On October 16, 2023 Aptose Biosciences Inc. ("Aptose" or the "Company") (NASDAQ: APTO, TSX: APS), a clinical-stage precision oncology company developing highly differentiated oral kinase inhibitors to treat hematologic malignancies, reported that two abstracts on tuspetinib, Aptose’s Phase 1/2 myeloid kinase inhibitor in development for acute myeloid leukemia (AML), have been accepted for poster presentations at the European School of Haematology (ESH) 6th International Conference: Acute Myeloid Leukemia "Molecular and Translational": Advances in Biology and Treatment, being held October 29-31, 2023, in Estoril, Portugal (Press release, Aptose Biosciences, OCT 16, 2023, View Source [SID1234635989]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Aptose is planning to hold a clinical update webcast on October 30, 2023, to provide additional up-to-date data on tuspetinib. Details will be forthcoming.

The posters accepted for presentation are listed below and can be viewed beginning October 29, 2023, on site at the ESH poster exhibit hall and online on the Aptose website here.

Poster Presentations

Tuspetinib Myeloid Kinase Inhibitor Safety and Efficacy as Monotherapy and Combined with Venetoclax in Phase 1/2 Trial of Patients with Relapsed or Refractory (R/R) Acute Myeloid Leukemia (AML)

Abstract Summary: Tuspetinib (TUS) is a potent once daily oral myeloid kinase inhibitor of SYK, mutated and unmutated forms of FLT3, JAK1/2, RSK, mutant forms of KIT, and TAK1-TAB1 kinases that mediate dysregulated cellular proliferation in acute myeloid leukemia (AML). As a single agent, TUS was well-tolerated and highly active across four dose levels among diverse AML genotypes and delivered a 42% CR/CRh across evaluable venetoclax (VEN) naïve patients at the 80mg daily RP2D. In the ongoing APTIVATE clinical study, tuspetinib is being evaluated clinically as monotherapy (TUS) and in combination with venetoclax (TUS/VEN) in a global Phase 1/2 trial of patients with R/R AML. The TUS/VEN doublet also has been well tolerated and has achieved multiple responses to date in patients who previously failed VEN (Prior-VEN failure AML), including Prior-VEN failure patients who also previously failed FLT3 inhibitors, all of whom represent emerging populations of high unmet medical need. Notably, TUS targets VEN resistance mechanisms and appears to re-sensitize Prior-VEN failure patients to VEN.
Tuspetinib Oral Myeloid Kinase Inhibitor Creates Synthetic Lethal Vulnerability to Venetoclax

Abstract Summary: Tuspetinib (TUS), a once daily oral agent, simultaneously suppresses a limited set of key oncogenic signaling pathways that mediate resistance to acute myeloid leukemia (AML) drugs by potently inhibiting SYK, mutated and unmutated forms of FLT3, JAK1/2, RSK, mutant forms of KIT, and TAK1-TAB1 kinases. TUS as a single agent produces complete remissions in relapsed/refractory (R/R) AML patients, and the tuspetinib/venetoclax (TUS/VEN) combination doublet achieves multiple responses among very difficult to treat AML subpopulations in the ongoing Phase 1/2 APTIVATE trial. We investigated the effects of TUS on key elements of the phosphokinome and apoptotic proteome in both parental and TUS-resistant AML cells. In parental cells, TUS acutely inhibits key oncogenic signaling pathways and shifts the balance of pro- and anti-apoptotic proteins in favor of apoptosis, suggesting that it may generate vulnerability to VEN. Indeed, acquired TUS resistance generated a synthetic lethal vulnerability to VEN of unusually high magnitude. Concurrent administration of TUS and VEN may eliminate cells that carry this form of TUS resistance at the start of therapy and discourage the emergence of TUS resistance during treatment.