8-K/A: Protagonist Therapeutics' Icotrokinra Shows Promise in Psoriasis and Ulcerative Colitis Trials

Protagonist Therapeutics reports positive Phase 3 results for Icotrokinra in psoriasis and Phase 2b results in ulcerative colitis, demonstrating its potential as a novel oral treatment.

Summary

• Protagonist Therapeutics announced positive topline results from the Phase 2b ANTHEM-UC study of icotrokinra in patients with ulcerative colitis.
• The study met its primary endpoint of clinical response in all icotrokinra dose groups.
• The highest dose of icotrokinra achieved a clinical response rate of 63.5% at Week 12, compared to 27.0% for placebo (p<0.001).
• 30.2% of patients treated with the highest dose of icotrokinra demonstrated clinical remission at Week 12 versus 11.1% of patients who received placebo (p<0.01).
• Clinical remission and response rates continued to improve through Week 28.
• Icotrokinra was well tolerated, with similar proportions of adverse events in the icotrokinra and placebo groups.
• Topline results from Phase 3 ICONIC-ADVANCE 1&2 studies show icotrokinra achieved co-primary endpoints and showed superiority to deucravacitinib in moderate-to-severe PsO.
• At Week 24, nearly half of patients treated with icotrokinra achieved completely clear skin (46% reached IGA 0 and 40% reached PASI 100).
• Nearly two-thirds (65%) of patients treated with once daily icotrokinra achieved an Investigators Global Assessment (IGA) score of 0/1 (clear or almost clear skin) and 50% achieved a Psoriasis Area and Severity Index (PASI) 90 response, compared to 8% and 4% receiving placebo, respectively (P<0.001 for both endpoints) at Week 16.
• Continued skin clearance improvement was reported at Week 24 with 74% of patients treated with icotrokinra achieving IGA 0/1 and 65% achieving PASI 90.
• Similar proportions of patients experienced adverse events (AEs) between icotrokinra (49%) and placebo groups (49%), with no new safety signals identified.

Sentiment

Score: 8

Explanation: The document presents positive clinical trial results for Icotrokinra in both psoriasis and ulcerative colitis, suggesting a promising future for the drug and the company. The sentiment is high due to the potential for Icotrokinra to become a leading oral treatment option.

Positives

• Icotrokinra demonstrated a statistically significant clinical response and remission in ulcerative colitis patients.
• The drug was well-tolerated in both ulcerative colitis and psoriasis trials, with adverse event rates similar to placebo.
• Icotrokinra showed superiority to deucravacitinib in psoriasis trials.
• The drug is administered orally, offering a more convenient treatment option compared to injectable biologics.
• The clinical remission and response rates in ulcerative colitis continued to improve through Week 28.

Risks

• The forward-looking statements are subject to risks and uncertainties that could cause actual results and events to differ materially from those anticipated.
• These risks include the ability to develop and commercialize product candidates, earn milestone payments, obtain regulatory approval, and compete successfully against competitors.

Future Outlook

Protagonist Therapeutics anticipates further progression of icotrokinra into more advanced clinical studies in ulcerative colitis and Crohns disease, and expects New Drug Application submissions to the FDA in 2025 for icotrokinra and rusfertide.

Management Comments

• Dinesh V. Patel, Ph.D., President and Chief Executive Officer at Protagonist, stated that icotrokinra has the potential to transform the treatment landscape in UC through its distinctive profile of efficacy, safety, tolerability, and convenience of a once-daily oral treatment.
• Dinesh V. Patel, Ph.D., President and Chief Executive Officer at Protagonist, said the new results from the superiority ICONIC-ADVANCE 1&2 studies involving head-to-head comparison with the oral therapeutic deucravacitinib, combined with the results from the ICONIC-LEAD study, reinforce icotrokinra's potential as a paradigm shifting, highly effective firstand only-in-class targeted oral IL-23 receptor antagonist for treatment of psoriasis.
• Dinesh V. Patel, Ph.D., President and Chief Executive Officer at Protagonist, stated that Icotrokinra offers a standout combination of complete skin clearance and favorable safety profile in a once-daily pill and continues to establish itself as a potential first-line systemic therapy for psoriasis.

Industry Context

The announcement positions Protagonist Therapeutics as a potential leader in the oral treatment of psoriasis and ulcerative colitis, competing with existing injectable biologics and other oral therapies. The head-to-head study against ustekinumab is particularly noteworthy, as it could establish icotrokinra as a superior option.

Comparison to Industry Standards

• Ustekinumab (Stelara) is a well-established injectable biologic used in the treatment of psoriasis and ulcerative colitis, and the ICONIC-ASCEND study will directly compare icotrokinra to this standard of care.
• Deucravacitinib (Sotyktu) is an oral TYK2 inhibitor approved for psoriasis, and icotrokinra has demonstrated superiority to this drug in clinical trials.
• Vedolizumab (Entyvio) is a biologic used in ulcerative colitis, and icotrokinra's Phase 2b results suggest it could be a competitive oral alternative.

Stakeholder Impact

• Positive results could lead to increased shareholder value.
• Successful development and commercialization of icotrokinra could provide a new treatment option for patients with psoriasis and ulcerative colitis.
• The collaboration with Johnson & Johnson and Takeda Pharmaceuticals benefits Protagonist through milestone payments and co-commercialization opportunities.

Next Steps

• Comprehensive results from the ANTHEM-UC study are being prepared for presentation at upcoming medical congresses.
• Johnson & Johnson is initiating the Phase 3 ICONIC-ASCEND study of icotrokinra versus ustekinumab.
• New Drug Application submissions to the FDA are expected in 2025 for icotrokinra and rusfertide.

Key Dates