Autolus Therapeutics Announces First Patient Dosed in Phase 1 Trial of Obecabtagene Autoleucel (Obe-Cel) in Patients with Progressive Multiple Sclerosis

LONDON and Gaithersburg, Md., Oct. 20, 2025 (GLOBE NEWSWIRE) -- Autolus Therapeutics plc (NASDAQ:AUTL), an early commercial-stage biopharmaceutical company developing, manufacturing and delivering next-generation programmed T cell therapies, announces that the first patient has been dosed in its Phase 1 BOBCAT trial of obecabtagene autoleucel (obe-cel) in patients with 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 and, with UCL, development partner of Autolus for obe-cel.

"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 UCLH consultant neurologist Wallace Brownlee, principal investigator on the trial. "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. This is an extremely exciting prospect, and I look forward to participating in the study so we can explore obe-cel's potential in this devastating disease."

The Phase 1 trial, expected to include up to 18 adult patients, will evaluate the safety, tolerability, and preliminary efficacy of obe-cel in participants with refractory progressive forms of multiple sclerosis. The primary endpoint is to assess safety and tolerability of obe-cel. Preliminary data will also be collected on the efficacy and biological effect of obe-cel using change from baseline in standard efficacy measures.

"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. 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," said Dr. Matthias Will, Chief Development Officer of Autolus.

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. It is approved in certain regions for adult r/r B-ALL and is under investigation for other autoimmune and B-cell driven hematological malignancies.

About Multiple Sclerosis

Multiple Sclerosis (MS) is a chronic inflammatory autoimmune disease affecting the central nervous system. It is estimated to impact approximately 1,000,000 individuals in the US¹, of which ~30% have progressive disease (primary or secondary progressive MS). Disease onset is typically in patients ages 20-50 years, making it a life-long debilitating disease. While disease modifying treatments are available and successful in some patients, none significantly alter the course of, or stop, progression and more than half of progressive MS patients experience disability progression despite receiving disease modifying agents². 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.

About Autolus Therapeutics plc

Autolus Therapeutics plc (NASDAQ:AUTL) is an early commercial-stage biopharmaceutical company developing, manufacturing and delivering next-generation T cell therapies and candidates for the treatment of cancer and autoimmune disease. Using a broad suite of proprietary and modular T cell programming technologies, Autolus is engineering precisely targeted and controlled T cell therapies that are designed to better recognize target cells, break down their defense mechanisms and eliminate these cells. Autolus has a marketed therapy, AUCATZYL®, and a pipeline of product candidates in development for the treatment of hematological malignancies, solid tumors and autoimmune diseases. For more information, please visit www.autolus.com.

About AUCATZYL® (obecabtagene autoleucel, obe-cel)

AUCATZYL is a B-lymphocyte antigen CD19 (CD19) chimeric antigen receptor (CAR) T cell therapy designed to overcome the limitations in clinical activity and safety compared to current CD19 CAR T cell therapies. AUCATZYL is designed with a fast target binding off-rate to minimize excessive activation of the programmed T cells. AUCATZYL was approved by the FDA for the treatment of adult patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia in 2024, and was granted conditional marketing authorization by the MHRA in the UK and by the EMA in the EU in 2025.

INDICATION

AUCATZYL® is a CD19-directed genetically modified autologous T cell immunotherapy indicated for the treatment of adult patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Cytokine Release Syndrome (CRS)

Cytokine Release Syndrome (CRS) occurred following treatment with AUCATZYL. CRS was reported in 75% (75/100) of patients including Grade 3 CRS in 3% of patients. The median time to onset of CRS was 8 days following the first infusion (range: 1 to 23 days) with a median duration of 5 days (range: 1 to 21 days). The most common manifestations of CRS included fever (100%), hypotension (35%), and hypoxia (19%).

Prior to administering AUCATZYL, ensure that healthcare providers have immediate access to medications and resuscitative equipment to manage CRS. During and following treatment with AUCATZYL, closely monitor patients for signs and symptoms of CRS daily for at least 14 days at the healthcare facility following the first infusion. Continue to monitor patients for CRS for at least 4 weeks following each infusion with AUCATZYL. Counsel patients to seek immediate medical attention should signs or symptoms of CRS occur at any time. At the first sign of CRS, immediately evaluate the patient for hospitalization and institute treatment with supportive care based on severity and consider further management per current practice guidelines.

Neurologic Toxicities

Neurologic toxicities including Immune Effector Cell-associated Neurotoxicity Syndrome (ICANS), which were fatal or life-threatening, occurred following treatment with AUCATZYL. Neurologic toxicities were reported in 64% (64/100) of patients, including Grade ≥ 3 in 12% of patients. The median time to onset of neurologic toxicities was 10 days (range: 1 to 246 days) with a median duration of 13 days (range: 1 to 904 days). Among patients with neurologic toxicities, the most common symptoms (> 5%) included ICANS (38%), headache (34%), encephalopathy (33%), dizziness (22%), tremor (13%), anxiety (9%), insomnia (9%), and delirium (8%).

Immune Effector Cell-associated Neurotoxicity Syndrome (ICANS)

ICANS events occurred in 24% (24/100) of patients, including Grade ≥ 3 in 7% (7/100) of patients. Of the 24 patients who experienced ICANS, 33% (8/24) experienced an onset after the first infusion, but prior to the second infusion of AUCATZYL.

The median time to onset for ICANS events after the first infusion was 8 days (range: 1 to 10 days) and 6.5 days (range: 2 to 22 days) after the second infusion, with a median duration of 8.5 days (range: 1 to 53 days).

Eighty-eight percent (21/24) of patients received treatment for ICANS. All treated patients received high-dose corticosteroids and 42% (10/24) of patients received anti-epileptics prophylactically. Prior to administering AUCATZYL, ensure that healthcare providers have immediate access to medications and resuscitative equipment to manage ICANS.

Counsel patients to seek medical attention should signs or symptoms of neurologic toxicity/ ICANS occur. At the first sign of Neurologic Toxicity /ICANS, immediately evaluate patients for hospitalization and institute treatment with supportive care based on severity and consider further management per current practice guidelines.

Effect on Ability to Drive and Use Machines

Due to the potential for neurologic events, including altered mental status or seizures, patients receiving AUCATZYL are at risk for altered or decreased consciousness or coordination in the eight weeks following AUCATZYL infusion or until resolution of the neurological event by the treating physician. Advise patients to refrain from driving and engaging in hazardous occupations or activities, such as operating heavy or potentially dangerous machinery, during this initial period.

Prolonged Cytopenias

Patients may exhibit cytopenias including anemia, neutropenia, and thrombocytopenia for several weeks after treatment with lymphodepleting chemotherapy and AUCATZYL. In patients who were responders to AUCATZYL, Grade ≥ 3 cytopenias that persisted beyond Day 30 following AUCATZYL infusion were observed in 71% (29/41) of patients and included neutropenia (66%, 27/41) and thrombocytopenia (54%, 22/41). Grade 3 or higher cytopenias that persisted beyond Day 60 following AUCATZYL infusion was observed in 27% (11/41) of patients and included neutropenia (17%, 7/41) and thrombocytopenia (15%, 6/41). Monitor blood counts after AUCATZYL infusion.

Infections

Severe, including life-threatening and fatal infections occurred in patients after AUCATZYL infusion. Non-COVID-19 infections of all grades occurred in 67% (67/100) of patients. Grade 3 or higher non-COVID-19 infections occurred in 41% (41/100) of patients. AUCATZYL should not be administered to patients with clinically significant active systemic infections. Monitor patients for signs and symptoms of infection before and after AUCATZYL infusion and treat appropriately. Administer prophylactic antimicrobials according to local guidelines.

Grade 3 or higher febrile neutropenia was observed in 26% (26/100) of patients after AUCATZYL infusion and may be concurrent with CRS. In the event of febrile neutropenia, evaluate for infection and manage with broad-spectrum antibiotics, fluids, and other supportive care as medically indicated.

Viral reactivation, potentially severe or life-threatening, can occur in patients treated with drugs directed against B cells. There is no experience with manufacturing AUCATZYL for patients with a positive test for human immunodeficiency virus (HIV) or with active hepatitis B virus (HBV) or active hepatitis C virus (HCV). Perform screening for HBV, HCV and HIV in accordance with clinical guidelines before collection of cells for manufacturing.

Hypogammaglobulinemia

Hypogammaglobulinemia and B-cell aplasia can occur in patients after AUCATZYL infusion. Hypogammaglobulinemia was reported in 10% (10/100) of patients treated with AUCATZYL including Grade 3 events in 2 patients (2%).

Immunoglobulin levels should be monitored after treatment with AUCATZYL and managed per institutional guidelines including infection precautions, antibiotic or antiviral prophylaxis, and immunoglobulin replacement.

The safety of immunization with live viral vaccines during or following treatment with AUCATZYL has not been studied. Vaccination with live viral vaccines is not recommended for at least 6 weeks prior to the start of lymphodepleting chemotherapy treatment, during AUCATZYL treatment, and until immune recovery following treatment with AUCATZYL.

Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome (HLH/MAS)

HLH/MAS including fatal and life-threatening reactions occurred after treatment with AUCATZYL. HLH/MAS was reported in 2% (2/100) of patients and included Grade 3 and Grade 4 events with a time of onset at Day 22 and Day 41, respectively. One patient experienced a concurrent ICANS events after AUCATZYL infusion and died due to sepsis with ongoing HLH/MAS that had not resolved. Administer treatment for HLH/MAS according to institutional standards.

Hypersensitivity Reactions

Serious hypersensitivity reactions, including anaphylaxis, may occur due to dimethyl sulfoxide (DMSO), an excipient used in AUCATZYL. Observe patients for hypersensitivity reactions during and after AUCATZYL infusion.

Secondary Malignancies

Patients treated with AUCATZYL may develop secondary malignancies. T cell malignancies have occurred following treatment of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T cell immunotherapies. Mature T cell malignancies, including CAR-positive tumors, may present as soon as weeks following infusion, and may include fatal outcomes. Monitor lifelong for secondary malignancies. In the event that a secondary malignancy occurs, contact Autolus at 1-855-288-5227 for reporting and to obtain instructions on the collection of patient samples for testing.

Adverse Reactions

The safety of AUCATZYL was evaluated in the FELIX study in which 100 patients with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL) received AUCATZYL at a median dose of 410 × 10⁶ CD19 CAR-positive viable T cells (range: 10 to 480 × 10⁶ CD19 CAR-positive viable T cells with 90% of patients receiving the recommended dose of 410 × 10⁶ +/- 25%).

The most common serious adverse reactions of any Grade (incidence ≥ 2%) included infections-pathogen unspecified, febrile neutropenia, ICANS, CRS, fever, bacterial infectious disorders, encephalopathy, fungal infections, hemorrhage, respiratory failure, hypotension, ascites, HLH/MAS, thrombosis and hypoxia. Nine patients (9%) experienced fatal adverse reactions which included infections (sepsis, pneumonia, peritonitis), ascites, pulmonary embolism, acute respiratory distress syndrome, HLH/MAS and ICANS. Of the 9 patients, five patients who died from infections had pre-existing and ongoing neutropenia prior to receiving bridging therapy, lymphodepletion chemotherapy treatment and/or AUCATZYL.

Please see full Prescribing Information, including BOXED WARNING and Medication Guide.

Forward-Looking Statements  

This press release contains forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995. Forward-looking statements are statements that are not historical facts, and in some cases can be identified by terms such as "may," "will," "could," "expects," "plans," "anticipates," and "believes." These statements include, but are not limited to, statements regarding the therapeutic potential and expected clinical benefits of obecabtagene autoleucel (obe-cel); the period during which the results of clinical studies or trials will become available; the timing or likelihood of regulatory filings and approvals for product candidates, along with regulatory developments in the US, EU, the UK and other foreign countries. Any forward-looking statements are based on management's current views and assumptions and involve risks and uncertainties that could cause actual results, performance, or events to differ materially from those expressed or implied in such statements. These risks and uncertainties include, but are not limited to, the risks that the impact of worsening macroeconomic conditions on Autolus' business, financial position, strategy and anticipated milestones, including Autolus' ability to conduct ongoing and planned clinical trials; Autolus' ability to obtain a clinical supply of current or future product candidates; the delay of any current or planned clinical trials, whether due to patient enrollment delays or otherwise; Autolus' ability to successfully demonstrate the safety and efficacy of its product candidates and gain approval of its product candidates on a timely basis, if at all; competition with respect to market opportunities; the risk that Autolus' preclinical or clinical programs do not advance or result in approved products on a timely or cost effective basis or at all; the results of early clinical trials are not always being predictive of future results; the cost, timing and results of clinical trials; that many product candidates do not become approved drugs on a timely or cost effective basis or at all; and possible safety and efficacy concerns. For a discussion of other risks and uncertainties, and other important factors, any of which could cause Autolus' actual results to differ from those contained in the forward-looking statements, see the section titled "Risk Factors" in Autolus' Annual Report on Form 10-K filed with the Securities and Exchange Commission, or the SEC, on March 20, 2025 as well as discussions of potential risks, uncertainties, and other important factors in Autolus' subsequent filings with the Securities and Exchange Commission. All information in this press release is as of the date of the release, and Autolus undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise, except as required by law. You should, therefore, not rely on these forward-looking statements as representing Autolus' views as of any date subsequent to the date of this press release.   

Contact:  

Amanda Cray 

+1 617-967-0207 

[email protected]