Aptose Announces Publication of Preclinical Data in AACR Journal Demonstrating Tuspetinib’s Unique Mechanism of Action and Synthetic Lethality on AML Cells When Combined with Venetoclax
12 Dezembro 2024 - 12:15PM
Aptose Biosciences Inc. (“Aptose” or the “Company”) (NASDAQ: APTO,
TSX: APS), a clinical-stage precision oncology company
developing highly differentiated targeted agents to treat
hematologic malignancies, today announced the publication of
preclinical data for Aptose’s lead hematology compound tuspetinib
(TUS) in Cancer Research Communications, a journal of the American
Association for Cancer Research (AACR), available online now
(link).
The publication,
entitled “Preclinical development of tuspetinib for
the treatment of acute myeloid leukemia,” is the
first preclinical profiling of tuspetinib, a well-tolerated, once
daily, oral kinase inhibitor currently in clinical development for
treatment of acute myeloid leukemia (AML). The publication defines
TUS activities on select oncogenic signaling targets, demonstrates
enhanced activity and safety of TUS when combined with other
agents, and illustrates synthetic lethality when combined with
venetoclax (VEN). Pharmacokinetic and toxicology studies revealed
that TUS is readily absorbed and achieves plasma concentrations
sufficient to inhibit the target kinases, it has a plasma half-life
that supports once daily dosing, and it demonstrates a favorable
safety profile.
Aptose is now enrolling newly diagnosed AML
patients in a Phase 1/2 clinical study to receive the tuspetinib +
venetoclax + azacitidine (TUS+VEN+AZA) triplet combination
(NCT03850574). Clinical studies in patients with relapsed or
refractory AML receiving TUS single agent or the TUS+VEN
combination have been completed.
“The non-clinical findings presented in the
publication suggest that TUS will demonstrate favorable safety and
a breadth of antileukemic activity across AML patient populations
with a diversity of adverse mutations, and the initial clinical
data is bearing that out,” said William G. Rice, Chairman,
President and Chief Executive Officer. “We are eager for the next
set of data in our triplet combination trial of TUS+VEN+AZA.”
Key findings:
- Tuspetinib inhibits a defined
cluster of oncogenic signaling kinases operative in AML
- TUS inhibits SYK, JAK1/2, RSK2,
mutant KIT, and wild type and mutant forms of FLT3
- TUS potently killed AML lines (GI50
= 1.3 to 5.2 nM) and Ba/F3 cells expressing wildtype (GI50 = 9.1
nM) or various mutant forms of FLT3 (GI50 = 2.5 – 56 nM)
- TUS dampens stroma-induced
activation of FLT3-ITD signaling in AML cells
- TUS prolongs survival in multiple
AML models
- Oral TUS markedly extended survival
in subcutaneously and orthotopically inoculated xenograft models of
FLT3 mutant human AML, was well tolerated, and delivered enhanced
activity when combined with venetoclax or 5-azacytidine
- TUS combines effectively with other
classes of agents to kill AML cells with mutations in RAS and other
difficult-to-treat adverse mutations
- TUS was 2.1-15-fold and a
4.5-13-fold more potent than gilteritinib at blocking fibrinogen
and immunoglobulin-mediated activation of SYK in KG-1a cells
- The most notable observation was
the marked and unexpected synthetic lethal vulnerability to
venetoclax and two MCL1 inhibitors in the TUS-resistant cells
About Aptose
Aptose Biosciences 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 therapeutics
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, oral kinase inhibitor tuspetinib (TUS) has
demonstrated activity as a monotherapy and in combination therapy
in patients with relapsed or refractory acute myeloid leukemia
(AML) and is being developed as a frontline triplet therapy in
newly diagnosed AML. For more information, please visit
www.aptose.com.
Forward Looking Statements
This press release may contain forward-looking
statements within the meaning of Canadian and U.S. securities laws,
including, but not limited to, statements relating to the
therapeutic potential of tuspetinib, its clinical development and
safety profile, including that it combines effectively with other
classes of agents and will demonstrate a favorable safety profile
and a breadth of antileukemic activity across an AML patient
population with a diversity of adverse mutations, as well as
statements relating to the Company’s plans, objectives,
expectations and intentions and other statements including words
such as “continue”, “expect”, “intend”, “will”, “should”, “would”,
“may”, and other similar expressions. Such statements reflect our
current views with respect to future events and are subject to
risks and uncertainties and are necessarily based upon a number of
estimates and assumptions that, while considered reasonable by us
are inherently subject to significant business, economic,
competitive, political and social uncertainties and contingencies.
Many factors could cause our actual results, performance or
achievements to be materially different from any future results,
performance or achievements described in this press release. Such
factors could include, among others: our ability to obtain the
capital required for research and operations and to continue as a
going concern; the inherent risks in early stage drug development
including demonstrating efficacy; development time/cost and the
regulatory approval process; the progress of our clinical trials;
our ability to find and enter into agreements with potential
partners; our ability to attract and retain key personnel; changing
market conditions; inability of new manufacturers to produce
acceptable batches of GMP in sufficient quantities; unexpected
manufacturing defects; and other risks detailed from time-to-time
in our ongoing quarterly filings, annual information forms, annual
reports and annual filings with Canadian securities regulators and
the United States Securities and Exchange Commission.
Should one or more of these risks or
uncertainties materialize, or should the assumptions set out in the
section entitled “Risk Factors” in our filings with Canadian
securities regulators and the United States Securities and Exchange
Commission underlying those forward-looking statements prove
incorrect, actual results may vary materially from those described
herein. These forward-looking statements are made as of the date of
this press release and we do not intend, and do not assume any
obligation, to update these forward-looking statements, except as
required by law. We cannot assure you that such statements will
prove to be accurate as actual results and future events could
differ materially from those anticipated in such statements.
Investors are cautioned that forward-looking statements are not
guarantees of future performance and accordingly investors are
cautioned not to put undue reliance on forward-looking statements
due to the inherent uncertainty therein.
For further information, please contact:
Aptose
Biosciences Inc.Susan
PietropaoloCorporate Communications & Investor
Relations201-923-2049spietropaolo@aptose.com
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