{"id":32690,"date":"2025-07-09T15:38:08","date_gmt":"2025-07-09T10:08:08","guid":{"rendered":"https:\/\/www.delveinsight.com\/blog\/?p=32690"},"modified":"2025-07-09T15:38:10","modified_gmt":"2025-07-09T10:08:10","slug":"metseras-glp-1-receptor-agonist-met-097i","status":"publish","type":"post","link":"https:\/\/www.delveinsight.com\/blog\/metseras-glp-1-receptor-agonist-met-097i","title":{"rendered":"MET-097i: A Fully Biased Ultra-long Acting GLP-1 Receptor Agonist"},"content":{"rendered":"\n<ul class=\"wp-block-list\">\n<li><em>MET-097i is the lead investigational therapy from Metsera, designed as a fully biased GLP-1 receptor agonist with ultra-long-acting properties. Administered via SC injection, it leverages Metsera\u2019s proprietary HALO platform and has shown a preliminary half-life of 15\u201316 days, indicating the potential for once-monthly dosing with flexible titration options.&nbsp;<\/em><\/li>\n\n\n\n<li><em>Metsera shared clinical findings from the Phase I\/II trial of MET-097i through two presentations, highlighting changes in body weight and tolerability outcomes following twelve weekly doses as well as a single monthly dose. The presentations are titled<\/em>\n<ul class=\"wp-block-list\">\n<li><em>A 12-week Trial of MET-097\u2014A Potent and Ultra-Long-Acting GLP-1 Receptor Agonist<\/em><\/li>\n\n\n\n<li><em>Safety, Tolerability, PK, and Efficacy of MET-097\u2014A Next-Generation Nutrient-Stimulated Hormone Peptide Analog for Chronic Weight Management.<\/em><\/li>\n<\/ul>\n<\/li>\n<\/ul>\n\n\n\n<p><strong>Presentation 1: A 12-week Trial of MET-097i\u2014A Potent and Ultra-long Acting GLP-1 Receptor Agonist<\/strong><\/p>\n\n\n\n<p><strong>Trial Design<\/strong><\/p>\n\n\n\n<p>Metsera conducted a randomized, double-blind, placebo-controlled Phase I\/II study to evaluate the efficacy, safety, tolerability, and pharmacokinetics of MET-097i\u2014a fully biased, ultra-long-acting GLP-1 receptor agonist. The trial enrolled 120 adult participants with obesity or overweight (BMI 27\u201338 kg\/m\u00b2) but without diabetes or significant comorbidities. The study included five cohorts, each receiving 12 once-weekly (QW) SC doses of MET-097i across various dose levels (0.4 mg to 1.2 mg), followed by a single higher-dose administration intended to simulate monthly dosing (2\u00d7 or 4\u00d7 the weekly dose).<\/p>\n\n\n\n<p>Participants were evenly distributed among treatment and placebo arms (20 MET-097i vs. 4 placebo per cohort), and primary efficacy was measured by percent change from baseline (%CFB) in body weight at Day 85. Additional assessments included metabolic parameters, Adverse Events (AEs), and tolerability, with follow-up through Day 115.<\/p>\n\n\n\n<p><strong>Results<\/strong><\/p>\n\n\n\n<p><em>Efficacy Outcomes<\/em><\/p>\n\n\n\n<p>Weekly administration of <strong>MET-097i resulted in substantial, dose-dependent weight loss<\/strong>, with placebo-subtracted percentage change from baseline at Day 85 reaching <strong>\u201311.3%<\/strong> in the 1.2 mg group, <strong>\u201310.3%<\/strong> in the 1.0 mg group, and <strong>\u20139.3%<\/strong> in the 0.8 mg group.<\/p>\n\n\n\n<p>Notably, <strong>weight loss did not plateau, indicating a sustained therapeutic effect<\/strong>. After a single high-dose monthly injection on Day 85, weight reduction continued through Day 115, with the 4\u00d7 monthly dose arm (1.2\/4.8 mg) showing placebo-corrected mean weight loss of \u201315.0%<strong>.<\/strong><\/p>\n\n\n\n<p><strong>Safety and Tolerability<\/strong><\/p>\n\n\n\n<p>The safety profile of MET-097i was in line with the GLP-1 class, with no unexpected AEs. Gastrointestinal side effects, primarily mild nausea and vomiting, were dose-dependent (up to 65% and 60% in the 1.2 mg group vs. 15% and 5% in placebo, respectively). One serious AE (calculous cholecystitis) was deemed treatment-related, but no discontinuations were attributed to adverse events.<\/p>\n\n\n\n<p><strong>Metabolic Effects<\/strong><\/p>\n\n\n\n<p>Notable improvements in cardiometabolic markers were observed, including a reduction in LDL cholesterol by up to \u201323.0 mg\/dL, a decrease in total cholesterol by \u201332.5 mg\/dL, and a systolic blood pressure drop of up to \u201311.6 mmHg in the 1.2 mg group, indicating broader metabolic benefits beyond weight loss.<\/p>\n\n\n\n<p><strong>Conclusion<\/strong><br>The Phase I\/II trial establishes MET-097i as a promising ultra-long-acting GLP-1 receptor agonist with the potential for monthly dosing and minimal titration. The agent induced robust, dose-dependent weight loss with sustained effects post-treatment, a favorable safety profile, and added metabolic benefits. These findings provide strong rationale for the ongoing Phase IIb trials investigating simplified weekly and monthly dosing regimens.<\/p>\n\n\n\n<p><strong>Presentation 2: Safety, Tolerability, PK, and Efficacy of MET-097\u2014A Next-generation Nutrient-stimulated Hormone Peptide Analog for Chronic Weight Management<\/strong><\/p>\n\n\n\n<p><strong>Trial Design<\/strong><\/p>\n\n\n\n<p>The study was a randomized, double-blind, placebo-controlled Phase I trial conducted at a single site (NCT06857617). Participants were adults with a BMI between 27 kg\/m<sup>2<\/sup> and 38 kg\/m\u00b2 and normal kidney function (eGFR \u226590 mL\/min), without diabetes or elevated cardiovascular risk factors. The trial featured two parts: Single Ascending Dose (SAD) and Multiple Ascending Dose (MAD) cohorts. In the SAD arm, participants were randomized 6:2 to MET-097 or placebo across seven escalating dose levels. In the MAD arm, six dose cohorts received weekly injections of MET-097 or placebo, with one group receiving four weeks of 0.8 mg followed by a 5<sup>th<\/sup> week of 1.6 mg to test the tolerability of accelerated titration.<\/p>\n\n\n\n<p><strong>Efficacy Outcomes<\/strong><\/p>\n\n\n\n<p>MET-097 demonstrated a clear <strong>dose-dependent reduction in body weight<\/strong>, with the 1.2 mg dose group achieving a <strong>7.5% mean weight loss from baseline by Day 36<\/strong>. Impressively, this effect was sustained even after the end of the dosing period, with a mean weight loss of <strong>8.1% at Day 57<\/strong> and <strong>7.5% at Day 85<\/strong>. These findings suggest that MET-097 not only induces significant short-term weight loss but also has the potential for durable efficacy with relatively few doses. The ability to escalate doses with minimal tolerability issues further enhances its clinical appeal.<\/p>\n\n\n\n<p><strong>Safety and Tolerability<\/strong><\/p>\n\n\n\n<p>Safety data were encouraging, with <strong>no serious TEAEs<\/strong> reported across all cohorts. Most adverse events were <strong>mild gastrointestinal symptoms<\/strong>, such as nausea and vomiting, consistent with the known class effects of GLP-1 receptor agonists. Notably, vomiting was largely confined to the first week of dosing, indicating a rapid onset of tolerance. Even in the cohort that underwent a twofold dose escalation in the final week, only a single case of moderate vomiting was observed, highlighting the favorable tolerability profile of MET-097.<\/p>\n\n\n\n<p><strong>Pharmacokinetics<\/strong><\/p>\n\n\n\n<p>Pharmacokinetic analysis revealed that MET-097 has a <strong>mean time to peak concentration of approximately 18 days<\/strong>, with predictable, dose-proportional plasma levels and minimal variability. The <strong>accumulation ratio after five weekly doses was approximately three<\/strong>, and a two-fold dose increase resulted in a predictable rise in drug exposure. These features are attributed to the drug\u2019s ultra-long half-life, which supports the potential for monthly dosing\u2014a major advantage over current weekly GLP-1-based therapies and a key differentiator in terms of patient adherence and convenience.<\/p>\n\n\n\n<p><strong>KOL Views<\/strong><\/p>\n\n\n\n<p>The first wave of obesity drugs was based mainly on the gut hormone GLP-1, but drugmakers are looking for medicines that target other hormones or help preserve muscle while losing fat for their next generation of drugs.<strong>\u2013 Expert Opinion<\/strong><\/p>\n\n\n\n<p>The data strengthen the view of MET-097i as the potential first ultra-long acting GLP-1 receptor agonist. The powerful reductions in weight affirm earlier studies. We are also excited by the emerging tolerability and dosing profile of MET-097i, which may offer versatility and meaningful advantages for patients.\u2013<strong> Expert Opinion<\/strong><\/p>\n\n\n\n<p><strong>Conclusion<\/strong><\/p>\n\n\n\n<p>The ADA 2025 data on MET-097 mark an important step forward in the evolution of GLP-1 therapies. With compelling early efficacy, simplified dosing, and a well-tolerated safety profile, MET-097 is well-positioned to meet the needs of patients who struggle with adherence to existing therapies. It is a promising addition to the growing obesity and cardiometabolic market, particularly as it targets the need for durable, high-compliance solutions.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Presentation 1: A 12-week Trial of MET-097i\u2014A Potent and Ultra-long Acting GLP-1 Receptor Agonist Trial Design Metsera conducted a randomized, double-blind, placebo-controlled Phase I\/II study to evaluate the efficacy, safety, tolerability, and pharmacokinetics of MET-097i\u2014a fully biased, ultra-long-acting GLP-1 receptor agonist. The trial enrolled 120 adult participants with obesity or overweight (BMI 27\u201338 kg\/m\u00b2) but [&hellip;]<\/p>\n","protected":false},"author":14,"featured_media":32692,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"_editorskit_title_hidden":false,"_editorskit_reading_time":0,"_editorskit_is_block_options_detached":false,"_editorskit_block_options_position":"{}","advgb_blocks_editor_width":"","advgb_blocks_columns_visual_guide":"","footnotes":""},"categories":[17126],"tags":[22599],"industry":[17225],"therapeutic_areas":[17240],"class_list":["post-32690","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-others","tag-ada-annual-conference","industry-pharmaceutical","therapeutic_areas-endocrinology-and-metabolic-disorders"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO Premium plugin v25.8 (Yoast SEO v25.8) - 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