Core Insights - Bicara Therapeutics Inc. presented preliminary data from a Phase 1b expansion cohort evaluating 750 mg of ficerafusp alfa in combination with pembrolizumab for treating HPV-negative recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) [2][3] - The data showed a 57% confirmed overall response rate with 10% of patients achieving a complete response and 29% of responders demonstrating deep responses of at least 80% tumor shrinkage [3][4] - The company plans to declare the optimal biologic dose for the pivotal FORTIFI-HN01 study in the first quarter of 2026 [5] Company Overview - Bicara Therapeutics is a clinical-stage biopharmaceutical company focused on developing bifunctional therapies for solid tumors, with ficerafusp alfa being its lead program [12] - Ficerafusp alfa is a first-in-class bifunctional antibody designed to enhance tumor penetration and drive durable responses by targeting both EGFR and TGF-β [10][12] - The FDA has granted Breakthrough Therapy Designation to ficerafusp alfa in combination with pembrolizumab for first-line treatment of R/M HNSCC [10] Clinical Data - The Phase 1b expansion cohort data indicated that 750 mg of ficerafusp alfa combined with pembrolizumab was well-tolerated, maintaining a safety profile consistent with previous studies [3][4] - Higher doses of ficerafusp alfa (1500 mg) showed greater TGF-β inhibition and immune activation, leading to deeper clinical responses, with a median depth of response of 82% compared to 63% at the 750 mg dose [4][5] - The totality of data suggests that increased TGF-β inhibition correlates with more durable outcomes for patients [5] Industry Context - HNSCC is one of the most common cancers globally, with an anticipated rise to one million new cases annually by 2030 [8] - Approximately 80% of patients with recurrent/metastatic HNSCC are HPV-negative, highlighting a significant unmet need for effective therapies [9]

Investment Highlights - Bicara Therapeutics is advancing ficerafusp alfa (FICERA), a bifunctional EGFR-directed antibody x TGF-β ligand trap, designed to enable tumor penetration by breaking barriers in the tumor microenvironment to drive deep and durable responses[8, 125] - FICERA + pembro offers a potential new 1L therapy for HPV-negative R/M HNSCC, with the FORTIFI-HN01 Ph 2/3 trial ongoing and enrolling[8, 125] - The company has a robust financial position with approximately $437 million in cash and equivalents[8, 125] Clinical Trial & Market Opportunity - There is a significant market opportunity with approximately 23,000 cases of R/M HNSCC annually in the U S, and a significant unmet need for better treatment options (13% 5yr survival)[8, 33, 125] - In a Ph 1b trial of FICERA + Pembrolizumab in HPV-neg, CPS≥1 1L R/M HNSCC, the confirmed ORR was 54% (15/28)[60, 75] - The same trial showed a median PFS of 9 9 months and a median OS of 21 3 months, with a 2-year OS rate of 46%[66, 72, 75] - The median DOR was 21 7 months, with DOR rates of 79% at 6 months, 65% at 12 months, and 57% at 18 months[69, 75] Expansion Opportunities - The company is expanding into other squamous cell carcinomas and solid tumors, with encouraging clinical activity observed in Ph 1b expansion cohorts to date[8, 125] - In 2L+ cutaneous squamous cell carcinoma (cSCC), FICERA monotherapy showed an ORR of 30% (7/23) and a mPFS of 7 0 months in PD-1-refractory patients[114] - In 2L+ squamous cancer of the anal canal (SCAC), FICERA + pembro showed a 25% ORR (7/28) and a 12-month PFS rate of 40 7%[118]