Poxel Sa · EURONEXT:POXEL
Poxel Sa — Investor Presentation (July 2021)
33 slides from Poxel Sa's investor presentation, Jul 12, 2021
Slide 1: New Strategic Direction: Increasing Focus on Rare Metabolic Diseases
New Strategic Direction: Increasing Focus on Rare Metabolic Diseases 12 July 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: Agenda
Agenda Topic Speaker Introduction & Strategy Thomas Kuhn, Poxel CEO Marc Engelen, MD, PhD (English) (Pediatric) Neurologist Department of Neurology and Pediatrics Adrenoleukodystrophy (ALD) Amsterdam University Medical Centers Overview Amsterdam Leukodystrophy Center Ben Lenail (French) Co-founder a
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 and rare diseases with underlying metabolic pathophysiology acetyl CoA METABOLIC INFLAMMATION DISORDERS (cellular energy homeostasis TISSUE DEGENERATION imbalances) & CE
Slide 5: Poxel's Increasing Focus on Rare Metabolic Diseases
Poxel’s Increasing Focus on Rare Metabolic Diseases A New Strategic Direction Building upon Recent Achievements • Following the recent approval of TWYMEEG® (Imeglimin) in Japan and associated potential future revenues, Poxel to accelerate and expand rare metabolic disease programs • In rare metaboli
Slide 6: TWYMEEG (Imeglimin): Approved in Japan
TWYMEEG® (Imeglimin): Approved in Japan Partnered in Asia1 with Diabetes Market Leader, Sumitomo Dainippon Pharma • June 23rd Approval in Japan triggered: o 3rd and final tranche of EUR 13.5 million from IPF loan received June 30, 2021 o Milestone payment of ~EUR 13.2 million (USD 15.8 million)2 fro
Slide 7: A New Chapter to Drive Shareholder Value
A New Chapter to Drive Shareholder Value Focus on Rare Metabolic Diseases and NASH Rare Metabolic ALD Diseases PXL065* Type 2 diabetes NASH D-TZD Platform PXL770* TWYMEEG® AMPK Platform (Imeglimin) External Partnered in Asia1 Opportunities with diabetes market leader in Japan • Phase 2a Biomarker PO
Slide 8: Robust Mid-to-Late Stage Metabolic Pipeline
Robust Mid-to-Late Stage Metabolic Pipeline Focus on Rare Metabolic Diseases and NASH Discovery/ PH Approved/ Partner/ Indication MOA PH 2 PH 3 Upcoming Milestones PC 1 Marketed Rights Type 2 Diabetes (T2D) • TWYMEEG approved for T2D in Japan on TWYMEEG® MRC June 23, 2021 T2D Japan / Asia1 Modulator
Slide 9: X-linked adrenoleukodystrophy (ALD): pathophysiology and clinical features
X-linked adrenoleukodystrophy (ALD): pathophysiology and clinical features Marc Engelen, MD, PhD (Pediatric) Neurologist Department of Neurology and Pediatrics Amsterdam University Medical Centers Amsterdam Leukodystrophy Center July 2021
Slide 10: ALD: a not so rare orphan disease
X-linked adrenoleukodystrophy (ALD): a not so rare orphan disease Genetics Prevalence • Monogenic, mutations in ABCD1 gene on Estimated US Prevalence* the X-chromosome 20,000 – 29,000 • Gene encodes ALD protein, a transporter present in peroxisomes required for metabolism of very long chain fatty ac
Slide 11: ALD: pathophysiology
ALD: pathophysiology ABCD1: Transports VLCFA into peroxisome for degradation (ABCD2 can serve as an alternative peroxisomal transporter) ABCD1 Defective ABCD1 leads to accumulation of VLCFA in tissues VLCFA cause axonal degeneration and secondary demyelination VLCFA accumulation:, inflammation? mito
Slide 12: ALD: diagnosis
ALD: diagnosis VLCFA levels ABCD1 mutation analysis Newborn screening C26:0 8 6 µmol/L plasma 4 2 In the U.S. > 60% of newborns screened 0 controls hemizygotes carriers Netherlands started in 2021 Kemp et al, Nature Reviews Endo, 2016 Huffnagel et al, Mol Genet Metab, 2017 12
Slide 13: ALD: clinical features
ALD: clinical features Leukodystrophy: Cerebral ALD (C-ALD) Adrenal Insufficiency Spinal cord disease : adrenomyeloneuropathy (AMN) Normal ALD Sensory ataxia Gait disorder Spasticity Powers et al, 2000 Huffnagel et al, 2019 13
Slide 14: ALD: clinical features
ALD: clinical features • Women – by > 60: • Men – by age 65: o ~90% have spinal cord disease o >90% have spinal cord disease o adrenal failure and cerebral disease are very o 80% have developed cerebral disease rare Engelen et al, Brain, 2014 Huffnagel et al, J Clin Endocrinol Metab 2019 14
Slide 15: Adrenoleukodystrophy: clinical features
Adrenoleukodystrophy: clinical features AMN - Kemp et al, Nature Reviews Endo, 2016 15
Slide 16: ALD: treatment
ALD: treatment • Adrenal insufficiency → glucocorticoid replacement therapy • Early stage (early onset) C-ALD → HSCT or ex-vivo Lenti-viral gene therapy (SKYSONA™ Bluebird Bio) HSCT does not prevent spinal cord disease (“AMN”) Untreated C-ALD • Advanced or later onset C-ALD → only supportive care
Slide 17: Towards objective outcome measures for clinical trials
Towards objective outcome measures for clinical trials Non-Invasive qMRI Optical coherence Postural Body Sway Biomarkers (like DTI and CSA) tomography • VLCFA • Neurofilament Light Chain • Others Huffnagal et al. Neurology 2019 van Ballegoij et al. Front Physiol 2020 van Ballegoij et al. Ann Clin Tr
Slide 18: ALD: treatment development and unmet needs
ALD: treatment development and unmet needs • AMN: o Slowly progressive – severe and disabling disease; no disease modifying therapy available o Delay progression of spinal cord disease o Prevent loss of mobility, bladder and bowel dysfunction o Improve quality of life o Both men and women • Cerebral
Slide 19: ALD – A Patient Perspective
ALD – A Patient Perspective Ben Lenail 19
Slide 20: Poxel ALD Program
Poxel ALD Program David E. Moller, MD – Chief Scientific Officer Pascale Fouqueray, MD, PhD, EVP Clinical Development and Regulatory Affairs 20
Slide 21: Harnessing AMPK and D-TZD Platforms to Address Rare Diseases
Harnessing AMPK and D-TZD Platforms to Address Rare Diseases with Metabolic Pathophysiology Two Programs Approaching Clinical Development for ALD TZD D-TZD AMPK Genomic Pathway gene Activates transcription Non-Genomic RXR Inhibits PPAR Pathways catabolic Inhibits inflammation (MPC; ACSL4) pathways a
Slide 22: Poxel Platforms – Potential to Target ALD Pathophysiology
Poxel Platforms – Potential to Target ALD Pathophysiology ABCD1: Transports VLCFA into peroxisome for degradation (ABCD2 can serve as an alternative peroxisomal transporter) Defective ABCD1 leads to accumulation of VLCFA ABCD1 in tissues VLCFA cause axonal degeneration and secondary demyelination D-
Slide 23: Two First-in-Class Advanced Lead Molecules
Two First-in-Class Advanced Lead Molecules PXL065 PXL770 • Deuterium stabilized R-stereoisomer of • Proprietary direct allosteric AMPK activator pioglitazone* • Preclinical: • Preclinical: o Metabolic, anti-inflammatory, o no (PPARg –driven) weight gain/fluid retention cytoprotective efficacy in NA
Slide 24: D-TZD's: Rationale and Strong Preclinical Data
D-TZD’s: Rationale and Strong Preclinical Data • Pioglitazone attenuates neuroinflammation and confers neuroprotection: o non-human primates with Parkinson’s disease1 J Neuroinflamm 2011; 8:91 Exp Neurol 2009; 216:321- o rodent acute brain ischemia2, spinal cord injury3 Exp Neurol 2017; 293:74- 4. B
Slide 25: D-TZD's: Clinical Results Support Pursuit of ALD/AMN
D-TZD’s: Clinical Results Support Pursuit of ALD/AMN Leriglitazone - Human PoC with PPARg - Related AEs • Phase 2/3 trial in adult AMN patients (n=116; 96 week) • Primary Endpoint: 6 min walk test - Failed (differences “observed in early symptomatic pts”) • Secondary / Exploratory: Body Sway - Sign
Slide 26: AMPK: Scientific Rationale and Strong Preclinical Data
AMPK: Scientific Rationale and Strong Preclinical Data • Deletion of AMPK in glial cells of ABCD1-null mice → mitochondrial dysfunction / low ATP1 • Reduced AMPK in patient-derived cells and brain tissue from ALD patients2,3 • AMPK activation with metformin* elevates ABCD2 levels in patient cell lin
Slide 27: Both PXL065 and PXL770 Mediate Neurologic Benefits
Both PXL065 and PXL770 Mediate Neurologic Benefits ABCD1-Null Mouse (12 wk Treatment) Electronic Microscopy of Sciatic Nerve Neurologic Tests (Balance Beam) WT ABCD1-Null untreated ABCD1-Null + PXL065 Cell shape change 60 6:0) ✱ ✱ ✱✱ Stellate cell shape (% of total cells) Wild-Type 40 KO ABCD1 Null
Slide 28: Poxel Lead Molecules vs. Selected Competitors
Poxel Lead Molecules vs. Selected Competitors Advanced Drug Candidates with Potential for Superior Clinical Results PXL065 PXL770 Leriglitazone* VK0214 ABX-002 Non-genomic PPARg Mechanism AMPK activator Thyroid receptor b Thyroid receptor b D-TZD (+ other TZD) Stage Ph2a – Ready Ph 2a – Ready Ph 2
Slide 29: Planned Phase 2A Studies in ALD/AMN
Planned Phase 2A Studies in ALD/AMN PXL770 and PXL065 in Two Separate Identical Studies Key inclusion criteria • Males with AMN Screening PXL770 / PXL065 1 Dose Each Follow • Age 18-65 Period up • No active cerebral Treatment period disease 12 weeks • 12 patients each stable baseline multiple testin
Slide 30: Upcoming Milestones
Upcoming Milestones Thomas Kuhn, CEO 30
Slide 31: Near-Term Milestones to Drive Poxel's Growth
Near-Term Milestones to Drive Poxel’s Growth NASH T2DM PXL065: ALD/Other Results from PXL065 & PXL770: DESTINY Ph 2 trial Cash PXL065 & PXL770: PXL065: Initiate Ph 2a Results from Ph 2a Complete enrollment biomarker POC trials biomarker POC trials of DESTINY Ph 2 trial in AMN in AMN 2021 2022 2023 T
Slide 32: Summary and Investment Highlights
Summary and Investment Highlights • Strategic Focus on rare metabolic indications and NASH o ALD: PXL065 and PXL770 Phase 2a biomarker Proof-of-Concept results by year end 2022; potential to advance into pivotal trial o NASH: PXL065 Phase 2 results anticipated Q3 2022; option to advance either PXL06
Slide 33: Question & Answer Session Concluding Remarks
Question & Answer Session Concluding Remarks 33