Dr. Rafael Bejar reports

APTOSE TUSPETINIB CLINICAL DATA FEATURED IN ORAL PRESENTATION AT THE 2023 ASH ANNUAL MEETING

A growing body of clinical data for Aptose Biosciences Inc.'s lead compound tuspetinib demonstrates significant benefit as a single agent and in combination with venetoclax in patients with relapsed or refractory acute myeloid leukemia in the continuing Aptivate phase 1/2 study. Data were presented in an oral presentation today at the 65th American Society of Hematology (ASH) annual meeting and exposition by lead investigator Dr. Naval G. Daver, MD, professor, director, leukemia research alliance program, Department of Leukemia, the University of Texas, MD Anderson Cancer Center, Houston, Tex.

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 and JAK1/2, mutant forms of KIT and 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 as a single agent or tuspetinib in combination with venetoclax. TUS and TUS/VEN delivered multiple composite complete remissions (CRcs) in this very ill AML population, while maintaining a favourable safety profile across all treated patients.

"Tuspetinib is clearly an active and surprisingly well-tolerated agent in one of the most challenging and heterogeneous disease settings in oncology: relapsed and refractory AML," said Dr. Daver. "Tuspetinib has demonstrated broad activity, including activity in patients with FLT3 wild-type AML (accounting for more than 70 per cent of the AML population), FLT3 mutated AML, NPM1 mutated AML, as well as in patients with mutations historically associated with resistance to targeted therapy. Most notably, TUS targets VEN resistance mechanisms, enabling TUS/VEN uniquely to treat the very ill prior-VEN AML population, including both FLT3 mutant and FLT3 wild-type disease. From a broader perspective, the growing body of anti-leukemic activity and continued favourable safety profile support advancement of tuspetinib in a TUS/VEN/HMA triplet for the treatment of front line newly diagnosed AML patients."

Dr. Daver also pointed out that while patients on the TUS/VEN therapy are early in their treatment cycles, most achieving a response remained on treatment, and that responses have begun to mature as dosing continues.

Highlights of Dr. Daver's ASH oral presentation

TUS as single agent:

• As a single agent at therapeutic doses of 80 to 160 milligrams in 68 evaluable patients, TUS was more active in VEN-naive patients, with an overall CRc rate of 29 per cent (eight out of 28):
  • This included a 42-per-cent CRc rate (five out of 12) in FLT3-mutated patients;
  • A 19-per-cent CRc rate (three out of 16) in FLT3-unmutated, or wild type, 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.
• Eighty mg was selected as the recommended phase 2 dose.
• Tuspetinib showed a favourable safety profile with only mild adverse events (AEs), 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-naive 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 per cent (nine out of 36), 43 per cent (three out of seven) in VEN-naive patients and 21 per cent (six out of 29) in prior-VEN patients.
  • Among FLT3 wild-type patients, TUS/VEN demonstrated an overall CRc rate of 20 per cent (five out of 25), 33 per cent (two out of six) in VEN-naive patients and 16 per cent (three out of 19) in prior-VEN patients.
  • Among FLT3 mutant patients, TUS/VEN demonstrated an overall CRc rate of 36 per cent (four out of 11), a complete response in a VEN-naive patient (one of one), 30 per cent (three out of 10) in prior-VEN patients and 44 per cent (four out of nine) in patients treated prior with an 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 wild type, representing approximately 70 per cent of AML patients.
  • TUS/VEN retains activity in the difficult-to-treat prior-VEN AML population.

"The wealth of data we have generated -- and continue to generate -- on tuspetinib points to a highly active, well-differentiated drug for AML populations that are in need of options beyond currently available therapies," said Dr. Rafael Bejar, MD, PhD, chief medical officer at Aptose. "Brisk patient enrolment in our Aptivate trial has led to a fast-growing database that includes many more patients at various stages of treatment. We look forward to reporting our next set of data in the first quarter of 2024."

The slides from Dr. Daver's presentation are available on Aptose's website.

About Aptose Biosciences Inc.

Aptose is a clinical-stage biotechnology company, developing precision medicines addressing unmet medical needs in oncology, with an initial focus on hematology. The company's small-molecule cancer therapeutic pipeline includes products designed to provide single-agent efficacy and to enhance the efficacy of other anti-cancer therapies and regimens without overlapping toxicities. The company's lead clinical-stage product, tuspetinib, is a once-daily oral therapy being studied as monotherapy and in combination therapy in the Aptivate international phase 1/2 expansion trial in patients with relapsed or refractory acute myeloid leukemia.

We seek Safe Harbor.