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

Palisade Bio…announced that Health Canada has cleared the Company’s Clinical Trial Application (CTA) for ASCENTRA-UC, its global Phase 2 study evaluating PALI-2108 in patients with moderately to severely active ulcerative colitis (UC) (GlobeNewswire) - "The clearance enables Palisade to advance clinical trial activities in Canada, expanding the study’s geographic reach and supporting planned enrollment....Primary efficacy results from the study’s 12-week induction period are expected in the second half of 2027....ASCENTRA-UC is a global, multicenter, randomized, double-blind, placebo-controlled, dose-ranging Phase 2 trial designed to evaluate the efficacy, safety, pharmacokinetics and pharmacodynamics of PALI-2108 in patients with moderately to severely active UC. The study is expected to enroll approximately 204 patients and will evaluate once-daily 15 mg and 30 mg doses of PALI-2108 compared with placebo."

P2 data • Trial status • Ulcerative Colitis

Palisade Bio Receives FDA Clearance of IND for PALI-2108 in Crohn’s Disease, Expanding Phase 2 Development Across IBD (GlobeNewswire) - "ASCENTRA-CD expected to enroll approximately 60 patients with moderate to severe Crohn’s disease...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 (SES-CD), based on blinded central endoscopic review....The Company anticipates first patient dosing in Q1 2027, and a primary efficacy readout in Q1 2028."

IND • New P2 trial • P2 data • Crohn's disease

Microbiome Beta-Glucuronidase Activity Does Not Limit Bioconversion or Pharmacokinetic Consistency of the Colon-Targeted PDE4 Prodrug PALI-2108 in Ulcerative Colitis (ACG 2026) - "In UC subjects, trough-region geometric CVs (~40â57%) compared favorably with apremilast variability metrics (NDA FDA)... Bioconversion of oral PALI-2108 to active PALI-0008 was found in HVs and UC subjects (Fig. 1). Baseline bacterial species and MetaCyc pathway alpha/beta diversity analyses were similar between groups."

PK/PD data • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

PALI-2108, a Next-Generation Oral PDE4 Inhibitor Prodrug, Demonstrates Localized Ileocolonic Exposure With Favorable Tolerability in IBD (ACG 2026) - "PK was consistent with delayed enteric release followed by localized ileocolonic bioactivation to PALI-0008, with delayed Tmax and prolonged exposure. Sustained colonic tissue concentrations were achieved while systemic Cmax remained attenuated. In FSCD patients, PK demonstrated favorable steady-state tissue:plasma ratios (Fig."

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

Gut-Targeted Inhibition of Phosphodiesterase 4 With PALI-2108 Demonstrates Early Endoscopic and Biomarker Improvements in Fibrostenotic Crohn's Disease: Results From a Phase 1b Study (ACG 2026) - "These first-in-indication findings support advancement of PALI-2108 in larger, controlled studies in FSCD. Figure: Table 1 Legend: BMI, body mass index; FSCD, fibrostenotic Crohnâs disease; SD, standard deviation Figure: Table 2 Legend: p < 0.05 by student t-test; cAMP, cyclic AMP; EOS, end of study; FSCD, fibrostenotic Crohnâs disease; FCAL, fecal calprotectin; SD, standard deviation; SES, simple endoscopic score"

Biomarker • P1 data • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Ulcerative Colitis

Development of Mucosal Transcriptomic Signatures to Predict Response to the Microbiome Activated Phosphodiesterase-4 (PDE-4) Inhibitor PALI-2108 in Ulcerative Colitis (ACG 2026) - "A putative PDE4/cAMP-associated transcriptomic signature stratifying UC patients by predicted therapeutic response was identified with (i) upregulation of S100A7, SERPINB3, and DEFB4A; (ii) enrichment of IL-17, NFkb, JAK-STAT, and TNF signaling; and (iii) concordance between gene- and pathwayâlevel activity (PROGENg). The model demonstrated an AUC of 0.67, with optimized gene sets achieving 100% sensitivity at 70% specificity and ~62.5% sensitivity at 90% specificity (Fig. 2)."

Chronic Obstructive Pulmonary Disease • Crohn's disease • Fibrosis • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Pulmonary Disease • Respiratory Diseases • Ulcerative Colitis • IL17A • SERPINB3

The Microbiome-Activated Phospohodiesterase (PDE)4 Inhibitor, PALI-2108 Leads to Rapid Clinical and Histologic Improvement in Moderate to Severe Ulcerative Colitis: A Phase 1a/1b Study (ACG 2026) - "In NHV, PALI-2108 demonstrated consistent delivery with sustained ileocolonic exposure across dosing regimens and controlled systemic peak concentrations exceeding the IC90 threshold. In UC, all patients achieved clinical response and a 50% reduction in endo-subscore (2 to 1) with 40% of patients achieving clinical remission. Mean mMayo score decreased by 62.8% after 7d compared to baseline (Fig."

Clinical • P1 data • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Mucositis • Ulcerative Colitis • CRP

DEVELOPMENT OF A MECHANISTICALLY ANCHORED PDE4/CAMP TRANSCRIPTOMIC BIOMARKER TO PREDICT RESPONSE TO PALI-2108 IN ULCERATIVE COLITIS (UEGW 2026) - No abstract available

Biomarker • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

PALI-2108, A NEW GI-ACTIVATED PDE4 INHIBITOR PROMOTES CLINICAL RESPONSE IN ULCERATIVE COLITIS PATIENTS WITHIN ONE WEEK OF TREATMENT (UEGW 2026) - No abstract available

Clinical • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

PALI-2108, A NOVEL, NEXT-GENERATION ORAL ONCE-DAILY PDE4 INHIBITOR EXHIBITS GUT-TARGETED DRUG EXPOSURE AND FAVORABLE SAFETY AND TOLERABILITY IN INFLAMMATORY BOWEL DISEASE (UEGW 2026) - No abstract available

Clinical • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease

GUT-TARGETED PDE4 INHIBITION WITH ONCE-DAILY PALI-2108 DEMONSTRATES EARLY CLINICAL AND BIOMARKER IMPROVEMENTS IN FIBROSTENOTIC CROHN'S DISEASE: RESULTS FROM A PHASE 1B STUDY (UEGW 2026) - No abstract available

Biomarker • Clinical • P1 data • Crohn's disease • Gastroenterology • Immunology • Inflammatory Bowel Disease

Key Takeaways from the Phase 1 Clinical Trial (GlobeNewswire) - "The Phase 1 clinical trial included five patients with UC and five patients with fibrostenotic Crohn’s disease (FSCD). In the UC cohort, 5 out of 5 patients achieved clinical response and 2 out of 5 achieved clinical remission based on Modified Mayo Score. In the FSCD cohort, PALI-2108 reduced mean SES-CD score by approximately 47.5% (a 3.8-point improvement), with 2 out of 5 patients achieving both endoscopic response and remission based on SES-CD....Additional PALI-2108 data to be presented at the American College of Gastroenterology (ACG) 2026 Annual Scientific Meeting and United European Gastroenterology (UEG) Week 2026."

P1 data • Crohn's disease • Ulcerative Colitis

Advancing PALI-2108 Into Phase 2 Development (GlobeNewswire) - "(i) Phase 2 ASCENTRA-UC: Received FDA clearance of the IND application for PALI-2108; Phase 2 UC clinical trial expected to commence in 2H 2026; Primary efficacy readout expected 2H 2027; (ii) Phase 2 ASCENTRA-CD: IND submission for the Phase 2 CD trial expected 2H 2026; Phase 2 CD clinical trial commencement targeted for 1Q 2027; Primary efficacy readout expected in early 2028."

IND • New P2 trial • P2 data • Crohn's disease • Ulcerative Colitis

Palisade Bio to Participate in the Leerink Partners Therapeutics Forum (The Manila Times) - "Management will participate in one-on-one meetings with institutional investors throughout the conference to discuss the Company's clinical development strategy, recent progress advancing PALI-2108 and upcoming milestones across its inflammatory bowel disease programs."

Clinical • Crohn's disease • Ulcerative Colitis

Palisade Bio…announced that the U.S. Food and Drug Administration (FDA) has cleared the Company’s Investigational New Drug (IND) application for PALI-2108, enabling initiation of the global Phase 2 ASCENTRA-UC clinical trial in patients with moderately to severely active ulcerative colitis (GlobeNewswire) - "The study is expected to enroll approximately 204 patients and evaluate two once-daily dose levels of PALI-2108, 15 mg and 30 mg, compared with placebo."

IND • New P2 trial • Ulcerative Colitis

Palisade Bio to Present on the Potential of PALI-2108 for Fibrostenotic Crohn’s Disease at New York Academy of Sciences Symposium (GlobeNewswire) - "Dr. Jones’ presentation...will discuss the significant unmet need associated with FSCD, the biological mechanisms underlying intestinal fibrosis and the potential role of locally bioactivated PDE4 inhibition as a novel therapeutic approach....The presentation will also highlight the scientific rationale supporting PALI-2108, Palisade’s locally bioactivated PDE4 inhibitor prodrug. In addition, Dr. Jones will discuss preclinical findings supporting PDE4 inhibition as a potential strategy for modulating key inflammatory and fibrotic pathways implicated in FSCD."

Preclinical • Crohn's disease

Anticipated Milestones (The Manila Times) - “IND submission for Phase 2 UC trial expected in 2Q 2026; IND submission for Phase 2 CD trial expected in 2H 2026; Phase 2 UC trial initiation targeted for Q3 2026; Phase 2 CD trial initiation targeted for Q1 2027.”

IND • New P2 trial • P1 data • Crohn's disease • Ulcerative Colitis

Palisade Bio reports phase 1a/b data showing colon‑targeted exposure (PharmaTimes) - "The company reported delayed ileocolonic activation, high tissue‑to‑plasma exposure and steady‑state concentrations of the active metabolite PALI‑0008 that remained above IC90 throughout the dosing interval...According to Palisade, steady‑state analyses showed pre‑dose trough concentrations of PALI‑0008 exceeded the IC90 threshold and were around 20 percent higher than single‑dose Cmax, indicating continuous target inhibition...Tissue‑to‑plasma ratios of about six‑fold supported preferential localisation of drug activity to the intestinal mucosa....Treatment with PALI‑2108 produced colon‑selective suppression of inflammatory and fibrotic pathways, including JAK–STAT, NF‑κB, TNF‑α and TGF‑β signalling."

P1 data • Ulcerative Colitis

Palisade Bio Announces Abstract Selected for Poster Presentation at Digestive Disease Week (DDW) 2026 (GlobeNewswire) - "Poster Presentation details are as follows:...Title: Gut-Targeted PDE4 Inhibition with PALI-2108 Demonstrates Rapid Clinical, Histologic and Biomarker Improvement in Ulcerative Colitis: Translational Findings from a Phase 1 Study; Session Date & Time: May 5, 2026 from 12:30 PM to 1:30 PM CDT."

P1 data • Ulcerative Colitis

Palisade Bio Reports Positive Topline Data from Phase 1b Clinical Study of PALI-2108 in Fibrostenotic Crohn’s Disease (GlobeNewswire) - "No serious adverse events (SAEs) reported...Pharmacokinetic profile supported once-daily dosing with measurable systemic and tissue exposure; patients achieved plasma drug concentrations above IC90 by the end of titration with doses as low as 20 mg daily; Tissue levels were above IC90, and increased over plasma by ~3x in ileum and ~5x in colon by Day 14...Mean fecal calprotectin (FCP) decreased by approximately 59% (268 → 110 µg/g) after 14 days of treatment...40% of patients achieved endoscopic response and 40% achieved endoscopic remission...These topline data will be presented by the Company’s President and Chief Medical Officer, Mitch Jones, MD, Ph.D., at the 4th Annual Precision Medicine in IBD Summit in Boston, MA....The full data set is expected to be presented at future leading medical conferences."

P1 data • PK/PD data • Crohn's disease

Company plans to advance PALI-2108 into a Phase 2 trial in moderate to severe Crohn’s disease, including evaluation of anti-fibrotic effects earlier in the disease course (GlobeNewswire)

New P2 trial • Crohn's disease

A Study of PALI-2108 in Healthy Volunteers, Patients With Ulcerative Colitis, and Patients With Fibrostenosing Crohn's Disease (clinicaltrials.gov) - P1 | N=6 | Active, not recruiting | Sponsor: Palisade Bio

First-in-human • New P1 trial • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Gut-Targeted PDE4 Inhibition with PALI-2108 Demonstrates Rapid Clinical, Histologic, and Biomarker Improvement in Ulcerative Colitis: Translational Findings from a Phase 1a Study (ECCO-IBD 2026) - "Reduced lymphocytes count and fecal calprotectin confirm anti-inflammatory mechanism. The gut-restricted prodrug design achieves sustained ileocolonic activation without peak-driven toxicity."

Biomarker • Clinical • First-in-human • P1 data • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Palisade Bio Appoints Global IBD Precision Medicine Leader Bram Verstockt, MD, PhD to Clinical Advisory Board (GlobeNewswire) - "Appointment strengthens Phase 2 development strategy for PALI-2108 in ulcerative colitis and fibrostenotic Crohn’s disease; Phase 2 ulcerative colitis IND submission planned for first half of 2026."

IND • New P2 trial • Crohn's disease • Ulcerative Colitis

Palisade Bio Appoints Leading Global IBD Experts, Laurent Peyrin-Biroulet, MD, PhD and David T. Rubin, MD, to Its Clinical Advisory Board (GlobeNewswire) - "Appointments strengthen Palisade Bio’s clinical strategy as PALI-2108 advances toward Phase 2 development in ulcerative colitis and fibrostenotic Crohn’s disease, with a Phase 2 UC IND submission planned for the first half of 2026."

Clinical • IND • New P2 trial • Crohn's disease • Ulcerative Colitis