Palisade Bio Identifies PDE4B as Potential Biomarker for Ulcerative Colitis Patient Stratification
核心洞察
Palisade Bio identifies PDE4B (搜索) expression as a potential biomarker for patient stratification in ulcerative colitis (搜索) (UC), with higher expression in colitis patients.
Data shows elevated PDE4B (搜索) expression in 70% of adult and 90% of pediatric UC patients, suggesting its utility in identifying suitable candidates for targeted therapies.
PALI-2108, an oral, colon-specific PDE4 inhibitor prodrug, is being advanced by Palisade Bio for UC treatment, with Phase 1 trials expected to commence before year-end.
Palisade Bio has announced the successful completion of refined patient selection strategies based on PDE4-related biomarkers and disease characteristics to optimize clinical outcomes for patients with ulcerative colitis (搜索) (UC). This development arises from their collaboration with Strand Life Sciences.
PDE4B Expression as a Biomarker
Through the collaboration with Strand Life Sciences, RNAseq datasets were analyzed, revealing that PDE4B (搜索) expression is significantly higher in most colitis patients, including both adult and pediatric cohorts. This suggests PDE4B could be a crucial factor in patient stratification. In adults, a PDE4B over-expression level was determined that the Company believes accurately identifies 70% of moderate to severe cases. In pediatric patients, a PDE4B over-expression level was determined that the Company believes accurately identifies 90% of those with moderate to severe colitis.
Dr. Mitch Jones, CMO of Palisade Bio, commented, "These findings underscore the potential of PDE4B (搜索) expression as a valuable tool in the precision medicine toolkit for colitis. By tailoring treatment strategies based on PDE4B levels, healthcare providers can offer more personalized and effective interventions for patients suffering from this challenging condition."
PALI-2108: A Targeted Therapeutic Approach
PALI-2108, Palisade Bio's lead program, is an orally administered, locally acting colon-specific PDE4 inhibitor prodrug in development for patients affected by UC. The company is on track to commence a Phase 1 human clinical study of PALI-2108 for the treatment of UC before the end of the year.
Preclinical Evidence
In a DSS-induced UC mouse model, researchers observed increased colon tissue PDE4B (搜索) levels with the induction of DSS colitis. Treatment with PALI-2108 resulted in significant reductions in colon tissue PDE4B expression in response to increasing doses of PALI-2108, closely correlated with increasing levels of colon tissue cAMP, and closely correlated to colon tissue inflammatory cytokines such as TNF-alpha (搜索). Researchers also noted a significant reduction in disease activity index score over time compared to the control treated group. Furthermore, body weight loss and changes in colon length were attenuated in increasing dosage groups, showcasing the potential for targeted efficacy.