Juno Therapeutics Highlights Data and Presentations Supporting Best-in-Class Strategy for JCAR017 at ASH

SEATTLE--(BUSINESS WIRE)-- Juno Therapeutics (NASDAQ: JUNO), a biopharmaceutical company developing innovative cellular immunotherapies for the treatment of cancer, today highlighted presentations and data from the 59th American Society of Hematology (ASH) Annual Meeting and Exposition in Atlanta, Georgia, December 9-12, 2017.

“Juno presented a wide range of data and new insights at ASH, including updated data in the TRANSCEND trial,” said Hans Bishop, Juno’s President and CEO. “Using a defined composition of cells at a precise dose, we have been able to gain critical insights into important potential associations that may contribute to JCAR017’s efficacy and tolerability profile that we believe has the potential to be best in class. We are confident that the investments we’ve made in our defined composition, scientific, and translational capabilities will allow us to better characterize and improve current and future CAR T products and product candidates for patients.”

During ASH, Juno also announced that JCAR017 had received the United States Adopted Name (USAN) lisocabtagene maraleucel (liso-cel).

Updated Data from TRANSCEND Trial of JCAR017

Data from the TRANSCEND study of JCAR017 (liso-cel) in patients with relapsed or refractory (r/r) aggressive B-cell non-Hodgkin lymphoma (NHL) were presented in an oral session by Dr. Jeremy Abramson, M.D. of Massachusetts General Hospital on Monday, December 11. JCAR017 is a defined composition CD19-directed CAR T cell product candidate using a 4-1BB costimulatory domain.

Data were based on a cutoff date of October 9, 2017 and add to those disclosed on November 1, 2017 in Abstract #581. The core group includes patients with Diffuse Large B-Cell Lymphoma (DLBCL; NOS and transformed from follicular lymphoma) who are ECOG Performance Status 0-1. The full analysis group represents all r/r patients in the DLBCL cohort, which includes patients with poor performance status (ECOG Performance Status 2) or with niche subtypes of aggressive NHL.

Enrollment of the pivotal cohort is ongoing with the core group at dose level 2, one of multiple previously evaluated doses.

Key results:

• In the core group at dose level 2 (DL2=100 million cells), the data showed a 3 month overall response rate (ORR) of 74% (14/19) and a 3 month complete response (CR) rate of 68% (13/19). Of patients that have reached 6 months of follow-up, 50% (7/14) were in CR. Across doses, 80% (16/20) of patients in core group with CR at 3 months stayed in CR at 6 months, and 92% (11/12) of patients in response at 6 months remained in response as of the data cutoff date.
• In the core group, 1% (1/67) experienced severe cytokine release syndrome and 15% (10/67) experienced severe neurotoxicity. 58% (39/67) had no CRS or NT of any grade.
• In the full group, 1% (1/91) experienced severe CRS and 12% (11/91) experienced severe NT. 60% (55/91) had no CRS or NT of any grade.
• The most common treatment-emergent adverse events (TEAEs) other than CRS and NT that occurred at ≥25% in the full group included neutropenia (49%), anemia (38%), fatigue (37%), thrombocytopenia (29%), nausea (27%), and diarrhea (25%). The most common TEAEs were similar between core and full groups.

Juno believes JCAR017’s safety profile could enable outpatient administration. A biologics license application filing is expected to be completed in the second half of 2018, with approval as early as the end of 2018.

Oral Presentations on JCAR017 Translational Insights

Two additional oral presentations reported new clinical correlates, and safety and efficacy insights associated with JCAR017.

On Saturday, December 9, Tanya Siddiqui, M.D., of City of Hope National Medical Center, presented exploratory analyses from Abstract #193 suggesting that patient factors independent of JCAR017 may impact safety and efficacy for DLBCL patients. These factors included:

• Baseline patient characteristics, including high tumor burden and markers of inflammation, were associated with high CAR T cell expansion and increased rates of CRS and NT.
• Data showed an approximately 8-fold increased risk for CRS and NT in patients with high baseline tumor burden.
• Baseline markers of inflammation were associated with more durable responses; with respect to tumor burden the association was less pronounced.

On the same day, Howard Stern, M.D., Ph.D., of Juno presented data from ASH Abstract #194, examining JCAR017 infiltration into tumor tissue and exploring potential mechanisms of resistance and relapse. Findings included:

• JCAR017 cells infiltrated tumors, and more infiltration trended with better response. At disease progression, tumors tended to express CD19 and lack CAR T cells.
• In patients whose disease progressed, no single resistance pathway appeared to be upregulated in the tumor at the time of progression, but well-known pathways such as PD-L1 and IDO were upregulated in different patients, suggesting that combinations with other immunotherapies may be beneficial.

Potential for Outpatient Administration of JCAR017

On Saturday, December 9, David Maloney, M.D., Ph.D. of Fred Hutchinson Cancer Research Center presented Poster #1552, highlighting preliminary data on the potential for outpatient administration of JCAR017 in patients with r/r DLBCL. The safety profile of JCAR017, including low rates of all grade and severe CRS and NT, supports evaluation of outpatient administration.

8 patients had received JCAR017 as an outpatient at multiple trial sites and were evaluable with 28 or more days post-infusion. Compared to inpatient administration, outpatient administration showed an approximate 40% reduction in hospital days. 88% (7/8) of patients remained outpatient for at least 3 days post CAR T administration.

The goal of JCAR017 outpatient administration is to increase access and reduce hospitalization days without impacting safety. Juno anticipates generating additional data to evaluate this potential both as part of the TRANSCEND trial and in additional studies.

Pharmacodynamics of JCAR017

In a presentation on Sunday, December 10, Mark Heipel presented Poster #2835, highlighting pharmacodynamics and blood analytes with clinical response to JACR017 in patients with r/r DLBCL. The presentation showed that JCAR017 CAR T cells expanded in the blood and bone marrow of all patients, but at different rates between patients and different NHL histologies.

Furthermore, an increase in CD8⁺ cell expansion was observed at dose level two compared to dose level one. Preliminary modeling suggests a potential therapeutic window for CAR T expansion may exist that limits toxicity and optimizes for durable response. Findings suggested that patient factors and tumor characteristics, apart from JCAR017 itself, are important to expansion and thus potentially response.

Manufacturing of JCAR017

In a poster presentation on Monday, December 11, Christopher G. Ramsborg, Ph.D., highlighted the product and process controls in manufacturing that enable the defined composition of JCAR017, including the delivery of precise doses of CD4⁺ and CD8⁺ CAR T cells. Three aspects of JCAR017 manufacturing and process control strategy contribute to low between-drug product lot variability:

• A precise, consistent flat dose of administered CD4⁺ and CD8⁺ CAR T cells within +/- 8% of target cell count.
• Control and optimization of CD4⁺ and CD8⁺ T cell culture conditions that result in low between-drug product lot variability of phenotypes (e.g., CCR7) and in vitro function (e.g., IL-2, TNF-α and IFN-γ production after antigen stimulation).
• Constant formulation and volume of drug product that contributes to consistent cell health.

Controls result in a commercial manufacturing process expected to be successful >95% with a consistent turnaround time <21 days.

Multiple Myeloma Presentations

Poster presentations showing preclinical data highlighted early, encouraging insights into the design of BCMA-directed CAR T cells. Juno plans to present additional data on its BCMA program and strategy next year. The presentations at ASH highlighted Juno’s fully human binder, and showed that the inhibition of TGFβ signaling and combination strategies with Lenalidomide may contribute to a potential best-in-class product for multiple myeloma.

About Juno

Juno Therapeutics is building a fully integrated biopharmaceutical company focused on developing innovative cellular immunotherapies for 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 multiple solid tumors and multiple myeloma. 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 (SCRI), 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. Juno’s product candidate JCAR017 (lisocabtagene maraleucel; liso-cel) was developed in collaboration with SCRI and others. JCAR017 is an investigational CART T therapy and is not approved for use in any country.

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 or translational data and the implications thereof; the timing of regulatory submissions or approvals; clinical trial plans; the potential best-in-class profile for JCAR017 (liso-cel); the potential for outpatient administration of JCAR017; Juno’s ability to harness its investments to better characterize and improve current and future CAR T products and product candidates for patients; the importance of controlling product composition; expected success rates and turnaround time for manufacturing; the potential of JCARH125 to be a best-in-class product; and the potential of the Celgene collaboration. 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; with respect to the timing of JCAR017 approval, the time it takes to complete enrollment of the pivotal cohort, the timing of Juno’s FDA submission, and the duration of FDA review; 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 ability to attract and retain key scientific, quality control/assurance, manufacturing or management personnel; 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 and its affiliates 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 1, 2017 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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