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 that its strategic
partner Takeda Pharmaceutical Company Limited (“Takeda”) has
exercised an option, pursuant to an existing collaboration
agreement between the two companies, to co-develop and
co-commercialize DNL593 (PTV:PGRN), an investigational,
brain-penetrant progranulin replacement therapy for the potential
treatment of frontotemporal dementia-granulin (FTD-GRN).
“We are excited to advance our collaboration with Takeda on the
development of DNL593 as a potential treatment for people with
FTD-GRN,” said Denali’s Chief Executive Officer, Ryan Watts, Ph.D.
“Pending acceptance of regulatory submissions, DNL593 will be the
sixth therapeutic candidate from our broad pipeline, and our second
Transport Vehicle (TV)-enabled molecule, in clinical development.
This progress underscores the potential of our TV platform
technology, which is designed to enable and enhance delivery of
biologic therapeutics to the brain for the treatment of
neurodegenerative diseases.”
“At Takeda, our focus is to develop transformative treatments
for patients suffering from devastating neurologic disorders. One
of the main challenges in the development of these medicines is to
achieve adequate biodistribution in target tissues, and Denali has
engineered a promising TV platform technology to transport biologic
therapeutics across the BBB and into the brain,” said Sarah Sheikh,
BM BCh, MSc, MRCP, Head, Neuroscience Therapeutic Area Unit at
Takeda. “Preclinical studies with DNL593 are encouraging and
demonstrate that Protein Transport Vehicle (PTV) can enhance the
uptake of peripherally administered progranulin (PGRN) by multiple
cell types in the brain, including neurons and microglia. We look
forward to working with Denali to deliver DNL593 as a potentially
transformative treatment for people living with FTD-GRN.”
In January 2018, Denali and Takeda entered into a collaboration
agreement, pursuant to which Takeda was granted an option for three
programs including PTV:PGRN. By exercising its option to the
PTV:PGRN program, Takeda obtains the right to develop and
commercialize DNL593 jointly with Denali. Denali will receive an
option fee and may also receive future milestone payments upon
achievement of certain clinical and regulatory milestone events as
well as certain sales-based milestones. Subject to the terms of the
collaboration agreement, the companies will share the development
and commercialization costs equally, and, if applicable, profits on
a worldwide basis.
About Frontotemporal Dementia (FTD)
FTD is the most common form of dementia in people under 60
years of age. While the progression of symptoms varies by
individual, FTD brings an inevitable decline in function together
with changes in personality and social behaviors, and
sometimes language and/or motor dysfunction. Mutations in the
granulin (GRN) gene, which encodes the progranulin (PGRN) protein,
generally result in reduced levels of PGRN and are amongst the most
common genetic causes of FTD. There are currently no approved
medications to stop or slow the progression of FTD or
FTD-GRN.
About DNL593 (PTV:PGRN)
DNL593 is an investigational, intravenously administered,
brain-penetrant progranulin (PGRN) replacement therapy enabled by
Denali’s Protein Transport Vehicle (PTV) technology. PGRN is known
to promote lysosomal function, in addition to having neurotrophic
and anti-inflammatory effects. Data from in vitro and
in vivo models providing nonclinical proof of concept for
DNL593 were published in the September 2, 2021, issue of the
scientific journal Cell. The studies demonstrated that DNL593
enhanced brain uptake of peripherally administered PGRN by multiple
cell types in the brain, including neurons and microglia. In
addition, DNL593 rescued both neurodegeneration and microglial
dysfunction in PGRN-deficient mice. These nonclinical data support
the potential for DNL593 to increase PGRN levels in the brain and
impact disease progression of FTD-GRN.
DNL593 has not been approved by any Health Authority. Denali
plans to submit a clinical trial application (CTA) with the
Medicines and Healthcare products Regulatory Agency (MHRA) for
DNL593 in the fourth quarter of 2021.
About Denali’s TV Platform
The blood-brain barrier (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 diseases
of the central nervous system (CNS) by preventing most drugs from
reaching the brain in therapeutically relevant concentrations.
Denali’s Transport Vehicle (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 fragments that bind to
specific natural transport receptors, such as transferrin receptor,
which are expressed at the BBB and deliver TV and its therapeutic
cargo to the brain through receptor-mediated transcytosis. In
animal models, antibodies and enzymes enabled by 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 neurodegenerative 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
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 business strategy, business plans and product candidates;
plans, timelines, and expectations related to DNL593 of both Denali
and Takeda, including with respect to its potential utility in
treating certain types of frontotemporal dementia and the
initiation of future clinical trials, and plans, timing, and
expectations regarding planned regulatory filings and milestone
payments with regard to this product candidate; plans, timelines
and expectations related to Denali’s TV technology platform and
other programs enabled by Denali’s TV platform; Denali's
priorities, regulatory approvals, timing, and likelihood of success
and expectations regarding the collaboration with Takeda; and
statements made by Denali's Chief Executive 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 realize the therapeutic
efficacy of its TV technology in human models as well as animal
models; Denali’s ability to enroll patients in its ongoing and
future clinical trials; Denali’s reliance on third parties for the
manufacture and supply of 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 Takeda; 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 DNL593, may not
translate in clinical studies, the uncertainty that product
candidates will receive the 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 and TV platform
technology; 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 Form 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.
Investor Relations Contact: |
Media Contacts: |
|
Laura Hansen, Ph.D.Vice
President, Investor Relations(650)
452-2747hansen@dnli.com |
Lizzie Hyland(646)
495-2706lizzie.hyland@fgh.com orMorgan
Warners(202) 295-0124morgan.warners@fgh.com |
|
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