Clasp Therapeutics

Clasp Therapeutics operates in the immuno-oncology sector, focusing on developing treatments for hard-to-treat cancers. The company was formally launched in March 2024, securing $150 million in a Series A financing round co-led by Catalio Capital Management, Third Rock Ventures, and Novo Holdings. This venture originates from years of foundational research at Johns Hopkins University by its scientific co-founders, Dr. Bert Vogelstein and Dr. Drew Pardoll. Dr. Vogelstein is a renowned cancer geneticist whose work has shaped the modern understanding of cancer as a genetic disease, particularly through his research on colorectal cancers and the sequential mutation of oncogenes. Dr. Pardoll is a pioneer in immuno-oncology, credited with key discoveries related to T cell regulation and the development of cancer immunotherapies, including work on the PD-1 pathway. The company, initially formed in 2020 as ManaT Bio, represents the convergence of their respective expertise in precision oncology and immunology.

The company's core business revolves around its proprietary platform for creating next-generation T cell engagers (TCEs), which are bispecific, antibody-like molecules. These TCEs, branded as pHLAre™ molecules, are engineered to target tumor-specific mutations with high precision. The business model involves developing a portfolio of these off-the-shelf therapeutics, each designed for patients who have a specific combination of a common oncogenic driver mutation (like p53 or KRAS) and a corresponding human leukocyte antigen (HLA) type, which is part of the immune system's signature. This dual-targeting mechanism allows the TCEs to bind simultaneously to a T cell and a cancer cell presenting the mutated peptide, thereby activating the patient's own T cells to destroy the tumor while sparing healthy tissues. This approach aims to overcome the toxicity issues associated with on-target, off-tumor effects seen in other cancer therapies.

Clasp's product is a suite of modular TCEs designed to function like personalized medicine but produced as off-the-shelf products. A key feature is the ability to target intracellular proteins, which are largely invisible to traditional antibody drugs, by recognizing the mutated protein fragments presented on the cell surface by HLA molecules. This strategy allows for durable tumor killing even with low levels of surface presentation and is expected to reduce the likelihood of treatment resistance. By creating therapies for various combinations of mutations and HLA types, Clasp aims to serve a broad patient population across many cancer types that are currently unresponsive to standard immunotherapies. The company, led by CEO Robert Ross, operates from facilities in Cambridge, MA, and Rockville, MD, and intends to use its substantial funding to advance its drug candidates into clinical trials and generate in-human data.

Keywords: T cell engagers, immuno-oncology, precision oncology, oncogenic mutations, HLA-presented peptides, hard-to-treat tumors, bispecific antibodies, cancer immunotherapy, Bert Vogelstein, Drew Pardoll, Johns Hopkins, Catalio Capital Management, Third Rock Ventures, Novo Holdings, off-the-shelf therapeutics, tumor-specific targeting, intracellular proteins, cancer genetics, immune system activation, pHLAre molecules, MANAs, neoantigens, molecular targeting, cancer vaccines, biologics