Denali Therapeutics Announces New DNL343 (eIF2B Agonist) Phase 1b Data in ALS To Be Presented at the Upcoming AAN Annual Meeting
April 10 2023 - 7:00AM
Denali Therapeutics Inc. (Nasdaq: DNLI), a biopharmaceutical
company developing a broad portfolio of product candidates
engineered to cross the blood-brain barrier (BBB) for the treatment
of neurodegenerative and lysosomal storage diseases, today
announced that new data from the 28-day treatment period of the
Phase 1b study of DNL343 in participants with amyotrophic lateral
sclerosis (ALS) will be presented at the 75th Annual Meeting of the
American Academy of Neurology (AAN), which will be held April
22-27, 2023, in Boston, Massachusetts. DNL343 is an
investigational, small molecule eIF2B activator designed to cross
the BBB with the potential of preventing or slowing ALS disease
progression. The DNL343 abstract is available here on the AAN
conference website. A PDF of the poster presentation will be made
available on Denali’s website under the Events section here after
the AAN poster session begins at 11:45 a.m. EDT on April 25, 2023.
As previously announced, DNL343 has been selected to enter the
Phase 2/3 HEALEY ALS Platform Trial; Denali expects that recruiting
will begin in mid 2023.
Denali previously announced initial interim Phase 1b results
after 20 participants who had been randomized to receive DNL343 or
placebo had completed the double-blind period of the study. The
data demonstrated that once-daily oral dosing with DNL343 for 28
days was generally well-tolerated and was associated with extensive
distribution in the cerebrospinal fluid as well as robust
inhibition of biomarkers associated with the integrated stress
response (ISR) as measured by CHAC1 gene expression and ATF4
protein levels in blood samples from study participants. The Phase
1b pharmacokinetic profile along with preclinical in vivo data are
consistent with extensive distribution of DNL343 in the central
nervous system (CNS).
The upcoming presentation at AAN will include data from all 29
participants with ALS from the randomized, placebo-controlled,
28-day treatment period of the Phase 1b study. The results remain
consistent with those previously reported as described above.
Details of the presentation schedule are as follows:
Title: The Integrated Stress Response Is
Modulated by eIF2B Agonist DNL343: Results from Phase 1 Healthy
Subject and Phase 1b ALS Patient Studies (Poster
#P8-010)Session: Poster Session 8
Date: Tuesday, April 25,
2023Time: 11:45 AM - 12:45 PM EDT
About DNL343 and the HEALEY ALS Platform
TrialModulation of eIF2B activity with DNL343 is a novel
and targeted investigational approach with first-in-class potential
for the treatment of ALS. eIF2B is an intracellular protein complex
that regulates protein synthesis and is required for neuronal
health and function. When neurons experience stress, activation of
the ISR pathway leads to suppression of eIF2B activity, resulting
in impaired protein synthesis and formation of stress granules.
Stress granules are thought to be a precursor of TDP-43
aggregation, which is a hallmark pathology in ALS. DNL343 is
designed to activate eIF2B and thereby restore protein synthesis,
disperse TDP-43 aggregates, and improve neuronal survival. DNL343
is an investigational therapeutic and has not been approved by any
regulatory authority for any commercial use.
The HEALEY ALS Platform Trial is a large-scale collaborative
effort made possible by contributions from patients and families,
clinical trial sites, industry partners and research collaborators
to evaluate multiple investigational therapies simultaneously with
the goal of accelerating the development of potential new
treatments for ALS. The platform trial is led by the Sean M. Healey
& AMG Center for ALS at Massachusetts General Hospital (MGH) in
collaboration with the Northeast ALS Consortium (NEALS).
Therapeutic candidates that enter the platform trial are chosen by
a group of expert ALS scientists and members of the Healey &
AMG Center.
About Denali Therapeutics Denali
Therapeutics is a biopharmaceutical company developing a broad
portfolio of product candidates engineered to cross the blood-brain
barrier (BBB) for the treatment of neurodegenerative and lysosomal
storage diseases. Denali 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 is based in South
San Francisco. For additional information, please visit
www.denalitherapeutics.com.
Cautionary Note Regarding Forward-Looking
StatementsThis 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, statements
regarding plans, timelines and expectations related to DNL343,
including the ongoing Phase 1b study, the initiation of patient
recruitment for the Phase 2/3 study, the therapeutic potential
benefit of modulating eIF2B, the therapeutic potential of DNL343 to
prevent, slow, or treat ALS, and the commercial potential of
DNL343; and the potential benefits of, likelihood of success of,
and expectations related to Denali's collaboration with the HEALEY
ALS Platform Trial. 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 transition to a late stage clinical drug development
company; Denali’s and its partners’ ability to initiate, enroll
patients in, conduct, and complete its ongoing and future clinical
trials, including the ongoing Phase 1b study and upcoming Phase 2/3
study of DNL343, on expected timelines; Denali’s reliance on third
parties for the manufacture and supply of its product candidates
for clinical trials; the potential for clinical trial results of
DNL343 to differ from preclinical, preliminary or expected results,
including the initial Phase 1b results for DNL343; the risk of
adverse events; risks related to Denali’s collaborations; the risk
that results from early clinical biomarker studies will not
translate to clinical benefit in late clinical studies; the risk
that DNL343 may not in the future receive regulatory approval as a
treatment for ALS or other indications for which it is being
developed; 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. In
light of these risks, uncertainties, and assumptions, the
forward-looking statements in this press release are inherently
uncertain and may not occur, and actual results could differ
materially and adversely from those anticipated or implied in the
forward-looking statements. Accordingly, you should not rely upon
forward-looking statements as predictions of future events.
Information regarding additional risks and uncertainties may be
found in Denali’s most recent Quarterly Report on Form 10-Q filed
with the Securities and Exchange Commission (SEC) on November 3,
2022, Denali’s Annual Report on Form 10-K filed with the SEC on
February 28, 2022, 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.
Investor Contact:Laura Hansen, Ph.D.(650)
452-2747hansen@dnli.com
Media Contact:Angela Salerno-Robin(212)
445-8219asalerno-robin@dna-comms.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