AUTO3

P1/2, N=73, Completed, Autolus Limited | Active, not recruiting --> Completed | Trial completion date: Nov 2024 --> Dec 2023 | Trial primary completion date: Nov 2024 --> Dec 2023

Overall, AUTO3 +/- pembrolizumab for r/r LBCL was safe, lending itself to outpatient administration, and delivered durable remissions in 54.4% of complete responders, associated with robust CAR-T expansion. Neither dual-targeting CAR-T nor pembrolizumab prevented relapse in a significant proportion of patients, and future developments include next-generation-AUTO3, engineered for superior expansion/persistence in vivo, and selection of CAR binders active at low antigen densities.

Building on these properties, we developed AUTO1/22 an autologous CAR T cell product co-transduced with two different lentiviral vectors encoding our existing CD19 CAR and a novel CD22CAR designed to recognise targets with low antigen density...Following fludarabine/cyclophosphamide lymphodepletion, patients received 1x106 /kg CAR+ T cells...Six of 12 patients had relapsed post allogeneic SCT, 6 had received prior Blinatumomab/Inotuzumab and 4 had relapsed after prior Tisagenlecleucel...Cytokine release syndrome (CRS) occurred in 11/12 patients (grade 1 n=5, grade 2 n=6) requiring Tocilizumab in 5 cases, but severe (≥ grade 3) CRS was not seen and no patients required ICU admission for CRS... Our data show that dual CD19/22 targeting CAR T cells generated by co-transduction show a favorable safety profile, with robust expansion/persistence and early efficacy in a heavily pre-treated cohort. To date with we have not observed antigen negative relapse. This contrasts to an incidence of 5/6 CD19 negative relapses in the 12 responders treated with single CD19 targeting CAR T cells (AUTO1) in an earlier cohort and suggests dual targeting may be effective in preventing antigen escape.

P1/2, N=73, Active, not recruiting, Autolus Limited | N=171 --> 73 | Recruiting --> Active, not recruiting

Relapses were probably due to limited long-term AUTO3 persistence. Strategies to improve CAR T cell persistence are needed to fully realize the potential of dual targeting CAR T cell therapy in B-ALL.

P1/2, N=171, Recruiting, Autolus Limited | Trial completion date: Mar 2022 --> Sep 2024 | Trial primary completion date: Mar 2022 --> Sep 2024

P1/2, N=171, Recruiting, Autolus Limited | Trial completion date: Mar 2021 --> Mar 2022 | Trial primary completion date: Mar 2021 --> Mar 2022

AUTO3 at RP2D dose range of > 50 x 106 CAR T cells with D-1 pembrolizumab induces durable complete remissions. None of the patients in CR experienced severe CRS or neurotoxicities of any grade. Outpatient cohort is currently enrolling.

Funding: Autolus Therapeutics. Clinical trial identification: EudraCT Number: 2016-004682-11.

P1/2, N=23, Completed, Autolus Limited | Active, not recruiting --> Completed | Trial completion date: Dec 2021 --> May 2020 | Trial primary completion date: Dec 2021 --> May 2020

Lymphodepletion was done with fludarabine and cyclophosphamide. Two out of 3 patients achieved CR at 450 x 106 cells on pem regimen B. Additional patients and longer follow up, as well as biomarkers, will be presented. Conclusion AUTO3 at > 50 x 106 CAR T cells with pembrolizumab induces CRs without severe CRS or neurotoxicities of any grade.

AUTO3 at > 50 x 106 CAR T cells with pembrolizumab induces CRs without severe CRS or neurotoxicities of any grade. Research Funding: Autolus Therapeutics

In this study, we are evaluating the safety and efficacy of AUTO3, a CAR T cell therapy designed to target CD19 and CD22 simultaneously followed by 3 doses of anti-PD1 monoclonal antibody pembrolizumab (Pem) treatment...All patients received lymphodepletion with 30 mg/m2/day fludarabine and 300 mg/m2/day cyclophosphamide for 3 days prior to AUTO3 infusion...Only one case (9%) of neurotoxicity was noted which was grade 3 and treated with steroids and tocilizumab... AUTO3, a novel bicistronic anti CD19/CD22 CAR T therapy, has a manageable safety profile in combination with Pem. Notable is the lack of severe CRS (0%). The efficacy data with 2/4 patients achieving CR at dose 150 x 10e6 cells is promising.