- Company to assess new molecules arising from
internal discovery and other companies to enhance suppression
of neurodegeneration through c-Abl inhibition –
- Selected non-proprietary name risvodetinib
for IkT-148009 evocative of 'reversal' -
BOSTON and ATLANTA, Aug. 21,
2023 /PRNewswire/ -- Inhibikase Therapeutics, Inc.
(Nasdaq: IKT) ("Inhibikase" or "Company"), a clinical-stage
pharmaceutical company developing protein kinase inhibitor
therapeutics to modify the course of Parkinson's disease,
Parkinson's-related disorders and other diseases of the Abelson
Tyrosine Kinases, is evaluating new molecules with multiple
mechanisms of action for c-Abl inhibition. Along with the
development of new molecules, IkT-148009 has now been granted the
non-proprietary name of risvodetinib (or
'risvo').
"The selectivity of IkT-148009 for the non-receptor Abelson
tyrosine kinases emerged from our discovery efforts leveraging our
RAMPTM medicinal chemistry approach. The selectivity of
IkT-148009 predicted a favorable safety profile and a favorable
safety profile has been seen thus far in the clinic," commented Dr.
Milton Werner, President and CEO of
Inhibikase. "The basis for this selectivity was visualized from the
x-ray crystal structure of IkT-148009 bound to its targets. These
structures have led to the design of second generation molecules
now in pre-clinical development. We believe these new designs could
further improve brain delivery and c-Abl inhibition in the central
nervous system. In addition, we are evaluating early stage
molecules from other companies that inhibit c-Abl without binding
to the enzyme active site. Such novel inhibitors, alone or in
combination with active site inhibitors like IkT-148009, may be an
improved approach to suppress neurodegeneration arising from c-Abl
activation inside and outside of the brain."
About IkT-148009 and Neurodegeneration
c-Abl
activation in response to alpha-synuclein invasion into neurons is
an early step in the course of Parkinson's disease. IkT-148009 is a
selective c-Abl kinase inhibitor that uniquely inhibits c-Abl and
the closely related Abl2/Arg enzyme, with limited inhibition of
other members of the Abl-kinase family, namely c-Kit or PDGFRa/b.
IkT-148009 has nearly 25x the potency of the anticancer agent
imatinib against c-Abl in enzyme inhibition assays. IkT-148009 is a
competitive inhibitor of c-Abl, meaning IkT-148009 binds more
tightly to the enzyme active site than its normal substrates and
prevents the enzyme active site from being occupied by its normal
binding targets inside neurons. By inhibiting c-Abl in neurons
where invading alpha-synuclein activated the enzyme, IkT-148009 can
suppress progression of neurodegeneration in animal models of
Parkinson's disease. An alternative approach to inhibition is to
lock the enzyme structure into an inactive state. Such inhibitors
hold c-Abl in a shape that precludes the enzyme active site from
being accessible to bind its normal targets in the first place.
Alone or in combination, this alternative inhibitor strategy might
hold c-Abl in a locked, inactive state in neurons that have not yet
been infiltrated by alpha-synuclein, while IkT-148009 could block
activated c-Abl in neurons that have already been invaded by
alpha-synuclein. These two approaches, separately or in
combination, could potentially improve the ability to block spread
of disease and more efficiently lead to clearance of the underlying
pathology associated with Parkinson's disease through processes
reactivated in the presence of c-Abl inhibition.
About risvodetinib
Following submission of a request
for an International Non-proprietary Name (INN) to the World Health
Organization ('WHO'), the WHO published the non-proprietary name of
risvodetinib as the official name of IkT-148009.
Following a 12 month response period, we have further submitted
this designation for IkT-148009 to the American Medical
Association's USAN non-proprietary naming program and requested
that risvodetinib be used to refer to IKT-148009 free
base and risvodetinib succinate to refer to the salt
form of IkT-148009. Going forward, we will refer to IkT-148009 as
risvodetinib or use the nickname
'risvo'.
About Parkinson's Disease
Parkinson's disease (PD) is
the second most prevalent neurodegenerative disorder, affecting up
to 1,200,000 persons in the United
States, with 90,000 new cases and 38,000 deaths annually. PD
is a progressive neurodegenerative disease that initiates with
misfolding of a small, non-essential protein known as
alpha-synuclein inside and outside of the brain. The common
features of PD include tremors at a resting state, slowing or lack
of control of movement and postural instability. These features of
the disease arise from degeneration of neurons that secrete
dopamine to transmit neurological signals. The degeneration of
these dopaminergic neurons in the brainstem, coupled with the
accumulation of alpha-synuclein protein aggregates in cell bodies
and terminals known as Lewy bodies, have long been thought to be
the cause of the disease. Less well known are the features of this
disease that can affect serotonin levels, cholinergic, and
norepinephrine neurons and nerve cells in the olfactory system,
cerebral hemisphere, brain stem, spinal cord, and peripheral
autonomic nervous system such as in the GI tract. Currently, these
non-dopaminergic features are not properly controlled with
dopamine-replacement or levodopa therapy. -Abl inhibition has
been shown to affect all these features in animal models of human
Parkinson's disease.
About Inhibikase
(www.inhibikase.com)
Inhibikase Therapeutics,
Inc. (Nasdaq: IKT) is a clinical-stage pharmaceutical company
developing therapeutics for Parkinson's disease and related
disorders. Inhibikase's multi-therapeutic pipeline focuses on
neurodegeneration and its lead program IkT-148009, an Abelson
Tyrosine Kinase (c-Abl) inhibitor, targets the treatment of
Parkinson's disease inside and outside the brain as well as other
diseases that arise from Ableson Tyrosine Kinases. Its
multi-therapeutic pipeline is pursuing Parkinson's-related
disorders of the brain and GI tract, orphan indications related to
Parkinson's disease such as Multiple System Atrophy, and drug
delivery technologies for kinase inhibitors such as IkT-001Pro, a
prodrug of the anticancer agent imatinib mesylate that the Company
believes will provide a better patient experience with fewer
on-dosing side-effects. The Company's RAMP™ medicinal chemistry
program has identified a number of follow-on compounds to
IkT-148009 to be potentially applied to other cognitive and motor
function diseases of the brain. Inhibikase is headquartered in
Atlanta, Georgia with offices in
Lexington, Massachusetts.
Social Media Disclaimer
Investors and others should
note that we announce material financial information to our
investors using our investor relations website, press releases, SEC
filings and public conference calls and webcasts. The company
intends to also use Twitter, Facebook, LinkedIn and
YouTube as a means of disclosing information about the
company, its services and other matters and for complying with its
disclosure obligations under Regulation FD.
Forward-Looking Statements
This press release contains
"forward-looking statements" within the meaning of the Private
Securities Litigation Reform Act of 1995. Forward-looking
terminology such as "believes," "expects," "may," "will," "should,"
"anticipates," "plans," or similar expressions or the negative of
these terms and similar expressions are intended to identify
forward-looking statements. These forward-looking statements are
based on Inhibikase's current expectations and assumptions. Such
statements are subject to certain risks and uncertainties, which
could cause Inhibikase's actual results to differ materially from
those anticipated by the forward-looking statements. Important
factors that could cause actual results to differ materially from
those in the forward-looking statements include our ability to
successfully conduct clinical trials and that results in our animal
studies may not be replicated in humans, as well as such other
factors that are included in our periodic reports on Form 10-K and
Form 10-Q that we file with the U.S. Securities and Exchange
Commission. Any forward-looking statement in this release speaks
only as of the date of this release. Inhibikase undertakes no
obligation to publicly update or revise any forward-looking
statement, whether as a result of new information, future
developments or otherwise, except as may be required by any
applicable securities laws.
Contacts:
Company Contact:
Milton H.
Werner, PhD
President & CEO
678-392-3419
info@inhibikase.com
Investor Relations:
Alex
Lobo
SternIR, Inc.
alex.lobo@sternir.com
View original content to download
multimedia:https://www.prnewswire.com/news-releases/inhibikase-therapeutics-initiates-development-of-second-generation-c-abl-inhibitors-and-names-ikt-148009-as-risvodetinib-301904847.html
SOURCE Inhibikase Therapeutics, Inc.