Aptose Biosciences Inc. released highlights from a clinical update event held October 30, 2023, in conjunction with the European School of Haematology (ESH) 6thInternational Conference: Acute Myeloid Leukemia "Molecular and Translational" Advances in Biology and Treatment, being held in Estoril, Portugal (the ESH 2023 Conference). The webcast event featured a comprehensive review of up-to-date clinical data for Aptose's lead compound tuspetinib (TUS) 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 (AML) treatments, including several combination therapies.

Tuspetinib (TUS) 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 (VEN) containing combination regimens and a new population of difficult-to-treat VEN relapsed patients (?VEN failures?) 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 (suppresses mutated FLT3, mutated KIT, SYK and mutated JAK1/2 of the JAK/STAT pathway, RSK2 of the RAS/MAPK pathway, key oncogenic growth and proliferation signals, and MCL-1 expression). 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 already have observed clinically, and an accelerated approval path may be available for VEN failure relapsed or refractory (R/R) AML patients treated with TUS/VEN. Clinical Findings: 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 (as of October 23, 2023), and patients continue being enrolled. Safety Profile: In the most recent data cut (October 23, 2023), the favorable safety profile remained consistent for TUS and TUS/VEN treated R/R AML patients: No TUS related adverse events (AEs) 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 (CPK); No TUS related dose-limiting toxicities (DLT) 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 (R/R) 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-naïve patients at the 80mg daily recommended phase 2 dose (RP2D); Tuspetinib demonstrated a 29% CR/CRh rate in VEN-naïve FLT3 unmutated (wildtype) 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 (HSCT); Durability was observed when HSCT was unavailable; Tuspetinib single agent response rates compare favorably to gilteritinib FLT3 inhibitor.