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 the results of its
Phase 1b clinical trial of LRRK2 inhibitor DNL201 in patients with
Parkinson’s disease and its Phase 1 clinical trial of LRRK2
inhibitor DNL151 in healthy volunteers.
Denali also announced that it submitted an IND for
DNL310 for Hunter syndrome, which is the company’s first submission
with a biotherapeutic product candidate engineered to cross the BBB
enabled by the Transport Vehicle technology. Furthermore, a CTA for
a Phase 1 first-in-human healthy volunteer study of EIF2B activator
DNL343, intended for the treatment of ALS and other
neurodegenerative diseases, has been approved. This is Denali’s
third small molecule program engineered to cross the BBB to advance
to clinical testing.
“We are pleased with the continued progress across
our pipeline, including a significant step forward for our LRRK2
program with encouraging clinical data in patients and healthy
subjects for two molecules,” said Ryan Watts, Ph.D., CEO. “We are
also enthusiastic about advancing two new molecules toward the
clinic, DNL343 for ALS and other neurodegenerative diseases and
DNL310 for Hunter syndrome, which is also expected to generate
proof-of-concept in humans for our Transport Vehicle blood-brain
barrier delivery platform.”
DNL201 and DNL151 (LRRK2 inhibitors) for
Parkinson’s disease
Phase 1b results with DNL201 in patients with
Parkinson’s disease met all biomarker goals by demonstrating
greater than 50 percent inhibition of pS935 LRRK2 and pRAB10 in
blood for both doses tested and improvement of the lysosomal
biomarker BMP (22:6-bis-monoacylglycero-phosphate) by 20 percent
and 60 percent in urine at the low and high dose, respectively.
DNL201 was generally well tolerated at the low dose
and the majority of subjects experienced either no or mild adverse
events (“AEs”). There was one SAE considered unrelated to drug. At
the high dose, the majority of subjects experienced either mild or
moderate AEs and there was one severe AE (headache) leading to dose
reduction and one study withdrawal (headache and nausea). All
treatment-related AEs were manageable and reversible.
Phase 1 results with DNL151 in more than 150
healthy volunteers also met all safety and biomarker goals. DNL151
was generally safe and well tolerated at all doses tested, and the
majority of subjects experienced either no or mild AEs. Target and
pathway engagement of greater than 50 percent and a dose-dependent
reduction of BMP in urine of up to 50 percent were observed at
clinically relevant doses. Given these positive data, the DNL151
Phase 1 and Phase 1b clinical trials have been expanded to study
higher doses.
Denali intends to select either DNL201 or DNL151 in
mid-2020 to advance into Phase 2/3 clinical trials in patients with
Parkinson’s disease.
“We are excited about the results from both the
DNL201 and DNL151 clinical trials which show that LRRK2 inhibition
is a promising and potentially disease-modifying approach to treat
Parkinson’s disease,” said Carole Ho, M.D., CMO. “We look forward
to further exploring the full therapeutic potential of LRRK2
inhibitors in future clinical studies.”
DNL310 (ETV:IDS) for Hunter
syndrome
Denali submitted an IND in late December 2019 for
DNL310, or ETV:IDS, a recombinant form of the iduronate 2-sulfatase
(“IDS”) enzyme engineered to cross the BBB using Denali’s
proprietary Enzyme Transport Vehicle technology. DNL310 is
intravenously administered and intended to improve overall clinical
manifestations of Hunter syndrome, including both peripheral and
neurological symptoms, which are not adequately addressed by
currently approved therapies. If Denali receives clearance of the
IND, it intends to initiate a Phase 1/2 clinical trial of DNL310 in
patients with Hunter syndrome.
DNL343 (EIF2B Activator) for ALS and other
neurodegenerative diseases
Denali submitted a CTA in early December 2019 for
DNL343, a small molecule brain-penetrant activator of EIF2B.
Mutations in EIF2B are genetically linked to neurodegenerative
diseases. Activation of EIF2B with DNL343 is expected to
restore protein synthesis and reduce formation of stress granules,
which are commonly associated with disease pathology in ALS and
Alzheimer’s disease. The CTA cleared in January 2020, and Denali
plans to initiate a Phase 1 clinical trial for DNL343 in healthy
volunteers.
Further data from the clinical trials with DNL201
and DNL151, and data from preclinical studies with DNL310 and
DNL343 will be shared at the J.P. Morgan 38th Annual Healthcare
Conference on January 14, 2020 at 8.30am PT in San Francisco. The
presentation will also be accessible by webcast through Denali’s
website at https://www.denalitherapeutics.com/investors/events.
About the DNL151 Phase 1b clinical
trial
This study (NCT04056689) is a 28-day, multicenter,
randomized, placebo controlled, double-blind Phase 1b clinical
trial in patients with mild-to-moderate Parkinson’s disease. Its
purpose is to evaluate safety, tolerability, pharmacokinetics,
pharmacodynamics, including target and pathway engagement
biomarkers as well as certain exploratory clinical endpoints, after
multiple oral doses of DNL151. To date, 25 patients have been
enrolled in the study, and the protocol has been amended to expand
the study with up to 10 additional patients. Final data readout
from this trial is expected to be presented in mid-2020. Further
details are available at ClinicalTrials.gov
About Denali
Denali is a biopharmaceutical company developing a
broad portfolio of product candidates engineered to cross the 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, Denali’s
plans and expectations to select either DNL151 or DNL201 in
mid-2020 to advance into Phase 2/3 clinical trials in Parkinson’s
disease patients; Denali’s expectations regarding what the results
of the DNL151 Phase 1b clinical trial will inform; Denali’s
expectations regarding patient enrollment in, and the timing,
objectives and results of, the DNL151 Phase 1b clinical trial;
Denali’s plans to conduct further clinical testing in connection
with its LRRK2 program; Denali’s expectations regarding what the
results of the DNL747 Phase 1b clinical trials will inform;
Denali’s expectations regarding anticipated regulatory and
development timelines and plans to initiate clinical trials for
DNL310 and DNL343, including timing and objectives; Denali’s
expectations that DNL310 will generate proof-of-concept in humans
of its Transport Vehicle BBB delivery platform; Denali’s
expectations with respect to anticipated benefits from the
activation of EIF2B with DNL343; and statements made by Denali’s
CMO and CEO.
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 early stages of clinical drug development; Denali’s
ability to complete the development and, if approved,
commercialization of its product candidates; Denali’s dependence on
successful development of its BBB technology; Denali’s ability to
conduct or complete clinical trials on expected timelines; Denali’s
ability to obtain the requisite regulatory approvals for its
product candidates; the uncertainty that any of Denali’s product
candidates will receive regulatory approval necessary to be
commercialized; Denali’s ability to continue to create a pipeline
of product candidates or develop commercially successful products;
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, and other risks,
including those described in Denali’s Annual Report on Form 10-K
filed with the SEC on March 12, 2019, Denali’s Quarterly Report on
Form 10-Q filed with the SEC on November 6, 2019 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.
Contacts:
Lizzie Hyland(646)
495-2706lhyland@gpg.com
or
Morgan Warners(202)
295-0124mwarners@gpg.com
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