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Cell, mRNA Therapy Biotech Raises $165M in Early Funds

T-cells illustration
T-cells (NASA.gov)

14 Sept. 2022. A new company, founded by university medical researchers, is developing cell therapies engineered with messenger RNA or mRNA to work inside the body. Capstan Therapeutics Inc., a biotechnology company begun last year in Philadelphia and San Diego, is raising $165 million in its seed and first venture rounds from pharmaceutical companies and life science venture investors.

The technology behind Capstan Therapeutics is based on pioneering research on cell engineering by co-founder Carl June at University of Pennsylvania medical school. June and colleagues at UPenn devised techniques for genetically engineering T-cells in the immune system to express chimeric antigen receptors, or CARs, on the T-cell surface. CARs provide T-cells with more specific targeting of diseased cells, and early applications of the technique were treatments for cancers that normally evade the immune system. In Aug. 2012, Science & Enterprise reported on a collaboration between June’s lab and drug maker Novartis to develop cancer immunotherapies.

Early CAR T-cell therapies required altering an individual’s T-cells in the lab and producing a complete replacement of the patient’s T-cells, a lengthy and risky process. And while clinical trials of CAR T-cells showed high rates of remission among cancer patients, they also reported high rates of adverse effects, including severe disease and death.

Administered in an out-patient setting

Capstan Therapeutics says it’s developing a safer form of engineered CAR T-cells that operate in vivo, or inside the body, rather than first modifying a patient’s T-cells in the lab. The company says its process is designed to treat a range of diseases, and be administered in an out-patient setting. To achieve these goals, Capstan employs synthetic mRNA that carry reprogramming instructions for T-cells, delivered with lipid or natural oil nanoscale particles. This technique is similar to delivery methods used in Covid-19 vaccines.

The company’s scientific founders — Carl June, Jonathan Epstein, Haig Aghajanian, Drew Weissman, Hamideh Parhiz, Ellen Puré, and Steven Albelda — with colleagues at UPenn demonstrated the technology in lab mice, with results published earlier this year in the journal Science. The team delivered CAR T-cells engineered inside the body with mRNA transported by lipid nanoparticles or LNPs to treat mice induced with cardiac fibrosis, or scarring on heart tissue, a symptom of heart failure. The team reported the treatments reduced scar tissue and restored heart functions in mice receiving the treatments.

“Research conducted at Penn,” says Epstein in a Capstan Therapeutics statement, “demonstrates the tremendous promise of harnessing mRNA and targeted LNP delivery to train a patient’s body to make CAR-T cells in vivo, potentially creating new treatment options.” Weissman adds, “Capstan is uniting several recent life science technological advances in a manner that can hopefully unlock the potential of these technologies to develop new medicines for patients across a wider range of diseases.”

At its founding in Nov. 2021, Capstan raised $63 million in seed funds led by Novartis Venture Fund and life science investor OrbiMed, with participation by RA Capital, and Vida Ventures. The company is raising another $102 million in its first venture round led by Pfizer Ventures, joined by the venture investing arms of Bayer, Eli Lilly and Co., and Bristol Myers Squibb, with Polaris Partners, Alexandria Venture Investments, and current investors.

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Disclosure: The author owns shares in Pfizer.

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