Slide 1: Full Year 2020 Financial and Corporate Update
Full Year 2020 Financial and Corporate Update March 25, 2021 1
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: Corporate Update During Coronavirus (COVID-19) Pandemic
Corporate Update During Coronavirus (COVID-19) Pandemic Proactive Corporate Initiatives • Continuous monitoring of the situation worldwide and its impact on our people, operations and plan • Employees used to working remotely due to global locations, supported by appropriate IT infrastructure Imegli
Slide 4: Poxel's Mission and Vision
Poxel’s Mission and Vision To discover, develop and commercialize innovative therapies for patients suffering from serious chronic diseases with underlying metabolic pathophysiology acetyl CoA METABOLIC INFLAMMATION DISORDERS (cellular energy homeostasis TISSUE DEGENERATION imbalances) & CELL DEATH
Slide 5: Three Pillars of Poxel's Strategy
Three Pillars of Poxel’s Strategy First-in-Class Programs Leading to Key Value Inflection Points Unique platforms AMPK D-TZD Pipeline Partnered in Asia1 with diabetes Oral First-in- Platform Platform expansion market leader in Japan Class Phase 2 External into new Sumitomo Dainippon Pharma Programs
Slide 6: Robust Mid-to-Late Stage Metabolic Pipeline
Robust Mid-to-Late Stage Metabolic Pipeline Indication MOA Discovery/PC PH 1 PH 2 PH 3 NDA review Partner/ Rights Upcoming Milestones Type 2 Diabetes (T2D) Imeglimin ▪ Target product launch in 20212 in T2D MRC Modulator Japan Japan / Asia1 T2D with Imeglimin ▪ Exploring options to move the CKD stage
Slide 7: Financial Update
Financial Update Full Year 2020 7
Slide 8: Revenue
Revenue Mostly reflecting the JNDA filing of Imeglimin in Japan • Includes the JPY 500 million milestone payment FY FY received from Sumitomo Dainippon Pharma for the In K€ 2020 2019 submission of the Imeglimin J-NDA 12 months 12 months • In a less extent, reflects the residual allocated Sumitomo Ag
Slide 9: Statement of Comprehensive Income as of Dec. 31, 2020
Statement of Comprehensive Income as of Dec. 31, 2020* Decrease in revenue and Opex, mostly reflecting the completion of the TIMES program 1 Mostly reflects the JPY 500 million (EUR December 31, December 31, In K€ 4.0 million) milestone payment that Poxel 2020 2019 received from Sumitomo Dainippon 1
Slide 10: Statements of Financial Position as of December 31, 2020
Statements of Financial Position as of December 31, 2020* Assets December 31, December 31, In K€ 2019 2019 1 Decrease reflects the end of the TIMES Intangible assets 16 642 16 614 program (and reinvoiced costs to Property, plant and equipment 2 224 2 323 Other non-current financial assets 246 477 Su
Slide 11: Statements of Financial Position: Shareholders' Equity and Liabilities
Statements of Financial Position as of Dec. 31, 2020* Shareholders’ Equity and Liabilities December 31, December 31, In K€ 2020 2019 1 Reflects the 2020 net loss and the 1 Total shareholders' equity 26 879 39 142 €17.7m fund raising in 2020 Non-current liabilities 2 Includes IPF loan (€16.5m) and PG
Slide 12: Statements of Cash Flow as of Dec. 31, 2020
Statements of Cash Flow as of Dec. 31, 2020* December 31, December 31, In K€ 2020 2019 Cash flows from operating activities before change in WC (26 040) (23 111) (-) Changes in working capital requirements (292) 2 582 Cash flows from operating activities (25 749) (25 693) 1 Reflects the €17.7m fund
Slide 13: Key Financial & Shareholder Information
Key Financial & Shareholder Information Market data Shareholder ownership2 9.9% Andera Partners 19.2% Bpi France Ticker: POXEL 56.7% Floating ISIN: FR0012432516 9.2% Founders Number of shares: 28,611,2541 5.0% Roivant Sciences Ltd Key financials Analyst coverage • As of 12/31/20 cash & cash equivale
Slide 14: Imeglimin
Type 2 Diabetes Imeglimin Key Partnership for Japan & Asia First in a New Class of Potential Anti-diabetic Therapies with a Differentiated Mechanism of Action Expected Regulatory Approval in Japan in 2021 14
Slide 15: Imeglimin: Novel Mechanism - Nearing Approval in Japan
Imeglimin: Novel Mechanism - Nearing Approval in Japan Partnered in Asia1 with Diabetes Market Leader, Sumitomo Dainippon Pharma o Successful Completion of Phase 3 Program in Japan 2018 2019 2020 2021 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 o J-NDA approval triggers milestone payment of ~€13.8M ($16.9M)2 and abilit
Slide 16: Imeglimin Phase 3 TIMES Program Overview
Imeglimin Phase 3 TIMES Program Overview (N=1,142) Robust and Consistent Efficacy in Monotherapy and as an Add-on Therapy TIMES 1* TIMES 2 TIMES 3 Monotherapy As an Add-on to Standard of Care Combination with Insulin Change in HbA1c – 24 Weeks Change in HbA1c (vs baseline) – 52 Weeks – 714 patients
Slide 17: Business Opportunity for Imeglimin in US, EU, Other Countries
Business Opportunity for Imeglimin in US, EU, Other Countries1 ▪ Data, materials, information, IP, and FDA regulatory filings transferred from Metavant2 to Poxel ▪ Exploring options to pursue for T2D patients with chronic kidney disease stages 3b/4 (CKD 3b/4); Ph3 ready product, incl. efficacy & saf
Slide 18: NASH Programs
NASH NASH Programs PXL770 - Direct AMPK Activator PXL065 – Deuterium-stabilized R-pioglitazone 18
Slide 19: PXL770 and PXL065: Novel, First-in-Class Product Candidates
PXL770 and PXL065: Novel, First-in-Class Product Candidates HALLMARKS OF NASH MΦ Lipid accumulation in Immune cells Hepatic stellate hepatocytes (macrophages - MΦ) Cellular damage-death cell activation Steatosis Inflammation Ballooning Fibrosis • First-in-Class - Novel Mechanisms • Daily oral admini
Slide 20: PXL770
NASH PXL770 Proprietary Program Direct AMPK Activator for the Treatment of NASH 20
Slide 21: PXL770 is a Direct AMP Kinase Activator
PXL770 is a Direct AMP Kinase Activator Mechanism, Preclinical Profile, Phase I Summary AMPK Overnutrition (metabolic syndrome, Caloric Restriction, NASH, Type 2 Diabetes) Exercise Activates catabolic pathways PXL770 Other benefits fatty acid oxidation • Reduces inflammation glucose uptake ↓ mac
Slide 22: PXL770 Phase 2a Design & Baseline Characteristics
PXL770 Phase 2a Design & Baseline Characteristics 500 mg QD n=29 Randomization Week 12 1:1:1:1 Key inclusion criteria 250 mg BID n=30 • NAFLD with / without T2DM 250 mg QD n=30 • CAP > 300 • MRI-PDFF > 10% PLACEBO n=31 • (ALT > 20 ♀; > 30 ♂)* Screening Run-in: 4 weeks Double-blind treatment:12 weeks
Slide 23: PXL770 Successful Phase 2a Results
PXL770 Successful Phase 2a Results Statistically Significant Results and Greater Efficacy in Patients with Diabetes Liver Fat Content (% Change from baseline) ALT (IU/L Change from baseline) NAFLD with / without T2DM T2D subgroup T2D subgroup 3 Pbo 250 QD 250 BID 500 QD Pbo 250 QD 250 BID 500 QD Pbo
Slide 24: T2D Subgroup - Improved Fasting Glucose & HbA1c
T2D Subgroup - Improved Fasting Glucose & HbA1c Despite Low Baseline Values Fasting Glucose HbA1c Baseline 144.0 mg/dL 143.7 mg/dL 134.8 mg/dL 121.5 mg/dL Baseline 6.69 % 7.15 % 6.73 % 6.57 % Pbo 250 QD 250 BID 500 QD Pbo 250 QD 250 BID 500 QD 10 0,2% 9,7 9,4 0,1 LS mean change from Baseline mg/dL m
Slide 25: PXL770 Profile
PXL770 Profile Phase 2A Efficacy Results (in T2D Subgroup) vs. Selected Oral Competitors# PXL770◊ Galmed Madrigal Viking Intercept Enanta Metacrine T2DM Aramchol1 Resmetirom2 VK28093 OCA 4,5 EDP-3056 MET4097 AMPK SCD1 THR-b TR FXR FXR FXR Relative % LFC decrease vs. baseline -27.2 -12.6 -32.9 -53-60
Slide 26: PXL770 - Translation of AMPK Activation Approach
PXL770 - Translation of AMPK Activation Approach Remaining Hypotheses to be Addressed in Phase 2b Rodent (in vivo) Human Cells (in vitro) NASH / NAFLD Patient ✓ ↓ steatosis score; ↓ liver ✓ ↓ de novo lipogenesis; ↓ Steatosis lipids; ↓ de novo ✓ ↓ de novo lipogenesis liver fat mass lipogenesis ✓ ↓ in
Slide 27: PXL770 Phase 2b Trial Design
PXL770 Phase 2b Trial Design On Track to Initiate in 2021 Randomization Week 52 1:1:1 PXL770 Dose 1 QD / ~100 patients Key inclusion criteria • Biopsy proven NASH patients PXL770 Dose 2 QD / ~100 patients • Prediabetic or diabetic patients Placebo QD / ~100 patients • Liver fat content (MRI-PDFF) Sc
Slide 28: NASH and Type 2 Diabetes – Strong Clinical Overlap
NASH and Type 2 Diabetes – Strong Clinical Overlap NASH with T2D - High Prevalence and Greater Unmet Medical Need • Approximately 40-50% of NASH • Insulin resistance greater in patients with both NASH patients have coexisting T2D1 and T2D vs. either alone4-6 • High prevalence of NAFLD (>60-70%) and
Slide 29: PXL770 - Safety & Conclusions
PXL770 - Safety & Conclusions • Well tolerated, with acceptable safety profile • Target engagement established (reduced DNL) • Significant improvements in multiple NASH-related parameters • Greater response in patients with T2D o consistent with lower endogenous AMPK “tone” hypothesis o additional g
Slide 30: PXL065
NASH PXL065 Proprietary Program MPC Inhibitor for the Treatment of NASH Utilizing the 505(b)(2) Regulatory Pathway 30
Slide 31: PXL065: Leveraging the Benefits of Pioglitazone With Reduced PPAR Activity
PXL065: Leveraging the Benefits of Pioglitazone With Reduced PPAR Activity • Pioglitazone used in T2D1,2 – most extensively studied molecule in NASH – multiple trials3 • Recommended for NASH by AASLD & EASL Practice Guidelines4 • Currently prescribed by ~14% of physicians for biopsy-proven NASH pat
Slide 32: Pioglitazone Demonstrated Strong Efficacy in NASH Trials
Pioglitazone Demonstrated Strong Efficacy in NASH Trials Comparison vs. Other Agents in Development 50% Oral Agents Parenteral Agents 45% 42% Patients with Improvement, % Placebo-Adjusted Treatment Effect for Resolution of NASH 40% without worsening of fibrosis 35% 32% 30% 30% 26% 25% 21% 20% 15% 15
Slide 33: PXL065 Profile in NASH Preclinical Models
PXL065 Profile in NASH Preclinical Models PXL065 (R-Pio) Retains Benefits of Pio; S-Pio Drives Weight Gain and Fluid Retention NASH Rodent Models1 Pio PXL-065 Body Weight Gain in Mouse Model2 Functional Parameters (0-11 days) Hepatic Triglycerides ✓ ✓ 6 **** **** p io **** **** **** Hepatic Free
Slide 34: PXL065 Ph1 Study Results
PXL065 Ph1 Study Results 15 mg vs. 45 mg Actos®1: Similar R-Pio Exposure; S-Pio Exposure Decreased ~5-fold Exposure to R-pio Exposure to S-pio • Single (SAD) and repeated (Phase 1b) oral dose studies completed • Stabilization and sustained higher exposure to R-pio (limited conversion to S-pio) • PK
Slide 35: PXL065 Ongoing Phase 2 in Biopsy-Proven NASH Patients
PXL065 Ongoing Phase 2 in Biopsy-Proven NASH Patients Single Streamlined Study - 505(b)(2) Pathway; Designed to Select Ph3 Dose(s) Randomization PXL065 7.5 mg QD / 30 patients Week 36 1:1:1:1 PXL065 15 mg QD / 30 patients Key inclusion criteria PXL065 22.5 mg QD / 30 patients • Biopsy-proven NASH pa
Slide 36: PXL770 and PXL065: NASH Value Proposition
PXL770 and PXL065: NASH Value Proposition • Two oral, first-in-class Phase 2 programs addressing an unmet medical need with large market opportunity • Differentiated approaches to control key pathways that lead to liver injury with innovative development strategies • PXL770 - differentiated Phase 2b
Slide 37: Pipeline Expansion
Additional Opportunities Pipeline Expansion Chronic and Rare Metabolic Indications Next Generation AMPK Activators Next Generation D-TZD’s* *Deuterium-modified thiazolidinediones. 37
Slide 38: Harnessing AMPK and D-TZD Platforms to Address Diseases with Metabolic Pathophysiology
Harnessing AMPK and D-TZD Platforms to Address Diseases with Metabolic Pathophysiology Next Generation Programs Approaching Clinical Candidate Selection (Both Platforms) AMPK MPC Acetyl Co-A Pyruvate TCA cycle ATP NADH FADH2 Activates Inhibits MRC catabolic Inhibits inflammation T pathways anabolic
Slide 39: Upcoming Milestones
Upcoming Milestones 39
Slide 40: Near-Term Milestones to Drive Poxel's Growth
Near-Term Milestones to Drive Poxel’s Growth NASH PXL065: Ph 2 recruitment completed T2DM Platform PXL770: Cash Clinical Pharmacology studies PXL770: (Hepatic impairment, Drug Drug Initiation of Ph 2b trial interaction, Bioavailability) PXL065: Results for Ph 2 trial 2021 2022 Exploring options to p
Slide 41: Thank You
Thank You 41
Slide 42: Contacts
Contacts Aurélie Bozza Investor Relations and Communication Director aurelie.bozza@poxelpharma.com +33 6 99 81 08 36 Catherine David Investor Relations & Communication Manager catherine.david@poxelpharma.com +33 7 64 57 61 78 www.poxelpharma.com 42