On May 14, 2024 Aptose Biosciences Inc. ("Aptose" or the "Company") (NASDAQ: APTO, TSX: APS), a clinical-stage precision oncology company developing highly differentiated oral targeted agents to treat hematologic malignancies, reported financial results for the first quarter ended March 31, 2024 (Press release, Aptose Biosciences, MAY 14, 2024, View Source [SID1234643209]). The Company will provide a corporate update webcast at 5:00 pm ET today, which will include slides focused on the new triplet pilot study expected to deliver clinical data in the second half of this year.
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"Tuspetinib (TUS) has now moved to triplet frontline (1L) treatment for newly diagnosed (ND) acute myeloid leukemia (AML) patients who need a superior 1L therapy. The introduction of venetoclax (VEN) to establish the venetoclax/hypomethylating agent (VEN+HMA) doublet was a major advancement in the frontline treatment of ND AML, but response rates still remain too low and survival too short in 1L therapy. Even more concerning, patients who fail a VEN-containing regimen respond poorly to subsequent salvage therapies in the relapsed or refractory (R/R) setting and have a dismal prognosis," said William G. Rice, Ph.D., Chairman, President and Chief Executive Officer of Aptose. "Our solution is the addition of TUS to VEN-HMA to increase response rates, prolong survival, safely improve quality of life, treat a broad spectrum of AML genetic subpopulations, and prevent ND AML patients from becoming resistant to VEN. We’re delighted to have an active protocol to initiate this pilot clinical study and look forward to sharing initial TUS+VEN+HMA triplet data before year-end."
Key Corporate Highlights
Tuspetinib Advancement to TUS+VEN+HMA Triplet Therapy Supported by Extensive Dose Exploration as TUS Single Agent and TUS+VEN Doublet – Tuspetinib, a convenient once daily oral agent that potently targets SYK, FLT3, mutated KIT, JAK1/2, and RSK2 kinases, is being developed for the treatment of patients with ND AML. Tuspetinib avoids many typical toxicities observed with other agents, showing no treatment related QTc prolongation or CPK elevations; no differentiation syndrome; and no drug-related myelosuppression during remission with no drug-related discontinuations or deaths. In the APTIVATE trial, Tuspetinib achieved broad activity across AML patients with a diversity of adverse genetics as a single agent (TUS) and in combination with venetoclax (TUS+VEN) in very ill relapsed/refractory (R/R) and heavily pre-treated AML populations. Blast reductions and responses were observed in patients with Prior-VEN, Prior-FLT3 inhibitor (FLT3i), and Prior-HSCT therapies, those with highly adverse genetics, including mutations in TP53 and RAS genes, and those with mutated or unmutated FLT3 genes. Patients naïve to VEN therapy achieved higher response rates.
Tuspetinib Protocol Now Ready for Triplet Therapy Pilot Study; Clinical Sites Being Activated – Tuspetinib is the ideal third agent for a 1L triplet because of its distinctly favorable safety profile. Tuspetinib enhances antileukemic activity when combined with VEN or HMA in pre-clinical models, Tuspetinib has demonstrated a broad scope of activity across genetic subgroups of AML, and Tuspetinib mechanistically cooperates with VEN to thwart drug resistance. The protocol was submitted to the U.S. Food and Drug Administration (FDA) in Q1, more than 45 days ago, and is currently being activated at clinical sites to initiate the TUS+VEN+AZA triplet pilot study. The new study will enroll ND AML patients who are ineligible to receive intensive induction chemotherapy due to age or co-morbidity. By definition, study participants will be VEN-naïve, FLT3i-naïve, and HMA-naïve, a group that has been shown to be highly responsive to triplet regimens. However, current triplet therapies containing kinase inhibitors can be limited by toxicities often requiring dose reductions of all three agents and are not being pursued in the larger FLT3-unmutated AML population. Clinical sites are now preparing to open the TUS+VEN+HMA triplet study, which is expected to commence enrollment early next quarter. Initial data are expected in the fourth quarter of this year.
Tuspetinib Abstract Accepted for Poster Presentation at EHA (Free EHA Whitepaper) – Aptose will deliver a clinical poster presentation at the European Hematology Association (EHA) (Free EHA Whitepaper) 2024 Hybrid Congress in Madrid, Spain (Poster ID # P557) that describes the safety and efficacy of tuspetinib (TUS) monotherapy and the TUS+VEN doublet in the APTIVATE Phase 1/2 trial with R/R AML patients. The data illustrate the safety and breadth of activity of TUS and TUS+VEN and support our launch of the TUS+VEN+HMA triplet frontline therapy in newly diagnosed AML. A separate preclinical abstract, which has been accepted for e-poster publication, demonstrates that TUS retains nanomolar potency against AML cells engineered to express the NRAS-G12D mutation or selected for resistance to venetoclax (Poster ID # P1756).
Tuspetinib Preclinical Studies Elucidate Mechanistic Cooperativity Among TUS and VEN – Aptose continues to investigate the mechanisms underlying the complementary activity between TUS and VEN. In addition to targeting certain VEN resistance mechanisms, TUS retains activity against VEN-resistant AML cell lines. Likewise, resistance to TUS creates a synthetic lethality for VEN with a 2000-fold increase in sensitivity to VEN. Other studies demonstrate TUS retains potent antitumor activity in preclinical models of human AML resistant to the gilteritinib FLT3 inhibitor (FLT3i), a finding that is clinically validated by response rates to TUS in R/R AML study participants with prior FLT3i treatment.
Nasdaq – On February 29, 2024, Aptose received a deficiency letter from the Listings Qualifications Department of The Nasdaq Stock Market LLC ("Nasdaq") regarding the previously announced private placement with Hanmi Pharmaceutical, Inc. ("Hanmi") which closed in January 2024. In response to the deficiency letter, Aptose submitted a plan to Nasdaq to regain compliance. On April 25, 2024, the Company received confirmation from Nasdaq that the Company had regained compliance with Nasdaq Listing Rule 5635(d) and determined that the matter is now closed. Pursuant to the Company’s plan to regain compliance, on April 26, 2024, the Company announced that it had amended the terms of the warrant agreement with Hanmi to prohibit the exercise of the warrants if such exercise would result in Hanmi owning more than 19.99% of the issued and outstanding shares of Aptose, unless shareholder approval is first obtained.
On April 2, 2024, Aptose received a second Notification Letter from Nasdaq stating that the Company was not in compliance with Nasdaq’s listing rules because the stockholders’ equity as of December 31, 2023, was below the minimum requirement of $2.5 million. The shareholder’s equity as of December 31, 2023 was negative $2.9 million. As of March 31, 2024, the shareholder’s equity is $137,000, positive. Aptose intends to submit a compliance plan on or before May 17, 2024, to monitor stockholders’ equity and, if appropriate, consider further available options to evidence compliance with the requirement.
Multiple Planned Value-creating Milestones Ahead
TUS and TUS+VEN data in R/R AML to support TUS+VEN+HMA in ND AML: EHA (Free EHA Whitepaper) 2024
Triplet pilot dose initiation planned in ND AML: Summer 2024
Triplet pilot dose escalation planned with early CR/MRD/safety data in ND AML: ASH (Free ASH Whitepaper) 2024
Triplet pilot completed with CR/MRD data and dose selection: EHA (Free EHA Whitepaper) 2025
Triplet Ph2/Ph3 pivotal program planned initiation: 2H 2025