bluebird bio Inc (NASDAQ:BLUE) will outline today key activities underway intended to advance the company’s LentiGlobin programs in transfusion-dependent β-thalassemia (TDT) and severe sickle cell disease (SCD). The presentation will focus on three key aspects of these activities: 1) potential improvements in transduction efficiency and manufacturing; 2) updates to the protocol for the company’s ongoing HGB-206 clinical trial in SCD; and 3) regulatory plans for the company’s LentiGlobin drug product candidate in TDT.

“At bluebird bio we have an incredibly ambitious goal: to deliver one-time, transformative therapies to patients with rare genetic diseases and cancer. We are relentless in our efforts to continue innovating in pursuit of that goal, and we have made substantial advances in the transduction and manufacturing processes, translational research, and clinical development,” said Nick Leschly, chief bluebird. “By incorporating manufacturing Process 2 into our LentiGlobin clinical trials, we believe we can achieve our ultimate goal of increasing hemoglobin production in patients treated with LentiGlobin drug product. In sickle cell disease we have used our early clinical data to identify and implement multiple distinct improvements with the potential to overcome the unique challenges presented by this complex disease. We are hopeful that the tremendous work done by our research and development teams will yield improved outcomes for patients in the clinic in 2017 and beyond, and that the regulatory progress we are making will enable us to bring these treatments to patients as quickly as possible. We anticipate seeing many catalysts across our programs in the next 15 months, including initial clinical data from our Phase 1 clinical study of our bb2121 product candidate in relapsed/refractory multiple myeloma and updates on our Lenti-D program in cerebral adrenoleukodystrophy.”

LentiGlobin Manufacturing Data: A Head-to-Head In Vitro Comparison of Process 1 and Process 2

bluebird bio has recently modified the process by which the patient’s cells are transduced in LentiGlobin clinical studies with the addition of enhancers during the manufacturing process. The goal of manufacturing Process 2 is to increase the percentage of cells successfully transduced, thereby increasing vector copy number (VCN) in the drug product that is given to the patient.

Using retained samples of CD34+ stem cells collected from patients in the HGB-204 (Northstar) and HGB-206 studies, the company was able to demonstrate in a head-to-head in vitrocomparison that manufacturing Process 2 substantially increased the percentage of cells transduced and VCN, as compared to manufacturing Process 1.

This in vitro data from Process 2 showed an average increase of approximately three-fold in vector-positive cells and VCN across all patient samples tested. Process 2 has been successfully scaled up for clinical manufacturing, and all LentiGlobin clinical trials moving forward will use manufacturing Process 2, including the Phase 3 HGB-207 (Northstar-2) trial and the Phase 1 HGB-206 clinical trial.

bluebird bio also highlighted progress it has made in moving from adherent manufacturing of lentiviral vectors to potentially more efficient suspension manufacturing, consistently achieving the targeted potency, purity and VCNs at increased scale.

LentiGlobin in Sickle Cell Disease: Addressing the Challenges and Promise of Gene Therapy

Based on an assessment of patient data presented at ASH 2015 and the underlying biology of SCD, the company believes that the following specific amendments to the protocol of the ongoing HGB-206 clinical trial may lead to improved patient outcomes through:

  • Improving or enhancing stem cell collection by both:
    (i) Suppression of sickle cell bone marrow pathology through required pre-stem cell harvest red blood cell transfusions, and
    (ii) Use of improved cell separation techniques and increase of the required minimum cell dose
  • Increasing percentage of cells transduced and VCN through implementation of manufacturing Process 2 for LentiGlobin drug product
  • Enhancing the engraftment of the LentiGlobin drug product by adjusting the target level of exposure to busulfan for pre-infusion conditioning; and
  • Additional exploratory alternative cell collection approaches through the mobilization and apheresis of patient CD34+ cells using plerixafor

To accommodate these changes to the protocol, the study enrollment has been expanded for a total enrollment of up to 29 patients.

LentiGlobin in Transfusion-Dependent β-thalassemia: Regulatory Progress

bluebird bio is working closely with regulatory agencies in the United States and Europe to bring LentiGlobin to patients with TDT who can benefit, as quickly as possible, and has reached general agreement with the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA), respectively, on the regulatory paths forward. Key elements of the company’s regulatory process include:

  • General agreement with the FDA on pivotal clinical trial designs across patient genotypes and age groups:
    • HGB-207 (Northstar-2) Phase 3 study in 15 adult and adolescent patients with TDT who do not have β00 genotypes, with an additional pediatric cohort of 8 patients for a total enrollment of approximately 23 patients
    • HGB-212 Phase 3 study in 15 adult, adolescent and pediatric patients with TDT who have β00 genotypes to launch in 2017, with a primary endpoint of transfusion reduction
    • Both studies will be conducted using manufacturing Process 2 and are designed to provide the basis for BLA submissions in the United States
  • Confirmation that, as part of the EMA Adaptive Pathways and PRIME programs, application for conditional approval for LentiGlobin in the EU would be based on data from the HGB-204 (Northstar) and HGB-205 studies of LentiGlobin, as well as available data from the HGB-207 (Northstar-2) and HGB-212 studies. (Original Source)

Shares of Bluebird are currently trading at $63.73, down $1.82 or -2.78%. BLUE has a 1-year high of $99.70 and a 1-year low of $35.37. The stock’s 50-day moving average is $61.07 and its 200-day moving average is $49.54.

On the ratings front, BLUE has been the subject of a number of recent research reports. In a report issued on September 29, Maxim analyst Jason McCarthy reiterated a Buy rating on BLUE, with a price target of $100, which implies an upside of 53% from current levels. Separately, on the same day, Jefferies’ Gena Wang reiterated a Buy rating on the stock and has a price target of $80.

According to, which ranks over 7,500 financial analysts and bloggers to gauge the performance of their past recommendations, Jason McCarthy and Gena Wang have a total average return of -4.3% and -15.3% respectively. McCarthy has a success rate of 37.5% and is ranked #3849 out of 4182 analysts, while Wang has a success rate of 40% and is ranked #4022.

The street is mostly Bullish on BLUE stock. Out of 9 analysts who cover the stock, 8 suggest a Buy rating and one recommends to Hold the stock. The 12-month average price target assigned to the stock is $103.50, which implies an upside of 58% from current levels.

bluebird bio, Inc. is a clinical-stage biotechnology company. The company develops next generation products based on the transformative potential of gene therapy to treat patients with severe genetic and orphan diseases. It has two clinical-stage programs in development for childhood cerebral adrenoleukodystrophy and beta-thalassemia/sickle cell disease and a preclinical oncology program in the chimeric antigen receptor T cells field.