Denali Therapeutics Regains Full Rights to Investigational Therapy DNL593 (PTV:PGRN) for GRN-related Frontotemporal Dementia (FTD-GRN)
- Denali plans to continue clinical development of DNL593, which is designed to deliver progranulin to the brain using TransportVehicle™ technology
- Results from ongoing Phase 1/2 study in patients with FTD-GRN expected by the end of 2026
“While we have greatly valued our partnership, we are pleased to regain full ownership of DNL593. We remain confident in the scientific rationale and the data generated to date, and we look forward to advancing DNL593 independently. We plan to report results from the ongoing Phase 1/2 trial by the end of 2026,” said
As previously disclosed, data from the ongoing Phase 1/2 study of DNL593, including biomarker results, are expected by the end of 2026. Enrollment in this study is completed with a total of 40 participants with FTD-GRN. Interim results from Part A of the Phase 1/2 study in healthy volunteers demonstrated dose-dependent increases in cerebrospinal fluid progranulin levels, consistent with robust brain delivery of DNL593. DNL593 was generally well tolerated, and there have been no significant safety signals to date.
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 the Denali TransportVehicle™ 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 central nervous system diseases by preventing most drugs from reaching the brain in therapeutically relevant concentrations. Denali’s TransportVehicle™ (TV) platform is a proprietary technology designed to effectively deliver large therapeutic molecules such as antibodies, enzymes and oligonucleotides throughout the whole body, including the brain, by crossing the BBB after intravenous administration. The TV platform is based on engineered Fc domains that bind to specific natural transport receptors, such as transferrin receptor and CD98 heavy chain amino acid transporter, 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 platform demonstrate more than 10- to 30-fold greater brain exposure than similar antibodies and enzymes without this technology. Oligonucleotides engineered with the TV platform demonstrate more than a 1,000-fold greater brain exposure in primates than systemically delivered oligonucleotides 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. The TV platform has been clinically validated and five TV-enabled programs are currently in clinical development.
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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, plans, timelines and expectations related to Denali’s TransportVehicle™ platform, including its potential application across current and future product candidates and its ability to deliver therapeutics to the brain; plans, timelines and expectations related to DNL593, including the timing and availability of data readouts from the ongoing Phase 1/2 study, the significance of interim data from the Phase 1/2 study including with respect to tolerability and safety, and the potential therapeutic benefit of DNL593; and statements by Denali’s Chief Executive Officer. Actual results may differ materially from those expressed or implied by these forward-looking statements due to a variety of risks and uncertainties. These include, but are not limited to, uncertainties related to the FDA’s policies and accelerated approval program; risks arising from adverse economic conditions and their impact on Denali’s business and operations; the possibility of events or changes that could lead to the termination of Denali’s collaboration agreements; challenges associated with Denali’s transition to a commercial company; the ability of Denali and its collaborators to complete the development and, if approved, the commercialization of product candidates; difficulties in patient enrollment for ongoing and future clinical trials; whether the current ongoing trials have been powered sufficiently to demonstrate approvability to regulatory agencies; reliance on third-party manufacturers and suppliers for clinical trial materials; dependence on the successful development of Denali’s blood-brain barrier platform technology and related programs; potential delays or failures in meeting expected clinical trial timelines; the risk that promising preclinical profiles may not be replicated in clinical settings; discrepancies between preclinical, early-stage or preliminary clinical results and outcomes from later-stage trials; the occurrence of significant adverse events or other undesirable side effects; the uncertainty surrounding regulatory approvals required for commercialization in the
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Source: Denali Therapeutics Inc.