Lilly to Acquire Novel CAR-T Innovator Orna Therapeutics for $2.4 Billion to Advance In Vivo Cell Therapy Platform

Eli Lilly has entered into a definitive agreement to acquire Orna Therapeutics, a biotechnology firm pioneering the development of immune cell therapies engineered directly within the body. The transaction is valued at up to $2.4 billion, including an upfront payment and milestone-based potential payouts.

Also read: UCB presented long-term BE HEARD trial in patients with Hidradenitis Suppurativa

Advancing In Vivo CAR-T and Genetic Medicine

Orna Therapeutics is building a pipeline of in vivo CAR-T candidates that could redefine treatment approaches for autoimmune conditions driven by B cells. Its most advanced program, ORN-252, is a CD19-targeted CAR-T therapy ready for clinical evaluation.

Rather than altering immune cells ex vivo, Orna’s approach enables a patient’s own body to produce the therapeutic cells internally, potentially resetting immune balance to address the root cause of autoimmune disease.

The company’s proprietary oRNA (circular RNA) technology underpins this innovation. Unlike conventional linear mRNA, oRNAs form naturally closed circular structures that enhance durability, stability, and protein expression. Preclinical data suggest this design could offer sustained therapeutic activity, paving the way for new genetic medicines that overcome limitations of existing RNA and cell therapy modalities.

Strategic Fit for Lilly’s Long-Term Innovation Goals

Through this acquisition, Lilly gains access to Orna’s expertise in circular RNA design, lipid nanoparticle formulation, and in vivo cell engineering. The deal reinforces Lilly’s commitment to advancing genetic medicines and developing next-generation platforms capable of addressing complex diseases at the cellular level.

Also read: Roche’s investigational therapy fenebrutinib shows breakthrough results in primary progressive multiple sclerosis (PPMS)

How Orna’s oRNA Technology Works

The oRNA molecules are created through self-circularization of linear RNA precursors, eliminating the need for traditional structural elements like caps, tails, or modified nucleotides. This design leads to:

Simplified manufacturing with straightforward purification steps and reduced risk of immune-related side effects.

Enhanced stability, as circular RNA exhibits a longer half-life compared to linear mRNA.

Stronger protein production, thanks to optimized sequences that boost internal ribosome entry site (IRES) activity.

Efficient formulation into lipid nanoparticles that can deliver therapies directly to target cells in the body.

Also read: FDA says no to AstraZeneca’s Saphnelo Subcutaneous Formulation for Lupus Patients

Orna’s FoRCE (Formulated oRNA Cell-based Evaluation) high-throughput screening platform enables rapid assessment of thousands of oRNA variants in multiple cell types. This allows the discovery of optimal combinations for therapeutic performance and precision delivery.

Traditional CAR-T therapies, including those developed by Bristol Myers Squibb, Gilead Sciences, and Johnson & Johnson, require extracting, modifying, and reinfusing a patient’s immune cells. Orna’s in vivo approach represents a fundamental shift, aiming to generate these potent immune cells within the patient’s body, offering a potentially simpler and more scalable treatment model.