Palisade Bio (NASDAQ:PALI) executives outlined the company’s strategic pivot, lead development priorities, and financing position during a fireside chat at Oppenheimer’s 36th Annual Healthcare Life Sciences Conference.
Company background and strategic pivot
Chief Executive Officer J.D. Finley said the company has been in existence for roughly 16 years and originated from science licensed from UC San Diego. He described a “re-transform[ation]” in the summer of 2023 following a Phase 2 readout on the company’s prior molecule that he said produced “lackluster results.”
Finley added that Palisade advanced the program from preclinical through completion of Phase 1a and 1b studies.
PALI-2108 and the prodrug rationale
During the discussion, Jones said PDE4 inhibitors have historically faced tolerability challenges, including CNS-related side effects such as headache and nausea, and GI-related adverse events such as secretory diarrhea. He cited roflumilast as an earlier, potent PDE4 inhibitor used in COPD with difficult tolerability, and contrasted that with apremilast (Otezla), which he said has been better tolerated. Jones also pointed to more recent approaches that have used topical or inhaled delivery methods.
Jones described Palisade’s candidate, PALI-2108, as an orally delivered, once-daily tablet and said the company believes it is the only PDE4 inhibitor in development with a once-daily formulation. He characterized it as a glucuronidated prodrug that is not active until it is bioactivated in the gut. In his description, the prodrug remains “gut restricted” until bacterial β-glucuronidase releases the active PDE4 inhibitor in the distal gut (terminal ileum and colon), after which the active agent can be absorbed and circulate systemically.
Jones said the delayed and locally targeted release is intended to avoid upper GI exposure associated with secretory diarrhea and to reduce peak concentration (Cmax), which he linked to improved tolerability for headache and nausea. He also emphasized that the approach still achieves systemic exposure levels that can reach IC90 despite local bioactivation.
Mechanism and early translational signals
Jones said the company is targeting immune cells in GI tissue and described PDE4B and PDE4D as being overexpressed in patient biopsy data the company has reviewed. He added that PALI-2108 primarily targets PDE4 isoforms A, B, and D.
Jones highlighted cyclic AMP as a key downstream mediator of PDE4 inhibition and said Palisade has demonstrated a 30% to 40% increase in cyclic AMP in ulcerative colitis (UC) patients over one week of treatment. He also referenced downstream effects on inflammatory cytokines such as TNF-α and interleukins (including IL-12 and IL-23) and said pathways such as JAK-STAT may be influenced via intracellular cyclic AMP.
Finley and Jones discussed an open-label, one-week UC study in five moderate-to-severe patients. Jones said the company observed biomarker improvements and reported a 63% improvement in modified Mayo score, “100% response,” and “40% remission” in that small cohort. He compared those results with publicly discussed outcomes in UC for apremilast and another PDE4 inhibitor program (mufimlast, described as China-only), while emphasizing the importance of being able to dose without dose-limiting tolerability issues.
Upcoming and ongoing development plans in UC and Crohn’s
Management said the lead clinical program is in moderate-to-severe UC, with plans to file an IND in the second quarter and begin enrollment in the third quarter of the year discussed during the conference. Finley said Palisade is targeting a top-line readout by the end of 2027, which he described as an aggressive timeline.
Jones said the company expects enrollment challenges in UC trials but stated Palisade has partnered with groups experienced in executing UC studies and is selecting sites intended to support faster enrollment and “control” factors that influence placebo response rates.
Palisade also discussed an ongoing Phase 1b study in fibrostenosing Crohn’s disease (FSCD). Jones called FSCD a major unmet need in IBD and said 75% of Crohn’s patients undergo surgery for a stricture in their lifetime, with 50% doing so within 10 years. He estimated at least 200,000 symptomatic U.S. patients with ileal strictures and said there are no approved therapies specifically for stenosis or fibrosis, leaving options such as balloon dilation and surgery.
Jones described the FSCD study as a two-week trial that will be the first time the company treats patients for two weeks and the first time it characterizes once-daily 30 mg dosing. He said the study is designed to assess:
- Drug levels in the ileum and colon, including superficial vs. deeper tissue
- Pharmacodynamic response via cyclic AMP measurements in the ileum
- RNA sequencing to evaluate pathway engagement
- Patient-reported outcomes (sPROs)
- Histology and staining for early signs of tissue remodeling
- Ileocolonoscopy and SES-CD scoring
Jones said the company plans to release data from the FSCD study during the quarter referenced in the conversation. He also discussed how tissue-based translational work, including RNA-Seq and single-cell expression analyses, could inform future combination strategies and broader Crohn’s development.
Cash runway, exploratory work, and partnering discussions
On funding, Finley referenced a $138 million financing event he described as a “re-IPO,” and said it provides runway to conduct “a full, definitive study in ulcerative colitis” and a Crohn’s study “in some form,” with roughly 12 months of additional runway beyond those efforts, extending “cash into 2029.” The company also noted it received an investment from the Crohn’s and Colitis Foundation’s IBD Ventures (referred to as an “IBD of Interest” program during the chat).
While emphasizing that more than 90% of the company’s focus remains on UC (with Crohn’s behind it), Jones said Palisade is exploring other potential areas where improved tolerability and once-daily systemic IC90 exposure could be relevant, mentioning possibilities such as IPF or COPD. He said the company is conducting small precision-cut tissue studies to understand how the drug works in multiple tissues, including skin, liver, lung, and gut.
Finley said corporate development efforts are still early, but the company is meeting regularly with large pharma companies primarily to increase awareness so that potential partners can follow the story as data emerges.
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.
