Cabaletta Bio (NASDAQ:CABA) executives said the company is advancing rese-cel across multiple autoimmune disease programs after presenting updated clinical and translational data at EULAR, with its lead registrational focus on myositis and a second planned pivotal program in systemic sclerosis.
Speaking at a Goldman Sachs-hosted discussion, Steven Nichtberger, CEO of Cabaletta Bio, said recent EULAR presentations included data from more than 50 patients treated with rese-cel, the company’s autologous 4-1BB CD19 CAR T therapy. Nichtberger said the results support Cabaletta’s view that rese-cel can “reliably reset the immune system” and produce durable, immunomodulator-free responses in most treated patients.
Myositis remains lead registrational program
Cabaletta highlighted EULAR data showing that five of six dermatomyositis patients and three of four anti-synthetase syndrome patients achieved immunomodulator-free remissions at week 16. A Cabaletta representative said patients in the study discontinue all immunomodulatory medicines before receiving a single weight-based dose of rese-cel, an approach also being used in the registrational study.
The company said adult dermatomyositis patients, along with the first juvenile dermatomyositis patient, achieved either a moderate or major Total Improvement Score response at week 16 while remaining off immunomodulators. Among patients achieving the primary endpoint, responses were maintained through the latest follow-up, which in dermatomyositis extends as long as about one and a half years.
The registrational myositis study is single-arm and is expected to enroll 17 patients, with 14 adult dermatomyositis patients and three anti-synthetase syndrome patients. The company also said it is prioritizing juvenile dermatomyositis data for submission with the planned myositis biologics license application, or BLA.
Cabaletta said it narrowed its guidance for the myositis BLA submission to the second half of 2027 to allow for more robust 16-week and 52-week outcomes in juvenile dermatomyositis. The company said inclusion of pediatric data could support eligibility for a priority review voucher if approved. A company representative noted that recent priority review vouchers have sold for roughly $180 million to $200 million, describing the potential voucher as a source of non-dilutive capital.
Durability differs across myositis subtypes
Cabaletta said durability has been stronger so far in dermatomyositis than in anti-synthetase syndrome. A company representative said anti-synthetase syndrome patients have shown rapid and deep responses, but some have later experienced disease activity requiring immunomodulatory medicines, beginning around month six or later.
The company said one possible explanation is that autoantibodies in some anti-synthetase syndrome patients may point to a CD19-negative cell subset that continues to drive disease activity. In dermatomyositis, Cabaletta said transient depletion of the B-cell population appears sufficient to maintain responses in patients followed so far.
Safety profile supports outpatient strategy
Nichtberger and other company executives repeatedly emphasized rese-cel’s safety profile as a differentiator. Nichtberger cited a Nature Biotechnology review and said rese-cel’s tolerability profile appears competitive within autologous CAR T approaches. He said 97% of patients had no ICANS, while 94% either had no cytokine release syndrome or had limited symptoms, typically fever.
The company said that in myositis patients treated to date, no ICANS has been observed, and all patients have had either no cytokine release syndrome or Grade 1 cytokine release syndrome. Cabaletta said this safety profile has allowed it to include outpatient dosing in the registrational setting and in phase 1/2 expansion cohorts.
Steve Gavel, Chief Commercial Officer of Cabaletta Bio, said site of care is a major commercial consideration for cell therapies. He said inpatient capacity has limited uptake of oncology CAR T therapies and argued that rese-cel’s safety profile could support treatment in hospital outpatient settings and, eventually, full outpatient settings. Gavel said outpatient administration could reduce burden for patients, hospitals and payers.
Systemic sclerosis planned as second pivotal study
Cabaletta also discussed plans to initiate a single-arm registrational study in systemic sclerosis in the fourth quarter. The company described systemic sclerosis as one of the highest-burden autoimmune diseases in terms of mortality and morbidity.
At EULAR, Cabaletta reported that systemic sclerosis responses appeared to increase over time while patients remained off disease-specific medications. The company said patients showed an average or median 7.5% improvement at week 36, contrasting that with approved medications that, in their registrational studies, showed either worsening or stabilization at week 52.
The planned systemic sclerosis registrational study is expected to enroll 25 patients and use a 52-week endpoint in patients with interstitial lung disease.
Preconditioning-free work and cash runway
Cabaletta said its preconditioning-free program is designed to preserve the immune-reset effect of rese-cel while avoiding chemotherapy-based preconditioning. In lupus, the company said the first two patients treated at the lowest dose without preconditioning showed substantial B-cell depletion, with one achieving what Cabaletta described as a hallmark of immune system reset from a depletion perspective and the other achieving a 90% decrease in peripheral B cells.
The company said it is enrolling higher-dose cohorts in both pemphigus and lupus. Cabaletta said eliminating preconditioning could be particularly important in lupus because many affected patients are women of childbearing potential.
Nichtberger said Cabaletta recently completed a $150 million financing that included existing investors, new mutual funds, sovereign wealth funds and Eli Lilly. He said the company has about $250 million in cash, which it expects will fund operations well into 2027. He said that runway is expected to cover delivery of pivotal myositis data in 2027 and the start of enrollment in scleroderma, while the company is not yet committing to disclosure timelines for preconditioning-free data.
About Cabaletta Bio (NASDAQ:CABA)
Cabaletta Bio is a clinical-stage biotechnology company pioneering chimeric autoantibody receptor T cell (CAAR-T) therapies for B cell–mediated autoimmune diseases. Its proprietary platform engineers patient-derived T cells to selectively target and eliminate pathogenic B cells that produce disease-driving autoantibodies, with the aim of preserving overall immune function and reducing off-target toxicity.
The company’s lead candidate, DSG3-CAART, is being evaluated in pemphigus vulgaris, a rare blistering disorder caused by autoantibodies against desmoglein 3.
