Obe-cel (obecabtagene autoleucel, AUTO1) 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.
Obe-cel, met its primary endpoint at an interim analysis of the pivotal phase 2 FELIX study for adult ALL. Additional data were presented at ASCO and EHA in June 2023, with subgroup analysis data presented at ASH in December 2023. Additional data is expected at medical conferences in H1 2024. A BLA submission was accepted by the US FDA in January 2024 with a PDUFA goal date of November 16, 2024.
Obe-cel is currently being investigated in ongoing clinical studies for B-NHL, CLL and pediatric ALL indications.
Obe-cel has been granted orphan drug designation by the FDA, PRIME designation in relapsed/ refractory B-ALL by EMA and ILAP designation by the MHRA in adult relapsed/ refractory ALL.
AUTO1/22 is a novel dual targeting CAR T cell based therapy candidate based on obe-cel. It is designed to combine the enhanced safety, robust expansion & persistence seen with the fast off rate CD19 CAR from obe-cel with a high sensitivity CD22 CAR to reduce antigen negative relapses. This product candidate is currently in a Phase 1 clinical trial for patients with r/r pediatric ALL.
Data presented at the EBMT meeting in April 2023 demonstrated a favorable safety profile and good efficacy in a heavily pre-treated cohort of patients and, importantly, no antigen negative relapses were observed indicating that the combining of Autolus' optimized CD22 CAR design with the CD19 CAR used in obe-cel may be effective in preventing antigen-loss driven relapse in pediatric B-ALL.
AUTO4 and AUTO5 are two programmed T cell therapies for the treatment of peripheral T-cell lymphoma targeting TRBC1 and TRBC2 respectively, and both employing a novel and differentiated treatment approach. Each are designed to selectively kill cancerous T cells in a manner that we believe will preserve a portion of the patient’s normal, healthy T cells to maintain immunity.
Since the uses a novel mechanism to target T cells, Autolus has also programmed the product candidate with the RQR8 “safety switch” in order to allow physicians to manage toxicity by eliminating the programmed T cells if a patient experiences severe adverse side effects from the treatment.
AUTO4 is currently being tested in a Phase 1 study in TRBC1-positive peripheral T cell lymphoma. Data presented at ICML in June 2023 demonstrated safety with no dose limiting toxicities and good durability in 2 out of 4 responding patients at the highest dose level tested, with ongoing complete metabolic responses (CMR) in two r/r PTCL patients at 15 and 18 months.
A programmed T cell therapy targeting GD2 in development for the treatment of neuroblastoma, osteosarcoma and SCLC.
A Phase 1 clinical trial with AUTO6 was sponsored and conducted by Cancer Research UK, or CRUK, and data demonstrated initial anti-tumor activity in this solid tumor indication.
Autolus is developing AUTO6NG, a next generation programmed T cell product candidate which is in pre-clinical development. AUTO6NG builds on preliminary proof of concept data from AUTO6. AUTO6NG incorporates additional cell programming modules to overcome immune suppressive defense mechanisms in the tumor microenvironment, in addition to endowing the CAR T cells with extended persistence capacity. In collaboration with UCL, the Company is undertaking a a Phase 1 study.
AUTO8 is our next-generation product candidate for multiple myeloma which comprises two independent CARs for the multiple myeloma targets, BCMA and CD19. We have developed an optimized BCMA CAR which is designed for improved killing of target cell that express BCMA at low levels. This has been combined with fast off rate CD19 CAR from obe-cel.
We believe that the design of AUTO8 has the potential to induce deep and durable responses and extend the durability of effect over other BCMA CARs currently in development.
In collaboration with UCL, the Company initiated a study in Q1 2022 and data presented at ASH in December 2023 demonstrated that AUTO8 was well tolerated, with responses observed in all patients.