Syncona Ltd GBP · LSE:SYNC
Syncona Ltd GBP — Spur Therapeutics — Investor Presentation (October 2024)
35 slides from Syncona Ltd GBP's investor presentation, October 2024
Slide 1: Toward More
Toward More October 2024
Slide 2: Legal Disclaimer
Legal Disclaimer This presentation includes 'forward-looking statements' regarding the operations of Spur Therapeutics. Spur Therapeutics’ actual results may differ from its expectations, estimates, and projections and, consequently, you should not rely on these forward-looking statements as predict
Slide 3: Toward the next generation of gene therapy
Toward the next generation of gene therapy Our vision Our mission Our approach To bring the transformative To redefine what gene To optimize every impact of genetic medicine therapy can do component of our product to millions of patients candidates, improving around the world genetic expression and
Slide 4: Shifting paradigm from modality as innovation toward gene therapies that set new standards of care
Shifting paradigm from modality as innovation toward gene therapies that set new standards of care First-generation gene therapies Next-generation of gene therapies Natural serotype capsids and wild-type Optimized capsids and transgenes transgenes Serious diseases Serious diseases Serious diseases S
Slide 5: Advancing the practice of genetic medicine
Advancing the practice of genetic medicine Optimizing every component of our product candidates Targeting well- defined diseases • Serious, chronic diseases • High unmet need • Right target with validated biology • Consistent delivery of Selective Capsid Optimized Genome Engineered Therapeutic thera
Slide 6: Expanding our impact to more prevalent conditions
Expanding our impact to more prevalent conditions Approximate Research / Disease Area Program Phase 1/2 Phase 3 Patient # Preclinical Gaucher Disease Type 1 ~18K LSDs FLT201 US, UK, EU4, Israel Adrenomyeloneuropathy ~8K–10K SBT101 US, UK, EU4 ~190K CNS GBA1 Parkinson’s Disease US, UK, EU4 >1M Lewy B
Slide 7: Seasoned team to drive progress and execution
Seasoned team to drive progress and execution Michael Parini, Chief Executive Officer and Director Pam Foulds, MD, Chief Medical Officer Henning Stennicke, PhD, Chief Scientific Officer 20+ years as a senior 20+ years of medical and 25+ years of scientific executive in leading clinical leadership le
Slide 8: Toward a new standard of care
FLT201 for Gaucher disease Toward a new standard of care 8
Slide 9: Targeting a chronic, progressive, and debilitating condition
Targeting a chronic, progressive, and debilitating condition Gaucher • Mutations in GBA gene cause deficiency of GCase enzyme needed to metabolize Gb-1 in the lysosome, Normal GCase disease resulting in accumulation of toxic substrate lyso-Gb1 GCase deficiency • Affects multiple organs, leading to e
Slide 10: Current standard of care still means debilitating symptoms and diminished quality of life
Current standard of care still means debilitating symptoms and diminished quality of life • Short half-life of wildtype GCase limits ERT's ability to reach and penetrate deeper tissues • Patients on biweekly ERT infusions are uncovered for most of their 2-week period After 10+ years on ERT, up to 60
Slide 11: Our longer-acting GCase85 specifically designed to address the shortcomings of existing treatment
Our longer-acting GCase85 specifically designed to address the shortcomings of existing treatment In preclinical studies, GCase85 structure FLT201 has shown: Two internal amino acid substitutions • High and durable expression and • Does not impinge on the active site favorable tolerability out past
Slide 12: Completed dosing in Phase 1/2 dose-finding study
Completed dosing in Phase 1/2 dose-finding study GALILEO-1 is a first-in-human, open-label, multicenter study of FLT201 2023 2024 2025 Patient population H1 H2 H1 H2 Adults with Cohort 1 Gaucher Type 1 4.5e11 on ERT or SRT vg/kg dose • Patients come off prior therapy Safety and tolerability • IM reg
Slide 13: GALILEO-1 trial of FLT201: What have we learned?
GALILEO-1 trial of FLT201: What have we learned? Highly compelling efficacy and safety data support 4.5e11 vg/kg dose for Phase 3 Clean safety Compelling efficacy 6/6 Favorable safety and tolerability Dramatic improvements in lyso-Gb1 levels in four patients with in all patients dosed 5/5 persistent
Slide 14: Dramatic reductions of toxic substrate in patients with persistently high levels despite prior treatment
Dramatic reductions of toxic substrate in patients with persistently high levels despite prior treatment Dried blood spot lyso-Gb1 concentration over time 4001-1001 66% reduction 1404-1001 17% reduction 1003-1002 96% reduction 140 140 120 500 concentration (ng/mL) concentration (ng/mL) concentration
Slide 15: FLT201 reduces lyso-Gb1 to near-normal levels within three months of single infusion
FLT201 reduces lyso-Gb1 to near-normal levels within three months of single infusion FLT201 drives lyso-Gb1 lower relative to ERT 450 Untreated 400 Severe disease Mean Lyso-Gb1 (ng/mL) 350 386.5 (76–911)2 DISEASE SEVERITY 300 250 Less severe 200 disease 202 208 (16–677)2 185.7 150 (99–416)3 (10–486)
Slide 16: Substantial decreases in bone marrow burden show FLT201 penetrating difficult-to-reach tissues
No meaningful Substantial decreases in bone marrow burden improvement in show FLT201 penetrating difficult-to-reach tissues ~80% of those with severe BMB after 8 years on ERT1,2 BMB score by MRI over time 4001-1001 1404-1001 10 10 • Improvements even in patients with BMB Total Score severe bone invo
Slide 17: BMB reaches near normal in patient with severe bone disease
BMB reaches near normal in patient with severe bone disease BMB at baseline = 15 BMB at 24 weeks = 1 MRI shows: • Clearance of diseased Gaucher cells • Reappearance of healthy fatty marrow 17
Slide 18: Sustained hemoglobin maintenance observed after withdrawal of ERT or SRT
Sustained hemoglobin maintenance observed after withdrawal of ERT or SRT Hemoglobin concentration over time 4001-1001 Last dose of ERT 1404-1001 Last dose of SRT 1003-1002 Last dose of SRT 20 20 20 Hemoglobin (g/dL) Hemoglobin (g/dL) Hemoglobin (g/dL) 18 18 18 16 W4 16 16 W5 W11 14 14 14 12 12 12 10
Slide 19: Sustained improvement or maintenance of platelets observed after withdrawal of ERT and SRT
Sustained improvement or maintenance of platelets observed after withdrawal of ERT and SRT Platelet count over time 4001-1001 Last dose of ERT 1404-1001 Last dose of SRT 1003-1002 Last dose of SRT 300 300 300 Platelet count (x10e3μL) Platelet count (x10e3μL) Platelet count (x10e3μL) 250 250 W5 250 2
Slide 20: Spleen and liver volume maintenance or improvement observed after withdrawal of ERT and SRT
Spleen and liver volume maintenance or improvement observed after withdrawal of ERT and SRT Spleen volume by MRI as a multiple of normal Liver volume by MRI as a multiple of normal 4001-1001 1404-1001 1003-1002 2001-1006 4001-1003 4001-1001 1404-1001 1003-1002 2001-1006 4001-1003 10 2 9 8 1.5 7 W11
Slide 21: Clinically meaningful improvement in fatigue and pain leading to improved functioning
Clinically meaningful improvement in fatigue Patients ranked fatigue #1 and pain #2 and pain leading to improved functioning as most important symptoms1 FACIT fatigue scale (0–52)2 Pain severity and interference (0-10)3 Improvement +21 52 (+ 2.8 to 6.8 considered 6 clinically meaningful4) 5 39 4 IMP
Slide 22: FLT201 has been well tolerated, with clean safety profile to date
FLT201 has been well tolerated, with clean safety profile to date • Infusions well tolerated; no infusion-related reactions • Treatment-related adverse events were mild to moderate • No dose-limiting toxicities • Any ALT elevations were mild and managed with immune therapy with no impact on efficacy
Slide 23: Toward a disease-modifying treatment: Parkinson's disease
Parkinson’s disease Toward a disease- modifying treatment 23
Slide 24: An opportunity for a best-in-class gene therapy for GBA1 Parkinson's disease
An opportunity for a best-in-class gene therapy for GBA1 Parkinson’s disease GCase deficiency leads to formation GBA1 • GBA mutations are most common genetic risk factor of Lewy bodies (alpha-synuclein for PD aggregates) and death of dopaminergic Parkinson’s • Associated with earlier onset and more
Slide 25: GCase85 demonstrates up to 20x greater activity levels compared to wild-type GCase
GCase85 demonstrates up to 20x greater activity levels compared to wild-type GCase Brain epithelial cell line (H4) Neuroblastoma cell line (NB1643) Neuronal cell line (SH-SY5Y) 600 567 25 50 500 20 20 40 38 GBA activity nmol/hr/ml GBA activity nmol/hr/ml GBA activity nmol/hr/ml 400 15 30 300 10 20 2
Slide 26: GCase85 shows greater brain distribution and higher enzyme levels than the wild type in vivo
GCase85 shows greater brain distribution and higher enzyme levels than the wild type in vivo GCase distribution in the brain GCase activity in brain regions GCase WT GCase85 Striatum Substantia nigra Rest of brain 1000 Caudate putamen GCase activity nmol/hr/mg 100 Substantia nigra 10 1 GBA1-WT GBA1
Slide 27: GCase85 more effectively reduces α-Synuclein accumulation in neuronal cells than wildtype
GCase85 more effectively reduces α-Synuclein accumulation in neuronal cells than wildtype ✱✱✱✱ ✱ GCase85 data α-Synuclein (pg/ml)/protein (ug/ul) ✱✱✱ ✱ ✱✱✱✱ ✱✱✱✱ 120000 indicates inverse GCase activity nmol/hr/ml 40 correlation between 30 80000 GCase activity levels 20 and α-Synuclein 10 40000 accum
Slide 28: Toward a first-in-class gene therapy: SBT101 for AMN
SBT101 for Adrenomyeloneuropathy (AMN) Toward a first-in-class gene therapy 28
Slide 29: AMN is a devastating neurodegenerative disease with no current treatments
AMN is a devastating neurodegenerative disease with no current treatments Adrenomyelo- • Caused by mutations in single X-linked gene ABCD1 • Default phenotype of X-ALD neuropathy • Characterized by progressive muscle weakness and (AMN) sensory loss, leading to loss of mobility, increased risk of fal
Slide 30: SBT101 alters underlying cause of disease in pre-clinical experiments supporting advancement to clinic
SBT101 alters underlying cause of disease in pre-clinical experiments supporting advancement to clinic Disease mechanism of action Pre-clinical proof-of-concept and safety demonstrated • Mutation in ABCD1 gene results in impaired peroxisomal β-oxidation and AAV9-ABCD1 lowers VLCFA to wild-type level
Slide 31: Ongoing PROPEL Phase 1/2 trial in AMN
Ongoing PROPEL Phase 1/2 trial in AMN First-in-human, open-label study Cohort 1 DSMB1 DSMB2 LOW DOSE Safety Safety Safety 1e14 Review Review Review LD group expanded after SAE in 2nd LD patient (per DSMB) 1st Safety Readout LD Safety Independent Data Safety Readout Monitoring Board recommended proce
Slide 32: Preliminary safety update
Preliminary safety update Pt # Month 1 Month 2 Month 3 Month 4 Month 5 Month 6 Month 7 Month 8 Month 9 Month 10 Month 11 Month 12 Month 13 LD 1 2 HD 3 4 • Well tolerated in all patients Safety • Patient 2 died of causes unrelated to drug; no changes to trial protocol or safety monitoring per DSMB Da
Slide 33: First patient in PROPEL trial shows improvement in body sway, an early predictor of disease progression
First patient in PROPEL trial shows improvement in body sway, an early predictor of disease progression Sway Average Amplitude AP Eyes Closed Feet Together Propel patient #1 • Average body sway amplitude Cygnet patient Cygnet mean in PROPEL patient 1 (yellow line) from baseline to month 6 IMPROVEMEN
Slide 34: Advancing the next generation of gene therapies
Advancing the next generation of gene therapies A potential first- Extending A potential first- Ambitious and best-in- the impact of in-class gene research class gene our longer- therapy for strategy to therapy for acting GCase85 AMN, a move gene Gaucher into GBA1 devastating therapy into disease Pa
Slide 35: Thank you
Thank you © 2024 Spur Therapeutics
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