Eli Lilly’s $7 billion deal for Kelonia Therapeutics on Monday was just the latest example of the sky-high prices that Big Pharmas are willing to pay for in vivo CAR-T tech. In fact, it was the company’s second play for the space this year—having bought Orna Therapeutics for up to $2.4 billion in February.
Lilly joined the likes of Gilead Sciences, which acquired in vivo CAR-T company Interius BioTherapeutics for $350 million in August 2025 and struck a deal with Pregene Biopharma worth up to $1.6 billion via Kite two months later. Last year also saw AbbVie buy Capstan Therapeutics for $2.1 billion, Bristol Myers Squibb acquire Orbital Therapeutics for $1.5 billion, and AstraZeneca pick up EsoBiotec for $1 billion.
But despite this recent “feeding frenzy,” Pitchbook’s Ben Zercher told Fierce he expects in vivo CAR-T dealmaking to slow—not from lack of interest, but from a shortage of viable acquisition targets.
He pointed to Johnson & Johnson and Novartis as notable Big Pharmas that still don’t own any in vivo CAR-T programs. In terms of biotechs still up for grabs, Zercher identified Umoja Biopharma as an obvious remaining target for hungry buyers.
Seattle-based Umoja has two candidates already in the clinic. One of these, the CD22-targeting autoimmune and non-Hodgkin lymphoma candidate UB-VV400/410, is in phase 1 studies in China. The other clinical-stage candidate is UB-VV111, a CD19-targeting in vivo CAR-T hematology asset also in a phase 1 study.
UB-VV111 has already caught the eye of AbbVie, which penned a $1.4 billion biobucks deal back in 2024 for the option to license the asset at a later date. That same deal also gave AbbVie the option to expand the pact to cover four additional in-situ candidates, aimed at targets selected by the Big Pharma.
Despite the attractiveness of Umoja’s in vivo gene delivery tech to potential buyers, the existing partnership with AbbVie could complicate a clean acquisition by another Big Pharma, Zercher suggested.
“Fewer buyers and fewer sellers will slow the pace of deals,” he said. “Buyers may also look offshore, where Chinese players like Starna Therapeutics are advancing in vivo CAR-T into the clinic.”
Suzhou-based Starna secured a 300 million RMB ($44 million) series B last October that was backed by the likes of Lilly Asia Ventures. The RNA biotech said at the time that part of the funds would be used to advance its in vivo CAR-T pipeline, which is led by an autoimmune-focused candidate that’s already in the clinic. Starna is also developing a clinical-stage vaccine for respiratory syncytial virus and a therapeutic vaccine for solid tumors.
Worth the money?
The limited pool of potential assets also means companies will need to maximize what they have. Zercher argued that the potential of in vivo CAR-T justifies high upfront prices—even for early-stage assets. That’s especially true because of the opportunity to expand beyond oncology into autoimmune indications, he pointed out.
“The dual-market potential justifies what would normally be seen as an overpay for early-stage assets,” he said.
Traditional autologous CAR-T therapy requires engineering a patient’s own T cells to fight cancer before reinfusing them into the body. In contrast, in vivo CAR-T uses gene editing to generate CAR-T cells within a patient’s body.
So far, in vivo CAR-Ts have shown early promise as a more efficient and potentially equally effective alternative, according to Leerink Partners analyst Daina Graybosch, Ph.D.
When it comes to Big Pharmas digging deep into their pockets to pay for these companies, she suggested there are two main motives.
“I think most of the deal flow is defensive,” Graybosch told Fierce in an interview. “Companies have invested heavily in [CAR-T] platforms with high barriers to entry. If disruption is coming, they need to be the disruptors.”
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Gilead’s strategy could potentially be viewed in this light. The drugmaker has tasted success with its approved autologous CAR-T therapies Yescarta and Tecartus, developed by its Kite Pharma unit. But this could be put at risk if in vivo approaches prove disruptive.
At the same time, Gilead has witnessed recent sales declines for its approved CAR-T drugs due to intense competition. Amid these external pressures, the pharma may be looking for an answer with next-gen tech.
Meanwhile, the main goal for newer entrants like Lilly may be to build a diversified portfolio of modalities, which helps navigate uncertainty.
“With cell therapy, we think we’re smarter than we are,” Graybosch said. “It’s helpful to have diversity in what you buy.”
Still, clinical data will ultimately decide the field’s fate. Graybosch noted the low toxicity observed in Kelonia’s early data, but is watching closely to see whether those results hold in larger patient populations, particularly in U.S. trials.
She is also focused on whether treatments can be delivered in outpatient settings rather than in intensive care, a key limitation of the treatments to date.
Graybosch said she is already keeping an eye on Umoja’s UB-VV111—which received FDA fast track designation last September—as well as Legend Biotech, which recently treated its first patient with an in vivo candidate and expects data later this year.
But in a rapidly evolving CAR-T landscape, Graybosch cautioned against overinterpreting early results.
“There’s a lot of overreactions to small data sets,” she told Fierce. “The first patients being put on any of these therapies are the worst patients to look at, because there’s something special about those people. They’re being watched in different ways. They have unusual access and the doctors are overselected.
“Forget all those,” she continued. “I’m more interested in 40- to 50-patient data sets with real follow-up to start to understand the potential and the challenges.”
Why Kelonia almost didn’t make it
While Kelonia’s story looks set to end with a hefty buyout by Lilly, the biotech certainly faced its own challenges along the way, according to Kelonia board member Bryan Roberts.
Despite promising science and clinical progress, there was a point when the lentiviral vector delivery specialist “failed spectacularly” to raise the capital needed to continue, according to Roberts, who is also a partner at Kelonia investor Venrock.
The trouble began in 2022, when the biotech market cooled after the bullish post-COVID-19 surge. That shift strained venture group Venrock’s ability to continue supporting the company after seeding Kelonia in late 2020.
For the next couple of years, Kelonia had to do more with less. “We got up to the brink of not having any money a couple times,” Roberts told Fierce in an interview.
An $800 million biobucks licensing deal with Astellas Pharma in early 2024 gave the biotech some breathing room, but Roberts said Venrock still had to provide a bridge loan to keep operations moving.
After an early trial of its BCMA-targeting in vivo CAR-T, dubbed KLN-1010, began in Australia, Kelonia again neared a cash crunch before securing a partnership with Johnson & Johnson in November 2025. The turning point, Roberts said, came with first-in-human data presented at the American Society of Hematology conference later that month, including a late-breaking oral presentation on the company’s lead asset, a BCMA-targeting in vivo CAR-T known as KLN-1010.
Although the dataset included just three patients, the company reported that refractory multiple myeloma patients in the phase 1 trial achieved minimal residual disease negativity at one month, which persisted through three months.
“That was what created a consensus view that Kelonia had something really interesting,” Roberts said. “The strength of the clinical data turned people around.”
Now, just a few months later, Kelonia and its lead asset are in line to become the property of Eli Lilly. The buyout features $3.25 billion upfront, with the potential to reach $7 billion altogether, including milestones. Roberts said Venrock’s investment could return more than 45 times its original stake.
“It’s possible to build these businesses more capital-efficiently,” Roberts said. “And clinical data trumps everything.”
Though Kelonia’s journey was a funding roller coaster, the ex vivo CAR-T market has remained on a steady upward trajectory. Roberts said the surge in interest can be explained by the fact that in vivo approaches aim to match the efficacy of their ex vivo predecessors while avoiding their significant drawbacks, including side effects, manufacturing delays and high costs.
“The goal is to match its efficacy and improve everything else,” Roberts said.
“We need more patients and more time, but I believe that’s achievable,” he added. “Ex vivo CAR-T will soon go the way of the buffalo.”
