Aptose Biosciences Inc. announced that a growing body of clinical data for Aptose?s lead compound tuspetinib (TUS), demonstrates significant benefit as a single agent and in combination with venetoclax (VEN) in patients with relapsed or refractory acute myeloid leukemia (R/R AML) in the ongoing APTIVATE Phase 1/2 study. Data were presented in an oral presentation now at the 65thAmerican Society of Hematology (ASH) Annual Meeting and Exposition by lead investigator Naval G. Daver, M.D., Professor, Director Leukemia Research Alliance Program, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX. Tuspetinib is a once-daily, oral, precision targeted kinase inhibitor that suppresses select kinases that drive the proliferation of AML.

These key kinase targets include the SYK, FLT3, JAK1/2, mutant forms of KIT, RSK2, and the TAK1-TAB1 kinases operative in AML, while avoiding non-therapeutic kinase targets to promote safety. Dr. Daver reported data from more than 100 relapsed/refractory patients from multiple international clinical sites, who had failed prior therapy and then were treated with tuspetinib (TUS) as a single agent or tuspetinib in combination with venetoclax (TUS/VEN). TUS and TUS/VEN delivered multiple composite complete remissions (CRcs) in this very ill AML population, while maintaining a favorable safety profile across all treated patients.

Highlights of Dr. Daver?s ASH oral presentation: TUS as Single Agent: As a single agent at therapeutic doses of 80-160 mg in 68 evaluable patients, TUS was more active in VEN-naïve patients, with an overall CRc rate of 29% (8/28); This included a 42% CRc rate (5/12) in FLT3-mutated patients; And a 19% CRc rate (3/16) in FLT3-unmutated, or wildtype, AML patients; Responses and blood counts improved with continuous dosing; Many bridged to an allogeneic stem cell transplant (HSCT); Durability was observed when HSCT was not performed; 80 mg was selected as the recommended phase 2 dose; Tuspetinib showed a favorable safety profile with only mild adverse events (AEs) and no dose-limiting toxicities (DLTs) up to 160 mg per day, and no drug discontinuations from drug related toxicity; TUS/VEN Combination Therapy: In the TUS/VEN doublet study, 49 patients were dosed with 80 mg of tuspetinib and 200 mg of venetoclax, with 36 evaluable (and 13 patients too early to assess); Patients were heavily exposed to Prior-VEN and Prior-FLT3 inhibitor treatment; TUS/VEN was active in both VEN-naïve and prior Prior-VEN relapsed/refractory patients; TUS demonstrated composite complete remission (CRc) rates: Among all evaluable patients, TUS/VEN demonstrated a CRc rate of 25% (9/36); 43% (3/7) in VEN-naïve patients, and 21% (6/29) in Prior-VEN patients. Among FLT3 wildtype patients, TUS/VEN demonstrated an overall CRc rate of 20% (5/25); 33% (2/6) in VEN-naïve patients, and 16% (3/19) in Prior-VEN patients; Among FLT3 mutant patients, TUS/VEN demonstrated an overall CRc rate of 36% (4/11); a complete response in a VEN-naïve patient (1/1); a 30% (3/10) in Prior-VEN patients; and 44% (4/9) in patients treated prior with a FLT3 inhibitor; Key findings: TUS/VEN is a well tolerated combination therapy; TUS/VEN is active across broad populations of R/R AML; TUS/VEN is active in FLT3 wildtype, representing ~70% of AML patients; TUS/VEN retains activity in the difficult-to-treat Prior-VEN AML population.