Chemomab Therapeutics Ltd. · NASDAQ:CMMB
Chemomab Therapeutics — AASLD 2024
19 slides from Chemomab Therapeutics's conference presentation, November 2024
Slide 1: CM-101 improved fibrosis biomarkers in patients with primary sclerosing cholangitis: The SPRING Study
CM-101 improved fibrosis biomarkers in patients with primary sclerosing cholangitis: The SPRING Study CL Bowlus1, ST Barclay2, D Joshi3, MC Londoño4, P Mantry5, R Safadi6, R Aricha7, C Cirillo7, M Frankel7, J Lawler7, I Vaknin7, A Mor7, D Thorburn8, on behalf of the SPRING Study investigators. 1Univ
Slide 2: Primary Sclerosing Cholangitis is a Rare Cholestatic Liver Disease with High Unmet Needs
Primary Sclerosing Cholangitis (PSC) is a Rare Cholestatic Liver Disease with High Unmet Needs • Unknown etiology but associated with inflammatory bowel disease in ~70% • Characterized by inflammation and fibrotic strictures of the bile ducts • Complications include those related to cirrhosis as wel
Slide 3: CCL24 is a Chemokine that Promotes Cell Trafficking and Regulates Inflammatory and Fibrotic Activities
CCL24 (eotaxin-2) is a Chemokine that Promotes Cell Trafficking and Regulates Inflammatory and Fibrotic Activities through the CCR3 Receptor CCL24 Secreting Cells Immune and CCL24 Epithelial The Cells Target CCR3 CCL24 – CCR3 promotes Causing more CCL24 The CCL24 inflammation and fibrosis inflammati
Slide 4: Background: CCL24 Levels are Elevated in PSC Patients and Associated with Cirrhosis
Background: CCL24 Levels are Elevated in PSC Patients and Associated with Cirrhosis CCL24 levels in liver tissue of healthy subjects Serum CCL24 level is higher in cirrhosis and vs. patients with PSC associated with risk of progression to cirrhosis Healthy Liver PSC Livers CCL24 Staining CCL24 (brow
Slide 5: Background: Rationale for Targeting CCL24 with CM-101 in PSC
Background: Rationale for Targeting CCL24 with CM-101 in PSC CM-101 Reduced Liver Injury and Fibrosis in the Mdr2 -/- Mouse CM-101 • Humanized monoclonal antibody • Neutralizes CCL24 • Well tolerated in phase 1studies Reduced Macrophage Recruitment and Attenuated Liver Biliary Epithelial Cell Prolif
Slide 6: Methods: SPRING Study Design
Methods: SPRING Study Design Phase 2, randomized, double-blind, placebo-controlled study of CM-101 in PSC Key Enrollment Criteria CM-101 Primary Sclerosing Cholangitis SPRING Study (NCT 04595825) PSC patients with large duct disease of >24 weeks duration • ALP > 1.5 ULN • Stable IBD allowed • Stable
Slide 7: Patient Disposition
Patient Disposition Patient Enrolled N=134 Screen failure N=57 Randomized N=77 Placebo CM-101 10mg/kg CM-101 20 mg/kg Intent-to-treat Intent-to-treat Intent-to-treat N=21 N=25 N=31 Safety Population Safety Population Safety Population Safety Population Randomized and N=20 N=25 N=31 received at least
Slide 8: Patient Demographics and Baseline Characteristics (Safety Population)
Results: Patient Demographics and Baseline Characteristics (Safety Population) Characteristic Placebo CM-101 (10 mg/kg) CM-101 (20 mg/kg) n=20 n=25 n=31 Age (year), mean, (range) 40.5 (23–75) 48.6 (23–74) 45.6 (23–67) Male Gender, n, (%) 13 (65%) 16 (64%) 17 (55%) Race, n, (%) White 19 (95%) 19 (76%
Slide 9: Safety and Tolerability Profile
Results: Safety and Tolerability Profile Treatment Emergent Adverse Events CM-101 CM-101 All N, (%) Placebo 10mg/kg 20mg/kg CM-101 n=20 n=25 n=31 n=56 Treatment Emergent Adverse Events (TEAE) 15 (75%) 18 (72%) 28 (90%) 46 (82%) Related to study drug 9 (45%) 7 (28%) 16 (52%) 23 (41%) Serious TEAE 1 (
Slide 10: Most Common Treatment Emergent Adverse Events
Results: Most Common Treatment Emergent Adverse Events Placebo CM-101 CM-101 CM-101 Treatment Emergent Adverse Events, n (%) 10mg/kg 20mg/kg (All) ≥10% Frequency n=20 n=25 n=31 n=56 Fatigue 6 (30%) 5 (20%) 11 (36%) 16 (29%) Headache 4 (20%) 2 (8%) 7 (23%) 9 (16%) Pruritis 2 (10%) 4 (16%) 2 (7%) 6 (1
Slide 11: Liver Biochemistries Tests
Results: Liver Biochemistries Tests Patients with baseline All patients moderate/advanced disease* 39.2 40 20 16.5 Median % change from Median % change from baseline at week 15 baseline at week 15 10.4 10 19.3 20 5.0 13.8 2.9 10.4 0.3 0 4.9 3.5 3.6 2.8 -2.5 -1.4 -1.7 -5.2 0 -10 -7.2 -2.1 -9.6 -5.2 -
Slide 12: Total Bilirubin
Results: Total Bilirubin Patients with baseline All patients moderate/advanced disease* 0 0 0 0 Median % change from Median % change from baseline at week 15 baseline at week 15 -5 -5 -10 -9.2 -8.9 -10 -10.7 p=0.07 -13.3 -15 Placebo 10mg/kg 20mg/kg Placebo 10mg/kg 20mg/kg n=16 n=22 n=28 n=7 n=14 n=1
Slide 13: Liver Stiffness Measurements
Results: Liver Stiffness Measurements Patients with baseline All patients moderate/advanced disease* p=0.12 p=0.16 * p=0.01 2 * p=0.01 change from baseline to week 15 6 change from baseline at week 15 1 4 1.04 LS mean (SE) LS mean (SE) 3.0 2 0 -0.72 -0.83 0 -1 -1.5 -1.4 -2 -2 Placebo 10mg/kg 20mg/kg
Slide 14: ELF Scores
Results: ELF Scores Patients with baseline moderate/advanced disease* ELF Components-Change from Baseline Over Time CM-101 20 mg/kg vs. Placebo through 15 weeks 40 TIMP1 All patients p=0.09 At 15 weeks 10 mg/kg vs. placebo, p= 0.016 change from baseline at week 15 20 20 mg/kg vs. placebo, p= 0.014 0
Slide 15: PRO-C3
Results: PRO-C3 Patients with baseline All patients moderate/advanced disease* p=0.1 p=0.1 change from baseline to week 15 5.0 2.11 change from baseline at week 15 8 6 2.5 LS mean (SE) 4 4.75 LS mean (SE) (ng/ml) 2 0.0 0 -2 -2.96 -3.03 -2.5 -0.45 -4 -1.50 -6 -5.0 Placebo 10 mg/kg 20 mg/kg Placebo 10
Slide 16: 5-D ITCH Total Scores
Results: 5-D ITCH Total Scores Pruritus 2 Placebo (n=16) 10 mg/kg (n=21) 1 20 mg/kg (n=26) change from baseline LS mean (SE) 0 -1 p=0.12 *p=0.047 -2 -3 Baseline 3 6 9 12 15 Week CM-101-treated patients experienced decreased pruritus scores across all timepoints compared to placebo *Pruritis assessme
Slide 17: Conclusions and Next Steps
Conclusions and Next Steps • CM-101 was well tolerated and had a safety profile comparable to placebo • CM-101 demonstrated dose dependent, anti-inflammatory, anti-fibrotic, and anti-cholestatic effects in patients with PSC • In a subgroup of patients with moderate to advanced disease, CM-101 showed
Slide 18: Acknowledgements
Acknowledgements • We thank the patients, their families, caregivers, the study investigator and research coordinators who participated in this study • Enrolling Spring Study Investigators: Sayed Assem (US) Stephen T Barclay (UK) Nimer Assy (Israel) Udi Zigmond (Israel) Justin Boike (US) Chenchu Ram
Slide 19: Thank You
Thank You CHEMOMAB THERAPEUTICS 19