Slide 1: Full Year 2022 Financial and Corporate Update
Full Year 2022 Financial and Corporate Update March 23, 2023
Slide 2: Agenda
Agenda 1. 2022 Summary & Early 2023 Corporate Update 2. Extended cash runway based on debt restructuring and new equity-linked financing (announced today) 3. Commercial Update - TWYMEEG 4. Financial Update – FY 2022 results 5. Clinical Update ▪ Rare Metabolic Disease Programs ▪ NASH 6. Conclusion &
Slide 3: Disclaimer
3 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”, “
Slide 4: 2022 Summary & Early 2023 Corporate Update (1/2)
2022 Summary & Early 2023 Corporate Update (1/2) Financing Update • Extension of the cash runway through Q2 2025 based upon: o A debt restructuring agreement, which postpones initiation of repayments until Q1 2025 at the latest, to be repaid with positive net royalty1 flow to Poxel anticipated to st
Slide 5: 2022 Summary & Early 2023 Corporate Update (2/2)
2022 Summary & Early 2023 Corporate Update (2/2) Clinical update • Rare disease: o Adrenoleukodystrophy (ALD): Phase 2 POC studies prepared to initiate, pending additional financing ▪ Additional regulatory designations: Orphan (EU & US); Fast Track (US) for ALD for both PXL770 & PXL065 o Autosomal-d
Slide 6: Today's announcement
Today’s announcement Debt Restructuring Agreements and New Equity-linked financing
Slide 7: Cash Runway Extended through Q2 2025
Cash Runway Extended through Q2 2025 Based on Debt Restructuring Agreements and New Equity-linked financing1 • Debt Restructuring o Agreements with lenders to postpone initiation of repayments to be repaid with positive net TWYMEEG royalties2, expected Q1 2025 at latest, under conservative forecast
Slide 8: Commercial Update
Commercial Update TWYMEEG® (Imeglimin) Sales in Japan
Slide 9: TWYMEEG Sales in Japan
TWYMEEG Sales in Japan Strong Growth Leading to 20% Increase of Sumitomo FY20221 Forecast2 Quarterly Sales Full Year 20221 Forecast2 + 20% 1.8 1.5 0.8 0.4 0.1 Apr- Jun 2022 Jul - Aug 2022 Oct - Dec 2022 Original Current JPY billions 1. Sumitomo Pharma fiscal year April-March. 9 2. Gross Sales and FY
Slide 10: TWYMEEG (Imeglimin): Strong Growth Trajectory
TWYMEEG® (Imeglimin): Strong Growth Trajectory Partnered in Asia1 with Diabetes Market Leader, Sumitomo Pharma • Commercial Strategy o Sumitomo #1 diabetes franchise; FY212 JPY 79B; o Positioning: TWYMEEG can be prescribed as add-on to any therapy and as monotherapy; Increasing combination use with
Slide 11: Board of Directors – Changes in Organization
Corporate Update Board of Directors – Changes in Organization Board of Directors New Board Advisory Committee • Resized to 4 current members • Creation of a new Board advisory committee composed of • Khoso Baluch as Chairman former Board members, who will continue to assist the Company in all its ac
Slide 12: Financial Update
Financial Update Full Year 2022
Slide 13: 2022 Revenue
2022 Revenue* Mainly reflecting royalty revenue from Sumitomo Pharma EUR (in thousands) FY FY • Revenue for 2022 reflects of JPY 95 million 2021 2022 (EUR 0.672 million) of royalty revenue from 12 12 Sumitomo Pharma, which represents 8% of months months TWYMEEG net sales in Japan Sumitomo Agreement
Slide 14: Statement of Comprehensive Income as of Dec. 31, 2022
Statement of Comprehensive Income as of Dec. 31, 2022* December 31, December 31, EUR (in thousands) 2021 2022 Reflects mainly JPY 95 million (EUR Revenue 13.397 674 0.672 million) of royalty revenue from Sumitomo Pharma, which represents Cost of sales (59) (672) 8% of TWYMEEG net sales in Japan Gros
Slide 15: Statements of Financial Position as of December 31, 2022 (Assets)
Statements of Financial Position as of December 31, 2022* Assets December December EUR (in thousands) 31, 2021 31, 2022 Mostly reflects DeuteRx portfolio Intangible assets 16,631 16,606 acquisition in 2018 Property, plant and equipment 1,716 1,323 Other non-current financial assets 206 211 Deferred
Slide 16: Statements of Financial Position as of December 31, 2022 (Liabilities)
Statements of Financial Position as of December 31, 2022* Shareholders’ Equity and Liabilities December 31, December 31, EUR (in thousands) 2021 2022 Total shareholders' equity 8,206 -18,241 Mostly reflects FY2022 net loss Employee benefits 370 252 Non-current financial liabilities 30,094 25,218 Pro
Slide 17: Statements of Cash Flow as of Dec. 31, 2022
Statements of Cash Flow as of Dec. 31, 2022* EUR (in thousands) December 31, December 31, 2021 2022 Cash flows from operating activities before (18,791) (18,477) change in WC (-) Changes in working capital requirements 1,898 (3,335) Reflects operating loss net of non cash Cash flows from operating a
Slide 18: Robust Mid-to-Late Stage Metabolic Pipeline
Robust Mid-to-Late Stage Metabolic Pipeline Focus on NASH and Rare Metabolic Diseases Discovery/ Approved/ Indication MOA PH 1 PH 2 PH 3 Recent & Upcoming Milestones PC Marketed NASH Non-Genomic • Positive Phase 2; Discussions for a potential pivotal PXL065 NASH program in NASH; leveraging 505(b)(2)
Slide 19: Rare Metabolic Disease Programs
Rare Metabolic Disease Programs PXL770 - AMPK Activator • Adrenoleukodystrophy (ALD) - Fast Track & Orphan Drug • Autosomal Dominant Polycystic Kidney Disease (ADPKD)
Slide 20: 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 21: Adrenoleukodystrophy
Adrenoleukodystrophy A Not-so-Rare Orphan Neurometabolic Disease Diagnosis & Clinical Genetics Prevalence Features • Monogenic, X-linked mutations in Estimated US Prevalence1 • Diagnosis – ABCD1 gene 20,000 – 29,000 • newborn screening – increasingly • Gene encodes a transporter present common (now
Slide 22: 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 23: Planned Phase 2a Studies in ALD/AMN
Planned Phase 2a Studies in ALD/AMN Fast Track & Orphan Designation for PXL770 & PXL065; Two Identical Studies Key inclusion criteria • Males with AMN Screening Follow Period PXL770 / PXL065 up • Age 18-65 • No active cerebral disease Treatment period • 12-24 patients each 12 weeks stable baseline m
Slide 24: ALD Opportunity Summary
ALD Opportunity Summary High Unmet Needs, Blockbuster Market Potential • Blockbuster market opportunity o US prevalence of 20,000-29,000; Global prevalence of 444,000 – 644,000 o Ability for premium pricing based upon other orphan drugs with similar prevalence o Potential Regulatory designations: ▪
Slide 25: ADPKD and Rationale for AMPK & PXL770
ADPKD and Rationale for AMPK & PXL770 ADPKD • 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 tolerabil
Slide 26: PXL770 Opportunity in ADPKD
PXL770 Opportunity in ADPKD Phase 2-Ready Asset with Orphan Drug Designation • Robust efficacy profile with target engagement in established ADPKD model systems: o reduced cyst growth in human and canine assays o in inducible kidney epithelium-specific Pkd1 knockout mouse: normalized kidney function
Slide 27: Clinical Update
Clinical Update PXL065 in NASH, results of Phase 2 NASH Trial (DESTINY-1)
Slide 28: 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 ALT/AST Steatosis Inflammation Fibrosis Promrat 20041 18 48 wks ✓ ✓ ✓ ✓ 6 Biopsy Trials Belfort 20062, Gastaldelli 20213 55 6 mos ✓ ✓ ✓ ✓ Ait
Slide 29: PXL065 Phase 2 Trial Design
PXL065 Phase 2 Trial Design: Single Streamlined Study - 505(b)(2) Pathway Randomization PXL065 7.5 mg QD / 25 patients Week 36 1:1:1:1 N=117 PXL065 15 mg QD / 32 patients Key inclusion criteria PXL065 22.5 mg QD / 30 patients • Biopsy-proven NASH patients Placebo QD / 30 patients • Liver fat content
Slide 30: 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 14 5 p = 0.07 LS Mean change from baseline (%) - SEM 12 0 p = 0.07 40% Number
Slide 31: PXL065 Fibrosis Response Compared to Other Candidates
PXL065 Fibrosis Response Compared to Other Candidates >1 Stage Fibrosis Improvement with no Worsening of NASH (FDA Approval Endpoint) Orals Injectables PXL065 Resmetirom Lanifibranor Obeticholic Acid Semaglutide Efruxifermin Phase 2b – 36 wks Phase 3 – 52 wks Phase 2b – 24 wks Phase 3 – 72 wks Phase
Slide 32: Safety Summary
Safety Summary • Good safety-tolerability • No dose dependent weight gain • No increase in edema • Summary of Treatment Emergent Adverse Events (TEAEs) o No relevant difference in the incidence of subjects presenting with TEAE (60 to 80%), mainly from grade 1 or grade 2 severity o Low incidence in s
Slide 33: Results Published in Journal of Hepatology
Results Published in Journal of Hepatology Nature Review: “Safer pioglitazone alternative is effective” 33
Slide 34: Phase 2 PXL065 Summary & Next Steps
Phase 2 PXL065 Summary & Next Steps • Primary efficacy endpoint met • Strong improvement in fibrosis observed (FDA approval endpoint) - effect size as good or better than leading competitors’ results o PXL065 has potential for better fibrosis benefit than Resmetirom (Phase 2 vs Phase 3 data), which
Slide 35: Conclusion
Conclusion Summary & Upcoming milestones
Slide 36: Summary Highlights
Summary Highlights • TWYMEEG in Japan – strong growth trajectory confirmed o Sales grew 90% over prior quarter; Sumitomo FY2022 forecast increased 20% o Confidence in increasing royalties facilitated debt restructuring • Significant extension of our cash runway through Q2 2025 o Based upon debt rest
Slide 37: 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 to advance in NASH as a partnered program NASH − Discussions for a potential pivotal program in NASH initiated • PXL770 development
Slide 38: Question & Answer Session
Question & Answer Session Participants can submit questions in the chat