Poxel Sa · EURONEXT:POXEL
Poxel Sa — Investor Presentation (December 2024)
36 slides from Poxel Sa's investor presentation, December 2024
Slide 1: Corporate Presentation
Corporate Presentation December 2024
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: Poxel's Mission & Key Investment Highlights
Poxel’s Mission & Key Investment Highlights To discover, develop and commercialize Strategic focus on rare metabolic diseases innovative therapies for patients suffering from serious chronic and rare diseases with underlying metabolic Strategic partnership for TWYMEEG® pathophysiology (Imeglimin), a
Slide 4: Key Financial & Shareholder Information
Key Financial & Shareholder Information Market data Shareholder ownership1 Bpi France 8% Founders 5.6% Ticker: POXEL ISIN: FR0012432516 Floating 86.3% Number of shares: 53.373.0881 Key financials Analyst coverage • As of 09/30/24 cash & cash equivalents: Degroof Petercam David Seynnaeve EUR 13.1 mil
Slide 5: Focus on Rare Metabolic Diseases with PXL770 and PXL065
Focus on Rare Metabolic Diseases with PXL770 and PXL065 ADPKD lead indication with PXL770; HCM and ALD being assessed for PXL065 Approved/ Indication MOA Preclinical PH 1 PH 2 PH 3 Recent & Upcoming Milestones Marketed AMPK Activator Programs • Orphan Drug Designation (2022) AMPK4 PXL770 ADPKD1 • Cl
Slide 6: Rare Metabolic Indications to Drive Value for Poxel
Rare Metabolic Indications to Drive Value for Poxel For lead asset Imeglimin, Poxel completed royalty monetization with OrbiMed PXL770 PXL065 Twymeeg / Imeglimin Focus for PXL770 on potential rare renal Pivot from NASH to multiple rare TWYMEEG (Imeglimin) marketed by and neurometabolic indications g
Slide 7: Summary of the Royalty Monetization with OrbiMed and Debt Restructuring
Summary of the Royalty Monetization with OrbiMed and Debt Restructuring with IPF Partners and PGE banks • One time cash payment of USD 50 million (bonds issuance) from OrbiMed • In return, OrbiMed to obtain the royalties received by Poxel1 from sales of Royalty Monetization with TWYMEEG® by Sumitomo
Slide 8: Main terms of the Royalty monetization agreement with OrbiMed
Main terms of the Royalty monetization agreement with OrbiMed based on TWYMEEG® sales USD 7.5M Payments based on Partnership proceeds with in a deposit account & potential partnerships Gross Upfront Quarterly payment of Sales-based Potential additional Payment: Royalties USD 1.25M payments proceeds
Slide 9: Accelerating & Expanding Rare Metabolic Disease Programs: PXL770
Rare Diseases Accelerating & Expanding Rare Metabolic Disease Programs PXL770 • AMPK Activator in Autosomal Dominant Polycystic Kidney Disease (ADPKD) • & in Adrenoleukodystrophy (ALD)
Slide 10: PXL770 – AMPK Direct Activator
PXL770 – AMPK Direct Activator Phase 2 Ready Compound Key attributes for ADPKD Proprietary direct allosteric AMPK Confirmed efficacy activator, in various Favorable safety Favorable tox and profile highly selective preclinical models PK profile, with nM potency with translation of in > 200 human wit
Slide 11: 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 12: PXL770 Opportunity in ADPKD
PXL770 Opportunity in ADPKD Clinic Ready Asset with Orphan Drug Designation (ODD) Full preclinical package available in • Robust efficacy profile with target engagement in established ADPKD model systems: Kidney International (2023) 103, 917–929; o reduced cyst growth in human and canine assays http
Slide 13: PXL770 – Complementary Treatment in ADPKD
PXL770 – Complementary Treatment in ADPKD Comparison and Potential Additional Benefit vs Tolvaptan Similar efficacy from historical data PXL770 potential benefit for both compounds using the same model in ADPKD Parameters PXL770 Tolvaptan1 • Tolvaptan alone slows down but 75 mg/kg bid 62 days treatm
Slide 14: PXL770 – Preliminary Clinical Development Plan
PXL770 – Preliminary Clinical Development Plan PoC Trial under Preparation 2025 2026 2027 2028 2029 2030 2031 2032 TKV eGFR Prep PoC Prep Phase 2 / 3 Optional OLE Submission Accelerated Acc. NDA prep NDA FDA Review approval NDA Full final FDA Full Submission approval POC trial Endpoints Primary : Sa
Slide 15: ADPKD Opportunity Summary
ADPKD Opportunity Summary High Unmet Needs, Blockbuster Market Potential Blockbuster Market Opportunity Clear Clinical Development • Global prevalence of 4/10,000 • Clinical PoC readout on TKV will significantly derisk ̶ 140,000 patients in US and EU pivotal program ̶ Similar prevalence in JP • Esta
Slide 16: 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 17: AMP Kinase Activation
AMP Kinase Activation Beneficial Role in ALD Pathophysiology C16:0 Fatty Acids pool Reduces Fatty Acid (FA) pool AMPK chain- Improves master sensor of elongation C22:0 VLCFA Mitochondrial cellular homeostasis ELOVL1 C24:0 dysfunction and lipid metabolism C26:0 VLCFA Increase FA oxydation Accumulatio
Slide 18: PXL770: Strong Preclinical Data
PXL770: Strong Preclinical Data • PXL770 is active in patient-derived cells and in the classical animal model Full preclinical package available in Journal of Pharmacology and Experimental Therapeutics June • Sufficient brain and spinal cord penetration expected in human to trigger 28, 2022, similar
Slide 19: 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 20: Accelerating & Expanding Rare Metabolic Disease Programs: PXL065
Rare Diseases Accelerating & Expanding Rare Metabolic Disease Programs PXL065 • Hypertrophic CardioMyopathy (HCM) • & in Adrenoleukodystrophy (ALD)
Slide 21: PXL065 in Hypertrophic Cardiomyopathy
PXL065 in Hypertrophic Cardiomyopathy Normal Heart Potentially lifelong therapy with start of treatment in children / adolescents Right atrium Left atrium • One of the most common genetic cardiac disorders, with a prevalence of ~ 1:250 to 1:500 Interventricular septum • Two most common genes involve
Slide 22: PXL065 can inhibit crucial disease mechanisms in HCM
PXL065 can inhibit crucial disease mechanisms in HCM and prevent pathologic myocardial remodeling • Pioglitazone - Possible HCM Benefits Based on Literature o In Vitro Pio inhibits angII induced rat cardiomyocyte hypertrophy1-3 Inhibits high glucose/insulin rat neonatal CM hypertrophy4 o In Vivo
Slide 23: PXL065 Opportunity in HCM
PXL065 Opportunity in HCM Preclinical Proof of Concept in a mouse model with typical HCM phenotype • Model – αMHC R719W/+ (with cyclosporine); n=10-13 per group; age 5-6 weeks; 7-week treatment • PXL065 15 mg/kg oral gavage vs vehicle Reduced Left Ventricular wall Improved Signaling Decreased Fibros
Slide 24: PXL065 – New Opportunity in HCM
PXL065 – New Opportunity in HCM Key attributes for HCM Favorable safety Deuterium stabilized Preliminary positive profile R-stereoisomer of preclinical data in in > 150 human Key opportunity pioglitazone. HCM. exposures up to 24 in pediatric Target pathways that Decreased weeks population, ameliorat
Slide 25: PXL065 Efficacy in ALD
PXL065 Efficacy in ALD Biochemical, Histologic and Functional Benefits Improved VLCFA level in AMN/ALD Mouse Suppression of Elevated VLCFA in ALD Model (ABCD1 -/-) Patient-Derived Cells Plasma abcd1-KO vs PXL065 Brain abcd1-KO vs PXL065 1.0 1.5 AMN - Fibroblasts ALD - Fibroblasts Hexacosanoic acid (
Slide 26: Optional Phase 2 Studies in ALD/AMN
Optional 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 PXL065 12 weeks /PXL770 stable baseline multiple testing po
Slide 27: PXL065 – Partnership Opportunity
NASH PXL065 – Partnership Opportunity Non-Genomic Pathway D-TZD Modulator for Treatment of NASH Utilizing the 505(b)(2) Regulatory Pathway
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 Belfort 20062, Gastaldelli 20213 55 6 mos 6 Biopsy Trials Ait
Slide 29: 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 Denifanstat Lanifibranor Semaglutide Tirzepatide Efruxifermin Pegozafermin Phase 2b Phase 3 Phase 2b Phase 2b Phase 3 Phase 2b Phase 2b Phase 2b 24 wks - QD 24 wks - QW I
Slide 30: 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 31: TWYMEEG (Imeglimin) – Ongoing Partnership
TWYMEEG® (Imeglimin) – Ongoing Partnership Approved in Japan and Marketed by Sumitomo Pharma
Slide 32: TWYMEEG (Imeglimin): Strong Growth Trajectory in JP
TWYMEEG® (Imeglimin): Strong Growth Trajectory in JP Partnered in Japan, with Diabetes Market Leader, Sumitomo Pharma Collaboration Summary Commercial Strategy Update 1. Current promotion focused on combination therapy: add-on to DPPIV inhibitors, the market leader class in JP, Royalties 2. Combinat
Slide 33: Sumitomo Pharma has returned rights to all territories ex-Japan
For Imeglimin, Sumitomo Pharma has returned rights to all territories ex-Japan under the agreement Poxel to continue regional partnering discussions Continued ongoing partnering discussions to Sizeable pool of diabetic patient with Chronic drive Imeglimin development ex-Japan Kidney Disease (CKD) •
Slide 34: Conclusion
Conclusion e pox
Slide 35: Strategic Focus on Rare Diseases
Strategic Focus on Rare Diseases Targeting Indications with High Unmet Needs • PXL770 development focused on rare diseases − significant opportunity for ADPKD, addressing underlying pathology − optional development in ALD RARE DISEASES • D-TZD platform potential in rare diseases under assessment − p
Slide 36: Contact
Contact investors@poxelpharma.com