Onconova Therapeutics Announces Publication of Preclinical Data Supporting Rigosertib’s Mechanism of Action as a Targeted A...
July 23 2020 - 8:00AM
Onconova Therapeutics, Inc. (NASDAQ: ONTX), a Phase 3-stage
biopharmaceutical company focused on discovering and developing
novel products to treat cancer, with an initial focus on
myelodysplastic syndromes (MDS), today announced the publication
(Molecular Cell 79, 180-190, 2020) of in vitro data further
supporting rigosertib’s role in modulating RAS cellular signaling.
“We believe this data sheds light on the
capacity of Onconova’s targeted anti-cancer agent rigosertib to
modulate the RAS pathway,” said Steven M. Fruchtman, M.D.,
President and CEO. “Mutations of the RAS pathway are the most
common mutations observed in cancer. In our opinion this paper
confirms the rationale to investigate rigosertib in the treatment
of RAS-driven malignant diseases which continue to have a high
unmet medical need. Onconova looks forward to further showcasing
efforts with this novel compound, including our virtual
presentation at the 2nd Annual RAS-Targeted Drug Development Summit
September 14-16, 2020.”
The study compared the composition and activity
of non-clinical grade rigosertib with clinical grade rigosertib
that is approved for investigational use in humans. The authors
found that non-clinical grade rigosertib used in in vitro studies
by others contained impurities and degradation products in
sufficient quantities to impact cellular function. In contrast,
clinical grade rigosertib, which has been used in all clinical
studies to-date, is free of this impurity. Using vincristine as a
control, the ability of both compounds to bind tubulin (a mechanism
of action seen in less targeted chemotherapy agents) was then
measured. In vitro assay results indicated that both non-clinical
grade rigosertib and the vincristine control showed tubulin binding
activity, while clinical-grade rigosertib did not exhibit
detectable tubulin-binding activity. Furthermore, cell lines
expressing mutant beta-tubulin remained sensitive to
rigosertib.
“We believe that the impurities found in
non-clinical grade rigosertib, but not clinical-grade rigosertib,
are responsible for the cellular effects observed such as tubulin
disruption. Impurities are often found in non-clinical grade
products and hence the reason these materials are not permitted in
clinical trials,” said Richard C. Woodman, M.D., Chief Medical
Officer. “The peer-reviewed data reported in Molecular Cell provide
new detail on how these impurities can influence chemical
properties, cellular functions and subsequently, potential
anticancer pathways. It is our opinion that this data supports
rigosertib’s mechanism of action as a modulator of RAS
signaling.”
“Rigosertib is a RAS mimetic that binds to RAS
binding domains of RAS effectors and inhibits growth of tumor cells
in pre-clinical models. Our studies showed that clinical grade
rigosertib does not exhibit tubulin binding activity. Clinical
studies conducted by Onconova Therapeutics are expected to provide
further insights into the clinical potential of this novel
compound,” added E. Premkumar Reddy, PhD, Professor of
Pharmacological and Oncological Sciences, The Tisch Cancer
Institute at the Icahn School of Medicine at Mount Sinai, who is
also on Onconova’s Board of Directors.
About Rigosertib
Rigosertib, Onconova’s lead candidate, is a
proprietary Phase 3 small molecule. A key publication in a
preclinical model reported rigosertib’s ability to block cellular
signaling by targeting RAS effector pathways (Divakar, S.K., et
al., 2016: "A Small Molecule RAS-Mimetic Disrupts RAS Association
with Effector Proteins to Block Signaling." Cell 165, 643).
Onconova is currently in the clinical development stage with oral
and IV rigosertib, including clinical trials studying single agent
IV rigosertib in second-line higher-risk MDS patients (pivotal
Phase 3 INSPIRE trial) and oral rigosertib plus azacitidine in
HMA-naive and refractory higher-risk MDS patients (Phase 2).
Investigator-initiated study (IIS) programs exploring oral
rigosertib in a variety of cancers with mutations of RAS and its
pathway are ongoing in solid tumors. Patents covering oral and
injectable rigosertib have been issued in the US and are expected
to provide coverage until at least 2037.
About Onconova Therapeutics,
Inc.
Onconova Therapeutics, Inc. is a Phase 3-stage
biopharmaceutical company focused on discovering and developing
novel drugs to treat cancer, with an initial focus on
myelodysplastic syndromes (MDS). Onconova has a pipeline of
proprietary targeted agents designed to work against specific
cellular pathways that are important in cancer cells. Advanced
clinical trials with the Company’s lead compound, rigosertib, are
aimed at what the Company believes are unmet medical needs of
patients with MDS. Onconova has conducted trials with two other
research compounds and has a pre-clinical program with a CDK4/6 and
ARK5 inhibitor, ON 123300.
For more information, please visit
https://www.onconova.com.
Forward-Looking Statements
Some of the statements in this release are
forward-looking statements within the meaning of Section 27A of the
Securities Act of 1933, as amended, Section 21E of the Securities
Exchange Act of 1934, as amended, and the Private Securities
Litigation Reform Act of 1995, and involve risks and uncertainties.
These statements relate to Onconova expectations regarding the
INSPIRE Trial and Onconova’s other development plans. Onconova has
attempted to identify forward-looking statements by terminology
including "believes," "estimates," "anticipates," "expects,"
"plans," "intends," "may," "could," "might," "will," "should,"
"approximately" or other words that convey uncertainty of future
events or outcomes. Although Onconova believes that the
expectations reflected in such forward-looking statements are
reasonable as of the date made, expectations may prove to have been
materially different from the results expressed or implied by such
forward-looking statements. These statements are only predictions
and involve known and unknown risks, uncertainties, and other
factors, including Onconova's ability to continue as a going
concern, maintain its Nasdaq listing, the need for additional
financing, the success and timing of Onconova's clinical trials and
regulatory approval of protocols, our collaborations including the
effective termination of the HanX license and securities purchase
agreements and plans for partnering certain territories, and those
discussed under the heading "Risk Factors" in Onconova's most
recent Annual Report on Form 10-K and quarterly reports on Form
10-Q. Any forward-looking statements contained in this release
speak only as of its date. Onconova undertakes no obligation to
update any forward-looking statements contained in this release to
reflect events or circumstances occurring after its date or to
reflect the occurrence of unanticipated events.
Press release contact information
Company Contact:Avi OlerOnconova Therapeutics,
Inc.267-759-3680
ir@onconova.ushttps://www.onconova.com/contact/
MediaDavid Schull, Russo Partners LLC: (212)
845-4271Nic Johnson, Russo Partners LLC: (212) 845-4242
InvestorsJan Medina, CFA, Russo Partners LLC:
(646) 942-5632
Onconova Therapeutics (NASDAQ:ONTX)
Historical Stock Chart
From Mar 2024 to Apr 2024
Onconova Therapeutics (NASDAQ:ONTX)
Historical Stock Chart
From Apr 2023 to Apr 2024