Eli Lilly and Company has entered into a definitive agreement to acquire Orna Therapeutics, a biotechnology firm focused on engineering immune cells directly inside the body using circular RNA technology. The deal could see Orna shareholders receive up to USD 2.4 billion in cash, including upfront and milestone-based payments tied to clinical development progress.

Orna is pioneering a new class of therapeutics that combine engineered circular RNA (oRNA) with Proprietary Lipid Nanoparticle (LNP) delivery systems. This approach is designed to enable patients’ bodies to generate their own cell therapies in vivo, potentially overcoming the logistical, cost and scalability challenges associated with traditional ex vivo cell therapies.

The company’s lead candidate, ORN-252, is a clinical trial-ready, CD19-targeted in vivo Chimeric Antigen Receptor T-cell (CAR-T) therapy aimed at treating B cell-driven autoimmune diseases. Early studies suggest that Orna’s circular RNA platform may enable more durable protein expression compared to existing RNA or cell therapy platforms, opening the door to treatments that were previously not feasible.

Francisco Ramírez-Valle, M.D., Ph.D., Senior Vice President and Head of Immunology research and early clinical development at Lilly, noted that while early autologous CAR-T therapies have shown promise in autoimmune diseases, their complexity and high costs limit widespread patient access. He said the collaboration with Orna could help unlock a new class of genetic medicines and in vivo cell therapies for patients with limited treatment options.

Joe Bolen, Ph.D., Chief Executive Officer of Orna Therapeutics, said the company’s circular RNA technology, combined with its lipid nanoparticle platform, has the potential to expand in vivo CAR-T therapies across a broad range of B cell-driven autoimmune disorders. He added that partnering with Lilly would help accelerate the development and commercialisation of these technologies.

Upon closing, Lilly will account for the transaction in accordance with GAAP and reflect it in its financial results and guidance. Legal and financial advisory roles were handled by Paul, Weiss, Rifkind, Wharton & Garrison LLP for Lilly, Lazard for Orna, and Goodwin Procter LLP as legal counsel to Orna.