PhenoNet has received the US FDA clearance to move ahead with a Phase 3 clinical trial of its lead Alzheimer’s disease candidate, PHENOGENE-1A, in patients with early-stage disease.

 

The trial will evaluate PHENOGENE-1A in both APOE4 carriers and non-carriers, with patients stratified by genotype. The approach is based in part on an exploratory numerical difference observed by APOE4 status in an earlier Phase 3 trial.

 

PHENOGENE-1A is an inhaled formulation of cromolyn, a compound with decades of clinical use, combined with PhenoNet’s proprietary targeted delivery technology. The company says the treatment is designed to achieve therapeutic concentrations in the brain and target three mechanisms implicated in Alzheimer’s disease: amyloid-β (Aβ) aggregation, inflammatory signaling and microglial clearance of Aβ.

 

The company is developing PHENOGENE-1A as a potential disease-modifying therapy aimed at slowing Alzheimer’s progression.

 

"Addressing the triggers of AD progression in diagnosed genotypes with a multifunctional therapeutic approach offers a new strategy to modify the disease course that could potentially benefit a large AD population," said David R. Elmaleh, PhenoNet, Founder and Chairman. 

 

"Very early intervention in non-APOE4 patients at the earliest clinical signs of cognitive and functional decline may help prevent or delay disease progression. Data from the non-APOE4 subgroup in our earlier trial support advancing PHENOGENE-1A into this Phase 3 study. We believe a genotype-stratified approach will provide a clearer understanding of how PHENOGENE-1A may benefit patients with Alzheimer's disease across different genetic subgroups."

 

The company’s chief medical officer, Atul Gupta, said the treatment could complement existing approaches by addressing disease mechanisms in the context of patients’ underlying genetic profiles.

 

"AD-modifying therapies that work alongside the underlying genotype pathophysiology of the disease can add significant value to existing treatment options. If successful, our multifunctional therapy has the potential to slow decline over the long term."

 

Gupta, who has extensive experience in neurodegenerative disease trials, will serve as a Principal Medical Monitor for the study.

 

David Greeley, a neurologist at Northwest Neurological, PLLC and Kingfisher Cooperative, LLC and a Fellow of the American Academy of Neurology, will serve as Principal Investigator.

 

"I am truly excited to serve as Principal Investigator of this Phase III study, as it holds the potential to advance a promising new therapy and contribute meaningfully to the treatment landscape for AD."

 

PhenoNet also points to intellectual property covering the drug, dosing, formulation and delivery technology behind PHENOGENE-1A.

 

"PhenoNet's proprietary technology includes intellectual property covering the drug, dosing, formulation, and delivery to ensure penetration to both blood and brain, and genotype treatment," said Peter Conti, Professor of Radiology, Pharmaceutical Sciences, and Biomedical Engineering at the University of Southern California.

 

PhenoNet expects to begin screening the first patients in January 2027. The Phase 3 study, designated PHENOAD-002, is a randomized, double-blind, placebo-controlled trial evaluating the safety and efficacy of inhaled PHENOGENE-1A in people with early Alzheimer’s disease, with participants stratified by APOE4 status.

 

The company expects to enroll approximately 648 participants at about 90 sites across North America and Europe. The primary endpoint will be assessed over 72 weeks.