Lilly to Acquire Circular RNA Therapeutics Company Orna Therapeutics for Up to $2.4 Billion in Push into In Vivo CAR-T

On February 9 local time, circular RNA therapy company Orna Therapeutics reached a final agreement with multinational pharmaceutical company Eli Lilly and Company, which will acquire Orna in an all-cash transaction. According to the agreement,Orna shareholders are expected to receive a total maximum consideration of $2.4 billion., including the upfront payment and subsequent payments based on specific clinical development milestones.

Orna is one of the representative platform companies in the post-mRNA era in recent years.Its core technology revolves around engineered circular RNA.and novel LNPBuild, by circularizing linear RNA within cells to form a stable structure, thereby enhancing the expression efficiency and therapeutic potential of RNA in vivo. This technology stems from research by Daniel G. Anderson's team at MIT and was incubated and established by the biopharmaceutical investment firm MPM.

The core target of this acquisition is Orna's layout in the field of in vivo cell engineering. Its leading project, ORN-252, targets CD19.in vivoCAR-T therapy has now entered the clinical trial preparation stage, aiming to treat B-cell-driven autoimmune diseases. According to Orna, preclinical experiments show that its circular RNA platform can achieve more durable therapeutic protein expression, with the potential to overcome the technical limitations of existing RNA and cell therapies.

From the strategic intent of Eli Lilly's acquisition this time, Orna's value lies not only in its circular RNA technology itself but also in the complete engineering platform it has built around In Vivo CAR: using engineered circular RNA as an expression vector, combined with an LNP system that has immunocyte tropism, achieving the possibility of directly driving CAR expression in vivo.

Eli Lilly noted in its announcement that while early autologous CAR-T therapies have demonstrated therapeutic potential for autoimmune diseases, the complex ex vivo manufacturing process, high costs, and stringent logistics requirements have limited the therapy's accessibility to a broader patient population. Orna’s in vivo cell therapy approach,Is expected to transform the current highly centralized and lengthy process of cell therapy into a more conventional drug-like, scalable form of administration.This is highly consistent with Eli Lilly's strategic direction of building a long-term innovation platform in the fields of immunology and genetic medicine.

In terms of industrialization, Orna has strengthened its technical validation through external collaborations. In 2022, Merck entered into multiple collaborations with Orna on circular RNA therapies, covering both vaccines and treatments, reflecting the interest of large pharmaceutical companies in this platform.

Orna has been continuously strengthening its delivery system capabilities in recent years. In May 2024, Orna announced the acquisition of ReNAgade Therapeutics, a company focused on RNA delivery, which has achieved targeted delivery to extrahepatic tissues in non-human primate models. After the integration, Orna plans to combine circular RNA technology, a novel LNP delivery system, and RNA editing tools to build a differentiated in vivo CAR-T platform, covering areas such as oncology and autoimmune diseases.

It is worth noting that,Orna and ReNAgade were both incubated and established by MPM BioImpact., and both received substantial financing support in their early stages: Orna completed a $100 million Series A financing in 2021 and a $221 million Series B financing in 2022; ReNAgade launched with a $300 million Series A financing in 2023. The pipeline of the merged company will cover multiple areas including oncology, autoimmune diseases, vaccines, and genetic disorders.

In vivo CAR-T therapy is moving from the proof-of-concept stage to a critical period of industrial layout. Recently, several multinational pharmaceutical companies have continued to increase their investment in the field of in vivo cell engineering, with related transactions mainly focusing on two major technological pathways:

First, an in vivo engineering solution centered on mRNA/LNP, emphasizing repeatable dosing and drug-like characteristics;

Second, a platform for in vivo cell modification that achieves long-term expression through technologies such as viral vectors. In terms of indication selection, the industry also shows a clear focus trend, with cell-driven autoimmune diseases becoming the first area to achieve breakthroughs.

Against this backdrop, Eli Lilly's acquisition of Orna to obtain its integrated capabilities in circular RNA, LNP delivery, and in vivo immune cell engineering can be seen as a systematic layout of a platform technology with long-term evolutionary potential before the critical node of clinical translation in the in vivo CAR-T field. The next step will be for the market to closely watch Eli Lilly's progress in integrating the platform, as well as the safety, controllability, and repeat-dosing capabilities demonstrated by in vivo CAR-T projects such as ORN-252 in clinical trials.