CAMBRIDGE, Mass. — PhenoNet, Inc. said the U.S. Food and Drug Administration has cleared the company to proceed with a Phase 3 clinical trial of PHENOGENE-1A, its inhaled treatment candidate for patients with early Alzheimer’s disease.
The FDA issued a “May Proceed” notification on Aug. 10, activating PhenoNet’s Investigational New Drug application. The study will include patients who carry the APOE4 gene variant as well as non-APOE4 carriers, with the groups stratified by genotype.
PHENOGENE-1A is an inhaled formulation of cromolyn, a compound with a decades-long clinical safety history, combined with PhenoNet’s proprietary targeted delivery technology. The therapy is designed to achieve therapeutic concentrations in the brain and act through several mechanisms associated with Alzheimer’s disease.
According to the company, those mechanisms include inhibiting amyloid-beta aggregation, suppressing pro-inflammatory cytokines and chemokines, and promoting microglial clearance of amyloid-beta. PhenoNet is developing the candidate as a disease-modifying therapy intended to slow Alzheimer’s progression.
The genotype-specific design of the Phase 3 trial follows an exploratory finding of a numerical difference based on APOE4 status in a previous Phase 3 study.
“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 Dr. David R. Elmaleh, Founder and Chairman of PhenoNet. “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.”
Dr. Atul Gupta, Chief Medical Officer of PhenoNet, said therapies designed to work alongside the underlying genetic characteristics of Alzheimer’s could complement existing treatment options.
“AD-modifying therapies that work alongside the underlying genotype pathophysiology of the disease can add significant value to existing treatment options,” Gupta said. “If successful, our multifunctional therapy has the potential to slow decline over the long term.”
Gupta, who has experience in neurodegenerative disease trials, will serve as a Principal Medical Monitor for the study.
Dr. 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,” Greeley said.
PhenoNet expects to begin screening patients in January 2027.
The Phase 3 study, known as PHENOAD-002, is expected to enroll about 648 participants at approximately 90 sites across North America and Europe. The randomized, double-blind, placebo-controlled trial will evaluate the safety and efficacy of inhaled PHENOGENE-1A in patients with early Alzheimer’s disease over 72 weeks.
The company said it also plans to seek a Special Protocol Assessment from the FDA to determine whether the trial design, if successful, could support a future New Drug Application under the 505(b)(2) regulatory pathway.
