A Phase 1 First-in-human Study to Investigate the Safety, Tolerability and Food Effect of ABBV-CLS-7262 (P6-4.002)

Abstract

<h3>Objective:</h3> To evaluate the first-in-human safety, tolerability and food effect of ABBV-CLS-7262 in healthy subjects. <h3>Background:</h3> ABBV-CLS-7262 is in development as a CNS-penetrant small molecule activator of eIF2B, which is the guanine nucleotide exchange factor for eukaryotic translation initiation factor 2 (eIF2). eIF2 is an important node in the Integrated Stress Response, which is believed to be persistently activated in various neurological diseases, including amyotrophic lateral sclerosis. By activating eIF2B, ABBV-CLS-7262 may attenuate the Integrated Stress Response and restore protein translation. <h3>Design/Methods:</h3> This multi-part Phase 1 study enrolled healthy male and female subjects between 18 and 65 years of age. A total of 125 subjects received ABBV-CLS-7262 and 33 received placebo. <h3>Results:</h3> ABBV-CLS-7262 was well-tolerated following oral administration of single and multiple ascending doses for up to 14 days. All adverse events (AEs) were mild to moderate in severity, and no dose-dependent patterns of AEs or laboratory abnormalities were identified. Following administration with a high-fat meal, the safety, tolerability, and pharmacokinetics were similar when compared to the fasting state. <h3>Conclusions:</h3> The observed safety, tolerability, and clinical pharmacology profile of ABBV-CLS-7262 support investigation of the product in further studies. <b>Disclosure:</b> Dr. Cho has received personal compensation for serving as an employee of Calico. Dr. Cho has stock in Roche. Dr. Jeong has received personal compensation for serving as an employee of AbbVie. An immediate family member of Dr. Jeong has received personal compensation in the range of $500,000-$999,999 for serving as a Consultant for Stryker. Dr. Jeong has stock in AbbVie. Dr. Malik has received personal compensation for serving as an employee of AbbVie. Dr. Malik has received personal compensation for serving as an employee of Calico Life Sciences. Dr. Boiser has received personal compensation for serving as an employee of AbbVie. Dr. Boiser has stock in AbbVie. Dr. Huang has received personal compensation for serving as an employee of AbbVie. Dr. Rosebraugh has received personal compensation for serving as an employee of AbbVie Inc. Dr. Rosebraugh has stock in AbbVie Inc..