Protagonist Therapeutics (PTGX) Status Update summary

Nomination and Pipeline Overview

• PN-477, a novel triple agonist peptide targeting GLP-1, GIP, and GCG receptors, is nominated for obesity treatment with both once-daily oral and once-weekly subcutaneous formulations, maximizing patient and physician flexibility.

• The pipeline includes additional programs in hematology and immunology, with advanced Phase 3 assets partnered with J&J and Takeda, and preclinical programs targeting IL-17 and oral hepcidin pathways.

Preclinical Data and Differentiation

• PN-477 demonstrates high potency, oral stability, and robust activity in obesity and glycemic control models, outperforming comparators like semaglutide, tirzepatide, and retatrutide in vitro.

• In DIO mouse models, oral PN-4770 achieved up to 50% body weight loss, with subcutaneous PN-477sc matching retatrutide's efficacy; preferential fat mass loss and improved glycemic control were observed.

• Significant and sustained weight loss was seen in monkeys and dogs, with no GI tolerability issues in non-rodent models, supporting both oral and injectable dosing.

Clinical Development and Strategy

• IND-enabling studies for PN-477 are underway, with Phase 1 clinical trials planned for the second half of 2025 or Q2 2026.

• Both oral and subcutaneous formulations will be developed in parallel, using the same chemical entity for manufacturing efficiency and scalability.

• The company maintains a strong cash position, with runway through at least the end of 2028, and is open to strategic partnerships but can advance PN-477 through phase 2 proof of concept independently.