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 upcoming presentations from Enzyme Transport Vehicle
(ETV) development programs, DNL310 (ETV:IDS) and DNL126 (ETV:SGSH),
to be given at the 19th Annual WORLDSymposium™, which will be held
February 22-26, 2023, in Orlando, Florida.
DNL310 is an investigational, ETV-enabled, brain-penetrant
enzyme replacement therapy designed to address the behavioral,
cognitive, and physical manifestations of MPS II (Hunter syndrome).
Denali is evaluating DNL310 in the global Phase 2/3 COMPASS study,
which is enrolling participants with MPS II in North America, South
America, and Europe, and in an open-label, single-arm Phase 1/2
study. DNL126 is Denali’s second most advanced ETV-enabled program
in development for the potential treatment of MPS IIIA (Sanfilippo
syndrome type A) for which Denali plans to submit an
Investigational New Drug (IND) application in the first half of
2023.
Presentations on DNL310 will include new interim data on
biomarkers, safety, exploratory clinical outcomes and an analysis
of toileting ability from the ongoing Phase 1/2 study as well as
the Phase 2/3 COMPASS study design. In addition, another 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 key clinical
outcomes from a phase 1/2 study of weekly intravenous DNL310
(brain-penetrant enzyme replacement therapy) in MPS
IISession: Clinical Applications Platform
PresentationsDate: Friday, February 24,
2023Time: 9:00 AM Eastern
TimeTitle: Interim analysis of key clinical
outcomes from a phase 1/2 study of weekly intravenous DNL310
(brain-penetrant enzyme replacement therapy) in MPS II (Poster
#248)Session: Clinical Applications – Poster
Session V Date: Friday, February 24,
2023Time: 3:00 PM - 4:00 PM Eastern Time
Title: COMPASS, A double-blinded randomized
phase 2/3 study of the efficacy and safety of intravenous DNL310
(brain-penetrant enzyme replacement therapy) in MPS II (Poster
#13)Session: Contemporary Forum – Poster Session
VII Date: Saturday, February 25,
2023Time: 3:00 – 4:00 PM Eastern Time
Title: DNL310 normalizes primary storage
substrates and biomarkers of lysosomal dysfunction in neuronopathic
MPS II: 2-year interim analysis of a phase 1/2 study (Poster
#48)Session: Contemporary Forum – Poster Session
VIIDate: Saturday, February 25,
2023Time: 3:00 – 4:00 PM Eastern Time
Title: DNL310-treated study participants with
MPS II show improvements in toileting
abilitiesSession: Contemporary Forum Poster
PresentationsDate: Saturday, February 25,
2023Time: 4:00 – 5:00 PM Eastern Time
Title: ETV:SGSH, a brain-penetrant enzyme
transport vehicle for SGSH, corrects heparan sulfate accumulation,
lysosomal lipid storage and inflammation in MPS IIIA mouse
brainSession: Contemporary Forum Platform
PresentationsDate: Saturday, February 25,
2023Time: 8:00 AM Eastern TimePDFs of the poster
presentations will be made available on Denali’s corporate website
under the Investor Events section on February 22, 2023, at
approximately 3:00 PM Eastern Time. PDFs of the oral presentations
will be posted on Denali’s corporate website under the Investor
Events section on the corresponding date and time of the
presentation.
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 physical, cognitive, and behavioral 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 blood-brain barrier, and as a result, cognitive and behavioral
symptoms experienced by the majority of patients with Hunter
syndrome 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 DNL310 (ETV:IDS)
DNL310 is an investigational fusion protein composed of IDS
fused to Denali’s proprietary ETV, which is engineered to cross the
blood-brain barrier via receptor-mediated transcytosis into the
brain. Preclinical studies demonstrate that DNL310 delivers IDS to
lysosomes, 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. In March 2021,
the U.S. Food and Drug Administration granted Fast Track
designation to DNL310 for the treatment of patients with Hunter
syndrome. 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 DNL310 Phase 2/3 COMPASS
study
Based on supportive clinical and preclinical data to date,
Denali is conducting the Phase 2/3 COMPASS study, which is expected
to enroll 54 participants with MPS II with and without
neuronopathic disease. The participants will be randomized 2:1 to
receive either DNL310 or idursulfase, respectively. Cohort A will
include children ages 2 to 6 with neuronopathic disease; cohort B
will include 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 DNL126 (ETV:SGSH) and MPS IIIA (Sanfilippo
syndrome type A)
MPS IIIA, 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. Type A 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. DNL126 is an investigational, ETV-enabled,
brain-penetrant SGSH replacement therapy designed to address the
behavioral, cognitive and physical manifestations of MPS IIIA.
About Denali’s Transport Vehicle
Platform
The blood-brain barrier is essential in maintaining the brain’s
microenvironment and protecting it from harmful substances and
pathogens circulating in the bloodstream. Historically, the
blood-brain barrier 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 Transport Vehicle platform is a
proprietary technology designed to effectively deliver large
therapeutic molecules such as antibodies, enzymes, proteins, and
oligonucleotides across the blood-brain barrier after intravenous
administration. The Transport Vehicle technology is based on
engineered Fc domains that bind to specific natural transport
receptors, such as transferrin receptors, which are expressed at
the blood-brain barrier and deliver the Transport Vehicle and its
therapeutic cargo to the brain through receptor-mediated
transcytosis. In animal models, antibodies and enzymes engineered
with the Transport Vehicle 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 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
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, statements regarding
Denali's plans, timelines, 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 it is a potentially
registrational trial; plans, timelines, and expectations related to
DNL126, including the expectation and timing of potential
regulatory submissions; expectations regarding Denali’s TV
technology platform, the therapeutic potential of DNL310 and
DNL126, and Denali’s TV platform. 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: risks to Denali’s business and operations caused
directly or indirectly by the 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 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 DNL310 and DNL126 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 28, 2022, and November 3, 2022,
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 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
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