Freeline Therapeutics Holdings PLC
Freeline Therapeutics — Investor Presentation (August 2023)
23 slides from Freeline Therapeutics's investor presentation, August 2023
Slide 1: Corporate Presentation
Corporate Presentation August 2023
Slide 2: Legal disclaimer
Legal disclaimer This presentation contains statements that constitute “forward looking statements” as that term is defined in the United States Private Securities Litigation Reform Act of 1995, including statements that express the opinions, expectations, beliefs, plans, objectives, assumptions or
Slide 3: Creating better gene therapies for chronic debilitating diseases
Creating better gene therapies for chronic debilitating diseases Potential first- and Extending innovation best-in-class lead program into Parkinson’s disease Highly differentiated gene therapy Lead research program leverages candidate FLT201 for Gaucher disease same novel GCase variant as FLT201 ty
Slide 4: Lead clinical program with first- and best-in-class potential
Lead clinical program with first- and best-in-class potential with research extending innovation into larger disease area Indication Approximate Research Preclinical Phase 1/2 Phase 3 patient # Gaucher Disease Type 1 ~18K FLT201 GBA1-linked Parkinson’s ~190K Disease Estimated patient numbers for Gau
Slide 5: FLT201 in Gaucher Disease
FLT201 in Gaucher Disease
Slide 6: FLT201: Potential first- and best-in-class gene therapy for Gaucher disease Type 1
FLT201: Potential first- and best-in-class gene therapy for Gaucher disease Type 1 HIGHLY DIFFERENTIATED SIGNIFICANT MARKET ENCOURAGING DATA & • Novel transgene encoding a OPPORTUNITY NEAR-TERM CATALYST rationally engineered longer- • Most common type of • Robust preclinical data acting GCase varian
Slide 7: 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 Deficiency of GCase enzyme needed Affects multiple organs, leading to wide range of to metabolize Gb-1 symptoms and shortening life span1 Normal GCase GCase function deficiency Reduced lung functio
Slide 8: Existing therapies poorly address certain aspects of disease
Existing therapies poorly address certain aspects of disease LENGTHY INFUSION PEAKS AND TROUGHS in enzyme levels between EVERY TWO WEEKS infusions allow harmful substrates to build back up Easier to reach organs: liver, spleen ERT Enzyme replacement Harder to reach therapy current standard organs: b
Slide 9: Despite treatment, many patients continue to have disease progression
Despite treatment, many patients continue to have disease progression and debilitating symptoms After 10+ years on ERT up to 60% still experience symptoms1 bone pain enlarged liver enlarged spleen low blood counts 68% have pulmonary dysfunction at baseline with most 43% 56% 61% 43% likely not having
Slide 10: FLT201 has potential to deliver continuous level of enzyme and penetrate deeper tissues
FLT201 has potential to deliver continuous level of enzyme and penetrate deeper tissues that ERT does not reach SINGLE DOSE Potent liver-directed AAVS3 capsid Easier to reach GCase organs: liver, spleen variant 85 with prolonged half-life = more enzyme available to be delivered to cell Harder to rea
Slide 11: Engineered GCase variant with substantially longer half-life than wildtype
Our scientists engineered GCase variant with substantially longer half-life than wildtype Key features of GCase variant 85 structure GCase variant Two internal amino acid substitutions W312C E235 A341C • Does not impinge on the active site E340 20-fold increase in half-life in lysosomal • Minimizes
Slide 12: FLT201 showed high GCase expression in non-human primates
FLT201 showed high GCase expression in non-human primates Plasma 10000 Achieved steady increases in GCase Male (n=3) GCase Activity (nmol/h/ml) 1000 Female (n=3) plasma levels • A single injection of 100 FLT201 was well tolerated • Resulted in a rapid increase of GCase in 10 plasma that was sustaine
Slide 13: FLT201 led to increased uptake in key tissues in Gaucher mice
FLT201 led to increased uptake in key tissues in Gaucher mice Untreated ERT (60 U/kg) 2x1012 vg/kg GBA1WT • Dose-dependent 2x1011 vg/kg 2x1012 vg/kg GBA1var85 increases in GCase to above normal levels in key tissues • Greater GCase uptake in key tissues than with Normal ERT or with short half-life w
Slide 14: Enhanced and sustained GCase uptake observed in key tissues compared to ERT
Enhanced and sustained GCase uptake observed in key tissues compared to ERT Untreated ERT ERT GBA1var85 (1h post-dose) (24h post-dose) (steady state) Spleen Bone marrow Lung Anti-GCase – DAB, Haematoxylin counterstain, AAV8 ERT=Velaglucerase alfa 14
Slide 15: FLT201 cleared harmful substrate in key tissues in Gaucher mice
FLT201 cleared harmful substrate in key tissues in Gaucher mice 2 Liver 10 Spleen Hexosylsphingosine (pmol/mg) Hexosylsphingosine (pmol/mg) 8 6 1 4 2 Robust substrate * * * * * * 0 0 elimination WT 0 2x1010 2x1011 2x1012 ERT WT 0 2x1010 2x1011 2x1012 ERT AAV8-FLT201 (vg/kg) AAV8-FLT201 (vg/kg) Gba9v
Slide 16: GALILEO-1 Phase 1/2 dose-finding trial design
GALILEO-1 Phase 1/2 dose-finding trial design First-in-human, open-label, multicenter study; dosing completed in cohort 1 Establish a dose that delivers sustained Patient population: Highest Dose increases in Higher Doses Adults with Gaucher Type 1 previously 1.1e13 vg/kg GCase activity to reduce tr
Slide 17: GBA1-linked Parkinson's Disease
GBA1-linked Parkinson’s Disease
Slide 18: Longer-acting GCase variant may provide opportunity for best-in-class gene therapy for GBA1-linked PD
Our longer-acting GCase variant may provide opportunity for best-in-class gene therapy for GBA1-linked PD EXTEND OUR INNOVATION HIGH UNMET NEED EARLY DATA SUPPORT • Leverages engineered • No disease-modifying MOVE INTO PD longer-acting GCase therapies exist for PD • Demonstrated superior variant wit
Slide 19: PD is a severe and progressive neurodegenerative disease with no approved disease-modifying therapies
PD is a severe and progressive neurodegenerative disease with no approved disease-modifying therapies GBA1 mutations are most common genetic risk factor Characterized by build-up in Parkinson’s disease of alpha-synuclein aggregates (Lewy bodies) and death of dopaminergic neurons 5-30x greater risk o
Slide 20: GBA1-linked PD is a substantial and well-defined patient subset
GBA1-linked PD is a substantial and well-defined patient subset PD is second most common neurodegenerative disease ~1.9M diagnosed PD patients in US, UK and EU4* ~190,000 estimated GBA1-linked PD population 5-15% have GBA1 mutations† * Source: GlobalData; (Benito-León et al., 2003; Bergareche et al.
Slide 21: GCase variant demonstrated up to 20-fold greater activity than wildtype in preclinical studies
Our GCase variant has demonstrated up to 20-fold greater activity levels compared to wildtype in preclinical studies Brain epithelial cell line Neuroblastoma cell line Neuronal cell line (H4) (NB1643) (SH-SY5Y) ✱✱✱ ✱✱✱✱ 1000 60 GBA activity nmol/hr/ml 30 GBA activity nmol/hr/ml ✱✱✱✱ GBA activity nmo
Slide 22: Freeline: Pioneering gene therapy
Freeline: Pioneering gene therapy FLT201 is a potential First-in-human clinical Extending impact first-and best-in-class data for FLT201 expected of our innovation into gene therapy for in Q3 2023 provides GBA1-linked Parkinson’s Gaucher disease Type 1 near-term catalyst disease 22
Slide 23: Thank you
FIREELI\E Thank you
Freeline Therapeutics Holdings — Investor Presentation (August 2023) on 6ix