The last couple of months have seen what amounts to a high-profile exodus from the cell therapy space.
Takeda kicked off the recent spate of departures, announcing early last month that it would not only halt investments in the modality, but also offload its pipeline and platform to an as-yet-unidentified external partner. This, after the Japanese multinational spent more than 8 years and hundreds of millions of dollars building its cell therapy business.
The dominoes started falling after that. Weeks later, Novo Nordisk revealed it would terminate all cell therapy work—including on a type 1 diabetes program—despite the pharma’s heavy metabolic disease focus—a move that left nearly 250 people jobless. Then, troubled Belgian biotech Galapagos shut down its cell therapy business after failing to find an external buyer for its assets.
Even before Takeda’s withdrawal, however, ominous signs were already looming in cell therapy. In January, for instance, an ad-hoc analysis of early data of Cargo Therapeutics’ lead asset firi-cel cast doubt on its clinical profile, ultimately forcing the biotech to abandon an ongoing mid-stage study and halve its headcount. Cargo in March terminated 90% of its staff and all development work.
That same month, Vertex Pharmaceuticals pulled the plug on a cell therapy-device combo for type 1 diabetes that packaged pancreatic islet cells in a proprietary device that would protect them against the immune system.
Despite this cloud over the space, there remains a lot of excitement about cell therapy. At the 2025 meeting of the American College of Rheumatology (ACR) last month, educational sessions about cell therapies—in particular CAR Ts—were “standing room only,” Lynelle Hoch, president of Bristol Myers Squibb’s Cell Therapy Organization, told BioSpace in a recent interview.
In this piece, BioSpace looks at some of the players continuing to ride this wave of excitement and push the boundaries of cell therapy’s potential—even as a growing number of their peers pull back.
BMS, Gilead and J&J Lead The Way in CAR T
“I can’t speak to why other companies are bailing,” Hoch said, but for BMS, there are plenty of reasons to stay. “BMS is uniquely positioned,” she continued. “We got in early and getting in early allowed us to build capabilities clinically, translationally and [in] manufacturing.”
Indeed, BMS is one of the few companies with FDA-approved cell therapies, and the only one with two CAR T assets that work against two different targets: Abecma, an anti-BCMA product indicated for relapsed or refractory multiple myeloma, and Breyanzi, which binds to CD19 and is approved for several blood cancers.
Despite this dominant position, the pharma continues to build out its CAR T capabilities. In October, for instance, BMS dropped $1.5 billion to acquire Orbital Therapeutics and its pipeline of RNA assets that can reprogram immune cells directly inside patients’ bodies. BMS is also exploring the use of CAR Ts for autoimmune diseases, widely considered a frontier for the modality.
Joining BMS at CAR T’s forefront is Gilead, which through its subsidiary Kite last month put down $120 million and promised up to $1.5 billion in milestones to partner with Chinese cell therapy specialist Pregene. Confirming the deal to Fierce Biotech, a spokesperson for Kite said Pregene would help the company to advance “in vivo” therapies. In August, Kite also swallowed Interius BioTherapeutics for $350 million, gaining its in vivo CAR T capabilities.
In parallel to the in vivo work, Gilead continues to advance its lead CAR T candidate anitocabtagene autoleucel (anito-cel) in partnership with California biotech Arcellx. Directed against the BCMA protein, anito-cel is being tested for relapsed or refractory multiple myeloma, for which the partners are running the Phase II iMMagine-1 and Phase III iMMagine-3 studies. Mid-stage data released in May pointed to a 97% overall response rate including a complete response/stringent complete response rate of 68%.
Gilead also has the late-stage axicabtagene ciloleucel, being tested for high-risk follicular and large B cell lymphoma. Like BMS, Gilead has two FDA-approved CAR T therapies, Yescarta and Tecartus, both designed to target CD19 and indicated for a variety of blood cancers.
Rounding out the trinity of CAR T pharma leaders is Johnson & Johnson, which has one commercial-stage asset in Legend Biotech-partnered Carvykti, a BCMA-directed therapy for relapsed or refractory multiple myeloma.
With $963 million in worldwide sales last year, Carvykti is rapidly gaining on BMS in this market (Breyanzi sold $747 million last year, while Abecma earned $406 million).
Carvykti’s market performance is supported by a strong clinical profile. In December last year, data from the Phase III CARTITUDE-4 study showed that 89% of Carvykti-treated participants had no detectable cancer cells at a median follow-up of three years, achieving high statistical significance versus current standard therapies.
Beyond Carvykti, J&J is also working on the CAR T candidate JNJ-4496, which in June hit a 100% objective response rate in a Phase Ib study of large B cell lymphoma—making it a compelling potential competitor to Gilead’s Yescarta, if approved.
Immatics Stands Out in Cancer with PRAME Focus
Aside from the big players and their biotech partners, many other smaller companies continue to brave the increasingly rough cell therapy waters. One of those is Germany- and Texas–based Immatics, which is building its pipeline around the oncology target PRAME.
Expressed in more than 50 different cancers, according to Immatics’ website, PRAME is a protein not typically found in healthy cells and in malignant tissues promotes unchecked growth and prevents cell death. PRAME has been detected in various malignancies, including endometrial, uterine, ovarian and lung cancers, as well as melanomas.
Leading Immatics’ efforts to target PRAME is anzu-cel, a T cell therapy that works by triggering a strong anti-cancer immune response once it recognizes PRAME. The asset is currently being evaluated in the Phase III SUPRAME trial as a second-line treatment for cutaneous melanoma.
SUPRAME is evaluating anzu-cel’s impact on progression-free and overall survival. Immatics does not plan on disclosing topline data from SUPRAME, according to its Q2 business report, in order to “protect the integrity” of the study.
Nevertheless, the biotech expects both interim and final analyses from the study to happen next year, building toward an FDA submission in the first half of 2027. If approved, Immatics anticipates launching anzu-cel in the latter part of 2027.
Aside from melanoma, anzu-cel is also being trialed for uveal melanoma, for which a Phase Ib readout last month showed a 67% confirmed objective response rate and an 88% disease control rate. The company has opened a Phase II cohort in this indication, looking to enroll around 30 patients across the U.S. and Germany. In partnership with Moderna, Immatics is also advancing a combination regimen of anzu-cel and the mRNA cancer vaccine mRNA-4203 for cutaneous melanoma and synovial sarcoma.
Kyverna Leverages CAR T for Autoimmune Diseases
One of the companies leading the charge in the autoimmune space is Kyverna Therapeutics, with its CAR T candidate KYV-101. Using a CAR construct designed by the National Institutes of Health for better tolerability, KYV-101 works by targeting the CD19 antigen found on B cells, while also seeking out the CD28 protein to stimulate T cells. This mechanism of action results in deep depletion of B cells, in turn addressing the underlying molecular driver of autoimmune diseases, according to the biotech.
Late last month, Kyverna touted a 100% response rate for KYV-101 in the Phase II/III KYSA-6 study in generalized myasthenia gravis (gMG). This readout came from six treated patients with moderate to severe disease, all of whom had previously received immunosuppressive therapies. Despite the small sample, analysts at William Blair were effusive about the findings, writing in an Oct. 30 note that KYV-101 set “a new efficacy standard in the field.”
The magnitude of KYV-101’s benefits, they added, makes it “differentiated from current therapies and other late-stage assets.” Kyverna now plans to advance to the Phase III portion of KYSA-6, for which enrollment will start before the end of the year.
Kyverna has a broad autoimmune development program for KYV-101 outside of gMG. Among its targets are stiff person syndrome, a rare disorder that develops when antibodies attack the glutamic acid decarboxylase enzyme, in turn compromising muscle control. KYV-101 is in a registrational Phase II trial in this indication, for which topline data are expected early next year, according to the biotech’s third-quarter report earlier this month. An FDA application is scheduled for the first half of 2026.
Other KYV-101 indications include lupus nephritis, multiple sclerosis, rheumatoid arthritis and systemic sclerosis.
Cabaletta Runs Sweeping Autoimmune CAR T Program
Likewise pushing the boundaries of CAR T technology beyond cancer is Cabaletta Bio, which has built a sprawling clinical program around its only asset CABA-201, an investigational cell therapy also known as resecabtagene autoleucel or rese-cel.
As in the case of Kyverna’s molecule, rese-cel is also designed to target CD19 to locate B cells. What makes Cabaletta’s approach unique, however, is its use of the 4-1BB domain, a particular chunk of a protein that helps boost the activity of T cells. Its particular structure, according to the biotech’s website, allows rese-cel to completely but temporarily deplete B cells in a patient’s body, in effect triggering an “immune system reset.”
Cabaletta is harnessing this mechanism to target a wide variety of autoimmune conditions, though its most advanced programs are in dermatomyositis, systemic sclerosis (SSc) and systemic lupus erythematosus (SLE).
At ACR, the biotech presented three Phase I/II readouts for rese-cel in these indications. In RESET-Myositis, Cabaletta dosed six patients, four of whom had dermatomyositis and two had antisynthetase syndrome. Results showed a “moderate or major improvement” in disease response 16 weeks after rese-cel treatment without the help of immunomodulators.
Based on these findings, Cabaletta is moving forward with a registrational cohort within RESET-Myositis, targeting these two indications. In line with FDA feedback, the biotech aims to enroll 14 patients into this group by year-end.
Also at ACR, Cabaletta demonstrated that rese-cel treatment led to SLE remission in three treated patients, while a fourth participant with lupus nephritis reached complete renal response. Meanwhile, in SSc, the cell therapy induced immune system reset, resulting in clinical benefits even without background immunomodulators. Cabaletta aims to align with the FDA this year for pivotal study designs in these indications.
The rese-cel program extends beyond these diseases and also includes gMG, relapsing and progressive multiple sclerosis and pemphigus vulgaris.
https://www.biospace.com/drug-development/6-companies-hanging-on-in-cell-therapy
