The RNA therapies and vaccines that have reached patients so far, and many others still in development, are linear—the molecule looks like an untied string. Merck sees advantages in Orna Therapeutics’ approach, which takes RNA and shapes it into a circle. The pharmaceutical giant sees this technology as a path to new drugs and vaccines, and it is pays $150 million in advance to start a research collaboration.
The alliance, announced Tuesday, will span multiple infectious disease and cancer programs. Specific indications in those therapeutic areas were not disclosed, but Orna could earn up to $3.5 billion in milestone payments, plus sales royalties, if products arising from the research reach the market. Merck also takes a stake in its new partner. It invested $100 million in Cambridge, Mass.-based Orna as one of the participants in the biotech $221 million Series B round of funding, which was also announced Tuesday.
Orna’s approach starts with linear RNA. The company’s technology causes linear RNA to form into a circle. Compared to linear RNA, advantages of the circular shape include greater stability in the body and the ability to produce larger amounts of therapeutic proteins, the company said. Orna also claims that circular RNA poses less risk of triggering an immune response.
Delivery is another advantage, according to the company. The circular form of Orna RNA can be more tightly packed into lipid nanoparticles (LNPs), allowing for greater payload capacity on these particles that deliver the therapy to cells. These particles can be engineered to target specific 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 initially focused on diseases that were not adequately treated by other types of drugs. The company’s flagship in-house program is cancer immunotherapy, where the CAR T-cell is produced inside the patient. This approach avoids the extensive ex vivo manufacturing process to produce these modified immune cells. It also eliminates the need for pretreatment, a treatment step in which chemotherapy reduces the number of T cells in the body to improve the resistance and efficacy of the transplanted immune cells. In addition to cancer, Orna’s pipeline also includes genetic diseases, including Duchenne muscular dystrophy, and research into a vaccine against Covid-19.
The collaboration with Merck follows that of Orna presentation of preclinical data in May during the annual meeting of the American Society for Gene and Cell 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 laboratory data showing that its technology can delivered to human cells A full-length RNA that encodes dystrophin, the key muscle protein missing from Duchenne patients. This is important because the gene that codes for dystrophin is large. Gene therapies currently being developed use a smaller version of the gene to make it fit the engineered virus that is used as a delivery vehicle.
Orna is not the only company pursuing circular RNA therapies. Last year, Pioneering flagship revealed Laronde, a biotech startup that raised 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 the molecule. Laronde claims that his technology can allow continuous production of a therapeutic protein because the circular shape of the RNA leaves no ends exposed to RNA-degrading enzymes. The company calls its molecules “infinite RNA.”
Merck’s agreement with Orna allows the startup to retain rights to its circular RNA and lipid nanoparticle technologies, which the company will use to continue development of its wholly owned cancer and genetic disease programs. With the Series B money, Orna said it plans to move its flagship 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 has officially launched and unveiled its technology along with plans to bring its approach to cancer immunotherapy. The startup also announced the close of $80 million Series A funding led by MPM Capital, Taiho Ventures and F2 Ventures. This round attracted the interest of major pharmaceutical companies: Gilead Sciences subsidiary Kite invested, as well as Bristol Myers Squibb, Astellas Venture Management and the biomedical research institutes Novartis. MPM and others joined Merck in investing in Orna’s latest funding round.
“In less than three years, Orna has taken its own circular RNA from the academic literature to first proof-of-concept data in preclinical models,” said Tom Barnes, Orna’s CEO and an entrepreneur at BioImpact Capital, an MPM affiliate, in a prepared statement. “Investors continue to recognize our world-class technology and the hard work of our team, and we are pleased to see such unwavering faith in circular RNA’s potential to revolutionize the way we treat disease.”
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