Orna Therapeutics, Inc.

Eli Lilly entered into a definitive agreement to acquire Orna Therapeutics for up to $2.4 billion in cash, gaining the latter's in vivo CAR-T pipeline that includes programmes designed to reset the immune system and address B-cell-driven autoimmune diseases."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, Lilly's head of immunology research and early clinical development.Orna's lead programme is ORN-252, a clinical trial-ready, CD19 targeting in vivo CAR-T therapy designed to treat B-cell-driven autoimmune diseases. The company's therapeutics utilise engineered circular RNA paired with lipid nanoparticles to allow the patient's own body to generate cell therapies that can treat underlying disease. Meanwhile, Lilly noted that Orna's "broad platform" provides for long-term innovation in genetic medicine and in vivo cell engineering.Under the agreed terms, Orna shareholders will receive an upfront payment and subsequent payments upon achievement of certain clinical development milestones.

iStock, SvetaZi The deal gets Lilly access to Orna’s in vivo CAR T technology. The biotech’s lead asset, which has yet to start clinical testing, is focused on B cell–driven autoimmune diseases. Eli Lilly has long resisted the CAR T space despite admitting that the treatments have promise. Now, the weight loss juggernaut has found an entry point via a $2.4 billion deal to acquire in vivo CAR T biotech Orna Therapeutics. CEO David Ricks has said in the past that issues with accessibility have limited the company’s interest in the modality. “The data is amazing,” Ricks told Reuters in 2019, “but practically, it’s not reaching many people.” The Indianapolis-based pharma is betting on Orna’s technology to address those concerns, according Monday’s announcement . The acquisition also signals that Lilly is not specifically focusing on CAR Ts for cancer but on autoimmune disorders, which other CAR T developers have also begun to explore. Orna’s pipeline is still preclinical, but lead asset Orna-252 is “clinical trial-ready,” according to the deal announcement. Orna-252 creates CD19-targeting CAR T cells, aimed at treating B cell–driven autoimmune diseases. That asset has shown its ability to deplete B cells in nonhuman primates, according to data presented in December 2025. CAR T CAR T and Related Therapies Home In on Autoimmune Disease Multiple players are exploring whether modalities designed to combat B cell malignancies can be repurposed against lupus, myasthenia gravis and other conditions traced to misdirected immune response. November 4, 2024 · 9 min read · Shawna Williams Read More Orna’s approach involves delivering a circular RNA molecule via a lipid nanoparticle (LNP) to induce cells to make CAR T cells in the body, rather than removing, modifying and then reintroducing patients’ cells, as traditional CAR T does. The in vivo strategy “offers lower manufacturing cost and shelf-availability,” according to analysts at William Blair, writing to investors Monday morning. “I’m very proud of what we achieved at Orna,” Tom Barnes, CEO of the Massachusetts-based biotech, wrote in a LinkedIn post Monday morning, “and of the team that did it. Orna . . . was the first circular RNA company and proselytized the value of circles over lines.” Using circular RNA to modify cells, instead of linear, simplifies manufacturing and purification processes, increases the half-life of the therapy and makes LNP formulations easier to make, according to Orna . Other projects in Orna’s pipeline include a gene editing collaboration with Vertex Pharmaceuticals to develop treatments for sickle cell disease and beta thalassemia, and a partnership with Merck to develop RNA vaccines. This is the latest bolt-on deal for Lilly this calendar year; In January, the pharma offered Seamless a potential $1.12 billion to develop gene editing therapies in hearing loss, Repertoire up to $1.9 billion to develop autoimmune treatments and InduPro could see a up to $950 million for cancer antibodies. Orna is also the second full acquisition of the year for Lilly, after the $1.2 billion buy of inflammatory disease biotech Ventyx Biosciences in January. On Feb. 8, Lilly also announced a collaboration with the Chinese firm Innovent Biologics, the seventh between the two companies. That deal has Lilly paying Innovent $350 million up front, with $8.5 billion in potential payments related to commercial milestones stemming from the partnership’s work on therapies in oncology and immunology.

Dive Brief:Eli Lilly will acquire biotechnology startup Orna Therapeutics, saying Monday it will pay up to $2.4 billion to buy the privately owned company and a technology able to reprogram immune cells within the body.The Indiana-based drugmaker didnt disclose how much upfront cash its shelling out for Orna, which specializes in circular RNA medicines that are believed to be more stable and easier to pair with the lipid nanoparticles used for delivery. But it noted in its statement that it intends to use Ornas technology to develop cell therapies for autoimmune conditions.In announcing the deal, Lilly cited its interest in Ornas lead project, which instructs immune cells to latch onto B cells that are attacking patients tissue in inflammatory diseases. The company presented data from preclinical studies at the American Society for Hematology meeting in December that its using to support advancing into Phase 1 studies.Dive Insight:The acquisition extends a streak of genetic medicine deals undertaken by Lilly, which has used collaborations and buyouts to amass a pipeline of gene therapies and gene editing treatments for high cholesterol, hearing loss and other conditions. Its also at least the fifth recent buyout of a company working on technology for making in vivo cell therapies, which could be more convenient alternatives to their complicated ex vivo counterparts.The deal also offers Ornas backers a return on their investment in a company thats drawn the interest of multiple large drugmakersbut has also reportedly laid off staff.Like the ex vivo treatments in which technicians genetically alter patient cells in a lab, Ornas lead program, called ORN-252, also aims to weaponize a persons immune defenders against disease.However, rather than modifying cells outside the body, Ornas treatment stimulates cells inside the body to produce a protein that can help them find a disease target in ORN-252s case, a protein flag on malfunctioning B cells.That target, CD19, is also the focus of an array of cancer-fighting cell therapies. Several companies are repurposing the approach against inflammatory diseases like lupus, following encouraging results from academic studies.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 Ramrez-Valle, Lillys senior vice president of immunology research and early clinical development, in a statement.The acquisition also hands Lilly some assets that have been partnered elsewhere. Orna previously struck deals with Vertex Pharmaceuticals to make in vivo gene therapies and with Merck & Co. to develop next-generation vaccines.Orna also has an alliance in place with Chinas Shanghai Simnova Biotech to develop a cancer cell therapy. '