Dr. William Rice reports

APTOSE REPORTS RESULTS FOR THE THIRD QUARTER 2023

Aptose Biosciences Inc. has released financial results for the three months and nine months ended Sept. 30, 2023, and has provided a corporate update.

"The data we presented last week during the European School of Hematology (ESH) conference on acute myeloid leukemia (AML) demonstrate the exciting potential for tuspetinib (TUS) in the treatment of the very ill relapsed/refractory AML population and as part of a front line triplet combination regimen in newly diagnosed AML," said Dr. William G. Rice, PhD, chairman, president and chief executive officer. "Investigator enthusiasm for our tuspetinib/venetoclax (TUS/VEN) doublet has led to brisk enrolment in the Aptivate trial. The number of evaluable patients and clinical responses continue to grow, and we look forward to reporting the next data set just a few weeks from now during the American Society of Hematology (ASH) meeting."

Key corporate highlights

Tuspetinib Aptivate expansion

Trial continuing -- Tuspetinib, a once-daily oral agent with a unique kinase targeting pattern, is being developed for the treatment of patients with R/R AML. As reported at ESH, more than 140 patients have been treated in the continuing Aptivate phase 1/2 clinical trial: Ninety-one patients have received TUS as a single agent, and 51 thus far have been treated in the TUS/VEN cohort, with keen investigator interest accelerating patient enrolment in the doublet arm. In the most recent data cut (Oct. 23, 2023), the favourable safety profile remained consistent for TUS- and TUS/VEN-treated R/R AML patients. TUS avoids many typical toxicities observed with other kinase, IDH1/2 and menin inhibitors.

Tuspetinib single agent active with favourable safety: As reported at ESH, 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-per-cent and 60-per-cent CR/CRh response rates across all patients and across FLT3-mutated patients, respectively, among evaluable VEN-naive patients at the 80 milligrams daily recommended phase 2 dose (RP2D). Tuspetinib demonstrated a 29-per-cent CR/CRh rate in VEN-naive FLT3 unmutated (wild type) AML at 80 mg daily RP2D, unlocking the potential for TUS to treat the additional 70 to 75 per cent of the AML population without FLT3-mutation not currently addressed by any approved tyrosine kinase inhibitors. Tuspetinib single agent response rates compared favourably with the marketed FLT3 inhibitor gilteritinib, which has not demonstrated meaningful activity in FLT3 unmutated AML.

TUS/VEN doublet delivers responses in tough-to-treat populations: As reported in the ESH update from a data cut taken on Oct. 23, 2023, the TUS/VEN doublet showed a 48-per-cent overall response rate (ORR) in 31 evaluable patients (15 of 31). Eighty-one per cent of those patients had previously failed VEN treatment, representing an increasing AML population in need of improved salvage therapies, and TUS/VEN had a 44-per-cent ORR in those VEN failure patients. TUS/VEN showed a 60-per-cent ORR (six of 10) in FLT3-mutant AML and a 43-per-cent (nine of 21) ORR in FLT3-wild type AML. Analyses from the Oct. 23 data cut included preliminary data from patients very early in their treatment, who may see their responses to treatment mature over time.

TUS targets VEN resistance mechanisms; ESH poster presentation: Aptose presented a poster at ESH, "Tuspetinib Oral Myeloid Kinase Inhibitor Creates Synthetic Lethal Vulnerability to Venetoclax," demonstrating the ability of TUS to suppress a set of key oncogenic signalling pathways that mediate resistance to AML drugs by potently inhibiting SYK, mutated and unmutated forms of FLT3, JAK1/2, RSK2, mutant forms of KIT, and TAK1-TAB1 kinases. Aptose researchers investigated the effects of TUS on key elements of the phospho-kinome and apoptotic proteome in both parental and TUS-resistant AML cells. In parental cells, TUS acutely inhibits key oncogenic signalling pathways and shifts the balance of pro- and anti-apoptotic proteins in favour 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, making cells more than 2,000 times more sensitive to VEN. 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.

Tuspetinib clinical data selected for oral presentation at 2023 ASH annual meeting: Aptose announced last week that clinical data for tuspetinib were selected for oral presentation at the 65th American Society of Hematology (ASH) annual meeting and exposition being held Dec. 9 to Dec. 12, 2023, in San Diego, Calif. Lead investigator Dr. Naval Daver, professor, director, leukemia research alliance program, Department of Leukemia, the University of Texas, MD Anderson Cancer Center, will present data from Aptose's continuing Aptivate trial of tuspetinib (TUS) single agent and the TUS/VEN doublet in relapsed/refractory patients with acute AML.

Multiple planned value-creating milestones ahead:

• Aptivate oral presentation at ASH 2023 by Dr. Daver;
• TUS/VEN incremental data readout in R/R AML planned: ASH 2023;
• TUS/VEN further data on duration of response in R/R AML planned: first quarter and second quarter 2024;
• TUS/VEN/HMA planned initiation of pilot triplet study in 1L AML: first half 2024;
• Extension into HR-MDS and CMML planned: fourth quarter 2023.

Conference call and webcast

Date:  Thursday, Nov. 9, 2023

Time:  5 p.m. ET

An audio-only webcast will be available.

The company will conduct a question-and-answer session.

Analysts interested in participating in the question-and-answer session will preregister for the event to receive the dial-in numbers and a unique PIN, which are required to participate in the conference call. They also will have the option to take advantage of a call-me button, and the system will automatically dial out to connect to the Q&A session.

The audio webcast also will be available through a link on the investor relations section of Aptose's website. A replay of the webcast will be available on the company's website for 30 days.

The press release, the financial statements, and management's discussion and analysis for the quarter ended Sept. 30, 2023, will be available on SEDAR+ and EDGAR.

About Aptose Biosciences Inc.

Aptose is a clinical-stage biotechnology company committed to 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 has two clinical-stage oral kinase inhibitors under development for hematologic malignancies: tuspetinib (HM43239), an oral, myeloid kinase inhibitor 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; and luxeptinib (CG-806), an oral, dual lymphoid and myeloid kinase inhibitor in phase 1 a/b stage development for the treatment of patients with relapsed or refractory hematologic malignancies.

We seek Safe Harbor.