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Protagonist Announces Nomination of PN-477, an Oral and Injectable GLP-1R, GIPR, and GCGR Triple Agonist Peptide Development Candidate for Obesity
A novel oral peptide PN-477o with once-daily dosing, high potency and activation of glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide
About this update from Protagonist Therapeutics, Inc.
[{"type":"text","content":"A novel oral peptide PN-477o with once-daily dosing, high potency and activation of glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), and glucagon (GCG) receptorsCompany will also develop a subcutaneous version, PN-477sc, as a once-weekly injectionIND-enabling studies underway, with Phase I study initiation expected in 2Q26Webcast and conference call to be held today at 4:30 pm ET NEWARK, CALIFORNIA / ACCESS Newswire / June 30, 2025 / Protagonist Therapeutics, Inc. (\"Protagonist\" or the \"Company\") today announced the selection of PN-477, a potential best-in-class GLP-1, GIP, GCG receptor triple agonist peptide with oral and subcutaneous routes of administration, as a development candidate for the treatment of obesity. The triple agonist PN-477 is designed to offer the optimal combination of total body weight loss, improved gastrointestinal (GI) tolerability and fat to lean mass ratio, with the dosing convenience of a once-daily oral agent and the added optionality of a once-weekly subcutaneous administration.\"We are very pleased to nominate development candidate PN-477, a promising potential best-in class oral GLP-1, GIP, GCG receptor tri-agonist peptide which has demonstrated optimal absolute and relative activity against all three hormone receptors in preclinical testing,\" said Dinesh V. Patel, PhD, President and CEO of Protagonist. \"PN-477 is specifically engineered to be orally stable with attention to the relative balance of potencies against the three receptors to potentially leverage their beneficial effects on weight loss and optimal body composition while mitigating their adverse effects. As with our previous drug candidates and late-stage assets, PN-477 is a testament to the power of our peptide technology platform, including the ability to deliver first- and best-in-class targeted oral and injectable peptide therapeutics.\"PN-477 has completed extensive preclinical evaluation including oral and metabolic stability, potency, pharmacokinetics and pharmacodynamics studies, and has demonstrated effects in preclinical models of obesity and glycemic control. PN-477 has shown potent in vitro activity in activating the GLP-1, GIP, and GCG receptors. PN-477 also demonstrated robust preclinical proof-of-concept in various animal studies including the diet induced obesity (DIO) preclinical m...