RNA therapies and vaccines that have reached patients so far, and many more still in development, are linear—the molecule looks like an untethered string. Merck sees advantages in the approach of Orna Therapeutics, which takes RNA and forms it into a circle shape. The pharmaceutical giant views this technology as a path to new drugs and vaccines, and it’s paying $150 million up front to start a research collaboration.
The alliance announced Tuesday will span multiple programs in infectious diseases and cancer. Specific indications in those therapeutic areas were not disclosed, but Orna could earn up to $3.5 billion in milestone payments, plus royalties from sales if any of products stemming from the research reach the market. Merck is also taking a stake in its new partner. It’s investing $100 million in Cambridge, Massachusetts-based Orna as one of the participants in the biotech’s $221 million Series B round of financing, which was also announced on Tuesday.
Orna’s approach starts with linear RNA. The company’s technology gets linear RNA to form into a circle. Compared to linear RNA, the circle shape’s advantages include greater stability in the body and the ability to produce larger quantities of therapeutic proteins, the company said. Orna also claims circular RNA poses less of a risk of sparking an immune response.
Delivery is another advantage the company claims. The circular shape of Orna’s RNA can be more tightly packed into lipid nanoparticles (LNPs), enabling a larger payload capacity on these particles that deliver the therapy to cells. These particles can be engineered to target particular tissues in the body. Orna’s LNPs come from its joint venture with ReNAgade Therapeutics, an RNA delivery company formed by MPM Capital and BioImpact Capital.
Orna’s research is initially focusing on diseases that are inadequately addressed by other types of medicines. The company’s lead internal program is a cancer immunotherapy in which the CAR T-cell is made inside the patient. This approach avoids the extensive ex vivo manufacturing process of producing these modified immune cells. It also eliminates the need for preconditioning, a step of the treatment in which chemotherapy reduces the number of T cells in the body to improve the persistence and efficacy of the transplanted immune cells. Beyond cancer, the Orna pipeline also spans genetic disease, including Duchenne muscular dystrophy, and Covid-19 vaccine research.
The Merck collaboration follows Orna’s presentation of preclinical data in May during the annual meeting of the American Society of Cell & Gene Therapy. In cancer, the company reported that its in vivo approach to CAR T led to the eradication of tumors in mice. Orna also presented data showing that its technology can deliver to human cells the full-length RNA that code for dystrophin, the key muscle protein that Duchenne patients lack. That’s important because the gene that codes for dystrophin is big. Gene therapies currently in development use a smaller version of the gene in order to get it to fit on the engineered virus that’s used as a delivery vehicle.
Orna isn’t the only company pursuing circular RNA therapies. Last year, Flagship Pioneering unveiled Laronde, a biotech startup that it backed with a $50 million Series A round of funding. Linear mRNA does not last long in the body because the ends of this string are exposed to enzymes in the cell that break down molecule. Laronde contends its technology could enable continuous production of a therapeutic protein because the RNA’s circle shape leaves no ends exposed to RNA-degrading enzymes. The company calls its molecules “endless RNA.”
Merck’s agreement with Orna allows the startup to keep the rights to its circular RNA and lipid nanoparticle technologies, which the company will use to continue development of its wholly owned programs in cancer and genetic diseases. With the Series B cash, Orna said it plans to advance its lead cancer program into human testing in 2024.
Orna is based on technology from MIT. The company was seeded and incubated by MPM Capital. Last year, Orna formally launched and unveiled its technology along with its plans to bring its approach to cancer immunotherapy. The startup also announced the close of an $80 million Series A financing led by MPM Capital, Taiho Ventures, and F2 Ventures. That round drew the interest of large pharmaceutical companies: Gilead Sciences subsidiary Kite invested, as did Bristol Myers Squibb, Astellas Venture Management, and the Novartis Institutes for Biomedical Research. MPM and others joined Merck in investing in Orna’s latest financing round.
“In under three years, Orna has taken proprietary circular RNA from academic literature to the first proof of concept data in preclinical models,” Tom Barnes, CEO of Orna and entrepreneur at BioImpact Capital, an MPM affiliate, said in a prepared statement. “Investors continue to recognize our premier technology and the hard work of our team, and we are pleased to see such unwavering belief in the potential of circular RNA to revolutionize how we treat disease.”
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