ImmunoGenesis Begins Phase 1/2 Trial of IMGS-101 Combo in Advanced Tumors

ImmunoGenesis, a biotech firm engaged in developing innovative immunotherapies, has announced the commencement of its Phase 1/2 clinical trial involving IMGS-101 (evofosfamide) at The University of Texas MD Anderson Cancer Center. This trial is significant as IMGS-101 is known for its ability to mitigate solid tumor hypoxia, a condition where low oxygen levels within tumors suppress immune responses. The trial aims to explore how IMGS-101 could potentially enhance the efficacy of immunotherapies in cancers resistant to immune-based treatments.

The clinical trial, which is open-label and multicenter, will assess the safety, pharmacokinetics, and anti-tumor activity of IMGS-101 combined with two checkpoint inhibitors, Balstilimab (anti-PD-1) and Zalifrelimab (anti-CTLA-4). The trial targets adult patients grappling with locally advanced or metastatic castration-resistant prostate cancer, pancreatic cancer, and HPV-negative squamous cell carcinoma of the head and neck. This research is conducted with Agenus, a company developing the checkpoint inhibitors Balstilimab and Zalifrelimab.

James Barlow, President and CEO of ImmunoGenesis, emphasized the significance of this trial as a milestone toward addressing immune resistance mechanisms in cancers. He highlighted their objective of reversing hypoxia to unleash the full potential of the immune system and transform treatment paradigms for cancers with high unmet needs. Dr. Charles Schweizer, Senior Vice President of Clinical Development at ImmunoGenesis, commented on the trial as an innovative approach to counteracting cancer immunotherapy challenges. He noted that hypoxia limits T-cell infiltration and suppresses immune responses, particularly in prostate, pancreatic, and head and neck cancers. IMGS-101 aims to reverse this condition, potentially restoring T-cell access and enhancing checkpoint inhibitor effectiveness in hard-to-treat cancers.

ImmunoGenesis is committed to revolutionizing immuno-oncology by countering immune resistance mechanisms. Their primary product, IMGS-001, is a dual-specific PD-L1/PD-L2 antibody in a phase 1a/b trial targeting immune-excluded tumors, which constitute a significant proportion of cancers. The company is also exploring additional strategies to combat immune resistance in these tumors, designing therapies to overcome immune exclusion and stimulate robust immune responses.

IMGS-101, also known as Evofosfamide, is a 2-nitroimidazole prodrug of the cytotoxin Br-IPM, initially developed as a hypoxia-activated prodrug. Dr. Michael A. Curran, founder of ImmunoGenesis from MD Anderson, has demonstrated that IMGS-101 effectively addresses hypoxia, one of the major immunosuppressive barriers. Pre-clinical models and a Phase 1 study have shown that IMGS-101 can restore T-cell function and potentially synergize with checkpoint inhibitors. ImmunoGenesis is advancing IMGS-101 as a hypoxia-reversal agent to prepare tumors for checkpoint inhibition.

Balstilimab, developed by Agenus, is a novel IgG4 monoclonal antibody designed to inhibit PD-1 from interacting with its ligands, showcasing clinical activity and tolerability across various tumors. Zalifrelimab, another Agenus development, is an IgG1 monoclonal antibody targeting CTLA-4 to prevent its interaction with CD80 and CD86, marking it as a foundational target in immuno-oncology. Both these agents are employed in combination with IMGS-101 in the ongoing trial to potentially revolutionize treatment outcomes for resistant cancer forms.