Juno Lymphoma Drug Impresses in Early Stage Study, But Fear of Cerebral Edema Looms

-- 80% overall response and 60% complete response

-- No severe cytokine release syndrome to date and 14% rate of severe neurotoxicity

-- Side effect profile plus cell persistence suggest potential for combination therapy

SEATTLE--(BUSINESS WIRE)--Juno Therapeutics, Inc. (NASDAQ:JUNO), a biopharmaceutical company developing innovative cellular immunotherapies for the treatment of cancer, today announced encouraging preliminary clinical data for JCAR017 in patients with relapsed or refractory (r/r) aggressive non-Hodgkin lymphoma (NHL) in a presentation at the 58^th American Society of Hematology (ASH) Annual Meeting. JCAR017 uses a defined CD4:CD8 cell composition and 4-1BB as the costimulatory domain, which differentiates it from other CD19-directed CAR T product candidates in clinical development.

“In particular, the side effect profile and persistence of CAR T cells that we observed, even in patients who relapsed, will allow us to explore higher doses and the possibility for combination therapies to potentially increase durable response rates.”

“Our potential best-in-class CAR T candidate, JCAR017, has demonstrated an impressive early response rate in these sick NHL patients,” said Mark J. Gilbert, M.D., Juno’s Chief Medical Officer. “In particular, the side effect profile and persistence of CAR T cells that we observed, even in patients who relapsed, will allow us to explore higher doses and the possibility for combination therapies to potentially increase durable response rates.”

In the multi-center Phase I trial (ASH Abstract #4192), led by principal investigator Jeremy Abramson, M.D., of Massachusetts General Hospital Cancer Center, patients with r/r diffuse large B cell lymphoma (DLBCL), follicular lymphoma grade 3B or mantle cell lymphoma (MCL) were treated with fludarabine/cyclophosphamide (flu/cy) lymphodepletion and JCAR017.

Key data include:

• In 22 safety-evaluable patients (19 r/r DLBCL, 1 follicular lymphoma grade 3B, and 2 MCL patients) treated at dose level 1, single-dose schedule, no severe cytokine release syndrome (sCRS) was observed. Grade 3-4 neurotoxicity was observed in 3/22 (14%) patients, all of whom received the steroid dexamethasone for neurotoxicity. A single patient received tocilizumab for early onset grade 2 CRS. The most frequently reported treatment-emergent adverse events were neutropenia (100%), decreased appetite (36%) and fatigue (32%).
• In 20 efficacy-evaluable patients with r/r DLBCL (N=19) and follicular lymphoma grade 3B (N=1) treated at dose level 1 (5x10⁷ cells), single-dose schedule, the overall response was 16/20 (80%) and complete response (CR) was 12/20 (60%) patients.
• For DLBCL patients treated more than three months prior to the data cut-off date, 8/19 (42%) patients continue to experience an ongoing response.
• In dose level 2 (1x10⁸ cells), 2/2 (100%) patients evaluable for efficacy have a complete response, and no patients evaluable for safety to date (N=3) have had sCRS or grade 3-4 neurotoxicity.

In addition, multiple patients had persistent cells at relapse, suggesting the potential for combination therapy to improve long-term outcomes. One of these patients subsequently achieved a second complete response after endogenous re-expansion of persistent T cells without second infusion.

The Phase I TRANSCEND trial continues, enrolling more patients at dose levels 1 and 2. Juno intends to initiate a pivotal trial in the U.S. in patients with r/r DLBCL in 2017. JCAR017 is also being studied in a Phase II study in children with r/r acute lymphoblastic leukemia.

ASH Investor and Analyst Event and Webcast

A 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 possibility for combination therapies to potentially increase durable response rates, 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.