Genentech licenses Alector's experimental brain-targeted enzyme for Parkinson's

In Short. Genentech paid Alector $100 million for exclusive rights to an experimental Parkinson's enzyme that has not been tested in people, with up to $1.17 billion more only if the program hits named development, regulatory and sales goals, and the deal does not show that Alector's brain carrier works in people.

AN ENZYME called glucocerebrosidase, or GCase, breaks down certain fatty molecules inside cells. The gene that carries the instructions for making GCase is GBA1. Faulty copies of GBA1 lower GCase activity and are a known risk factor for Parkinson's disease, according to a 2022 review in the Journal of Neural Transmission by Sophia Vieira and Anthony Schapira. That review cites a large multicenter study that found an odds ratio of about 5.4 for GBA1 mutations among people with Parkinson's compared with controls, and it places GBA1 among the strongest genetic risk factors for the disease identified so far. The enzyme's substrates include glucosylceramide and glucosylsphingosine. When GCase is low, those lipids can accumulate.

Replacing a missing enzyme by infusion already treats some diseases elsewhere in the body. The same review notes that enzyme replacement is used for Gaucher disease, which is caused by two faulty copies of GBA1, but that infused enzyme does not penetrate the blood-brain barrier. That barrier is the lining of blood vessels in the brain. It keeps most large molecules in the blood from reaching brain cells. The barrier is why a treatment that works in the liver or spleen has not worked as a way to restore GCase inside the brain.

On Monday, Genentech, a member of the Roche Group, took exclusive worldwide rights to an Alector program built for that crossing. The candidate, AL050, joins an engineered GCase to a carrier Alector calls Alector Brain Carrier, which the company designed to transport therapeutics from the blood into the brain. Alector says the engineered enzyme is optimized for greater activity and a longer half-life, and that once delivered it is meant to break down glucosylsphingosine and glucosylceramide in neurons and other brain cells. AL050 has not been tested in people. In its August business update, Alector reported that preclinical studies had shown higher GCase activity in the brains of rodents and non-human primates, and less toxic substrate in a rodent model of GBA disease, with no apparent blood-related findings in those studies. Those animal results are Alector's. Boris L. Zaïtra, head of Roche corporate business development, said in Alector's announcement that by partnering with companies such as Alector, Roche aims to delay or halt the progression of Parkinson's so patients keep their independence longer.

Under the license, announced Oct. 5 and signed Sept. 30 according to Alector's Form 8-K with the U.S. Securities and Exchange Commission, Genentech is responsible for development, regulatory work, manufacturing and commercialization in all indications. Alector will assign Genentech ownership of certain existing patents specific to the GCase candidates. Alector retains ownership of the brain-carrier platform and full rights to apply it across its own pipeline of candidates outside GCase programs. Genentech will pay Alector $100 million upfront. Alector is also eligible for up to an additional $1.17 billion if the program reaches named development, regulatory and commercial milestones. That larger figure is a ceiling. It is paid only if those goals are met, and it is not money paid today. Alector is also eligible for tiered royalties on net sales. Alector's release does not give the rates. The 8-K says they range from single-digit to double-digit percentages. The full license agreement is not attached to the 8-K. Alector says it intends to file the agreement later as an exhibit to a subsequent periodic report, with confidential portions redacted. The 8-K also states that Genentech may end the agreement for convenience on prior written notice, and that either side may end it for insolvency or uncured material breach.

Alector says the payment gives it enough cash to fund its operations into 2029. The company says the cash will support its own brain-targeted programs, including a subcutaneous anti-amyloid antibody headed toward clinical data in Alzheimer's disease and RNA programs against tau and synuclein that it plans to advance toward filings to start human studies.

What Genentech paid for now is exclusive rights to one enzyme program that has not been tested in people. The larger figure depends on human trials that have not yet started. The deal does not show that the carrier works in people.