PALI-2108

PALI-2108: Targeted PDE4 Inhibition for Inflammatory Bowel Disease

Advancing Towards Two Upcoming Phase 2 Clinical Trials in Ulcerative Colitis (UC) and Crohn’s Disease (CD)

PALI-2108 is a once-daily oral PDE4 inhibitor prodrug designed to be selectively bioactivated in the ileum and colon, initiating targeted PDE4 inhibition at sites of disease while enabling systemic distribution of the active drug. It is currently being developed for the treatment of ulcerative colitis (UC) and Crohn’s disease (CD), addressing a significant unmet need for therapies that can deliver consistent and durable control of intestinal inflammation.

In a Phase 1a and two Phase 1a/b clinical studies, PALI-2108 demonstrated positive results across both UC and Fibrostenotic Crohn’s Disease (FSCD), including early clinical activity, favorable tolerability and pharmacokinetics consistent with localized activation in the lower intestine.

Positive Results in Two Phase 1b Clinical Trials

Ulcerative Colitis and Fibrostenotic Crohn’s Disease Phase 1a
Ulcerative Colitis Phase 1b Trial
Fibrostenotic Crohn’s Disease Phase 1b Trial

PALI-2108 Key Highlights

Oral Dosing Once-Daily

Preferred by patients and clinicians and an important goal for large pharma

Novel Target

Designed to target PDE4 enzymes in treating inflammatory and fibrotic bowel diseases

Gut-Activated Prodrug

Only PDE4 inhibitor prodrug being activated in the terminal ileum and colon with both high local tissue delivery and slow-release into the systemic bloodstream

Improved Tolerability

Minimizes common PDE4 inhibitor-related side effects, such as CNS and GI toxicity

Potential for Combination Therapies

Safety profile supports future oral or IV/SQ combination therapies

PALI-2108 Only Bio-Active in the GI System

Significant Unmet Need in Inflammatory Bowel Disease

Chronic condition characterized by persistent inflammation in the digestive tract in early adulthood with alternating periods of activity and remission.

A substantial proportion of patients do not achieve durable response with current first-line therapies.

Market Expected to Grow to $20B by 20312

Inflammatory Bowel Disease (IBD) is a group of chronic, immune-mediated conditions that cause persistent inflammation of the gastrointestinal tract, primarily including Ulcerative Colitis (UC) and Crohn’s disease (CD). UC involves continuous inflammation and ulceration of the colon and rectum, leading to symptoms such as abdominal pain, diarrhea and rectal bleeding. Crohn’s disease (CD) is characterized by transmural inflammation that can affect any part of the gastrointestinal tract and may lead to complications such as fibrosis, strictures and obstruction, resulting in symptoms including abdominal pain, cramping and bloating. Together, these conditions highlight the need for precision therapies that address both inflammatory and fibrotic pathways in IBD.

Current IBD Market3,4

Ulcerative Colitis

1.95 Million Cases

$7.7 Billion Market

Crohn’s Disease

1.63 Million Cases

$8 Billion Market

  1. Kappelman MD, Moore KR, Allen JK, Cook SF. Recent trends in the prevalence of Crohn’s disease and ulcerative colitis in a commercially insured US population NIH external link. Digestive Diseases and Sciences. 2013;58(2):519–525. doi:10.1007/s10620-012-2371-5
  2. Global Data
  3. Centers for Disease Control and Prevention; Inflammatory Bowel Disease
  4. United European Gastroenterology

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