Palisade Bio, Inc. · NASDAQ:PALI
Palisade Bio — STAR Annual Meeting 2025
18 slides from Palisade Bio's conference presentation, September 2025
Slide 1: Next-Generation Precision Therapies for Immune, Inflammatory and Fibrotic Diseases
NASDAQ: PALI palisadebio.com Next-Generation Precision Therapies for Immune, Inflammatory and Fibrotic Diseases September 2025 STAR Annual Meeting
Slide 2: Forward Looking Statements
Forward Looking Statements Statements in this presentation that are not statements of historical fact are forward-looking statements. Such forward-looking statements include, without limitation, statements regarding our research and pre-clinical and clinical development plans, expected near and long
Slide 3: PALI-2108 - Lead Program Targeting FSCD
PALI-2108 - Lead Program Targeting FSCD Advancing Toward IND Submission for Phase 2 study in H1 2026 Only PDE4 inhibitor in development targeting the terminal ileum and colon for treatment of fibrostenotic Crohn’s disease (FSCD) and ulcerative colitis (UC) Only extended release once daily PDE4 inhib
Slide 4: FSCD One of the Largest Unmet Medical Needs in IBD
FSCD One of the Largest Unmet Medical Needs in IBD Strictures are a driven by interplay of FSCD patients experience higher The current standard of care (SOC) is inflammatory and fibrotic pathways health and economic burden (1) (2) inadequate • Corticosteroids - lead to high recurrence. 4x Hospitaliz
Slide 5: PALI-2108 Designed to Bio-Activate Locally and Deliver Anti-Inflammatory and Anti-Fibrotic Effects
PALI-2108 Designed to Bio-Activate Locally and Deliver Clinically Proven Anti-Inflammatory and Anti-Fibrotic Effects of PDE4s Prodrug Form Localized Bio-Activation Targets PDE4 B/D ▪ It is an oral prodrug that bio- ▪ This raises cAMP levels, reduces enzymes activates locally in the distal inflammato
Slide 6: Completed Phase 1a/b Study with NHV and UC Patients
Completed Phase 1a/b Study with NHV and UC Patients 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 Topline Data Expected Q2 2025 Single Ascending Dose (n~40) Double-Blind Double-Blind • Primary Endpoint Si
Slide 7: Phase 1a Confirms PALI-2108 was Safe and Well Tolerated
Phase 1a Confirms PALI-2108 was Safe and Well Tolerated SAD Safety and Tolerability 15mg 50mg 150mg 250mg 450mg Active PBO Active PBO Active PBO Active PBO Active PBO Number of subjects 6 2 6 2 6 2 6 2 6 2 PALI-2108 Ph1a Findings: TEAEs, possibly 0 0 0 0 0 0 0 0 22 1 related (n) ✓ 84 patients treate
Slide 8: Phase 1 SAD/MAD PK Demonstrates Superior Exposure to Other PDE4s
Phase 1 SAD/MAD PK Demonstrates PK Characteristics and Superior Exposure to Other PDE4s • Single Ascending Dose (SAD) Dose Proportionality and Extended Half-Life Enabling • PALI-2108 (prodrug; NOT SHOWN) Daily Dosing • Tmax: ~3–4h → consistent with small intestinal dissolution (Eudragit + prodrug de
Slide 9: Phase 1 MAD Colon Tissue Pharmacokinetics
Phase 1 MAD Colon Tissue Pharmacokinetics Tissue PK 36 Hours Post Dose Demonstrates Extended- Release PK and Potential for Daily Dosing Tissue PK Observations from MAD: ✓ Colon Tissue Concentrations approached IC90 36h post dose - demonstrating therapeutic concentrations and extended-release tissue
Slide 10: Phase 1b UC Cohort Patient Disposition and Safety
Phase 1b UC Cohort Patient Disposition and Safety • Safe and Well-Tolerated: UC Patient Enrollment n=5 UC Patient • No clinically significant change in PE, vital signs, safety lab tests and EKG Cohort Details • PDE4-related TEAEs were mild and quickly resolved Active • 5 patients with moderate • Suc
Slide 11: Mechanistic and Inflammatory PD were Improved
Mechanistic and Inflammatory PD were Improved cAMP, PDE4B and TLC, CalPro and hs CRP ~71% decrease ✓ Tissue cAMP was increased in 4/5 patients (~27% mean increase) as expected due to inhibition of PDE4 enzyme ✓ Tissue lymphocytes was decreased in 4/5 (mean ~29% reduction; ~40% by individual mean app
Slide 12: Colon Tissue Histologic Scores were Improved
Colon Tissue Histologic Scores were Improved 58% decrease 56% decrease 36% decrease UC Patients UC Patients UC Patients ✓ Tissue Histology: Improvements observed in: ✓ Nancy Index was decreased ~58% ✓ Robarts Histopathology Index was decreased ~56%. ✓ Geboes Score was decreased ~36%. 12
Slide 13: Clinical Response and Remission Demonstrated by Modified Mayo Score
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
Slide 14: Key Colon Tissue Fibrosis Pathways for FSCD were Engaged
Key Colon Tissue Fibrosis Pathways for Fibrostenotic Crohn’s Disease (FSCD) were Engaged UC Patients Healthy Sum Colon Tissue Fibrosis Biomarkers (186 fibrotic gene markers) were elevated in UC patients at Baseline compared to Normal Healthy Volunteers (NHV) and reduced by the study endpoint (EOS) 1
Slide 15: Summary PALI-2108 Phase 1b UC Cohort Topline Data Summary
Summary PALI-2108 Phase 1b UC Cohort Topline Data Summary ✓Clinical Response was achieved in 100% of patients ✓Mean mMayo Score reduction of 62.8% or ~4 points ✓Clinical Remission was achieved in 40% of patients ✓Histologic improvement was achieved across multiple indices ✓Inflammatory biomarkers we
Slide 16: Sustained Tissue Concentration of PDE4 Active Across the Ileum and Colon
PALI-2108: Sustained Tissue Concentration of PDE4 active (PALI-0008) Across the Ileum and Colon Tissue Levels of Active Bioactivated PALI-2108 (PALI-0008) and Shows Drug Concentration in Ileum Ascending and Descending Colon 12 hours After Twice Daily (BID) Dosing in Dog 16
Slide 17: PALI-2108 Demonstrated Dose Response on Fibrotic Pathways in DSS Mouse Model
PALI-2108 Demonstrated Dose Response on Fibrotic Pathways In DSS Mouse Model PDE4 Inhibitor Effect PALI-2108 Demonstrated Greater Antifibrotic on Fibrotic Pathways Effect Compared to Apremilast PDE4 Inhibitor Attenuates Collagen Deposition and Reverses Activation of Mucosal Fibroblasts Normal DSS Mi
Slide 18: FSCD Phase 1b Study Design (Ongoing)
FSCD Phase 1b Study Design (Ongoing) Study Designed for First Fibrostenotic Crohn’s Disease (FSCD) Safety, Tolerability, PK and PD Open Label Period Ph1b Safety and PK Readout (n~6-12) Screening (4 weeks) (2 weeks) • Safety and tolerability: AEs, Labs, and EKGs Cohort (n~12) Open Label Phase 1b • PK