Abstract Details

Title An Investigator Initiated Study of KYV-101, a CD19 CAR T Cell Therapy, in Participants with Treatment Refractory Progressive Multiple Sclerosis

Topic Multiple Sclerosis

Presentation(s) S3 - Multiple Sclerosis: Clinical Trials (1:12 PM-1:24 PM)

Poster/Presentation
Number 002

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.

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).

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 0.33×10⁸CAR-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.

Authors/Disclosures
Sasha Gupta, MD (University of California, San Francisco) PRESENTER	Dr. Gupta has nothing to disclose.
Madhav R. Seshadri, MD	Dr. Seshadri has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbvie. Dr. Seshadri has received personal compensation in the range of $500-$4,999 for serving as a Consultant for AstraZeneca. Dr. Seshadri has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BeiGene. Dr. Seshadri has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Kite. The institution of Dr. Seshadri has received research support from Kyverna.
Robin R. Lincoln (University of California San Francisco)	Robin R. Lincoln has nothing to disclose.
Naomi Okinishi, MPH	Ms. Okinishi has nothing to disclose.
Nancy Shum	Miss Shum has nothing to disclose.
Samantha Shenoy, NP	Mrs. Shenoy has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen. Mrs. Shenoy has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Janssen.
Jenai M. Wilmoth, RN	Mrs. Wilmoth has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Gilead. Mrs. Wilmoth has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi Genzyme.
Stephen L. Hauser, MD (UCSF Weill Institute for Neurosciences)	Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for NGM Bio. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Moderna. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BD. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Pheno Therapeutics. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Nurix Therapeutics. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Gilead. Dr. Hauser has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Accure. Dr. Hauser has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alector. Dr. Hauser has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Annexon. Dr. Hauser has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Hinge Therapeutics. Dr. Hauser has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for Neurona. Dr. Hauser has a non-compensated relationship as a Clinical Trial/Primary Investigator with Roche that is relevant to AAN interests or activities. Dr. Hauser has a non-compensated relationship as a Clinical Trial/Primary Investigator with Novartis that is relevant to AAN interests or activities.
Bruce A. Cree, MD, PhD, MAS, FAAN (UCSF, Multiple Sclerosis Center)	The institution of Dr. Cree has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. The institution of Dr. Cree has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for EMD Serono. The institution of Dr. Cree has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. The institution of Dr. Cree has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sanofi. The institution of Dr. Cree has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for TG Therapeutics. The institution of Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Autobahn. The institution of Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Avotres. The institution of Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Dr. Cree has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Horizon. Dr. Cree has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Neuron23. Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Boston Pharma. Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Hexal/Sandoz. Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Kyverna. Dr. Cree has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Immunic AG. The institution of Dr. Cree has received research support from Genentech. The institution of Dr. Cree has received research support from Kyverna. Dr. Cree has received publishing royalties from a publication relating to health care.