Juno Therapeutics, Inc. (NASDAQ: JUNO), a biopharmaceutical company developing innovative cellular immunotherapies for the treatment of cancer, today announced in a presentation at the 58 th American Society of Hematology (ASH) Annual Meeting encouraging early data for JCAR014 in patients with chronic lymphocytic leukemia (CLL) who failed treatment with ibrutinib. Insights from studies of the translational product, JCAR014, are being applied to the development of JCAR017 for the treatment of B-cell malignancies. Both JCAR014 and JCAR017 use a 4-1BB co-stimulatory domain and defined 1:1 cell ratio of CD4:CD8 T cells.

"The responses and durability we've seen in this study are notable and demonstrate the potential for further investigation of JCAR017 for patients with relapsed/refractory high-risk CLL," said Mark J. Gilbert, M.D., Juno's Chief Medical Officer. "This is especially important, given recent data that show these patients, who progress early on ibrutinib, have poor clinical outcomes with a median survival of approximately three months. In addition, emerging response criteria, such as undetectable disease in the bone marrow at the molecular level by deep sequencing, appear to correlate with long-term response duration."

The Phase I study (ASH Abstract #56), conducted by Cameron Turtle, MBBS, Ph.D., of the Fred Hutchinson Cancer Research Center, evaluated 24 heavily pre-treated patients, all of whom had failed ibrutinib, the standard-of-care treatment for CLL. Patients had received a median of five previous therapies, including three who failed prior allogeneic stem cell transplants. Patients received lymphodepletion with either fludarabine/cyclophosphamide (flu/cy) (N=21) or non-flu/cy (N=3) prior to infusion of JCAR014.

Key data for the flu/cy cohort include:
  • Two of 24 (8%) patients developed grade 3-5 severe cytokine release syndrome (sCRS) and 6/24 (25%) patients developed grade 3-5 severe neurotoxicity. The most frequent severe Treatment Emergent Adverse Events were febrile neutropenia (75%), CRS (29%), fever (17%), lung infection (13%), encephalopathy (13%), and hypotension (13%). There was one treatment-related mortality (4%) in the trial in a patient who received flu/cy lymphodepletion, with both grade 5 CRS and cerebral edema.
  • Of 17 efficacy-evaluable patients with bone marrow disease at the start of the trial and treated with flu/cy and the two lowest doses of JCAR014, 15/17 (88%) had a complete marrow response by flow cytometry. Fourteen of the complete bone marrow response patients had a response assessment by the more sensitive method of IgH deep sequencing, with 7/14 (50%) having no detectable disease. All seven of these patients are alive and progression free with follow-up ranging from 3 to 26 months. The complete marrow response by flow cytometry was similar in patients documented to be ibrutinib-refractory at 86% (12/14).
  • In patients with PET-avid disease at baseline and treated with flu/cy and the two lowest doses of JCAR014, 8/11 (73%) had a partial response (PR) or complete response (CR) at four weeks, with 7/11 (64%) having a CR.
  • In patients evaluated for efficacy at four weeks using IWCLL criteria and treated with flu/cy and the two lowest doses of JCAR014, 14/19 (74%) had a PR or CR, with 4/19 (21%) being a CR. All patients with either a CR or PR remain alive, with follow-up ranging from 3 to 26 months. There is no obvious early difference in time to progression between a CR and PR by IWCLL criteria. The response data were similar in patients documented to be ibrutinib-refractory, with overall response rate of 69% (11/16) and a CR rate of 25% (4/16).

Plans to study JCAR014 in combination with ibrutinib in CLL are underway, with a cohort expected to begin enrollment in early 2017. Juno is evaluating the use of this data with JCAR014 as a monotherapy and in combination with ibrutinib in support of a potential Juno-sponsored trial with JCAR017 in CLL.

ASH Investor and Analyst Event and Webcast

The Juno ASH Investor and Analyst Event and webcast will be held Monday, December 5, 2016 at 8:30 p.m. Pacific Time. The webcast can be accessed live on the Investor Relations page of Juno's website, www.JunoTherapeutics.com, and will be available for replay for 30 days following the event.

ABOUT JUNO

Juno Therapeutics is building a fully integrated biopharmaceutical company focused on re-engaging the body's immune system to revolutionize the treatment of 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 clinical responses in clinical trials in refractory leukemia and lymphoma conducted to date. Juno's long-term aim is to 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, the University of California, San Francisco, and The National Cancer Institute. Juno Therapeutics has an exclusive license to the St. Jude Children's Research Hospital patented technology for CD19-directed product candidates that use 4-1BB, which was developed by Dario Campana, Chihaya Imai, and St. Jude Children's Research Hospital.

ABOUT THE JUNO-CELGENE COLLABORATION

Celgene Corporation and Juno Therapeutics formed a collaboration in June 2015 under which the two companies will leverage T cell therapeutic strategies to develop treatments for patients with cancer and autoimmune diseases with an initial focus on chimeric antigen receptor (CAR) and T cell receptor (TCR) technologies. In April 2016, Celgene exercised its option to develop and commercialize the Juno CD19 program outside North America and China.

FORWARD-LOOKING STATEMENTS

This press release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995, Section 27A of the Securities Act of 1933, and Section 21E of the Securities Exchange Act of 1934, including statements regarding Juno's mission, progress, and business plans, clinical trial results and the implications thereof, the potential of JCAR017 to treat patients with CLL, clinical trial plans and timing, and the potential of the collaboration between Juno and Celgene. Forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially from such forward-looking statements, 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 Juno's product development activities and clinical trials; Juno's ability to obtain regulatory approval for and to commercialize its product candidates; Juno's ability to establish a commercially-viable manufacturing process and manufacturing infrastructure; regulatory requirements and regulatory developments; success of Juno's competitors with respect to competing treatments and technologies; Juno's dependence on third-party collaborators and other contractors in Juno's research and development activities, including for the conduct of clinical trials and the manufacture of Juno's product candidates; Juno's dependence on Celgene for the development and commercialization outside of North America and China of Juno's CD19 product candidates and any other product candidates for which Celgene exercises an option; Juno's dependence on JW Therapeutics (Shanghai) Co., Ltd, over which Juno does not exercise complete control, for the development and commercialization of product candidates in China; Juno's ability to obtain, maintain, or protect intellectual property rights related to its product candidates; amongst others. For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to Juno's business in general, see Juno's Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission on November 9, 2016 and Juno's other periodic reports filed with the Securities and Exchange Commission. These forward-looking statements speak only as of the date hereof. Juno disclaims any obligation to update these forward-looking statements.

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