Promis Neurosciences (NASDAQ:PMN) reported blinded six-month interim data from its Phase 1b PRECISE-AD trial of PMN310, an investigational antibody designed to selectively target toxic amyloid-beta oligomers in patients with mild cognitive impairment due to Alzheimer’s disease and early Alzheimer’s disease.
The company said the interim review covered safety and biomarker data only and did not include unblinded clinical outcome measures. Top-line results, including clinical efficacy measures, are expected in early 2027 after completion of 12 months of dosing.
Trial Enrollment and Design
Patients were randomized to receive 12 monthly intravenous infusions of PMN310 at doses of 350 milligrams, 700 milligrams or 1,400 milligrams, or placebo. Each dose cohort used a 3-to-1 randomization of drug to placebo, according to Chief Medical Officer Larry Altstiel.
The mean patient age was approximately 73 years, with women representing 58% of enrolled participants. All patients were amyloid-positive by PET imaging and had tau-based or p-tau217-based biomarkers consistent with Alzheimer’s pathology, Altstiel said.
The study population included 11% APOE4 homozygotes and 50% APOE4 heterozygotes. Altstiel said the distribution was statistically indistinguishable from a meta-analysis of more than 100,000 Alzheimer’s patients.
Blinded Safety Results
As of July 22, the company reported no cases of ARIA-E, or amyloid-related imaging abnormalities with edema, in the blinded safety population. Promis also reported no treatment-related serious adverse events, no treatment-related discontinuations and one non-serious probable infusion reaction that did not alter dosing.
The total ARIA rate was 4.4%, consisting entirely of mild, asymptomatic ARIA-H cases detected radiographically. Altstiel said the cases did not require changes in dosing or treatment continuation.
ARIA is a significant safety consideration for approved anti-amyloid therapies. Altstiel said the company’s observed ARIA-H rate appeared to track with rates expected in untreated placebo populations, while the absence of ARIA-E was encouraging. The trial used MRI scans at screening, baseline, month two, month four and month six to monitor for ARIA.
Warma said the company believes the interim safety profile supports PMN310’s differentiated approach of targeting oligomers while avoiding amyloid plaques and monomer species.
Biomarker Findings
In the pooled, blinded patient population, Promis reported a roughly 15% decline from baseline in plasma p-tau217 at day 169. The company said 68.5% of patients experienced a decline in p-tau217, while 31.5% had increased levels.
Promis also reported a 13.3% decline in cerebrospinal fluid microtubule-binding region tau 243, or MTBR-tau243, at six months. According to the company, 62.5% of patients showed lower levels from baseline and 37.5% showed increases.
Altstiel said both biomarkers are generally expected to rise during the course of untreated Alzheimer’s disease. He characterized the biomarker changes as an early, biologically coherent signal of potential target engagement, while emphasizing that the data remain blinded and are not definitive evidence of clinical benefit or disease modification.
“This is by no means a declaration of victory,” Altstiel said. “It does suggest an early and biological coherent signal that shows that we have target engagement.”
External Perspectives and Next Steps
Michael Weiner, professor emeritus at the University of California, San Francisco, said the combination of no ARIA-E cases and the biomarker data was encouraging, particularly the MTBR-tau243 result. However, he cautioned that the Phase 1b study is small and was not designed or powered primarily to establish clinical efficacy.
Will Mantyh, a behavioral neurologist at the University of Minnesota, said a therapy with low ARIA risk could potentially broaden access to anti-amyloid treatment, including among APOE4 homozygotes and patients currently discouraged from using available therapies because of safety concerns.
Promis expects to complete dosing by December 2026. Warma said the final analysis is expected to include safety, a broader biomarker panel and clinical outcome measures after the study data are unblinded in early 2027.
About Promis Neurosciences (NASDAQ:PMN)
Promis Neurosciences, Inc is a clinical‐stage biopharmaceutical company focused on the discovery and development of novel therapeutics for central nervous system disorders. The company’s research programs target cognitive impairment and other neurological symptoms associated with diseases such as Alzheimer’s disease and multiple sclerosis.
Leveraging a proprietary small‐molecule discovery platform, Promis Neurosciences advances both preclinical and early clinical candidates designed to modulate neural pathways involved in memory, learning and neuroinflammation.
