Built on science.
Driven by patients

The research and development behind PharmatrophiX’s pipeline is a case study in targeted, deep neurobiology, specifically focusing on the signaling pathways that govern whether a neuron and synapse lives or dies. The pipeline is built on decades of research into the mechanistic overlap between neurodegenerative diseases and neurotrophins and their receptors.

• The Problem: Within neurodegenerative diseases such as Alzheimer’s and others, degenerative signaling networks are triggered within neurons and other cells leading to the degeneration of these cells and synaptic connections.
• The Solution: Neurotrophin receptors modulate these signaling networks. Dr. Longo’s academic laboratory is among the first to create small molecules modulating these receptors, thereby opening up the powerful biology of these receptors and their mechanisms to therapeutic development. Many of these mechanisms also underlie synaptic resilience which makes it possible for patients with amyloid and tau in their brains to maintain normal cognition.

This receptor acts as a biological “toggle switch” capable of promoting neuronal and synaptic survival or degeneration :

• Degeneration Signal: When bound by certain toxic proteins (like pro-NGF or amyloid), p75 triggers degenerative signaling and progressive synapse loss.
• Survival Signal: When activated by mature neurotrophins, it can promote neuron and synaptic survival and neurite outgrowth.
• Strategy: PharmatrophiX developed molecules to selectively bind to p75, blocking the “death” signals while simultaneously promoting the “survival” pathways.

LM11A-31. This compound represents a breakthrough in multifactorial biology because it addresses several aspects of neurodegeneration at once:

• Synaptic Protection: In preclinical models, it has been shown to protect synapses from pathologic forms of amyloid and tau.
• Tau Reduction: The drug affects 8 mechanisms linked to tau pathology resulting in the reduction of the accumulation of pathological forms of tau.
• Inflammation Modulation: Reduces disease-associated microglial activation, reducing the negative aspects of the brain’s inflammatory response.

With decades of foundational neuroscience research in neurotrophin receptor modulation, our pipeline is advancing disease-modifying therapies across multiple neurodegenerative indications.

• Early Discovery: Identification of additional neurotrophic receptor modulators.
• Preclinical Breadth: Testing the p75 ligands in a wide range of preclinical models, including Alzheimer’s, PSP, Huntington’s, and others.
• Clinical Validation: LM11A-31 has completed Phase 1 safety and pharmacokinetic trials and a Phase 2a trial (NCT03069014) and published in Nature Medicine.