PD-1/VEGF bispecifics and the next IO backbone
Episode Summary Host Patrick McManus speaks with Scott E. Smith, MD, PhD, FACP, Chief Medical Officer at Kapadi, about PD-1/VEGF bispecific antibodies and their implications for immuno-oncology. The opening also considers China’s growing role in oncology innovation and the challenge of making locally generated evidence relevant to global development. Patrick asks whether ivonescimab is a new molecular design class or a more convenient way to combine familiar targets. Scott discusses cooperative binding, HARMONi-2 and HARMONi-6, and the unanswered question of whether the bispecific format offers an advantage over two separate antibodies. The conversation then turns to programs built on pembrolizumab: what should change for new studies, trials already underway, and settings where VEGF-directed therapy is unsuitable or unproven? Key Takeaways Dual PD-1 and VEGF targeting has precedents. Ivonescimab’s cooperative binding remains a mechanistic hypothesis to test against appropriate alternatives. A new backbone could change comparator choice, differentiation, and the relevance of studies using pembrolizumab as their default control. The decision depends on indication, trial maturity, the partner drug’s rationale, and whether patients can receive VEGF-directed therapy. Featured Expert Scott E. Smith, MD, PhD, FACP, is Chief Medical Officer at Kapadi and a physician-scientist with more than 20 years of leadership in hematology, oncology, and clinical research. As Senior Vice President and Global Head of Hematology at Parexel, he oversaw global clinical trial operations across more than 20 countries. As founder and CEO of Chemosabe Consulting, he has advised more than 15 pharmaceutical and biotechnology companies on clinical development and immunotherapy strategy, contributing to the launch of four hematology and oncology therapies. Previously, Dr. Smith served as Associate Cancer Center Director and Section Chief of Hematology at Loyola University Medical Center, where he expanded clinical programs and led teams of more than 50 professionals. His work includes bone marrow transplantation, CAR T-cell therapy, precision medicine initiatives, and review for the FDA Orphan Products Development Program. He has authored more than 150 peer-reviewed publications and abstracts and has spoken at international meetings including ASH and ASCO. Dr. Smith earned his MD and PhD at Wayne State University and is board certified in Internal Medicine, Hematology, and Medical Oncology. Continue the Conversation Questions about your oncology development strategy? Contact Kapadi: https://kapadi.com/contact. Subscribe to Humaneva Insights for future episodes.
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