AMG 133 is a First-in-Class Investigational Bispecific Molecule That Activates GLP-1R and Inhibits GIPR

Phase 1 Results Showed up to 14.5% Reduction in Body Weight at the Highest Dose After 12 Weeks

Initiating Phase 2 Study in Early 2023

THOUSAND OAKS, Calif., Dec. 1, 2022 /PRNewswire/ -- Amgen (NASDAQ:AMGN) today announced new Phase 1 data from AMG 133, a novel bispecific glucose-dependent insulinotropic polypeptide receptor (GIPR) antagonist and glucagon-like peptide-1 (GLP-1) receptor agonist molecule. This first-in-human study was designed to evaluate the safety, tolerability, pharmacokinetic and pharmacodynamic effects of AMG 133 in people with obesity and without diabetes (NCT04478708). These data will be presented as part of an oral presentation on Saturday, Dec. 3 at the 20^th World Congress of Insulin Resistance, Diabetes and Cardiovascular Disease (WCIRDC) Hybrid Conference.

"AMG 133 was designed based on preclinical and human genetic data that strongly suggest GIPR inhibition as a strategy for weight loss, especially in combination with GLP-1 agonism," said David M. Reese, M.D., executive vice president of Research and Development at Amgen. "We are encouraged by these Phase 1 results with once-monthly dosing of AMG 133, specifically, the degree, rate and durability of the weight loss. We look forward to initiating the Phase 2 study early next year."

Participants were randomized (3:1) to receive subcutaneous AMG 133 or placebo either as a single ascending dose (SAD) or multiple ascending doses (MAD). The MAD cohorts showed mean percent changes in body weight (BW), ranging from -7.2% at the lowest dose (140mg Q4W), to -14.5% at the highest dose (420mg Q4W) by day 85. A substantial degree of weight loss was maintained beyond the treatment period, which will be shared as part of the oral presentation. Most treatment emergent adverse events (TEAEs) were mild and transient. The majority of the TEAEs were GI-related with the most common being nausea and vomiting, most events resolved within 48 hours.  Based on these data, a Phase 2 trial will be initiated early next year to further study the attributes of this molecule.

Amgen will host a webcast call for the investment community in conjunction with WCIRDC at 8:00 a.m. ET on Monday, Dec. 5, 2022. For more information visit: https://investors.amgen.com/.

About Obesity
Obesity is a serious, chronic disease that affects a significant proportion of the world population. In the US alone, 74% of adults are either obese or overweight¹, including 42% who are obese². The worldwide prevalence of obesity has tripled over the past 40 years and continues to rise in nearly every demographic.³ Obesity is linked to a marked reduction in quality of life and an array of serious medical complications⁴, placing a significant burden on healthcare systems globally.⁵ Despite the scale of the disease, the formal recognition of obesity as a chronic disease by the American Medical Association (2013) and the European Health Commission (2021), and medical guidelines recommending pharmacologic treatment in appropriate individuals, only 1-3% of patients globally are prescribed medication.^6,7

About AMG 133
AMG 133 is a bispecific glucose-dependent insulinotropic polypeptide receptor (GIPR) antagonist and glucagon-like peptide-1 (GLP-1) receptor agonist molecule. AMG 133 mimics the agonist effects of GLP-1 and antagonizes the effects of glucose-dependent insulinotropic polypeptide (GIP). Amgen moved into this Phase 1 study based on human genetic insights and preclinical evidence that suggested synergistic effects with GIP receptor blockade and GLP-1 receptor agonism on weight loss and improvement in other metabolic parameters.

About the Phase 1 Study and Future Development
The randomized, double-blind, placebo-controlled single and multiple ascending dose study of AMG 133 enrolled people with a Body Mass Index (BMI) of ≥30.0 kg/m2 and ≤40.0 kg/m2 without other medical conditions. Participants were randomized (3:1) to receive subcutaneous AMG 133 or placebo either as a single ascending dose (SAD) or multiple ascending doses (MAD). Participants were assigned to six SAD cohorts (n=49; mean age 48 years, BMI 33.4 kg/m2, and BW 99.5 kg) and three MAD cohorts (n=26; mean age 46 years, BMI 33.5 kg/m2, and BW 96.9 kg). Pharmacokinetics and body weight (BW) were measured and safety and tolerability were monitored. Most treatment emergent adverse events (TEAEs) were mild and transient.⁸ The majority of the TEAEs were GI-related with the most common being nausea and vomiting, most events resolved within 48 hours.

Amgen plans to initiate Phase 2 testing with a dose-ranging study in early 2023, where long-term effects in an expanded number of patients will be further characterized.

About Amgen 
Amgen is committed to unlocking the potential of biology for patients suffering from serious illnesses by discovering, developing, manufacturing and delivering innovative human therapeutics. This approach begins by using tools like advanced human genetics to unravel the complexities of disease and understand the fundamentals of human biology. 

Amgen focuses on areas of high unmet medical need and leverages its expertise to strive for solutions that improve health outcomes and dramatically improve people's lives. A biotechnology pioneer since 1980, Amgen has grown to be one of the world's leading independent biotechnology companies, has reached millions of patients around the world and is developing a pipeline of medicines with breakaway potential. 

Amgen is one of the 30 companies that comprise the Dow Jones Industrial Average and is also part of the Nasdaq-100 index. In 2022, Amgen was named one of the "World's Best Employers" by Forbes and one of "America's 100 Most Sustainable Companies" by Barron's.

For more information, visit Amgen.com and follow us on Twitter, LinkedIn, Instagram, TikTok and YouTube.

Amgen Forward-Looking Statements
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CONTACT: Amgen, Thousand Oaks
Jessica Akopyan, 805-440-5721 (media)
Arvind Sood, 805-447-1060 (investors) 

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SOURCE Amgen