Autolus Therapeutics presents clinical data updates at ASH Annual Meeting 2023

Autolus Therapeutics announced two oral presentations and two poster presentations at the American Society of Hematology Annual Meeting, December 9-12, 2023, including an oral presentation highlighting data from a pooled analysis of the FELIX Phase Ib/II study of obe-cel, an autologous fast off-rate CD19 CAR T therapy, in relapsed/refractory adult B-ALL; and as a poster presentation a long-term update on the pooled ALLCAR19 and FELIX phase 1b studies, evaluating obe-cel in adult patients with r/r B-ALL as well from the ALLCAR19 study patients with B-NHL and B-CLL. Finally, in an oral presentation pre-clinical and Phase I clinical data from AUTO8, a BCMA/CD19 co-targeting CAR T cell candidate, evaluated in patients with refractory multiple myeloma. Obe-cel is an autologous chimeric antigen receptor T cell product using a fast off-rate CD19 binding domain designed to reduce toxicity and increase long-term persistence. A pooled analysis of data from all patients across all cohorts in the FELIX Phase Ib/II study were presented. Median vein-to-release time was 22 days. Across all patients, treatment with obe-cel resulted in a high response rate with CR/CRi rate of 78% in evaluable patients. Additionally, obe-cel showed a favorable safety profile; grade greater than or equal to 3 CRS was 2% and grade greater than or equal to3 ICANS was 7%, with most severe cases of immunotoxicity occurring in patients with high leukemic burden in the bone marrow. The event free survival estimate at 12-months was 50% across all patients, with only 17% of responders proceeding to stem cell transplant while in remission. For patients who had morphologic disease, defined as greater than or equal to5% BM blasts or presence of EMD regardless of BM blast status, at lymphodepletion, 74% responded with CR or CRi, and 95% of evaluated responders were MRD-negative. For patients who did not have morphologic disease at lymphodepletion, 100% were MRD-negativeSection after obe-cel infusion. Subgroup analysis demonstrated that EFS and safety, particularly rate of CRS and ICANS, were better in patients with lower disease burden at lymphodepletion. Cellular kinetic data shows high expansion and long-term persistence of CAR T cells in most responders. AUTO8 is a dual targeting autologous CAR T therapy targeting BCMA and CD19 using two independently expressed CARs for R/R multiple myeloma. The MCARTY study is an iterative, staggered design trial with two separate parallel cohorts for direct comparison of D8 BCMA CAR and AUTO8. As of November 13, 2023, 11 patients have been infused with either BCMA CAR at 50 million or 150 million cells, or AUTO8 at 50 million or 150 million. At a median follow-up of 6 months we observed 100% response rate, with 3 PR, 1 VGPR, 7 CR/sCR. Two patients remained in ongoing sCR greater than 12 months. No cases of ICANS or CRS greater than or equal to Gr 3 were observed across all subjects during the period. While persistence data from the dual targeting cohort is immature, it demonstrates expansion of three CAR populations and suggests a trend to increased persistence of D8 BCMA CAR expressing T cells. The MCARTY trial is ongoing and continues to recruit patients. The clinical activity of obe-cel has been explored in adults with R/R B-ALL in a Phase I study, and a Phase Ib/II study. Additionally, obe-cel has been tested in patients with R/R B-cell chronic lymphocytic leukemia and R/R B-cell non-Hodgkin lymphoma. Data from the pooled analysis of r/r ALL patients treated with obe-cel in the ALLCAR19 and FELIX Ib studies demonstrate high remission rates of 81%. After a median follow-up of 3 years and without subsequent transplant 41% of patients continue in complete remission. The estimated EFS rate with censoring of subsequent transplant or new treatment was 45% at 36 months; all patients in ongoing remission were MRD negative at last assessment and median duration of response was not reached. In the CLL and NHL cohorts of the ALLCAR19 study and with over 2 years follow up, high response rates and durable responses were observed. Low grade or low frequency grade over 3 CRS/ICANS was observed across all indications and all dosing regimens. Excellent expansion and persistence of CAR T cells was evident across the studies. In summary, obe-cel shows durable remissions in a range of B-cell malignancies with a consistent safety profile.