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 diseases and lysosomal storage diseases, today
announced upcoming presentations from its Enzyme Transport Vehicle
(ETV) development programs, tividenofusp alfa (DNL310) and DNL126
(ETV:SGSH), to be given at the 20th Annual WORLDSymposium™, which
will be held February 4-9, 2024, in San Diego, California.
WORLDSymposium™
Presentation Details on DNL310 and DNL126 Presentations on
DNL310 will include new two-year data on clinical outcomes and
previously presented data on biomarkers from the ongoing Phase 1/2
study in MPS II. In addition, an oral presentation will highlight
data from preclinical studies of DNL126 in an MPS IIIA mouse model.
The presentation schedule at WORLDSymposium™ is as follows:
Title: Interim Analysis of a Phase 1/2 Study of
Weekly Intravenous DNL310 (Brain-Penetrant Enzyme Replacement
Therapy) in Mucopolysaccharidosis Type IISession:
Clinical Applications Platform PresentationsDate:
Wednesday, February 7, 2024Time: 9:00 AM Pacific
Time
Title: Somatic Outcomes in a Phase 1/2 Study of
Weekly Intravenous DNL310 (Brain-Penetrant Enzyme Replacement
Therapy) in Mucopolysaccharidosis Type II (Poster
#43)Session: Clinical Applications – Poster
Session IIIDate: Wednesday, February 7,
2024Time: 3:00 PM - 5:00 PM Pacific Time
Title: DNL310 Phase 1/2 Case Study Demonstrates
Properties of Raw, Standard and Growth Scale Scores for Adaptive
Behavior Scales (Poster #80)Session: Contemporary
Forum – Poster Session IVDate: Thursday, February
8, 2024Time: 3:00 – 5:00 PM Pacific Time
Title: DNL310 Normalizes Primary Storage
Substrates, Corrects Biomarkers of Lysosomal Dysfunction and
Reduces Biomarkers of Neuronal Injury (Neurofilament Light Chain)
in MPS II: 2-Year Interim Analysis of a Phase 1/2 Study (Poster
#34)Session: Contemporary Forum – Poster Session
IVDate: Thursday, February 8,
2024Time: 3:00 – 5:00 PM Pacific Time
Title: ETV:SGSH, a Brain-Penetrant Enzyme
Transport Vehicle for SGSH, Improves Lysosomal and Microglial
Morphology, Degeneration and Cognitive Behavior in MPS IIIA
MiceSession: Contemporary Forum Platform
PresentationsDate: Thursday, February 8,
2024Time: 1:00 PM Pacific Time
Denali is also participating in or sponsoring the
following events being held at the
WORLDSymposium™:
Title: 3rd Annual Robert J. Gorlin Symposium –
Beyond the Blood Brain barrier: Strategies for Treating the
CNSCourse Director: Jeanine R. Jarnes, PharmD,
MSc, BCOP, BCPSDate: Tuesday, February 6,
2024Time: 5:15 – 7:30 PM Pacific Time
Title: From Prevailing to Pioneering – Current
and Emerging Biomarkers in Neurodegenerative Lysosomal
DiseasesDate: Wednesday, February 7,
2024Time: 5:15 – 6:15 PM Pacific Time
About MPS II (Hunter syndrome)
MPS II, also called Hunter syndrome, is a rare genetic disease
that affects over 2,000 individuals, primarily males, world-wide,
and leads to behavioral, cognitive, and physical symptoms
ultimately resulting in shortened lifespan. MPS II is caused by
mutations in the iduronate-2-sulfatase (IDS) gene, which leads to a
deficiency of the IDS enzyme. Symptoms often begin emerging around
age two and include physical complications, including organ
dysfunction, joint stiffness, hearing loss and impaired growth, and
neurocognitive symptoms with impaired development. The disease is
characterized by a buildup of glycosaminoglycans (GAGs) in
lysosomes — the part of the cell that breaks down materials
including GAGs. The current standard of care enzyme replacement
therapy partially treats the physical symptoms but does not cross
the BBB, and as a result, cognitive and behavioral symptoms
experienced by the majority of patients with MPS II are not
addressed. Therapies that address behavioral, cognitive, and
physical manifestations of the disease are one of the greatest
unmet needs for this community.
About tividenofusp alfa (DNL310)
Tividenofusp alfa (DNL310) is an investigational fusion protein
composed of IDS fused to Denali’s proprietary ETV, which is
engineered to cross the BBB via receptor-mediated transcytosis into
the brain. Preclinical studies demonstrate that DNL310 delivers IDS
to lysosomes in the brain, where it is needed to break down GAGs.
DNL310 is engineered for broad delivery of IDS into cells and
tissues throughout the body, including the brain, with the goal of
addressing the behavioral, cognitive, and physical manifestations
of MPS II. In March 2021, the U.S. Food and Drug
Administration granted Fast Track designation to DNL310 for
the treatment of patients with MPS II. In May 2022,
the European Medicines Agency granted DNL310 Priority
Medicines designation. DNL310 is an investigational product
candidate and has not been approved by any Health Authority.
About the Phase 2/3 COMPASS study
Based on supportive clinical and preclinical data to date,
Denali is conducting the Phase 2/3 COMPASS study of DNL310, which
is expected to enroll 54 participants with MPS II with and without
neuronopathic disease. The participants are randomized 2:1 to
receive either DNL310 or idursulfase, respectively. Cohort A
includes children ages 2 to 6 with neuronopathic disease; cohort B
includes children ages 6 to 17 without neuronopathic disease. The
Phase 2/3 COMPASS study is being conducted globally in North
America, South America, and Europe. Upon completion of the ongoing
Phase 1/2 study, and together with data from the global COMPASS
study, this combined data package is intended to support
registration. More information about the COMPASS study can be found
here.
About MPS IIIA (Sanfilippo syndrome Type A)
MPS III, also called Sanfilippo syndrome, is a rare, genetic
lysosomal storage disease that causes neurodegeneration. There are
four main types of MPS III, depending on the enzyme affected. Among
these, Type A is the most common and is caused by genetic defects
that result in reduction in the activity of N-sulfoglucosamine
sulfohydrolase (SGSH), an enzyme responsible for degrading heparan
sulfate in the lysosome. There are no approved treatments for MPS
IIIA. A natural history study of biomarkers and adaptive behavior
in MPS IIIA is ongoing; more information can be found here.
About DNL126 (ETV:SGSH)
DNL126 (ETV:SGSH) is an investigational, intravenously
administered, ETV-enabled N-sulfoglucosamine sulfohydrolase (SGSH)
replacement therapy designed to cross the BBB for the potential
treatment of MPS IIIA. A Phase 1/2 study of DNL126 in MPS IIIA is
ongoing; more information can be found here.
About Denali’s Transport Vehicle (TV)
Platform
The BBB is essential in maintaining the brain’s microenvironment
and protecting it from harmful substances and pathogens circulating
in the bloodstream. Historically, the BBB has posed significant
challenges to drug development for central nervous system diseases
by preventing most drugs from reaching the brain in therapeutically
relevant concentrations. Denali’s TV platform is a proprietary
technology designed to effectively deliver large therapeutic
molecules such as antibodies, enzymes, proteins, and
oligonucleotides across the BBB after intravenous administration.
The TV technology is based on engineered Fc domains that bind to
specific natural transport receptors, such as transferrin
receptors, which are expressed at the BBB and deliver the TV and
its therapeutic cargo to the brain through receptor-mediated
transcytosis. In animal models, antibodies and enzymes engineered
with the TV technology demonstrate more than 10- to 30-fold greater
brain exposure than similar antibodies and enzymes without this
technology. Improved exposure and broad distribution in the brain
may increase therapeutic efficacy by enabling widespread
achievement of therapeutically relevant concentrations of product
candidates.
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
diseases 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 Denali’s planned presentations and events at the 2024
WORLDSymposium™; Denali's plans and expectations related to DNL310,
the ongoing Phase 2/3 COMPASS study, and the open-label, single-arm
Phase 1/2 study, including the expectation that the studies may
support registration; expectations related to DNL126 and the
ongoing natural history study; and expectations related to Denali’s
TV technology platform and its therapeutic efficacy. 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 dependence on successful development
of its BBB platform technology and TV-enabled product candidates;
Denali’s ability to initiate and enroll patients in its current and
future clinical trials; Denali’s ability to conduct or complete
clinical trials 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 to
differ from preclinical, early clinical, preliminary or expected
results; the risk of significant adverse events, toxicities, or
other undesirable side effects; the risk that results from early
clinical biomarker studies will not translate to clinical benefit
in late clinical studies; the risk that product candidates may not
receive regulatory approval necessary to be commercialized;
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; 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 and
Quarterly Reports filed on Forms 10-K and 10-Q filed with the
Securities and Exchange Commission (SEC) on February 27, 2023, and
November 7, 2023, respectively, and Denali’s future reports to be
filed with the SEC. Denali does not undertake 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 and Media Contact:
Laura Hansen, Ph.D.Vice President, Investor
Relationshansen@dnli.com
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