An experimental Alector drug designed to bring the immune system into the fight against Alzheimer’s disease has pulled out of a research alliance with pharma giant AbbVie.
Antibody drug AL003 has entered Phase 1 testing, with South San Francisco-based Alector in its most recent financial report It’s reviewing the next steps for experimental therapies.in a Regulatory filing Late Thursday, the biotech revealed that AbbVie had decided to end the program. AbbVie issued the notice on June 30, but the document did not provide further explanation.
With AL003, Alector aims to treat Alzheimer’s in a way similar to the successful treatment of cancer. So-called “checkpoint” proteins on immune cells prevent them from recognizing tumors. By blocking these proteins, a class of drugs called checkpoint inhibitors enables immune cells to target and kill cancer cells.
Alector focuses on the brain’s immune cells. AL003 is an antibody designed to target CD33, a receptor expressed on microglia, an immune cell of the central nervous system. By blocking this protein, the Alector drug promises to enable microglia to track proteins associated with Alzheimer’s disease progression. Last November, Alector reported Phase 1 data showing the drug’s CD33 involvement in the blood and central nervous system at doses that study participants could tolerate. No word was given on the selected dose or any planned Phase 2 testing.
William Blair analyst Miles Minter spoke with Alector executives about the termination plan. In a note to investors Friday morning, he said they told him that both Alector and AbbVie had concluded that AL003 did not exhibit sufficient biological activity to support continued development. But he added that this shortcoming doesn’t doom Alector’s approach to neurodegenerative diseases.
“This suggests that the problem is with the molecules, rather than the overall strategy of treating immune modulation by targeting microglial activation. [Alzheimer’s disease] By addressing other targets, including TREM2,” Minter said.
TREM2 is another receptor found on microglia, while Alector is one of several companies targeting it as a potential Mobilizing immune cells to fight neurodegenerative diseasesAL002 is the second Alector drug covered by the alliance with AbbVie, and the TREM2-targeting molecule is currently in Phase 2 testing in patients with early Alzheimer’s disease. Data is expected in 2023.
The discontinuation of AL003 is disappointing, but “fail fast” early in program development is preferable to long-term problems, Minter said. Investors’ focus will continue to be on Alector’s state-of-the-art projects, he added. In addition to AL002, in partnership with AbbVie, the biotechnology has already undergone Phase 3 testing with AL001 in patients with frontotemporal dementia. In this disease, Alector is designed to boost levels of precursor granulin, a protein that regulates immune activity in the brain. AL001 is an antibody that binds to a protein that causes the degradation of pregranulin. About a year ago, GlaxoSmithKline agrees to pay Alector $700 million upfront to share in development of AL001 and AL101an early-stage project with potential applications in Alzheimer’s and Parkinson’s diseases.
Alector’s alliance with AbbVie dates back to 2017, when AL003 and AL002 were still in preclinical stages. AbbVie paid $205 million in cash and purchased $20 million in equity to begin the collaboration, which requires Alector to handle R&D on both projects by completing Phase 2 testing. At that point, AbbVie will likely continue development, paying $250 million to exercise its options for each project. Development costs beyond the second phase will be shared between the two companies. The partners will also share in the commercialization if the drug hits the market. The deal enables Alector to make milestone payments of up to $242.8 million per project.
Photo by AbbVie
