Palisade Bio Receives Canadian Patent for PALI-2108 Composition
Palisade Bio announced that the Canadian Intellectual Property Office has granted patent number 3,174,137 for the composition of PALI-2108, its orally...
Breakthrough Clinical Results
Palisade Bio announced that the Canadian Intellectual Property Office has granted patent number 3,174,137 for the composition of PALI-2108, its orally administered, first-in-class, ileocolonic-targeted PDE4 B/D inhibitor. PALI-2108 is being developed for the treatment of fibrostenotic Crohn’s disease (FSCD) and ulcerative colitis (UC). The patent provides composition-of-matter protection for PALI-2108 through May 28, 2041. Palisade Bio is advancing the development of PALI-2108 in its Phase 1b FSCD study, with patient dosing expected to commence in H2 2025 and topline data expected in Q1 2026.
Key Highlights
- Canadian patent granted for PALI-2108 composition, providing protection through May 2041.
- PALI-2108 is a first-in-class, ileocolonic-targeted PDE4 B/D inhibitor.
- PALI-2108 is in development for fibrostenotic Crohn’s disease (FSCD) and ulcerative colitis (UC).
- Phase 1b FSCD study with PALI-2108 is expected to commence patient dosing in H2 2025.
Incidence and Prevalence
Global Estimates of Crohn's Disease Incidence and Prevalence
Prevalence Rates
Recent epidemiological data reveals significant geographic variation in the prevalence of Crohn's Disease (CD), one of the main types of Inflammatory Bowel Disease (IBD).
A 2024 study from Canterbury, New Zealand identified an exceptionally high prevalence, with CD affecting 386 per 100,000 persons (95% CI 370-402). This region has the highest reported prevalence of IBD in Oceania, with almost three times as many individuals having IBD compared to 2005.
In contrast, a 2018 Brazilian study in Espírito Santo found a much lower CD prevalence of 14.1 per 100,000 inhabitants. This highlights the substantial regional differences in disease burden.
The United States faces a significant challenge with CD currently affecting approximately 3 million people according to 2024 data. Historical data from Minnesota showed a prevalence of 90.5 per 100,000 population in 1980.
Incidence Rates
Current incidence rates also show marked regional differences:
- A 2025 Korean nationwide study reported CD incidence rates of 11.6 per 100,000 person-years
- Brazil reported an incidence of 2.4 per 100,000 inhabitants/year in 2018
- Historical data from Minnesota (1943-1982) showed an incidence of 4.0 per 100,000 person-years
- In South Africa, significant ethnic variations were observed with incidence rates of 1.8, 2.6, and 0.3 per 100,000 per year in coloured, white, and black populations respectively
- Among Jewish populations in South Africa, incidence rates were notably higher at 10.4 per 100,000
Future Projections
Forecasts suggest continuing changes in CD epidemiology:
- By 2032, CD prevalence is estimated to surpass ulcerative colitis in Hong Kong and the United States
- The age-standardized prevalence of IBD for 2032 is forecasted at 105.88 per 100,000 in Hong Kong, 645.79 in Japan, and 629.85 in the United States
- Incidence of IBD is estimated to increase annually by 3.3% in Hong Kong and 2.88% in Japan over the next decade
Demographic Patterns
Important demographic patterns have emerged:
- In Canterbury, the majority of IBD patients were New Zealand European (92.9%) with much lower rates in other ethnic groups
- Older adults (65+ years) comprised 21% of the IBD population in Canterbury
- In the United States, there was an uptrend in the mean age of IBD patients from 52.3 years in 2010 to 55.8 years in 2020
- Mortality rates were higher amongst the elderly and White adults in the US, with White adults having higher age-adjusted mortality rates than Black adults in CD (0.94 vs. 0.50)
These findings demonstrate that CD remains a global healthcare challenge with significant regional, ethnic, and demographic variations in both prevalence and incidence rates.
Key Unmet Needs and Target Populations for Crohn's Disease
Unmet Therapeutic Needs
Treatment resistance remains a significant challenge in Crohn's disease management, with many patients experiencing primary non-response, secondary loss of response, or adverse events. Clinical trials often report response rates below 60%, highlighting the limitations of current therapies.
Complex and recurrent disease management continues to be challenging, driving the expansion of minimally invasive approaches which have emerged as valid and potentially superior options for these difficult cases.
Drug delivery challenges persist, including lack of precise drug targeting, inadequate retention in the inflamed colon, and low bioavailability. Novel colon-targeted drug delivery systems are being developed to address these issues.
Mucosal healing has emerged as a critical therapeutic goal associated with sustained clinical remission, reduced hospitalizations, and fewer surgery rates, yet achieving this outcome remains difficult with current treatments.
Target Populations
Small bowel Crohn's disease patients (30-45% of cases) represent a key target population due to their higher risk of progression to stricturing and penetrating disease. This group is generally less responsive to biologics and may require higher drug trough levels for endoscopic healing.
Perianal Crohn's disease (pCD) patients are prioritized for new treatments, with studies showing ustekinumab may be more effective than vedolizumab or anti-TNFs as 2nd or 3rd-line therapy after failing 1st-line anti-TNF treatment.
Patients with refractory anoperineal fistulas are being treated with advanced dual-targeted therapy, most frequently combining infliximab and ustekinumab.
Biologic-naïve CD patients are targeted for early intervention with ustekinumab, showing significantly better outcomes when treatment begins within six months of diagnosis.
Elderly-onset IBD patients (diagnosed at 60+ years) receive specialized attention due to their unique clinical characteristics, with studies showing infliximab and ustekinumab exhibiting higher one-year persistence in this population.
Patients with a history of cancer, often excluded from clinical trials, are increasingly considered for advanced therapies based on emerging real-world data.
Immunocompromised patients face special challenges as diagnosis might be missed or delayed due to similar presentation to other conditions, and these patients may have increased infection risks.
Research and Clinical Trial Gaps
Clinical trial design faces challenges including complex designs, ethical concerns regarding placebo use, recruitment difficulties, and escalating costs. The landscape is shifting toward greater inclusivity and improved patient diversity.
Delayed diagnosis remains problematic, as seen in studies of Egyptian patients where diagnoses were found to be delayed despite clinical presentation comparable to worldwide patterns.
Personalized treatment approaches considering patient factors and disease characteristics are crucial but not yet fully implemented in clinical practice.
Novel therapeutic pathways being explored include selective Janus kinase inhibitors, anti-adhesion molecules, IL-23 selective inhibitors, and several other promising mechanisms to overcome limitations of existing treatments.
Study Design Parameters
Study Design Parameters and Endpoints in Key Crohn's Disease Trials
Study Designs
Randomized controlled trials are the predominant design for evaluating Crohn's disease treatments. Key designs include:
- Randomized, double-blind, placebo-controlled phase 2 studies (e.g., risankizumab trial across North America, Europe, and Asia)
- Prospective studies comparing treatments (e.g., azathioprine vs. budesonide)
- Multicenter, retrospective, observational cohort studies (e.g., assessing ustekinumab's long-term effectiveness)
- Prospective, single-center, cross-sectional studies (e.g., investigating effects of disease duration on fecal calprotectin)
Clinical trials in Crohn's disease have evolved significantly over the last 15 years, moving from early trials with small sample sizes and subjective assessments to more rigorous designs following the advent of anti-TNF agents in the late 1990s.
Patient Selection Criteria
Modern trials typically include: - Patients aged 18-75 years with moderate-to-severe Crohn's disease (CDAI 220-450) - Patients with mucosal ulcers in the ileum or colon with CDEIS ≥7 (≥4 for isolated ileitis) - Both treatment-naïve and biologic-experienced patients - Patients with steroid-dependent Crohn's ileocolitis or proximal colitis
Primary Endpoints
Key primary endpoints include: - Clinical remission defined as CDAI <150 at week 12 - Mucosal healing and histologic remission - Maintenance of clinical remission (e.g., HBI ≤5) - Endoscopic remission defined as SES-CD ≤2
Secondary Endpoints
Trials frequently assess: - Crohn's Disease Endoscopic Index of Severity (CDEIS) score reduction - Average histology score (AHS) reduction - Steroid-free remission - Mucosal healing - Steroid discontinuation - Need for treatment optimization
Assessment Methods
Disease activity and treatment response are evaluated through: - Ileocolonoscopy with regional biopsies for mucosal healing and histologic activity - Clinical examination and laboratory tests - CDAI (Crohn's Disease Activity Index) calculation - IBDQ (Inflammatory Bowel Disease Questionnaire) - HBI (Harvey-Bradshaw Index) for clinical activity - Biomarkers including CRP, ESR, fecal calprotectin - EASE-CD (Endoscopic ulcer Activity Score for Evaluating CD), scoring from 0-100
Novel Approaches
Recent innovations include: - Artificial intelligence models using whole-slide images to predict treatment response - Deep learning models based on intestinal ultrasound images (AUC of 0.73 for predicting mucosal healing) - Nomogram models utilizing biomarkers to forecast endoscopic activity - Clustering-enhanced weakly supervised learning frameworks
Timeline Assessment
Modern trials typically include: - Follow-up assessments at week 12-26 and week 44-56 - Safety assessment in patients receiving at least one dose of study drug
This evolution reflects a shift from subjective clinical scores to more objective disease activity parameters and ambitious endpoints like mucosal healing and corticosteroid-free remission.
