FDA Clears Palisade Bio IND for PALI-2108 in Crohn's Disease, Opening Phase 2 ASCENTRA-CD Trial
核心洞察
Palisade Bio received FDA clearance of its IND for PALI-2108, allowing initiation of the Phase 2 ASCENTRA-CD trial in moderate to severe Crohn's disease (搜索).
ASCENTRA-CD is an open-label, single-arm study expected to enroll about 60 adults, with first patient dosing targeted for Q1 2027.
The primary endpoint is endoscopic response at Week 12, defined as at least a 50% reduction in SES-CD under blinded central review, with readout targeted for Q1 2028.
Palisade Bio has received clearance from the U.S. Food and Drug Administration for its Investigational New Drug application for PALI-2108, enabling the company to begin the Phase 2 ASCENTRA-CD trial in patients with moderate to severe Crohn's disease (搜索). The Denver-based clinical-stage company announced the clearance on Sept. 22, 2026.
The clearance extends Palisade's Phase 2 development program for PALI-2108 across both major forms of inflammatory bowel disease, adding Crohn's disease (搜索) to an existing ulcerative colitis (搜索) program.
"FDA clearance of the ASCENTRA-CD IND marks another significant milestone for PALI-2108 and meaningfully expands our Phase 2 development program across inflammatory bowel disease," said Mitch Jones, M.D., Ph.D., president and chief medical officer of Palisade Bio. "Crohn's disease (搜索) remains a progressive condition where many patients experience inadequate response or loss of response to existing therapies. We believe PALI-2108's differentiated prodrug design, once-daily oral dosing and targeted activation within the ileum and colon provide a compelling foundation for development in this population."
Trial Design and Endpoints
ASCENTRA-CD is a multicenter, open-label, single-arm Phase 2 study designed to evaluate the efficacy, safety, pharmacokinetics and pharmacodynamics of PALI-2108 in approximately 60 adults with moderate to severe Crohn's disease (搜索). Patients will undergo a 14-day dose titration to a target dose of PALI-2108 30 mg administered orally once daily. The study comprises a 12-week induction phase followed by a 36-week maintenance phase.
The primary endpoint is endoscopic response at Week 12, defined as at least a 50% reduction from baseline in the Simple Endoscopic Score for Crohn's Disease (搜索) (SES-CD), assessed through blinded central endoscopic review. Key secondary endpoints at Week 12 include clinical remission, endoscopic remission, PRO-2 remission, a patient-reported outcome covering abdominal pain and stool frequency, clinical response, and combined clinical remission and endoscopic response. Additional maintenance assessments will continue through Week 48.
Palisade anticipates first patient dosing in the first quarter of 2027 and a primary efficacy readout in the first quarter of 2028.
Prior Clinical Experience
PALI-2108 has already been evaluated in patients with fibrostenotic Crohn's disease (搜索), providing direct clinical experience with ileal and colonic tissue exposure, PDE4 (搜索) target engagement and endoscopic activity. ASCENTRA-CD is designed to extend those findings into a broader moderate to severe Crohn's disease population using centrally read endoscopic response at Week 12 as the primary endpoint.
"Importantly, we enter Phase 2 with direct clinical experience demonstrating favorable tolerability, targeted tissue exposure, PDE4 (搜索) target engagement and encouraging early biological and endoscopic activity," Jones said.
Prodrug Mechanism and Development Rationale
Crohn's disease (搜索) is a chronic, progressive inflammatory condition in which persistent or recurrent inflammation can lead to irreversible tissue remodeling, fibrosis and bowel disability.
PALI-2108 is a once-daily oral PDE4 (搜索) inhibitor prodrug designed for targeted activation in the terminal ileum and colon. Following oral administration, the drug is activated in the terminal ileum and colon, generating high local intestinal exposure while also supporting sustained systemic exposure and a differentiated pharmacokinetic profile. Across Phase 1 studies in healthy volunteers and in patients with ulcerative colitis (搜索) and fibrostenotic Crohn's disease (搜索), PALI-2108 demonstrated favorable safety and tolerability, differentiated pharmacokinetics and sustained PDE4 inhibition above IC90, supporting advancement into Phase 2 development.
Palisade notes that despite the availability of multiple biologic and small-molecule therapies, many patients with ulcerative colitis (搜索) and Crohn's disease (搜索) do not achieve durable remission, lose response over time, or discontinue treatment because of safety or tolerability limitations. The company believes PALI-2108 has the potential to address these limitations through once-daily oral dosing, targeted lower-intestinal bioactivation and broad PDE4 (搜索)-mediated anti-inflammatory activity.
With ASCENTRA-UC in ulcerative colitis (搜索) and ASCENTRA-CD in Crohn's disease (搜索), Palisade is advancing a clinical development program for PALI-2108 across the two major forms of inflammatory bowel disease, designed to generate a broader dataset on the efficacy, safety and pharmacology of the candidate.