Vigil Neuroscience reported a strong safety profile and 50% sTREM2 reduction in an early-stage trial for VG-3927, potentially representing a new avenue for treating Alzheimer’s disease.
In a possible redemption for the TREM2 space in Alzheimer’s disease, Vigil Neuroscience announced positive early-stage data Thursday for its TREM-2 agonist antibody, VG-3927.
The Massachusetts-based biotech, which launched in 2020 with partial backing from Amgen, reported that it is moving VG-3927 into Phase II trials as a likely once-daily oral therapy for Alzheimer’s disease (AD).
In the Phase I trial, VG-3927 showed high brain penetrance, a tolerable safety profile and a 50% reduction in sTREM2, a soluble variant of a brain cell receptor that increases in concentration during early symptomatic phases of Alzheimer’s.
“We are highly encouraged by today’s update,” William Blair analyst Sarah Schram wrote in an investor note Thursday. “Importantly, PK and sTREM2 reduction observed in the elderly cohort was consistent with healthy volunteers and similar across evaluated TREM2 and ApoE genetic variants, supporting development in AD across genotypes.”
Shares of Vigil were up 18% in premarket trading Thursday after the announcement.
Vigil’s pipeline is focused on microglia, neuronal cells that act as immune cells in the brain, behaving as a kind of molecular garbage collector, scanning for plaques, inflammation and other potentially harmful detritus. Mutations and loss of TREM2, a receptor on the surface of microglia whose expression is restricted to the brain, is associated with late-onset Alzheimer’s. Vigil’s molecule is a novel mechanism that acts as an agonist for TREM2.
Vigil’s success comes on the heels of a high-profile TREM2 failure, when Alector’s AbbVie-partnered antibody AL002 failed in a Phase II trial in November 2024, prompting layoffs.
“The open question here is how much the Alector failure in AD might diminish strategic interest, but given that the first Abeta attempts were outright failures, it seems reasonable that a partner might be interested in a fundamentally different approach to modulating TREM2--via a small molecule vs AL002, which was a monoclonal antibody,” Stifel analyst Paul Matteis wrote in a Thursday note.
Thursday’s news is positive for the Alzheimer’s drug discovery space, which has remained relatively fallow since Eli Lilly’s Kisunla was approved in July 2024, joining Eisai and Biogen’s Leqembi, also an anti-amyloid antibody, on the U.S. market. Eisai and Biogen’s original anti-amyloid drug Aduhelm, was discontinued in January 2024. Despite these new options, the amyloid hypothesis has come under greater scrutiny in recent years, highlighted by Leqembi’s July 2024 rejection in Europe.
