Alector Maps Brain-Delivery Pipeline for Alzheimer’s, Parkinson’s Therapies

Key Points

• Alector is building a brain-delivery pipeline using its transferrin receptor-based Alector Brain Carrier, with programs spanning Alzheimer’s, Parkinson’s disease and Lewy body dementia. A Roche-Genentech licensing deal for its GCase program extends the company’s financial runway into 2029.
• The lead Alzheimer’s candidate, AL137, is a subcutaneous brain-enabled anti-amyloid antibody designed to remove plaques while retaining full immune-effector function. A Phase 1 healthy-volunteer study is planned for April 2027, followed by an Alzheimer’s patient study in late 2027.
• Alector’s brain-delivered siRNA programs target tau (AL164) and alpha-synuclein (AL062), with reported preclinical knockdown of up to 76% and approximately 90%, respectively. Both programs are targeted for first-in-human testing in the second quarter of 2028.

Alector NASDAQ: ALEC outlined its strategy to advance brain-penetrant therapies for neurodegenerative diseases, highlighting an anti-amyloid beta antibody for Alzheimer’s disease and two siRNA programs targeting tau and alpha-synuclein.

Chief Executive Officer and co-founder Arnon Rosenthal said the company has shifted from its earlier focus on novel immune checkpoint targets toward a portfolio of bispecific antibodies, enzyme-replacement therapies and nucleic acid therapies supported by its Alector Brain Carrier platform. The technology is designed to facilitate passage across the blood-brain barrier through the transferrin receptor.

Rosenthal said a recent licensing agreement with Genentech and Roche for Alector’s brain-enabled GCase enzyme program in Parkinson’s disease and Lewy body dementia extended the company’s financial runway into 2029. He said the agreement also validated Alector’s brain-delivery technology.

AL137 Alzheimer’s Program

Alector’s lead disclosed program, AL137, is a brain-enabled anti-amyloid beta antibody intended for Alzheimer’s disease. The company said the antibody targets pyroglutamate-3 amyloid beta, an epitope also targeted by Eli Lilly’s donanemab and remternetug.

Rosenthal said AL137 was designed with three intended attributes: binding to amyloid plaques, retention of full IgG1 effector function to recruit microglia, and enhanced brain uptake through the company’s transferrin receptor-based carrier. He said the company believes full effector function is necessary for effective plaque removal, arguing that antibodies with reduced effector function have not demonstrated sufficient clinical benefit.

The company presented preclinical findings showing AL137 bound amyloid plaques in human Alzheimer’s brain sections and supported microglial phagocytosis in cell-based assays. Alector also reported that its carrier increased brain exposure in preclinical studies and produced broad distribution across the brain in an Alzheimer’s mouse model.

Alector plans to administer AL137 subcutaneously rather than intravenously. Rosenthal said the company expects this approach could lower peripheral exposure peaks and potentially reduce risks including infusion reactions, anemia and amyloid-related imaging abnormalities, or ARIA.

The company said its carrier binds a more secluded transferrin receptor epitope than certain other brain-shuttle approaches. According to Alector, this design reduced the ability to recruit immune cells to reticulocytes while retaining the antibody’s ability to recruit immune cells at amyloid plaques. In nonclinical studies, the company reported transient reticulocyte reductions but no hematologic adverse effects at tested doses.

• Alector plans to begin a Phase 1 healthy-volunteer study of AL137 in Australia around April 2027.
• The initial study is expected to assess four dose levels, safety and cerebrospinal-fluid exposure.
• A placebo-controlled multiple-dose Phase 1b study in Alzheimer’s patients is planned in the U.S. and Australia beginning in the fourth quarter of 2027.
• The company expects an initial safety and exposure package by the third quarter of 2027 and imaging, biomarker and safety data by the third or fourth quarter of 2028.

Rosenthal said Alector is targeting approximately 90% amyloid plaque removal within three to six months of monthly dosing, while acknowledging that the company’s projections are based on preclinical and modeling work. The patient study is expected to use amyloid PET imaging and biomarkers including p-tau217.

Brain-Enabled siRNA Portfolio

Eric Brown, Alector’s director of antibody discovery and protein engineering, presented the company’s antibody-oligonucleotide conjugate platform, which uses the same brain carrier to deliver siRNA cargoes into the brain following subcutaneous dosing.

The first program, AL164, targets MAPT, the gene encoding tau. Brown said tau pathology accumulates largely inside neurons, making it difficult to address with conventional antibodies. He cited evidence that tau burden is associated with neurodegeneration in Alzheimer’s disease and that tau mutations can cause familial tauopathies.

Alector reported that AL164 achieved up to 76% MAPT messenger RNA knockdown in non-human primate brain regions after three subcutaneous loading doses. The company also reported no treatment-related adverse events in studies of AL164 or its parental molecule at doses of up to 30 mg per kilogram of siRNA equivalent. Alector said it is initiating chemistry, manufacturing and controls work, with a planned first-in-human study in the second quarter of 2028.

The second siRNA program, AL062, targets alpha-synuclein, a protein associated with Parkinson’s disease and Lewy body dementia. Brown said the molecule showed a three-picomolar IC50 in vitro and no significant off-target gene reductions in the company’s high-concentration testing. In human transferrin receptor knock-in mice and non-human primates, Alector reported approximately 90% alpha-synuclein knockdown across multiple brain regions following subcutaneous loading doses.

AL062 is also planned to enter first-in-human testing in the second quarter of 2028. Brown said the two siRNA programs use the same brain carrier and are being manufactured in parallel, which Alector expects will create development and manufacturing efficiencies.

Development and Partnering Plans

Chief Financial Officer and Chief Business Officer Neil Berkley said Alector intends to advance AL137, AL164 and AL062 internally toward clinical testing, while remaining open to discussions with potential partners. Rosenthal said siRNA will be a major near-term focus, though the company may continue to use antibodies or enzyme-replacement approaches when those modalities are better suited to a target.

Alector also said it has not disclosed plans to change its at-the-market equity offering program.

About Alector (NASDAQ:ALEC)

Alector, Inc is a clinical-stage biotechnology company focused on developing therapies for neurodegenerative diseases. The company's approach, known as immuno-neurology, seeks to use the immune system to protect brain health and address biological mechanisms involved in conditions such as Alzheimer's disease, frontotemporal dementia and Parkinson's disease.

Alector's pipeline includes latozinemab, an antibody designed to increase levels of progranulin, a protein associated with the health and function of brain cells.

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