Slide 1: PXL770 Topline Phase 2a Results
PXL770 Topline Phase 2a Results
Slide 2: Disclaimer
Disclaimer Some of the statements contained in this presentation constitute forward-looking statements. Statements that are not historical facts are forward-looking statements. Forward-looking statements generally can be identified by the use of forward-looking terminology such as “may”, “will”, “ex
Slide 3: Mission and Vision
Mission and Vision To discover, develop and commercialize innovative therapies for patients suffering from serious chronic diseases with underlying metabolic pathophysiology • Mid-to-late stage first-in-class pipeline: Type 2 diabetes (globally partnered) and NASH • Pipeline expansion in chronic and
Slide 4: Poxel Mid-to-Late Stage Metabolic Pipeline
Poxel Mid-to-Late Stage Metabolic Pipeline Due to COVID-19, the Company Continues to Monitor All Developments that Might Impact the Timelines for Achievement of our Corporate Objectives Indication MOA Discovery/PC PH 1 PH 2 PH 3 NDA review Partner/ Rights Upcoming Milestones Type 2 Diabetes Imeglimi
Slide 5: PXL770 is a Direct AMP Kinase Activator
PXL770 is a Direct AMP Kinase Activator AMPK Activation Restores Metabolic Balance & Inhibits Inflammation AMPK Overnutrition (metabolic Caloric Restriction, syndrome, NASH, Type 2 Exercise Diabetes) PXL770 1) Activates catabolic pathways 3) Other benefits • Fatty acid oxidation • Glucose uptake • R
Slide 6: PXL770 - Translation of NASH Efficacy Parameters
PXL770 - Translation of NASH Efficacy Parameters Rodent (in vivo) Human Cells (in vitro) NASH/NAFLD Patient ✓ ↓ steatosis score; ↓ liver ✓ ↓ de novo lipogenesis ✓ ↓ de novo lipogenesis; lipids; ↓ de novo lipogenesis ↓ liver fat mass Steatosis ✓ ↓ inflammation score; ↓ ✓ ↓ cytokine secretion liver le
Slide 7: Preclinical Efficacy Profile – Improvements in all Core NASH Features
Preclinical Efficacy Profile – Improvements in all Core NASH Features Data Observed in Multiple Rodent Models Supports Potential for PXL770’s Beneficial Clinical Effects A. NASH Vehicle PXL770 A. Improved liver steatosis B. Decreased liver (and adipose tissue) inflammation C. Decreased profibrogenic
Slide 8: Preclinical Data Demonstrate Potential Synergy of PXL770/AMPK Activation with Other Agents
Preclinical Data Demonstrate Potential Synergy of PXL770/AMPK Activation with Other Agents in Development PXL770 Other PXL770 / Semaglutide (GLP-1) Mechanisms Liver lipid content Mouse NASH Model 1500 Liver lipid content (mg) Effects in #### Adipose Tissue # 1000 Low grade inflammation **** **** ***
Slide 9: Phase I Program Summary
Phase I Program Summary Favorable PK, Safety, Target Engagement, Efficacy Signals • Healthy Subjects (Single & Multiple Dose Studies) Fructose-stimulated de novo lipogenesis 30 Versus baseline (at week 4) (N=12) o 132 subjects 25 DE NOVO LIPOGENESIS (%) o linear, dose-proportional exposure 20 o term
Slide 10: PXL770: Phase 2a Study Design
PXL770: Phase 2a Study Design Phase 2a 12-week, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel Group Trial • N = 120 presumed NASH patients with and without Type 2 diabetes • Inclusion criteria: increased hepatic fat (assessed via CAP and MRI-PDFF) • Trial assessed efficacy and
Slide 11: Baseline Characteristics
Baseline Characteristics Placebo PXL770 250 mg QD PXL770 250 mg BID PXL770 500 mg QD N 31 30 30 29 Age, mean (SD) 51.5 (12.17) 52.5 (12.93) 50.6 (12.26) 55.7 (12.63) Male, N (%) 15 (48.4%) 13 (43.3%) 7 (23.3%) 7 (24.1%) BMI (kg/m2), mean (SD) 35.4 (5.9) 35.2 (6.3) 36.6 (6.3) 35.1 (4.95) T2DM, N(%) 1
Slide 12: Significant Relative Decrease in Liver Fat Mass Measured by MRI-PDFF at 12 Weeks
Significant Relative Decrease in Liver Fat Mass Measured by MRI-PDFF at 12 Weeks Changes from Baseline vs. Placebo PXL770 250 PXL770 250 PXL770 500 Placebo mg QD mg BID mg QD 0 • Proportion of patients achieving -0.7% -2.3% LS mean change from Baseline ≥ 30 % reduction in liver fat mass: 27.6% of pa
Slide 13: More Pronounced Effect on Relative Decrease in Liver Fat Mass in Type 2 Diabetes Subgroup
More Pronounced Effect on Relative Decrease in Liver Fat Mass (MRI-PDFF) in Patient Subgroup with Type 2 Diabetes Changes from Baseline and vs. Placebo PXL770 PXL770 PXL770 250 mg 250 mg 500 mg Placebo QD BID QD 1.2% 0 • Approximately 47% of patients with NASH also have Type 2 diabetes1 -5 -6.1% LS
Slide 14: Significant Relative Decrease in ALT at the Top Dose
Significant Relative Decrease in ALT at the Top Dose Changes from Baseline vs. Placebo ALT U/L PXL770 PXL770 PXL770 • Baseline mean ALT values range from 250 mg 250 mg 500 mg 37 to 41 UI/L (normal range : 6 – 41 Placebo QD BID QD UI/L) 2 LS mean change from Baseline 1 0 0,3 0 -2 -4 -6 -6,3 -8 -10 p
Slide 15: Significantly Improved Glycemia - Despite Low Baseline HbA1c
Significantly Improved Glycemia - Despite Low Baseline HbA1c Changes from Baseline vs. Placebo HbA1c (%) PXL770 PXL770 PXL770 • Baseline HbA1c range from 6 to 6.3 % 250 mg 250 mg 500 mg (normal range < 6.5%) Placebo QD BID QD Baseline 6.03 % 6.29 % 6.19 % 6.11 % 0,05 LS mean change from Baseline 0,0
Slide 16: PXL770 Phase 2a Safety Summary
PXL770 Phase 2a Safety Summary • Well tolerated in all three treatment groups • Total number of patients experiencing treatment emergent adverse events (TEAEs) in each PXL770- treated group (20-23) similar to placebo (21) • TEAE’s mainly mild to moderate; AE’s relating to GI organ class most common
Slide 17: PXL770 Phase 2a Results Summary
PXL770 Phase 2a Results Summary • Oral first-in-class agent observed to produce statistically significant efficacy o reduction in liver fat mass o observed to improve other key measures of ALT and HbA1c • Greater response observed in patients with type 2 diabetes – higher risk and substantial sized
Slide 18: PXL770 Paves the Way for Other Therapeutic Applications
PXL770 Paves the Way for Other Therapeutic Applications AMPK Biology Impacts Pathways Involved in Many Metabolic Diseases AMPK Activates Inhibits catabolic Inhibits inflammation apoptosis pathways anabolic pathways Exploring applications of current and next generation AMPK activators in biologically
Slide 19: Contacts
Contacts Jonae R. Barnes Senior Vice President, Investor Relations, Corporate Communications and Public Relations jonae.barnes@poxelpharma.com +1 617-818-2985 Aurélie Bozza Investor Relations and Communication Director aurelie.bozza@poxelpharma.com +33 6 99 81 08 36 19