Allogene Therapeutics (ALLO) investor relations material

ALPHA3 study design and objectives

• ALPHA3 is a frontline consolidation trial for large B-cell lymphoma using cema-cel, an off-the-shelf allogeneic CAR T cell targeting CD19.

• Patients in remission after standard frontline therapy are tested for minimal residual disease (MRD) using a sensitive ctDNA-based assay.

• MRD-positive patients are randomized to either observation or cema-cel treatment to assess if early intervention improves long-term outcomes.

• The primary focus of the upcoming futility analysis is the rate of MRD clearance at day 45 post-randomization.

• Data will be shared publicly, including MRD clearance rates in both arms and some safety information.

Expectations and benchmarks for success

• A 25–30% absolute improvement in MRD clearance between cema-cel and observation arms is considered a strong outcome.

• Historical data from similar trials show modest MRD clearance deltas (e.g., 11% in a bladder cancer study), yet still led to positive clinical outcomes.

• MRD status is highly prognostic for relapse; clearing MRD correlates with improved event-free survival (EFS).

• The study is designed to capture patients with minimal disease burden, where CAR T efficacy is typically higher.

• Safety data will be provided, with most patients managed as outpatients.

Operational progress and MRD testing adoption

• Initial enrollment challenges were addressed by training clinicians to consider trial participation for patients in remission.

• MRD testing is gaining rapid adoption due to its superior prognostic value and ease of use compared to PET-CT.

• About 50% of trial sites are community practices, many new to CAR T therapy.

• MRD testing penetration is currently low but expected to grow quickly, especially with Natera's acquisition of Foresight Diagnostics.

• Serial MRD testing post-frontline therapy is anticipated to identify up to 30% of patients as MRD positive.