Junshi Biosciences Announces Approval for Toripalimab as First-Line Treatment for HER2-expressing Urothelial Carcinoma in China.

Junshi Biosciences announced that the sNDA for toripalimab, in combination with disitamab vedotin, as a 1st-line treatment for HER2-expressing urothelial carcinoma has been accepted by the NMPA. Toripalimab is a PD-1 inhibitor approved for the second-line and above treatment of advanced UC in China. The sNDA is based on a phase 3 clinical trial that showed toripalimab in combination with disitamab vedotin significantly improved PFS and OS compared to gemcitabine in combination with cisplatin/carboplatin. Toripalimab has a good safety profile with no new safety signals identified.

Palisade Bio, Inc. (Nasdaq: PALI) has announced compelling new data from its ongoing clinical program evaluating PALI-2108, a first-in-class, ileocolonic-targeted PDE4 inhibitor. The company reported positive topline results from its Phase 1b open-label cohort in patients with moderate-to-severe ulcerative colitis (UC), demonstrating a 100% clinical response rate with strong biomarker and histology improvements.

The 7-day, open-label Phase 1b study enrolled five patients with moderate-to-severe UC, receiving titrated BID dosing of PALI-2108 (30 mg BID). Key highlights include:

- 100% clinical response (5/5 patients) with a mean reduction of 62.8% in modified Mayo score (−4.0 point absolute change)
- One patient achieved clinical remission
- Fecal calprotectin decreased in 4/5 patients (mean 70%)
- Plasma hsCRP decreased by 15%
- Histologic improvement across multiple indices, including Nancy Index (58%), Robarts Histopathology Index (56%), and Geboes Score (36%)
- Mechanistically, colon tissue analyses confirmed PDE4 inhibition and immunomodulation, with increased tissue cAMP levels, decreased tissue lymphocytes, and decreased PDE4B expression
- RNAseq data confirmed downregulation of inflammatory, fibrotic, and CDx biomarkers from baseline to end-of-study

PALI-2108 was well tolerated, with 95% of treatment-emergent adverse events (TEAEs) rated mild and transient, and no serious adverse events (SAEs), SUSARs (suspected unexpected adverse reactions), or discontinuations.

In parallel, Palisade Bio completed a comprehensive Phase 1a study in 84 healthy volunteers, demonstrating that the PDE4 inhibitor active metabolite (PALI-0008) remained detectable in colon tissue ≥36 hours post-dose, maintaining levels near or above IC90. Steady-state trough concentrations exceeded IC90 with minimal accumulation, supporting a once-daily dose regimen of 30 mg for both UC and fibrostenotic Crohn’s disease (FSCD).

Based on these findings, Palisade Bio plans to complete a Phase 1b study in patients with fibrostenotic Crohn’s disease by the second half of 2025. The company's previously completed Phase 1a and 1b studies in ulcerative colitis, along with the upcoming FSCD study, will form the foundation for submitting a Phase 2 Investigational New Drug (IND) application and clinical protocols to the U.S. Food and Drug Administration (FDA) in the first half of 2026.

The company believes that PALI-2108's localized approach to delivering PDE4 inhibition, minimizing systemic exposure, and optimizing mucosal tissue concentration will transform the treatment landscape for autoimmune, inflammatory, and fibrotic diseases.

References:

[1] https://www.morningstar.com/news/globe-newswire/9508110/palisade-bio-reports-100-clinical-response-in-phase-1b-ulcerative-colitis-cohort-with-novel-pde4-inhibitor-pali-2108