Results of Phase 1/II Northstar (HGB-204) study and ongoing, Phase III Northstar-2 (HGB-207) study of LentiGlobin Gene Therapy for beta-thalassemia. - bluebird bio.

bluebird bio, Inc. announced that new data from the completed Phase 1/II Northstar (HGB-204) study in adolescents and adults with transfusion-dependent beta-thalassemia (TDT) and any genotype, and its ongoing, Phase III Northstar-2 (HGB-207) multicenter clinical study of LentiGlobin investigational gene therapy in patients with TDT and non-beta0/beta0 genotypes, will be presented in an oral session on June 16 at the 23rd Annual Congress of the European Hematology Association by Franco Locatelli, M.D., Ph.D., of the IRCCS Ospedale Pediatrico Bambino Gesù of Rome, Italy.

People with TDT (transfusion-dependent beta -thalassemia need regular blood transfusions to survive, but chronic transfusions carry risks, including unavoidable iron overload that can result in multi-organ damage and shortened life expectancy. Eliminating or reducing the need for transfusions may reduce the long-term complications associated with TDT and current standards of care.

LentiGlobin Gene Therapy for Transfusion-Dependent beta-Thalassemia (TDT) in Patients with non-beta0/beta0 Genotypes: Updated Results from Northstar-2 (Abstract #1510) .Presenter: Franco Locatelli, M.D., Ph.D., Professor of Pediatrics, University of Pavia, Italy and Director, Department of Pediatric Hematology and Oncology, IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy . Oral Session: Cell and Gene Therapy: Clinical Results Date & Time: Saturday, June 16, 2018, 11:45 a.m. – 12:00 p.m.

The safety and efficacy of LentiGlobin in patients with TDT were evaluated in the Phase 1/II Northstar study (HGB-204) . To further improve clinical results, a refined manufacturing process was used to produce LentiGlobin drug product (DP). The aim of the ongoing Phase III Northstar-2 study (HGB-207) is to evaluate the efficacy and safety of LentiGlobin DP with manufacturing refinements in patients with TDT and non-beta 0/beta 0 genotypes. Data from Northstar and Northstar-2 will be included in the oral presentation.

Northstar-2 (HGB-207) results include (as of May 15, 2018): 1. 11 patients had been infused with LentiGlobin and the median follow-up was 8.5 months (range: 0.3 – 16.2 months). 2. 7 of 8 patients are producing greater than 7.6 g/dL of HbAT87Q and are maintaining total hemoglobin levels of 11.1 – 13.3 g/dL by 6 months. 3. These 7 patients with greater than 6 months follow-up remain transfusion free for 4.7 – 15.1 months. 4. For the 11 study participants, the median DP vector copy number (VCN) was 3.4 (range: 2.4 – 5.6) copies/diploid genome, and the median proportion of transduced CD34+ cells was 82% (range: 53 – 90%).5. The safety profile of LentiGlobin to date is similar to that observed in the Northstar study, and consistent with myeloablative conditioning with single-agent busulfan. No grade 3 or higher DP-related adverse events (AE) have been observed. 6. All study participants remain enrolled in the trial, and there have been no reports of graft-versus-host disease (GvHD).

Northstar (HGB-204) results include (as of March 7, 2018): 1. All 18 patients have completed the primary two-year study and are continuing into the long-term follow-up study LTF-303. 2. 8 of 10 patients with non-beta 0/ beta 0 genotypes were transfusion independent for a median of 33 months as of last follow-up. 3. For the 18 study participants, the median DP VCN was 0.7 (range: 0.3 – 1.5) copies/diploid genome, and the median proportion of transduced CD34+ cells was 32% (range: 17 – 58%). 4.The safety profile of LentiGlobin DP continues to be consistent with myeloablative conditioning with single-agent busulfan. There have been no reports of GvHD and no deaths on the study. 5 One serious AE of HIV infection was reported 23 months after infusion. HIV was contracted from typical exposure and is not related to treatment with LentiGlobin. This was confirmed by two laboratory tests that differentiate between HIV and the lentivirus used in LentiGlobin.

Comment: Treatment with new versions of LentiGlobin spurred normal or near-normal production of the oxygen-transporting protein hemoglobin in a handful of patients with beta-thalassemia, while boosting anti-sickling hemoglobin in four patients with severe sickle cell disease. The results mark progress for LentiGlobin after an earlier version had run into hurdles that prompted bluebird to change how it manufactured the therapy.