Objective:

This phase 1 study is to document the presence of KYV-101 chimeric antigen receptor (CAR)-T cells in the central nervous system (CNS) through their detection in cerebral spinal fluid (CSF) and surmise depletion of CNS resident B cells via anti-CD19 CAR-T cells through clearance of oligoclonal bands (OCB)s and/or normalization of IgG index in adult participants with treatment-refractory progressive multiple sclerosis (MS).

Background:

Despite the success of B cell depleting therapies in suppressing disease activity in relapsing forms of MS, many patients with progressive forms of MS continue to experience worsening disability. This may be due to CNS resident B cells that are resilient to peripheral B cell depletion by anti-CD20 monoclonal antibodies. CD19-targeted CAR-T cells offers the promise to deplete B cells in the peripheral immune system and within the CNS.

Design/Methods:

This is an open-label, single ascending dose study of KYV-101, autologous CD3+ T cells genetically engineered to express a fully human, second generation anti-CD19 CAR (KYV-101). Participants will be age 25-70 with treatment refractory progressive MS. Five participants will be at dose-level 1 of 0.33×10⁸ CAR-T cells intravenously after a preconditioning regime. Five other patients (DL2) will receive  1×10⁸ CAR T cells. Key study procedures include CSF, MRI, and monitoring of standard laboratory parameters, neurologic status, patient reported outcomes, and EDSS regularly through the follow up period.

Results:

A 55 year old female with EDSS 6, was dosed on 8/27/24 without cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome. Further details of her CAR expansion are being analyzed. We will continue enrolling participants and look for safety and tolerability of KYV-101.

Conclusions:

 The present trial will provide preliminary data which we expect will support the use of CD19 CAR T-cell therapy for this disease. All available data will be presented at the time of the conference.