Anti-CD19 chimeric antigen receptor T cell therapy (Takara Bio)

LONDON, UK I December 08, 2022 I Autolus Therapeutics plc (Nasdaq: AUTL), a clinical-stage biopharmaceutical company developing next-generation programmed T cell therapies, today announces that the Phase 2 pivotal FELIX clinical trial of obecabtagene autoleucel (obe-cel) in relapsed/refractory (r/r) adult Acute Lymphoblastic Leukemia (ALL) has met its primary endpoint, based on a pre-planned interim analysis of 50 patients with morphological disease, as verified by an independent data monitoring committee (IDMC). The primary endpoint for the FELIX Phase 2 trial is the Overall Remission Rate (ORR), defined as the proportion of patients achieving Complete Remission (CR) and Complete Remission with Incomplete Blood Count Recovery (CRi) as assessed by an independent response review committee (IRRC). Based on 50 patients evaluated for efficacy, the ORR for obe-cel was 70%. Obe-cel showed comparable expansion and initial persistence (median follow-up 6.4 months) to the data observed in the prior ALLCAR19 study. The safety analysis was based on 92 patients treated with obe-cel and evaluable for safety. The Company observed that 3% of patients experienced Grade 3 or higher CRS, whilst 8% experienced Grade 3 or higher ICANS, and 23% of patients experienced any grade ICANS. “Obe-cel’s high level of anti-leukemia activity combined with a well manageable tolerability profile is a significant step forward in this underserved disease setting, which is characterized by the explosive growth of the leukemia and the poor condition of many patients,” said Dr. Jae Park, Associate Attending Physician at Memorial Sloan Kettering Cancer Center. “The expansion and initial persistence of obe-cel are encouraging from a long-term outcome perspective and I look forward to the next data update and the potential of obe-cel as a treatment for ALL.” “We are really pleased with the consistency of data from the interim analysis of the FELIX study with our prior results from the ALLCAR19 study in adult patients with relapsed / refractory ALL,” said Dr. Claire Roddie, Associate Professor Haematology, Cancer Institute, University College London (UCL) . “We are delighted to be announcing that our first pivotal trial conducted has met its primary endpoint based on our interim analysis, and we believe that we are one step closer to bringing this potentially innovative treatment to an underserved ALL patient population,” said Dr. Christian Itin, Chief Executive Officer of Autolus. “We look forward to supplementing this interim data with longer follow up data to more fully explore the clinical benefit of obe-cel, and to work towards the submission of a Biologics License Application (BLA) by the end of 2023 to the U.S. Food and Drug Administration (FDA).” “We would like to thank patients and their families, our treating physicians and the clinical development and manufacturing teams for their trust, commitment and determination to deliver this study during a challenging pandemic-impacted environment.” The trial has completed screening patients for entry into the morphological cohort as the pre-specified goal of approximately 90 patients enrolled has been reached, and Autolus plans to present the results from the FELIX trial at a medical conference in mid-2023, with longer follow up planned to be reported at the end of 2023. About Autolus Therapeutics plc Autolus is a clinical-stage biopharmaceutical company developing next-generation, programmed T cell therapies for the treatment of cancer. Using a broad suite of proprietary and modular T cell programming technologies, Autolus is engineering precisely targeted, controlled and highly active T cell therapies that are designed to better recognize cancer cells, break down their defense mechanisms and eliminate these cells. Autolus has a pipeline of product candidates in development for the treatment of hematological malignancies and solid tumors. For more information, please visit www.autolus.com . About obe-cel (AUTO1) Obe-cel is a CD19 CAR T cell investigational therapy designed to overcome the limitations in clinical activity and safety compared to current CD19 CAR T cell therapies. Designed to have a fast target binding off-rate to minimize excessive activation of the programmed T cells, obe-cel may reduce toxicity and be less prone to T cell exhaustion, which could enhance persistence and improve the ability of the programmed T cells to engage in serial killing of target cancer cells. In collaboration with Autolus’ academic partner, UCL, obe-cel is currently being evaluated in a Phase 1 clinical trial for B-NHL. Autolus has progressed obe-cel to the FELIX trial, a pivotal trial for r/r adult ALL. About obe-cel FELIX clinical trial Autolus’ Phase 1b/2 clinical trial of obe-cel is enrolling adult patients with r/r B-precursor ALL. The trial had a Phase 1b component prior to proceeding to the single arm, Phase 2 clinical trial. The primary endpoint is ORR, and the secondary endpoints include duration of response, minimal residual disease (MRD) negative CR rate and safety. The trial is designed to enroll approximately 100 patients across 30 of the leading academic and non-academic centers in the United States, United Kingdom, and Europe. [NCT04404660] SOURCE: Autolus Therapeutics

Autolus Therapeutics plans to gather longer follow-up data on its cell therapy before filing for FDA approval. Autolus Therapeutics is almost ready to make a late play for the CD19 CAR-T cell therapy space. The biotech now has phase 2 data showing its asset hit the primary endpoint at an interim analysis and is setting out plans for further data to file for FDA approval next year and try to join Bristol Myers Squibb, Gilead Sciences and Novartis on the market.  Novartis’ Kymriah came to market in 2017, and Gilead won FDA approval for Tecartus in Autolus’ lead indication last year. But, having applied technologies designed to reduce toxicity and T-cell exhaustion to its asset, Autolus is trying to set its therapy apart from the pack and carve out a slice of the market. The company took a step toward that goal with the release of top-line data from its phase 2 FELIX trial after the market closed on Thursday. At a preplanned analysis of 50 adult patients with relapsed or refractory acute lymphoblastic leukemia, investigators linked the CD19 cell therapy, obe-cel, to a 70% response rate, meaning the study met its primary endpoint.  Across the 92-subject safety data set, 3% of patients had grade 3 or higher cytokine release syndrome and 8% experienced grade 3 or higher immune effector cell-associated neurotoxicity syndrome, both of which are associated with other CAR-T cell therapies.  Autolus did not provide a more detailed breakdown of the primary endpoint and safety data nor share a look at the secondary endpoints. The only other tidbit is that expansion and initial persistence are comparable to the results of the earlier ALLCAR19 study after a median follow-up of 6.4 months. Having chalked up the primary endpoint success, Autolus now plans to gather longer follow-up data on the cell therapy before filing for FDA approval by the end of next year. The biotech, leveraging the perks of its regenerative medicine advanced therapy designation, met with the FDA earlier in the year. While the FDA has recently taken a tougher line in some areas, Autolus plans to seek approval in an indication covered by an approved CD19 CAR-T cell therapy on the strength of data from a single-arm clinical trial.  Autolus shares fell after the release of the data, although the stock offering, which the biotech disclosed minutes after the trial results, may have driven the decline. By the end of the day, Autolus had confirmed investor fears by pricing a $150 million stock offering at $2. The stock closed at $2.99 before the data drop. Autolus’ shares fell roughly 30% in premarket trading to around $2.10.   The biotech held the stock offering despite the clinical readout strengthening its finances. The study data triggered a $35 million payment from Blackstone Life Sciences, as did the achievement of a manufacturing milestone