Protagonist Therapeutics, Inc (PTGX)

Protagonist Therapeutics is a clinical-stage biopharmaceutical company that develops peptide-based new chemical entities from its proprietary peptide discovery platform. The platform engineers structurally constrained peptides designed to combine key advantages of orally delivered small molecules and injectable antibody drugs. These peptides can be designed to overcome the instability of traditional peptides and allow oral, subcutaneous, intravenous or rectal delivery. The company's programs focus on two disease areas: hematology and blood disorders, and inflammatory and immunomodulatory diseases.

The most advanced asset is rusfertide, an injectable hepcidin mimetic in development for polycythemia vera (PV) and other blood disorders. Phase 2 REVIVE results showed a higher responder rate than placebo in the randomized withdrawal portion (69.2% versus 18.5%) and a reduction in the need for phlebotomy. The Phase 2 PACIFIC and THRIVE trials are also reported. The global Phase 3 VERIFY trial in about 250 PV patients has been initiated, and a two-year rat carcinogenicity study is ongoing. In January 2024 the company agreed to license rusfertide worldwide to Takeda, subject to HSR Act waiting periods. The terms include a $300 million upfront payment, up to $330 million in milestones, royalties of 10% to 17% on ex-U.S. sales and an equal U.S. profit and loss share. The second asset, JNJ-2113 (formerly PN-235), is an oral IL-23 receptor antagonist peptide partnered with Johnson & Johnson (JNJ) under a 2017 collaboration. After a positive Phase 2b FRONTIER 1 trial in plaque psoriasis, JNJ started Phase 3 ICONIC trials in psoriasis and the Phase 2b ANTHEM-UC trial in ulcerative colitis. The company has earned $172.5 million from JNJ and remains eligible for up to about $795 million in milestones plus royalties of 6% to 10%. The wholly owned PN-943, an oral gut-restricted alpha 4 beta 7 integrin antagonist for IBD, completed a Phase 2 trial in ulcerative colitis, and no further internal resources will go to its development. Earlier programs include a preclinical oral hepcidin mimetic and an oral IL-17 peptide antagonist program announced in January 2024 for conditions such as hidradenitis suppurativa, spondyloarthritis, plaque psoriasis and psoriatic arthritis.

The target markets are rare blood disorders and immune-mediated diseases. PV is a rare myeloproliferative neoplasm marked by overproduction of red blood cells and elevated cardiovascular and thrombotic risk. Current treatments include aspirin, therapeutic phlebotomy, hydroxyurea, interferons and ruxolitinib. The company cites claims data showing that 78% of treated U.S. PV patients do not keep hematocrit below 45%, which it sees as an unmet need. For JNJ-2113, the competitive landscape includes injectable antibody drugs such as the IL-23 antibodies Stelara and Tremfya, as well as Sotyktu, Cosentyx and Taltz. The text does not describe the company's suppliers, manufacturing arrangements or headquarters.