OTL-102 / Genethon, Kyowa Kirin - LARVOL DELTA

Study of Gene Therapy Using a Lentiviral Vector to Treat X-linked Chronic Granulomatous Disease (clinicaltrials.gov) - P1/2 | N=10 | Completed | Sponsor: University of California, Los Angeles | Recruiting ➔ Completed | N=16 ➔ 10 | Trial completion date: Dec 2028 ➔ Dec 2024 | Trial primary completion date: Dec 2026 ➔ Sep 2024

Enrollment change • Gene therapy • Trial completion • Trial completion date • Trial primary completion date • Viral vector • Gene Therapies • Immunology • Primary Immunodeficiency

Study of Gene Therapy Using a Lentiviral Vector to Treat X-linked Chronic Granulomatous Disease (clinicaltrials.gov) - P1/2 | N=16 | Recruiting | Sponsor: University of California, Los Angeles

Gene therapy • Trial completion date • Trial primary completion date • Viral vector • Gene Therapies • Immunology • Primary Immunodeficiency

Study of Gene Therapy Using a Lentiviral Vector to Treat X-linked Chronic Granulomatous Disease (clinicaltrials.gov) - P1/2 | N=16 | Recruiting | Sponsor: University of California, Los Angeles | Active, not recruiting ➔ Recruiting

Enrollment open • Gene therapy • Viral vector • Gene Therapies • Immunology • Primary Immunodeficiency

G1XCGD.01: Gene Therapy for X-linked Chronic Granulomatous Disease (X-CGD) (clinicaltrials.gov) - P1/2 | N=3 | Active, not recruiting | Sponsor: Genethon | Trial completion date: Sep 2022 ➔ Sep 2032 | Trial primary completion date: Sep 2022 ➔ Sep 2032

Gene therapy • Trial completion date • Trial primary completion date • Viral vector • Gene Therapies • Immunology • Primary Immunodeficiency • CD34

Gene Therapy for X-linked Chronic Granulomatous Disease (clinicaltrials.gov) - P1/2 | N=3 | Active, not recruiting | Sponsor: Genethon | Trial completion date: Jun 2024 ➔ Jun 2034 | Trial primary completion date: Jun 2024 ➔ Jun 2034

Gene therapy • Trial completion date • Trial primary completion date • Viral vector • Gene Therapies • Immunology • Primary Immunodeficiency • CD34

Study of Gene Therapy Using a Lentiviral Vector to Treat X-linked Chronic Granulomatous Disease (clinicaltrials.gov) - P1/2 | N=16 | Active, not recruiting | Sponsor: University of California, Los Angeles | Recruiting ➔ Active, not recruiting

Enrollment closed • Gene Therapies • Immunology • Primary Immunodeficiency

Transcriptional Mapping of Human Hematopoietic Stem and Progenitor Cells Discriminates Chronic Granulomatous Disease Patients Able to Benefit from Gene Therapy Treatment (ASGCT 2022) - P1/2 | "These transcriptomic alterations could facilitate myeloid differentiation during a secondary challenge and drive the HSC defect by impairing the long-term engraftment ability in two out of 4 treated patients. Those identified pathways will help identify targeted treatments before GT to protect HSC functionality and allow a more efficient therapeutic approach for CGD patients."

Clinical • Gene Therapies • Immunology • Infectious Disease • Primary Immunodeficiency • Transplantation

Study of Gene Therapy Using a Lentiviral Vector to Treat X-linked Chronic Granulomatous Disease (clinicaltrials.gov) - P1/2; N=16; Recruiting; Sponsor: University of California, Los Angeles; Active, not recruiting ➔ Recruiting; N=10 ➔ 16; Trial completion date: Dec 2021 ➔ Dec 2024; Trial primary completion date: Apr 2021 ➔ Apr 2024

Clinical • Enrollment change • Enrollment open • Trial completion date • Trial primary completion date • Gene Therapies • Immunology • Primary Immunodeficiency

Gene Therapy for X-linked Chronic Granulomatous Disease (clinicaltrials.gov) - P1/2; N=3; Active, not recruiting; Sponsor: Genethon; Recruiting ➔ Active, not recruiting; Trial completion date: Dec 2023 ➔ Jun 2024; Trial primary completion date: Dec 2023 ➔ Jun 2024

Clinical • Enrollment closed • Trial completion date • Trial primary completion date • CD34

Gene Therapy for X-linked Chronic Granulomatous Disease (X-CGD) (clinicaltrials.gov) - P1/2; N=3; Active, not recruiting; Sponsor: Genethon; Recruiting ➔ Active, not recruiting; Trial completion date: Mar 2020 ➔ Sep 2022; Trial primary completion date: Mar 2020 ➔ Sep 2022

Clinical • Enrollment closed • Trial completion date • Trial primary completion date • CD34

Study of Gene Therapy Using a Lentiviral Vector to Treat X-linked Chronic Granulomatous Disease (clinicaltrials.gov) - P1/2; N=10; Active, not recruiting; Sponsor: University of California, Los Angeles; Recruiting ➔ Active, not recruiting; Trial completion date: Dec 2020 ➔ Dec 2021; Trial primary completion date: Dec 2018 ➔ Apr 2021

Clinical • Enrollment closed • Trial completion date • Trial primary completion date

Orchard Therapeutics Reports 2018 Financial Results and Reviews Recent Business Highlights (GlobeNewswire, Orchard Therapeutics Limited) - "Upcoming Data Presentations & Remaining 2019 Milestones: Release engraftment data in 10 patients from a cryopreserved formulation clinical trial of OTL-101 for ADA-SCID...Design and engage regulators on the registrational trial for OTL-102 for patients with X-CGD...During 2018, the company recognized $2.1 million in net product sales from Strimvelis....Research and development expenses were $205.3 million in 2018...The increase was primarily driven by the acquisition of Strimvelis...Selling, general and administrative expenses were $31.4 million in 2018...due to personnel costs to support public company operations, as well as costs to market Strimvelis..."

P1/2 data • Regulatory • Sales

EFFECTIVE LENTIVIRAL GENE THERAPY FOR X-LINKED CHRONIC GRANULOMATOUS DISEASE (EBMT 2019) - P1/2; "...G-CSF and Plerixafor-mobilized CD34+ selected hematopoietic stem and progenitor cells were transduced ex vivo with G1XCGD LV. Subjects received near-myeloablative conditioning with single agent busulfan, targeted to net area-under-the-curve of 70,000 ng/ml*hr... These results are the first demonstration of effective autologous lentiviral GT at 12 months in severely affected X-CGD patients without evidence of genotoxicity. Corrected neutrophil function has been observed in 6 patients for >12 months and has been associated with significant clinical improvement, freedom from infections, and resolution of chronic inflammation. Results are supportive of extended clinical trials evaluating the safety and efficacy of G1XCGD LV-based gene therapy."

Len tiviral Vector Gene Therapy for X-linked Chronic Granulomatous Disease Corrects Neutrophil Function (CIS 2019) - "...Following transplant of G1XCGD LV ex vivo transduced autologous HSCs into busulfanconditioned XCGD patients, there was long-term restoration of oxidase activity in peripheral blood polymorphonuclear neutrophils (PMN) at 12 months in 6 of 9 severely affected XCGD patients without evidence of genotoxicity...G-CSF plus Plerixafor-mobilized CD34+ HSCs were transduced with ex vivo G1XCGDLV... These results demonstrate corrected PMN function within 1 month in X-CGD patients treated with autologous GT. PMN oxidase activity was sustained at levels which restore biochemical function and provide clinically beneficial levels of immunity for 12 months in 6/7 patients. Grant Support: Supported by research grants from the: California Institute of Regenerative Medicine (CLIN2-08231; FA1-00613-1), the Gene Therapy Resource Program from NHLBI, NIH (CRB-SSS-S-15- 004351 1840), the NIAID Intramural Program, NET4CGD (FP7 EU grant agreement no."

Orchard Therapeutics presents clinical proof-of-concept data for OTL-102 for the treatment of X-CGD (GlobeNewswire) - "Orchard Therapeutics...presented additional clinical proof-of-concept data evaluating OTL-102...for the treatment of X-linked chronic granulomatous disease (X-CGD) during an oral presentation at the 2019 Transplantation and Cellular Therapy Meetings of ASBMT and CIBMTR in Houston...'This proof-of-concept data set for OTL-102 demonstrates efficacy across multiple markers of clinical benefit in 6 of 7 evaluable patients treated for X-CGD at twelve months,'...We are in the process of designing a registrational trial and intend to seek regulatory input this year on the clinical development path forward.'"

Clinical data • New trial • Regulatory

Effective Lentiviral Gene Therapy for X-Linked Chronic Granulomatous Disease (X-CGD) (TCT-ASBMT-CIBMTR 2019) - "...G-CSF and Plerixafor-mobilized CD34+ selected hematopoietic stem and progenitor cells were transduced with G1XCGD LV ex vivo. Pts received myeloablative conditioning with single agent busulfan (targeted to net AUC of 70,000 ng/ml*hr)... These Results are the first demonstration of effective autologous lentiviral GT at 12 mo in severely affected X-CGD pts without evidence of genotoxicity. Corrected neutrophil function has been observed in 6 pts for >12 mo and associated with clinical improvement, freedom from infections, and resolution of chronic inflammation. The Results are supportive of extended clinical trials evaluating the safety and efficacy of G1XCGD LV-based GT."

Late-breaking abstract

Orchard Therapeutics announces acceptance of late-breaking abstracts of OTL-101 for ADA-SCID and OTL-102 for X-CGD at the 2019 Transplantation and Cellular Therapy Meetings of ASBMT and CIBMTR (GlobeNewswire) - "Orchard Therapeutics...announced that new clinical data for OTL-101 and OTL-102 will be presented in oral and poster presentations at the Transplantation and Cellular Therapy (TCT) Meetings of the American Society of Blood and Marrow Transplantation (ASBMT) and Center for International Blood and Marrow Transplant Research (CIBMTR) to be held on February 20-24, 2019 in Houston, TX."

Clinical data • P1/2 data

Orchard Therapeutics highlights recent accomplishments and 2019 strategic priorities as a global leader in gene therapy (GlobeNewswire) - "2019 Strategic Priorities: Primary Immune Deficiencies: Release two-year follow-up data in 20 patients from the fresh formulation registrational trial of OTL-101 in adenosine deaminase severe combined immune deficiency (ADA-SCID); Release engraftment data in 10 patients from a cryopreserved formulation clinical trial of OTL-101 in ADA-SCID; Design and engage regulators on registrational trial for OTL-102 in X-linked chronic granulomatous disease (X-CGD), which recently achieved clinical proof-of-concept."

Clinical data • Trial status