Denali Therapeutics Announces Positive Clinical Results From LRRK2 Inhibitor Program for Parkinson’s Disease
August 01 2018 - 3:30PM
Denali Therapeutics Inc. (NASDAQ: DNLI), a biopharmaceutical
company developing a broad portfolio of product candidates for
neurodegenerative diseases, today announced positive results from
its Phase 1 clinical study with DNL201, a small molecule inhibitor
of leucine-rich repeat kinase 2 (LRRK2).
In a randomized, double blind, placebo-controlled, oral dose
study in healthy subjects, DNL201 achieved its safety,
pharmacokinetic, and pharmacodynamic objectives. DNL201 was
generally well tolerated with no serious adverse events at doses
that achieved high levels of cerebrospinal fluid (CSF) exposure,
robust target engagement as measured by two blood-based biomarkers
of LRRK2 activity, and effects on biomarkers of lysosomal
function.
Mutations in the LRRK2 gene are the most frequent genetic cause
of Parkinson’s disease and a major driver of lysosomal dysfunction,
which contribute to the formation of Lewy body protein aggregates
and neurodegeneration. LRRK2 regulates lysosomal genesis and
function, which is impaired in Parkinson’s disease and may be
restored by LRRK2 inhibition, thereby potentially positively
modifying disease progression in patients with a genetic LRRK2
mutation as well as in patients with sporadic Parkinson’s
disease.
In the study of DNL201, more than 100 healthy subjects,
including healthy elderly subjects, received either single or
multiple ascending doses or placebo. Based on the clinical data
from this study, Denali intends to advance DNL201 into a Phase 1b
clinical study in Parkinson’s disease patients with and without a
genetic LRRK2 mutation by year-end 2018. Detailed clinical data
from the Phase 1 study with DNL201 will be presented at a future
medical conference.
“We conclude from this clinical trial that DNL201 was able to
achieve the targeted level of LRRK2 inhibition at doses that were
safe and well tolerated. We are pleased that the trial was a
success in all these key measures. The trial data give us
confidence to proceed with further clinical testing in Parkinson’s
patients and provide a solid basis for selection of the optimal
dose for future clinical trials in patients,” said Carole Ho, M.D.,
Chief Medical Officer.
“We are leading the way in testing LRRK2 inhibitors in humans
with the goal of bringing a disease modifying therapeutic to
patients suffering from Parkinson’s disease," said Ryan Watts,
Ph.D., CEO. "We are also encouraged to see mounting evidence
supporting a role of LRRK2 inhibition in the broader sporadic
Parkinson’s disease population, in addition to Parkinson’s disease
genetically associated with a LRRK2 mutation.”
A Phase 1 dose escalation study with DNL151, a second small
molecule inhibitor of LRRK2, is ongoing in the Netherlands.
About Denali
Denali is a biopharmaceutical company developing a broad
portfolio of therapeutic candidates for neurodegenerative
diseases. Denali pursues new treatments by rigorously
assessing genetically validated targets, engineering delivery
across the blood-brain barrier and guiding development with
biomarker monitoring to demonstrate target engagement and
select patients. Denali is based in South San Francisco. For
additional information, please
visit www.denalitherapeutics.com.
Cautionary Note Regarding Forward Looking
Statements
This press release contains forward-looking statements within
the meaning of the Private Securities Litigation Reform Act of
1995. Forward-looking statements expressed or implied in this press
release include, but are not limited to, plans to progress DNL201
into a Phase 1b clinical study in Parkinson’s disease patients with
and without a genetic LRRK2 mutation by year-end 2018, results of
targeting mutations of LRRK2 to develop disease modifying
medicines for Parkinson’s disease patients, the effects of
restoring LRRK2 activity to normal levels and potential benefits to
both patients with LRRK2 mutations and idiopathic Parkinson’s
disease who exhibit lysosomal dysfunction, Denali’s plans to
conduct further clinical testing in this area, statements regarding
dose selection for future clinical trials, Denali’s plans to
present the clinical data from the Phase 1 study with DNL201, and
statements made by Denali’s CMO and CEO.
Actual results are subject to risks and uncertainties and may
differ materially from those indicated by these forward-looking
statements as a result of these risks and uncertainties, including
but not limited to, risks related to: Denali’s early stages of
clinical drug development; Denali’s ability to complete the
development and, if approved, commercialization of its product
candidates; Denali’s dependence on successful development of its
BBB platform technology and product candidates currently in its
core program; Denali’s ability to conduct or complete clinical
trials on expected timelines; the uncertainty that any of Denali’s
product candidates will receive regulatory approval necessary to be
commercialized; Denali’s ability to continue to create a pipeline
of product candidates or develop commercially successful products;
Denali’s ability to obtain, maintain, or protect intellectual
property rights related to its product candidates; implementation
of Denali’s strategic plans for its business, product candidates
and BBB platform technology; and other risks, including those
described in Denali’s Annual Report on Form 10-K filed with
the SEC on March 19, 2018, Denali’s Quarterly Report
on Form 10-Q filed with the SEC on May 11, 2018 and Denali’s
future reports to be filed with the SEC. The forward-looking
statements in this press release are based on information available
to Denali as of the date hereof. Denali disclaims any
obligation to update any forward-looking statements, except as
required by law.
Contacts:
Lizzie Hyland(646)
495-2706lhyland@gpg.com
or
Morgan Warners(202)
295-0124mwarners@gpg.com
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