Cabaletta’s new data slice for its investigational CD19-CAR T cell therapy shows “robust benefit” for patients with lupus and dermatomyositis without the need for steroids or immunosuppressants, according to a group of analysts.
The updated phase 1/2 data come from the first 10 patients dosed with resecabtagene autoleucel (rese-cel), previously known as CABA-201, which were presented at the American Association for the Advancement of Science annual meeting last week in Boston. The patients are part of Cabaletta’s RESET program across inflammatory muscle condition myositis, systemic lupus erythematosus (SLE) and systemic sclerosis (SSc).
Last month, the biotech shared safety data showing rese-cel was well tolerated among eight patients, with the new update including data on two more patients in SLE/lupus nephritis (LN), plus initial efficacy data.
As of Jan. 8, 2025, 10 patients had been dosed with a one-time infusion of rese-cel and had at least one month of follow-up.
In the SLE trial, three out of four patients in the non-renal cohort achieved remission as of the most recent follow-up visit. The first patient dosed in the LN group achieved a complete renal response (CRR).
All six SLE and LN patients are off all immunosuppressants and steroids as of the data cut-off date.
As for dermatomyositis (DM), the first patient dosed maintained a major total improvement score three months post-infusion. The patient is also immunosuppressant free and is undergoing a steroid taper.
The new data show "robust benefit in lupus and DM,” William Blair analysts wrote in a Feb. 18 note, pointing to improvements in disease severity across all patients.
“Overall, we continue to view the early efficacy across multiple indications as encouraging, especially given that all patients are now off immunosuppressants and some appear to be in, or trending toward, a drug-free disease remission state,” the analysts wrote.
Additionally, the first two immune-mediated necrotizing myopathy (IMNM) patients to be dosed continued to show gradual improvement, which is consistent with published research and indicates a differing response among myositis subtypes, according to Cabaletta.
The first SSc patient dosed with rese-cel in the severe skin group demonstrated clinically meaningful skin improvements across an increasing number of body areas at three months, plus improvement in lung function, after discontinuing all disease-specific therapies, according to the biotech.
On the safety side, of all 10 patients, nine (90%) experienced either no cytokine release syndrome (CRS) or a grade 1 CRS (fever). Immune effector cell-associated neurotoxicity syndrome was reported in one patient.
The William Blair analysts see the SLE/LN and DM data as “most compelling,” adding that the findings could support discussions with the FDA about registrational trial alignment. Notably, both indications have received fast-track designation from the agency.
Cabaletta, for its part, plans to "meet with the FDA to align on registrational trial designs in the first half of 2025," chief medical officer David J. Chang, M.D., said in a statement.
As of Feb. 13, Cabaletta has enrolled 26 patients across the RESET program, which consists of six trials in IIM, SLE, SSc, generalized myasthenia gravis, multiple sclerosis and pemphigus vulgaris (PV) across 50 sites in the U.S. and Europe. The biotech plans to share initial data from the PV trial later this year.
“We look forward to additional updates on the durability of responses as we believe that follow-up of six-months-plus will enable a more productive analysis of the data,” William Blair analysts wrote.
Based on the design of the RESET program and initial regulatory guidance, William Blair analysts believe the therapy “could rapidly advance through clinical development for multiple indications and potentially be first-in-class.”
Despite William Blair's positive outlook, Cabaletta’s stock has dipped slightly, falling 4% over the last five days to rest at $2.22 as of 10:30 a.m. ET on Feb. 19.