Cabaletta Bio Selects Systemic Sclerosis For Second Registrational Trial
Cabaletta Bio outlined a study of approximately 25 patients with systemic sclerosis-associated interstitial lung disease, with enrollment expected to begin in the fourth quarter.
Cabaletta Bio, Inc. (CABA), a late-stage biotechnology company developing cell therapies for autoimmune diseases, selected systemic sclerosis-associated interstitial lung disease for its second registrational study of rese-cel. The decision gave its expansion beyond myositis a defined disease target and trial design after the company said in May that it would choose another pivotal indication following clinical presentations in June.
The company selected the indication after receiving complete early-stage systemic sclerosis data and feedback from the U.S. Food and Drug Administration. Cabaletta expects the single-arm study to begin in the fourth quarter of 2026, using a primary endpoint based on forced vital capacity at 52 weeks. Patients in the earlier study showed improvements in skin and lung disease activity while off immunomodulators and off or tapering steroids.
Myositis remained the company's first planned route to a marketing application. Cabaletta continues to expect results from its 17-patient registrational cohort in mid-2027 and, if successful, plans its first Biologics License Application in the second half of 2027. The company plans to include juvenile myositis data alongside the registrational results and said that inclusion could support a potential FDA Priority Review Voucher.
The supporting clinical evidence came from a separate Phase 1/2 population. At the European Alliance of Associations for Rheumatology congress, Cabaletta reported that 80% of 10 evaluable adults with dermatomyositis or antisynthetase syndrome would have met the registrational cohort's primary endpoint. All dermatomyositis responders maintained their responses through up to 1.5 years of follow-up. Those observations preceded the results still awaited from the registrational study.
Treatment delivery was another focus. Across all 17 Phase 1/2 myositis patients reported at the congress, cytokine release syndrome was absent or limited to Grade 1 fever, and none experienced immune effector cell-associated neurotoxicity syndrome. An outpatient dosing option was already incorporated in the myositis trial. Chief Executive Steven Nichtberger said expanding that option across the RESET development program remained a priority and that the reported safety profile supported its use.
Cabaletta also extended its approach without preconditioning into RESET-MG, its generalized myasthenia gravis study. The change drew on previously reported myasthenia gravis results and emerging findings from its lupus and pemphigus vulgaris cohorts. In May, the company highlighted responses at the lowest dose without preconditioning in pemphigus vulgaris; the latest update included data from both diseases and advancement of higher-dose cohorts. The lowest dose might represent a threshold dose in those trials.
Manufacturing preparations broadened alongside the clinical program. Cabaletta selected ElevateBio as an additional contract development and manufacturing partner alongside Lonza. The company expects both partners to support the transition from clinical to commercial supply, using a substantially closed and partially automated process introduced before registrational evaluation. The addition followed the April announcement of a 10-year commercial supply agreement with automated manufacturing company Cellares.
Clinical data presented at the gene and cell therapy annual meeting showed comparable CAR T cell expansion and B cell depletion kinetics for rese-cel produced on Cellares' Cell Shuttle platform relative to its current clinical manufacturing processes. The Cellares agreement is expected to provide capacity for thousands of batches annually with minimal capital investment.
Second-quarter research and development expenses rose to $44.4 million from $37.6 million a year earlier. The quarterly net loss widened to $51.0 million from $45.1 million, while general and administrative expenses totaled $7.6 million.
Cash, cash equivalents and short-term investments totaled $225.1 million at June 30, including proceeds from the May financing. That balance is expected to fund Cabaletta's operating plan into mid-2027—the same period in which it expects the myositis registrational results, ahead of its planned application later that year.
Stronger demand supports expansion as pricing diverges