Slide 1: Full Year 2021 Financial and Corporate Update
Full Year 2021 Financial and Corporate Update March 22, 2022
Slide 2: Disclaimer
2 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 3: 2021 Summary Highlights
2021 Summary Highlights • 2021, the year of Poxel’s first approved and launched product… o Imeglimin approved in June and TWYMEEG® launched in September in Japan as novel Type-2-Diabetes treatment ▪ Poxel received JPY 1.75 billion (EUR 13.2 million) milestone payment for the approval of TWYMEEG ▪ Tr
Slide 4: Poxel's Key Investment Highlights
Poxel’s Key Investment Highlights Strategic focus on rare metabolic A New Chapter to Drive Shareholder Value diseases and NASH Launch of Entitled to significant royalties following TWYMEEG® first drug approval and launch in Japan in 2021 for TWYMEEG® (Imeglimin) for Type 2 Expand in Diabetes 2021 Ra
Slide 5: Robust Mid-to-Late Stage Metabolic Pipeline
Robust Mid-to-Late Stage Metabolic Pipeline Focus on Rare Metabolic Diseases and NASH Approved Discovery/ Indication MOA PH 1 PH 2 PH 3 / Upcoming Milestones PC Marketed NASH Non-Genomic • Phase 2 results expected Q3 2022 PXL065 NASH TZD1 • 505(b)(2) pathway AMPK2 • Successful Phase 2a Study PXL770
Slide 6: TWYMEEG (Imeglimin): Launched in Japan in 2021
TWYMEEG® (Imeglimin): Launched in Japan in 2021 Partnered in Asia1 with Diabetes Market Leader, Sumitomo Dainippon Pharma • Launch Update o Launch activities and promotional efforts in Japan = High awareness among prescribers Collaboration Summary ▪ full sales force mobilized, launching Phase 4 & me
Slide 7: Financial Update
Financial Update Full Year 2021
Slide 8: 2021 Revenue
2021 Revenue* Mainly reflecting the milestone payment for the approval of TWYMEEG EUR (in thousands) FY FY • Revenues for 2021 include the following 2021 2020 payments from Sumitomo Dainippon 12 months 12 months Pharma: o JPY 1.75 billion (EUR 13.2 million) milestone payment for the approval of TWYM
Slide 9: Statement of Comprehensive Income as of Dec. 31, 2021
Statement of Comprehensive Income as of Dec. 31, 2021* EUR (in thousands) December December 31, 2021 31, 2020 (adjusted)** Revenue 13,397 6,806 Mostly reflects a €13.2m milestone Cost of sales (59) payment (approval of Imeglimin in Japan) Gross margin 13,339 6,806 Research and development Research a
Slide 10: Statements of Financial Position as of December 31, 2021 (Assets)
Statements of Financial Position as of December 31, 2021* Assets EUR (in thousands) December December 31, 2021 31, 2020 Adjusted** Mostly reflects DeuteRx portfolio acquisition in 2018 Intangible assets 16,631 16,642 Property, plant and equipment 1,716 2,224 Other non-current financial assets 206 24
Slide 11: Statements of Financial Position as of December 31, 2021 (Liabilities)
Statements of Financial Position as of December 31, 2021* Shareholders’ Equity and Liabilities EUR (in thousands) December 31, December 31, 2021 2020 Adjusted** Total shareholders' equity 8,206 27,065 Mostly reflects FY2021 net loss Employee benefits 370 395 Non-current financial liabilities 30,094
Slide 12: Statements of Cash Flow as of Dec. 31, 2021
Statements of Cash Flow as of Dec. 31, 2021* EUR (in thousands) December December 31, 2021 31, 2020 Adjusted ** Cash flows from operating activities before change (18,791) (26,040) in WC Reflects net operating loss (-) Changes in working capital requirements 1,898 (292) Cash flows from operating act
Slide 13: Early 2022 Corporate Update Highlights
Early 2022 Corporate Update Highlights • Actively pursuing various financing options to extend cash runway, including dilutive and non-dilutive sources, as well as discussions with IPF Partners • Continuing preparation for launch of first clinical studies in rare diseases, starting with Phase 2a cli
Slide 14: Accelerating & Expanding Rare Metabolic Disease Programs
Rare Diseases Accelerating & Expanding Rare Metabolic Disease Programs Starting with existing platforms: PXL065 - D-TZD’s (Fast Track) PXL770 - AMPK Activator
Slide 15: 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 activator2 pioglitazone1 • Preclinical: • Preclinical: o metabolic, anti-inflammatory, cytoprotective o no (PPAR–driven) weight gain/fluid retention efficacy in NAS
Slide 16: Adrenoleukodystrophy
Adrenoleukodystrophy A Not-so-Rare Orphan Neurometabolic Disease Genetics Prevalence Diagnosis • Monogenic, X-linked mutations in Estimated US Prevalence1 • Newborn screening – increasingly ABCD1 gene 20,000 – 29,000 common (now >60% of newborns • Gene encodes a transporter present in US) in peroxis
Slide 17: ALD Clinical Features and Disease Course
ALD Clinical Features and Disease Course Three Major Overlapping Subtypes C-ALD Lesions (MRI) Addison’s Disease Cerebral ALD (C-ALD): • damage to brain white 100 AMN ♂ matter; cognitive % of afflicted patients impairment; loss of vision/hearing; impaired adrenal insufficiency 75 balance-movement; de
Slide 18: Both Poxel Lead Molecules are Active in ALD Models
Both Poxel Lead Molecules are Active in ALD Models • TZD’s1-4 and AMPK5-8 activation – independently implicated as therapeutic approaches • Both PXL065 and PXL770: o correct disease pathology in cells from patients with C-ALD and AMN (fibroblasts and lymphocytes) o improve elevated VLCFA in vivo in
Slide 19: Both PXL065 and PXL770 Mediate Neurologic Benefits
Both PXL065 and PXL770 Mediate Neurologic Benefits ABCD1-Null Mouse (12 week Treatment) Electronic Microscopy of Sciatic Nerve Neurologic Tests (Balance Beam) ✱✱✱ C26 Spinal Cord WT ABCD1-null untreated ABCD1-null + PXL065 ✱✱✱✱ 10 Wild-Type C26 content (ng/ml) 8 Abcd1-null PXL770 6 5 4 ✱ ✱✱ Score (B
Slide 20: Planned Phase 2a Studies in ALD/AMN
Planned Phase 2a Studies in ALD/AMN PXL770 and PXL065 (Fast Track Designation) in Two Separate Identical Studies Key inclusion criteria • Males with AMN Screening Follow Period PXL770 / PXL065 up • Age 18-65 • No active cerebral disease Treatment period • 12 patients each 12 weeks stable baseline mu
Slide 21: 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: ▪ US
Slide 22: Opportunity in Polycystic Kidney Disease (ADPKD)
Opportunity in Polycystic Kidney Disease (ADPKD) AMPK - a Compelling Target – PXL770 has Completed Preclinical Assessment • Autosomal-dominant genetic form of kidney disease o prevalence ≈140,000 in US (qualifies for orphan designation) o high unmet need (>50% develop end-stage renal disease); one a
Slide 23: NASH: PXL065 and PXL770
NASH PXL065 Non-Genomic Pathway D-TZD Modulator for Treatment of NASH Utilizing the 505(b)(2) Regulatory Pathway PXL770 Direct AMPK Activator
Slide 24: PXL770 and PXL065: Novel, First-in-Class Product Candidates
PXL770 and PXL065: Novel, First-in-Class Product Candidates HALLMARKS OF NASH MΦ Lipid accumulation in Immune cells Hepatic stellate hepatocytes (macrophages - MΦ) Cellular damage-death cell activation Steatosis Inflammation Ballooning Fibrosis First-in-Class - Novel Mechanisms Daily oral administra
Slide 25: PXL065 Ongoing Phase 2 in Biopsy-Proven NASH Patients
PXL065 Ongoing Phase 2 in Biopsy-Proven NASH Patients Topline Results Expected Q3 2022 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 • Liver fat content (MRI-PDFF) ≥ 8% P
Slide 26: 2022 Upcoming Milestones
2022 Upcoming milestones • TWYMEEG® sales: o Pursuing efforts to raise awareness and knowledge of TWYMEEG amongst prescribing physicians by our partner Sumitomo Dainippon Pharma following launch in September 2021 o Poxel entitled to receive sales-based payments and escalating royalties of 8 - 18% on
Slide 27: Question & Answer Session
Question & Answer Session • Participants can submit questions in the chat