Cabaletta Bio (NASDAQ:CABA) used a fireside chat at TD Cowen’s 46th Annual Health Care Conference to highlight progress across its autoimmune cell therapy program, with executives emphasizing upcoming clinical readouts, a push toward non-preconditioning regimens, and a manufacturing strategy built around full automation.
Pivotal myositis study begins enrollment; more pivotal planning underway
CEO and co-founder Steven Nichtberger said the company recently initiated enrollment in a pivotal 17-patient myositis trial. He described it as a single-arm study structure that Cabaletta has “agreed with FDA repeatedly over the past year.”
Non-preconditioning strategy: early pemphigus signals and lupus expansion
Management repeatedly returned to the potential of administering its CD19 CAR T-cell therapy, rese-cel, without lymphodepleting preconditioning (i.e., no fludarabine or cyclophosphamide). Nichtberger called “no preconditioning” a long-standing “holy grail” for CAR T and said the company believes higher dosing could potentially overcome the lack of preconditioning, given rese-cel’s safety profile.
CMO David Chang discussed data previously presented in pemphigus vulgaris patients treated at the same starting dose used with preconditioning—1 million cells per kilogram—but without any preconditioning. In the first three no-preconditioning patients, Chang said Cabaletta saw evidence of responses:
- One patient had a partial response, with partial B-cell depletion, partial clinical improvement, and partial expansion resembling what is seen with full preconditioning.
- Two other patients “did quite well” in terms of expansion, B-cell depletion, and clinical improvement.
However, management also noted variability: Nichtberger said some patients did not respond well, which led the company to conclude it may be at a “threshold dose.” Chang said Cabaletta is pursuing higher dosing and expects to report on patients receiving the higher dose later this year, though he said the company has not disclosed the specific higher dose level.
Chang added that the no-preconditioning concept is being extended to lupus. He said Cabaletta has opened a lupus cohort that will not receive preconditioning and will start at the same 1 million cells per kilogram dose, with the company hoping to report acute data later this year.
How Cabaletta frames “durability” and immune reset
Asked how investors should evaluate durability prior to multi-year follow-up, Chang described two markers Cabaletta uses. First, the company looks at the phenotype of repopulating B-cells two to three months after depletion to assess whether cells appear “transitional naive,” which he said suggests a new B-cell population coming from bone marrow and may be predictive of an immune reset. Second, Cabaletta is evaluating BAFF (B-cell activating factor) levels, which Chang said rise in response to B-cell depletion and may correlate with deeper depletion including in lymph nodes.
Safety profile in autoimmune patients; limited ICANS reported
Chang said Cabaletta has reported on 40 patients across four indications in its RESET study (myositis, lupus, systemic sclerosis, and myasthenia gravis). Across those 40 patients, he said 95% experienced either Grade 1 cytokine release syndrome (CRS) or no CRS. He contrasted that with oncology CAR T experience, where he cited higher rates and more severe CRS.
On neurotoxicity, management said Cabaletta has not had an ICANS case in over a year, which they attributed to instituting stricter requirements preventing dosing if patients show any evidence of fever or infection.
Nichtberger argued that rese-cel’s most common side effect has been transient fever, sometimes managed with acetaminophen and sometimes with tocilizumab. He also said Cabaletta does not prophylax with steroids or tocilizumab. Looking ahead, he referenced a BLA filing “scheduled for next year.”
Manufacturing bet: Cellares automation and a lower-capital model
A central theme of the discussion was Cabaletta’s manufacturing partnership with Cellares, which Nichtberger described as a fully automated approach requiring no human intervention during production. He said Cabaletta believes this model can drive what it expects to be the “lowest cost of goods in the industry” for an autologous CAR T product, with minimal capital investment and “healthy margins.”
Nichtberger described the Cellares “Cell Shuttle” as an integrated system capable of manufacturing 16 patient samples simultaneously, potentially across different products. He said the system could reduce the need for clean rooms and specialized technicians, and he offered an example that treating 1,000 patients in the first year would require two Cell Shuttles. He also argued that autoimmune patients’ generally better health could reduce manufacturing failures commonly seen in oncology settings.
Chief Commercial Officer Steve Gavel, who recently joined the company, said the autoimmune population is “fundamentally much healthier” than end-stage cancer patients, which he said can improve inbound T-cell material and manufacturing outcomes. Gavel also pointed to the commercial insurance mix in younger autoimmune populations versus the Medicare inpatient environment typical of oncology CAR T launches, and he suggested outpatient administration could become more feasible as a result.
As near-term catalysts, management pointed to upcoming Phase I/II releases across the portfolio in the first half of the year, planned no-preconditioning updates in lupus and higher-dose pemphigus later this year, and initial safety data from patients dosed with product made on the Cellares platform. Nichtberger also said Cabaletta learned via a Cellares LinkedIn post that a first patient’s product had been successfully manufactured and cleared quality control, with dosing expected imminently.
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.
