Aptose Biosciences presents highlights from webcast on tuspetinib

Aptose Biosciences released highlights from a clinical update event held today, October 30, 2023, in conjunction with the European School of Haematology 6th International Conference: Acute Myeloid Leukemia “Molecular and Translational”: Advances in Biology and Treatment, being held in Estoril, Portugal. The webcast event featured a comprehensive review of up-to-date clinical data for Aptose’s lead compound tuspetinib by Rafael Bejar, MD, PhD, Aptose’s Chief Medical Officer, and featured Naval G. Daver, MD, Professor, Director Leukemia Research Alliance Program, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX. Dr. Daver is the lead investigator on Aptose’s APTIVATE trial of tuspetinib and is recognized for significant achievements in the development of novel acute myeloid leukemia treatments, including several combination therapies. 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 other kinases are avoided to promote safety. AML care has shifted toward venetoclax containing combination regimens and a new population of difficult-to-treat VEN relapsed patients is emerging. Tuspetinib’s safety, activity, mechanism of action, and convenient dosing make it ideal for combination therapy. Importantly, TUS directly targets VEN resistance mechanisms. This means that TUS targets pathways and may lead to re-sensitizing VEN-resistant cells to VEN when given in combination. TUS/VEN may safely and successfully treat these VEN failures, as we already have observed clinically, and an accelerated approval path may be available for VEN failure relapsed or refractory AML patients treated with TUS/VEN.Aptose provided updated clinical findings from the ongoing APTIVATE study of tuspetinib: Patient Enrollment: More than 140 patients have been treated with tuspetinib to date; 91 patients have received TUS as a single agent; Aptose anticipated dosing up to 30 patients with TUS/VEN by the ESH 2023 Conference; however, investigator enthusiasm resulted in dosing of 49 patients, and patients continue being enrolled. Safety Profile: In the most recent data cut, the favorable safety profile remained consistent for TUS and TUS/VEN treated R/R AML patients: No TUS related adverse events of QTc prolongation; No observed differentiation syndrome; No TUS related non-hematologic serious AEs; No TUS related deaths; No rhabdomyolysis or AEs of elevated creatine phosphokinase; No TUS related dose-limiting toxicities from 20 mg level through 160 mg level; One DLT of muscle weakness at 200 mg; Occurred in patient with high exposure; Not rhabdomyolysis No muscle destruction; Avoids many typical toxicities observed with other FLT3, IDH1/2, and menin inhibitors; In TUS/VEN doublet, no unexpected or new safety signals were observed. Tuspetinib Single Agent: Tuspetinib as a single agent was well-tolerated and highly active among relapsed or refractory AML patients with a diversity of adverse genotypes. TUS single agent delivered 42% and 60% CR/CRh response rates across all patients and across FLT3-mutated patients, respectively, among evaluable VEN-naive patients at the 80mg daily recommended phase 2 dose. Tuspetinib demonstrated a 29% CR/CRh rate in VEN-naive FLT3 unmutated AML at 80 mg daily RP2D, unlocking the potential for TUS to treat the additional 70-75% of the AML population without FLT3-mutation not currently addressed by any approved tyrosine kinase inhibitors; Responses were achieved across four dose levels; Responses were shown to mature over time with sustained blood count recovery during continuous dosing; Several responders were bridged to potentially lifesaving transplant; Durability was observed when HSCT was unavailable; Tuspetinib single agent response rates compare favorably to gilteritinib FLT3 inhibitor. TUS/VEN Doublet: Patients who have failed venetoclax treatment represent an increasing AML population in need of improved salvage therapies; Over 90% of recent U.S. patients enrolled in the APTIVATE trial were VEN failures; VEN resistance involves mutations in multiple pathways to evade BCL-2 blockade; Tuspetinib directly targets pathways involved in VEN resistance; By shutting down these pathways, tuspetinib appears to re-sensitize prior-VEN failures to venetoclax; Overall Response Rates with TUS/VEN Doublet: 31 evaluable patients showed an ORR 48%; 81% of patients were VEN failures; 44% ORR in VEN failures; 60% ORR in FLT3-mutant; 43% ORR in FLT3-wildtype; Most patients are very early in treatment, having initiated dosing in the past 2-6 weeks, and responses are expected to mature over time