Bicara Therapeutics Touts Breakthrough Ficerafusp Data, Picks 1,500 mg Dose for FORTIFY-HNS Trial

Bicara Therapeutics (NASDAQ:BCAX) used its presentation at the 44th Annual J.P. Morgan Healthcare Conference to outline its 2026 corporate outlook and highlight 2025 milestones centered on its lead clinical program, ficerafusp alfa, a bifunctional antibody designed to modulate the tumor microenvironment through EGFR-directed targeting coupled with localized TGF-β inhibition.

CEO Claire Mazumdar said the company is focused on “targeted tumor modulation” using bifunctional antibodies in which one arm targets the tumor and the other delivers a tumor modulator directly to the tumor microenvironment. The goal, she said, is improved efficacy, durability, and safety by localizing activity at the tumor site.

Lead program and rationale in HPV-negative head and neck cancer

Mazumdar described ficerafusp alfa as the “first and only EGFR-directed antibody bound to a TGF-β ligand trap” aimed at solid tumors. The company’s lead development focus is frontline recurrent and metastatic HPV-negative head and neck cancer, where Mazumdar said tumors typically have high levels of EGFR and TGF-β and are characterized by a fibrotic, immunosuppressive tumor microenvironment that can limit tumor penetration by therapies such as cetuximab or immunotherapies such as pembrolizumab.

She said HPV-negative disease represents roughly 80% to 90% of the frontline recurrent and metastatic head and neck market and is associated with worse outcomes and limited treatment options. The company’s thesis is that combining tumor-localized TGF-β inhibition with EGFR targeting can improve immune cell penetration and enhance durability when used with anti-PD-1 therapy.

2025 milestones: data disclosures, Breakthrough Designation, and pivotal trial start

Mazumdar said 2025 included multiple development milestones for ficerafusp alfa, including long-term follow-up data sets that she said showed “significant depth and durability of response” and “meaningful overall survival benefits compared to standard of care” in HPV-negative head and neck cancer. She added that these data supported the U.S. Food and Drug Administration granting Breakthrough Therapy Designation for the HPV-negative subtype.

The company also initiated its pivotal study, FORTIFY-HNS, a seamless phase II/III trial evaluating ficerafusp alfa plus pembrolizumab in frontline recurrent and metastatic HPV-negative head and neck cancer. Mazumdar said the study design supports a potential accelerated approval pathway.

Dose selection and 2026 execution priorities

During the presentation, Mazumdar said Bicara selected the 1,500 mg dose from the phase II portion of FORTIFY-HNS as the “go-forward” dose for the phase III portion, noting the decision occurred earlier than anticipated. She said an FDA interaction supported the decision and that dose selection enables the company to accelerate enrollment, targeting substantial enrollment by the end of 2026 and an interim analysis by mid-2027. Bicara is planning for a potential early launch timeline of early 2028, contingent on the program’s progress.

In the Q&A, Mazumdar said the dose decision reflected the “totality of the data,” including tumor microenvironment TGF-β inhibition, response consistency, and efficacy signals. President and CEO Ryan Kohlhepp added that Breakthrough Therapy Designation granted in October helped open a “productive dialogue” with the FDA that continued through dose selection discussions.

The company also outlined commercial planning steps, including an intention to hire a chief commercial officer and build a commercial foundation ahead of a potential U.S. launch. Management said commercial buildout could be further expanded following an interim analysis milestone.

Clinical data highlights shared from ASCO 2025 and ESMO Asia

Mazumdar highlighted long-term follow-up results presented at ASCO 2025 from 30 HPV-negative patients treated frontline with ficerafusp alfa 1,500 mg plus pembrolizumab. She reported a confirmed response rate of 54%, with 21% complete responses. She also said 80% of responders achieved at least 80% tumor shrinkage, with a median time to response of 1.4 months. Mazumdar said responses occurred regardless of PD-L1 combined positive score (CPS) and were observed even in patients with bulky tumors.

On durability, Mazumdar said median duration of response was 21.7 months, and she cited a median overall survival of greater than 21 months in the ASCO-presented data set, which she contrasted with real-world outcomes she said are seven to nine months median overall survival for many HPV-negative patients. She also characterized the molecule as “well tolerated” and designed to spare a TGF-β isoform historically associated with toxicities.

Additional data were presented at ESMO Asia from the 750 mg dose, which Mazumdar said showed strong response rates and a consistent safety profile versus the higher dose. She said the 1,500 mg dose demonstrated higher TGF-β inhibition in the tumor microenvironment and was believed to drive greater depth of response.

Pipeline expansion into metastatic colorectal cancer and other tumor types

While head and neck cancer remains the company’s “beachhead” indication, management said it plans to explore other solid tumors that share an EGFR/TGF-β “biological fingerprint,” including metastatic colorectal cancer and potentially pancreatic cancer, while maintaining financial discipline.

Mazumdar said the company initiated two proof-of-concept cohorts in third-line MSS RAS wild-type metastatic colorectal cancer evaluating ficerafusp alfa as monotherapy and in combination with pembrolizumab, noting standard-of-care response rates in this setting are about 2% to 6%. She said the company expects early data in the second half of 2026.

In the Q&A, Mazumdar also discussed preclinical work in KRAS-mutant colorectal and pancreatic cancer suggesting that combining ficerafusp alfa with KRAS inhibitors could address resistance mechanisms and improve durability. Kohlhepp added that Bicara’s head and neck clinical data is helping establish the contribution of TGF-β inhibition—particularly in durability—which the company believes could translate to additional tumor types.

Management reiterated previously disclosed cash runway guidance from the company’s Q3 update, stating it had “north of $400 million” intended to fully fund the pivotal study through its confirmatory endpoint.

Looking ahead, Bicara characterized its key 2026 drivers as executing the pivotal FORTIFY-HNS trial toward a mid-2027 interim analysis, building commercial readiness with key hires, and generating additional clinical readouts in head and neck cancer and colorectal cancer.

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.