Coexistence, not conflict, in cell therapy platform war

In February, Eli Lilly acquired circular RNA specialist Orna Therapeutics in a deal worth up to $2.4 billion, then in April followed it up with a $7 billion deal for lentiviral delivery company Kelonia Therapeutics. In the same space, Gilead's Kite Pharma struck a $1.64 billion deal with China's Pregene Biopharma in late 2025, AbbVie paid $2.1 billion for Capstan Therapeutics around the same time, while AstraZeneca acquired EsoBiotec for up to $1 billion in March 2025.

In vivo cell therapy — the target of all of these deals  — aims to engineer a patient's cells inside the body. The mechanism is a single intravenous infusion, bypassing the leukapheresis, cleanroom manufacturing, and weeks-long vein-to-vein timelines that have constrained ex vivo cell therapies since Kymriah's (tisagenlecleucel) approval in 2017.

In theory it is the platform that makes other cell therapies obsolete, but a panel at BPI Europe in Vienna last month (entitled, with deliberate provocation, “The Platform Wars” and moderated by this author) painted a more measured picture. Covering autologous, allogeneic, and in vivo modalities, albeit in only 30 minutes, the discussion landed not on a single winner but on a future in which each platform finds its own therapeutic niche.

Autologous CAR-T is the established platform, with seven FDA-approved products collectively generating over $5 billion in annual revenue. But a decade after Kymriah, the manufacturing and supply chain model has barely changed.

“It's still one automated closed loop per patient, so the growth is very linear,” said Liedewij Vandewal, senior consultant at Deloitte's NextGen Therapies Centre of Excellence, who works with companies trying to make autologous manufacturing viable at scale. While automation has helped with contamination control and closed processing, she said quality control (QC) remains a major pain point and the geographic constraint — patients needing to be near the manufacturing sites — continues to be a logistical problem.

Some companies have explored a decentralized model via bedside or hospital-based production, moving the process to the patient rather than the other way around. Belgium-based Galapagos, for example, built a decentralized platform for its CAR-T candidate that delivered fresh cells with a seven-day vein-to-vein time. (The company has since announced its exit from the cell therapy space entirely.)

Vandewal cautioned that decentralization shifts the complexity rather than eliminating it as sites must be equipped, staffed, and qualified to handle GMP manufacturing, and not every hospital is able to implement this.

Claire Wartel, director of regulatory affairs at Sartorius Polyplus, pointed to new integrated systems — including her firm’s recently launched Sartorius Evo Cell platform — as progress towards running multiple patient batches in parallel with reduced footprint. But despite tech innovations, she was candid about where the field stands.

“To be able to continue on this modality, we definitely need to bring new equipment to speed up and to reduce the cost of goods,” Wartel said.

Allogeneic, or off-the-shelf, CAR-T was supposed to solve autologous's scaling problems but has yet to produce an FDA-approved product. Investor enthusiasm has waned accordingly, with the CEO of one specialist recently telling Fierce Biotech the field is in a “nuclear winter.”

But interim data published by Allogene Therapeutics in April from its pivotal phase 2 ALPHA3 trial of cema-cel in lymphoma suggests a thaw, with the treatment arm significantly outperforming observation and most patients managed as outpatients.

The panel did not dwell on the data but addressed the structural challenges. Vandewal questioned the robustness of the platform, noting that allogeneic introduces batch-to-batch variability tied to donor cells. Thus if a single batch fails, multiple patients are affected. “We haven't seen the results yet that they are durable and that it can withstand effects longer than six or twelve months,” she said.

However, she added that allogeneic's limitations could become advantages in the right indication. “It might be a very interesting modality for autoimmune diseases. The short-term effects are more interesting there, so that might be the perfect solution.”

The logic, therefore, points towards coexistence rather than competition: autologous for oncology, where durable response matters, and allogeneic for autoimmune conditions, where shorter-term B-cell depletion may actually be the point. It is a division that would echo how monoclonal antibodies and small molecules carved out distinct but overlapping roles across the biologics era.

And then there is in vivo, where the money is loudest but the data is thinnest. A phase 1 study of EsoBiotec's ESO-T01 — an anti-BCMA in vivo CAR-T co-developed with Pregene and since acquired by AstraZeneca — published in Nature Medicine in March showed responses in four of five multiple myeloma patients, three of them stringent complete remissions, without lymphodepleting chemotherapy. But all five experienced serious adverse events, one fatally, and it was only five patients.

Furthermore, manufacturing challenges do not simply disappear with in vivo, Vandewal said. The therapies still require viral vectors, currently produced in small-scale systems, and scaling those processes up introduces its own problems.

“If you want to scale that up, they're very sensitive,” she said. “It's very difficult to see how they will react. That's a lot of unknowns.”

Wartel added that regulatory expectations for in vivo therapies will be “exponentially” higher than for ex vivo approaches, given that gene-modifying vectors are being delivered systemically. She drew a parallel with the early years of adeno-associated virus (AAV) gene therapy, a field that also took longer to mature than its initial hype suggested.

The upside, both panelists agreed, is in vivo therapies could reach patients in geographies and healthcare settings where the infrastructure for ex vivo manufacturing is missing, thus justifying the investment, even if the timeline is longer than the dealmaking suggests.

So, as the panel was asked, what does the landscape look like in five to ten years? The billions being spent on in vivo are very unlikely to render the other modalities obsolete, but rather just make the map more complicated. “Let's meet in five years' time,” this author told the panel. “Let's see where we're at.”