PALI-2108 / GiiAnt Pharma, Palisade Bio - LARVOL DELTA

Palisade Bio Appoints Sharon Skare as Vice President, Global Head of Clinical Operations (The Manila Times) - "Her extensive experience leading global clinical operations in IBD and her proven success guiding programs through pivotal phases and inspections will be invaluable as we advance PALI-2108 into our planned Phase 2 studies."

New P2 trial • Inflammatory Bowel Disease

Palisade Bio Announces First Patients Dosed in Phase 1b Study of Oral First-In-Class PDE4 Inhibitor Prodrug, PALI-2108, for the Treatment of Fibrostenotic Crohn’s Disease (FSCD) (GlobeNewswire) - "The open-label, exploratory Phase 1b study will enroll approximately 6 to 12 patients with FSCD....Topline safety, PK, and PD data anticipated in Q1 2026....Data from this study, together with results from the Phase 1a/1b ulcerative colitis (UC) program, are expected to support Phase 2 Investigational New Drug (IND) submissions to the U.S. Food and Drug Administration (FDA) in the first half of 2026."

IND • P1 data • Trial status • Crohn's disease

Palisade Bio continues to advance the development of PALI-2108 in its Phase 1b FSCD study with patient dosing expected to commence in H2 2025 and topline data expected in Q1 2026 (GlobeNewswire) - "Data from the FSCD Phase 1b, together with results from Palisade’s completed Phase 1a/1b trials in UC, will support the Company’s planned Phase 2 IND submission to the U.S. Food and Drug Administration (FDA) in the first half of 2026."

IND • New P1 trial • Crohn's disease • Ulcerative Colitis

Palisade Bio Granted Canadian Patent Covering Composition of Lead Product Candidate PALI-2108 (GlobeNewswire) - "The patent covers the composition of PALI-2108, the Company’s orally administered, first-in-class, ileocolonic-targeted PDE4 B/D inhibitor in development for the treatment of FSCD and UC....The patent provides composition-of-matter protection for PALI-2108 through May 28, 2041."

Patent • Crohn's disease • Ulcerative Colitis

Palisade Bio Announces Closing of Upsized $138 Million Public Offering of Common Stock and Including Full Exercise of Over-Allotment Option - "Proceeds to support upcoming Phase 2 clinical development program for PALI-2108 in Ulcerative Colitis."

Financing • New P2 trial • Ulcerative Colitis

Palisade Bio Reports Positive PALI-2108 Phase 1b Clinical Data (GlobeNewswire) - "PALI-2108 demonstrated favorable safety, with no serious adverse events, lab abnormalities, or EKG concerns. Phase 1b data demonstrated 100% clinical response and promising signals regarding the efficacy of PALI-2108 in ulcerative colitis (UC) using FDA-defined endpoints....Patient dosing in the Phase 1b FSCD study is expected to begin in 2H 2025; Phase 2 IND submissions anticipated in 1H 2026."

IND • New P1 trial • P1 data • Crohn's disease • Ulcerative Colitis

Palisade Bio Receives Health Canada Clearance for Phase 1b Trial of PALI-2108 in Fibrostenotic Crohn’s Disease (FSCD) (GlobeNewswire) - "Dosing is expected to begin in the second half of 2025, with topline safety, PK, and PD readouts anticipated in the first quarter of 2026....Continued progress toward Phase 2 IND submissions in Q1 2026."

New trial • P1 data • Crohn's disease

Phase 1 Study Evaluating PALI-2108 in Healthy Volunteers and Ulcerative Colitis Patients. (clinicaltrials.gov) - P1 | N=89 | Completed | Sponsor: Palisade Bio | Recruiting ➔ Completed

Trial completion • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Palisade Bio Receives Notice of Allowance for Composition of Matter Patent Covering Lead Product Candidate PALI-2108 in China (GlobeNewswire) - "Palisade Bio...announced that the China National Intellectual Property Administration has issued a Notice of Allowance for a patent covering PALI-2108, the Company’s novel, locally-activated, terminal ileum and colon-targeted phosphodiesterase-4 B/D (PDE4 B/D) inhibitor being developed for fibrostenotic Crohn’s disease (FSCD) and moderate to severe ulcerative colitis (UC). Once issued, the allowed patent titled, 'Gut Microbiota-Activated PDE4 Inhibitor Prodrug,' will cover claims on the composition of matter for PALI-2108 in China with a base patent term currently extending into 2045, subject to extension to account for time required to fulfill requirements for regulatory approval....'We remain highly confident in the potential of PALI-2108 and are diligently executing on multiple near-term clinical milestones and expected data readouts in the next 12-18 months'."

Clinical data • Patent • Crohn's disease • Ulcerative Colitis

Palisade Bio Reports Positive Phase 1a Results for PALI-2108, a First-in-Class Terminal Ileum and Colon-Targeted PDE4 B/D Inhibitor for Fibrostenotic Crohn’s Disease and Ulcerative Colitis (GlobeNewswire) - P1 | N=90 | NCT06663605 | Sponsor: Palisade Bio | "No serious adverse events (SAEs) or laboratory/EKG-related adverse events were observed across SAD, MAD and FE cohorts; In the SAD study (15–450 mg), only mild and reversible treatment-emergent AEs (TEAEs) occurred, limited to the highest dose (450 mg); MAD cohorts (15, 30, and 50 mg BID over 7 days, as well as 30 mg titrated over 7 days) showed mostly minor TEAEs and most often at higher doses, with a moderate event at 50 mg BID leading to withdrawal; PK analysis confirmed the delayed-release, terminal ileum-targeted and colon-targeted profile of PALI-2108....Based on these results, Palisade Bio plans to initiate an additional safety and tolerability and PK/PD exploration Phase 1b cohort in FSCD."

P1 data • Trial status • Crohn's disease • Ulcerative Colitis

PALI-2108, A COLON-SPECIFIC PDE4 INHIBITOR PRODRUG, IS BIOACTIVATED IN THE COLON AND REDUCES COLON TISSUE PDE4B IN A DOSE-DEPENDENT MANNER, INCREASING C-AMP AND SUPPRESSING TNF-Α IN A MOUSE MODEL OF COLITIS (DDW 2025) - "Interestingly the elevation of cAMP levels leads to a reduction of cytokine TNF-α levels close to normal levels associated with reduced levels of inflammation in the PALI-2108 treatment cohorts, Cyclosporin A or apremilast treatment did not lower TNFa levels as much as PALI-2108 treatment (see Figure 2)... PALI-2108 is a colon-specific PDE4 inhibitor for the treatment of UC and other inflammatory bowel diseases (IBD). By preventing the degradation of intracellular cAMP, PALI-2108 modulates downstream pro-inflammatory factors and promotes anti-inflammatory cytokines within the lamina propria. Our preclinical data demonstrate that PALI-2108 effectively reduces colitis symptoms in a dose-dependent manner, supporting its potential as a viable alternative for treating UC."

Preclinical • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Ulcerative Colitis • TNFA

A BIOINFORMATIC APPROACH TO PALI-2108 TREATMENT IN ULCERATIVE COLITIS REVEALS THE POTENTIAL FOR ANTI-FIBROTIC EFFICACY WITH LOCAL PDE4 INHIBITION IN INTESTINAL FIBROSIS (DDW 2025) - " We identified cAMP-regulated signatures that demonstrated ~100% sensitivity and 70% specificity for predicting infliximab response in UC patients in silico...Fig 2: Fibrotic Pathway Expression Score for cohorts treated with, apremilast and PALI-2108 in a DSS mouse model of colitis... Our findings suggest that cAMP-regulated drivers of inflammation are activated in both UC and fibrostenotic CD. Therapy leading to a reduction of cAMP regulated inflammation could offer new treatment options for patients. PALI-2108's potential to engage antifibrotic pathways may provide a novel therapy to treat fibrostenotic CD."

Clinical • Crohn's disease • Fibrosis • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Palisade Bio Presents Positive Preclinical Data Highlighting Potential of PALI-2108 as a Promising Colon-Specific PDE4 Inhibitor for the Treatment of Ulcerative Colitis and Other Inflammatory Bowel Diseases (The Manila Times) - "Palisade Bio, Inc...today announced the presentation of positive preclinical data from PALI-2108, an orally administered, colon-specific phosphodiesterase-4 (PDE4) inhibitor prodrug in development for patients with ulcerative colitis (UC)....We continue to make encouraging progress in our ongoing Phase 1a/b study of PALI-2108 in UC and expect to report topline data from the completed Phase 1a portion of the study by the end of May 2025....PALI-2108 treatment significantly improved clinical parameters of colitis, including the DAI, body weight, and colon length in a dose-dependent manner. PALI-2108 administration resulted in a marked dose-dependent reduction of PDE4B expression in colon tissues, with higher cAMP levels and a notable suppression of TNF-α compared to standard treatments like cyclosporine A and apremilast."

P1 data • Preclinical • Inflammatory Bowel Disease • Ulcerative Colitis

Palisade Bio Completes Dosing in Phase 1a Portion of Ongoing Phase 1a/b Study of PALI-2108 (GlobeNewswire) - "Palisade Bio, Inc...today announced the completion of enrollment and dosing in all five Phase 1a SAD cohorts, all four MAD cohorts, and the food effects crossover in the Phase 1a portion of its ongoing Phase 1a/b study of PALI-2108 for the treatment of Ulcerative Colitis (UC)....Preliminary results show no SAEs and no TEAEs related to laboratory values or EKGs to date. The majority of observed TEAEs were considered mild, with only a single withdrawal in the highest 50 mg twice-daily dosage (BID) MAD cohort. Several of the MAD cohorts, ranging from 15 mg BID to 30 mg BID, were completed within the expected therapeutic dose range, again showing no SAEs or TEAEs related to laboratory values or EKGs....The Company is on track to report topline data from the Phase 1a portion of the study by the end of May 2025."

P1 data • Trial status • Ulcerative Colitis

Palisade Bio Commences Dosing in First Ulcerative Colitis Patient Cohort in Ongoing Phase 1a/b Study of PALI-2108 (GlobeNewswire) - "Palisade Bio...provided an update on its ongoing Phase 1a/b study of PALI-2108 for the treatment of Ulcerative Colitis (UC). The Company has commenced dosing of the first UC patient in the final cohort of its Phase 1a/b study of PALI-2108. In addition to completing the five previous Phase 1a SAD cohorts, the first three of four MAD cohorts have now been completed. Importantly, there have been no SAEs and no TEAEs related to laboratory values or EKGs. The majority of observed TEAEs were considered mild, with a single withdrawal at the highest MAD dose level....'We look forward to further evaluations, and we remain on track to report topline data in the first half of 2025'."

P1 data • Trial status • Ulcerative Colitis

Palisade Bio Announces Two Abstracts Selected to be Showcased as Poster of Distinction and Poster Presentation at Leading GI Forum, Digestive Disease Week (DDW) 2025 (GlobeNewswire) - "Palisade Bio, Inc...today announced that it has been selected to present data from its lead program PALI-2108 for the treatment of ulcerative colitis at Digestive Disease Week (DDW) 2025 being held May 3–6, in San Diego, California."

Preclinical • Ulcerative Colitis

Palisade Bio Participates in Virtual Investor “What This Means” Segment (Palisade Bio Press Release) - "Palisade Bio, Inc....announced the release of a Virtual Investor 'What This Means' segment....As part of this segment, Dr. Heyer discussed the Company’s positive preclinical data for its lead product candidate, PALI-2108, which was recently presented at the 2025 Crohn’s and Colitis Congress and what this means for Palisade’s UC development program."

Preclinical • Ulcerative Colitis

Palisade Bio, Inc. Announces Receipt of Cash Proceeds from Canada’s SR&ED Tax Incentive Program for Reimbursement of Development Costs of PALI-2108 for Treatment of Ulcerative Colitis (UC) (GlobeNewswire) - "Palisade Bio, Inc...today announced the receipt of CAD$1.39 million Canadian SR&ED credits for reimbursement of prior pre-clinical costs for PALI-2108 incurred under the company’s joint development plan with Giiant. 'This non-dilutive funding, which resulted from our pre-clinical studies previously conducted in Montreal under our co-development agreement with Giiant, bolsters our efforts to potentially bring a solution to patients,'...'We are pleased with the continued progress made with our PALI-2108 program and look forward to reporting topline data in the first half of 2025 from our ongoing Phase 1a/b study.'"

Financing • P1 data • Ulcerative Colitis

Palisade Bio Presents Positive Preclinical Data of PALI-2108 for the Treatment of Ulcerative Colitis (GlobeNewswire) - "PALI-2108 reduced colitis symptoms in mice without causing CNS toxicity, suggesting it could be a novel treatment for UC; It effectively converts to the active PDE4 inhibitor, PALI-0008, in the colon following oral administration in mice, dogs, and humans; PALI-2108 showed superior potency and target engagement in preclinical studies compared to other PDE4 inhibitors; It demonstrated dose-dependent efficacy in a mouse UC model, outperforming standard treatments; No systemic safety issues were observed in mice, dogs, or monkeys; PK modeling supports twice-daily dosing during induction and once-daily during maintenance, leveraging the drug’s extended-release properties."

Preclinical • Ulcerative Colitis

PALI-2108, A COLON SPECIFC PDE4B INHIBITOR PRODRUG IS ACTIVATED IN THE COLON AND REDUCES ULCERATIVE COLITIS SYMPTOMS IN AN ACUTE COLITIS DSS MOUSE MODEL (CCCongress 2025) - "Here we demonstrated the effectiveness of PALI-2108 in reducing colitis symptoms in this standard colitis mouse model.Better-tolerated oral PDE4 inhibitors remain an unmet need in IBD and we show that PALI-2108 is a colon specific PDE4 inhibitor that reduces colitis symptoms in the DSS mouse model in a dose-dependent manner in the absence of CNS toxicity seen in systemic exposure with PDE4 inhibitors. This should present a novel alternative for UC patients and we have initiated a phase 1 study to test the safety of PALI-2108 in healthy volunteers and Ulcerative Colitis patients."

Preclinical • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Ulcerative Colitis

Palisade Bio Selected for Poster Presentation at the 2025 Crohn’s & Colitis Congress (GlobeNewswire) - "Palisade Bio, Inc...today announced that its abstract has been accepted for poster presentation at the Crohn’s & Colitis Congress being held February 6-8, 2025 in San Francisco, CA."

Preclinical • Ulcerative Colitis

Palisade Bio Completes All Five SAD Cohorts and Advances to MAD Cohorts of Phase 1a/b Study of PALI-2108 for Treatment of Ulcerative Colitis (GlobeNewswire) - P1 | N=90 | NCT06663605 | Sponsor: Palisade Bio | "Preliminary data from the SAD portion of the study, which evaluated doses ranging from 15 mg to 450 mg of PALI-2108, support that the drug was well-tolerated across all dose levels. Importantly, there were no treatment-related dose reductions, serious adverse events (SAEs), or treatment-related laboratory abnormalities observed. Treatment-emergent adverse events (TEAEs) were mild and occurred only at the highest dose of 450 mg. Importantly, there were no EKG abnormalities or other serious safety concerns, underscoring the favorable safety profile of PALI-2108...'The preliminary data from the SAD cohorts have reinforced our confidence in PALI-2108’s safety profile, and we remain on track to report topline data in the first half of 2025.'"

P1 data • Ulcerative Colitis

Palisade Bio Announces Preliminary Data from Phase 1 Clinical Study of PALI-2108 for the Treatment of Moderate-to-Severe Ulcerative Colitis Appears to be Safe and Well Tolerated in Treated Subjects (GlobeNewswire) - P1 | N=90 | NCT06663605 | Sponsor: Palisade Bio | "Palisade Bio, Inc...announced preliminary results from its first three single ascending dose (SAD) cohorts in its ongoing Phase 1 human clinical study for PALI-2108 for the treatment of Ulcerative Colitis (UC)....Preliminary results appear to indicate that PALI-2108 was safe and well tolerated in the first three cohorts (n=24; 6:2 active to placebo) at 15mg, 50mg, and 150mg, with no treatment related dose reductions, no Treatment Related Adverse Events (TRAEs), no Serious Adverse Events (SAEs), and no treatment related lab abnormalities in any subject. Preliminary PK data from the first cohorts demonstrated delayed release of the PDE4 inhibitor active suggesting PALI-2108 is performing as designed with colonic bioactivation....The Company is on track to report topline data from this study in the first half of 2025."

P1 data • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Colonic Bioactivation and Potent TNFa Inhibition of PALI-2108 in Human ex-vivo Studies: A Promising PDE4 Inhibitor Prodrug for the Oral Treatment of Ulcerative Colitis (ACG 2024) - "Approved PDE4 inhibitors include roflumilast for COPD and apremilast for psoriasis... We demonstrated effective intestinal hydrolysis of PALI-2108 prodrug into PALI-0008 using routine stool samples from 6 healthy patients and 6 patients with UC. PALI-2108 was spiked into stool homogenate (100 μM) and homogenate was subsequently incubated for 24 hours. Concentrations were measured and the prodrug-to-drug conversion percentage at 24 hours was a mean of 90.1% across samples."

Preclinical • Chronic Obstructive Pulmonary Disease • Dermatology • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Pain • Psoriasis • Respiratory Diseases • Ulcerative Colitis

Palisade Bio Reports Third Quarter 2024 Financial Results and Outlines Key Accomplishments and Next Steps to Advance Lead Program PALI-2108 (GlobeNewswire) - "Upcoming Target Milestones: Phase 1 topline data expected in the first half of 2025; and Initiate Phase 1b/2a in the second half of 2025."

New P1/2 trial • P1 data • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis