P3006 - The Pharmacokinetics of Long-Acting GLP-1 Analogue (NM-002) in Patients With Short Bowel Syndrome

Patrick H. Griffin, MD, Sireesh Appajosyula, PharmD, Matthew Bryant, PharmD, Nir Barak, MD
9 Meters Biopharma, Raleigh, NC

Introduction: Glucagon-like peptide-1 (GLP-1) analogues are known to slow down gastric and intestinal motility. NM-002 is a long-acting GLP-1 analogue designed to be used in patients with short bowel syndrome (SBS). The aim of this study was to explore the pharmacokinetic profile of NM-002 in patients with SBS.

Methods: Adult patients with SBS were randomized to receive either 50 mg, 100 mg, or 150 mg of NM-002 on Day 1 and Day 15 of the study. Levels of NM-002 were measured with an electrochemiluminescence (ECL) immunoassay, where human anti-Exendin-4 antibody and anti-XTEN biotinylated antibody were used to capture NM-002 molecules and SULFO-TAG Streptavidin bound to the biotinylated NM-002 that was used to generate an electrochemiluminescence signal. This signal was compared to signals generated with known standards of NM-002; the concentration of the NM-002 was back-calculated from the 4-parameter 1/y² non-linear regression of the standards. The accuracy and precision of this method was validated to be within -3.80% to 12.18%.

Results: Nine SBS patients (5m/4f) were recruited to the study; the average age was 51.8 years and an average BMI was 22.1 kg.m^-2. Three subjects received 50 mg dose, 4 subjects received 100 mg dose and 2 subjects received 150 mg dose. One of the 50 mg patients did not receive a second dose due to a protocol violation. The mean half-life ranged between 300 and 750 hours and was independent of the dose administered.




The pharmacokinetic profile of NM-002 are shown in the table and graph below (Mean + SD).

Discussion: The pharmacokinetic profile of NM-002, a long-acting GLP-1 analogue, shows dose dependent effect with accumulation at Day 15 supporting its extended half-life time. These pharmacokinetic data support twice monthly fixed dosing regimen (or better).



Disclosures:


Patrick H. Griffin, MD, Sireesh Appajosyula, PharmD, Matthew Bryant, PharmD, Nir Barak, MD. P3006 - The Pharmacokinetics of Long-Acting GLP-1 Analogue (NM-002) in Patients With Short Bowel Syndrome, ACG 2021 Annual Scientific Meeting Abstracts. Las Vegas, Nevada: American College of Gastroenterology.