University of Pennsylvania scientists who pioneered advances in cell therapy and messenger RNA have revealed A new venture with the goal of taking cell-based therapies to a new frontier: engineering these treatments inside the patient. Capstan Therapeutics is embarking on this journey backed by $165 million raised to date from a prominent syndicate of biotech backers, including five major pharmaceutical companies.
Capstan’s initial focus is the development of in vivo chimeric antigen receptor, or CAR T, therapies. CAR T drugs are currently made from a patient’s own T cells, which are engineered in a laboratory before being infused back into the patient. Penn’s research led to Kymriah, Novartis’ cancer treatment, which became the first approved CAR T-therapy.
Wednesday’s Capstan launch comes nine months later publication from Penn’s research in the journal Science showing that engineering work can be done inside a body, building on earlier published research showing that cells engineered in the lab can target cardiac fibrosis. According to a mouse study published in Science, scientists used mRNA to deliver instructions that reprogrammed T cells in vivo to recognize damaged heart cells. These cells were able to reduce heart damage and restore heart function.
Now Capstan, whose scientific co-founders at Penn include cell therapy pioneer Carl June and mRNA expert Drew Weissman, is working to bring this in vivo engineering to humans. The research described in the published papers is now Capstan’s flagship program. This in vivo CAR T-therapy is an intravenously administered dose of mRNA packaged inside a lipid nanoparticle that targets CD5, a protein expressed by T cells. The mRNA encodes an antigen that causes T cells to pursue cells expressing fibrosis activation protein, a target of fibrosis.
Unlike the viral vectors used for some genetic drugs, the use of lipid nanoparticles will allow the therapy to be re-dosed as needed. This is because viral vectors trigger the body to produce antibodies that prevent re-dosing and also trigger a dangerous immune response. In addition to the ability to engineer immune cells into the body, Capstan says his approach could also be used to deal with pathogenic cells by targeting their DNA as a way to treat genetic diseases. Besides fibrosis, Capstan’s other disease targets include cancer, inflammation and monogenic diseases, which are disorders caused by a variation in a single gene. The company said the goal is for these treatments to be performed on an outpatient basis.
“Capstan brings together several recent technological advances in the life sciences in a way that we hope can unlock the potential of these technologies to develop new medicines for patients across a wider range of diseases,” Weissman said in a prepared statement.
Capstan is not the only company working to develop therapies that work in vivo on cells. Precision Biosciences, which has partnerships with Novartis and Eli Lilly, is developing such therapies for inherited blood disorders, liver disease, and more. Pfizer is pursuing in vivo genetic medicines for diseases of the muscle, liver and central nervous system in partnership with Beam Therapeutics. Bayer researches in vivo genetic medicines in partnership with Mammoth Biosciences. Startups have also entered the mix with viral vector alternatives which may pave the way for new in vivo drugs.
Capstan is led by President and CEO Laura Schover, whose experience includes CEO roles at Silverback Therapeutics and Synthorx. The money behind Capstan is split into a $63 million seed round of funding last November led by Novartis Venture Fund and OrbiMed. RA Capital Management and Vida Ventures joined this investment. Capstan said it recently closed a $102 million Series A round of funding led by Pfizer Ventures. This round was joined by Leaps by Bayer, Eli Lilly, Bristol Myers Squibb, Polaris Partners, Alexandria Venture Investments, as well as all previous investors of the startup.