Protagonist Announces Nomination of PN-477, an Oral and Injectable GLP-1R, GIPR, and GCGR Triple Agonist Peptide Development Candidate for Obesity
Protagonist Therapeutics (NASDAQ:PTGX) has announced the nomination of PN-477, a novel GLP-1, GIP, and GCG receptor triple agonist peptide, as a development candidate for obesity treatment. The drug candidate features both oral (PN-477o) and injectable (PN-477sc) formulations, designed for once-daily and once-weekly administration respectively.
The company reports that PN-477 has demonstrated potent in vitro activity in activating all three targeted receptors and has shown robust preclinical proof-of-concept in various animal studies, including diet-induced obesity mouse models, normal dogs, and cynomolgus monkeys. The candidate is engineered to be orally stable with balanced potencies against the three receptors to potentially maximize weight loss benefits while minimizing adverse effects.
Protagonist has initiated IND-enabling studies and expects to begin Phase 1 clinical trials in the second quarter of 2026. The company positions PN-477 as a potential best-in-class treatment option, aiming to offer weight loss comparable to the best injectable treatments while providing the flexibility of both oral and injectable administration routes.
Protagonist Therapeutics (NASDAQ:PTGX) ha annunciato la nomina di PN-477, un nuovo peptide agonista triplo dei recettori GLP-1, GIP e GCG, come candidato allo sviluppo per il trattamento dell'obesità. Il candidato farmaco è disponibile in due formulazioni: orale (PN-477o) e iniettabile (PN-477sc), progettate rispettivamente per somministrazioni quotidiane e settimanali.
L'azienda riferisce che PN-477 ha dimostrato una potente attività in vitro nell'attivare tutti e tre i recettori target e ha mostrato un solido proof-of-concept preclinico in diversi studi su animali, inclusi modelli murini di obesità indotta da dieta, cani normali e scimmie cynomolgus. Il candidato è stato progettato per essere stabile per via orale con potenze bilanciate contro i tre recettori, al fine di massimizzare i benefici nella perdita di peso minimizzando gli effetti avversi.
Protagonist ha avviato studi per l'approvazione IND e prevede di iniziare le prove cliniche di Fase 1 nel secondo trimestre del 2026. L'azienda punta a posizionare PN-477 come un'opzione terapeutica potenzialmente best-in-class, offrendo una perdita di peso paragonabile ai migliori trattamenti iniettabili, con la flessibilità di entrambe le vie di somministrazione, orale e iniettabile.
Protagonist Therapeutics (NASDAQ:PTGX) ha anunciado la nominación de PN-477, un nuevo péptido agonista triple de los receptores GLP-1, GIP y GCG, como candidato para el desarrollo de un tratamiento para la obesidad. El candidato a medicamento cuenta con formulaciones tanto orales (PN-477o) como inyectables (PN-477sc), diseñadas para administración diaria y semanal, respectivamente.
La compañía informa que PN-477 ha demostrado una potente actividad in vitro activando los tres receptores objetivo y ha mostrado un sólido proof-of-concept preclínico en varios estudios con animales, incluidos modelos de ratones con obesidad inducida por dieta, perros normales y monos cynomolgus. El candidato está diseñado para ser estable por vía oral con potencias equilibradas contra los tres receptores, con el fin de maximizar los beneficios en la pérdida de peso y minimizar los efectos adversos.
Protagonist ha iniciado estudios para la habilitación IND y espera comenzar los ensayos clínicos de Fase 1 en el segundo trimestre de 2026. La compañía posiciona a PN-477 como una opción de tratamiento potencialmente best-in-class, buscando ofrecer una pérdida de peso comparable a los mejores tratamientos inyectables, con la flexibilidad de ambas vías de administración, oral e inyectable.
Protagonist Therapeutics (NASDAQ:PTGX)는 비만 치료를 위한 개발 후보 물질로서 PN-477을 지명했다고 발표했습니다. PN-477은 GLP-1, GIP, GCG 수용체를 모두 활성화하는 새로운 삼중 작용 펩타이드입니다. 이 약물 후보는 하루에 한 번 복용하는 경구용(PN-477o)과 주 1회 투여하는 주사제(PN-477sc) 두 가지 제형으로 개발되었습니다.
회사는 PN-477이 세 가지 표적 수용체 모두에서 강력한 시험관 내 활성을 보였으며, 식이 유도 비만 마우스 모델, 정상 개, 사이노몰구스 원숭이 등 다양한 동물 실험에서 견고한 전임상 개념 증명을 확인했다고 보고했습니다. 이 후보 물질은 경구 투여 시 안정적이며 세 수용체에 대해 균형 잡힌 효능을 지니도록 설계되어 체중 감량 효과를 극대화하고 부작용을 최소화하는 것을 목표로 합니다.
Protagonist는 IND 승인 준비 연구를 시작했으며 2026년 2분기에 1상 임상시험을 개시할 예정입니다. 회사는 PN-477을 주사제 최고 수준의 치료 효과와 경구 및 주사 투여 방식의 유연성을 모두 제공하는 잠재적 베스트인클래스 치료 옵션으로 자리매김하고자 합니다.
Protagonist Therapeutics (NASDAQ:PTGX) a annoncé la nomination de PN-477, un nouveau peptide agoniste triple des récepteurs GLP-1, GIP et GCG, comme candidat au développement pour le traitement de l'obésité. Ce candidat médicament se décline en formulations orale (PN-477o) et injectable (PN-477sc), conçues respectivement pour une administration quotidienne et hebdomadaire.
L'entreprise rapporte que PN-477 a démontré une puissante activité in vitro en activant les trois récepteurs ciblés et a montré une preuve de concept préclinique solide dans diverses études animales, incluant des modèles murins d'obésité induite par régime, des chiens normaux et des singes cynomolgus. Le candidat est conçu pour être stable par voie orale avec des puissances équilibrées contre les trois récepteurs, afin de maximiser les bénéfices en termes de perte de poids tout en minimisant les effets indésirables.
Protagonist a lancé des études préparatoires à l'IND et prévoit de débuter les essais cliniques de phase 1 au deuxième trimestre 2026. L'entreprise positionne PN-477 comme une option thérapeutique potentiellement best-in-class, visant à offrir une perte de poids comparable aux meilleurs traitements injectables tout en offrant la flexibilité des voies d'administration orale et injectable.
Protagonist Therapeutics (NASDAQ:PTGX) hat die Nominierung von PN-477, einem neuartigen Triple-Agonisten-Peptid für die Rezeptoren GLP-1, GIP und GCG, als Entwicklungskandidaten für die Behandlung von Fettleibigkeit bekanntgegeben. Der Wirkstoffkandidat liegt in oraler (PN-477o) und injizierbarer (PN-477sc) Form vor, die für die tägliche beziehungsweise wöchentliche Anwendung konzipiert sind.
Das Unternehmen berichtet, dass PN-477 eine starke in vitro Aktivität bei der Aktivierung aller drei Zielrezeptoren gezeigt hat und in verschiedenen präklinischen Tierversuchen, darunter diätinduziertes Fettleibigkeitsmodell bei Mäusen, normale Hunde und Cynomolgus-Affen, einen überzeugenden Proof-of-Concept erbracht hat. Der Kandidat wurde so entwickelt, dass er oral stabil ist und ausgewogene Wirkstärken gegen die drei Rezeptoren aufweist, um potenziell den Gewichtsverlust zu maximieren und Nebenwirkungen zu minimieren.
Protagonist hat IND-fähige Studien eingeleitet und plant, im zweiten Quartal 2026 mit Phase-1-Studien zu beginnen. Das Unternehmen positioniert PN-477 als potenziell best-in-class Behandlungsoption, die eine Gewichtsabnahme vergleichbar mit den besten injizierbaren Therapien bietet und gleichzeitig die Flexibilität beider Verabreichungswege, oral und injizierbar, ermöglicht.
- Novel drug candidate offering both oral (once-daily) and injectable (once-weekly) administration options
- Demonstrated potent activity in preclinical studies across multiple animal models
- Potential best-in-class treatment targeting three receptors (GLP-1, GIP, and GCG)
- Engineered for optimal balance of receptor activation and oral stability
- Phase 1 clinical trials not expected to begin until Q2 2026
- No human clinical data available yet to validate preclinical results
Insights
Protagonist advances into hot obesity market with novel oral triple-agonist peptide, targeting 2026 clinical trials with potential differentiation from current GLP-1s.
Protagonist's nomination of PN-477 represents a strategic entry into the booming obesity therapeutics market, currently dominated by injectable GLP-1 receptor agonists. What makes this candidate particularly noteworthy is its triple-agonist mechanism targeting GLP-1, GIP, and glucagon receptors simultaneously, potentially offering enhanced efficacy over single-target therapies.
The most significant competitive advantage appears to be the dual development strategy - pursuing both an oral daily formulation (PN-477o) and injectable weekly option (PN-477sc). The oral version could address a major limitation of current market-leading obesity treatments like semaglutide and tirzepatide, which are injection-only. Protagonist's approach potentially offers greater patient choice and market penetration.
Preclinical data shows activity across all three targeted receptors with a pharmacokinetic profile supporting the proposed dosing schedules. The company specifically highlights the potential for improved body composition outcomes (better fat-to-lean mass ratio) and potentially improved GI tolerability compared to existing options - both key differentiators if proven in human studies.
While promising, investors should note the relatively early stage - IND-enabling studies are ongoing with Phase 1 trials not expected until Q2 2026, putting this candidate several years behind market leaders. Nevertheless, given the projected long-term growth of the obesity market and demand for oral options, PN-477 represents a significant opportunity for Protagonist to establish itself in this therapeutic area.
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) receptors
Company will also develop a subcutaneous version, PN-477sc, as a once-weekly injection
IND-enabling studies underway, with Phase I study initiation expected in 2Q26
Webcast 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 mouse model, normal dogs, and cynomolgus monkeys. Overall, PN-477 has the right balance of potency, oral and in-vivo stability, and pharmacokinetic properties to enable parallel development both as a once-daily oral (PN-477o) and once-weekly injectable (PN-477sc) treatment options. IND enabling studies of PN-477 are underway and initiation of Phase 1 clinical studies is anticipated in the second quarter of 2026.
"While GLP-1 agonists have dominated the market thus far, there remains a broad opportunity for novel therapeutics with better body weight loss, higher ratio of fat to lean mass loss, tolerability and additional beneficial effects in obesity-related comorbidities. A triple GLP-1, GIP, GCG receptor agonist peptide that offers weight loss on par with the best injectable treatments options, as well as the optionality provided by both oral and injectable routes of administration, would be an important therapeutic breakthrough and represents another potential blockbuster drug opportunity for Protagonist," added Dr. Patel. "We look forward to moving PN-477 into first-in human clinical Phase 1 studies in the second quarter of 2026."
Conference Call and Webcast Details
The dial-in numbers for Protagonist's investor update on Monday, June 30th at 4:30 pm ET are:
US-based Investors: 1-877-407-0752
International Investors: 1-201-389-0912
Conference Call ID: 13754335
The webcast link for the event can be found here: https://viavid.webcasts.com/starthere.jsp?ei=1724439&tp_key=584cdd1e86
A replay of the presentation will be available on the Company's Investor Relations Events and Presentations webpage following the event.
About Protagonist
Protagonist Therapeutics is a discovery through late-stage development biopharmaceutical company. Two novel peptides derived from Protagonist's proprietary discovery platform are currently in advanced Phase 3 clinical development, with New Drug Application submissions to the FDA potentially in 2025. Icotrokinra (formerly, JNJ-2113) is a first-in-class investigational targeted oral peptide that selectively blocks the Interleukin-23 receptor ("IL-23R") which is licensed to J&J Innovative Medicines ("JNJ"), formerly Janssen Biotech, Inc. Following icotrokinra's joint discovery by Protagonist and JNJ scientists pursuant to the companies' IL-23R collaboration, Protagonist was primarily responsible for development of icotrokinra through Phase 1, with JNJ assuming responsibility for development in Phase 2 and beyond. Rusfertide, a mimetic of the natural hormone hepcidin, is currently in Phase 3 development for the rare blood disorder polycythemia vera (PV). Rusfertide is being co-developed and will be co-commercialized with Takeda Pharmaceuticals pursuant to a worldwide collaboration and license agreement entered in 2024 under which the Company remains primarily responsible for development through NDA filing. The Company also has a number of pre-clinical stage drug discovery programs addressing clinically and commercially validated targets, including IL-17 oral peptide antagonist PN-881, obesity triple agonist peptide PN-477, and oral hepcidin.
More information on Protagonist, its pipeline drug candidates and clinical studies can be found on the Company's website at https://www.protagonist-inc.com/.
Cautionary Note on Forward-Looking Statements
This press release contains forward-looking statements for purposes of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Forward-looking statements include statements regarding the potential benefits of PN-477, and the timing of PN-477 clinical development. In some cases, you can identify these statements by forward-looking words such as "anticipate," "believe," "may," "will," "expect," or the negative or plural of these words or similar expressions. Forward-looking statements are not guarantees of future performance and are subject to risks and uncertainties that could cause actual results and events to differ materially from those anticipated, including, but not limited to, our ability to develop and commercialize our product candidates, our ability to earn milestone payments under our collaboration agreements with Janssen and Takeda, our ability to use and expand our programs to build a pipeline of product candidates, our ability to obtain and maintain regulatory approval of our product candidates, our ability to operate in a competitive industry and compete successfully against competitors that have greater resources than we do, and our ability to obtain and adequately protect intellectual property rights for our product candidates. Additional information concerning these and other risk factors affecting our business can be found in our periodic filings with the Securities and Exchange Commission, including under the heading "Risk Factors" contained in our most recently filed periodic reports on Form 10-K and Form 10-Q filed with the Securities and Exchange Commission. Forward-looking statements are not guarantees of future performance, and our actual results of operations, financial condition and liquidity, and the development of the industry in which we operate, may differ materially from the forward-looking statements contained in this press release. Any forward-looking statements that we make in this press release speak only as of the date of this press release. We assume no obligation to update our forward-looking statements, whether as a result of new information, future events or otherwise, after the date of this press release.
Investor Relations Contact
Corey Davis, Ph.D.
LifeSci Advisors
cdavis@lifesciadvisors.com
+1 212 915 2577
Media Relations Contact
Virginia Amann
ENTENTE Network of Companies
virginiaamann@ententeinc.com
+1 833 500 0061 ext. 1
SOURCE: Protagonist Therapeutics
View the original press release on ACCESS Newswire
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