# A randomized double-blind placebo controlled Phase 1 SAD study in male and female healthy volunteers to assess safety, pharmacokinetics, and transient biomarker changes by the ABCA1 agonist CS6253

> **NIH NIH R44** · ARTERY THERAPEUTICS, INC. · 2023 · $2,482,205

## Abstract

PROJECT SUMMARY
Late-onset or sporadic Alzheimer's disease (AD) constitute 95 percent of all AD and APOE4 is the dominating
genetic risk factor. While there are three major APOE allelic variants (APOE2, APOE3, and APOE4), APOE4
carriers have an increased risk of developing AD, and up to 66% of individuals with AD-type dementia cases
and 64% with mild cognitive impairment, also carry the APOE4 allele. There are currently no treatments for
APOE4 driven AD or other dementias. Artery Therapeutics, Inc. (Artery; ATI) has developed a novel chemical
entity for the treatment of APOE4 driven dementias, including AD. CS6253 is a 2nd-generation selective ATP-
Binding-Cassette A1 (ABCA1) transporter agonist peptide derived from the C-terminal of apoE. CS6253 is a
safe, potent, and druggable ABCA1 agonist. ATI's preclinical data in cell systems and two different apoE4
transgenic mice models have demonstrated that CS6253 engages ABCA1 as a target, improves apoE
lipidation, prevents hippocampal amyloid-β (Aβ) pathophysiology, and improves cognition. In IND-enabling
studies, which showed excellent safety and pharmacokinetics properties, it was demonstrated that in primates,
CS6253 treatment over 9 days showed pronounced dose-response reductions in cerebrospinal fluid (CSF)
concentrations of Aβ42, Aβ40, and APP, and other markers. These data strongly support and extend our
efficacy results in mice pharmacology models and are predictive of efficacy in humans. Thus, with this SBIR
proposal, we will advance CS6253 into early clinical trials. In Aim 1, ATI will establish qualifying methods for
GMP drug product and stability at -20C for CofA and release for Phase 1 Clinical Trial Material. GMP drug
product will complete the CMC section (GMP drug substance is already produced) which will be added to the
clinical and nonclinical sections of the IND, for submitting the IND. The aim 1 milestone is to open the IND,
i.e. receive FDA buy-in for initiating the CS6253 Phase 1 trial. We are confident of a successful IND based on
the August 2020 pre-IND meeting with FDA where consensus was reached regarding key aspects of the
program including CMC, nonclinical and the initial clinical trials. In Aim 2, we will perform a randomized double
blind placebo controlled single ascending dose trial in healthy 50-70 y.o. men and women (n=8/cohort, 6
active: 2 placebo, total n=32) who will be characterized but not stratified for APOE isoform. Participants will
receive a single intravenous (iv) administration of CS6253 at 4 single ascending doses. Our Aim 2 milestone
is to establish safety and pharmacokinetics (plasma and CSF) in humans and a safe starting dose for the
multiple ascending dose (MAD) study. We will also explore transient effects on lipids and AD biomarkers by
CS6253 including temporal plasma – CSF dynamics of apolipoproteins and AD markers.
This project will determine CS6253's pharmacokinetics (plasma and CSF) and single dose safety, and prepare
for Phase 1 MAD studies of up ...

## Key facts

- **NIH application ID:** 10734158
- **Project number:** 4R44AG076299-02
- **Recipient organization:** ARTERY THERAPEUTICS, INC.
- **Principal Investigator:** Jan Johansson
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $2,482,205
- **Award type:** 4N
- **Project period:** 2023-01-15 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10734158

## Citation

> US National Institutes of Health, RePORTER application 10734158, A randomized double-blind placebo controlled Phase 1 SAD study in male and female healthy volunteers to assess safety, pharmacokinetics, and transient biomarker changes by the ABCA1 agonist CS6253 (4R44AG076299-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10734158. Licensed CC0.

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