verbrinacogene setparvovec (FLT180a) / Spur Therapeutics - LARVOL DELTA

Freeline Reports First Quarter 2021 Financial Results and Recent Business Highlights (GlobeNewswire) - "Continued enrollment in the ECLIPSE run-in study for FLT180a for the treatment of Hemophilia B, supports enrollment in the Phase 1/2 dose-confirmation trial...Selected Anticipated Milestones in 2021: Report four-year durability data for FLT180a from the Company’s Phase 1/2 dose-finding trial in Hemophilia B...Complete IND/CTA enabling studies for FLT 210 for Hemophilia A."

Enrollment status • P1/2 data • Trial primary completion date • Hemophilia

Phase 1/2 Dose Confirmation Study of FLT180a in Hemophilia B (clinicaltrials.gov) - P1/2 | N=6 | Terminated | Sponsor: Freeline Therapeutics | Trial completion date: Nov 2023 ➔ May 2023 | Active, not recruiting ➔ Terminated | Trial primary completion date: Nov 2023 ➔ May 2023; Freeline has decided to pause development of FLT180a for business priorities

Trial completion date • Trial primary completion date • Trial termination • Viral vector • Hematological Disorders • Hemophilia • Rare Diseases • AFP

A Long-Term Follow-Up Study of Haemophilia B Patients Who Have Undergone Gene Therapy (clinicaltrials.gov) - P1/2 | N=10 | Terminated | Sponsor: Freeline Therapeutics | Trial completion date: Dec 2035 ➔ May 2023 | Active, not recruiting ➔ Terminated | Trial primary completion date: Dec 2035 ➔ May 2023; Freeline has decided to pause development of FLT180a for business priorities

Trial completion date • Trial primary completion date • Trial termination • Gene Therapies • Hematological Disorders • Hemophilia • Rare Diseases

Factor IX Expression within the Normal Range Prevents Spontaneous Bleeds Requiring Treatment Following FLT180a Gene Therapy in Patients with Severe Hemophilia B: Long-Term Follow-up Study of the B-Amaze Program (ASH 2021) - P1/2 | "B-AMAZE is the first HB gene therapy study to achieve normal levels of FIX activity using relatively low vector doses. Results suggest that a dose of 7.7e11 vg/kg, coupled with a short course of prophylactic immune management, has the potential to achieve durable FIX activity in the normal range (50-150%) and thereby prevent spontaneous bleeds and normalize hemostasis in the event of traumatic bleeds."

Clinical • Allergy • Cardiovascular • Gene Therapies • Hematological Disorders • Hemophilia • Rare Diseases • Thrombosis

Phase 1/2 Dose Confirmation Study of FLT180a in Hemophilia B (clinicaltrials.gov) - P1/2 | N=9 | Active, not recruiting | Sponsor: Freeline Therapeutics | Recruiting ➔ Active, not recruiting

Enrollment closed • Hematological Disorders • Hemophilia • Rare Diseases • AFP

Phase 1-2 Trial of AAVS3 Gene Therapy in Patients with Hemophilia B. (PubMed, N Engl J Med) - P1/2 | "Sustained factor IX levels in the normal range were observed with low doses of FLT180a but necessitated immunosuppression with glucocorticoids with or without tacrolimus. (Funded by Freeline Therapeutics; ClinicalTrials.gov numbers, NCT03369444 and NCT03641703; EudraCT numbers, 2017-000852-24 and 2017-005080-40.)."

Journal • P1 data • P1/2 data • Cardiovascular • Gene Therapies • Hematological Disorders • Hemophilia • Rare Diseases • Thrombosis

Results from B-LIEVE, a Phase 1/2 Dose-Confirmation Study of FLT180a AAV Gene Therapy in Patients with Hemophilia B (ISTH 2022) - "Safety data and FIX levels for the first cohort treated in B-LIEVE will be presented. Conclusion(s): Sustained FIX expression in the normal range is an important therapeutic goal for hemophilia B gene therapy. We will present results from B-LIEVE, a Phase 1/2 study of FLT180a designed to confirm the dose and immune management approach that consistently enables FIX expression within the normal range."

Clinical • P1/2 data • Gene Therapies • Hematological Disorders • Hemophilia • Rare Diseases

Freeline Announces First Patient Dosed in the Phase 1/2 B-LIEVE Dose-Confirmation Trial in Hemophilia B (GlobeNewswire) - "Freeline Therapeutics...announced that the first patient was dosed in its Phase 1/2 B-LIEVE dose-confirmation clinical trial of FLT180a for the treatment of hemophilia B, a debilitating genetic bleeding disorder caused by a deficiency in the clotting factor IX protein....The Company expects to report initial safety and biomarker data from the first dose cohort of the B-LIEVE trial in the first half of 2022. Should dosing of additional patients in the first dose cohort or dosing of the second cohort be necessary, Freeline expects those to be completed by the end of the third quarter of 2022. The Company expects to report further updated safety and biomarker data in both the second half of 2022 and the first half of 2023 and to initiate Phase 3 pivotal trial start-up activities in the first half of 2023."

New P3 trial • P1/2 data • Trial status • Hemophilia

Lysis and Clarification Strategies for AAV Suspension Processes (ASGCT 2022) - "Our lead AAV gene therapy candidate, FLT180a, is planned to be manufactured for commercial use on an adherent large-scale manufacturing platform (the iCELLis® 500 system), which was chosen for optimal potency and quality of vectors...The optimal lysis and clarification strategy identified in this study can simplify further downstream processing using the suspension cell platform, while enabling increased vector yields and reduced cost per dose during manufacturing compared to other approaches. Furthermore, our study shows that the optimal lysis and clarification strategy can contribute to the ability of our animal derived component-free suspension manufacturing platform to achieve potency and quality attributes comparable to those achieved by our adherent iCellis® platform."

Gene Therapies

Investigating the Oxygen Control Before and After Fixed Bed in the iCELLis® Nano Bioreactor to Create a More Robust Scale-Down Model for the iCELLis® 500 Bioprocess (ASGCT 2022) - "A commercial-scale platform for manufacturing adeno-associated virus (AAV) gene therapies has been developed using the iCELLis® 500 system in conjunction with a proprietary plasmid system for our lead clinical program (FLT180a), which provides very high cell-specific productivity, vector potency, and reduced levels of replication-competent AAV...In conclusion, a two-probe DO% measurement in the iCELLis® nano was established to regulate the oxygen supply after the fixed bed to further optimize the iCELLis® nano model toward a more accurate representation of the large-scale iCELLis® 500 process. This work further supports process robustness and validation on the small scale iCELLis® nano."

Gene Therapies

Study design for B-LIEVE, a Phase 1/2 dose-confirmation trial of FLT180a gene therapy for haemophilia B (WFH 2022) - "The B-LIEVE study will finalize a dose for the future Phase 3 trial of FLT180a that is intended to consistently enable FIX expression in the normal range for patients with haemophilia B. Additional key information regarding dose selection, IM, and study design will be presented."

P1/2 data • Gene Therapies • Hematological Disorders • Hemophilia • Rare Diseases

DOSE SELECTION AND STUDY DESIGN FOR B-LIEVE, A PHASE 1/2 DOSE CONFIRMATION CLINICAL TRIAL OF FLT180A GENE THERAPY FOR PATIENTS WITH HAEMOPHILIA B (EAHAD 2022) - "B-LIEVE is a Phase 1/2 dose-confirmation study of FLT180a that was designed based on the results of B-AMAZE and multiple modelling approaches. The B-LIEVE study will finalise a dose for the future Phase 3 trial that is intended to consistently enable FIX expression in the normal range for patients with haemophilia B. Additional details of the dose selection and study design will be presented."

Clinical • P1/2 data • Gene Therapies • Hematological Disorders • Hemophilia • Rare Diseases

Phase 1/2 Dose Confirmation Study of FLT180a in Hemophilia B (clinicaltrials.gov) - P1/2; N=9; Recruiting; Sponsor: Freeline Therapeutics; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Hematological Disorders • Hemophilia • Rare Diseases • AFP

Phase 1/2 Dose Confirmation Study of FLT180a in Hemophilia B (clinicaltrials.gov) - P1/2; N=9; Not yet recruiting; Sponsor: Freeline Therapeutics

Clinical • New P1/2 trial • Hematological Disorders • Hemophilia • Rare Diseases • AFP

Freeline Presents Long-Term Follow-Up Data from Phase 1/2 B-AMAZE Trial in Hemophilia B at the 2021 ASH Annual Meeting and Announces Early Initiation of Phase 1/2 B-LIEVE Dose-Confirmation Trial (GlobeNewswire) - P1/2, N=10; B-AMAZE (NCT03369444); "Freeline Therapeutics Holdings plc...today presents long-term follow-up data from its Phase 1/2 B-AMAZE dose-finding trial...at the 63rd American Society of Hematology (ASH) Annual Meeting and Exposition....Freeline also announced the first trial site in the Phase 1/2 B-LIEVE dose-confirmation trial of FLT180a has been initiated, one quarter ahead of its latest guidance. The Company anticipates an interim data readout from the B-LIEVE trial in the middle of 2022....Results suggest that a dose of 7.7e11 vg/kg, coupled with a short course of prophylactic immune management, has the potential to achieve durable FIX activity in the normal range (50-150%). and thereby prevent spontaneous bleeds and normalize hemostasis in the event of traumatic bleeds."

P1/2 data • Trial status • Genetic Disorders • Hemophilia

Freeline Reports New Data from Fabry Disease Program, Pipeline and Company Updates, Including Appointment of Pamela Foulds, MD as Chief Medical Officer, and Third Quarter 2021 Financial Results (GlobeNewswire) - "The Company is engaging with regulatory authorities to update the study protocol for the Phase 1/2 B-LIEVE dose-confirmation trial of FLT180a. The protocol changes and subsequent review shifts guidance by approximately one quarter for the FLT180a program, with study start expected in the first quarter of 2022 instead of by year-end 2021. We are currently evaluating the timing of our Phase 3 pivotal trial and filing of a Biologics License Application and will provide more concrete guidance next year. The Company continues to anticipate interim data readouts in 2022....The Company expects to complete ongoing preclinical studies of FLT210 for the treatment of hemophilia A by year end...Based on data generated in these studies to date, the Company is evaluating whether additional studies will enhance an IND filing and the necessity of conducting these additional studies."

Clinical protocol • P1/2 data • Preclinical • Trial initiation date • Genetic Disorders • Hemophilia

Freeline Announces 2022 Corporate Priorities and Guidance (GlobeNewswire) - "Freeline Therapeutics Holdings plc...today announced its 2022 corporate priorities and provided updated guidance....Following this review, the Company has decided to halt further development of our preclinical work for FLT210 in hemophilia A, given the additional work needed. Freeline will seek to explore potential third-party partnership opportunities to progress this important work....Initiated the B-LIEVE study, a Phase 1/2 dose-confirmation study of FLT180a manufactured at commercial scale and using a starting dose of 7.7e11 vg/kg and a short course of prophylactic immune management, in Q4 2021....The Company expects to complete dosing of the first dose cohort in the B-LIEVE study and report data from the first dose cohort in the first half of 2022."

Discontinued • Trial status • Genetic Disorders • Hemophilia

Freeline Therapeutics to Present FLT180a Data at the 2021 ASH Annual Meeting (GlobeNewswire) - "Freeline Therapeutics Holdings plc...today announced that data from its long-term follow-up study to its Phase 1/2 B-AMAZE clinical trial of FLT180a for the treatment of hemophilia B will be presented at the 63rd American Society of Hematology (ASH) Annual Meeting and Exposition, being held in Atlanta, Georgia and virtually on Saturday, December 11 through Tuesday, December 14, 2021."

P1/2 data • Genetic Disorders • Hemophilia

A Factor IX Gene Therapy Study (FIX-GT) (clinicaltrials.gov) - P1/2; N=10; Terminated; Sponsor: University College, London; N=24 ➔ 10; Trial completion date: Jun 2021 ➔ Oct 2020; Recruiting ➔ Terminated; Terminated early due to challenges during the COVID-19 pandemic and a change in requirements of data to be submitted for marketing authorisation.

Clinical • Enrollment change • Trial completion date • Trial termination • Gene Therapies • Hematological Disorders • Hemophilia • Rare Diseases

Freeline Provides Executive Leadership Team Update; Company to Provide Corporate Update and Second Quarter 2021 Financial Results on Monday, August 16 (GlobeNewswire) - "The Company reiterates its guidance across key upcoming milestones before year end 2021, which remains unchanged and includes....Initiating clinical trial sites for FLT180a Phase 1/2 dose-confirmation study in Hemophilia B and presenting updated durability data from its Phase 1/2 dose-finding study by year end."

P1/2 data • Trial status • Genetic Disorders • Hemophilia

[VIRTUAL] Practical Application of FIX-Padua Field Study Results Enables a Comparison of FIX:C Results Across AAV Gene Therapy Trials Independent of FIX:C Assay Reported (ISTH 2021) - "To support the development of verbrinacogene setparvovec (FLT180a), an investigational AAV gene therapy for the treatment of haemophilia B (HB) that expresses the gain-of-function FIX-Padua variant, an international multicentre field study was conducted to characterise FIX-R338L activity across 15 commonly used FIX activity (FIX:C) assays...Conclusions : FIX:C ratios derived from our FIX-R338L field study permit direct, reliable comparison of FIX:C assay results. Our Calculator enables estimation of activity results, which facilitates a meaningful comparison of different investigational FIX-R338L-based HB gene therapies."

Gene Therapies • Hematological Disorders • Hemophilia • Rare Diseases

[VIRTUAL] Practical Application of FIX-Padua Field Study Results Enables a Comparison of FIX:C Results Across AAV Gene Therapy Trials Independent of FIX:C Assay Reported (ISTH 2021) - "To support the development of verbrinacogene setparvovec (FLT180a), an investigational AAV gene therapy for the treatment of haemophilia B (HB) that expresses the gain-of-function FIX-Padua variant, an international multicentre field study was conducted to characterise FIX-R338L activity across 15 commonly used FIX activity (FIX:C) assays...Conclusions : FIX:C ratios derived from our FIX-R338L field study permit direct, reliable comparison of FIX:C assay results. Our Calculator enables estimation of activity results, which facilitates a meaningful comparison of different investigational FIX-R338L-based HB gene therapies."

Gene Therapies • Hematological Disorders • Hemophilia • Rare Diseases

Freeline Reports Full Year 2020 Financial Results and Business Highlights (GlobeNewswire) - "Plan to initiate Phase 1/2 dose-confirmation trial for FLT180a by the end of 2021 to confirm both the dose and the immune management regimen for the planned pivotal Phase 3 clinical trial. The Company is targeting full enrollment of the Phase 1/2 dose-confirmation trial during the first half of 2022 and a six-month data readout by the end of 2022....Plan to report up to four-year durability data for FLT180a from the Phase 1/2 dose-finding clinical trial by the end of 2021....Plan to complete preclinical proof-of-concept studies of the safety, efficacy and durability of FLT210 to support an IND filing in 2022....Research and development (R&D) expenses for the year ended December 31, 2020 were $76.1 million...driven by an increased investment in activities related to the current and proposed clinical trials for FLT180a..."

Commercial • Enrollment status • IND • New P1/2 trial • P1/2 data • Preclinical • Hemophilia

Freeline Therapeutics Updates Clinical Development Plan for its FLT180a Hemophilia B Program (GlobeNewswire) - "Freeline now plans to conduct dose confirmation in a FLT180a Phase 1/2 trial instead of in the Phase 2b part of the previously planned Phase 2b/3 pivotal trial....To meet its objectives of initiating the clinical trial sites for the dose confirmation trial by the end of 2021, while in parallel, working to meet FDA’s Chemistry, Manufacturing and Control ('CMC') requirements in advance of commencing the planned Phase 3 pivotal trial. The Company is targeting a data readout for the Phase 1/2 dose confirmation trial by the end of 2022, initiation of the Phase 3 pivotal trial by the middle of 2023 and filing of a Biologic License Application ('BLA') with the FDA by the end of 2024."

BLA • New P3 trial • P1/2 data • Trial initiation date • Hemophilia

[VIRTUAL] FOLLOW‐UP ON A NOVEL ADENO ASSOCIATED VIRUS (AAV) GENE THERAPY (FLT180A) ACHIEVING NORMAL FIX ACTIVITY LEVELS IN SEVERE HEMOPHILIA B (HB) PATIENTS (B‐AMAZE STUDY). (EAHAD 2021) - "B-AMAZE is the first HB gene therapy clinical trial to achieve normal levels of FIX activity using relatively low doses of vector. Results support further work to achieve and maintain normal levels of FIX activity in a larger number of patients."

Clinical • Gene Therapies • Hematological Disorders • Hemophilia • Rare Diseases