Autolus Therapeutics has achieved a significant milestone in expanding CAR-T cell therapy beyond oncology by dosing the first patient in its Phase 1 BOBCAT trial of obecabtagene autoleucel (obe-cel) for progressive multiple sclerosis (PMS). The patient was treated at University College London Hospitals NHS Foundation Trust (UCLH), a leading CAR-T and neurological disorders treatment center in the United Kingdom.
The Phase 1 trial represents a groundbreaking approach to treating progressive MS, a debilitating autoimmune disease with limited therapeutic options. "Progressive MS is a debilitating disease, and there are limited treatment options available, particularly for those whose disease continues to deteriorate despite long-term treatment with currently available B-cell targeting therapies," said Wallace Brownlee, UCLH consultant neurologist and principal investigator on the trial.
Novel Mechanism Targets MS Pathophysiology
Obe-cel is a B-lymphocyte antigen CD19 chimeric antigen receptor (CAR) T cell therapy designed with a fast target binding off-rate to minimize excessive activation of the programmed T cells. The therapy's CAR-T mediated B-cell depletion approach aims to suppress both autoimmune and CNS-compartmentalized inflammatory pathways that play key roles in driving MS disease progression.
"Obe-cel's CAR T mediated B-cell depletion approach holds the promise of suppressing both autoimmune and CNS-compartmentalized inflammatory pathways which play key roles in driving disease. If successful in clinical trials, obe-cel could transform outcomes for PMS patients with a one-time treatment," Brownlee explained.
Trial Design and Patient Population
The Phase 1 trial is expected to include up to 18 adult patients and will evaluate the safety, tolerability, and preliminary efficacy of obe-cel in participants with refractory progressive forms of multiple sclerosis. The primary endpoint focuses on assessing safety and tolerability of obe-cel, while preliminary data will also be collected on efficacy and biological effects using change from baseline in standard efficacy measures.
Dr. Matthias Will, Chief Development Officer of Autolus, emphasized the therapy's established safety profile: "Given obe-cel's well-characterized safety profile having been studied in more than 400 patients to date, we are hopeful about the impact this therapy can have for this patient population in need of new treatment options."
Addressing Significant Unmet Medical Need
Multiple Sclerosis is a chronic inflammatory autoimmune disease affecting the central nervous system, estimated to impact approximately 1,000,000 individuals in the US, of which approximately 30% have progressive disease (primary or secondary progressive MS). Disease onset typically occurs in patients ages 20-50 years, making it a life-long debilitating condition.
Current treatment limitations are substantial. While disease-modifying treatments are available and successful in some patients, none significantly alter the course of or stop progression. More than half of progressive MS patients experience disability progression despite receiving disease-modifying agents. There remains a high unmet need for new therapies for patients who continue to progress despite being treated with highly effective agents for at least six months.
Established Safety Profile in Oncology
Obe-cel is currently approved in certain regions for adult relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) under the brand name AUCATZYL. The therapy was approved by the FDA in 2024 and granted conditional marketing authorization by the MHRA in the UK and by the EMA in the EU in 2025.
The therapy's safety profile has been extensively characterized through the FELIX study, which evaluated 100 patients with relapsed or refractory B-cell acute lymphoblastic leukemia. In this study, cytokine release syndrome (CRS) occurred in 75% of patients, with Grade 3 CRS in 3% of patients. Neurologic toxicities were reported in 64% of patients, including Grade ≥3 in 12% of patients.
Expanding CAR-T Applications
The initiation of this trial represents a significant expansion of CAR-T cell therapy applications from hematological malignancies into autoimmune diseases. "Dosing the first patient in PMS is an important milestone for Autolus and the MS community. We believe obe-cel's mechanism of action, underpinned by its unique fast-off rate CAR mechanism, makes obe-cel well-suited to address aberrant inflammatory and immune pathways for PMS patients," Will stated.
The therapy is also under investigation for other autoimmune and B-cell driven hematological malignancies, suggesting potential broader applications beyond its current approved indication and the progressive MS trial.
