PALI-2108: Completed Phase 1b Clinical Trial in Ulcerative Colitis

Demonstrated Positive Results in Phase 1b Trial in
Ulcerative Colitis

Double-Blind, Placebo-Controlled, Safety, Tolerability, PK and PD Study of PALI-2108 in NHV and Open-Label Study of a Patient Cohort with UC

Phase 1b UC Cohort Patient Disposition and Safety

  • Safe and Well-Tolerated:
      • No clinically significant change in PE, vital signs, safety lab tests and EKG
      • PDE4-related TEAEs were mild and quickly resolved
  • Successful Titration Strategy:
      • Using a 5-day dose titration regimen led to good tolerability
      • Few TEAEs by end of titration related to Cmax and BID dosing
  • Time-Limited Adverse Events:
      • TEAEs occurred within 2-3 days of treatment, with reduction in frequency and severity over time
  • Extended-Release PK:
      • PK suggests daily dosing and lower initial titration expected to achieve plasma and tissue IC50/90 goals with excellent Day 7 tolerability

Mechanistic and Inflammatory PD Were Improved cAMP, PDE4B and TLC, CalPro and hs CRP

Tissue cAMP was increased in 4/5 patients (~27% individual mean increase) as expected due to inhibition of PDE4 enzyme

Tissue lymphocytes was decreased in 4/4 (mean ~29% reduction; ~40% by individual mean approach)1

Tissue PDE4B was decreased in 5/5 patients (mean ~71% reduction)

Fecal calprotectin was decreased in 4/5 patients by a mean of ~70.3%

hsCRP was decreased by a mean of ~15.2%

Colon Tissue Histologic Scores Were Improved

Tissue Histology Improvements Observed in:

  • Nancy Index was decreased ~58%
  • Robarts Histopathology Index was decreased ~56%
  • Geboes Score was decreased ~36%

Clinical Response and Remission Was Demonstrated by Modified Mayo Score

  • Modified Mayo Score was reduced in 5/5 patients with mean absolute reduction of 62.8% from baseline

  • Clinical Response was achieved in 5/5 (100%) of patients (≥30% or ≥3-point drop in modified Mayo score (with rectal bleeding subscore of 0 or 1)

  • Clinical Remission was achieved in 2/5 (40%) of patients

Clinical Trials: NCT06663605

PALI-2108 Overview

Ulcerative Colitis & Fibrostenotic Crohn’s Disease: Completed PALI-2108 Phase 1a Clinical Trial

Fibrostenotic Crohn’s Disease: Completed PALI-2108 Phase 1b Clinical Trial