Palisade Bio Advances PALI-2108 Into Phase II for Ulcerative Colitis and Crohn’s

Key Points

• Palisade Bio is advancing PALI-2108 into Phase II for ulcerative colitis and Crohn’s disease after Phase I showed favorable safety, intestinal tissue exposure and early clinical and endoscopic signals, though the exploratory cohorts were small.
• The company has received clearance for the ASCENTRA-UC Phase IIb trial, which plans to enroll about 204 ulcerative colitis patients, and ASCENTRA-CD, an open-label study of about 60 Crohn’s patients. Palisade expects key data from the programs during 2027 and early 2028.
• Palisade reported approximately $125 million in cash and no long-term debt, saying its existing resources should fund operations through major clinical milestones, including top-line Phase II readouts.

Palisade Bio NASDAQ: PALI said it is advancing its lead drug candidate, PALI-2108, into Phase II studies for ulcerative colitis and Crohn’s disease after completing its Phase I program.

Chief Executive Officer JD Finley said PALI-2108 is a once-daily oral phosphodiesterase 4, or PDE4, inhibitor designed as a prodrug that is bioactivated in the terminal ileum and colon. The company’s strategy is to target drug activity in intestinal tissue while seeking to avoid some tolerability limitations associated with systemic PDE4 inhibitors.

“PDE4 inhibition is a well-validated anti-inflammatory mechanism,” Finley said. “But historically, PDE4 inhibitors have been constrained in addressing IBD because of the limited therapeutic window.”

Phase I findings and development rationale

According to Palisade Bio, its Phase I work showed favorable safety and tolerability, sustained plasma drug exposure above the IC90 threshold, and distribution in ileal and colonic tissue. The company also reported activity across inflammatory and fibrotic pathways, along with early clinical and endoscopic signals in small patient cohorts.

Chief Medical Officer Mitch Jones said the Phase I program extended beyond safety and pharmacokinetic measurements, including exploratory cohorts of ulcerative colitis patients and patients with fibrostenotic Crohn’s disease.

In the ulcerative colitis cohort, Jones said all five patients achieved clinical response after seven days of treatment, while two achieved endoscopic response and remission. He said the findings were also supported by improvements in histology, inflammatory markers and pharmacodynamic measures.

In the fibrostenotic Crohn’s disease cohort, Palisade Bio reported a 47.5% mean reduction in SES-CD score after 14 days, with two of five patients achieving endoscopic response and remission. Jones emphasized that the cohorts were small and exploratory but said the signals were supported by tissue exposure and evidence of target engagement.

The company believes the prodrug design could reduce upper gastrointestinal exposure to the active PDE4 inhibitor and provide a more gradual release profile. Jones said upper-GI exposure can contribute to secretory diarrhea, while rapid changes in bloodstream concentrations may contribute to nausea and headache.

ASCENTRA-UC trial moves forward

Finley said Palisade Bio received a U.S. investigational new drug clearance in June for ASCENTRA-UC, its global Phase IIb study in moderately to severely active ulcerative colitis. The company also announced clearance from Health Canada to proceed with the study in Canada.

ASCENTRA-UC is a randomized, double-blind, placebo-controlled trial expected to enroll approximately 204 patients. Participants will be assigned equally to receive 15 milligrams of PALI-2108 once daily, 30 milligrams once daily, or placebo during a 12-week induction period.

The primary endpoint is clinical remission at week 12 using the modified Mayo score. Jones said the company expects approximately half of enrolled patients to have failed a first-line advanced therapy, enabling analysis of advanced-therapy-naive and advanced-therapy-experienced populations.

• The study is designed with approximately 90% power under assumptions of a 12.5% placebo remission rate and a 20-percentage-point treatment benefit over placebo.
• Palisade Bio has activated roughly two-thirds of its 30 planned U.S. sites.
• The global program is expected to include approximately 115 sites across North America, Eastern Europe and Western Europe.

Jones said the company remains confident in its guidance for a second-half 2027 timeline, citing site activation progress, patient screening and enrollment modeling.

Crohn’s disease program broadens

Palisade Bio also received IND clearance for ASCENTRA-CD, an open-label Phase II study in moderate to severe Crohn’s disease. The trial is expected to enroll about 60 patients.

Finley said the company elected to expand beyond fibrostenotic Crohn’s disease because its initial experience provided evidence of ileal and colonic tissue exposure, pharmacodynamic activity and early endoscopic improvement. He said moderate-to-severe Crohn’s disease represents a larger patient population and has a more established clinical and regulatory development path, while fibrostenotic disease remains a longer-term opportunity.

The ASCENTRA-CD study will use centrally read endoscopic response at week 12 as its primary objective measure, according to Jones. The company also plans to assess clinical outcomes, biomarkers, pharmacokinetics and pharmacodynamics. Finley said the open-label design could allow Palisade Bio to report data during 2027, while the company currently expects to disclose 12-week endoscopic response data in the first quarter of 2028.

Cash position

Finley initially stated that Palisade Bio had approximately $25 million in cash, then corrected the figure to approximately $125 million in cash based on the company’s June 10-Q filing. He said the company had no long-term debt and expects existing cash to fund operations through major clinical milestones, including top-line readouts from both Phase II programs.

About Palisade Bio (NASDAQ:PALI)

Palisade Bio, Inc is a clinical-stage biopharmaceutical company focused on developing therapies for gastrointestinal diseases and conditions associated with intestinal inflammation, impaired gut-barrier function and complications following surgery.

The company's lead product candidate is LB1148, an orally administered, non-absorbed pan-serine protease inhibitor. Palisade Bio is evaluating LB1148 for its potential to limit the harmful effects of digestive enzymes, reduce inflammation and support intestinal healing during the postoperative period.

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