Our technology is built on a novel prodrug design that enhances the pharmacology of a validated therapeutic target: Phosphodiesterase 4 (PDE4). PDE4 is a critical enzyme that regulates intracellular levels of cyclic adenosine monophosphate (cAMP), a key messenger controlling inflammation and immune response. By breaking down cAMP, PDE4 drives the production of pro-inflammatory molecules, contributing to immune, inflammatory, and fibrotic diseases.

Traditional PDE4 inhibitors have shown clinical benefit, but their use has been limited by tolerability challenges due to rapid absorption and high peak drug levels. Additionally, previous oral therapies have targeted pre-dose steady state (SS) trough IC50, requiring twice-daily (BID) dosing and characterized by short half-life (t1/2) and high maximum concentration (Cmax) values. In contrast, Palisade Bio’s PALI-2108 is a prodrug that is released slowly and locally, resulting in a longer half-life, lower Cmax, and the potential for once-daily (QD) dosing. By modifying how the active PDE4 inhibitor is delivered and absorbed, our approach provides:

• Improved pharmacokinetics – steady, sustained exposure rather than sharp peaks.
• Enhanced tolerability – reducing gastrointestinal side effects that have historically limited PDE4 therapies.
• Once-daily dosing potential – offering convenience and improved patient compliance.

This differentiated approach unlocks the full therapeutic potential of PDE4 inhibition, positioning Palisade Bio to advance safer and more effective treatments for immune, inflammatory, and fibrotic diseases.

Our innovative PDE4 inhibitor prodrug allows us to leverage a validated PDE4 target with potential to avoid systemic exposure and improve safety.

Highly Differentiated PDE4i Prodrug Improves PK and Tolerability, and Enables Daily Dosing

1. On July 9, 2025, Merck announced its plans to acquire Verona Pharma for $10B, which will close in 4Q25.
2. In addition to targeting PDE4, OHTUVAYRE also targets PDE3.