Autolus Therapeutics (AUTL) Status update summary

Unmet needs and treatment landscape in adult ALL

• Adult relapsed/refractory B-cell ALL has poor outcomes, with less than 40% five-year survival and median survival of 6-9 months after first relapse, highlighting a significant unmet need for new therapies.

• Nearly half of R/R adults are ineligible for allogeneic transplant, making CAR T-cell therapy a critical option, especially for those relapsed after transplant.

• CAR T-cell therapy, particularly obe-cel, offers durable remissions and is shifting the paradigm for transplant-ineligible patients, especially those with high-risk features or post-immunotherapy relapse.

• Product phenotype, manufacturing reliability, and toxicity profile are key differentiators among CAR-T therapies.

Efficacy and safety of obe-cel in clinical and real-world settings

• FELIX study reported a 77% overall response rate with obe-cel, with durable remissions and 40% of patients in remission at two to three years without transplant.

• Lower disease burden at infusion correlates with better outcomes; majority of responses were MRD negative.

• Obe-cel demonstrates a favorable safety profile with lower rates of severe CRS and neurotoxicity, enabling treatment of older and frailer patients.

• Real-world data from the ROKA/ROCCA consortium show nearly 95% day 28 response rates and over 70% MRD negative CR, with minimal high-grade toxicities.

• No high-grade CRS observed and only 3% high-grade ICANS in real-world data; response rates and safety profile are improved compared to the FELIX trial.

Expansion of obe-cel use and evolving treatment strategies

• Obe-cel is increasingly used in outpatient settings and for patients who would not have been eligible for CAR T previously, including those with comorbidities or high-risk genetics.

• Transplantation is less frequently offered post-obe-cel, as many patients achieve durable remissions.

• Real-world experience supports broadening obe-cel use across disease burdens and patient profiles.

• Case studies highlight durable MRD-negative remissions in high-risk and complex patients, including those with CNS involvement and Down syndrome.