Slide 1: Half Year 2022 Financial and Corporate Update
Half Year 2022 Financial and Corporate Update September 21, 2022
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: Agenda
Agenda ▪ Recent developments and Corporate highlights ▪ Thomas Kuhn, CEO ▪ H1 2022 Financials ▪ Anne Renevot, EVP, CFO ▪ Clinical Update in Rare Diseases & Focus on PXL065 Phase 2 DESTINY-1 results ▪ David Moller, EVP, Chief Scientific Officer ▪ Stephen Harrison, MD, President, Summit Clinical Resea
Slide 4: Poxel Recent Strategic Developments
Poxel Recent Strategic Developments • Positive results from Phase 2 NASH Trial (DESTINY-1) for PXL065 • Primary efficacy endpoint met: statistically significant improvements in the relative decrease in liver fat content at 36-weeks for all doses. • PXL065 was observed to be safe and well tolerated w
Slide 5: Year to date 2022 Highlights
Year to date 2022 Highlights • Strengthening the value of PXL065 and PXL770 • PXL065: New US patent provides additional protection through 2041 and could expand protection worldwide, with the potential for an additional 5 years through patent term extension • PXL065 & PXL770: FDA Fast Track and Orph
Slide 6: Robust Mid-to-Late Stage Metabolic Pipeline
Robust Mid-to-Late Stage Metabolic Pipeline Focus on Rare Metabolic Diseases and NASH Discovery/ Approved/ Indication MOA PH 1 PH 2 PH 3 Upcoming Milestones PC Marketed NASH Non-Genomic • Positive Phase 2; Initiation of discussions for a PXL065 NASH potential pivotal program in NASH; leveraging TZD1
Slide 7: Financial Update
Financial Update First Half 2022
Slide 8: H1 2022 Revenue
H1 2022 Revenue* Mainly reflecting royalty revenue from Sumitomo Pharma EUR (in thousands) H1 2021 H1 2022 • Revenue for the first half of 2022 6 months 6 months reflects JPY 11 million (EUR 81 thousand) of royalty revenue from Sumitomo Pharma which represents Sumitomo Pharma Agreement 13,274 83 8%
Slide 9: Statement of Comprehensive Income as of June 30, 2022
Statement of Comprehensive Income as of June 30, 2022* June 30, 2021 June 30, 2022 EUR (in thousands) Adjusted** Reflects JPY 11 million (EUR 81 thousand) of royalty revenue from Sumitomo Revenue 13,274 83 Pharma which represents 8% of TWYMEEG net sales in Japan. Cost of sales (83) Gross margin 13,2
Slide 10: Statements of Financial Position as of June 30, 2022 (Assets)
Statements of Financial Position as of June 30, 2022* Assets December June 30, EUR (in thousands) 31, 2021 2022 Mostly reflects DeuteRx portfolio acquisition in 2018 Intangible assets 16,631 16,615 Property, plant and equipment 1,716 1,572 Other non-current financial assets 206 143 Total non-current
Slide 11: Statements of Financial Position as of June 30, 2022 (Equity and Liabilities)
Statements of Financial Position as of June 30, 2022* Shareholders’ Equity and Liabilities December June 30, EUR (in thousands) 31, 2021 2022 Total shareholders' equity 8,206 -3,594 Employee benefits 370 237 Non-current financial liabilities 30,094 26,155 Provisions 318 74 Non-current liabilities 30
Slide 12: Statements of Cash Flow as of June 30, 2022
Statements of Cash Flow as of June 30, 2022* June 30, June 30, EUR (in thousands) 2021 2022 Adjusted** Cash & cash equivalent as of the opening 40,203 32,287 date Cash flows from operating activities (16,067) (13,301) Cash flows from investing activities 10 (70) Cash flows from financing activities
Slide 13: Key Financial & Shareholder Information
Key Financial & Shareholder Information Market data Shareholder ownership2 Bpi France 17.9% Ticker: POXEL Founders ISIN: FR0012432516 9.5% Floating Number of shares: 29 242 2511 72.6% Key financials Analyst coverage • As of 6/30/22 cash & cash equivalents: Bryan Garnier Alex Cogut EUR 16.1 million (
Slide 14: Additional Opportunities in Rare Diseases
Additional Opportunities in Rare Diseases Adrenoleukodystrophy (ALD) Autosomal Dominant Polycystic Kidney Disease (ADPKD)
Slide 15: AMP Kinase Activation
AMP Kinase Activation PXL770 and Next Generation Molecules AMPK Overnutrition (metabolic Caloric Restriction, syndrome, NASH, Type 2 Exercise Diabetes) PXL770 Activates catabolic Other benefits pathways • Reduces inflammation • Fatty acid oxidation ↓macrophage and dendritic • Glucose uptake cell act
Slide 16: ALD: AMPK Rationale and Strong Preclinical Data
ALD: AMPK Rationale and Strong Preclinical Data • Deletion of AMPK in disease cells → mitochondrial dysfunction1 ; reduced AMPK in patient-derived cells and patient brain tissue2,3 • AMPK activation evidence of efficacy in patient cells and animal model3,4 • PXL770 is active in patient-derived cells
Slide 17: ADPKD and AMPK
ADPKD and AMPK • Autosomal-dominant genetic form of CKD • 140,000 patients in US; fourth leading cause of CKD • >50% develop renal failure by age 50 → dialysis, transplant • 1 drug approved - tolvaptan - used to attenuate progression; severe liver AE’s and poor tolerability (polyuria) T Why AMPK ? •
Slide 18: PXL770 Opportunity in ADPKD
PXL770 Opportunity in ADPKD AMPK - Compelling Target; Phase 2-Ready Asset • Pathophysiology - altered kidney metabolism, activation of growth pathways that AMPK inhibits; AMPK activation shown to attenuate disease in preclinical models1-4 • PXL770 – robust efficacy profile in established model syste
Slide 19: DESTINY-1 results
DESTINY-1 results Phase 2 NASH Trial for PXL065
Slide 20: Pioglitazone Extensively Studied and Effective in NASH
Pioglitazone Extensively Studied and Effective in NASH Recommended Use by AASLD-EASL - not Prescribed due to Common AE’s Study N Duration Improvements in NASH Enzymes Steatosis Inflammation Fibrosis Promrat 20041 18 48 wks ✓ ✓ ✓ ✓ 6 Biopsy Trials Belfort 20062 55 6 mos ✓ ✓ ✓ Aithal 20083 74 12 mos ✓
Slide 21: PXL065: Oral NCE Derived from Pioglitazone
PXL065: Oral NCE Derived from Pioglitazone • Pioglitazone, TZDs*: 2 enantiomers that rapidly interconvert; both genomic (PPAR) and non- genomic mechanisms • PXL065 is deuterium-stabilized single stereoisomer (NCE); selectively mediates non-PPAR effects of pioglitazone – retains efficacy in preclin
Slide 22: Phase 2 Trial Design
Phase 2 Trial Design Single Streamlined Study - 505(b)(2) Pathway 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 patients Placebo QD / 30 patients • Liver fat content (MRI-PDFF) ≥
Slide 23: Summary of Subject Disposition
Summary of Subject Disposition Randomized subjects N = 117 ITT & Safety set PXL065 7,5mg PXL065 15mg PXL065 22,5mg Placebo N = 25 N = 32 N = 30 N = 30 Completers: 21 (84%) Completers: 23 (72%) Completers: 27 (90%) Completers: 24 (80%) Reasons for study discontinuation: Reasons for study discontinuat
Slide 24: Summary of Demographic and Baseline Characteristics
Summary of Demographic and Baseline Characteristics ITT Set PXL065 7,5mg QD PXL065 15mg QD PXL065 22,5mg QD Placebo Overall (N = 25) (N = 32) (N = 30) (N = 30) (N = 117) Age (years), mean (SD) 50.7 (17.3) 54.1 (10.9) 53.4 (12.4) 54.8 (10.2) 53.4 (12.6) Ethnicity, n (%) Hispanic or latino 11 (44.0) 8
Slide 25: Primary Efficacy Endpoint - Relative Change in LFC
Relative Change in LFC (%) from Baseline to Week 36 Primary Efficacy Endpoint - Primary Analysis - ITT Set Relative Change in LFC (%) from Baseline to Week 361 Relative Reduction in LFC (%) ≥ 30% from Baseline to Week 362 PXL065 PXL065 PXL065 PXL065 PXL065 PXL065 Placebo 7.5 mg QD 15 mg QD 22.5 mg Q
Slide 26: Change from Baseline to Week 36 in Liver Function Tests
Change from Baseline to Week 36 in Liver Function Tests Secondary Efficacy Endpoints – ITT Set 10.0 ALT AST GGT ALP Mean ALT Change (Pooled PXL065) BL 54.2 71.6 58.7 61.0 45.3 49.7 47.3 50.8 48.8 62.4 67.0 91.0 93.4 94.7 88.5 98 5.0 3.1 0.0 LS Mean change from baseline (U/L) - SEM -2.8 -4.9 -4.2 -5.
Slide 27: Individual Patient ALT Change from Baseline
Individual Patient ALT Change from Baseline (IU/L) Positive Trends in all PXL065 Dose Groups Absolute Change from Baseline in ALT (U/L) at Week 36 - Placebo Absolute Change from Baseline in ALT (U/L) at Week 36 - PXL065 7.5 mg ITT Population ITT Population 120 120 Placebo 7.5 mg Planned Treatment Pl
Slide 28: Improved Biomarkers of Fibrogenesis - Fibrosis Risk Scores
Improved Biomarkers of Fibrogenesis - Fibrosis Risk Scores Exploratory Efficacy Endpoints - ITT Set Pro-C3 PIIINP ELF Placebo PXL065 7.5 mg QD PXL065 15 mg QD PXL065 22.5 mg QD Placebo PXL065 7.5 mg QD PXL065 15 mg QD PXL065 22.5 mg QD Placebo PXL065 7.5 mg QD PXL065 15 mg QD PXL065 22.5 mg QD LS Me
Slide 29: Responses in Liver Histology – Fibrosis
Responses in Liver Histology – Fibrosis Exploratory Efficacy Endpoint– Completers with Biopsy* ≥ 1 point improvement in NASH ≥ 1 point improvement in fibrosis CRN fibrosis score without worsening of NASH PXL065 PXL065 PXL065 PXL065 PXL065 PXL065 Placebo 7.5 mg QD 15 mg QD 22.5 mg QD Placebo 7.5 mg Q
Slide 30: PXL065 Fibrosis Response Comparison to Other Candidates
PXL65 Fibrosis Response Comparison to Other Candidates >1 Stage Fibrosis Improvement with no Worsening of NASH* PXL065 Resmetirom Lanifibranor Obeticholic Acid Semaglutide Efruxifermin Phase 2b – 36 wks Phase 2b – 36 wks Phase 2b – 24 wks Phase 3 – 72 wks Phase 2b – 72 wks Phase 2b – 24 wks Injectab
Slide 31: Responses in Liver Histology - NASH
Responses in Liver Histology - NASH Exploratory efficacy endpoint – Completers with Biopsy ≥ 2-point improvement in NAS without NASH Resolution with no worsening in NASH Resolution with ≥ 1 point worsening of fibrosis score Fibrosis score improvement in NASH CRN Fibrosis Score PXL065 PXL065 PXL065 P
Slide 32: Responses in Liver Histology – Pooled PXL065
Responses in Liver Histology – Pooled PXL065 Post Hoc Analysis – Completers with Biopsy Steatosis %%Worsening Worsening % Improvement Fibrosis PLX065 N=69 12% 42% PLX065 N=69 10% 42% Placebo N=23 22% 17% Placebo N=23 26% 17% Inflammation Ballooning PLX065 N=69 7% 54% PLX065 N=69 3% 52% Placebo N=23
Slide 33: Metabolic Parameters - HbA1c and Insulin Sensitivity
Metabolic Parameters - HbA1c and Insulin Sensitivity Secondary Efficacy Endpoint – ITT Set HbA1c (%) Serum C-peptide (nmol/L) PXL065 PXL065 PXL065 PXL065 PXL065 PXL065 Placebo 7.5 mg QD 15 mg QD 22.5 mg QD Placebo 7.5 mg QD 15 mg QD 22.5 mg QD Baseline 6.18 6.21 6.07 6.27 Baseline 1.759 1.845 1.757
Slide 34: Metabolic Parameters - Adiponectin and Lipids
Metabolic Parameters - Adiponectin and Lipids Exploratory Efficacy Endpoint - ITT Set Placebo PXL065 7.5 mg QD PXL065 15 mg QD PXL065 22.5 mg QD Baseline 4.02 3.67 3.44 4.28 8.000 LS Mean change from baseline (µg/mL) - SEM 7.000 p < 0.0001 6.000 p = 0.0014 5.000 p = 0.0639 • No change in total / LDL
Slide 35: Change from Baseline in Body Weight to Week 36
Change from Baseline in Body Weight (kg) to Week 36 Safety Endpoint - Safety Set Placebo PXL065 7.5 mg QD PXL065 15 mg QD PXL065 22.5 mg QD Baseline 6.000 100.5kg 92.3 kg 105.0 kg 101.0 kg p = 0.4288 LS Mean change from baseline (kg) - SEM 5.000 p = 0.0056 4.000 p = 0.1944 3.000 2.000 2.36 1.000 1.0
Slide 36: Placebo Adjusted Change in Body Weight
Placebo Adjusted Change in Body Weight Comparison to Published Pioglitazone Results 6 PXL065 Pioglitazone 5 Phase 2 – 36 wks 24 wks studies Change in weight (kg) 4.7# 4 4.1 3 3.2# 2.5 2 1 1.2 0.7 0 7.5 mg 15 mg 22.5 mg 30 -> 45 mg 45 mg2 45 mg3 and -500kcal/d1 Limited potential for body weight gain
Slide 37: Timecourse of Body Weight and Incidence of Edema
Timecourse of Body Weight (kg) and Incidence of Edema Safety Endpoint - Safety Set MeanPercent Mean % Change fromfrom Change Baseline Weight Baseline (kg) (kg) Weight by Treatment Group by Treatment group 10.0 Pitting Peripheral Edema Edema Weight (kg) Mean Percent Change from Baseline +/- SEM 7.5 N
Slide 38: Overall Frequency of Treatment Emergent Adverse Events
Overall Frequency of Treatment Emergent Adverse Events Safety Endpoint - Safety Set • No relevant difference in the incidence of subjects presenting with TEAE (60 to 80%), mainly from grade 1 or grade 2 severity • Low incidence in subjects presenting with related TEAE (12 to 27%) • One death (placeb
Slide 39: Dose Proportionality in Exposure
Dose Proportionality in Exposure Greater R- vs. S-stereoisomer as previously reported from Phase 1 Cmax at steady state 15000 AUC0-24 at steady state R-Pio R-Pio S-Pio S-Pio Predicted AUC0-24 (ng.h/mL) Predicted Cmax (ng/mL) 10000 5000 0 7.5 mg 15 mg 22.5 mg 7.5 mg 15 mg 22.5 mg 7.5 mg 15 mg 22.5 mg
Slide 40: Conclusions
Conclusions • Achieved primary endpoint (liver fat content) at all 3 doses • Non-invasive NASH tests show positive effects • Strong effect to reduce fibrosis (and prevent worsening); favorable trends in other histology endpoints including increasing number of patients who reach both endpoints of fib
Slide 41: Next Steps & Conclusion
Next Steps & Conclusion e soos
Slide 42: Strategic Focus on NASH and Rare Diseases
Strategic Focus on NASH and Rare Diseases Targeting Indications with High Unmet Needs - Differentiated Molecules Can Make The Difference Next steps • PXL065 prioritized for further development in NASH NASH − Discussions for a potential pivotal program in NASH will be initiated. • PXL770 development
Slide 43: Question & Answer Session
Question & Answer Session Participants can submit questions in the chat