Freeline Therapeutics Holdings Plc
Freeline Therapeutics — Investor Presentation (August 2022)
36 slides from Freeline Therapeutics's investor presentation, Aug 9, 2022
Slide 1: Corporate Presentation
Corporate Presentation 9 August 2022
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: Pioneering transformative gene therapies with best-in-class and/or first-in-class potential
Pioneering transformative gene therapies with Freeline best-in-class and/or first-in-class potential High protein expression at low doses enabled by potent, proprietary capsid Transforming the lives of patients with systemic Targeting diseases where high protein expression at debilitating diseases D
Slide 4: Three clinical programs with best-in-class and/or first-in-class potential
Three clinical programs with best-in-class and/or first-in-class potential FLT180a FLT190 FLT201 For treatment of For treatment of For treatment of hemophilia B Fabry disease Gaucher disease2 Demonstrated Factor IX (FIX) activity at Data from lowest dose cohort show promising Novel protein engineere
Slide 5: Human Hepatocyte Transduction
Platform Technology: AAVS3 capsid engineered to more efficiently transduce human hepatocytes AAVS3 transduction significantly higher compared to other AAVS3 achieved nearly 6-fold higher transduction serotypes and untreated control compared to AAV8 Transduction efficiency of AAVS3 in vitro compared
Slide 6: Clinical data demonstrated greater potency of AAVS3 relative to competitors
Mean 52-week Factor IX Activity Level in Patients with Hemophilia B Clinical data 50 Similar efficacy; about 50x lower dose demonstrated greater potency of 40 Factor IX (FIX) activity level (%) Mean: Mean: Mean: 40.5% 41.0% 41.5% AAVS3 relative to 30 =2 =3 = 54 competitors 20 Mean: 22.0% = 15 10 The
Slide 7: Company Strategy: Pioneering innovations that transform the lives of patients
Company Strategy: Pioneering innovations that transform the lives of patients 1 2 3 Leverage highly potent Execute clinical Invest in future innovations capsid and platform programs to generate by leveraging capabilities to deliver data demonstrating the Freeline’s unique best-in-class and value of
Slide 8: Lean organization with core gene therapy discovery and development capabilities
Lean organization with core gene therapy discovery and development capabilities Experienced and innovative Leading industry experts in Operational efficiency leadership team clinical development enhances financial flexibility for future growth and platform Lean organization of ~180 FTEs Cash runway
Slide 9: Hemophilia B
Hemophilia B
Slide 10: Hemophilia B Overview
Hemophilia B Overview Disease Characteristics: Blood Coagulation Cascade Clinical Manifestations • Rare, X-linked, congenital bleeding Frequent, disorder caused by deficiency of spontaneous coagulation Factor IX (FIX) bleeding • Depending on the severity of the disease, symptoms can range from Abnor
Slide 11: Challenge: First-generation capsids do not adequately protect patients from bleeds
Challenge: First-generation capsids do not adequately protect patients from bleeds Mean 52-week Factor IX Activity Level >100% 100 Factor IX (FIX) activity level (%) FIX activity levels achieved 50 50% ~47% using first-generation 52-week 52-week Mean: 41% Mean: 41.5% capsids are in the mild range =3
Slide 12: Opportunity: Best-in-class therapy providing durable FIX activity
Opportunity: Best-in-class therapy providing durable FIX activity at levels protecting patients from bleeds and FIX replacement therapy Market need1 Hemophilia B target product profile Patients Predictably provide durable FIX activity Will wait for a gene therapy that delivers durable FIX at protect
Slide 13: B-AMAZE Phase 1/2 dose-finding trial design
B-AMAZE Phase 1/2 dose-finding trial design Features of B-AMAZE • Targeted normal range of FIX levels • Adaptive dosing design to facilitate dose finding • Prophylactic immune management plus reactive as needed for vector-related transaminitis Dose 2 Duration Dose 4 1.28x1012 vg/kg • 26 weeks for B-
Slide 14: FLT180a delivered durable FIX expression in B-AMAZE for up to 3.5 years
FLT180a delivered durable FIX expression, strongly decreasing both bleeding rates and need for FIX replacement in B-AMAZE for up to 3.5 years • Dose-dependent increases in FIX for all patients • 9 of 10 patients had sustained FIX activity at a median follow-up of 27.2 (19.1-42.4) months. • 5 patient
Slide 15: FLT180a clinical development plan
FLT180a clinical development plan B-LIEVE: Phase 1/2 trial to confirm the dose and immune management regimen for use in a pivotal Phase 3 trial ECLIPSE Run-in Study Phase 1/2 Dose-Finding Trial and - Fully enrolled to supply patients to Phase 1/2 dose-confirmation trial EOP2 Meeting are Complete B-A
Slide 16: FLT180a generated protective FIX levels in first cohort of B-LIEVE trial
FLT180a generated protective FIX levels with no bleeding or need for FIX replacement in first cohort of B-LIEVE trial • FLT180a dose of 7.7e11 vg/kg plus proactive immune management* • Rapid increase of FIX levels, reaching normal range (93, 92 and 80 IU/dL) for the three patients through days 77, 5
Slide 17: Anticipated FLT180a milestones
Anticipated FLT180a milestones FLT180a – Hemophilia B Phase 1/2 B-LIEVE dose-confirmation trial 2022 2023 H1 H2 H1 H2 Completed dosing of Report updated safety and Follow-up the first cohort efficacy data Reported initial safety and Conclude evaluation of efficacy data strategic options, including p
Slide 18: Fabry Disease
Fabry Disease
Slide 19: Fabry Disease Overview
Fabry Disease Overview Disease Characteristics: Fabry Disease Mechanism Clinical Manifestations Globotriaosylceramide (Gb3) • Rare X-linked lysosomal storage disorder (LSD) resulting from Stroke Normal Abnormal deficient activity, or absence, of α α-Gal α-Gal A Galactosidase A (α-Gal A) A function (
Slide 20: Challenge: No curative therapy exists and high unmet need remains for Fabry disease
Challenge: No curative therapy exists and high unmet medical need remains for Fabry disease patients receiving ERT Fabry disease patient perspectives1 ERT treatment burden Limitations of ERT “Travelling to and from the hospital, the time spent for infusions, and trying to keep my spirit up and • Lif
Slide 21: Opportunity: Patients need sustained levels of α-Gal A eliminating the need for ERT
Opportunity: Patients need a therapy that delivers sustained levels of α-Gal A eliminating the need for ERT Fabry disease target Competitor landscape Urgent market need1 product profile • Short half-life ERT therapies Patients do not deliver sustained Attracted to freedom from bi-weekly infusions Du
Slide 22: FLT190 treatment for Fabry disease: potential efficacy demonstrated in Fabry mouse model
FLT190 treatment Meaningful increase in α-Gal A expression leading to reduction in pathologic substrate in key tissues for Fabry disease: Potential efficacy Kidney α-Gal A activity levels Heart α-Gal A activity levels demonstrated in 300 400 Fabry mouse model 300 α-Gal A in Kidney α-Gal A in Heart 2
Slide 23: MARVEL-1 Phase 1/2 dose-finding trial design
MARVEL-1 Phase 1/2 dose-finding trial design Part I: Highest Dose Phase 3 Trial: Adaptive trial: Higher Doses To establish a dose of Patients previously 1.3e13 vg/kg Previously treated treated with ERT or patients FLT190 that delivers chaperone therapy1 Higher Dose If needed sustained increased 4.5e
Slide 24: Durable α-Gal A activity over years in Patient 2
Durable α-Gal A activity over 2 years in Patient 1 and near-normal levels in Patient 2 ~40% increase in total Average Plasma α-Gal A2 Activity Following Treatment with 7.5e11 vg/kg of FLT190 Patient 2 dose with ~400% increase in activity1 • No rise in ALT/AST levels; 21.9 received optimized immune N
Slide 25: Anticipated FLT190 milestones
Anticipated FLT190 milestones FLT190 – Fabry disease Phase 1/2 MARVEL-1 dose-finding trial 2022 2023 H1 H2 H1 H2 Reported updated safety and efficacy data from Dose in second cohort Dose additional patient(s) the first cohort Accelerated escalation to the Report updated safety and Provide a program
Slide 26: Gaucher Disease (Type 1)
Gaucher Disease (Type 1)
Slide 27: Gaucher disease (Type 1) Overview
Gaucher disease (Type 1) Overview Gaucher Disease Mechanism Clinical Manifestations Disease Characteristics: Glucocerebroside (GL-1) • Rare genetic LSD resulting from deficiency of glucocerebrosidase Normal Abnormal (GCase) Glucocerebrosidase GCase (GCase) function (Gaucher) • Leads to accumulation
Slide 28: Challenge: No curative therapy exists for Gaucher disease (Type 1) patients
Challenge: No curative therapy exists for Gaucher disease (Type 1) patients receiving lifelong ERT or SRT Gaucher disease patient perspectives1 Limitations of ERT and SRT ERT treatment burden • Lifelong intravenous infusions every two “… It would be a lot easier if I didn’t have to do the weeks plac
Slide 29: Opportunity: Freeline has most advanced AAV gene therapy program for Gaucher disease
Opportunity: Freeline has most advanced AAV gene therapy program for Gaucher disease (Type 1) Gaucher disease target Competitor landscape Urgent market need1 product profile • Limited competition in the Patients Durable increased Gaucher gene therapy market Attracted to freedom from bi-weekly GCase
Slide 30: FLT201 produces a more stable GCase variant with higher expression
FLT201 produces a more stable GCase variant that achieves higher expression levels Structure of GCase variant: GCase variant 85 Key features of GCase variant > 20-fold increase in In vitro stability: 10 of 86 GCase half-life in lysosomal protein variants showed improved pH compared with stability co
Slide 31: FLT201 produces more stable protein; higher uptake in Gaucher mice
FLT201 produces more stable protein; higher uptake in Gaucher mice Increased protein stability 300 sustains higher GCase FLT201 dose: 2x1012 vg/kg Higher GCase levels compared with GCase activity in blood (µmol/h/ml) 200 expression at low doses velaglucerase alpha1 and increased uptake in key tissue
Slide 32: FLT201 clears substrate in key tissues in Gaucher mice
FLT201 clears substrate in key tissues in Gaucher mice Wild-type mice Untreated GCase tissue penetration AAV8-FLT201 and enzymatic activity leads ERT to substrate level reduction * * * * * * across key tissues • Dose-dependent reductions of lyso-GB1 observed in all tissues analyzed, including bone m
Slide 33: FLT201 demonstrates high levels of GCase expression in non-human primates
FLT201 demonstrates high levels of GCase expression in non- human primates Plasma Achieves steady increases in GCase plasma levels 10000 17-002 Females 17-037 17-056 1000 GCase activity (µmol/h/ml) 17-020 • A single injection of FLT201 500 Males 17-036 was well tolerated 250 17-076 100 • Resulted in
Slide 34: Phase 1/2 dose-finding trial design
Phase 1/2 dose-finding trial design Adaptive trial design Trial to evaluate safety and tolerability of FLT201 and Part I: Highest Dose Phase 3 Trial: establish a dose that Higher Doses Patients previously 1.1e13 vg/kg Previously treated delivers sustained treated with ERT or patients Higher Dose If
Slide 35: Anticipated FLT201 milestones
Anticipated FLT201 milestones FLT201 – Gaucher disease (Type 1) Phase 1/2 dose-finding trial 2022 2023 H1 H2 H1 H2 Report updated safety and Dose patients efficacy data Report initial safety and Dose additional patients efficacy data (if needed) 35
Slide 36: Thank you
Thank you 9 August 2022
Freeline Therapeutics Holdings — Investor Presentation (August 2022) on 6ix