Syncona Ltd GBP · LSE:SYNC
Syncona Ltd GBP — Syncona — Investor Presentation (May 2024)
30 slides from Syncona Ltd GBP's investor presentation, May 13, 2024
Slide 1: Syncona Investor Webinar: Freeline Therapeutics
Synconaltd.com Syncona Investor Webinar: Freeline Therapeutics 13 May 2024
Slide 2: Overview of today's session
Overview of today’s session Chris Hollowood, SIML CEO Market backdrop Syncona update including Freeline acquisition Michael Parini, Freeline CEO Overview of the business Strategy and pipeline Pamela Foulds, Freeline CMO Overview of the FLT201 Gaucher disease programme including commercial potential
Slide 3: Syncona: Company update
Synconaltd.com Syncona: Company update Chris Hollowood, SIML CEO
Slide 4: Market activity beginning to normalise
Market activity beginning to normalise Value returning at late-stage Average Enterprise Value of a Biotech listed on US exchanges by stage of development 2 Private and public financing environment remains challenging $1,200 31-Dec-21 16-Jun-22 31-Dec-22 19-May-23 30-Jun-23 15-Sep-23 19-Jan-24 Valuat
Slide 5: Working to maximise value
Working to maximise value Last 12 months have brought challenges to management teams across biotech Capital allocation focused on maximising Actively managing our portfolio Recent examples value for shareholders Autolus completed a strategic Focus on allocating capital towards Working to widen finan
Slide 6: Freeline: an exciting opportunity for shareholders
Freeline: an exciting opportunity for shareholders Aligns with Syncona model and capital allocation focus Exciting lead programme Strong data from Gaucher programme published to date in an area of high unmet need with platform potential Opportunity to leverage technology to move into larger indicati
Slide 7: Advancing the next generation of gene therapies
Advancing the next generation of gene therapies Michael Parini, Freeline CEO
Slide 8: Freeline: A bold ambition to redefine gene therapy
Freeline: A bold ambition to redefine gene therapy Unlock the true potential of gene therapy to change the lives Our Purpose of patients and their families Develop next-generation gene therapies to set new standards Our Goal of care for chronic, debilitating and life-threatening diseases Our Approac
Slide 9: Creating the next generation of gene therapies
Creating the next generation of gene therapies Targeting • Serious, chronic diseases • Right target with validated biology well-defined • High unmet need • Consistent delivery of therapeutic protein highly likely diseases to improve patient outcomes Optimizing every component of our product candidat
Slide 10: Growing pipeline of first- and best-in-class programs
Growing pipeline of first- and best-in-class programs with potential to expand into larger disease areas DISEASE AREA PROGRAM APPROXIMATE DISCOVERY / PHASE 1/2 PHASE 3 PATIENT # PRECLINICAL GAUCHER DISEASE TYPE 1 ~18K LSDs FLT201 US, UK, EU4, Israel ~190K GBA1 PARKINSON’S DISEASE US, UK, EU4 CNS >1M
Slide 11: FLT201 in Gaucher Disease
FLT201 in Gaucher Disease Pamela Foulds, Freeline CMO
Slide 12: Gaucher disease type 1 is a debilitating, chronic and progressive disorder
Gaucher disease type 1 is a debilitating, chronic and progressive disorder with life-altering symptoms Normal GCase GCase function deficiency Gaucher disease • Mutations in GBA gene cause deficiency of GCase enzyme needed to metabolize Gb-1 in the lysosome, resulting in accumulation of toxic substra
Slide 13: No substantial advances in treatment in last two decades
No substantial advances in treatment in last two decades PRE-1991 1991-2002 2002-PRESENT No disease-modifying ERT is only disease- Despite emergence therapies modifying treatment of SRT, ERT remains standard of care FLT201 Potential one-time Life-threatening disease, Meaningful advance but SRT offer
Slide 14: Despite ERT, many patients continue to have debilitating symptoms
Despite treatment with ERT, many patients continue to have debilitating symptoms and diminished quality of life After 10+ years on ERT, up to Gaucher takes a toll on patients’ 60% overall well-being, including: • Feelings of sadness, disappointment and still experience symptoms, including bone pain,
Slide 15: Ongoing GALILEO-1 Phase 1/2 dose-finding study
Ongoing GALILEO-1 Phase 1/2 dose-finding study First-in-human, open-label, multicenter study 2023 2024 2025 Patient H1 H2 H1 H2 population Adults with Cohort 1 Identify Gaucher Phase 3 Type 1 on 4.5e11 vg/kg dose ERT or SRT dose Safety and tolerability Dose first GCase activity patient in Efficacy b
Slide 16: Robust and continuous expression in plasma GCase
Robust and continuous expression in plasma GCase and clear evidence of cellular uptake Significant increases in plasma Increases in leukocyte GCase GCase in patients up to 38 weeks. activity demonstrates cellular GCase activity remained at uptake of GCase85 from plasma. supraphysiological levels Leu
Slide 17: FLT201 reduces lyso-Gb1 to near-normal levels within three months
FLT201 reduces lyso-Gb1 to near-normal levels within three months of single infusion 450 Untreated FLT201 drives lyso-Gb1 lower 400 Severe disease relative to ERT 386.5 (76 – 911)2 Mean Lyso-Gb1 (ng/mL) 350 Lyso-Gb1 an established biomarker of DISEASE SEVERITY 300 disease and treatment response. 250
Slide 18: Maintenance of hemoglobin and improvement in platelets
Maintenance of hemoglobin and improvement in platelets observed post withdrawal of ERT and SRT Hemoglobin concentration over time Platelet count over time Patient 1 Patient 2 Patient 3 Patient 4 Patient 1 Patient 2 Patient 3 Patient 4 20 280 260 18 W5 240 W11 Normal Male 220 16 W11 W4 200 W9 W5 180
Slide 19: Emerging data demonstrate beneficial effect on Bone Marrow Burden
Emerging data demonstrate beneficial effect on Bone Marrow Burden (BMB) BMB score by MRI over time PATIENT 1 PATIENT 2 Improvements even in patients 10 6 8 5 with severe BMB* BMB Total Score BMB Total Score 4 6 4 3 Early signs of clinical improvement 2 2 observed in BMB as of 12 to 38 weeks 1 0 0 po
Slide 20: Clinically meaningful improvement in fatigue
Clinically meaningful improvement in fatigue Patient 1: FACIT fatigue scale (0 – 52) Patient reported significant Improvement +21 (+ 2.8 to 6.8 considered improvements in fatigue and clinically meaningful1) 52 ability to perform daily activities • Has energy IMPROVEMENT 39 • Able to do usual activit
Slide 21: FLT201 has been well-tolerated with clean safety profile
FLT201 has been well-tolerated with clean safety profile to date Safety • Infusions well tolerated; no reactions • No serious adverse events • No severe adverse events or dose-limiting toxicities • Any modest ALT elevations managed with immune therapy with no impact on efficacy • Non-serious adverse
Slide 22: FLT201: Differentiated profile with opportunity to set new SoC
FLT201: Differentiated profile with opportunity to set new SoC FLT201 ERT SRT FLT201 1 ERT SRT Efficacy Efficacy Safety / Tolerability Safety / Tolerability TreatmentTreatment Burden Burden Cost2 Cost LifetimeLifetime 1FLT201 target product profile; 2ERT and SRT have annual costs per patient of c.$6
Slide 23: GBA1 Parkinson's Disease
GBA1 Parkinson’s Disease Pamela Foulds, Freeline CMO
Slide 24: Longer-acting GCase85 provides opportunity for best-in-class gene therapy for GBA1 Parkinson's
Our longer-acting GCase85 provides opportunity for best-in-class gene therapy for GBA1 Parkinson’s disease GCase deficiency leads to formation GBA1 Parkinson’s disease of Lewy bodies (alpha-synuclein • GBA mutations are most common genetic risk factor for PD aggregates) and death of dopaminergic • A
Slide 25: GCase85 demonstrated up to 20-fold greater activity than wildtype
GCase85 demonstrated up to 20-fold greater activity levels compared to wildtype in preclinical studies Brain epithelial cell Brain epithelial cellline line Neuroblastoma cell Neuroblastoma cell lineline Neuronal Neuronalcell line cell line (NB1643) (SH-SY5Y) (H4)(H4) (NB1643) (SH-SY5Y) ✱✱✱ ✱✱✱✱ 1000
Slide 26: GCase85 shows greater brain distribution and higher enzyme levels in vivo
GCase85 shows greater brain distribution and higher enzyme levels than wildtype GCase in vivo GCase distribution in the brain GCase wt GCase85 GCase activity in brain regions Caudate putamen GCase activity nmol/hr/mg 1000 Striatum Substantia nigra Rest of brain 100 10 1 Substrntia nigra T 5 T 5 T 5
Slide 27: Summary
Summary Michael Parini, Freeline CEO
Slide 28: Anticipated upcoming milestones
Anticipated upcoming milestones GAUCHER DISEASE FLT201 • Complete dosing in Phase 1/2 GALILEO-1 trial in Q2 2024 • Report additional data from Phase 1/2 GALILEO-1 trial in H2 2024 • Initiate Phase 3 trial in 2025 GBA1-PD Leveraging GCase85 • Select development candidate in H2 2024 28
Slide 29: Advancing the next generation of gene therapies
Advancing the next generation of gene therapies FLT201: A potential Extending the impact Ambitious research first-and best-in-class of our longer-acting strategy to move gene gene therapy for GCase85 into therapy into larger Gaucher disease GBA1 Parkinson’s patient populations backed by compelling d
Slide 30: Thank you.
Thank you. FREELNE