Good day, and thank you for standing by. Welcome to the Bicara MHNCS Clinical Call Update. At this time, all participants are in a listen-only mode. After the speaker's presentation, there'll be a question-and-answer session. To ask a question during the session, you'll need to press star one one on your telephone. You will then hear an automated message advising your hand is raised. To restore your question, please press star one one again. Please be advised that today's recorded call is being recorded. I would now like to turn the call over to your speaker for today, Jenna Cohen, Chief Corporate Affairs Officer of Bicara Therapeutics. Please go ahead.
Thank you, and good morning, everyone. It's a pleasure to welcome you to Bicara Therapeutics' conference call. Yesterday, coinciding with the data presentation at the 2026 Multidisciplinary Head and Neck Cancer Symposium by Dr. Dan Zandberg of the UPMC Hillman Cancer Center, we issued a press release highlighting data from that presentation. You can access the press release, as well as the slides that we'll be reviewing today, by going to the Investors section of our company website. Before we begin, please note that the statements made during the call today will include forward-looking statements for purposes of the Safe Harbor Provisions under the Private Securities Litigation Reform Act of 1995, as amended.
These forward-looking statements are based on our current expectations and assumptions, and actual results may differ materially from those indicated during this call as a result of various important factors, including those discussed in the Risk Factors section of our most recent quarterly report on Form 10-Q for the period ending September 30th, 2025, which is on file with the Securities and Exchange Commission. Any forward-looking statement made on this call represents our views only as of today, and except as required by law, we disclaim any obligation to update or revise any forward-looking statements. Joining us on the call today are Claire Mazumdar, Chief Executive Officer, and Dr. Bill Schelman, Executive Vice President of Clinical Development at Bicara Therapeutics.
Claire will review ficerafusp alfa, or FICERA, the first and only EGFR TGF-β bifunctional antibody that is being studied in the pivotal FORTIFI-HN01 trial in first-line recurrent metastatic HPV-negative head and neck squamous cell cancer, or HNSCC. Bill will review the preliminary safety and efficacy data from a less frequent dose of ficerafusp alfa, 2,000 mg dosed every other week in combination with pembrolizumab, presented yesterday at the conference. Together, Bill and Claire will outline our plan to explore a less frequent dosing regimen for ficerafusp alfa. Ryan Cohlhepp, President and Chief Operating Officer, and Tanya Green, Chief Development Officer, are also on the line and will join us for Q&A. I'll now turn the call over to Claire.
Thank you, Jenna. Good morning, everyone, and thank you for joining the call this morning. We are thrilled to be in Palm Springs this morning after announcing another significant milestone in our development program for ficerafusp alfa yesterday during the Multidisciplinary Head and Neck Cancer Symposium plenary presentation. Not only have we further expanded the clinical experience observed with ficerafusp alfa in frontline recurrent and metastatic head and neck squamous cell carcinoma to 90 total patients, where we collectively observe a generally well-tolerated safety profile and consistent efficacy with rapid and deep responses. But we now also have clinical data in hand, which supports further exploration of an alternative dosing regimen for ficerafusp alfa. By exploring less frequent dosing, we hope to offer patients and clinicians optionality by maximizing convenience, particularly when dosed in combination with pembrolizumab.
We believe we can achieve this while maintaining the rapid, deep, and durable responses that are the differentiating hallmarks of ficerafusp alfa's clinical profile. Ficerafusp alfa is the first and only bifunctional EGFR-directed antibody combined with a TGF-β ligand trap designed to drive tumor penetration. One of the key challenges in the treatment of many solid tumors has been the inability of immune cells to penetrate the tumor and eliminate the cancer. Ficerafusp alfa was specifically designed to combat this challenge. The EGFR arm helps to localize TGF-β inhibition to the tumor to break down barriers in the tumor microenvironment. In doing so, ficerafusp alfa enables tumor penetration specifically by reducing fibrosis, immunosuppression, and T-cell exclusion, and reverses TGF-β-driven resistance mechanisms that are upregulated upon treatment with EGFR or checkpoint inhibitors. Taken together, these effects drive deep and durable responses that may lead to better outcomes and survival for patients.
Despite the advancement of immunotherapy, there remains a significant unmet medical need for improved treatment outcomes for patients with HPV-negative head and neck cancer. The current standard of care, pembrolizumab, provides response rates of only 19% as a single agent and 36% in combination with chemotherapy, but median overall survival remains poor at only 12-13 months. Importantly, for people living with HPV-negative disease, real-world data consistently show worse survival outcomes as low as seven to nine months compared to the overall population when treated with standard of care. Our data to date has demonstrated that ficerafusp alfa can improve outcomes compared to standard of care pembrolizumab, chemotherapy. Ficerafusp alfa has shown a 2- to 3-fold improvement in response rates, complete response rate, duration of response, and overall survival.
This is a striking advance in the treatment of HPV-negative head and neck cancer, and we know of no other therapy that has demonstrated these results in such a difficult-to-treat tumor type. Checkpoint inhibitor combination regimens, both approved and in development, can deliver strong response rate, but at the expense of durability, leading to little to no impact on overall survival benefit. The addition of ficerafusp alfa to pembrolizumab maintains the strong immunotherapy-like durability of almost 22 months, more than triple the median duration of response of pembro plus chemotherapy at just 6.7 months, while also improving long-term clinical outcomes, including survival. This durability of response, driven by the TGF-β targeting mechanism, clearly distinguishes ficerafusp alfa from other investigational agents in head and neck cancer. As a reminder, our pivotal study, FORTIFI-HN01, began with a phase II dose optimization portion to satisfy the Project Optimus requirements from the FDA.
Patients were randomized to either receive 1,500 mg of ficerafusp alfa weekly in combination with pembro, 750 mg of ficerafusp alfa weekly in combination with pembro, or placebo plus pembro monotherapy. Just last month, we announced that we had reached alignment with the FDA, that 1,500 mg of ficerafusp alfa, dosed weekly in combination with pembro, is the go-forward dose for the phase III FORTIFI-HN01 pivotal study. We have officially moved into the phase III portion of the study, and patients are being randomized in a 2-to-1 randomization to 1,500 mg of ficerafusp alfa with pembro or to standard of care pembrolizumab. Importantly, in this seamless design, enrollment never paused. The first patients treated with the 1,500 mg dose will be included in both the ORR analysis for a potential accelerated approval and in the final overall survival analysis to support a full approval.
Bicara has built incredible momentum in just the first two months of this year. We initiated the phase III portion of our pivotal study earlier than anticipated, and today we can share more about our plan to explore less frequent dosing for ficerafusp, to broaden patient and clinician optionality while maintaining the differentiated efficacy that is a hallmark of ficerafusp's clinical profile, driven by the underlying mechanism of action with TGF-β inhibition. With that, I'll hand the call over to Bill to review today's data.
Thanks, Claire. On behalf of my clinical and medical colleagues at Bicara, it's a pleasure to join you today to review the data that was shared by Dr. Dan Zandberg of UPMC at the 2026 MHNCS plenary session. I want to extend a heartfelt thank you to Dr. Zandberg and all other investigators and patients taking part in the phase I-b and FORTIFI studies for their contributions to our program. Today's presentation highlights preliminary data from our phase I-b expansion cohort, evaluating 2,000 mg of ficerafusp alfa every other week in combination with pembrolizumab. This cohort enrolled frontline patients with HPV-negative, recurrent or metastatic head and neck squamous cell carcinoma, whose tumors had a CPS score of ≥1.
It's important to note that this exploratory cohort is evaluating both a higher dose of ficerafusp alfa than is currently being used in the pivotal study and also a less frequent dosing regimen. These patients present with a high disease burden and poor prognosis, making them fundamentally different from HPV-positive patients. As shown in the demographics and baseline characteristics, this cohort includes a significant proportion of patients with bulky tumors, many measuring 5 cm or greater, underscoring the aggressive nature of HPV-negative disease. This biology translates into markedly different clinical behavior. More than 80% of patients in this HPV-negative cohort had local regional recurrence, either alone or with distant metastases, a hallmark of this disease.
Finally, the demographics and baseline characteristics in this cohort are consistent with our other first-line HPV-negative cohorts treated with ficerafusp alfa at both 1,500 mg and 750 mg weekly, as well as with prior registrational trials like KEYNOTE-048 and real-world clinical practice. This consistency reinforces the relevance and applicability of our data to the broader treatment landscape. In terms of safety, similar with what has been previously reported, the combination of ficerafusp alfa and pembrolizumab continues to demonstrate a well-tolerated safety profile. As we escalated to 2,000 mg, we have not seen any new adverse events, and the severity of expected events has remained consistent with prior experience.
As expected with this combination, the safety events fell into two main categories: EGFR-related events, such as rash, which is consistent with what is typically observed with other approved EGFR antibodies like cetuximab, and potential TGF-β-related events, including mild epistaxis and gingival bleeding, which, when observed, resolve quickly without intervention. There was one Grade 4 event of an electrolyte imbalance, hypokalemia, that was possibly related to ficerafusp alfa, which resolved with standard replacement therapy and did not require ficerafusp alfa dose modification. There were no treatment-related deaths, and discontinuation rates were low. Overall, the safety profile of ficerafusp alfa plus pembrolizumab in this cohort was manageable and generally consistent with ficerafusp alfa's established profile at other doses administered weekly. Preliminary efficacy data is shown here: 2,000 mg of ficerafusp alfa every other week demonstrated consistently high response rates and, importantly, rapid and deep responses.
Notably, there was a 48% confirmed response rate and an 85% disease control rate in the 27 efficacy-evaluable HPV-negative patients. As we look at different patient subgroups, we continue to see robust and consistent responses across the CPS populations, including in the CPS 1-19 population, as well as consistent clinical activity in patients with both low and high tumor burden. Even at less frequent dose, we see deep and rapid responses that are the hallmark of the ficerafusp alfa clinical profile. Seventy-seven percent of responders achieved a deep response of greater than 80% tumor shrinkage, and we see a striking 26% complete response rate. The median time to response was rapid at 1.6 months.
We continue to believe that the strong depth of response ties back to ficerafusp's unique mechanism of action, whereby TGF-β inhibition enables tumor penetration that is absolutely critical to driving durability and long-term survival. We know that deep responses yield durable responses, and that's observed in this cohort as well, even when ficerafusp alfa was dosed less frequently. The results on this slide are notable. While the overall data for this cohort are still maturing, as of the data cutoff, the vast majority of responders, and in particular, the deep responders, remained in response, including several beyond 20 months. When patients are deriving benefit from a treatment, they stay on therapy.
These data clearly show that even when ficerafusp alfa is given at a higher dose, but less frequently, patients are staying on therapy longer than what has been observed with other pembrolizumab combination approaches, suggesting sustained efficacy with no trade-off on tolerability. Now, with a growing body of PK translational and clinical data, including the 90 patients at varying doses and schedules, we have established a clear understanding of the exposure-response relationships of both the EGFR and TGF-β components of ficerafusp alfa. These insights have positioned us to identify a dosing schedule to optimize efficacy, safety, and schedule. I'll now hand the call back to Claire to talk more about our strategy here.
Thank you, Bill. Now that we've reviewed the clinical data from yesterday's plenary at MHNCS, I'd like to outline some additional data that our team has been looking at in-house to inform our plan to explore an alternative dosing regimen, which includes a loading- phase and every three-week maintenance phase for ficerafusp alfa, alongside our pivotal study, as well as what that plan is. Last December, at ESMO Asia, we presented initial biomarker data showing a clear relationship between higher ficerafusp alfa dose levels, increased TGF-β inhibition in the tumor, and deeper clinical responses. Today, we are sharing an updated analysis. On the left, you see paired tumor biopsies from patients treated with ficerafusp alfa plus pembro, taken at baseline and at cycle 2, day 1. These samples directly measure intratumoral TGF-β inhibition via phospho-SMAD2, the downstream biomarker of TGF-β activity.
On the right, we show blood-based cytokine data measuring systemic immune activation across all three ficerafusp alfa dosing regimens. Importantly, the trends are consistent. Higher but less frequent dosing continues to drive robust TGF-β inhibition and increased immune activation. These results support advancing a less frequent dosing schedule for ficerafusp alfa, as we can maintain the TGF-β inhibition that we believe underlies deeper and more durable responses, while potentially improving patient convenience and compliance. The biomarker data is important because it demonstrates that greater TGF-β inhibition at higher doses of ficerafusp alfa, regardless of schedule, drives deeper tumor penetration. The paired biopsies shown here highlight the clear increase in T- cell infiltration from baseline to cycle 2, day 1, with ficerafusp alfa at 2,000 mg every other week. This is what meaningful tumor penetration looks like, and we know now that ficerafusp alfa can achieve this both at weekly and less frequent dosing.
Next, we evaluated whether a less frequent dosing schedule of ficerafusp alfa could still sustain TGF-β inhibition in the tumor microenvironment, critical for the deep and durable responses that define ficerafusp alfa's clinical profile. When comparing median depth of response and the proportion of deep responders at the same 24-week follow-up, the data are clear. The highest dose tested, 2,000 mg, delivers deep responses even when dosed less frequently than the pivotal 1,500 mg regimen. These findings strengthen our conviction that robust TGF-β inhibition drives the depth and durability seen to date, and that a less frequent dosing regimen can achieve equal or greater clinical impact. In summary, data presented to date tell us that higher but less frequent 2,000 mg dose of ficerafusp alfa delivers, one, a well-tolerated safety profile aligned with what we've consistently seen with ficerafusp alfa plus pembro.
Two, comparable or greater TGF-β inhibition and cytokine activation, supporting durable immune engagement. And three, rapid and deep responses reflecting ficerafusp's mechanism of enhancing tumor penetration through TGF-β inhibition. Taken together, these data give us a clear foundation for pursuing less frequent dosing. Our priority is to maintain ficerafusp's potential best-in-class profile, defined by depth and durability of response, while creating practical dosing options for patients and providers. While our market research confirms that ficerafusp's differentiated efficacy will drive adoption, we believe it's important to create optionality for patients and clinicians. The totality of clinical and PK/PD data signals a straightforward path to offering additional dosing flexibility, especially given real-world use alongside pembrolizumab. Ficerafusp alfa's bifunctional design, using EGFR targeting to localize TGF-β inhibition directly within the tumor microenvironment, drives rapid tumor penetration and shrinkage. As tumor burden decreases, the level of TGF-β inhibition required to maintain response also declines.
This biology creates a natural opportunity to extend the dosing interval after the initial loading phase, while preserving potency. By optimizing ficerafusp's relative dose intensity over time, we can better match treatment to the evolving needs of both the tumor and the patient. We've now studied ficerafusp alfa at three doses and across two dosing regimens. These data give us a robust, coherent understanding of ficerafusp alfa's kinetics, and our additional pharmacokinetic and pharmacodynamic modeling further strengthens this picture. The findings show that TGF-β inhibition drives rapid and deep responses within the first few cycles, and that this inhibition remains sustained even with less frequent dosing. In other words, long-term weekly administration is not required to maintain the level of inhibition associated with deep, durable responses.
Building on the biology and the totality of the data, we plan to develop ficerafusp alfa with a dosing regimen that begins with a loading phase and transitions to an extended interval every three-week maintenance schedule. This approach leverages ficerafusp alfa's mechanism to maintain strong pathway engagement while reducing dosing frequency. We will provide further details on this loading maintenance regimen once we've achieved regulatory alignment on this approach and development strategy. While we expect to initially seek accelerated approval for ficerafusp alfa with a 1,500 mg weekly regimen from FORTIFI-HN01, we believe that a parallel randomized study will allow us to have a loading and maintenance data available by the time of potential approval, creating a compelling path for earlier adoption of this streamlined regimen.
In summary, we are very pleased with the safety and efficacy observed at a higher and less frequent dose of ficerafusp alfa at 2,000 mg every two weeks. We remain confident that the depth of response observed with ficerafusp alfa reflects its differentiated mechanism. TGF-β inhibition promotes effective tumor penetration, setting off a robust immune response that underlies the durability and long-term benefit we are seeing. That clinical differentiation can be maintained as we work to expand patient choice around dose regimen. Before I turn over to the operator, I'd like to take a moment to thank everyone who is or has participated in our phase I-b and FORTIFI studies for putting their hope and trust in ficerafusp alfa and Bicara.
Our clinical trial investigators who have been thoughtful collaborators, particularly Dr. Dan Zandberg, who presented these data yesterday here in Palm Springs, and the passionate team of people at Bicara, who are working relentlessly to bring ficerafusp alfa to the world as quickly as possible. And with that, we'll take some questions. Operator?
Thank you. As a reminder, if you would like to ask a question, please press star one one on your telephone. If you would like to remove yourself from the queue, press star one one again. We also ask that you please wait for your name and company to be announced before proceeding with your question. One moment while we compile the Q&A roster. The first question for today will be coming from Tyler Van Buren of TD Cowen. Your line is open.
Hey, guys. Good morning, and thank you very much for the very interesting data presentation. You know, one of the more interesting statements in the release was the statement that preliminary efficacy data demonstrated enhanced durability when we first read the release. So curious to get your expanded thoughts on that and what you're seeing with the 2,000 mg dose on durability as it relates to the 1,500 mg data and why that might be. Is this specifically referring to the depth of response at 24-week data and the percent of responders with deep responses that you kind of just showed towards the end? And then, just a second question, just on the topic of durability, I believe the phase I-b/II OrigAMI study of RYBREVANT FASPRO was announced yesterday, and the median PFS was 7.7 months.
So curious to get your thoughts on that data and the potential competitive implications for you guys.
Thank you for your question, Tyler. So when alluding to the durability question for the 2,000 mg every two weeks, as you saw in the presentation, we also shared a swimmer plot that showed very strong durability in some of our early responders, going out beyond two years in terms of duration of response. While our median duration of response is not yet mature and neither is our median PFS, we do believe it's trending quite strong, on the scale of what we've seen at the 1,500 mg dose. So really speaking to why, you know, the deep responses are leading to high duration of response, and ultimately overall survival. To your second question around, the data that was presented yesterday, also here at the, the head and neck meeting from OrigAMI-4 .
So RYBREVANT or amivantamab showed in combination with pembro a 7.7-month median PFS. What we've been able to demonstrate with the 1,500 mg dose, if you may remember at ASCO last year, was a median PFS of just under 10 months at 9.9 months. We also believe that the data from the 2,000 mg every two weeks is trending quite strong and will also exceed what was seen with amivantamab plus pembro yesterday. So we do believe, again, the differentiated profile of ficerafusp alfa is really focused on these deep responses that are translating to durable responses, while the other EGFRs or EGFR bispecifics are really delivering a durability of a targeted therapy consistent with what we've seen across the board with cetuximab, petosemtamab, and amivantamab.
Thank you. One moment for the next question. The next question is coming from the line of Eric Schmidt of Cantor Fitzgerald. Your line is open.
Yeah, my thanks also for a really interesting and comprehensive update. Maybe first, Claire, some of the biomarkers that you're looking at here to guide dosing are systemic markers of inflammation, as you noted in your presentation. I guess we would hope that in some ways, what's happening in the tumor is even more potent in terms of TGF-β inhibition. So can you talk about, you know, how you're looking to rely upon both intra-tumoral as well as systemic markers, and what kind of weight you're putting on each of those aspects of information that you have? And then, just a quick one, the one case of hypokalemia, is there a mechanistic rationale for that? Thank you very much.
Thank you for your question, Eric. So I'll speak to the first question and then pass your safety question to Bill. So in terms of biomarker data, we're really looking at the totality of data. So we do have a number of intra-tumoral focuses, which is why we presented both the phospho-SMAD2 paired biopsy data, which shows, you know, across the doses that have been studied, a consistent TGF-β inhibition. As you know, of course, phospho-SMAD2 is measured by immunohistochemistry or IHC, which is a pretty sustained marker and doesn't give you the dynamic effects of what you're seeing if you look at TGF-β inhibition via just systemic TGF-β inhibition. And so those are also—w e've also seen those, and those do seem to be consistent across the even less frequent dosing regimens.
We've also been able to show, you know, T-cell infiltration by immunohistochemistry and spatial transcriptomics that have really certified the fact that we're seeing tumor microenvironment remodeling even at the less frequent dosing. And it's the totality of, I would say, biomarker data as well as PK data, that is reinforcing our thinking around a loading and maintenance dose, as well as clinical data. And to your hypokalemia question, I'll pass it over to Bill.
Yeah. Thank you, Eric. So with respect to hypokalemia, this is, this is consistent with what's seen—what has been seen with other EGFR inhibitors, including cetuximab. So with EGFR inhibitors, electrolyte imbalances, including hypokalemia, are not unanticipated, and is fairly common. The management of this with standard replacement therapy also is very common.
Thank you. One moment for the next question. The next question will be coming from the line of Stephen Willey of Stifel. Your line is open.
Yeah, good morning. Thanks for taking the question. Maybe just a couple of housekeeping ones with respect to the data presentation itself. Do we know what the median duration of follow-up is on this cohort? And then do you happen to know if the incidence rate of just dose modifications, whether those are holds or reductions, are any more significant with the QTW dosing schedule relative to what you've seen at, at 1,500 mg? And then I just have a quick follow-up.
Thanks for your question, Steve. So this cohort was actually enrolled in two portions. We initially started this cohort about two years ago and then switched to enrolling the 750 mg weekly cohort to satisfy Project Optimus. And so the, I believe, the vast majority of patients were enrolled in the second part of the study to total 30 patients. So you have the first group of patients with over two years' worth of follow-up, which is why you saw the strong durability on those patients. The other patients have less than 12 months follow-up, and so we do hope to be able to provide, you know, a fulsome update once we've achieved median PFS, median DOR, and the like. And I believe your second question was focused—
I was just—
Will you repeat the second question?
Focused on whether or not you had seen a higher incidence rate of dose modifications with the QTW.
No, we have, we have not. We have not. So in terms of the AE profile, I would say it's quite consistent in terms of dose holds and dose modifications, very low in both cases and very similar to the 1,500 mg weekly dose.
Okay. And then, maybe just lastly, I know you need to reach some level of regulatory alignment on this loading and maintenance dosing strategy, but can you maybe just kinda provide a little bit of an overview in terms of, you know, when you expect to approach FDA, when you think you might have that guidance in hand in terms of what a parallel randomized study would need to look like? And any guess as to how many data points, how many patients you may need to have represented within that trial specifically? Thanks.
Our intent is to have, you know, the fulsome data in hand by the time of our approval to be able, you know, to go to the FDA and allow flexibility for patients. So we do anticipate, you know, being able to get regulatory guidance in time to run the study. Again, this would be a parallel study in parallel to FORTIFI-HN01, much smaller and likely a randomized study looking at, you know, our weekly dosing randomized to the loading maintenance dose. Thank you.
All right. Thanks for taking the questions.
Thank you. One moment for the next question. Our next question is coming from the line of Kelsey Goodwin of Piper Sandler. Your line is open.
Perfect. Hey, good morning, and thanks for taking my questions. Maybe just taking a step back from a competitive standpoint, I guess, how important do you think it is to have an additional dosing schedule in the first place in an eventual label? You know, how competitive is QW versus Q2W versus Q3W in your opinion? And then sorry, maybe just to follow up a bit on that last question, do you have a sense of when you might have, you know, regulatory alignment, when you might be able to start the parallel study? Thank you.
Thank you for your question, Kelsey. So as we mentioned in the call, we do our market research tells us that the differentiated profile in terms of depth of response and durability of response and the strong overall survival we've seen in our cohorts, will really differentiate Bicara, ficerafusp alfa, even in a weekly regimen. And so we do believe that a weekly regimen will lead to significant adoption. What we're really trying to do here with the loading maintenance dose is create an optionality for investigators and patients as we think about, you know, what is the best clinical profile for this molecule. And so it's really about, again, ensuring that we see these rapid, deep responses in the loading phase and being able to create flexibility, especially in combination with pembrolizumab in the maintenance phase.
Our intent right here, and from a regulatory standpoint, is again not to get ahead of our regulatory conversations, and we'll provide an update when we have them.
Thank you. One moment for the next question. Our next question is coming from the line of Judah Frommer of Morgan Stanley. Your line is open.
Yeah, hi, guys. Thanks for the update here. Can you just remind us how many centers you're in with the pivotal trial at this point? What overlap is between trials of petosemtamab or amivantamab within those centers? I think you've said it's very low. And then just curious, from investigators, I guess, given kind of depth of response and durability, does it seem like there is demand for a less frequent dosing schedule, or is that more alignment with kind of the other clinical competitors out there? Thanks.
Thank you for your question, Judah. So as of today, we've built significant momentum in FORTIFI-HN01, especially now that we're in the phase III portion of the study. I believe we have 111 sites on ClinicalTrials.gov, with significant momentum building in Europe and outside of the United States as well. I would say there is, you know, today, still minimal overlap in terms of sites between ourselves and the petosemtamab study, LiGeR-HN1. And the amivantamab study, which I believe is an OrigAMI study, has just begun recruiting. But as you may be aware, again, this is a differentiated patient population. They are randomizing to pembro plus chemo, and we are not seeing significant overlap today from that standpoint.
To your question, you know, we are here at the, at a head and neck meeting here in Palm Springs . And the feedback has been extremely positive on the data for ficerafusp alfa, even compared to the other EGFR inhibitors. I think what we're hearing is, again, that the differentiated profile, both in terms of depth of response durability, but I think also importantly, safety really shows that ficerafusp alfa is really the best in class. One of the key feedbacks we've been hearing from investigators who have worked with all three molecules has been really the ficerafusp alfa safety profile is also quite differentiated. And so we do believe, again, that the weekly profile will not be an impediment to the best-in-class profile and being able to have the largest market share.
But we do think from a life cycle perspective, being a, again, able to create optionality and flexibility for our patients. Bill, anything you'd also add in terms of the feedback we've been hearing?
Yeah, Claire. Consistent with what Claire has been saying, we've been hearing feedback about the differentiated profile in terms of the rapidity, depth and durability of the responses. In terms of the dosing schedule, having a less frequent dosing regimen does allow flexibility and more convenience for patients. And so, while not taking away from what we see on a weekly regimen, we are hearing that this provides optionality and flexibility for patients. This also inform the life cycle and other opportunities for ficerafusp alfa.
Thank you. One moment for the next question. Our question will be coming from the line of Reni Benjamin of Citizens Bank. Your line is open.
Hey, great. Thanks for taking the questions, and congratulations on this data. Just to kind of flush out a little bit more regarding the dosing regimen, can you— you know, you said you've you plan on moving to the loading dose in a, in a Q3 weekly maintenance. Can you talk a little bit more about, like, how you might be thinking about this? Are there going to be multiple loading doses, and then a maintenance regimen? Is there the potential for a loading dose, then going to a Q1 weekly, and then a maintenance regimen? I'm a little bit kind of confused as to how this is going to look.
And just kind of related to it, is the next study going to be kind of a dedicated cohort to give you a good sense as to how it'll move forward, or does it go right into a potential registrational study? I just have a quick safety follow-up after that.
Great question, Reni. So the loading and maintenance, the way we were currently thinking about it is, again, a loading dose at 1,500 mg weekly, so similar to the pivotal dose that we're taking into the phase we've taken into the phase III portion. So allow, again, for these rapid, deep responses for a certain amount of cycles, and then moving to a higher dose, but at every three-week maintenance dose, really, to be able to create optionality. And the reason we chose Q3W is, again, in combination with pembro, it allows for same, you know, every three-week visits. And so the plan for, again, this study is to run a parallel study. We have, you know, we have looked at our molecule at a number of different doses, and so we do believe in the safety of this molecule.
This would be, again, a randomized study that would allow us to, to bridge to a potential data set in time for approval.
Got it. Great. Thanks for the clarification. And then just related to the safety aspect, you know, we saw the grade 3 anemia was a little bit higher in this cohort than prior doses. Can you maybe talk a little bit about that? You know, was it an early onset or not? Was it manageable largely with supportive care? Just any sort of color around that.
Yes. So, you know, anemia is a hypothesized TGF-β-related event. What we have typically seen with our molecule is that anemia is a later- stage adverse event that tends to happen, you know, once patients have achieved, you know, long, longer-term follow-up with deep and durable responses. What we are seeing, again, at this higher dose is a slightly higher rate of anemia, which we believe is really predicated on the mechanism of action of this molecule, in which, you know, by the time we've achieved deep and durable responses, there is less TGF-β within the tumor microenvironment, and so there's more systemic TGF-β inhibition.
One of the things that Bill can speak to is that typically our patients, especially head and neck HPV-negative patients with high tumor burdens, do have high levels of baseline anemias, and so this is something.
Yeah. Thanks, Claire. As Claire mentioned, these patients often come in with anemia as a result of their prior therapies and as a result of their tumors. So patients with head neck cancer do have high baseline levels of anemia. We see a mild increase of the anemia. And to the point of management, these patients are well managed with standard supportive measures, iron supplementation. They don't require a high level of transfusions and usually require just dose holds and not other dose modifications. So it's fairly well managed with standard supportive measures.
Terrific. Thanks for taking the questions.
Thank you. One moment for the next question. Our question is coming from the line of Richard Law of Goldman Sachs. Your line is open.
Oh, hi, this is Jane, for Rich. So my question is, so first, are you going to, oh, so first, what is the planned dosing regimen for the loading dose plus Q3W? And is the plan to commercialize the three dosing options, if approved, the 1,500 mg QW, 2,000 mg Q2W, and then the loading plus the Q3W? And then, are you going to conduct, bridging studies in parallel with the first-line pembro study? And what will be the design of the bridging study to require FDA? Thank you.
As I answered previously, we do again anticipate a loading dose of 1,500 mg weekly, moving then to a Q3W dose. We are anticipating regulatory feedback and do not wanna get ahead of regulatory conversations, but we are predicating a study that would run in parallel to our pivotal study, to be able to have the data in hand for in time for approval. Thank you.
Thank you, Claire. Do you expect the efficacy and safety of this new loading plus Q3W dosing regimen to be different from the 1,500 mg QW dosing regimen, and why?
Again, we've seen consistency across the 1,500 mg weekly as well as the 2,000 mg every two-week cohort. We do anticipate, based off of the totality of PK, PD, and clinical data, a strong efficacious profile that allows for rapid, deep responses and durable responses that lead to outsized overall survival. Thank you for your question.
One moment for the next question. Our next question is coming from the Jeet Mukherjee of BTIG. Please go ahead.
Great. Thank you for taking the question. Two from me. Maybe just on the patient baseline features, seems as though patients with local regional only disease was maybe a higher proportion as a part of this 2,000 mg cohort versus the 1,500 mg once weekly seen in ASCO. So if you could just elaborate, does this perhaps correspond to less aggressive disease, or overall, how do you compare the two patient populations? And I have a follow-up.
Thank you for your question, Jeet. In fact, patients with local regional disease only tend to do worse, and so are far more sick and have higher radiation, highly fibrotic tumors. Interestingly, they respond typically less well to pembrolizumab. Again, the skewing to local regional disease only just speaks to how difficult to treat these patients are, and the fact that we're seeing such strong, deep, and durable responses again speaks to being able to address the sickest patients in HPV- negative head and neck cancer.
Great, thanks. As a follow-up, obviously, this 2,000 mg once every two-week data looks quite compelling, but you've obviously articulated a plan to move forward with a loading plus once every three-week maintenance strategy with a randomized study. I guess maybe my question there is why not, you know, move forward with this 2,000 mg cohort in hand? You spoke to optionality. This certainly seems to provide that. So, you know, what really gives confidence on maybe trying a slightly different novel regimen here instead of going forward with 2,000 mg? Thanks.
That's a great question, and again, I think it's the totality of clinical data as well as safety data, wanting to optimize on both fronts, ensuring that we see these rapid, deep responses, but we're also able to maintain those and creating a tolerability profile that's able to keep patients on for long term. And so being able to optimize across all three of these fronts really led us to a loading and maintenance dose. Thank you.
Thank you. I would now like to turn the call back over to Claire Mazumdar, CEO, for closing remarks. Please go ahead.
Thank you all for joining this call today. We're thrilled to be here again in Palm Springs with the head and neck investigators, and thank you for your time. Thank you.
Thank you all for joining the conference call today. You may now disconnect.