Bicara Therapeutics (NASDAQ:BCAX) outlined its clinical and development strategy for its lead bifunctional antibody program, FICERA, during a presentation and fireside chat at TD Cowen’s 46th annual health care conference. Ryan Cohlhepp, the company’s President and COO, said the company is advancing FICERA—an EGFR and TGF-beta bifunctional—into a pivotal study in frontline HPV-negative recurrent/metastatic head and neck cancer, while also evaluating the molecule in additional tumor types.
Company focus and rationale for HPV-negative head and neck cancer
Cohlhepp said Bicara’s approach centers on bifunctional antibodies designed to address limitations seen with prior TGF-beta efforts, particularly challenges achieving adequate levels of TGF-beta inhibition in the tumor microenvironment. He described head and neck cancer as a “fibrotic immunosuppressive solid tumor” and argued that HPV-negative disease represents a distinct subset characterized by higher EGFR expression, elevated serum TGF-beta, and higher rates of therapeutic resistance.
Clinical data highlights for FICERA
Reviewing previously presented data for FICERA dosed at 1,500 mg weekly, Cohlhepp highlighted:
- Confirmed overall response rate (ORR): 54%
- Complete response (CR) rate: 21%
- Depth of response: 80% of responders achieved tumor shrinkage of 80% or greater
- Median time to response: 1.4 months
- Median duration of response (DOR): 21.7 months
He also said responses were observed across PD-L1 combined positive score (CPS) subgroups (including CPS 1–19 and CPS greater than 20) and across tumor sizes, including patients with large tumors exceeding 70 mm.
Cohlhepp argued that depth of response correlated with outcomes, stating that patients with 80% or greater shrinkage showed separation in Kaplan-Meier curves for duration of response, progression-free survival, and overall survival. He summarized the program’s potential impact as a meaningful increase in the responder population while maintaining “immunotherapy-like” durability.
Tolerability and translational findings
On safety, Cohlhepp said FICERA has shown on-target adverse events consistent with EGFR inhibition, including acneiform rash. He also pointed to hypothesized TGF-beta-related events, including transient grade 1–2 mucosal bleeding and epistaxis (nosebleeds).
From a translational standpoint, he discussed paired biopsy data using phospho-SMAD2 as a downstream marker of TGF-beta signaling. According to Cohlhepp, reductions in phospho-SMAD2 were observed across doses, with dose responsiveness suggesting increased TGF-beta activity at higher dose levels.
FORTIFY trial status, dose selection, and potential accelerated approval path
Cohlhepp provided an update on the ongoing pivotal FORTIFY study in frontline HPV-negative recurrent/metastatic head and neck cancer. The trial originally included three arms (FICERA 750 mg plus pembrolizumab, FICERA 1,500 mg plus pembrolizumab, and a pembrolizumab monotherapy control). He said the company aligned with the FDA to move forward with 1,500 mg weekly as the go-forward dose, dropped the 750 mg arm, and is now enrolling with a 2-to-1 randomization of FICERA plus pembrolizumab versus pembrolizumab alone.
On enrollment, Cohlhepp said momentum has increased after opening Europe, with additional geographies planned including Asia Pacific and South America. He said the company expects roughly 60% of enrollment to come from outside the U.S., consistent with many global studies. He reiterated prior guidance for a response-rate top-line readout in mid-2027, which he said could support a potential 2028 approval timeline.
Discussing regulatory expectations for an accelerated approval filing based on ORR, Cohlhepp said FDA feedback has been consistent around needing a doubling of the control arm response rate, referencing response rates from KEYNOTE-048 (19% in CPS ≥1) and LEAP-010 (around 25%). He said the company has increased confidence in its response estimate by demonstrating consistency across more than 90 patients from three datasets (750 mg, 1,500 mg, and 2,000 mg every two weeks).
He also said the FDA is expected to review overall survival (OS) at interim analyses, and suggested that focusing on an HPV-negative-only population could support earlier separation of survival curves versus pembrolizumab. While he did not provide a specific OS hazard ratio target, he said key opinion leaders generally view a two- to three-month OS improvement as clinically meaningful and that the company believes it can surpass that based on depth and durability of response.
Dosing strategy, commercial preparation, and expansion beyond head and neck
Cohlhepp said Bicara is planning an alternative dosing schedule intended to align with pembrolizumab administration. The company’s plan includes an initial loading phase of 1,500 mg weekly, followed by a maintenance phase designed to extend dosing to every three weeks. He said the goal is to preserve efficacy while improving convenience and tolerability in the maintenance period.
He also noted the company completed an additional capital raise “last week,” which he said would support commercial buildout and enable “critical hires” in 2026. Bicara plans to build out commercial leadership in 2026 as it prepares for a planned launch in 2028, while maintaining financial discipline and evaluating opportunities for FICERA beyond head and neck cancer.
Outside head and neck cancer, Cohlhepp said Bicara is enrolling cohorts in colorectal cancer (CRC) and expects to disclose data in the second half of the year. He described two third-line CRC cohorts: one monotherapy and one in combination with pembrolizumab. He characterized third-line CRC as a difficult setting and cited single-digit response rates for current standards like Lonsurf, while mentioning a reported 15% response rate from Incyte’s TGF-beta/PD-1 approach presented at ESMO. He said Bicara is looking for a “signal” that could support moving earlier in treatment.
Cohlhepp also said there is a mechanistic rationale for evaluating FICERA in pancreatic ductal adenocarcinoma (PDAC), given the company’s focus on tumors with both EGFR and TGF-beta relevance. He said PDAC would likely be pursued as a combination strategy and that the company is monitoring the evolving landscape to determine the most appropriate setting and partner.
About Bicara Therapeutics (NASDAQ:BCAX)
Bicara Therapeutics is a clinical-stage biopharmaceutical company dedicated to developing novel neurohormone-based therapies for psychiatric and neurological disorders. The company’s research focuses on harnessing endogenous signaling pathways in the brain, with the goal of offering new treatment options for conditions that remain inadequately addressed by existing medications. Bicara applies proprietary peptide engineering and intranasal delivery platforms to optimize central nervous system uptake and therapeutic effect.
The company’s lead candidates include PST-001, an intranasal vasopressin-1A receptor antagonist in development for postpartum depression, and PST-002, an oxytocin receptor modulator being investigated for social anxiety and autism spectrum disorder.
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