# In Vivo Studies of a Novel HDAC Inhibitor for Treating Hemoglobin Disorders

> **NIH NIH R42** · CETYA THERAPEUTICS, INC. · 2020 · $550,046

## Abstract

PROJECT SUMMARY
The β-hemoglobinopathies are prevalent genetic blood diseases with few treatment options. It is estimate that
7% of the world's population carries an abnormal hemoglobin gene with 400,000 infants born annually with a
severe life threatening hemoglobinopathy. Drug mediated induction of normal, but developmentally silenced,
fetal hemoglobin (HbF) expression reduces anemia and ameliorates clinical severity in the β-
hemoglobinopathies. Histone deacetylase (HDAC) 1, 2, and 3, are components of the NURD repressor
complex, which promotes silencing of the fetal γ-globin genes in adult erythroid cells. Prior generation HDAC
inhibitors increase HbF in patients with β-hemoglobinopathies, but had limitations for pharmaceutical
application and/or required titration to reduce anti-proliferative effects. Cetya has generated a library of high
potency HDAC inhibitors, one of which, CT-101, has demonstrated efficacy in inducing HbF expression in β-
thalassemia and sickle cell erythroid progenitors and in the β-YAC mouse model that contains the normal
human β-globin gene locus,without significant anti-proliferative effects. We will test the central hypothesis
that CT-101 has a sufficiently wide margin of activity, without significant inhibition of erythroid cell growth, to be
developed as a new agent for treatment of β-hemoglobinopathies. We propose to conduct studies to evaluate
CT-101 in the β-YAC model to optimize dose and schedule, and then confirm efficacy in the Townes sickle cell
disease mouse model. Cetya will scale the CT-101 manufacturing process and produce sufficient quantities to
support the murine studies and oral formulation development. The goal of this project is to develop the new
high-potency HDAC inhibitor CT-101 for an IND and clinical therapeutics. To test our hypothesis the following
aims will be completed. Aim 1. Test the hypothesis that CT-101 induces HbF expression in the preclinical β-
YAC and Townes sickle cell disease mouse models through epigenetic histone modifications. Aim 2. Scale the
manufacturing processes and produce sufficient quantities of CT-101 to conduct IND-enabling studies required
for a Phase I clinical study. Aim 3. Develop an oral dosage formulation of CT-101 suitable for human
administration. The expected outcome of this Phase 2 project is to develop CT-101 as an oral effective HbF
inducer. Our experimental approach rests on the scientifically validated concept of the inhibition of sickle
hemoglobin polymerization by HbF and red blood cell sickling by reversing a well-known epigenetic γ-globin
gene silencing mechanism. Development of the potent HDAC inhibitor CT-101 will impact the field and
addresses an unmet need for additional disease modifying therapy for β-hemoglobinopathies.

## Key facts

- **NIH application ID:** 10019584
- **Project number:** 5R42HL136068-03
- **Recipient organization:** CETYA THERAPEUTICS, INC.
- **Principal Investigator:** Louis H Junker
- **Activity code:** R42 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $550,046
- **Award type:** 5
- **Project period:** 2017-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10019584

## Citation

> US National Institutes of Health, RePORTER application 10019584, In Vivo Studies of a Novel HDAC Inhibitor for Treating Hemoglobin Disorders (5R42HL136068-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10019584. Licensed CC0.

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