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CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Bicara Therapeutics, a clinical-stage biotechnology company developing dual-action biologics to elicit a potent and durable immune response, today announced the publication of a manuscript in Cancer Research, a journal of the American Association for Cancer Research (AACR), describing the design and characterization of its lead program, BCA101, a first in class dual-action bifunctional antibody designed to inhibit EGFR and disable TGF-β directly at the tumor site. “Over the last two decades, targeting EGFR alone has demonstrated variable clinical success while targeting TGF-β independently has shown limited clinical benefit. The bifunctional antibody fusion design of BCA101 provides a unique approach to addressing the complexities of the tumor microenvironment in EGFR expressing tumors. The data to date show that BCA101 inhibits EGFR and neutralizes TGF-β simultaneously to induce immune activation and suppress tumor growth,” said senior author Pradip Nair, Associate Research Director at Syngene International. “Our findings suggest that the dual action of BCA101 may potentially offer improved clinical efficacy and a superior safety pro to current approaches that separately inhibit EGFR and sequester TGF-β.” The manuscript describes the important roles of the EGFR and TGF-β signaling pathways as mediators of tumorigenesis, and how the crosstalk between them contributes to cancer progression and drug resistance. The authors detail how BCA101, an anti-EGFR IgG1 monoclonal antibody linked to the extracellular domain of human TGF-β receptor II, is able to bind EGFR, inhibit tumor proliferation, while functionally neutralizing TGF-β and restoring the cytolytic activity of the local immune cells. Data suggest that BCA101 has a potential advantage over EGFR inhibitors, such as cetuximab, in activating the immune cells within the tumor microenvironment known to be suppressed by the presence of TGF-β. In addition, BCA101 in combination with anti-PD1, further improved tumor inhibition in both EGFR-expressing mouse models and humanized mice bearing PC-3 xenografts. Taken together, these data suggest that BCA101 may exert superior anti-tumor effects as a monotherapy, and in combination, by targeting both EGFR and TGF-β simultaneously. “Based on these findings, we are working to rapidly advance BCA101 through the clinic because we believe this therapy can be very impactful across multiple tumor types in patients who both express EGFR and have elevated levels of TGF-β,” said Rachel Salazar, SVP of R&D Strategy and Operations at Bicara Therapeutics. Bicara has previously reported promising clinical data from its ongoing Phase 1/1b study of BCA101 in head and neck cancer, including efficacy as both a monotherapy and in combination with pembrolizumab. Preclinical data, also being presented today at the 2023 AACR Annual Meeting further support BCA101’s mechanism of action and provide evidence of its potential to induce durable anti-tumor responses in various tumor types. The paper, entitled “BCA101 is a tumor-targeted bifunctional fusion antibody that simultaneously inhibits EGFR and TGF-β signaling to durably suppress tumor growth,” is published online today and can be accessed here. About Bicara Therapeutics Bicara Therapeutics is a clinical-stage biotechnology company developing first-in-class biologics engineered to bring together the precision of targeted therapy and the power of tumor modulators. The company’s bifunctional antibodies are designed to deliver an immunomodulatory payload directly to the tumor microenvironment to ramp up immune cell activity, potentially offering long-lasting efficacy. Bicara’s lead asset, BCA101, a first-in-class EGFR / TGF-β-trap bifunctional antibody, is currently enrolling patients in a Phase 1/1b study. Bicara’s experienced team brings deep expertise across immunology, oncology, clinical development, business development and operational strategy. More information is available at .