Benzinga | Dec 14, 2021 07:06AM EST

Cabaletta Bio Reports Top-line Biologic Activity Data From Two Lowest Dose Cohorts In DesCAARTes Trial In Patients With Mucosal Pemphigus Vulgaris

Cabaletta Bio, Inc. (NASDAQ:CABA), a clinical-stage biotechnology company focused on the discovery and development of engineered T cell therapies for patients with B cell-mediated autoimmune diseases, today reported top-line data on biologic activity from the two lowest dose cohorts in the DesCAARTes(tm) Phase 1 clinical trial of DSG3-CAART for the treatment of patients with mucosal Pemphigus Vulgaris (mPV).



As of December 12, 2021, six patients, comprising the two lowest dose cohorts (20 million and 100 million DSG3-CAART cells administered without lymphodepletion) had completed three to six months of follow-up for evaluation of DSG3-CAART biologic activity. Patients enrolled had persistent mild to moderate disease severity prior to infusion despite receiving or having received systemic medication for treatment of their mPV symptoms prior to enrollment. Parameters being used in the trial to evaluate potential biologic activity include persistence of DSG3-CAART, change in level of DSG3 autoantibodies, change in mPV therapy or need for new systemic rescue therapy, and change in disease activity (e.g., as assessed by Pemphigus Disease Area Index (PDAI) and Oral Disease Severity Score (ODSS)). Prior to infusion, disease activity scores improved in five of six participants in the absence of any protocol directed additions to baseline therapy. Of those five participants, one had a decline in DSG3 autoantibody levels ?20% during that period. Top-line data on biologic activity among the first six participants in the lowest dose cohorts are:

* In cohort A1, participants received 20 million DSG3-CAART cells: Two of three participants had DSG3 autoantibody levels that rose ?20% along with disease activity scores (e.g., PDAI and ODSS) that worsened within six months after DSG3-CAART infusion, with one of these participants receiving additional systemic medication. Both participants reduced or discontinued selected systemic therapies prior to DSG3-CAART infusion, as required by the protocol. One of three participants had modest DSG3 autoantibody levels and mild disease activity at infusion and had a negative DSG3 level at six months along with disease activity scores of zero on both scales at six months with no systemic medications for mPV since DSG3-CAART infusion. As permitted by protocol, this participant was enrolled due to worsening symptoms despite receiving two different systemic therapies within 9 months of DSG3-CAART infusion. The systemic therapies may have impacted clinical scores and DSG3 levels, both of which improved between screening and infusion.

* In cohort A2, participants received 100 million DSG3-CAART cells: Two of three participants maintained stable DSG3 autoantibody levels that have not persistently changed +/- 20% of pre-infusion levels through four months. Through the six month follow-up period, one of these patients maintained stable disease activity scores, while the other patient maintained stable scores initially before subsequently worsening. Both patients did not require any new systemic medications post-infusion through the entire follow-up period. One of three participants had DSG3 autoantibody levels that rose ?20% from pre-infusion levels despite stable disease activity scores with four months of follow-up. This participant subsequently received systemic medication to improve disease activity after DSG3-CAART infusion.

* DSG3-CAART persistence was not observed above the assay's threshold for quantification in any participant from the first two cohorts at three months post-infusion.

Additional data on the initial cohorts in the DesCAARTes(tm) trial are anticipated to be presented at medical meetings and/or scientific sessions in 2022.

"As the first targeted cell therapy clinical trial for patients with a B cell-mediated autoimmune disease, the DesCAARTes(tm) trial was designed with patient safety as the top priority. By starting with these low-dose cohorts, we have been able to administer the product to autoimmune patients, with no dose-limiting toxicities or clinically relevant adverse events observed to date," reported David J. Chang, M.D., Chief Medical Officer of Cabaletta. "While clear signs of DSG3-CAART biologic activity were not observed to date in the two lowest cell dose cohorts, the emerging clinical and serological data in one of the six patients who has improved since DSG3-CAART infusion is notable. Patients in the fourth dosing cohort are currently being dosed with 2.5 billion cells, which is 25 and 125 fold greater than the two dose cohorts reported today. Based on communications with the U.S. Food and Drug Administration (FDA) dating to the first half of 2021, as well as the safety data reported from our first three dosing cohorts, we plan to expand the DesCAARTes(tm) trial to evaluate higher dose cohorts and consolidated dosing regimens and, subject to an IND amendment, an enhanced manufacturing process. Our engagements and interactions with patients, investigators, and advocacy groups have given us confidence that patients with mPV are highly interested in a deep, durable, and potentially curative therapy, and we look forward to advancing the trial to potentially identify an optimal dose regimen that maximizes the opportunity for patients to achieve those goals, while maintaining a favorable safety profile."

The first additional cohort in the dose escalation phase of the DesCAARTes(tm) trial is anticipated to be the A5 cohort, in which patients will receive between 5.0-7.5 billion DSG3-CAART cells with a consolidated fractionated infusion regimen including only two fractions -- 30% followed by 70%. The planned enhanced manufacturing process aims to amplify the already present cell subtypes in the product in order to potentially improve product potency and trafficking to tissue where the target B cells reside.

"Based on the reported safety data from the first three cohorts, the observation of dose-dependent increases in persistence previously reported in Cohort A3 relative to the first two cohorts, and consultation with investigators, advisors, and the FDA, we now have the opportunity to expand the trial to evaluate higher dose cohorts, consolidated dosing and, subject to an IND amendment, an enhanced manufacturing process," said Steven Nichtberger, M.D., Chief Executive Officer and Co-founder of Cabaletta. "With six sites activated and dosing underway in the fourth cohort at a dose of 2.5 billion DSG3-CAART cells, we anticipate reporting top-line biologic activity from the 500 million cell cohort A3 as well as 28-day safety data from the 2.5 billion cell cohort in the first quarter of 2022."