In a move that underscores Big Pharma’s race to harness next-generation genetic medicine, Eli Lilly to buy Orna Therapeutics in a transaction that could deliver up to $2.4 billion in cash to Orna’s shareholders.

Eli Lilly & Co. announced Monday that it has agreed to acquire the biotechnology firm, with payments structured as a combination of upfront cash and additional payouts tied to the achievement of specific clinical development milestones.

The deal places Lilly squarely in the fast-evolving field of engineered RNA therapeutics — a frontier scientists describe as both promising and technically complex.

Engineering Immunity From Within

Based in Watertown, Massachusetts, Orna Therapeutics focuses on engineering immune cells directly inside the body — known as in vivo approaches — rather than extracting and modifying them outside the patient.

The company is advancing a new class of treatments built on engineered circular RNA paired with proprietary lipid nanoparticles. The goal: enable the body itself to produce therapeutic cells capable of targeting underlying diseases.

At the center of Orna’s pipeline is ORN-252, a therapy ready to enter clinical trials. The program targets in vivo Chimeric Antigen Receptor T-cell, or CAR-T, therapy for B cell-driven autoimmune diseases. Unlike traditional CAR-T methods that require ex vivo cell manipulation, Orna’s approach seeks to simplify delivery and broaden patient access.

Addressing Complexity in Cell Therapy

“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 to the broader population of patients who need them,” said Francisco Ramírez-Valle, Eli Lilly’s senior vice president and head of immunology research and early clinical development.

He added that Lilly looks forward to collaborating with Orna’s team to potentially unlock what he described as an entirely new class of genetic medicines.

According to the companies, preliminary experiments suggest Orna’s circular RNA platform may provide more sustained expression of therapeutic proteins and open the door to medicines that are “not feasible” using existing RNA or cell therapy technologies.

A Shared Vision for Genetic Medicines

Orna Chief Executive Joe Bolen said the company’s circular RNA technology, combined with its lipid nanoparticle delivery platform, could pave the way for in vivo CAR-T therapies across a broad spectrum of B cell-driven autoimmune conditions.

“We are excited to join forces with Lilly, an industry leader in the development of patient-centric therapeutics to realize the full potential of these technologies,” Bolen said.

The acquisition reflects Lilly’s broader push into cutting-edge immunology and genetic medicine, as pharmaceutical giants increasingly invest in platforms that promise durable, scalable treatments.

Legal Advisers

Eli Lilly was advised on the transaction by Paul Weiss Rifkind Wharton & Garrison LLP. The advisory team included partners Krishna Veeraraghavan, Chelsea Darnell and Jeffrey D. Osterman.

Full details regarding the Goodwin Procter LLP legal team representing Orna were not immediately available Monday.

As the deal advances, regulatory and clinical milestones will determine whether this high-stakes partnership delivers on its promise — a reminder that in biotechnology, as in exploration, the boldest steps often carry both risk and transformative potential.