The RNA therapies and vaccines that have reached patients so far, and many more still in development, are linear – the molecule looks like an untied string. Merck sees benefits in Orna Therapeutics’ approach, which takes RNA and shapes it into a circle shape. The pharma giant sees the technology as a pathway to new drugs and vaccines, and it’s paying $150 million up front to start a research collaboration.
The alliance announced on Tuesday will cover several programs in the field of infectious diseases and cancer. Specific indications in these therapeutic areas were not disclosed, but Orna could earn up to $3.5 billion in milestone payments, plus royalties on sales if any of the research-based products arrive. on the market. Merck is also taking a stake in its new partner. It is investing $100 million in Cambridge, Mass.-based Orna as one of the participants in the biotech’s $221 million Series B funding round, which was also announced on Tuesday.
Orna’s approach starts with linear RNA. The company’s technology allows linear RNA to form a circle. Compared to linear RNA, the 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 is less likely to trigger an immune response.
Delivery is another advantage claimed by the company. The circular shape of Orna’s RNA can be more tightly packed into lipid nanoparticles (LNPs), allowing greater payload capacity on these particles that deliver therapy to cells. These particles can be designed 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 initially focused on diseases that were insufficiently treated with other types of drugs. The company’s main in-house program is 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 in treatment in which chemotherapy reduces the number of T cells in the body to improve the persistence and effectiveness of transplanted immune cells. Beyond cancer, the Orna pipeline also covers genetic diseases, including Duchenne muscular dystrophy, and Covid-19 vaccine research.
The Merck collaboration follows Orna’s presentation of the preclinical data in May at 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 provide human cells with the full RNA that codes for dystrophin, the key muscle protein that Duchenne patients lack. It’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 adapt it to the modified virus which is used as a delivery vehicle.
Orna is not the only company offering circular RNA therapies. Last year, Flagship Pioneering unveiled Laronde, a biotech startup it backed with $50 million in Series A funding. Linear mRNA does not last long in the body because the ends of this chain are exposed to enzymes in the cell which break down the molecule. Laronde argues that his technology could enable continuous production of a therapeutic protein because the circular shape of RNA leaves no ends exposed to RNA-degrading enzymes. The company calls its molecules “endless RNA.”
Merck’s agreement with Orna allows the startup to retain the rights to its circular RNA and lipid nanoparticle technologies, which the company will use to further develop its wholly-owned cancer and genetic disease programs. With the Series B money, Orna said she plans to advance her lead cancer program toward human testing in 2024.
Orna is based on MIT technology. The company was created and incubated by MPM Capital. Last year, Orna officially launched and unveiled its technology and plans to bring its approach to cancer immunotherapy. The startup also announced the closing of an $80 million Series A funding round led by MPM Capital, Taiho Ventures and F2 Ventures. This round attracted the interest of major pharmaceutical companies: Kite, a subsidiary of Gilead Sciences, invested, as did Bristol Myers Squibb, Astellas Venture Management and the Novartis Institutes for Biomedical Research. MPM and others have joined Merck to invest in Orna’s latest round of financing.
“In less than three years, Orna has taken proprietary circular RNA from academic literature to early proof-of-concept data in preclinical models,” said Tom Barnes, CEO of Orna and entrepreneur at BioImpact Capital, a subsidiary of BPM, in a prepared statement. “Investors continue to recognize our cutting-edge technology and the hard work of our team, and we are thrilled to see such unwavering belief in the potential of circular RNA to revolutionize the way we treat disease.”
Photo by Getty Images