Eli Lilly to Acquire Orna Therapeutics in Deal Valued at Up to $2.4 Billion

Global pharmaceutical major 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 human body. The acquisition marks a significant move by Lilly to expand its capabilities in next-generation genetic medicines and in vivo cell therapies.

Under the terms of the agreement, Orna shareholders could receive up to $2.4 billion in cash, comprising an upfront payment along with additional milestone-based payments tied to clinical development progress. The companies did not disclose the exact upfront amount.

Advancing In Vivo CAR-T and Circular RNA Therapies

Founded to overcome the limitations of traditional cell therapies, Orna Therapeutics is developing a new class of treatments based on engineered circular RNA (circRNA) combined with proprietary lipid nanoparticle (LNP) delivery systems. This approach enables a patient’s own body to generate therapeutic immune cells, potentially eliminating the need for complex ex vivo cell manufacturing.

Orna’s lead program, ORN-252, is a clinical trial–ready, CD19-targeting in vivo CAR-T therapy designed to treat B cell–driven autoimmune diseases. Preclinical experiments suggest that Orna’s circular RNA platform may deliver more durable protein expression than conventional RNA technologies, opening the door to therapies that are not feasible with existing RNA or cell therapy platforms.

Addressing the Limits of Traditional CAR-T Therapies

While early autologous CAR-T therapies have shown promise in autoimmune conditions, their widespread use has been constrained by high costs, logistical complexity, and manufacturing challenges. Lilly believes Orna’s in vivo approach could significantly broaden patient access.

“Early autologous CAR-T studies have shown the promise of cell therapy for patients with autoimmune diseases, but the complexity, cost, and logistics of ex vivo approaches make it challenging to deliver these breakthroughs at scale,” said Francisco Ramírez-Valle, M.D., Ph.D., Senior Vice President and Head of Immunology Research and Early Clinical Development at Lilly. He added that the collaboration could unlock “an entirely new class of genetic medicines and cell therapies for patients who today have limited or no treatment options.”

Strategic Fit for Lilly’s Immunology Pipeline

For Lilly, the acquisition strengthens its immunology and genetic medicine pipeline, aligning with its focus on patient-centric and scalable therapeutic platforms. Orna’s technology has the potential to extend CAR-T–like benefits beyond oncology into autoimmune and inflammatory diseases, an area of growing clinical and commercial interest.

Joe Bolen, Ph.D., Chief Executive Officer of Orna Therapeutics, said the partnership with Lilly would help accelerate the development of in vivo CAR-T therapies. He noted that combining Orna’s circular RNA and LNP platforms with Lilly’s global development and commercialization capabilities could help realize the full potential of the technology.

Transaction and Advisory Details

Lilly will determine the accounting treatment of the transaction in accordance with Generally Accepted Accounting Principles (GAAP) once the deal closes, after which it will be reflected in the company’s financial results and guidance.

• Legal counsel to Lilly: Paul, Weiss, Rifkind, Wharton & Garrison LLP

• Financial advisor to Orna: Lazard

• Legal counsel to Orna: Goodwin Procter LLP

A Broader Signal for the Biotech Sector

The acquisition highlights continued big pharma interest in RNA-based and in vivo cell therapies, particularly platforms that promise to reduce cost and complexity while expanding patient access. As autoimmune diseases remain an area of high unmet need, Lilly’s move positions it at the forefront of a potential shift toward body-generated cell therapies as the next frontier in immunology treatment.