The RNA therapeutics and vaccines that have reached patients so far, and many more are still in development, are linear—the molecule looks like an untethered rope. Merck sees advantages in Orna Therapeutics’ approach, which takes RNA and forms it into a circle.The pharma giant sees the technology as a pathway to new drugs and vaccines $150 million paid Start research collaborations in advance.
The alliance announced Tuesday will cover multiple programs in infectious diseases and cancer. Specific indications for these therapeutic areas were not disclosed, but Orna could earn up to $3.5 billion in milestone payments and royalties from sales if any products resulting from the research reach the market. Merck has also taken a stake in its new partner. As one of the biotech players, it is investing $100 million in Cambridge, Massachusetts-based Orna. $221 million in Series B financing financing, which was also announced on Tuesday.
Orna’s approach starts with linear RNA. The company’s technology makes linear RNAs form a circle. The company says the advantages of circular shape compared to linear RNA include greater stability in vivo and the ability to produce more therapeutic proteins. Orna also claims that circular RNAs have less risk of triggering an immune response.
Delivery is another advantage the company claims. The round shape of Orna’s RNA allows for tighter packing into lipid nanoparticles (LNPs), giving these particles greater payload capacity to deliver therapeutics to cells. These particles can be designed to target specific tissues in the body. Orna’s LNP comes 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 other types of drugs could not adequately address. The company’s main internal program is cancer immunotherapy, in which CAR T cells are made in a patient. This approach avoids the extensive ex vivo manufacturing process for producing these modified immune cells. It also eliminates the need for preconditioning, a therapeutic step in which chemotherapy reduces the number of T cells in the body to improve the persistence and efficacy of transplanted immune cells. In addition to cancer, the Orna pipeline also covers genetic diseases, including Duchenne muscular dystrophy and Covid-19 vaccine research.
Merck’s collaboration follows Orna’s introduce Preclinical data presented in May at the annual meeting of the American Society for Gene and Cell Therapy.On the cancer side, the company reported that Its in vivo approach to CAR T resulted in the eradication of tumors in mice. Orna also provided lab data showing that its technology can delivery to human cells Full-length RNA encoding dystrophin, a key muscle protein that Duchenne patients lack. This is important because the gene encoding dystrophin is large. Gene therapies currently in development use smaller versions of genes to make them suitable for engineered viruses to be used as delivery vehicles.
Orna isn’t the only company pursuing circular RNA therapeutics. last year, Flagship Pioneer Unveiled Laronde, a biotech startup, raised $50 million in Series A funding. Linear mRNA doesn’t last long in the body because the end of the line is exposed to enzymes in the cell that break down the molecule. Laronde believes that his technology can sustainably produce therapeutic proteins because the rounded shape of the RNA doesn’t expose the ends to RNA-degrading enzymes. The company calls its molecule “endless RNA.”
Merck’s agreement with Orna allows the startup to retain rights to its circular RNA and lipid nanoparticle technologies, which it will use to continue developing its wholly-owned programs in cancer and genetic diseases. With the Series B cash, Orna said it plans to advance its leading cancer program into human testing in 2024.
Orna is based on MIT technology. The company was seeded and incubated by MPM Capital. last year, Ona officially launched and announced its technology and plans to apply its methods to cancer immunotherapy. The startup also announced the closing of an $80 million Series A round led by MPM Capital, Taiho Ventures and F2 Ventures. The round attracted interest from big pharma: Gilead Sciences subsidiary Kite invested, as did Bristol-Myers Squibb, Astellas Risk Management and the Novartis Institute for Biomedical Research. MPM and others, along with Merck, invested in Orna’s latest funding round.
“In less than three years, Orna has taken a proprietary circular RNA from the academic literature to the first proof-of-concept data in a preclinical model,” said Orna’s CEO and MPM affiliate BioImpact Capital Ventures Tom Barnes said in a prepared statement. “Investors continue to recognize our best-in-class technology and the hard work of our team, and we are delighted to see the strong belief in circular RNAs’ potential to revolutionize the way we treat disease.”
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