PHENOGENE-1A is based on a compound with an established clinical safety profile, paired with a proprietary targeted delivery to better target the brain and blood; first patient screening expected January 2027.
Today, PhenoNet, Inc. announced that the U.S. Food and Drug Administration (FDA) has notified the company that it may proceed with a Phase 3 clinical trial of its lead candidate, PHENOGENE-1A, in patients with early Alzheimer's disease (AD), including both APOE4 and non-APOE4 gene carriers. The agency issued the "May Proceed" notification on August 10, 2026, activating the company's Investigational New Drug (IND) application.
PHENOGENE-1A is an inhaled formulation of cromolyn, a compound with decades of clinical use, that incorporates PhenoNet's proprietary targeted delivery technology. This approach is designed to achieve therapeutic concentrations in the brain, acting through three plausible mechanisms implicated in Alzheimer's disease: inhibition of amyloid-ß (Aß) aggregation, suppression of pro-inflammatory cytokines and chemokines, and promotion of microglial phagocytosis of Aß. PHENOGENE-1A is being developed as a disease-modifying therapy intended to slow the progression of Alzheimer's disease. The Phase 3 trial will enroll both APOE4 carriers and non-carriers, stratified by genotype, to evaluate PHENOGENE-1A efficacy across genotypes. This genotype-specific trial design was informed by an exploratory observation of a numerical difference by APOE4 status in a prior Phase 3 trial.
"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, PhenoNet, Inc. 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."
"AD-modifying therapies that work alongside the underlying genotype pathophysiology of the disease can add significant value to existing treatment options," added Dr. Atul Gupta, Chief Medical Officer of PhenoNet, Inc. "If successful, our multifunctional therapy has the potential to slow decline over the long term." Dr. Gupta has extensive experience in neurodegenerative disease trials and will serve as a Principal Medical Monitor in the trial.
"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," said Dr. David Greeley, a neurologist at Northwest Neurological, PLLC and Kingfisher Cooperative, LLC and a Fellow of the American Academy of Neurology.
"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 Dr. Peter Conti, Professor of Radiology, Pharmaceutical Sciences, and Biomedical Engineering at the University of Southern California. Dr. Conti, a diagnostic radiologist and expert in neurodegenerative imaging at the USC Keck School of Medicine, serves as a key scientific advisor to the company.
PhenoNet expects to begin screening the first patients in January 2027. The Phase 3 trial, PHENOAD-002, is titled "A Phase 3 Randomized, Double-blind, Placebo-controlled trial to Evaluate the Safety and Efficacy of Inhaled Cromolyn (PHENOGENE-1A) in Participants with Early Alzheimer's Disease (AD) Stratified by APOE4 Status
The trial will enroll approximately 648 participants across roughly 90 sites in North America and Europe and will assess the primary endpoint over 72 weeks. With the FDA's 'May Proceed' notification for the active IND, the company intends to pursue a Special Protocol Assessment (SPA) to confirm that the PHENOAD-002 trial design, if successful, can support a future 505(b)(2) NDA submission.
About PhenoNet, Inc
PhenoNet, Inc. (www.phenonet.us) is a privately held biotechnology company headquartered in Cambridge, Massachusetts. The company is advancing the development and commercialization of drugs for the treatment of neurodegenerative diseases such as Alzheimer's disease and Amyotrophic Lateral Sclerosis. Its lead candidate, PHENOGENE-1A (for early Alzheimer's disease in APOE4/non-APOE4 patients and for ALS), is designed to modify disease progression by addressing neuroinflammation and other key triggers of degeneration. PhenoNet, Inc. aims to transform treatment approaches for patients facing urgent, unmet medical needs.
Forward-Looking Statements
Except for historical information contained in this press release, including the FDA notification that the company may proceed with its Phase 3 trial, the realization of these forward-looking statements is primarily dependent on the success of our lead product candidate. We may not be able to successfully commercialize this potential product. Among other reasons, failure could result from the conduct and results of clinical trials, FDA requirements, failure to complete development of our drug, inability to secure financing, unforeseen market conditions, and future events that could hinder commercialization.
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Contacts:
Annabelle Elmaleh, MA
Assistant Director, Business Development
azelmaleh@phenonet.us
