Flush with cash from its obesity/diabetes dual blockbuster tirzepatide, Eli Lilly signaled earlier this month that it intended to invest some of that money into new deals to strengthen its pipelines in oncology, neuroscience, and immunology.
Lilly has begun delivering on that promise through a pair of business development deals announced this week. The pharma giant said it will shell out $2.4 billion to acquire genetic medicine developer Orna Therapeutics, whose lead programs apply in vivo chimeric antigen receptor (CAR) T-cell therapies targeting forms of autoimmune diseases and cancers.
In addition, Lilly committed up to $8.85 billion—including $350 million upfront—to launch a seventh collaboration with Chinese-based biotech Innovent Biologics, this one focused on developing new treatments in oncology and immunology.
The deals come a week after Daniel Skovronsky, MD, PhD, Lilly’s chief scientific and product officer and the president of Lilly Research Laboratories, told analysts Lilly was prepared to spend significant capital to build up its pipeline beyond metabolic disorders—where it generated a combined $36.507 billion last year in sales from tirzepatide, the dual-action glucagon-like peptide receptor 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) drug it markets in diabetes as Mounjaro® and in obesity as Zepbound®.
“Thumb on the scale”
“Across our non-obesity work, which is, of course, oncology, neuroscience, and immunology, we have our thumb on the scale for investment decisions. We see lots of good opportunities in those areas, and we’re reinvesting some of the proceeds from the obesity opportunity to make sure we can further accelerate growth in those promising areas,” Skovronsky said on February 4 on Lilly’s Q4 2025 earnings call.
Skovronsky responded to a question from Seamus Fernandez, a senior managing director and equity research analyst covering the global biopharmaceutical and biotechnology sectors for Guggenheim Securities: “While you can’t take your eye off the ball on obesity, just wondering why you couldn’t attack immunology broadly in the same way as you have obesity, investing earlier, faster, and more aggressively given the substantial generation that we’re starting to see from the overall portfolio?
“What are the issues that would prevent you from doing something like this, whether it be by your internal efforts or perhaps a more aggressive business development approach?” Fernandez asked. “It seems like this is a cash-driven opportunity where there’s a lot of spend, but a huge amount of upside opportunity with a $170 billion total market out there to access.”
The Orna and Innovent deals did not lift Lilly’s stock, which closed Monday down 1.28% to $1,044.67 from $1,058.18 on Friday, after jumping nearly 5% soon after the start of trading to $1,106.94. Lilly shares dipped another nearly 2% Tuesday, closing at $1,025.00.
Based in the Boston suburb of Watertown, MA, privately held Orna uses engineered circular RNA from its own circular RNA technology platform (oRNA®) paired with novel lipid nanoparticles (LNPs) to allow the patient’s own body to generate its cell therapies. oRNAs are engineered as linear RNAs that undergo autocatalytic circularization, designed for higher efficiency, followed by proprietary purification steps. The company uses proprietary internal ribosome entry site (IRES) technology to maximize protein output and adapts LNPs to create oRNAs that it says can safely reach sites in the body where they are needed.
By using self-circularization from a linear RNA precursor, Orna says it has achieved unmatched advantages over traditional linear mRNA therapies, including simplified production (no caps, no tails, no modified nucleotides), simplified purification (thus lower risk of adverse immune reactions), longer RNA half-life intended to achieve increased durability and stability, increased protein expression, ease in working with larger-size RNAs, and easier, more straightforward formulation into lipid nanoparticles.
Entering the clinic
Orna’s pipeline is co-led by the two cell therapy programs of ORN-252, which is based on the company’s panCAR™ immune cells and is expected to enter the clinic and begin first-in-human clinical trials this year. One is a CD19-targeting in vivo CAR being developed to treat B-cell-driven autoimmune diseases; the other is a dual-action CD19 and BCMA-targeting in vivo CAR designed to treat B-cell malignancies.
“Orna acquisition expands Lilly’s capability in oncology/immunology space without material impact on the overall business,” Evan David Seigerman, a managing director and head of healthcare research at BMO Capital Markets, commented in a research note. “In vivo CAR T remains a risky area, as it is an early technology without validation from large-scale clinical trials and is becoming increasingly competitive.”
Seigerman cited expansions into in vivo CAR T development last year through acquisitions by Bristol Myers Squibb (of Orbital Therapeutics for $1.5 billion); AbbVie (of Capstan Therapeutics for up to $2.1 billion); and Gilead Sciences (of Interius BioTherapeutics for $350 million).
“Despite this, we believe Lilly’s strong balance sheet and cash flow can support this higher-risk program, and Orna’s in vivo CAR-T platform has the potential to expand Lilly’s capabilities in the oncology and immunology space,” Seigerman added.
At the 67th American Society of Hematology (ASH) Annual Meeting in Orlando, FL, Orna announced positive preclinical data for ORN-252 showing robust B cell depletion in humanized mice in vivo at doses as low as 0.03 mg/kg, plus complete peripheral and splenic B cell depletion in nonhuman primates (NHPs) at doses as low as 0.1 mg/kg. In a humanized mouse lupus model, ORN-252 showed robust B cell depletion with concurrent reduction in double-stranded DNA (dsDNA) titers compared to rituximab, the cancer and autoimmune treatment marketed by Genentech and Biogen as Rituxan®.
Also in Orna’s pipeline: A gene editing program partnered with Vertex Pharmaceuticals and intended to treat sickle cell disease and beta thalassemia; and a program with Merck & Co. designed to apply protective antigens and unspecified “other strategies” to treat infectious disease and other disorders. The company said it is also exploring undisclosed “new disease areas where oRNA® and LNP technologies can address unmet need.”
“We see this acquisition by LLY as complementary to a growing pipeline of in vivo-based therapies,” David Risinger, a senior managing director and senior research analyst covering diversified biopharmaceuticals with Leerink Partners, wrote in a research note.
That pipeline, Risinger noted, included the pipeline of Verve Therapeutics, the gene-edited therapy developer acquired by Lilly last year for up to $1.3 billion. Verve’s lead program is VERVE-102, a first-in-class in vivo gene editing therapy designed to treat heterozygous familial hypercholesterolemia (HeFH) and atherosclerotic cardiovascular disease by targeting PCSK9.
In April 2025, Verve announced positive initial data from the Phase Ib Heart-2 trial (NCT06164730) assessing VERVE-102 in HeFH and/or premature coronary artery disease. Among 14 participants across three dose levels, a single VERVE-102 infusion yielded dose-dependent decreases in blood PCSK9 protein levels and low-density lipoprotein cholesterol (LDL-C), with a mean reduction in blood LDL-C of 53% and a maximum of 69% seen among four participants in the 0.6 mg/kg dose cohort.
Lilly agreed to pay an undisclosed upfront payment, plus future payments tied to achieving clinical development milestones, totaling up to $2.4 billion.
“Entirely new class”
“We look forward to working with Orna colleagues to potentially unlock an entirely new class of genetic medicines and cell therapies for patients who today have limited or no treatment options,” said Francisco Ramírez-Valle, MD, PhD, Lilly’s senior vice president, head of immunology research and early clinical development, in a statement.
With Innovent, Lilly agreed to partner on new antibody treatments in oncology and immunology—two of the Chinese biotech’s therapeutic areas of interest. Others include cardiovascular and metabolic, ophthalmologic, and unspecified other major diseases.
Innovent said it will lead the development of programs from concept through clinical proof-of-concept (Phase II clinical trial completion) in China, drawing on its own antibody technology platforms and what it called efficient clinical execution. Through the collaboration, Innovent has granted Lilly an exclusive license to develop and commercialize the programs worldwide outside Greater China, with Innovent retaining rights in Greater China.
“We’re delighted to partner with Lilly, our trusted global pharmaceutical partner for over 10 years, to pursue novel medicines to improve treatment outcomes for patients with cancer and immune disorders,” said Michael Yu, PhD, founder, chairman of the board, and CEO of Innovent. “This alliance moves beyond traditional licensing to create a seamless, end-to-end innovation ecosystem that combines our agile discovery and early-stage development engine with Lilly’s extensive global scale and creates a highly efficient model for cross-border synergy.”
The Innovent and Orna deals follow a busy January for Eli Lilly in which it rang in 2026 by agreeing to acquire inflammatory-mediated disease drug developer Ventyx Biosciences for approximately $1.2 billion, then inked an up-to-$1.12 billion-plus collaboration with Seamless Therapeutics to apply its next-generation gene-editing approach, based on programmable recombinases, to develop and commercialize hearing loss treatments.
