Orchard Therapeutics (NASDAQ: ORTX), a leading commercial-stage biopharmaceutical company dedicated to transforming the lives of patients with serious and life-threatening rare diseases through innovative gene therapies, today will present two-year follow-up data in 20 patients from the registrational trial evaluating OTL-101, an autologous, ex vivo, hematopoietic stem cell gene therapy for the treatment of severe combined immune deficiency due to adenosine deaminase deficiency (ADA-SCID) during the President's Symposia at the 2019 Transplantation and Cellular Therapy Meetings of ASBMT and CIBMTR in Houston, TX.

ADA-SCID is a rare, life-threatening, inherited disease caused by mutations in the ADA gene. Deficiencies of the ADA enzyme leads to dysfunction of cells of the immune system, including B, T and natural killer cells. Patients with ADA-SCID are unable to fight off and frequently succumb to complications from bacterial, viral and fungal infections.

"With some patients in this trial approaching 5 years of follow-up, treatment with OTL-101 continues to be well-tolerated with higher rates of overall and event free survival for patients with ADA-SCID compared to a historical control group of patients receiving hematopoietic stem cell transplants," said Donald B. Kohn, M.D., professor of Microbiology, Immunology & Molecular Genetics at the University of California, Los Angeles and the principal investigator of the study. "We are very encouraged by the results and look forward to advancing this potentially transformative treatment option for patients with this serious and life-threatening condition."

Bobby Gaspar, M.D., Ph.D., chief scientific officer of Orchard commented, "These results demonstrate that by engrafting autologous, gene-modified, long-term repopulating hematopoietic stem cells, we are able to see durable recovery of the immune system. With 100% overall survival and 100% event free survival in this trial maintained at 24 months, we believe OTL-101 has the potential to enable patients with ADA-SCID to lead healthier lives with restored immunity to fight infections."

Andrea Spezzi, M.D., chief medical officer of Orchard continued, "For the remainder of 2019, we are focused on completing the clinical and manufacturing activities to enable a BLA filing in 2020, bringing us closer to our goal of providing patients with a new treatment option."

The reported data are the complete 24 month results from a trial evaluating the safety and efficacy of OTL-101. OTL-101 was administered post-busulfan conditioning in 20 pediatric patients, who lacked a medically eligible donor for bone marrow transplantation. Patients were followed for 24 months post treatment and compared with a historical control cohort of 26 patients with ADA-SCID who underwent hematopoietic stem cell transplant (HSCT), 12 from matched related donors (MRD) and 14 without a MRD. The median age at treatment for patients receiving OTL-101 was 9.0 months and 7.3 months for patients treated with HSCT.

Efficacy Data

• Treatment with OTL-101 resulted in 100% overall survival (OS) and 100% event free survival (EvFS) at 24 months

• For OS, there was a difference of 12% (95% CI: -5.6, 31.2, p = 0.121) between the patients treated with OTL-101 compared with HSCT overall
• For EvFS, there was a statistically significant difference of 44% (95% CI: 22.8, 65.2, p = 0.001) between the patients treated with OTL-101 compared with HSCT overall

• Genetically modified cells, as indicated by increasing and then sustained vector copy number in both peripheral blood mononuclear cells and granulocytes, were detectable in all patients treated with OTL-101 and were maintained through 24 months post-treatment. A similar pattern was observed in ADA enzyme activity.

• Evidence of immune reconstitution was observed in patients treated with OTL-101

• By 24 months post-treatment, 90% of patients receiving OTL-101 were able to stop immunoglobulin replacement therapy compared with 55% receiving HSCT overall   
• Over 24 months, none of the patients treated with OTL-101 restarted enzyme replacement therapy (ERT) after stopping 30 days post-treatment per protocol, whereas three patients in the historical control group received long-term ERT after HSCT and seven required additional rescue HSCT

Safety Data

• Treatment with OTL-101 was well-tolerated and had a positive benefit-risk profile

• There were no deaths or reports of graft-versus-host disease (GvHD) in the patients treated with OTL-101

• In the historical HSCT control group, five acute and three chronic GvHD events were reported, including one death due to GvHD

• Nine out of the 20 patients who received OTL-101 experienced a total of 27 serious adverse events (SAEs)

• The most frequent SAEs were infections and gastrointestinal events
• One SAE of bacteremia was deemed related to treatment with OTL-101 and resolved with antibiotics  
• Two cases of immune reconstitution inflammatory syndrome were deemed unrelated to OTL-101 and resolved with corticosteroids
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