Alector has granted Genentech worldwide rights to develop and commercialise its AL050 programme, a brain-penetrant engineered glucocerebrosidase (GCase) enzyme replacement therapy (ERT). 

As part of the deal, Alector will receive a $100 million upfront payment, with potential for up to $1.17 billion in additional milestone payments, as well as tiered royalties on net sales. 

AL050 is designed to address GCase deficiency, a driver of neurodegeneration in Parkinson’s disease that is most pronounced in – but not limited to – carriers of GBA1 mutations.  

It combines an Alector-engineered GCase, optimised for greater enzymatic activity and a longer half-life, with Alector’s ABC, which is designed to transport therapeutics across the blood-brain barrier.  

Delivered into the brain, the enzyme is intended to break down glucosylsphingosine and glucosylceramide, lipids that accumulate in neurons and other brain cells upon GCase deficiency and contribute to neurodegeneration, with the aim of reducing cellular dysfunction and slowing disease progression. 

“Deficient GCase activity is increasingly recognised as a contributor to Parkinson’s disease, and there is still no approved therapy that addresses the underlying enzyme deficiency,” said Dr Arnon Rosenthal, Chief Executive Officer of Alector. “The challenge in treating GCase deficiency is twofold: engineering an enzyme with optimal activity and durability and successfully delivering it to the brain. AL050 addresses this by pairing an engineered GCase enzyme with our proprietary Alector Brain Carrier technology designed to cross the blood-brain barrier.” 

“This partnership extends our cash runway into 2029, providing resources to advance our fully active, subcutaneously delivered, brain-enabled anti-Aβ antibody to multi-cohort clinical data in Alzheimer’s patients, and move our subcutaneously delivered, brain-enabled Tau siRNA and alpha- synuclein siRNA programmes through IND-enabling studies and to IND filings,” added Dr Rosenthal.