– Biotech expert and renowned Alzheimer’s disease researcher, David M. Holtzman, M.D., joins Switch’s Scientific Advisory Board to support advancement of company’s novel neurodegenerative pipeline –

– Company announces its first development candidate, a liver-sparing APOE RNAi therapy for treatment of Alzheimer’s disease in APOE4 carriers – 

– Switch also announces development program inhibiting MAPT production and progress in developing molecules with cell-specific activation in microglia and astrocytes –

SOUTH SAN FRANCISCO, Calif – December 3, 2024 – Switch Therapeutics, a biotechnology company developing novel three-stranded RNA that function as conditionally activated siRNA (CASi) therapeutics for central nervous system (CNS) diseases, announced today the appointment of Dr. David M. Holtzman to its Scientific Advisory Board and disclosed pipeline programs targeting APOE (apolipoprotein E) and MAPT (microtubule-associated protein tau) for treatment of neurodegenerative diseases.

Dr. Holtzman is a world-renowned physician-scientist and brings more than three decades of experience researching and treating neurological diseases with a specific expertise in Alzheimer’s disease (AD). He is currently scientific director of the Hope Center for Neurological Disorders, director of the Knight Alzheimer’s Disease Research Center and professor of neurology at Washington University in St. Louis. Dr. Holtzman has been elected to the National Academy of Medicine and the National Academy of Inventors and is a Fellow of the American Association for the Advancement of Science.  His notable research and accomplishments include showing, in part, how APOE4 contributes to AD, developing a method to measure protein synthesis and clearance in the CNS and developing cerebrospinal fluid and plasma biomarkers for AD.

“Dr. Holtzman brings invaluable experience to our team both as a treating physician and with his extensive neurodegeneration and APOE-specific research background that will support the advancement of CASi-APOE and future neurodegeneration programs. The nomination of CASi-APOE as our lead development candidate is a big step for Alzheimer’s patients. APOE4 carriers have limited treatment options, though 60% of Alzheimer’s disease patients are APOE4 carriers compared to 25% of the general population,” said Dee Datta, Ph.D., co-founder and CEO of Switch Therapeutics. “This is an exciting time for Switch as we prepare to advance our pipeline towards the clinic.”

Switch’s CASi-APOE program is designed to knock down APOE in the CNS without affecting APOE in the liver, where it plays a vital role in systemic lipid homeostasis. 

“I am delighted to be joining Switch’s Scientific Advisory Board during a key phase of the company’s growth in the neurodegenerative space,” said Holtzman.  I am especially enthusiastic about the unique profile of CASi-APOE which blocks APOE production in the brain, while sparing the liver. APOE4 carriers need treatment options, and CASi-APOE is particularly exciting as genetic knockdown of APOE has been shown in animal models of Alzheimer’s to reduce both amyloid-beta and tau levels, two key hallmarks of Alzheimer’s disease.”

Switch has initiated IND-enabling studies and plans to conduct a Phase 1 trial in patients with AD who are APOE4 carriers in 2026. By the end of 2024, Switch anticipates naming its second development candidate, targeting production of tau, which is directly responsible for neurodegenerative diseases called tauopathies, including primary and secondary tauopathies such as progressive supranuclear palsy and Alzheimer’s disease, among others. Switch’s MAPT program knocks down tau at the genetic level, thus preventing intra-cellular tau production. Switch also is advancing two earlier CASi programs with cell-specific activity, one limited to microglia and the second program directed at astrocytes. Targeting these cells individually will enable cell-specific genetic knockdown of disease targets for which broad suppression is unsafe.