INDIANA UNIVERSITY AND PHARMATROPHIX PRESENT FINDINGS ON PERFORMANCE OF ORAL THERAPEUTIC, LM11A-31, TO REDUCE DECLINE OF BRAIN FUNCTIONAL-NETWORK CONNECTIVITY IN ALZHEIMER'S DISEASE

New findings presented at featured research session (FRS) during the Alzheimer's Association International Conference demonstrate statistically significant slowing of decline in brain network function with LM11A-31 vs placebo linked to cognitive domains and synaptic resilience

MENLO PARK, Calif., July 13, 2026 /PRNewswire/ -- Indiana University and PharmatrophiX, a privately-held, clinical-stage biopharmaceutical company pioneering the development of disease-modifying drugs targeting neurodegenerative diseases, today unveiled a new analysis leveraging a novel application of metabolic brain functional-network connectivity mapping that suggests PharmatrophiX's lead candidate, LM11A-31, may help support the integrity of brain communication networks in people with mild-to-moderate Alzheimer's disease. The analysis was presented at The Alzheimer's Association International Conference (AAIC) in London.

"LM11A-31 is designed to protect the synapses – the connections between neurons – that enable the brain to function as an integrated network. What makes these findings particularly important is that advances in brain imaging and network analysis now allow us to measure the activity of those networks directly in living patients," said Frank M. Longo, MD, PhD, Co-Founder of PharmatrophiX. "Together with the previously reported pre-clinical studies and phase 2a AD trial biomarker findings that found statistically significant changes relevant to synaptic resilience, these results strengthen our understanding of how our mechanism of action may influence the underlying biology of Alzheimer's disease."

The novel brain mapping technology, developed by a team of researchers at the Indiana University School of Medicine, can use brain metabolic activity measurements to create "metabolic network maps" that quantify brain network function as related to cognition to reveal the progression of Alzheimer's and other neurodegenerative diseases. This emerging technology will play a key role in the evaluation of therapeutic effects in neurodegenerative disorders that are particularly relevant to cognitive function.

The Indiana University research team led by Paul R. Territo, PhD, and Juan Antonio Chong Chie, PhD, processed 18F-FDG-PET scan data from 159 participants in the Phase 2a trial of LM11A-31 with mild to moderate Alzheimer's disease. The trial consisted of three groups (placebo, low-dose, high-dose) at two timepoints (baseline (BL), 26-week follow-up (26w)). The data was analyzed in a blinded fashion using metabolic covariance analysis, hierarchical clustering, shortest-path, and efficiency analysis to assess whole-brain and regional network changes over the 26-week trial period.

"Alzheimer's disease is not simply a disease of individual brain regions – it is a disease of disrupted brain networks. Memory and other cognitive and daily functions depend on the ability of neurons to communicate as an integrated system," said Territo, Professor of Medicine, Indiana University. "By measuring how these networks perform in terms of efficiency, and how these quantitative measures change with time and by sex, we can gain a deeper understanding of the biological effects of a therapy and obtain measures of brain function that are as closely related to cognition as currently possible."

Researchers found that LM11A-31 was associated with dose-dependent effects in whole-brain metabolic connectivity, network efficiency and functional brain systems linked to cognitive domains such memory and other functions, with the strongest effects observed in participants receiving the higher 400 mg dose. Prior studies published from Dr. Territo's lab demonstrated that males and female Alzheimer's patients exhibit different patterns of brain network change over time. Analysis of the effects of LM11A-31 also found sex-dependent patterns on network effects. The overall findings suggest that LM11A-31 may help preserve and reorganize the brain networks that support cognitive function in Alzheimer's disease. This activity is consistent with effects seen in mouse versions of Alzheimer's disease.

"These findings, together with our Phase 2a biomarker results, provide encouraging evidence that LM11A‑31 may help preserve the brain networks supporting cognition and strongly support the rigorous clinical development of this program for people living with Alzheimer's disease." David Setboun, CEO, Pharm.D. of PharmatrophiX.

About PharmatrophiX

PharmatrophiX is a clinical-stage biopharmaceutical company focused on the discovery and development of disease-modifying therapies for neurodegenerative diseases. PharmatrophiX was co-founded by Frank Longo, MD, PhD, and Anne Chun Longo. The company is advancing a pipeline of small-molecule drugs targeting p75 as well as the TrkB and TrkC receptors designed to prevent fundamental neurodegenerative mechanisms and to promote synaptic resilience with an emphasis on extensive collaboration with leading academic groups, disciplined clinical development and strategic collaboration.

About LM11A-31

PharmatrophiX's lead asset is a first-in-class small molecule (LM11A-31) targeting the p75 neurotrophin receptor. In published pre-clinical studies across multiple neurodegenerative disease models, LM11A-31 has been found to render synapses resilient to pathological forms of amyloid and tau, reduce the accumulation and spread of a broad range of pathological tau species, and reduce disease-associated microglial and astrocyte dysfunction. These activities are consistent with the known extensive overlap between the intracellular degenerative signaling networks regulated by the p75 receptor and degenerative networks upregulated in Alzheimer's and related neurodegenerative diseases.

About the PharmatrophiX LM11A-31 Alzheimer's Disease Program

PharmatrophiX has completed a Phase 2a safety- and biomarker-focused RCT study assessing mild-moderate Alzheimer's disease in 242 enrolled participants, LM11A-31 demonstrated significant beneficial effects in five biomarker categories: structural MRI, FDG-PET, CSF synaptic and glial biomarkers, CSF proteomic modules with high significant weighting for synaptic proteins and plasma p-tau217. ADAS-cog13 and MMSE scores progressed significantly and as expected in the placebo group, with a 50% reduction of progression with both scores observed in the drug-treated group. A favorable safety profile was reported and no treatment-related amyloid-related imaging abnormalities were reported (Shanks et al Nature Medicine 2024; NCT03069014; EudraCT 2018-001071-20). With encouraging clinical findings to date, and their consistency with extensive pre-clinical studies and underlying mechanisms, planning is underway for a phase 2b/3 Alzheimer's disease trial.              

For more information visit www.pharmatrophix.com

About the Indiana University School of Medicine

The IU School of Medicine is the largest medical school in the U.S. and is annually ranked among the top medical schools in the nation by U.S. News & World Report. The school offers high-quality medical education, access to leading medical research and rich campus life in nine Indiana cities, including rural and urban locations consistently recognized for livability. According to the Blue Ridge Institute for Medical Research, the IU School of Medicine ranks No. 15 in 2025 National Institutes of Health funding among all public medical schools in the country.

For more news, visit the IU School of Medicine Newsroom: medicine.iu.edu/news

SOURCE PharmatrophiX