Cabaletta Bio recently announced new clinical data for rese-cel (resecabtagene autoleucel) at the European Alliance of Associations for Rheumatology (EULAR) 2026 Congress, held June 3-6 in London, UK, supporting its registrational strategy across multiple autoimmune diseases, including dermatomyositis (DM), systemic sclerosis (SSc), and lupus.¹ Data from 52 evaluable patients across myositis, lupus, and SSc cohorts were presented in multiple oral and poster sessions, as well as a company-sponsored satellite symposium.¹

The presentations include findings from the phase 1/2 RESET-Myositis (NCT06154252), RESET-SSc (NCT06328777), and RESET-SLE (NCT06121297) trials, each evaluating rese-cel, an autologous chimeric antigen receptor (CAR) T cell therapy engineered with a fully human CD19 binder and a 4-1BB co-stimulatory domain.¹ The data also encompass the first patient with juvenile dermatomyositis (JDM) treated with rese-cel and initial pharmacokinetic/pharmacodynamic (PK/PD) findings from the first 2 patients with lupus to receive preconditioning-free (PC-free) rese-cel.¹

In RESET-Myositis, 83% (5/6) of patients with DM achieved an immunomodulator-free (IM-free), moderate to major Total Improvement Score (TIS) response at 16 weeks following rese-cel treatment.¹ All 5 of those patients maintained their IM-free response through the latest follow-up, with durations as long as 1.5 years.¹ Among patients with antisynthetase syndrome (ASyS), 75% (3/4) achieved the same IM-free, moderate to major TIS response at 16 weeks; durability in these patients was variable, consistent with published academic CD19-CAR T data.¹

The first patient with JDM achieved an IM-free, moderate TIS response at 16 weeks, maintained through the latest follow-up at 32 weeks.¹ Across all 17 patients with myositis, 100% (17/17) experienced either no cytokine release syndrome (CRS) or transient fever (Grade 1 CRS); no immune effector cell-associated neurotoxicity syndrome (ICANS) of any grade was observed.¹

Overall, 80% (8/10) of patients with DM and ASyS in the phase 1/2 cohort would have met the primary end point of the registrational cohort, according to Cabaletta.¹ Patient enrollment is progressing in the registrational, single-arm DM/ASyS cohort; topline data are anticipated in mid-2027.¹

Rese-cel Safety and Efficacy in RESET-SSc and RESET-SLE

In RESET-SSc, patients demonstrated overall improvement in skin and lung disease activity while off immunomodulators and off or tapering steroids, with responses appearing to improve with longer follow-up.¹ Among patients with interstitial lung disease (ILD) at screening, a median improvement of 7.5% in percent predicted forced vital capacity (FVC) was observed at 36 weeks of follow-up.¹ Additionally, 83% (5/6) of patients achieved the revised Composite Response Index in Systemic Sclerosis (rCRISS)-25, and 67% (4/6) achieved rCRISS-50 at 36 weeks while off all immunomodulators.¹

In SSc safety data, 87% (13/15) of patients experienced either no CRS or Grade 1 CRS; 93% (14/15) experienced no ICANS, with 1 previously reported Grade 3 ICANS case.¹ Cabaletta plans to initiate a single-arm registrational study of approximately 25 patients with SSc-ILD with an FVC-based primary end point at 52 weeks in the fourth quarter of 2026.¹

In RESET-SLE, 75% (6/8) of patients with 12 months of follow-up achieved the Definition of Remission in SLE (DORIS) while remaining off immunomodulators for the full follow-up duration.¹ Among PC-free lupus patients, initial PK/PD findings suggest the lowest PC-free rese-cel dose may represent a threshold dose; 1 of the 2 patients achieved deep B cell depletion comparable to what has been observed in lupus patients treated with rese-cel plus preconditioning.¹ One PC-free patient experienced Grade 1 CRS and no ICANS was observed.¹

Pan-translational PK/PD data presented at the conference showed a short-term rese-cel activity phase resulting in deep B cell depletion and evidence of immune system reset, with B cells repopulating at a median of approximately 2 months, potentially minimizing the risk of prolonged B cell aplasia.¹

"Over 80% of the phase 1/2 dermatomyositis patients would have achieved the pivotal primary endpoint and all five of these patients maintained their response through the latest follow-up as long as 1.5 years," said David J. Chang, MD, Chief Medical Officer of Cabaletta Bio, in the news release.¹ "The unanticipated clinical activity at the lowest dose of PC-free rese-cel further supports the potential to expand the market, and we believe with the optimal dose, preconditioning may not be required for many patients to achieve immune reset in lupus and other autoimmune diseases."¹

According to Cabaletta, rese-cel's biologic license application submission strategy for myositis is planned to include both JDM and adult DM, which may qualify the company for a priority review voucher given its Rare Pediatric Disease Designation for JDM treatment.^1,2 Dose-ranging data for PC-free rese-cel are planned across multiple autoimmune indications based on the safety profile and activity observed at the lowest dose in lupus and pemphigus vulgaris.¹

References

1. Cabaletta Bio announces new rese-cel data and development updates across autoimmune portfolio, including encouraging early PC-free lupus findings, at EULAR 2026 Congress. News release. Cabaletta Bio. June 3, 2026. Accessed June 3, 2026. https://www.cabalettabio.com/news-media/press-releases/detail/149/cabaletta-bio-announces-new-rese-cel-data-and-development
2. Cabaletta Bio reports first quarter 2026 financial results and provides business update. News release. Cabaletta Bio. May 14, 2026. Accessed June 3, 2026. https://www.cabalettabio.com/investors/news-events/press-releases/detail/148/cabaletta-bio-reports-first-quarter-2026-financial-results

Frequently Asked Questions

What did the RESET-Myositis phase 1/2 data show for rese-cel in dermatomyositis?

In the phase 1/2 RESET-Myositis cohort, 83% (5/6) of patients with DM achieved an IM-free, moderate-to-major TIS response at 16 weeks following rese-cel treatment; all 5 maintained their response through the latest follow-up, up to 1.5 years. Overall, 80% (8/10) of patients with DM and ASyS would have met the registrational cohort's primary endpoint, according to Cabaletta Bio.

What is the registrational strategy for rese-cel in systemic sclerosis?

Cabaletta plans to initiate a single-arm registrational study of approximately 25 patients with SSc-ILD in the fourth quarter of 2026, using an FVC-based primary end point at 52 weeks, based on phase 1/2 RESET-SSc data and FDA feedback.

What is PC-free rese-cel and what did early lupus data show?

PC-free rese-cel refers to rese-cel administered without a lymphodepleting preconditioning regimen. In the first 2 PC-free lupus patients, initial PK/PD findings suggest the lowest dose tested may be a threshold dose; 1 patient achieved deep B cell depletion comparable to preconditioning cohort outcomes, and no ICANS was observed in either patient.