Epigenetic medicines
Changing gene expression to change lives.
Appia advances first-in-class, disease-modifying therapies that reverse the abnormal epigenetic modifications underlying Alzheimer's Disease and related dementias.
Columbia University spin-out · Epigenetic medicines for neurodegeneration
Appia's Story
A company built on the epigenetics of memory.
Appia Pharmaceuticals was founded in 2014 as a drug development company focused on modulating gene transcription factors. Our medicines are developed from a technology platform built around the acetylation of gene transcription factors — the epigenetic switch that determines which genes a cell can access and express.
Appia is a Columbia University academic spin-out that runs a lean biotechnology model, drawing on certified contract research organizations, academic collaborations, and a team of expert consultants and financial officers.
A large portfolio of patents covers both our composition of matter and its use across neurodegenerative indications.
EZ115HAT
A first-in-class, oral, brain-penetrant activator of the histone acetyltransferases p300, CBP, PCAF, and TIP60 — the same enzymes reduced in the Alzheimer's brain. In preclinical models of tau and amyloid-β pathology, EZ115HAT restored synaptic plasticity and memory. IND submission is planned for Q2 2027.
Pipeline
Decades of epigenetics research, reaching the clinic.
The benefits of decades of epigenetics research have made their way into medical practice. Appia is advancing a family of proprietary compounds that reverse the abnormal epigenetic modification patterns found in the brain during neurodegeneration — restoring the histone acetylation that supports memory and synaptic health.
EZ115HAT
EZ115HAT is a first-in-class, oral, brain-penetrant small-molecule activator of the histone acetyltransferases p300, CBP, PCAF, and TIP60 — enzymes shown to be reduced in the Alzheimer's brain. By restoring acetylation at lysine residues where it is diminished, EZ115HAT re-opens chromatin to transcription, supporting the gene expression that underlies learning and memory. No approved drugs act in this space, and none with EZ115HAT's mechanism are known to be in clinical development.
What differentiates EZ115HAT
Novel mechanism
A first-in-class approach that addresses Alzheimer's through an upstream epigenetic mechanism, with no other drugs known to be in development against this target.
Robust preclinical efficacy
In transgenic mouse models of tau and amyloid-β elevation, chronic treatment rescued deficits in synaptic plasticity and in spatial and associative memory.
Potent, on-target activity
Increases histone acetylation with low-nanomolar potency (EC50 ≈ 60 nM).
Excellent drug-like properties
High oral bioavailability (≈86% in beagle dogs), rapid absorption, and demonstrated blood–brain barrier penetration, with brain levels exceeding plasma.
Favorable safety profile
Activates memory-related HATs directly, avoiding the toxicity and lack of selectivity that limited earlier HDAC-inhibitor approaches.
Strong intellectual property
Composition-of-matter and use patents filed (U.S. provisional and PCT), with projected coverage to 2043 and beyond.
Development Plan
From toxicology to proof-of-concept.
Toxicology studies and GLP scale-up synthesis are ongoing, with an IND submission planned for Q2 2027, followed by a first-in-human Phase 1 study and a Phase 2a proof-of-concept study in patients.
Beyond Alzheimer's
A platform, not a single compound.
EZ115HAT emerged from a proprietary platform of more than 90 novel HAT modulators. Beyond Alzheimer's Disease, the mechanism offers expansion potential across other neurodegenerative disorders, including Alzheimer's Disease Related Dementia (ADRD) and Huntington's Disease.
Rationale
Epigenetics and acetylation.
Epigenetics is the mechanism that changes gene expression by "marking" DNA or its associated proteins, without changing the DNA sequence itself. Modifying histones — the proteins around which DNA is wound — by adding or removing acetyl groups causes chromatin to open or close. It is not surprising, then, that dysregulation of histone acetylation can lead to disease.
We focus our research on the enzymes that acetylate histones: histone acetyltransferases (HATs). Their activation increases gene transcription and protein synthesis. Appia develops small molecules that enhance HAT activity to counteract the loss of acetylation seen in Alzheimer's Disease and related dementias.
A hallmark of Alzheimer's Disease
Dysregulation of histone acetylation.
With age and disease progression, histone acetylation declines in the brain — driven in part by reduced levels of the HAT enzymes CBP, p300, PCAF, and TIP60. The consequences cascade:
↓ Reduced HAT activity → a clear, targetable mechanism
EZ115HAT & Alzheimer's
A differentiated approach.
Most Alzheimer's programs have targeted tau or amyloid-β directly, with limited late-stage success. Appia acts instead on the epigenetic mechanisms that underlie synaptic plasticity, mitigating the harmful effects of tau and amyloid-β oligomers, which impair long-term potentiation — a synaptic surrogate of memory.
EZ115HAT selectively increases acetylation at lysine sites known to lose acetylation in Alzheimer's Disease (including H3K4, H3K9 and H3K14) through p300, CBP, PCAF, and TIP60. In preclinical studies, chronic treatment rescued defects in synaptic plasticity and in both fear and spatial memory across transgenic mouse models of tau elevation and of amyloid deposition — the latter even after amyloid plaques had appeared. Combined with its oral bioavailability, brain penetration, and clean safety profile, these data make EZ115HAT a compelling candidate for Alzheimer's Disease and related dementias.
The Team
The people behind Appia.
In 1986, Mr. Auriana co-founded the Federated Kaufmann Funds which became one of the country's fastest-growing small-cap growth funds. He retired in 2015.
Mr. Lerner was a senior analyst and co-head of the investment area of the Federated Kaufmann Funds.
Professor of Pathology & Cell Biology, Department of Medicine and Taub Institute at Columbia University.
Chairman of the Department of Medicine at Columbia University and Chief of Medicine at New York Presbyterian/Columbia University Medical Center; Founding Director, Organic Chemistry Collaborative Center (OCCC).
Contact us