6 December 2018 - - US-based gene therapy specialist bluebird bio, Inc. (NASDAQ: BLUE) and US-based biopharmaceutical company Celgene Corp. (NASDAQ: CELG) announced initial data from the ongoing Phase 1 clinical study of bb21217 (CRB-402), an investigational next-generation anti-BCMA CAR T cell therapy being studied in patients with relapsed/refractory multiple myeloma, the companies said.

The data were presented by Nina Shah, M.D., University of California, San Francisco, as an oral presentation at the 60th annual meeting of the American Society of Hematology.

bb21217 is an investigational anti-BCMA CAR T cell therapy that uses the bb2121 chimeric antigen receptor molecule with a manufacturing process designed to improve CAR T cell functional persistence.

It has exhibited improved functional persistence and increased anti-tumor activity in preclinical animal studies.

bb21217 is being evaluated in the ongoing dose escalation part of the Phase 1 CRB-402 study in adults with relapsed/refractory multiple myeloma who have received at least three prior treatments, including a proteasome inhibitor and immunomodulatory agent (or are double refractory).

Patients included in these preliminary Phase 1 results had a median age of 63 years (min; max: 44 69 years).

They had received a median of seven prior lines of therapy (min; max: 4 17 lines) and 83 % of patients received a prior autologous stem cell transplant. Fifty-eight % of patients had high-risk cytogenetics.

All treated patients received a dose of 150 x 106 CAR+ T cells. The median follow-up after bb21217 infusion was 26 weeks (min; max: 4 51 weeks).

The primary endpoint is safety measured by frequency of adverse events, dose limiting toxicity and changes in laboratory results. Secondary endpoints include disease specific response criteria based on the International Myeloma Working Group Uniform Response Criteria for Multiple Myeloma.

The safety results, reported as of the data extract of October 18, 2018, were manageable and consistent with known toxicities of CAR T therapies.

Eight of the 12 patients (67 %) treated with bb21217 developed cytokine release syndrome ; four Grade 1, three Grade 2, one Grade 3 case and no Grade 4 cases.

Additionally, three of the 12 patients (25 %) experienced neurotoxicity, including one Grade 1, one Grade 2 and one Grade 4 case. All CRS and neurotoxicity events resolved and no deaths occurred on study.

Following the Grade 4 neurotoxicity event, patients were divided into two groups based on tumor burden and dosing continued at 150 x 106 CAR+ T cells for a total of 12 subjects treated at this dose level.

Of the 12 patients who received treatment with bb21217, 83% achieved an objective clinical response by IMWG criteria.

As of the data extract, responses are ongoing in nine of 10 patients, including three with a complete response or stringent complete response, two with a very good partial response and four with a partial response.

Evidence of myeloma in the bone marrow, known as minimal residual disease, was undetectable at a minimum of two time points, by next-generation sequencing at a sensitivity level of 10-5 or better in all responders who had evaluable bone marrow samples with some as early as day 15.

CAR+ T cell expansion was observed during the first 30 days following treatment in all evaluable patients with anti-BCMA CAR+T cells showing sustained persistence in all patients with six or more months of follow-up.

The ongoing Phase 1 CRB-402 study is assessing a higher dose of 300 x106 CAR+ T cells in both high and low tumor burden cohorts.

bb2121 and bb21217 are bluebird bio's lead investigational anti-BCMA CAR T therapies being developed in collaboration with Celgene.

Chimeric antigen receptors are receptor proteins that have been engineered to give T cells the ability to target a specific protein. bb2121 and bb21217 are designed to recognise and kill plasma cells, notably malignant myeloma cells, that express the B cell maturation antigen.

bluebird bio's clinical development programme for bb21217 includes the ongoing Phase 1 CRB-402 two-part (dose escalation and dose expansion), non-randomised, open label study with sites in the United States. For more information visit: clinicaltrials.gov using identifier NCT03274219.

bb21217 is not approved for any indication in any geography.

Celgene is engaged primarily in the discovery, development and commercialisation of innovative therapies for the treatment of cancer and inflammatory diseases through next-generation solutions in protein homeostasis, immuno-oncology, epigenetics, immunology and neuro-inflammation.