Slide 1: Half Year 2023 Financial and Corporate Update
Half Year 2023 Financial and Corporate Update September 26, 2023
Slide 2: Agenda
Agenda 1. H1 2023 Corporate & Business Update 2. Financial Update – H1 2023 results 3. Rare Metabolic Disease Programs Opportunities 4. Conclusion 5. Q&A 2
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: H1 2023 Summary (1/2)
H1 2023 Summary (1/2) • 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, supported by the strong growth trajectory of TWYMEEG® (Imeglimin) sa
Slide 5: H1 2023 Summary (2/2)
H1 2023 Summary (2/2) • Progress rare diseases and NASH plan o Continued preparing ALD plan with Phase 2 proof-of-concept (POC) studies ready to launch, pending additional financing o In July, Poxel was chosen as the winner of the 2023 edition of the I-nov contest, financed by the French State, for
Slide 6: H1 2023 Highlights
H1 2023 Highlights Thomas Kuhn, CEO
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 until Q1 2025 at latest (under conservative forecast) ▪ Positive net royalties (royalties above 8%2) and sa
Slide 8: TWYMEEG (Imeglimin) in Japan: Strong Growth Trajectory
TWYMEEG® (Imeglimin) in Japan: Strong Growth Trajectory Strong Growth Trend In 20221, Confirmed by 2023 Sumitomo Pharma Forecast2 TWYMEEG Revenue Trends o Sales in Japan for FY22 (JPY 2.2B, EUR 15.0M) exceeded prior guidance by more than 20% o Sumitomo Pharma FY23 forecast (JPY4.2B, EUR 28.9M) = 90%
Slide 9: TWYMEEG (Imeglimin): Commercial Strategy
TWYMEEG® (Imeglimin): Commercial Strategy Partnered in Asia1 with Diabetes Market Leader, Sumitomo Pharma • Commercial Strategy o Sumitomo Pharma #1 diabetes franchise; FY212 JPY 79B; Collaboration Summary o Positioning: TWYMEEG can be prescribed as add-on to any therapy and as monotherapy; Increasi
Slide 10: Corporate Update Changes in Organization
Corporate Update Changes in Organization Management team Board of Directors Thomas Kuhn (Pharm D, Pascale Fouqueray (MD, PhD) Khoso Baluch Pascale Boissel MBA) EVP, Clinical Development & Chairman of the Independent Chief Executive Officer Regulatory Affairs, Board Board member Co-founder and Co-fou
Slide 11: Financial Update
Financial Update H1 2023 Results
Slide 12: H1 2023 Revenue
H1 2023 Revenue* Mainly reflecting royalty revenue from Sumitomo Pharma EUR (in thousands) H1 2022 H1 2023 • Revenue for H1 2023 reflects of JPY 148 6 months 6 months million (EUR 0.955 million) of royalty revenue from Sumitomo Pharma, which Sumitomo Agreement 83 955 represents 8% of TWYMEEG net sal
Slide 13: Income Statement as of June 30, 2023
Income Statement as of June 30, 2023* EUR (in thousands) June 30, 2022 June 30, 2023 Reflects mainly JPY 148 million (EUR Revenue 83 955 0.955 million) of royalty revenue from Sumitomo Pharma, which represents Cost of sales (83) (955) 8% of TWYMEEG net sales in Japan Gross margin Research and develo
Slide 14: Statements of Financial Position as of June 30, 2023 (Assets)
Statements of Financial Position as of June 30, 2023* Assets December 31, June 30, 2023 EUR (in thousands) 2022 Intangible assets 16 606 19 Primarily reflects the impairment loss for Property, plant and equipment 1 323 892 the entire value of PXL065, €16,6m to best reflect the current value of PXL06
Slide 15: Statements of Financial Position as of June 30, 2023 (Equity and Liabilities)
Statements of Financial Position as of June 30, 2023* Shareholders’ Equity and Liabilities December 31, June 30, 2023 EUR (in thousands) 2022 Total shareholders' equity -18 241 -25 315 Change in Shareholders’ equity mostly reflects H1 2023 net loss partially offset by Employee benefits 252 177 capit
Slide 16: Statements of Cash Flow as of June 30, 2023
Statements of Cash Flow as of June 30, 2023* June 30, June 30, EUR (in thousands) 2022 2023 Cash & cash equivalent as of the opening 32 287 13 058 date Reflects operating loss net of non cash accounting adjustments Cash flows from operating activities (13 301) (7 841) Cash flows from investing activ
Slide 17: Robust Mid-to-Late Stage Metabolic Pipeline
Robust Mid-to-Late Stage Metabolic Pipeline Focus on Rare Metabolic Diseases and NASH Approved/ Indication MOA Preclinical PH 1 PH 2 PH 3 Recent & Upcoming Milestones Marketed Rare Metabolic Indications AMPK3 • Fast Track & Orphan Drug Designations (2022) PXL770 ALD1 Activator • Phase 2 launch pendi
Slide 18: Rare Metabolic Disease Programs Opportunities
Rare Metabolic Disease Programs Opportunities PXL770 - AMPK Activator • Adrenoleukodystrophy (ALD) - Fast Track & Orphan Drug • Autosomal Dominant Polycystic Kidney Disease (ADPKD)
Slide 19: Adrenoleukodystrophy
Adrenoleukodystrophy A Not-so-Rare Orphan Neurometabolic Disease Diagnosis & Genetics Prevalence Clinical 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 >6
Slide 20: AMP Kinase Activation
AMP Kinase Activation Beneficial Role in ALD Pathophysiology C16:0 Fatty Acids pool Reduces Fatty Acid (FA) pool AMPK chain- Improves C22:0 master sensor of elongation VLCFA Mitochondrial cellular homeostasis ELOVL1 C24:0 dysfunction and lipid metabolism C26:0 VLCFA Increase FA oxydation Accumulatio
Slide 21: PXL770: Strong Preclinical Data
PXL770: Strong Preclinical Data • PXL770 is active in patient-derived cells and in the classical animal model • Sufficient brain and spinal cord penetration expected in human to trigger similar VLCFA1 reduction as observed in animal models in these tissues AMN - Fibroblasts Plasma VLCFA in Abcd1 Low
Slide 22: PXL770 - Phase 2 Ready Molecule with Demonstrated Human Target Engagement
PXL770 - Phase 2 Ready Molecule with Demonstrated Human Target Engagement and Translation Established Human Safety (> 200 Subjects; up to 12 Weeks) Rodent (in vivo) Human Cells (in vitro) Human Patient ✓ ↓ steatosis score ✓ ↓ de novo lipogenesis ✓ ↓ de novo lipogenesis Steatosis ✓ ↓ liver lipids ✓ ↓
Slide 23: Poxel Lead Molecules vs. Other ALD Pipeline
Poxel Lead Molecules vs. Other ALD Pipeline Advanced Drug Candidates with Potential for Superior Clinical Results ) PXL7701 Leriglitazone2,3 VK02144 Mechanism AMPK activator PPAR Thyroid receptor Stage Ph 2a – Ready Ph 2b/3 Ph 1b Human ALD VLCFA No VLCFA or ABCD2 effects VLCFA not reported Ce
Slide 24: Planned Phase 2 Studies in ALD/AMN
Planned Phase 2 Studies in ALD/AMN Preparation Underway Key inclusion criteria Screening Follow Period PXL770 / PXL065 up • Males with adrenomyeloneuropathy (AMN) • No active cerebral disease Treatment period • 2 cohorts of 12 patients for PXL770 12 weeks stable baseline multiple testing post treatm
Slide 25: Pivotal Program
Pivotal Program Interim analysis Key inclusion criteria Screening Ph 3 – 1 dose vs placebo Ph4 • Males with AMN OLE – 24 months Period 24 months 12 months • No active cerebral disease • ~150 patients randomized Conditional approval Full approval 2:1 active-placebo on surrogate PBST on 6-min WT Endpo
Slide 26: ALD Opportunity Summary
ALD Opportunity Summary High Unmet Needs, Blockbuster Market Potential Blockbuster Market Opportunity Expedited Clinical Development • Global prevalence of 444,000 – 644,000 • Established safety profile of PXL770 mitigates risk & ̶ US prevalence of 20,000-29,000; may reduce clinical development time
Slide 27: ADPKD And The Role Of AMPK
ADPKD And The Role Of AMPK Intracellular Energy Sensor Overnutrition (metabolic Caloric Restriction ADPKD syndrome, NASH, T2DM) Exercise • Autosomal-dominant genetic form of chronic Kidney disease (ADPKD, 2-Deoxyglucose DKD) kidney disease (CKD); 140,000 patients in US; salsalate fourth leading caus
Slide 28: PXL770 Opportunity in ADPKD
PXL770 Opportunity in ADPKD Phase 2-Ready Asset with Orphan Drug Designation (ODD) • Robust efficacy profile with target engagement in established ADPKD model systems: • reduced cyst growth in human and canine assays • in inducible kidney epithelium-specific Pkd1 knockout mouse: normalized kidney fu
Slide 29: ADPKD Opportunity Summary
ADPKD Opportunity Summary High Unmet Needs, Blockbuster Market Potential Blockbuster Market Opportunity Clear Clinical Development • Prevalence of • Phase 2 readout on TKV will significantly de-risk phase ̶ 140,000 patients in US and EU 3 program ̶ Similar prevalence in JP • Established safety profi
Slide 30: Conclusion
Conclusion Summary & Upcoming milestones
Slide 31: Summary Highlights
Summary Highlights • Significant extension of our cash runway through Q2 2025 o Based upon debt restructuring and new equity-linked financing facility, assuming full drawdown • TWYMEEG in Japan – strong growth trajectory confirmed o Sales grew 23% over prior quarter; Sumitomo Pharma FY2023 forecast
Slide 32: Strategic Focus on Rare Diseases
Strategic Focus on Rare Diseases Targeting Indications with High Unmet Needs • PXL770 development focused on rare diseases − subject to additional financing, launch of a Phase 2 clinical trial in ALD • Potential to advance PXL770 into Phase 2 for ADPKD RARE DISEASES − significant opportunity address
Slide 33: Question & Answer Session
Question & Answer Session Participants can submit questions in the chat