Aptose's Tuspetinib Triple Drug Therapy Featured at the 2025 ASH Annual Meeting; High Rate of Frontline Clinical Responses Continues Across AML Populations

Executive Summary

• Aptose presented updated Phase 1/2 data from the TUSCANY trial showing high response rates (90% overall, 100% at 80 mg and 120 mg doses) for the tuspetinib + venetoclax + azacitidine triplet in newly diagnosed AML patients.
• Responses were observed across diverse genetic sub‑populations—including FLT3‑WT/ITD, NPM1c, TP53/complex karyotype, RAS and MDS‑related mutations—with 78% of responders achieving MRD‑negative status.
• The regimen was well tolerated with no dose‑limiting toxicities, no drug‑related deaths, and a favorable transfusion‑independence profile (8/10 evaluable patients).

Key Details

• Study: TUSCANY Phase 1/2 trial; poster presented at ASH 2025, Orlando, FL.
• Doses Evaluated: 40 mg, 80 mg, 120 mg tuspetinib (TUS) in combination with standard venetoclax (VEN) and azacitidine (AZA).
• Efficacy – CR/CRh Rates:
• Overall across all dose levels: 90% (9/10 patients).
• 80 mg cohort: 100% (all evaluable patients).
• 120 mg cohort: 100% (all evaluable patients).
• Genetic Sub‑group Responses:
• FLT3‑WT, FLT3‑ITD, NPM1c – responses observed.
• TP53 biallelic/complex karyotype and RAS mutations – responses observed.
• MDS‑related mutation cohort – responses observed.
• MRD Negativity: 78% of responding subjects achieved MRD‑negative status by central flow cytometry.
• Safety:
• No dose‑limiting toxicities (DLTs) at any evaluated dose level.
• No prolonged myelosuppression in Cycle 1 for patients achieving remission.
• No drug‑related deaths, differentiation syndrome, QTc prolongation, or CPK elevation reported.
• Febrile neutropenia in 2 subjects (16.7%); only 1 case attributed to TUS.
• 8 of 10 evaluable patients attained red‑cell and platelet transfusion independence for > 8 weeks post‑best response.
• Transplantation: Two subjects proceeded to stem‑cell transplantation and returned for TUS maintenance therapy.
• Higher Dose Exploration: Preliminary data from a newly enrolled 160 mg cohort show early blast clearance, MRD negativity, and formal responses within the first few weeks (data not included in poster).
• Quote: “Tuspetinib… continues to perform well, achieving 100% clinical response in the two higher doses we have evaluated to date,” said Rafael Bejar, MD, PhD, Chief Medical Officer.

Notable Quotes

“We recently commenced treating patients at the highest dose level of 160 mg TUS and have already achieved early responses. With no dose‑limiting toxicities and activity across diverse mutations, TUS+VEN+AZA targets AML’s greatest unmet needs and largest populations.” – Rafael Bejar, MD, PhD, Chief Medical Officer, Aptose Biosciences

All forward‑looking statements are subject to risks and uncertainties as described in the release.