Denali Therapeutics Announces Decision to Advance DNL151 into Late Stage Clinical Studies in Parkinson’s Patients
August 06 2020 - 08:07AM
Denali Therapeutics Inc. (NASDAQ: DNLI), a biopharmaceutical
company developing a broad portfolio of product candidates
engineered to cross the blood-brain barrier (“BBB”) for treatment
of neurodegenerative diseases, today announced that DNL151 has been
selected to progress into late stage studies in Parkinson’s disease
patients with a kinase activating mutation in LRRK2 and in sporadic
Parkinson’s disease patients.
“Safety and biomarker data from studies of our two LRRK2
molecules in Parkinson’s patients support moving DNL151 into late
stage clinical studies with the aim of addressing the devastating
clinical decline and pathology of disease in Parkinson’s patients,"
said Carole Ho, M.D., Chief Medical Officer. “Our collaboration
partner Biogen is a respected leader in neurodegenerative diseases
and brings deep scientific and development expertise in Parkinson’s
disease which will allow us to accelerate our development plan and
we believe increase the likelihood of ultimate success.”
LRRK2 is a regulator of lysosomal function, which is impaired in
Parkinson’s disease and may be restored by LRRK2 inhibition.
Inhibition of LRRK2 activity may slow the progression of
Parkinson’s disease in patients with and without known genetic
risks based on restoration of lysosomal function. Mutations in the
LRRK2 gene can cause Parkinson’s disease and are a major driver of
lysosomal dysfunction, which contributes to neurodegeneration.
DNL151 has completed dosing of 162 healthy volunteers in an
ongoing Phase 1 clinical study and 25 Parkinson’s patients in a
Phase 1b clinical study. Denali is currently completing further
dose escalation cohorts in an expanded Phase 1 and an additional
cohort in the Phase 1b study to define the full therapeutic window
of the molecule. Based on the clinical data to date that have been
generated in Europe, DNL151 appears to have an acceptable safety
and tolerability profile, and has met desired target engagement
goals. An Investigational New Drug application for DNL151 was
cleared by the U.S. Food and Drug Administration in July 2020 and
enables expansion of our clinical studies for DNL151
globally. Based on the totality of preclinical and clinical
data to date, both DNL201 and DNL151 (two chemically distinct LRRK2
inhibitors) have met Denali’s requirements to proceed into further
late stage clinical studies. However, Denali has
selected DNL151 due to pharmacokinetic properties that provide
additional dosing regimen flexibility.
Denali and Biogen are working to finalize the clinical
development plans for the LRRK2 program and intend to commence two
separate Parkinson’s disease studies, one in patients with a kinase
activating mutation in LRRK2 and the other in patients with
sporadic disease. Patient enrollment is expected to commence in
2021.
About Denali’s LRRK2 program
Denali has two CNS-penetrant small molecules that inhibit LRRK2
in clinical studies, DNL201 and DNL151.
DNL 201 has successfully completed a Phase 1 study in 122
healthy volunteer subjects and a Phase 1b study in 28 Parkinson’s
disease patients. DNL201 has been generally safe and well tolerated
in doses tested and met all target engagement and biomarker goals.
Based on this, DNL201 has met the bar for progression into further
clinical studies.
DNL151 has successfully completed dosing of 162 healthy
volunteers in an ongoing Phase 1 study in healthy volunteer
subjects and completed dosing in 25 Parkinson’s disease patients in
a Phase 1b clinical study. DNL151 met safety, target engagement and
biomarker goals in the Phase 1 healthy volunteer study. Denali is
currently completing further dose escalation cohorts in an expanded
Phase 1 and Phase 1b study to define the full therapeutic window.
Target and pathway engagement of greater than 50 percent and a
dose-dependent reduction of BMP in urine of up to 50 percent were
observed at clinically relevant doses in healthy volunteers. The
DNL151 Phase 1b study (NCT04056689) in Parkinson’s disease patients
is a 28-day, multicenter, randomized, placebo controlled,
double-blind clinical trial in patients with mild-to-moderate
Parkinson’s disease being conducted in the U.S. and Europe. Its
purpose is to evaluate safety, tolerability, pharmacokinetics,
pharmacodynamics, including target and pathway engagement
biomarkers as well as certain exploratory clinical endpoints, after
multiple oral doses of DNL151. To date, 25 patients have been
enrolled in the study, and the protocol has been amended to expand
the study with up to 10 additional patients. Both the Phase 1
healthy volunteer and Phase 1b Parkinson’s patient studies are
anticipated to complete in 2020.
Further information on clinical studies with DNL151, DNL201 and
Denali’s efforts in Parkinson’s disease can be found on
clinicaltrials.gov and EngageParkinsons.com – Denali’s Parkinson’s
disease patient engagement website for patients, caregivers and
healthcare professionals.
About Denali
Denali Therapeutics is a biopharmaceutical company developing a
broad portfolio of product candidates engineered to cross the BBB
for neurodegenerative diseases. Denali Therapeutics pursues new
treatments by rigorously assessing genetically validated targets,
engineering delivery across the BBB and guiding development through
biomarkers that demonstrate target and pathway engagement. Denali
Therapeutics 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, timelines and
expectations related to DNL 201, DNL151 and other LRRK2 inhibitor
molecules; expectations regarding the proposed collaboration with
Biogen; the potential benefits and results of Denali’s
collaboration agreement with Biogen; expectations regarding the
commencement of, and timing of patient enrollment in, clinical
trials; expectations regarding the timing of completion of ongoing
clinical trials; and statements made by Denali’s Chief Medical
Officer.
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: any and all risks to Denali’s business and
operations caused directly or indirectly by the evolving COVID-19
pandemic; the risks that the proposed transaction with Biogen may
not be completed in a timely manner or at all; the possibility that
certain closing conditions to the proposed transaction with Biogen
will not be satisfied, including the finalization of a definitive
collaboration agreement; risks related to obtaining the requisite
regulatory approvals, including those required under antitrust
laws; the risk of the occurrence of any event, change or other
circumstance that could give rise to the termination of the
agreements with Biogen (including without limitation the failure to
timely obtain requisite regulatory approvals); Denali’s early
stages of clinical drug development; Denali’s and its partners’
ability to complete the development and, if approved,
commercialization of its product candidates; Denali’s and its
partners’ ability to enroll patients in clinical trials; Denali’s
reliance on third parties for the manufacture and supply its
product candidates for clinical trials; Denali’s dependence on
successful development of its BBB platform technology; Denali’s and
its partners’ ability to conduct or complete clinical trials on
expected timelines; the risk that preclinical profiles of Denali’s
product candidates, such as DNL151, may not translate in clinical
trials and that such product candidates may not sufficiently modify
Parkinson’s disease; the uncertainty that 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;
developments relating to Denali’s competitors and its industry,
including competing product candidates and therapies; 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; Denali’s ability to obtain additional
capital to finance its operations, as needed; Denali’s ability to
accurately forecast future financial results in the current
environment; general economic and market conditions; and other
risks and uncertainties, including those described in Denali’s most
recent Annual Report on Form 10-K, most recent Quarterly Report on
Form 10-Q 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:Morgan Warners(202)
295-0124mwarners@gpg.com
or
Lizzie Hyland(646) 495-2706lhyland@gpg.com
Denali Therapeutics (NASDAQ:DNLI)
Historical Stock Chart
From Feb 2024 to Mar 2024
Denali Therapeutics (NASDAQ:DNLI)
Historical Stock Chart
From Mar 2023 to Mar 2024