Eli Lilly has taken a decisive step into the rapidly evolving field of in vivo CAR-T therapy through the acquisition of Orna Therapeutics in a deal valued at up to $2.4 billion. The transaction positions Lilly among a growing group of major pharmaceutical companies investing in next-generation genetic and cell therapy platforms.
While the total deal value has been disclosed, Lilly has not specified how much will be paid upfront versus milestone-based payments tied to clinical progress.
Why This Acquisition Matters
Traditional CAR-T therapies require extracting a patient’s immune cells, engineering them outside the body, and reinfusing them — a complex and costly process that limits scalability. In contrast, in vivo CAR-T therapies aim to reprogram immune cells directly inside the patient’s body, potentially simplifying manufacturing and expanding access.
Orna Therapeutics has built its platform around engineered circular RNA (oRNA) combined with lipid nanoparticles. This approach is designed to generate CAR-T cells within the body itself, removing the need for ex vivo cell manipulation.
According to Lilly, early experimental data suggests that Orna’s circular RNA platform may provide more durable expression of therapeutic proteins compared to traditional linear RNA approaches. If validated in clinical studies, this could open the door to therapies that are not feasible with existing RNA or cell therapy technologies.
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Spotlight on ORN-252
At the center of the acquisition is ORN-252, a CD19-targeting in vivo CAR-T therapy described by Lilly as “clinical trial-ready.” The candidate is being developed for B-cell-driven autoimmune diseases.
Autoimmune disorders such as lupus and certain inflammatory conditions are increasingly being explored as targets for CAR-T therapy. Early autologous CAR-T studies have demonstrated meaningful potential in resetting dysfunctional immune systems. However, cost, manufacturing complexity, and logistical challenges have limited broader implementation.
Francisco Ramírez-Valle, M.D., Ph.D., head of immunology research and early clinical development at Lilly, acknowledged these barriers:
“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.”
By integrating Orna’s in vivo platform, Lilly aims to explore a more accessible pathway to immune reprogramming.
A Broader Strategic Trend
Lilly’s move follows a wave of acquisitions in the in vivo CAR-T space:
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Gilead Sciences acquired Interius BioTherapeutics for $350 million and entered a deal with Pregene worth up to $1.6 billion.
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AbbVie acquired Capstan Therapeutics for $2.1 billion last year.
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Bristol Myers Squibb purchased Orbital Therapeutics for $1.5 billion.
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AstraZeneca acquired EsoBiotec for $1 billion.
These transactions reflect strong industry interest in genetic medicine platforms capable of delivering cell therapies directly inside patients.
Lilly had signaled its intent to explore this area months earlier when it began recruiting leadership focused on CAR-T biology. The Orna acquisition formalizes that strategic direction.
From MIT Research to Big Pharma Integration
Founded in 2021, Orna Therapeutics launched with $100 million in funding and a mission to bring engineered CAR constructs directly to immune cells within the body. The company’s platform is rooted in research from MIT by Alex Wesselhoeft, Ph.D., and Professor Dan Anderson, Ph.D.
Orna has since developed what Lilly describes as a “broad platform” capable of supporting multiple in vivo CAR-T programs — effectively creating a pipeline engine rather than a single-asset play.
Looking Ahead
With this acquisition, Lilly secures full ownership of Orna’s circular RNA platform and in vivo cell engineering capabilities. The company believes this could represent a long-term innovation opportunity in genetic medicine and immune system modulation.
If successful, in vivo CAR-T therapies could redefine how autoimmune and potentially other immune-mediated diseases are treated — offering a more streamlined alternative to today’s cell therapy infrastructure.
The coming years will determine whether circular RNA-based in vivo CAR-T approaches can translate early scientific promise into clinical reality. For now, Lilly has placed a significant strategic bet on the future of genetic medicine.
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