Denali Therapeutics Provides Broad Update on Its RIPK1 Program Partnered With Sanofi
10 June 2020 - 6:30AM
Denali Therapeutics Inc. (NASDAQ: DNLI), a biopharmaceutical
company developing a broad portfolio of product candidates
engineered to cross the blood-brain barrier (“BBB”) for
neurodegenerative diseases, today announced the results from its
Phase 1b studies with small molecule RIPK1 inhibitor DNL747 in
Alzheimer’s disease and ALS, and provided a broad RIPK1 program
update including DNL788 and DNL758.
“Together with our partner Sanofi, we have decided to pause
clinical studies with DNL747 and focus our efforts on accelerating
development of DNL788, which we believe has superior drug
properties and a more rapid path toward proof-of-concept clinical
studies in patients in multiple neurological indications," said
Ryan Watts, Ph.D., CEO. “We’d like to thank all patients who took
part in these studies. Your participation is critical in the
ultimate success of developing medicines for these terrible
diseases.”
RIPK1, receptor-interacting serine/threonine-protein kinase 1,
is a critical signaling protein in the TNF receptor pathway, which
regulates inflammation and cell death in tissues throughout the
body.
Data from 31 patients in two 29-day Phase 1b studies in
Alzheimer’s disease and ALS, and additional data from six ALS
patients in an open label extension study, showed that DNL747 was
safe and well tolerated at the dose tested with no significant
treatment related adverse events. Target engagement of
approximately 80% median inhibition of pRIPK1 in blood at trough
drug concentration was achieved.
In parallel to the clinical studies, chronic toxicity studies
with DNL747 in cynomolgus monkeys showed dose- and
duration-dependent adverse preclinical findings at exposures higher
than those tested in the clinic. These findings, which are
considered off-target and molecule-specific, impact the ability to
increase the dose of DNL747 and achieve higher levels of target
inhibition without time consuming additional clinical safety
studies in patients to evaluate the long-term safety and
tolerability.
“Due to emerging evidence that higher levels of target
inhibition may be required for maximizing efficacy, and challenges
to achieving higher doses imposed by molecule-specific toxicity
findings with DNL747, we are pausing additional studies with this
molecule," said Carole Ho, M.D., Chief Medical Officer. “However, I
am encouraged by the emerging pathway biomarker data in Alzheimer’s
disease and ALS patients, and our experience and learnings with
DNL747 should allow us to progress quickly with clinical studies
for DNL788. Importantly, DNL788 appears to have a superior
preclinical therapeutic window compared to DNL747, facilitating
development in multiple indications, including Alzheimer’s disease,
ALS and multiple sclerosis.”
Data from the completed Phase 1 study with
peripherally-restricted RIPK1 inhibitor DNL758 in healthy volunteer
subjects display an encouraging profile, as the molecule appears
safe and tolerable at doses tested. Denali partner Sanofi is
responsible for development of DNL758 and is currently planning
further clinical studies in multiple indications based on
successful Phase 1 data.
(a) SAR443060, (b) SAR443820, (c) SAR443122
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 http://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 DNL747, DNL788 and DNL758 of both Denali
and Sanofi; Denali’s and Sanofi’s intentions to accelerate DNL788
for development in neurological indications, with plans to initiate
clinical testing by early 2021; expectations regarding development
of DNL788 in multiple indications; plans for further clinical
studies of DNL758 in multiple indications; and statements made by
Denali’s CEO and 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; 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 ability to
enroll patients in its ongoing and future clinical trials; Denali’s
reliance on third parties for the manufacture and supply its
product candidates for clinical trials; the risk of the occurrence
of any event, change or other circumstance that could give rise to
the termination of Denali’s collaboration agreements, including the
collaboration agreement with Sanofi; Denali’s dependence on
successful development of its BBB platform technology; Denali’s
ability to conduct or complete clinical trials on expected
timelines; the risk that preclinical profiles of Denali’s product
candidates, such as DNL788, may not translate in clinical studies,
and 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 From 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:
Lizzie Hyland(646)
495-2706lhyland@gpg.com
or
Morgan Warners(202)
295-0124mwarners@gpg.com
Denali Therapeutics (NASDAQ:DNLI)
Historical Stock Chart
From Jun 2024 to Jul 2024
Denali Therapeutics (NASDAQ:DNLI)
Historical Stock Chart
From Jul 2023 to Jul 2024