Palisade Bio Stifel 2026 Healthcare Conference

to Q&A. Great. Well, thanks for having us, Alex.

Happy Veterans Day, I guess. Thanks to all of you for taking time to learn about our story. Palisade Bio is a clinical stage company addressing inflammatory and fibrotic diseases. Our lead drug, PALI-2108, is an oral once-daily PDE4 inhibitor that's activated in the terminal ileum in the colon. Many of you probably know that there are a number of PDE4 inhibitors that have been repurposed from other inflammatory and fibrotic diseases to be used in IBD. The problem with those is that in order to push the dose high enough to be effective in IBD, it triggers a lot of adverse events. Our prodrug approach gets around those. We deliver high concentrations of drug in the terminal ileum and the colon while maintaining sustained systemic exposure and fewer adverse events and much higher tolerability.

We completed phase I studies earlier this year, at the very beginning of this year, that demonstrated that the drug is working as it was designed. We're currently in two phase II studies, one for ulcerative colitis and the other for Crohn's disease. The ulcerative colitis study has enrolled its first patient. The Crohn's study has received IND clearance, and we're in the process right now of activating sites and should be starting enrolling on that fairly soon.

Yep. Therapeutic index with our drug, I think, gives us the optimism that we're going to be able to show improved efficacy with a good safety and tolerability profile.

Mitch, you want to take that?

Yeah, sure. I mean, so previously apremilast, which is a twice-daily generation 2 pan-inhibitor of PDE4, demonstrated about a 20% placebo-adjusted remission rate. More recently, in an IP patient randomized study out of China, mufemilast, another PDE4 that's orally delivered at 45 mg twice daily or 60 mg twice daily, demonstrated a dose response and clinical remission rates that are arguably sort of best in indication. I think the learnings here, and that's at 44% placebo-adjusted remission. I think the learnings here are apremilast sort of underdosed, maybe appropriate for psoriasis. When you look at mufemilast and push the dose, you can get to sort of indication-leading clinical remission rates.

Yeah. The drug was specifically engineered for IBD. It came out of the Merck Frosst labs in Montreal. The question that they were trying to answer when they were designing the drug was, how can you capture the therapeutic potential of a PDE4 inhibitor while still improving the therapeutic window? Our drug starts out as an active prodrug.

It bypasses the upper GI tract before it is activated. It is converted into an active drug, we call it PALI-0008, in the terminal ileum and colon when it gets exposed to high concentrations of beta-glucuronidase. We are trying to obviously maintain a better balance between systemic and tissue concentrations. Like I said, the upper GI tract exposure is what triggers diarrhea, but it is then when you have high spikes in concentration in plasma that you get the other side effects of nausea, vomiting, headache.

Our phase I results demonstrated that we were able to achieve IC90 steadily in plasma while maintaining like seven times the concentration in local tissues. We think that shows that the drug is behaving as it was originally intended.

Sure, yeah. We've conducted a phase I SAD, MAD, and food effect study. We've also conducted a five-patient translational ulcerative colitis study in moderate to severe patients, and then a five over one week, and then a five-patient fibrostenotic Crohn's study over two weeks. In the normal healthy studies, and treated over 100 patients have been exposed to the drug. In the normal healthy studies, we were able to push single dosing and multiple dosing pretty significantly. We demonstrated that the drug should be given once daily and that the drug should be given in the fed state. We took the max tolerable dose for our SAD, MAD, food effect study into a five-patient ulcerative colitis study. We treated patients for one week. PDE4s are extremely fast-acting drugs. We saw 100% response and 40% remission after just one week of treatment. That's by modified Mayo score.

We also saw that biomarkers confirmed this. Objective biomarkers saw a 70% reduction in PDE4B, a 30% improvement in cyclic AMP, the PD biomarker, a 70% reduction in fecal calpro, 15% in CRP. So, improvements in different biomarkers, different tissues and samples, and different types of objective measures. In the Crohn's study, we went with our once-daily dosing at 20, 25, and 30 mg. We saw two adverse events in the entire study over two weeks, discomfort and fatigue. We saw a 40% response, 40% remission by SES-CD score, a 4-point reduction from a baseline of eight, basically. Then again, biomarkers that supported that improvement in SES-CD score.