Juno's Investigational CAR T Cell Product Candidate JCAR014 Demonstrates Encouraging Clinical Responses and Translational Insights in Patients With B-Cell Cancers

SEATTLE, June 1, 2015 (GLOBE NEWSWIRE) -- Juno Therapeutics, Inc. announced today that clinical data from a chimeric antigen receptor (CAR) T cell product candidate, JCAR014, demonstrated encouraging clinical responses in patients with B-cell cancers. Clinical results will be presented in an oral presentation today at the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago.

"We are gaining important translational insights from the JCAR014 trial, and these data highlight the potential to meaningfully improve cell expansion and cell persistence in non-Hodgkin lymphoma (NHL) patients, as well as more broadly in patients with different cancers across our portfolio of cellular immunotherapies," said Mark Frohlich, M.D., Juno EVP of development and portfolio strategy. "We are encouraged by the early evidence that these improved in vivo properties are translating into improved efficacy for patients, and we will apply these and other learnings to our multi-center trial for JCAR017 in NHL that we intend to begin in the second half of 2015."

In an oral presentation on Monday, June 1, 2015 by Cameron J. Turtle, MBBS, Ph.D. of the Fred Hutchinson Cancer Research Center entitled, "Immunotherapy with CD19-specific chimeric antigen receptor (CAR)-modified T cells of defined subset composition" updated Phase I results in a total of 52 patients treated with JCAR014 against B-cell malignancies will be reported from this ongoing trial:

  • Twenty-four patients with acute lymphoblastic leukemia (ALL), 23 patients with non-Hodgkin lymphoma (NHL), and 5 patients with chronic lymphocytic leukemia (CLL) were treated with JCAR014.
  • CD19 CAR T cells of defined subset composition demonstrated potent anti-tumor activity: CR as documented by flow cytometry was observed in 21/23 (91%) of evaluable patients with relapsed or refractory (r/r) B-cell ALL; complete or partial responses were observed in 12/19 (63%) of patients with r/r NHL; and complete responses were obtained in 2/5 patients with r/r chronic lymphocytic leukemia.
  • Translational insights included:
    • Dramatically improved CAR T cell peak and persistence following optimization of the lymphodepletion conditioning regimen.
    • Early indications that these improved kinetic properties are translating to improved clinical activity with complete or partial responses in 6/7 (86%) of evaluable NHL patients.
    • The CAR T in vivo expansion in NHL with this optimization of the lymphodepletion regimen is similar to what was previously observed in the ALL portion of this trial. Correspondingly, and similar to previously reported ALL data, the highest dose of 2X107 cells/kg exceeds the maximally tolerated dose, as two treatment-related deaths were observed in NHL with this cell dose. There have been no treatment-related deaths to date at 2x106 cells/kg or lower, and the side effect profile has been consistent with what has been previously reported.
    • CAR T cell persistence may be limited by transgene immunogenicity directed against the murine scFv in a subset of patients.
    • Increased CAR T cell expansion and persistence in ALL patients with higher bone marrow disease burden.
  • Severe CRS was reported in 7/24 (29%) of ALL patients and 4/28 (14%) of CLL/NHL patients.

JCAR014 is in an ongoing Phase I/II trial in patients with r/r B cell malignancies, including ALL, NHL and CLL. Juno intends to continue enrolling patients in this trial through 2015 in order to gain insights into various factors that may improve the expansion and persistence of these CAR T cells in the body. These findings may be applicable across the company's portfolio of product candidates and help advance the development of next-generation therapies for patients with hematologic and solid organ cancers. Juno currently does not plan to advance JCAR014 into registration trials.

About Juno's Chimeric Antigen Receptor (CAR) and T Cell Receptor (TCR) Technologies

Juno's chimeric antigen receptor (CAR) and T cell receptor technologies (TCR) genetically engineer T cells to recognize and kill cancer cells. Juno's CAR T cell technology inserts a gene for a particular CAR into the T cell, enabling it to recognize cancer cells based on the expression of a specific protein located on the cell surface. Juno's TCR technology provides the T cells with a specific T cell receptor to recognize protein fragments derived from either the surface or inside the cell. When either type of engineered T cell engages the target protein on the cancer cell, it initiates a cell-killing response against the cancer cell.

About Juno Therapeutics, Inc.

Juno Therapeutics is building a fully integrated biopharmaceutical company focused on revolutionizing medicine by re-engaging the body's immune system to treat cancer. Founded on the vision that the use of human cells as therapeutic entities will drive one of the next important phases in medicine, Juno is developing cell-based cancer immunotherapies based on chimeric antigen receptor and high-affinity T cell receptor technologies to genetically engineer T cells to recognize and kill cancer. Juno is developing multiple cell-based product candidates to treat a variety of B-cell malignancies as well as solid tumors. Several product candidates have shown compelling evidence of tumor shrinkage in the clinical trials in refractory leukemia and lymphoma conducted to date. Juno's long-term aim is to improve and leverage its cell-based platform to develop new product candidates that address a broader range of cancers and human diseases. Juno brings together innovative technologies from some of the world's leading research institutions, including the Fred Hutchinson Cancer Research Center, Memorial Sloan Kettering Cancer Center, Seattle Children's Research Institute, and The National Cancer Institute.

Juno Forward Looking Statements

This press release contains forward-looking statements, including statements regarding the clinical development of our product candidates, the safety and efficacy of our product candidates as well as their potential, the encouraging nature of clinical data observed to date, insights and potential improvements in addressing multiple indications, and the application of learnings in other trials, if at all. Forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially and reported results should not be considered as an indication of future performance. These risks and uncertainties include, but are not limited to: risks associated with the success, cost and timing of our product development activities and clinical trials; the approval and commercialization of our product candidates; and risks of increased regulatory requirements, amongst others. These forward-looking statements speak only as of the date hereof. Juno Therapeutics disclaims any obligation to update these forward-looking statements.

CONTACT: Investor Relations: David Walsey, W2O Group 858-617-0772 dwalsey@w2ogroup.com Media: Julie Normart, W2O Group 415-946-1087 jnormart@w2ogroup.com

Source:Juno Therapeutics