Bicara Therapeutics (NASDAQ:BCAX) is developing tumor-targeting bifunctional antibodies, with its lead candidate ficerasfusp alfa designed to address both EGFR and TGF-beta biology in cancer, company President and Chief Operating Officer Ryan Cohlhepp said during a conference session moderated by Barclays Senior Biotech Analyst Carter Gould.
Cohlhepp said Bicara was founded in 2020 and licensed intellectual property from Biocon that year. Since then, the company has advanced ficerasfusp alfa—an EGFR/TGF-beta bifunctional antibody—into later-stage development, including a registrational trial in recurrent/metastatic head and neck cancer. Bicara initiated that trial in the first quarter of last year and expects top-line data in mid-2027, he said.
Mechanism and clinical rationale in HPV-negative head and neck cancer
He said prior attempts to inhibit TGF-beta in cancer have struggled to demonstrate activity, in part because of challenges achieving sufficient drug levels in the tumor microenvironment. Bicara’s approach uses EGFR targeting to help localize the TGF-beta “trap” in tumors, with the goal of generating both EGFR-driven antitumor activity and TGF-beta-driven effects that may help overcome acquired resistance mechanisms.
Response depth, durability, and comparisons discussed
Discussing data previously presented in HPV-negative head and neck cancer, Cohlhepp pointed to what he characterized as deep and durable responses. He noted that at ASCO 2023, Bicara reported early signals including “several” complete responses. As the dataset matured, he said the 1,500 mg dose—selected to carry forward into the pivotal trial—has shown a 21% complete response rate. He also said another 9% of patients were not categorized as complete responses but had a 100% reduction in their primary tumor.
On durability, Cohlhepp contrasted response patterns he described for pembrolizumab (pembro). He said pembrolizumab monotherapy yields responses in roughly one in five patients and that those responders see about a 24-month duration of response, but that relatively few patients respond. In Bicara’s HPV-negative population, he said ficerasfusp alfa demonstrated a confirmed response rate of 55% and a 21.7-month median duration of response.
He also referenced investigator-sponsored studies combining cetuximab with pembrolizumab or nivolumab, which he said showed duration of response of around 13 months. Cohlhepp argued that the durability signal supports a meaningful contribution from the TGF-beta component, aligning with the company’s expectation that TGF-beta’s clinical impact would be reflected in duration of response, progression-free survival, and overall survival.
Toxicity profile and TGF-beta “trap” design
Asked about tolerability compared with older “classic” TGF-beta approaches, Cohlhepp said Bicara’s TGF-beta-binding element is based on the extracellular domain of TGF-beta receptor 2. He said historical TGF-beta programs saw cardiomyopathy that was attributed to TGF-beta 2, and that Bicara’s design provides greater specificity for TGF-beta 1 and 3, which he described as cancer-associated forms—an approach he said helps mitigate prior TGF-beta toxicities.
Phase III design, endpoints, and approval pathway
Cohlhepp said the registrational study began as a three-arm trial to satisfy FDA dose-optimization expectations under Project Optimus, evaluating two doses of ficerasfusp alfa versus pembrolizumab monotherapy. He said Bicara later aligned with the FDA and advanced with a single 1,500 mg dose into the Phase III portion.
According to Cohlhepp, the Phase III trial includes two primary endpoints:
- Overall response rate (ORR)
- Overall survival (OS) follow-up
He described a “single trial” approach under FDA’s Project FrontRunner, in which ORR could support a potential accelerated approval, with continued blinded follow-up to OS to support full approval later. He said an ORR analysis would be triggered at roughly 350 patients, while total enrollment is expected to be about 600 to 650 patients. He added that the FDA has asked for at least six months of follow-up on most patients to assess response maintenance, and that regulators may also perform sensitivity analyses on OS trends at that time.
When asked about powering assumptions for OS, Cohlhepp said KEYNOTE-048’s reported overall survival did not disclose HPV-positive versus HPV-negative breakdown, complicating sizing. He also cited the LEAP-010 study (lenvatinib plus pembrolizumab), where pembrolizumab monotherapy was observed at 17.8% in that trial, which he suggested may reflect trial-specific inclusion/exclusion dynamics. For Bicara’s HPV-negative-only population, he said pembrolizumab monotherapy ORR “bounds” were likely around 8% to 18%, and that the company sized the trial to be clinically meaningful and to increase confidence in meeting the OS endpoint.
Dosing strategy, HPV testing, financing, and expansion plans
Cohlhepp said Bicara has evaluated multiple dosing regimens—750 mg weekly, 1,500 mg weekly, and 2,000 mg every two weeks—totaling close to 100 patients across cohorts. He said EGFR is fully saturated at 750 mg, and that doses above that help isolate incremental benefit attributed to the TGF-beta component. Bicara’s strategy, he said, is to initiate therapy with a weekly 1,500 mg “loading phase” of up to 12 weeks, after which most patients have reached best response; the company then aims to extend the dosing interval in maintenance to align with pembrolizumab’s schedule. He said Bicara plans an additional randomized trial, to run in parallel with the pivotal study, and expects those data to inform strategic decisions such as pricing around the time of first approval.
On patient selection, Cohlhepp said HPV testing in head and neck cancer is “super routine” and typically performed at initial diagnosis. He said Bicara is developing a PCR HPV test with a partner for potential co-approval, though he added that payers have indicated comfort with existing IHC testing and that HPV status has not impeded enrollment.
Cohlhepp also said Bicara raised $172 million about a week and a half before the conference, with proceeds intended to support building commercial and medical affairs infrastructure. He described head and neck cancer as an “approachable” first launch due to a concentrated prescriber base and said the company plans to build a U.S. commercial organization while maintaining optionality for ex-U.S. partnering or infrastructure buildout.
Beyond frontline head and neck cancer, Cohlhepp said Bicara has cohorts open in colorectal cancer and has observed monotherapy activity in cutaneous and anal canal cancers. He also highlighted locally advanced head and neck cancer as a potential opportunity, noting that radiation increases TGF-beta levels. He said Bicara is using published work on TGF-beta signatures, along with internal research, to prioritize indications where both EGFR and TGF-beta play critical roles, rather than “just chase EGFR.”
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.
