is a doubling of the control arm. Whether you look at, I think the one of the biggest data sets obviously is KEYNOTE-048, which showed a 19% response rate in the CPS one and greater population. Slightly more contemporary to that was the LEAP-010 trial, which showed around 25%. Either way, you know, we feel really confident in our response rate data. You know, one of the things that we benefited from is, if you look across and you pull the three datasets, the 750, the 1,500 mg, and even the 2,000 every two weeks, you now have, you know, the consistency across 90 patients plus.
We have really been able to decrease and tighten the confidence interval. We have a high degree of confidence regardless of whether the control arm is at 19 or 25, our ability to, you know, meet the threshold required by the FDA.
Great. What about overall survival at that interim? Are they gonna take a look at overall survival?
Yeah, we fully anticipate they will. Again, you know, you look at the LEAP-010 data and where you have the Kaplan-Meier crossed there at around 12 months. What we would fully anticipate, you know, regulators, you know, I think particularly the FDA, you kinda wanna make sure that the curves continue to separate. I do think that that's where, you know, the selection of an HPV-negative population, by itself is to our benefit. You know, I fully expect. If you look at the real world data, pembrolizumab 8 and HPV-negative, you know, has delivered around nine to 10 months.
We do expect that you'll have, you know, probably, you know, an earlier separation of the curves between ourselves and pembrolizumab control arm in the FICERA trial, relative to some of the other trials that are being conducted, again, because of the selection of HPV-negative. I fully anticipate the FDA will look at that data. They'll do their own analyses for overall survival, and we feel good about where that's likely to trend at the time that we do our submission for ORR.
As we think about the fully mature kind of median OS confirmatory endpoint, is there a OS hazard ratio that you all are targeting or you think is necessary or a minimum hazard ratio and, I guess, you know, how are you thinking about... I guess either that or the treatment benefit that you have to show relative to what you just mentioned?
Yeah. I mean, again, you know, I think we're, you know, we've powered our trial, you know, in a way that, you know, is gonna be clinically meaningful. You know, I think the, what you will hear from KOLs, you know, relative to what's available today is that, you know, a two to three-month increase is clinically meaningful. We believe that we have the potential, you know, given with, our durability and our depth that we should, you know, be able to surpass that and, you know, think that we're positioned to be able to do that.
You know, and I think particularly again, the selection and doing a trial on HPV-negative only, I think sets us up to be able to differentiate and show a best in class profile as it relates to overall survival. You know, I think we have been able to characterize the contribution of TGF-beta relative to the secondary components of some of the other agents out there and feel really good that the TGF-beta is gonna be able to differentiate and to set FICERA apart.
Great. Given the recent decision to move forward with the 1,500 mg dose, I think this is a move that we all anticipated for some time. You just needed to generate the final data, maybe just elaborate on your confidence in moving forward with the 1,500 mig and not the 750 and any sort of FDA feedback you got on that.
Yeah. A high degree of confidence. I mean, I agree with you. I mean, I think, you know, 1,500 mg, you know, very early onset, a very high bar. So, you know, 750 was gonna have to really deliver something, you know, outstanding in order to to overtake 1,500 mg. You know, what I can say is, you know, I think we've really benefited from having the open label dataset, for both 750 and 1,500 mg to look at the two. It was part of the data the FDA saw that granted us Breakthrough designation in October of last year. The FDA also was able to look at the early patients in the FORTIFI trial.
They had access to that data, when we ultimately made the decision, and the FDA was completely supportive of moving forward with 1500 mg. It was a very favorable interaction and again, you know, with FDA fully supporting the selection of 1500.
Great. The presentation you gave recently when you showed the 200 mg data was interesting, and you just reiterated here, but 750, 1,500, 2,000, very similar response rates.
Yeah
Time to response. Maybe, you know, kind of a dose-related change in kind of depth of response and durability that we're seeing. Which, you know, on one hand could be a little confusing to some because it's 2,000 mg, which is a higher dose, but exposure is stretched out over two weeks instead of one week. I don't know, curious to get your thoughts on that, why, you know, really are seeing greater depth and durability with 2,000, and can we get data from all three of these potentially at ASCO or relatively?
Yeah
Soon that kind of reinforces this?
Yeah. We're gonna continue to update the data. I think, you know, we wanna, again, be able to get the data out there that supports the role that our drug has around durability, and you're seeing it across different doses. You know, in terms of, you know, the data that we presented at 2,000 mg every two weeks, I think the 750 data set, the 1,500 mg data set, and the 2,000 really allowed us to probe and to characterize the contribution of not only EGFR, but TGF-beta. I think it paints a really nice picture. You see between 750 and 1,500 mg that you see greater depth at the higher dose. At 2,000 mg, our median depth is 100%.
I think what that data tells us is that you're seeing incremental dose responsiveness on the TGF-beta side of this molecule. As you go higher, you're able to drive more depth. You know, I think again, with that data, you know, and with depth brings durability. Again, which sets us up nicely for a paradigm where we're gonna go with 1,500 mg for a period of time, and then transition to the maintenance phase at a higher dose every three weeks. Again, I think what that does, what we know is you look at the 1,500 mg data where we've got the greatest amount of follow-up. We know the vast majority of patients are in response at six weeks. Our median time to response is 1.4 months.
We also know that most patients have reached their maximum depth within 12 weeks. We're gonna hit the tumor hard. We're gonna get rapid responses. We're gonna get deep responses and then be able to transition to a maintenance phase to maintain our durability and give the patients the convenience of coming in every three weeks when they're coming in for their pembro dosing. Again, I think we have been able to position by our understanding of our data so well across those three different cohorts to be able to optimize this drug for, you know, superior efficacy and convenience.
Got it. It sounds like you guys can achieve the best response in the first quarter with weekly 1,500 migs, and then potentially after that move to the every three weeks, which lines up perfectly with pembro.
Yeah. And what we know too, again, you know, going back to the rationale for this molecule, we designed FICERA to, you know, using EGFR to get to the tumor. You think about, again, you know, as you debulk and you decrease tumor size, you've got way less of a TGF-beta sink, when you get six to 12 weeks in. Our ability to stretch that interval knowing that we need to get less drug on board once we have significantly reduced the tumor size, again, you know, with a very keen understanding of the biology and the mechanism of our drug, again, we've got the ability to dial this in for an optimal outcome.
Got it. Okay. obviously, there's been a lot of focus on you guys and Mirati now Genmab's program. you know, obviously, if this is a large market, two products can be successful.
Mm-hmm
C urious to understand how large you think the frontline head and neck opportunity is at the moment.
Yeah. I think it, you know, again, you know, Merck has guided, you know, multiple times to head and neck being about 10%-15% of pembro sales. Global sales are probably around $2.5 billion. That's in a market where only one in five patients are responding to pembro monotherapy, and they're getting about five-six months of duration. You think about, you know, the data that we've demonstrated, you know, the possibility of keeping, you know, a large proportion of patients on for a year or more, and increasing the responder population by almost 3x. I think this very easily is a $5 billion+ market across, as you think about, you know, this class. It's a big market.
I think there's a clear recognition of it. you know, obviously, you know, I think, you know, there's a greater recognition of the size of this market than what there was even a year or so ago.
What about from a competitive landscape perspective, amivantamab? They had some data that people, you know, were interested in at ESMO. We've gotten some more data recently. Curious to hear how you're thinking about how amivantamab might impact the market and your competitive position.
I mean, I think, you know, obviously they've taken a different, trial approach with a registrational trial. They're going on top of chemotherapy. I think it probably will lead to a slightly different population being recruited than what, you know, we're gonna recruit in FORTIFI. You know, I think, you know, one of the unknowns there ultimately is, you know, how their, how their overall survival's gonna play out. What we've seen in a couple of cases now, you know, with pembrolizumab plus chemo, but also lenvatinib plus pembrolizumab, toxic regimens often don't have great duration of response which often leads to minimal impact in overall survival. The addition of chemotherapy to pembrolizumab in the KEYNOTE-048 trial, while increased the response rate by 17%, you only saw a 1.3-month increase in overall survival.
In the case of lenvatinib plus pembrolizumab, you actually, it was inferior because patients discontinued so early. I think it's early. We have to see ultimately the tolerability profile of ami. What we're hearing is many patients are having to come in to get weekly supportive care which really begins to deteriorate the convenience advantage of every three weeks. Again, I, you know, we continue to believe that we've got the best program as it relates to both efficacy and safety and then being able to realize the convenience advantage of every three weeks by, you know, having a durable drug that people are able to stay on.
Great. In the last couple minutes, maybe we'll just ask one question on CRC and one question on PDAC. Just CRC, the update you're gonna have later in the year, can you help set the expectation for what type of patients you're treating and what would be an impressive outcome in those patients?
Yeah. We've got two cohorts open. We've got both in the third line setting. One is a monotherapy cohort, the other is in combination with pembrolizumab. You know, as you look at the, obviously the third line setting, it's a tough population. You know, as you look there, I think the current standard is Lonsurf, single-digit response rates. You know, we saw data at ESMO from Incyte which was their, using their TGF-beta PD-1, showed a 15% response rate. Again, that's in the absence of EGFR targeting. Again, I think we recognize the challenge in a third line setting. We are looking for a signal there that will support us, you know, developing and potentially moving further up line.
Okay. Finally, why are you guys excited about PDAC, and what's the next steps for that program?
Yeah. I think PDAC, you know, One of the things that's always been important to us at Bicara is going into tumor types where there was a rationale for both EGFR and TGF-beta. You know, we wanna, you know, seek those tumors. PDAC is one of those. You know, obviously it's a rapidly evolving landscape, and so one that we're watching closely to determine what the appropriate place to go in, whether it's, you know, and what the right combination is. You know, I think obviously will be a combination play for us. So we're watching that and, you know, figuring out what the appropriate partner is to, you know, go into that setting.
Sounds good. With that, we'll go ahead and wrap up. Ryan-
Great.
Thank you very much for your time.
Thanks, Tyler.
Thanks, everyone.