Autolus Therapeutics plc announced three abstracts to be presented at the European Hematology Association (EHA) Congress, June 13-16, 2024. Title: obecabtagene autoleucel in adult relapsed/refractory B cell acute lymphoblastic leukemia: Survival and potential impact of CAR T-cell persistence and stem cell transplantation in the FELIX study. Session Title: s419 Acute lymphoblastic leukemia - Clinical 1: Immunotherapy: antibodies and CAR-T cells.

Session date and time: June 14 from 14:45 - 16:00 CEST. Session room: N104. Final Abstract Code: S114.

Presenting Author: Dr. Claire Roddie. Summary of Findings: This is an encore presentation of the findings presented at ASCO 2024. The overall response rate (ORR) (Complete Response/CRi) in all patients who received obe-cel in the FELIX study was 78% (99/127 patients).

At the February 7, 2024, data cut-off date, the majority of ongoing responders showed durable responses. Among the responding patients, at a median follow up of 21.5 months (range: 8.6?41.4), 40% were in ongoing remission without subsequent stem cell therapy (SCT) or other non-protocol specified therapy, while 18% proceeded to subsequent SCT while in remission, 5% started new anti-cancer therapy while in remission and 36% relapsed or died. The median event-free survival (EFS) was 11.9 months and median overall survival (OS) was 23.8 months and the estimated 12-month EFS and OS rates were 49.5% and 61.1% respectively.

Title:obecabtagene autoleucel (obe-cel, AUTO1) for relapsed/refractory adult B-cell acute lymphoblastic leukemia (R/R B-ALL): The impact of inotuzumab (INO)-containing bridging therapy on treatment outcomes. Session Title: Poster session. Session date and time: June 14 from 18:00 - 19:00 CEST.

Final Abstract Code: P418. Presenting Author: Dr. Jae H. Park. Summary of Findings: INO-containing bridging therapies were effective in reducing BM disease prior to lymphodepletion and administration of obe-cel.

The data suggests that reducing BM blasts as much as possible prior to lymphodepletion predicts EFS and OS outcomes; however, patients with high disease burden at screening are still at higher risk of relapse overall. Bridging therapy with INO was utilized in patients with higher disease burden (median 81.5% blasts at screening vs 40% in bridging therapy w/o INO group) and helped minimize the risk of CRS and ICANS without increasing liver toxicity. Choice of bridging therapy prior to obe-cel treatment, though influenced by clinical care variables, may impact outcomes for patients with R/R B-ALL.

Further studies comparing bridging with INO-containing therapies or chemotherapy are warranted. Title: Droplet digital PCR and flow cytometry sensitivity for measuring CAR T-cell kinetics in adult patients with relapsed/refractory B-cell acute lymphoblastic leukemia treated with obecabtagene autoleucel. Session Title: Poster session.

Session date and time:, June 14 from 18:00 - 19:00 CEST. Final Abstract Code: P1469. Presenting Author: Dr. Claire Roddie.

Summary of Findings: A strong correlation was observed between flow cytometry and ddPCR assays for assessment of CAR T levels in peripheral blood. ddPCR is a more sensitive technology than flow cytometry for monitoring CAR T persistence. Flow cytometry assays developed specifically for CAR T monitoring may be sufficiently sensitive to be of clinical relevance.

The data suggest that loss of CAR T persistence is associated with shorter EFS and may be taken into consideration, together with other parameters such as measurable residual disease (MRD), to help inform clinical monitoring post-obe-cel infusion. A validation cohort using an appropriately developed CAR T marking flow cytometry assay versus a ddPCR assay would be required to conclude on the most appropriate methods to inform clinical outcomes. 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.

Obe-cel is designed with a fast target binding off-rate to minimize excessive activation of the programmed T cells. In clinical trials of obe-cel, this ?fast off-rate? profile reduced toxicity and T cell exhaustion, resulting in improved persistence and leading to high levels of durable remissions in r/r Adult ALL patients.

The results of the FELIX trial, a pivotal trial for adult ALL, have been submitted and accepted by the FDA with a PDUFA target action date of November 16, 2024. A regulatory submission to the EMA was made in the first half of 2024. In collaboration with Autolus?

academic partner, UCL, obe-cel is currently being evaluated in a Phase 1 clinical trials for B-NHL. Autolus? Phase 1b/2 clinical trial of obe-cel enrolled adult patients with relapsed /refractory B-precursor ALL.

The trial had a Phase 1b component prior to proceeding to the single arm, Phase 2 clinical trial. The primary endpoint was overall response rate, and the secondary endpoints included duration of response, MRD negative CR rate and safety. The trial enrolled over 100 patients across 30 of the leading academic and non-academic centers in the United States, United Kingdom and Europe.