Takeda Exercises Option to Co-Develop and Co-Commercialize DNL593, a Brain-Penetrant Progranulin Replacement Therapy for Frontotemporal Dementia

News on November 17, 2021 /BioValleyBIOON/ -- Denali Therapeutics, a company dedicated to developing drugs capable of crossing the blood-brain barrier (BBB) for the treatment of neurodegenerative diseases, recently announced that its strategic partner, Takeda Pharmaceutical Company Limited, has exercised an option under an existing collaboration agreement between the two companies to co-develop and commercialize.DNL593 (PTV:PGRN), a brain-penetrant progranulin replacement therapy for the treatment of frontotemporal dementia (FTD-GRN) caused by progranulin mutations (GRN+).

In January 2018, Denali and Takeda entered into a collaboration agreement under which Takeda obtained options for three programs, including PTV:PGRN. By exercising its option for the PTV:PGRN program, Takeda gained the right to co-develop and commercialize DNL593 with Denali. Denali will receive an option fee and is eligible to receive milestone payments upon achieving specific clinical, regulatory, and sales milestones. According to the terms of the collaboration agreement, the two companies will equally share development and commercialization costs globally, as well as profits, if applicable.

Sarah Sheikh, Head of Takeda’s Neuroscience Therapeutic Area: "At Takeda, our focus is on developing transformative treatments for patients with devastating neurological diseases. One of the main challenges in developing these drugs is achieving sufficient biodistribution in the target tissue, and Denali has designed a promising TV technology to deliver biologic therapeutics across the blood-brain barrier into the brain. The preclinical studies of DNL593 are encouraging and demonstrate protein transport."Vector(PTV) can enhance the uptake of peripherally administered progranulin (PGRN) through various types of cells in the brain, including neurons and microglia. We look forward to collaborating with Denali Therapeutics to provide DNL593 as a potential transformative treatment for patients with FTD-GRN."

Frontotemporal Dementia (FTD) is the most common form of dementia in individuals under the age of 60. Although symptom progression varies from person to person, FTD inevitably leads to functional decline along with changes in personality and social behavior, and sometimes results in language and/or motor dysfunction. The granulin (GRN) gene encodes progranulin (PGRN).GRN gene mutations typically lead to reduced PGRN levels and are the most common cause of FTD.GeneticsOne of the reasons. Currently,There are no approved drugs that can stop or slow the progression of FTD or FTD-GRN.

DNL593 is a protein transport developed by Denali Therapeutics Inc.Vector(PTV) TechnologyAchievedIntravenous Administration, Brain-Penetrant Progranulin (PGRN) Replacement TherapyPGRN is known to promote lysosomal function, in addition to having neurotrophic and anti-inflammatory effects. Data from in vitro and in vivo models provided non-clinical proof of concept for DNL593, published in the September 2, 2021 issue of the scientific journal Cell.

Research shows,DNL593 enhances brain uptake of peripherally administered PGRN through multiple cell types in the brain, including neurons and microglia.In addition, DNL593 rescued neurodegeneration and microglial dysfunction in PGRN-deficient mice. These non-clinical data support the potential of DNL593 to increase PGRN levels in the brain and impact FTD-GRN disease progression.

Currently, DNL593 has not been approved by any regulatory authority. Denali Therapeutics plans to submit an application to the UK Medicines andHealth ProductsSubmit DNL593 to the Administration (MHRA)Clinical TrialApplication (CTA).

The blood-brain barrier (BBB) is crucial for maintaining the microenvironment of the brain and protecting it from harmful substances and pathogens circulating in the blood. Historically, the BBB has posed significant challenges to drug development for central nervous system (CNS) diseases by preventing most drugs from reaching the brain at therapeutically relevant concentrations. Denali's transportVector(TV) Platform is a patented technology designed to effectively deliver large therapeutic molecules, such as antibodies, enzymes, proteins, and oligonucleotides, across the BBB after intravenous injection. The TV technology is based on an engineered Fc fragment that binds to specific natural transport receptors, such as the transferrin receptor, which is expressed on the BBB, and delivers the TV and its therapeutic agents into the brain through receptor-mediated transcytosis. In animal models, antibodies and enzymes delivered via the TV technology showed 10 to 30 times higher brain exposure compared to similar antibodies and enzymes without the technology. Improved exposure and widespread distribution in the brain can enhance therapeutic efficacy by broadly achieving therapeutically relevant concentrations of candidate products. (Bioon.com)

Source of the original text:Denali Therapeutics Announces Strategic Partner Takeda Exercises Option to Co-Develop and Co-Commercialize DNL593 (PTV:PGRN)