Ayutara ...
Lead Candidate

PALI-2108

First-in-class oral PDE4 prodrug with enhanced gastrointestinal safety and superior anti-inflammatory efficacy.

Molecular Innovation

PALI-2108 is a novel prodrug designed to overcome the dose-limiting GI toxicity of traditional PDE4 inhibitors while maintaining potent anti-inflammatory activity.

  • 95% reduction in emetic response vs. apremilast
  • 3x higher therapeutic index in preclinical models
  • Oral bioavailability: 87%
PALI-2108 Molecule
Prodrug Activation

Mechanism of Action

Precision activation in inflamed tissue minimizes systemic exposure

1
Oral Administration

PALI-2108 is absorbed intact in the GI tract with minimal local irritation.

2
Tissue-Specific Activation

Enzymatic cleavage in inflamed tissues releases active metabolite.

3
PDE4 Inhibition

Potent suppression of pro-inflammatory cytokines (TNF-α, IL-17, IL-23).

Superior Safety Profile

No nausea/vomiting in Phase I (n=48)
Zero CNS events (headache, depression)
Once-daily dosing with food
Safety

Clinical Development Timeline

Phase I Complete

Safety established in 48 healthy volunteers

Phase IIa Initiated

Psoriasis efficacy study (n=120) – Q3 2025

Phase IIb Planned

Ulcerative colitis – Q1 2026

Preclinical & Phase I Data

87%

Bioavailability

95%

GI Safety Improvement

3.2x

Therapeutic Index

Scientific Publications

Publication
Nature Medicine

2025

Tissue-specific PDE4 inhibition via prodrug activation

Publication
J. Med. Chem.

2024

Design and synthesis of PALI-2108

Publication
Clinical Trials

Ongoing

Phase IIa psoriasis study protocol

Future Indications

Expanding beyond dermatology into high-unmet need inflammatory diseases

IBD

Ulcerative Colitis, Crohn's

Psoriatic Arthritis

Joint + Skin Efficacy

Neuroinflammation

Multiple Sclerosis

Pediatric IBD

Age 6+