Autolus Therapeutics Presents Clinical Data Updates at the American College of Rheumatology Convergence 2025

Rhea-AI Summary

Autolus Therapeutics (NASDAQ: AUTL)50x10^6 cells (±20%) with median follow-up of 8.9 months (range 6.0–13.8).

Key findings: no DLTs, no ICANS, no Grade ≥2 CRS; remission by DORIS in 83.3% (5/6); complete renal response in 50% (3/6); all patients tapered steroids to ≤5 mg/day; deep B-cell depletion followed by naïve B-cell reconstitution. Company expects to dose first Phase 2 LN patient before year-end 2025 and reports alignment with the FDA on trial design.

Positive

• DORIS remission achieved in 83.3% (5/6) of patients
• Complete renal response in 50% (3/6) of patients
• No ICANS or Grade ≥2 CRS reported through median 8.9 months
• 50 million cell target dose selected for Phase 2
• FDA alignment on Phase 2 design and plan to dose first patient by year-end 2025

Negative

• Very small sample size: n=6 limits generalizability
• Median follow-up 8.9 months limits long-term durability evidence

Insights

Clinical Development Strategist

Phase 1 data show high remission rates and an encouraging safety signal; Phase 2 dosing planned by year-end 2025.

obe-cel produced deep B‑cell depletion and clinical improvements in heavily refractory systemic lupus erythematosus patients, with remission (DORIS) in 83.3% and complete renal response in 50% of treated patients at a median follow-up of 8.9 months. No dose‑limiting toxicities, no ICANS, and no Grade ≥2 CRS were reported, and all patients tapered steroids to ≤5mg/day—facts that support tolerability and biological activity in this cohort.

The program’s near-term progress depends on sustaining responses in larger numbers, confirmatory safety in broader populations, and the agreed Phase 2 design with the FDA. The small sample (n=6) and short median follow‑up constrain confidence; ongoing durability data and any emerging safety signals are the primary risks to the program’s registrational path.

Watch: ongoing response durability, safety outcomes in additional patients, and initiation of the Phase 2 LUMINA trial (first patient dosing anticipated by year-end 2025). Expect informative readouts and enrollment milestones over the next 6–18 months that will materially affect program valuation and regulatory momentum.

10/27/2025 - 07:00 AM

• Data from the Phase 1 CARLYSLE study in severe refractory systemic lupus erythematosus (srSLE) suggests obe-cel is well tolerated with no ICANS or high-grade CRS; 50 million cell dose selected for Phase 2 pivotal study
• Preliminary efficacy data demonstrate achievement of definition of remission in SLE (DORIS) in 83% of patients and complete renal response (CRR) in 50% of patients; all responses and remissions are ongoing with no evidence of disease activity at a median follow-up of 8.9 months
• All patients had refractory lupus nephritis; 4/6 patients had significantly impaired kidney function
• Patients received no other lupus directed therapy; steroids were tapered in all patients to 5mg by month six
• Company remains on track to dose first patient in Phase 2 trial in lupus nephritis (LN) by year-end 2025
  
  

LONDON and GAITHERSBURG, Md., Oct. 27, 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 follow-up data from the ongoing CARLYSLE trial, a Phase 1 dose confirmation clinical trial of obe-cel in severe refractory systemic lupus erythematosus (srSLE), will be presented during a poster session at the American College of Rheumatology Convergence 2025.

“Data from the CARLYSLE study shows that obe-cel has the potential to make a meaningful clinical impact in patients with severe refractory SLE who are currently without approved treatment options. We observe durable responses in up to 12 months of follow up and an encouraging safety profile in this difficult to treat patient population. All patients were able to reduce glucocorticosteroids to physiological levels, and responses, including kidney responses, occur early and are durable. The deep depletion of the B-cell lineage seen with obe-cel suggests the possibility of an immune reset and continues to underscore the paradigm shift that CD19 CAR T cell therapy may represent for these patients,” said Dr. Maria Leandro, consultant rheumatologist at UCL Hospitals and senior lecturer at University College London. “We are excited to expand on this data set at another upcoming meeting before year-end.”

Abstract: 2458
Title: Obecabtagene autoleucel (obe-cel), a CD19-targeting autologous chimeric antigen receptor T-cell therapy (CAR T) with a fast off-rate binding domain, in patients with severe, refractory systemic lupus erythematosus (srSLE): preliminary results from the Phase I CARLYSLE study
Session date and time: Tuesday, October 28, 2025; 10:30am - 12:30pm Central Time
Presenting Author: Maria Leandro, MD

Summary: As of August 21, 2025, six patients with srSLE received the obe-cel target dose of 50x10⁶ (±20%). After a minimum follow-up of 6 months (median follow-up 8.9 months [range 6.0 - 13.8]), obe-cel continues to be well tolerated in all patients, with no dose limiting toxicities (DLTs), immune effector cell-associated neurotoxicity syndrome (ICANS) or Grade ≥2 cytokine release syndrome (CRS). Preliminary efficacy data demonstrated remission in 83.3% (n=5) of patients as measured according to Definition of Remission in SLE (DORIS) and a complete renal response (CRR) in 50% (n=3) of patients, without evidence of new disease activity at last follow-up visit. At months six, the SLEDAI-2K score improved in 5/6 patients by a more than 10 point reduction and the kidney component of SLEDAI-2K resolved in the same 5/6 patients, with all non-renal manifestations completely resolved by month four. SLEDAI-2K score reduction and clinical benefit were observed in all patients. Additionally, all patients achieved steroid tapering to ≤5mg/day post obe-cel infusion. Deep B-cell depletion was observed in all patients shortly after infusion and was followed by predominantly naïve B-cell reconstitution, suggesting an obe-cel driven immune reset.

These follow-up data from the ongoing CARLYSLE clinical trial support progressing obe-cel into a planned Phase 2 study in srSLE patients with active lupus nephritis. The Company has aligned with the U.S. Food and Drug Administration (FDA) on the Phase 2 trial design and potential registrational path to approval and continues to anticipate dosing the first patient in the Phase 2 clinical trial before year-end 2025.

“These data suggest the safety profile observed in srSLE patients is consistent with our considerable experience in acute leukemia and, combined with sustained renal remissions observed, forms a strong foundation for the Phase 2 LUMINA trial. Leveraging our established commercial presence and manufacturing capabilities, we believe we are well positioned to potentially be first to market with a CAR T therapy in srSLE,” said Dr. Christian Itin, Chief Executive Officer of Autolus.

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^® (obecabtagene autoleucel), 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^® (obe-cel, AUTO1)
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 on November 8, 2024, and was granted conditional marketing authorization by MHRA in the UK and 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

WARNING: CYTOKINE RELEASE SYNDROME, NEUROLOGIC TOXICITIES, and SECONDARY HEMATOLOGICAL MALIGNANCIES Cytokine Release Syndrome (CRS) occurred in patients receiving AUCATZYL. Do not administer AUCATZYL to patients with active infection or inflammatory disorders. Prior to administering AUCATZYL, ensure that healthcare providers have immediate access to medications and resuscitative equipment to manage CRS [see Dosage and Administration (2.2, 2.3), Warnings and Precautions (5.1)]. Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), including fatal or life-threatening reactions, occurred in patients receiving AUCATZYL, including concurrently with CRS or after CRS resolution. Monitor for neurologic signs and symptoms after treatment with AUCATZYL. Prior to administering AUCATZYL, ensure that healthcare providers have immediate access to medications and resuscitative equipment to manage neurologic toxicities. Provide supportive care and/or corticosteroids, as needed [see Dosage and Administration (2.2, 2.3), Warnings and Precautions (5.2)]. T cell malignancies have occurred following treatment of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T cell immunotherapies [see Warnings and Precautions (5.8)].

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%).

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 (range: 1 to 23 days) with a median duration of 5 days (range: 1 to 21 days). Sixty-eight percent of patients (51/75) experienced CRS after the first infusion, but prior to the second infusion of AUCATZYL with a median time to onset of 6 days (range: 1 to 10 days). Among patients with CRS, the most common manifestations of CRS included fever (100%), hypotension (35%) and hypoxia (19%). The primary treatment for CRS was tocilizumab (73%; 55/75), with patients also receiving corticosteroids (21%; 16/75).

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 7 days following each infusion. Continue to monitor patients for CRS for at least 2 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). Fifty-five percent of patients (35/64) experienced neurologic toxicities after the first infusion but prior to the second infusion of AUCATZYL with a median time to onset of 6 days (range: 1 to 11 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.

During and following AUCATZYL administration, closely monitor patients for signs and symptoms of Neurologic Toxicity/ICANS. Following treatment with AUCATZYL, monitor patients daily for at least 7 days. Continue to monitor patients for at least 2 weeks following treatment with AUCATZYL. Avoid driving for at least 2 weeks after each infusion. 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.

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 
a.cray@autolus.com

FAQ

What were the CARLYSLE Phase 1 results for Autolus (AUTL) presented Oct 27, 2025?

Six patients at the 50x10^6 cell dose showed 83.3% DORIS remission, 50% complete renal response, no DLTs, no ICANS and no Grade ≥2 CRS at median 8.9 months follow-up.

What dose of obe-cel will Autolus (AUTL) use in the Phase 2 lupus nephritis trial?

The Phase 2 plan uses a target dose of 50 million cells (50x10^6 ±20%) selected from CARLYSLE Phase 1 data.

When does Autolus (AUTL) expect to dose the first patient in the Phase 2 LN trial?

Autolus continues to anticipate dosing the first Phase 2 lupus nephritis patient before year-end 2025.

How was safety described for obe-cel in the CARLYSLE study for AUTL?

Safety reported no dose-limiting toxicities, no ICANS, and no Grade ≥2 CRS through the reported follow-up period.

Did patients reduce steroid use after obe-cel in the CARLYSLE trial (AUTL)?

Yes; all patients tapered glucocorticosteroids to ≤5 mg/day by month six post-infusion.

What evidence of immune effects did obe-cel show in CARLYSLE for AUTL?

All patients had deep B-cell depletion shortly after infusion, followed by predominantly naïve B-cell reconstitution, suggesting an immune reset.