Denali Therapeutics Announces Achievement of RIPK1 Milestone for Phase 2 Clinical Trial Initiation in Multiple Sclerosis by Sanofi
26 January 2023 - 12:00AM
Denali Therapeutics Inc. (Nasdaq: DNLI), a biopharmaceutical
company developing a broad portfolio of product candidates
engineered to cross the blood-brain barrier for the treatment of
neurodegenerative diseases and lysosomal storage diseases, today
announced that its partner Sanofi has commenced dosing in a Phase 2
study of SAR443820 (DNL788) in individuals with multiple sclerosis.
SAR443820 is a central nervous system (CNS)-penetrant
investigational small molecule inhibitor of RIPK1.
“Multiple sclerosis is a chronic and disabling,
inflammation-mediated neurodegenerative disease with limited
treatment options that target disease progression1,” said Nazem
Atassi, M.D., Global Head of Early Neurology Development at Sanofi.
“RIPK1 inhibition with SAR443820 is a novel therapeutic approach
that may reduce inflammation and cell death associated with disease
progression in multiple sclerosis. SAR443820 has demonstrated
robust target engagement and CNS penetration at doses that were
generally well tolerated in Phase 1 studies in healthy volunteers,
and we are eager to learn more from this Phase 2 study of SAR443820
in multiple sclerosis as we strive to bring innovative therapies to
people with unmet medical needs.”
“Following the initiation of the Phase 2 HIMALAYA study in ALS
with SAR443820 last year by Sanofi, this Phase 2 study in multiple
sclerosis marks another important milestone for our RIPK1 program,”
said Carole Ho, M.D., Chief Medical Officer at Denali. “We look
forward to collaborating with Sanofi as we aim to make a meaningful
difference for individuals living with neurodegenerative diseases
by delivering novel treatment options.”
About SAR443820 and Sanofi RIPK1 Inhibitor
Collaboration
In 2018, Denali and Sanofi entered into a broad partnership for
the global development and commercialization of CNS-penetrant and
peripherally restricted RIPK1 inhibitors. RIPK1 is a critical
signaling protein in a canonical inflammatory and cell death
pathway. Increased RIPK1 activity in the brain drives
neuroinflammation and cell necroptosis and contributes to
neurodegeneration. RIPK1 inhibition has been shown to have
beneficial effects in preclinical models of amyotrophic lateral
sclerosis (ALS), multiple sclerosis, Alzheimer's disease, and other
diseases.
SAR443820 is a CNS-penetrant RIPK1 inhibitor and was discovered
by Denali scientists. Sanofi leads Phase 1 and Phase 2 development
of SAR443820 for ALS and multiple sclerosis and leads
co-development of SAR443820 with Denali in Phase 3 clinical trials
for ALS, multiple sclerosis and Alzheimer’s disease. Sanofi
completed a Phase 1 trial of SAR443820 in healthy volunteers in
which robust target engagement was demonstrated at doses that were
generally well tolerated. Based on these results, Sanofi initiated
the HIMALAYA global Phase 2 study of SAR443820 in ALS in 2022, with
an anticipated enrollment of approximately 260 participants.
Under the collaboration agreement, Denali will receive a
milestone payment of $25 million from Sanofi for initiation of the
Phase 2 study with SAR443820 in multiple sclerosis. Denali is
entitled to receive additional development and regulatory milestone
payments. Denali will share profits and losses equally with Sanofi
for CNS-penetrant products sold in the United States and China, and
Denali is entitled to receive royalties on net sales for
CNS-penetrant products sold outside of the United States and
China.
Sanofi is also conducting two Phase 2 clinical studies with
another RIPK1 inhibitor, SAR443122 (eclitasertib; DNL758), in
cutaneous lupus erythematosus and ulcerative colitis. SAR443122
(eclitasertib) is a peripherally restricted RIPK1 inhibitor and was
discovered by Denali scientists. Sanofi is responsible for the
development and commercialization of SAR443122 (eclitasertib) and
covers all costs related to the program. Denali is entitled to
receive development, regulatory and sales milestone payments and
royalties on product sales.
SAR443820 and SAR443122 (eclitasertib) are investigational
therapeutics that have not been approved by any regulatory
authority for any commercial use.
About Denali TherapeuticsDenali Therapeutics is
a biopharmaceutical company developing a broad portfolio of product
candidates engineered to cross the blood-brain barrier for
neurodegenerative diseases and lysosomal storage diseases. Denali
pursues new treatments by rigorously assessing genetically
validated targets, engineering delivery across the blood-brain
barrier 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 both Denali’s and Sanofi’s plans, timelines,
expectations, and milestones related to SAR443820 (DNL788) and
SAR443122 (DNL758); statements made by Denali’s Chief Medical
Officer; statements made by Sanofi’s Global Head of
Early Neurology Development; Denali’s priorities, regulatory
approvals, timing and likelihood of success and expectations
regarding its collaborations; Denali's expectations regarding
milestone payments and royalties on product sales; expectations
regarding Denali’s product candidates and the therapeutic potential
of SAR443820 (DNL788) and SAR443122 (DNL758); and the ongoing Phase
2 studies of SAR443820 (DNL788) in ALS and SAR443122 (DNL758) in
cutaneous lupus erythematosus and ulcerative colitis. 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: any and all risks to Denali’s
business and operations caused directly or indirectly by the
ongoing COVID-19 pandemic; Denali’s early stages of clinical drug
development; Denali’s dependence on successful development of its
BBB platform technology and TV-enabled product candidates; Denali’s
and its partners’ ability to enroll patients in its ongoing and
future clinical trials; the potential for clinical trial results of
Denali’s product candidates to differ from preclinical, early
clinical, preliminary or expected results; Denali’s reliance on
third parties for the manufacture and supply of its product
candidates for clinical trials; Denali’s and its partners' ability
to conduct or complete clinical trials on expected timelines; the
risk that the expected benefits of Fast Track designation for
SAR443820 (DNL788) will not materialize; the risk that SAR443820
(DNL788) and SAR443122 (DNL758) may cause serious adverse events,
toxicities or other side effects; the risk that SAR443820 (DNL788)
and SAR443122 (DNL758) may not in the future receive regulatory
approval as a treatment for ALS, MS, Alzheimer’s disease, cutaneous
lupus erythematosus, ulcerative colitis, or other indications
necessary to be commercialized; risk of the occurrence of any
event, change or other circumstance that could give rise to the
termination of Denali’s collaboration agreements; Denali’s and its
partners’ ability to complete the development and, if approved,
commercialization of its product candidates on expected timelines;
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; and other risks and uncertainties. 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 Annual Report on Form 10-K and 10-Q filed with
the Securities and Exchange Commission (SEC) on February 28, 2022
and November 3, 2022, respectively, 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 or revise any
forward-looking statements, to conform these statements to actual
results or to make changes in Denali’s expectations, except as
required by law.
Investor Contact:
Laura Hansen, Ph.D. Vice President, Investor
Relations (650) 452-2747 hansen@dnli.com
Media Contact:
Angela Salerno-Robin(212)
445-8219asalerno-robin@dna-comms.com
1 Multiple sclerosis: Diagnosis & treatment. Mayo Clinic
website. Available at:
https://www.mayoclinic.org/diseases-conditions/multiple-sclerosis/diagnosis-treatment/drc-20350274.
Accessed January 2023.
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