Palisade Bio (NASDAQ:PALI) said it generated encouraging safety, pharmacokinetic and early efficacy signals from an open-label Phase 1b study of PALI-2108 in fibrostenotic Crohn’s disease, a difficult-to-treat population where patients often progress from inflammation to structural fibrosis and may ultimately require surgical intervention.
On the company’s conference call, Chief Executive Officer JD Finley said the two-week readout was “an important milestone” and supported the company’s view that PALI-2108 could be a “differentiated next-generation therapy” designed to address both inflammation and fibrosis. The trial’s primary objective was safety and tolerability, which Finley said established “a strong foundation to move into longer duration studies.”
Phase 1b fibrostenotic Crohn’s design and patient profile
Jones characterized the cohort as having “significant disease burden,” with mean disease duration of more than 15 years. He said 80% of participants were receiving concomitant biologics such as Humira or Remicade during the study. Baseline mean SES-CD was 8 and mean fecal calprotectin was “nearly 300.”
Clinical Advisory Board member Dr. Florian Rieder added that an SES-CD of 8 is on “the milder side of moderate” compared with conventional moderate-to-severe luminal Crohn’s trials, but emphasized the cohort’s longer disease duration, greater tissue damage, and higher prior biologic exposure made them less likely to respond to an anti-inflammatory intervention.
Safety and tolerability findings
Jones said PALI-2108 was “well tolerated” with no serious adverse events and no treatment discontinuations. He also reported “no PDE4-related adverse events whatsoever,” referencing typical PDE4-associated events such as nausea, headache, vomiting and diarrhea.
Two mild treatment-emergent adverse events—one abdominal discomfort and one fatigue—were deemed possibly drug-related, Jones said. In response to an analyst question, he stated the events occurred in different patients and neither came from the high-dose cohort.
Addressing expectations for adverse-event timing, Jones said that in Palisade’s Phase 1 studies (SAD, MAD and food-effect), PDE4 adverse events typically peaked “48–72 hours” after dosing initiation, generally when steady state is reached.
PK/PD data and early signals of activity
According to Jones, all patients achieved plasma pre-dose trough concentrations above the IC90 by day 14. He also reported a robust increase in ileal cyclic AMP of approximately 41% to 43% and said fecal calprotectin declined by a mean of 59% during treatment and “rebounded after treatment was withdrawn.” Jones said the company observed a “tight correlation” between cyclic AMP and fecal calprotectin, which he described as supporting a translational link between the drug’s mechanism and reduced inflammatory burden.
On tissue exposure, Jones said the study demonstrated tissue concentrations above those in plasma at steady state, including more than 3x in the ileum and 5x in the colon. He contrasted that with prior ulcerative colitis work in which colon tissue levels were roughly one-to-one with systemic levels during the elimination phase.
While emphasizing the limitations of the small, single-arm design, Jones said the trial showed objective endoscopic changes after two weeks, with 40% of patients achieving endoscopic response and 40% achieving endoscopic remission. He reported a mean absolute SES-CD reduction of 3.8 points, representing a 47.5% improvement from baseline over the two-week period.
Rieder also cited an individual case in which a non-passable stenosis at inclusion “either completely or almost completely resolved after only two weeks of treatment,” which he called “quite impressive,” while cautioning against overinterpretation given the small sample size.
Strategy: focus on luminal Crohn’s next, with UC program progressing
Management indicated the next development step is a broader moderate-to-severe luminal Crohn’s program. Finley said the company had wanted to review the fibrostenotic Crohn’s data before making final design decisions and now sees “a pretty clear indication” that luminal Crohn’s is likely the next path.
Jones said luminal Crohn’s offers a “more straightforward, well-established regulatory path” and represents a larger opportunity. He also said the company views Agomab as “blazing a trail” for a fibrostenotic Crohn’s regulatory pathway, suggesting Palisade could be a “fast follower” later. Rieder supported the sequencing as “reasonable” and said the anti-inflammatory effect seen in this hard-to-treat cohort increases confidence for testing in moderate-to-severe luminal Crohn’s disease, while not excluding future fibrostenosis studies.
On trial execution timelines, Jones said Palisade has selected PSI as its CRO and Iterative Health as an enrollment partner, and has built a plan around site selection and patient recruitment to avoid bottlenecks. He said the company is “on track for a second quarter IND filing” and is “confident” it can achieve top-line data “by the end of 2027.”
Finley also reviewed prior company milestones, including positive Phase 1b ulcerative colitis data reported last August that showed 100% clinical response and 40% clinical remission after one week in a small open-label cohort. He said those results supported a $138 million financing and contributed to a strategic investment from the Crohn’s & Colitis Foundation earlier this year.
Looking ahead, Jones said the company is evaluating a range of fibrosis-related biomarkers and pathway engagement, including planned work with the Cleveland Clinic and Rieder’s lab involving single-cell expression analyses of gut tissue cell populations and peripheral blood mononuclear cells.
About Palisade Bio (NASDAQ:PALI)
Palisade Bio, Inc is a clinical‐stage biotechnology company focused on pioneering localized immunotherapies for the treatment of cancer and inflammatory diseases. The company leverages a proprietary prodrug platform designed to activate therapeutic agents selectively within the tumor microenvironment or sites of inflammation. Its core strategy centers on stimulating the innate immune system via toll‐like receptor 9 (TLR9) agonism to drive targeted immune responses while minimizing systemic exposure and toxicity.
The company’s lead product candidate, PDS0108, is an intratumoral TLR9 agonist prodrug currently in Phase 1/2 clinical trials for patients with advanced solid tumors.
