Artery Therapeutics, Inc.

CS6253 Sequential Subcutaneous Pharmacokinetic Study Followed by Phase 2A Placebo-controlled Trial With Three Fixed Doses in APOE4 Mci and Ad Patients to Assess Safety, PK, and Biomarker Effects - Project Summary Artery Therapeutics, Inc. (ATI) Is Developing CS6253, a Highly Differentiated, Cholesterol-transport Focused Treatment for the Indication of Hereditary APOE4-ASSOCIATED Dementia Including Mci-ad, Targeting the Atp- Binding-cassette-transporter A1 (ABCA1). We Now Propose Two Sequential CS6253 Studies to Delineate Mechanism and Show Proof of Concept (POC) in Homozygous APOE4 Early Ad Patients. in the Recently Performed Phase 1 Sad-mad Study in Healthy Men and Women CS6253 Showed Favorable Safety/tolerability and Pharmacokinetics (PK), Apoe Target Engagement and an Amyloid-clearance Signal Consistent With Previous Mouse Model (boehm, 2016) and Primate (noveir, 2022) Studies. in the Phase 1 Study We Also Performed an Exploratory Iv-sc Bioequivalence Sub-study Showing That a Single CS6253 SC Bolus Injection of 1 MG/KG Was Safe With a 79% Bioavailability (compared to Iv Injection) and Within the Exposure Range of the Successful Targeted Replacement Mice Studies (boehm, 2016). We Now Need to Show That Multiple-fold Higher Exposure Levels Can Be Reached by SC Route of Administration Prior to Commencing Phase 2A Mechanism/proof of Concept (POC) Studies, Covering a Wider Exposure Range, to Evaluate Safety, PK, and Pharmacodynamics (PD) Effects. Thus, Our Objectives Are to Perform a Subcutaneous (SC) Injection PK Feasibility Study With the ABCA1 Agonist CS6253, and Provided Prespecified Drug Exposure Success Criteria Are Met, Then Perform a 28-DAY Phase 2A Mechanism/poc Study in 48 APOE4-CARRIERS With Mild Cognitive Impairment (mci), of Which Half Are Homozygous, to Assess Safety, Tolerance, PK, Plasma and CSF Biomarker Effects. We Will Assess; 1) CS6253’S ABCA1 Target Engagement by Following Change in CSF and Plasma Apoe (total and Isomer Specific Protein and Glycosylation Levels) and Lipidation (primary Effect); 2) Test Amyloid-clearance Hypothesis by Following CSF and Plasma AΒ42, AΒ40, AΒ42/40-RATIO (secondary); 3) ABCA1 Cholesterol-transport Salutary Effects by Following Plasma and CSF Changes in P-tau 181, 217, 231, Gfap, NFL, and TREM2 (tertiary); 4) Explore Direct VS Indirect CS6253 Effect by Assessing Upregulation of Natural ABCA1 Agonists as Apoe and Small Apoa-i Particles in Plasma and CSF (exploratory); 5) Inform on Optimal Dosing-regimen, Patient Population (homozygous VS Heterozygous) and Power for Subsequent Phase 2-3 Studies (trial Preparatory). With a Positive Outcome From These Important Studies in the APOE4 Carrier Patient Population the Next Regulatory- Clinical Development Steps Are to Propose Breakthrough Designation With the Fda and Assess CS6253 Effects on Cognition in a Phase 2-3, 9 Month Randomized Controlled Trial (RCT) in Homozygous APOE4 Carriers With Ad/adrd.