VEL-03: IND-enabling development of a novel therapeutic approach for treatment of non-small cell lung cancer and other solid tumors

Project Summary/Abstract Lung cancer is the leading cause of cancer-related death in the U.S. and worldwide. Non-small cell lung cancer (NSCLC) makes up 85% of all lung cancers. Despite advancements in targeted cancer therapies, NSCLC has a 5-year survival rate of less than 30%. Current treatment challenges include limited responses to radiotherapies and targeted therapies, immune resistance in "immune cold" tumors, and complex tumor microenvironment alterations. In response to the pressing need for effective lung cancer treatments, Velorum Therapeutics has developed VEL-03, a first-in-class pan-cancer metabolic targeting therapy. Preliminary data demonstrate disruption of tumor metabolism by targeting heme uptake, a critical factor in cancer growth and progression. VEL-03, a proprietary heme-sequestering protein, demonstrates consistent efficacy by inhibiting tumor growth in various cancer models, while sparing normal cells. Moreover, VEL-03 reshapes the tumor microenvironment, enhancing its synergy with radiation therapy. Collectively, our results identify VEL-03 as a promising therapy for many hard-to-treat cancers, both as a monotherapy and as a potential combination treatment. This Direct to Phase II proposal will: 1) evaluate VEL-03’s therapeutic efficacy in combination with radiation therapy and Cisplatin, 2) scale up manufacturing for IND-enabling studies, and 3) conduct maximum tolerated dose and dose- finding toxicology studies with pharmacokinetic and pharmacodynamic endpoints. Successful completion of these Aims will lay the foundation for IND-enablement and subsequent clinical studies of VEL-03 as a single- agent and in combination with existing anti-tumor agents. Our overall goal is to advance VEL-03 towards clinical studies with rapid proof-of-concept, addressing a significant unmet need first in lung cancer treatment and potentially benefiting patients with many types of hard-to-treat cancers.