Syncona Ltd GBP · LSE:SYNC
Syncona Ltd GBP — Spur Therapeutics — Investor Presentation (February 2025)
33 slides from Syncona Ltd GBP's investor presentation, February 2025
Slide 1: February 2025
February 2025
Slide 2: Forward-looking statements
This presentation includes “forward-looking statements” regarding reliance upon any forward-looking statements, which speak only as the operations of Spur Therapeutics. Spur Therapeutics’ actual of the date made. Spur Therapeutics does not undertake or accept results may differ from its expectations
Slide 3: Toward more: vision and mission
Imagine a world where a single dose of genetic medicine could truly alter the course of a disease—and the course of people’s lives. This is the vision that spurs us forward. That drives us on our mission to redefine what gene therapy can do, so we can bring its transformative impact to more people.
Slide 4: Toward tailored gene therapies
Toward tailored gene therapies Where many first-generation Tailored gene therapies offer more therapies fall short • Optimized for specific diseases to • Safety drive higher efficacy at lower doses • No improvement on • Improved outcomes, including standard of care changing the course of the disease
Slide 5: Optimizing every component of our product candidates
Optimizing every component of our product candidates to realize outsized clinical results at lower doses Selective capsids Optimized genomes Engineered therapeutic gene Improved tissue targeting, Promoter design and codon Increased half-life, stability, and more efficient transfers of optimization i
Slide 6: Moving from rare to more prevalent conditions
Moving from rare to more prevalent conditions Program Approximate Patient # Research / Preclinical Phase 1/2 Phase 3 FLT201 ~18K Gaucher Disease Type 1 US, UK, EU4, Israel Leveraging GCase85 SPR301 ~190K GBA1 Parkinson’s Disease US, UK, EU4 Future program >1M Lewy Body Dementia US SBT101 ~8K–10K AMN
Slide 7: GCase85: An enzyme with transformative potential
GCase85: An enzyme with transformative potential Our rationally engineered GCase85 offers 6X a longer half-life and increased stability, supporting greater activity levels at lower doses. longer half-life in serum than the wildtype 21X longer half-life in lysosomal pH— 2 amino acid substitutions lea
Slide 8: Gaucher disease can be debilitating, even with current treatments
Gaucher disease can be debilitating, even with current treatments. Our new therapy candidate could change that—and change lives. 8
Slide 9: Targeting a chronic, progressive, and life-altering condition
Targeting a chronic, progressive, and life-altering condition Gaucher disease type 1 Many people experience GCase deficiency leads to a buildup of toxic substrates, debilitating symptoms despite Gb-1 and lyso-Gb1, impacting multiple organ systems. lifelong treatment on ERT (current standard of care)
Slide 10: A need for a new treatment
A need for a new treatment The enzyme used in ERT has a short half-life, leaving patients without enzyme coverage between doses and with lingering symptoms. Up to of people with severe % 80 % bone marrow burden showed no meaningful improvement after 8 years on ERT2 2 De Fost 2006; low ERT dose cohor
Slide 11: FLT201: A first-in-class gene therapy candidate for Gaucher disease
FLT201: A first-in-class gene therapy candidate for Gaucher disease AAVS3 capsid has much Optimized genome focuses Engineered GBA transgene higher transduction efficiency expression in the liver encodes more stable GCase85 than other AAVs Demonstrating compelling efficacy and safety profile Data fro
Slide 12: GALILEO-1 trial results: Demonstrated safety and efficacy
GALILEO-1 trial results: Demonstrated safety and efficacy Data support selection of low dose of 4.5e11 vg/kg for planned Phase 3 trial Clean safety Compelling efficacy1 6/6 5/5 5/5 1/1 Favorable safety Dramatic improvements Maintenance or Dramatic improvement and tolerability in all in lyso-Gb1 in f
Slide 13: Dramatic and sustained reductions in lyso-Gb1 levels
GALILEO-1 trial results: Dramatic and sustained reductions in lyso-Gb1 levels One of the best predictors of disease severity and clinical response, lyso-Gb1 is a potential endpoint for 6-month approval pathway Patient A Patient B Patient C Patient D Patient E 63% reduction 13% reduction 96% reductio
Slide 14: FLT201 reduces lyso-Gb1 to near-normal levels
GALILEO-1 trial results: FLT201 reduces lyso-Gb1 to near-normal levels FLT201 drives lyso-Gb1 lower relative to ERT 450 400 350 386.5 Mean Lyso-Gb1 (ng/mL) Severe disease 300 (76-911)2 250 200 208 202 150 Less severe disease More severe 185.7 100 (16-677)2 disease at start (99-416)3 N=48 143 Baselin
Slide 15: Sustained improvement or maintenance of hemoglobin and platelets
GALILEO-1 trial results: Sustained improvement or maintenance of hemoglobin and platelets observed after withdrawal of ERT or SRT Reductions are seen quickly in heme and platelets when patients come off ERT/SRT1 Hemoglobin concentration over time in individual study patients Normal Hb [female] 11.0-
Slide 16: Spleen and liver volume maintenance or improvement
GALILEO-1 trial results: Spleen and liver volume maintenance or improvement observed after withdrawal of ERT and SRT Spleen volume by MRI as a multiple of normal in individual Liver volume by MRI as a multiple of normal in individual study study patients patients 10 2 9 1.5 8 7 W11 1 W4 W5 3 W4 W9 W
Slide 17: Improvement or maintenance of bone marrow burden
GALILEO-1 trial results: Improvement or maintenance of bone marrow burden (BMB) BMB correlates with bone necrosis, fractures, bone pain and joint replacements and remains one of the greatest unmet needs in Gaucher disease Patient A Patient B Patient C Patient D Patient E 10 10 10 10 10 8 8 8 8 8 6 6
Slide 18: Clinically meaningful improvement in patient with significant bone disease
GALILEO-1 trial results: Clinically meaningful improvement in patient with significant bone disease MRI shows clearance of diseased cells and reappearance of healthy fatty marrow Baseline femur score: 3 Month 12 femur score: 1 18
Slide 19: Substantial improvement in fatigue and pain
GALILEO-1 trial results: Substantial improvement in fatigue and pain leading to improved functioning FACIT fatigue scale (0–52)1 Pain severity and interference (0-10)2 Improvement +21 52 (+ 2.8 to 6.8 considered 6 • clinically meaningful3) • 5 39 4 IMPROVEMENT IMPROVEMENT 3 26 2 13 1 0 Dosing Week 4
Slide 20: Well tolerated, with a favorable safety profile
GALILEO-1 trial results: Well tolerated, with a favorable safety profile • No dose-limiting toxicities Summary of Adverse Drug Reactions for FLT201 and Immune Management (n≥2) • Two cases of ALT elevations above normal Adverse Drug Reactions (ADR) # events (# patients) range deemed related to therap
Slide 21: The potential of GCase85 expands beyond Gaucher disease
The potential of GCase85 expands beyond Gaucher disease— to hundreds of thousands of people living with GBA1 Parkinson’s. 21
Slide 22: A debilitating disease with a clear, unmet need
A debilitating disease with a clear, unmet need Progressive, neurodegenerative GBA1 Parkinson’s disease condition with no disease- GCase deficiency leads to accumulation of α-synuclein, modifying therapy a hallmark of Parkinson’s 515 - % of people with Parkinson’s disease have GBA1 mutations1 ~190K
Slide 23: SPR301: A potentially disease-modifying treatment for GBA1 Parkinson's
SPR301: A potentially disease-modifying treatment for GBA1 Parkinson’s with a highly differentiated profile AAV9 capsid is known for Optimized genome boosts Engineered GBA1 transgene effective transduction of brain cells neuronal cell expression while encodes engineered GCase85, at low doses minimiz
Slide 24: Superior distribution throughout the brain compared to wildtype
SPR301 preclinical study results: Superior distribution throughout the brain compared to wildtype GCase85 distributes broadly and cross-corrects non-transduced cells Distribution in the brain Activity in brain regions GCase WT GCase85 Striatum Substantia nigra Rest of brain 1000 Caudate putamen GCas
Slide 25: Potential for greater efficacy with a favorable safety profile
SPR301 preclinical study results: Potential for greater efficacy with a favorable safety profile Wider therapeutic window, with 25-fold lower dose showing Higher, sustained activity levels in the brain more effectively reduce equivalent lyso-Gb1 reduction as high-dose AAV9-wtGCase α-synuclein in neu
Slide 26: AMN is another neurodegenerative condition with no disease-modifying treatment
AMN is another neurodegenerative condition with no disease-modifying treatment available. At least, not yet. 26
Slide 27: A progressive, devastating condition without a true treatment
A progressive, devastating condition without a true treatment Progressive, neuro-degenerative Adrenomyeloneuropathy (AMN) condition with no disease- Caused by a mutation in X-linked gene ABCD1 modifying therapy, leading to mobility loss, risk of falls, Long-chain sensory loss, and debilitating pain
Slide 28: SBT101: A potential first-in-class gene therapy for AMN
SBT101: A potential first-in-class gene therapy for AMN AAV9 capsid is ideal for Selected promoters drive higher Key therapeutic gene is a copy of spinal targeting levels of expression in the spine the human ABCD1 gene to produce the missing enzyme Achieving elevated expression and decreasing toxic
Slide 29: SBT101 alters underlying cause of disease in pre-clinical experiments
SBT101 alters underlying cause of disease in pre-clinical experiments supporting advancement to clinic Preclinical proof-of-concept and safety demonstrated AAV9-ABCD1 lowers VLCFA to wt levels ex vivo in 0.35 mixed mouse ABCD-/- Glial Cell Culture 0.30 C26:0 (nmol/mg 0.25 Protein) 0.20 0.15 0.10 0.0
Slide 30: Ongoing PROPEL Phase 1/2 trial in AMN
Ongoing PROPEL Phase 1/2 trial in AMN First-in-human, open-label study Lower Dose Higher Dose 2023 2024 2025 H1 H2 H1 H2 H1 Report updated Spur safety data acquisition Well tolerated in all patients = patient to be dosed Patient 2 died of causes unrelated to drug; no changes to trial protocol or saf
Slide 31: Moving toward more
Moving toward more • Optimizing every component of our product candidates to realize outsized clinical results at lower doses • Advancing gene therapy candidates with the potential to set new standards of care in Gaucher disease, GBA1 Parkinson’s disease, and AMN • Ambitious research strategy to mov
Slide 32: A team known for making an impact
A team known for making an impact Michael Parini Pam Foulds, Henning Chief Executive Officer and Director MD Stennicke, PhD • 20+ years as a senior executive in Chief Medical Officer Chief Scientific Officer leading biopharmaceutical companies • 25+ years of medical and clinical • 25+ years of scien
Slide 33: Help us spur gene therapy forward.
Help us spur gene therapy forward. 33
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