Palisade Bio at Stifel forum: pde4 bet advances into phase 2

Palisade Bio (PALI) showcased its clinical strategy during the Stifel 2026 Virtual Immunology and Inflammation Forum, focusing on PALI-2108, a once-daily oral PDE4 inhibitor prodrug for inflammatory and fibrotic diseases. The company highlighted early data supporting the approach, but acknowledged the typical risks associated with a clinical-stage biotech, including small Phase I numbers, the need for efficacy confirmation in larger studies, and prolonged waiting periods for readouts.

PALI-2108 is designed to deliver PDE4 inhibition directly to the distal ileum and colon, potentially avoiding tolerability issues that have limited the class. Phase I data demonstrated clinical activity in ulcerative colitis (UC) and fibrostenotic Crohn’s disease, with 5 of 5 patients responding in the UC cohort and a 47.5% mean SES-CD reduction in the Crohn’s cohort. Palisade Bio has initiated two Phase II studies: ASCENTRA-UC in UC and ASCENTRA-CD in Crohn’s disease.

As of June 2024, Palisade Bio had $125 million in cash with no long-term debt, and expects the cash to fund major milestones in both programs. The company aims to establish PALI-2108 as a monotherapy with meaningful efficacy and a differentiated safety profile. PALI-2108 is a prodrug that activates locally in the terminal ileum and colon, minimizing exposure in the upper gastrointestinal tract and reducing side effects associated with PDE4 inhibitors.

Chief Medical Officer Mitch Jones explained that the drug's design helps avoid side effects such as nausea, vomiting, diarrhea, and headache often seen with systemic PDE4 inhibitors. He pointed out the challenge with PDE4 drugs, citing apremilast and afamelanotide as examples. Jones highlighted that Palisade Bio's prodrug approach eliminates direct exposure to upper GI tissues and the resulting secretory diarrhea.

Phase I trials produced early signals of both activity and tolerability, with five UC patients achieving clinical responses after 7 days on 30 mg twice daily, two experiencing endoscopic response and remission. In fibrostenotic Crohn’s disease, five patients treated with 20 to 30 mg once daily showed a 47.5% mean SES-CD score reduction, with two patients achieving endoscopic response and remission.

The Phase I program included single-dose and multiple-dose testing up to 100 mg a day (50 mg twice daily), showing pharmacologically relevant exposure throughout the dosing interval without typical PDE4 adverse events.