Palisade Bio, Inc. · NASDAQ:PALI
Palisade Bio — IBD Innovate 2024
27 slides from Palisade Bio's conference presentation, April 2024
Slide 1: Advancing PALI-2108: Discovery to Strategic Positioning
palisadebio.com NASDAQ CM: PALI Advancing PALI-2108: Discovery to Strategic Positioning Cristophe Mellon (Giiant Pharma) & Mitch Jones (Palisade Bio) IBD Innovate Boston, April 2024
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: Christophe Mellon, PhD
Christophe Mellon, PhD Chief Executive Officer, Giiant Pharma 3
Slide 4: Journey to PALI-2108
Journey to PALI-2108 ORIGINALLY GT-0008 Teams at Montreal Merck Campus REPURPOSED TOWARDS GI 8+ years of development for COPD INDICATIONS Highly selective to PDE4 enzyme IP created in 2021 by making a prodrug 20x more potent than Apremilast Money raised in tranches early 2021 Unsuitable properties t
Slide 5: PALI-2108: Selectivity and Potency of its API
PALI-2108: Selectivity and Potency of its API Against a panel of 209 enzymes and receptors PALI-0008 was found to be exclusively selective for PDE4 PDEs Inhibition at 10 mM (%) PDE1A PDE3A PDE5A1 PDE6C PDE7A1 PDE8A1 PDE9A2 PDE10A1 PDE11A4 PALI-0008 0 4 0 0 0 16 1 0 0 PDE4 IC50 (nM) PDE4A1 PDE4B1 PDE
Slide 6: Concept: Precision Delivery Using Bacterial Gradient
Concept: Precision Delivery Using Bacterial Gradient We leverage connection PALI-2108 between the bacterial metabolic capabilities along Esterases the GI tract to sugar structure Glucoronidases to design prodrugs for site specific release PALI-2108 6
Slide 7: PALI-2108 Converts to PALI-0008 In Vivo, High in GI Tissues
PALI-2108 Converts to PALI-0008 In Vivo, High in GI Tissues PALI-2108, PO 5 MG/KG, MICE C57Bl/6: Plasma and Colon Levels of PALI-0008 PALI-2108 Plasma PALI-0008 levels in healthy PALI-2108 Proximal Colon mice dosed PO with PALI- PALI-2108 Distal Colon 2108. PALI-0008 is favorably distributed to the
Slide 8: Efficacy in 7-Day Colitis Model
Efficacy in 7-Day Colitis Model Cumulative Disease Activity Index (DAI) in DSS acute colitis mouse model showed that PALI-2108 at 21, 4 and 0.75 mg/kg BID as well as 1.5 mg/kg QD significantly decreased the mean DAI score compared to DSS control. Superior to Apremilast which demonstrated efficacy in
Slide 9: In Vivo Target Engagement Demonstration in Mice
In Vivo Target Engagement Demonstration in Mice PO dosing of Apremilast (150 mg/kg, and PALI-2108 (15 mg/kg, 24 h) followed by Western on colon homogenates to demonstrate resistance to heat denaturation Melt and shift curves for PDE4D of Melt and shift curves for PDE4D of animals dosed with Apremila
Slide 10: Prodrug Administration Curbs Side-Effects
Prodrug Administration Curbs Side-Effects Route of Analysed Species Compound Dose (mpk) Cmax (nM) Emesis Admin Compound PO administration of PALI- 11 prodrug PALI-2108 at 43 2108 mg/kg was well tolerated PALI- PALI- Dog PO; QD 43 28 NO while PO administration of 2108 0008 PALI-0008 resulted in PALI-
Slide 11: Mitch Jones, MD, PhD
Mitch Jones, MD, PhD Chief Medical Officer, Palisade Bio 11
Slide 12: Strategic Shift in Prioritization to Newly Licensed Assets for Treatment of Inflammatory Bowel Diseases
Strategic Shift in Prioritization to Newly Licensed Assets for Treatment of Inflammatory Bowel Diseases We entered into an exclusive worldwide licensing agreement to develop and commercialize proprietary oral prodrug therapies that act locally targeting multi-billion-dollar IBD market Company Secure
Slide 13: Our Oral IBD Development Pipeline
Our Oral IBD Development Pipeline Oral Prodrug Therapies that Act Locally at Site of Disease IND/CTA- Program Discovery Phase 1 Phase 2 Phase 3 Highlights Enabling Ongoing IND/CTA-enabling tox studies PALI-2108 Ulcerative Colitis Rapidly advancing towards IND/CTA filing in 2024 Lead optimization com
Slide 14: PDE4 is an Established Dual Acting Anti-Inflammatory and Anti-Fibrotic Target
PDE4 is an Established Dual Acting (Pleiotropic) Anti-Inflammatory and Anti-Fibrotic Target COPD (Roflumilast; AstraZeneca): Anti-fibrotic indications such as chronic obstructive pulmonary disease Psoriasis and Psoriatic Arthritis (Apremilast; Amgen): Anti- inflammatory indications validated by appr
Slide 15: PALI-2108: Our Differentiated Approach to Ulcerative Colitis
PALI-2108: Our Differentiated Approach to Ulcerative Colitis Novel PDE4 Inhibitor Pre-IND/CTA Candidate Oral Prodrug Therapies That Act Locally at Site of Disease KEY DIFFERENTIATION ✓ Oral Dosing ✓ Locally Active ✓ Limited Systemic Activity (improved safety) ✓ Superior Cytokine Blocking Profile ✓ P
Slide 16: PALI-2108: Mechanism of Action
pee OE IVERY PALI-2108: Mechanism of Action © a ty 2e > “829 =» Bacterial enzyme e PALI-2108 PALI-0008 SUPERIOR TNF-a PDE4INHIBITORPRODRUG —_—PDE4 INHIBITOR BLOCKING PROFILE . Be leering an A daa sqghOCAL ACTIVATION ° > aii? 2 _ ye we aot "2. =o rt a-® LIMITED . _ tiL-lo 5 ae eS e ] : " 4 ey <x TNF-
Slide 17: PALI-2108: Locally Active
Potential to overcome systemic PDE4 PALI-2108: Locally Active toxicities of nausea and vomiting Compelling Efficacy Demonstrated in Multiple Phase 2 Studies with Systemic PDE4 Inhibitors but with Dose Limiting Toxicity Mild-to-Moderate Active UC1 Moderate-to-Severely Active UC2 Placebo 25 mg group*
Slide 18: PALI-2108 Development Plan Through Phase 1a/b
PALI-2108 Development Plan Through Phase 1a/b Q2 Q3 Q4 Q1 Q2 Q3 Q4 H1 H2 2023 2023 2023 2024 2024 2024 2024 2025 2025 GMP Manufacturing IND/CTA-enabling Studies IND/CTA Regulatory Interactions Submission Initiation of Phase 1a/b Ph1 a/b Clinical Study First Patient In Topline Data 18
Slide 19: Precision Medicine Approach
Precision Medicine Approach Identifying Patients Likely to Respond to PDE4 ✓ Elevated express of PDE4 in chronic UC Inhibitor Therapy in UC patients correlates with disease activity by Mayo score1 TRANSCRIPTOMICS ✓ Elevated expression of inflammatory cytokines has been shown in chronic UC • Expressi
Slide 20: Thank you! Questions & Answers
Thank you! Questions & Answers 20
Slide 21: The IBD Patient Journey
ULCERATIVE COLITIS Of patients have moderate-to-severely ~40-50% active disease The IBD 70% Of patients with active disease will have active disease the next year Patient Journey 30% Of patients in remission will have active disease the next year Of patients with long-lasting UC and Patients and cli
Slide 22: Current Standard-of-Care Therapies Have Limited Effectiveness
Current Standard-of-Care Therapies Have Limited Effectiveness No Standard Regimen for Managing All IBD Patients The Approach to Treatment Needs to Be Tailored for the Individual CURRENT FACTORS THAT DETERMINE TREATMENT APPROACH TREATMENT APPROACH 5-ASA is generally first line for ulcerative colitis
Slide 23: Ulcerative Colitis Competitive Landscape
Ulcerative Colitis Competitive Landscape Most Effective Therapies Have Black Box Warning, New Therapies Are Not as Effective Placebo-Adjusted Overall Remission Route of Safety Drug Company Indication FDA Approval Clinical Remission Rate Administration Considerations Moderate-to-severely active UC wi
Slide 24: Potential Future Ulcerative Colitis Competitive Landscape
Potential Future Ulcerative Colitis Competitive Landscape UC Market is Expected to Evolve By 2028 with New Therapies We Believe PALI-2108 Has a Significant Advantage Over Current Projections and has Potential to Take Significant Market Share Placebo-Adjusted Overall Remission Route of Safety Drug Co
Slide 25: Big Pharma is Active in IBD and Spending Big Dollars for Earlier Stage Programs
Big Pharma is Active in IBD and Spending Big Dollars for Earlier Stage Programs Company Acquirer Date Lead Asset Phase at Deal MOA Upfront Total Deal Royalties Current Status Anti-TL1A Oct 2023 RVT-3101 Phase 3 Ready Mab $7.1 Billion $7.2 Billion NA Phase 3 Prep Anti-TL1A Oct 2023 TEV'574 Phase 2b M
Slide 26: Program Team
Program Team JD Finley, MT Mitch Jones, MD, PhD Joie Bernard, PhD Adarsh Patel, MS, MBA CEO CMO Sr. Director, Clinical and Assoc. Director, Technical Operations Translational Research Christophe Mellon, PhD Jon Daniels, PhD Patrick Colin, B. Pharm, PhD CMC & Medicinal Chemistry Safety & Tox & Reg (C
Slide 27: Clinical Advisory Board
Clinical Advisory Board Bruce Sands MD, MS Florian Rieder, MD Dr. Burrill B. Crohn Professor of Medicine, Icahn School Associate Staff in the Department of Gastroenterology, of Medicine at Mount Sinai and System Chief, Division Hepatology, and Nutrition, as well as an Investigator in of Gastroentero