On June 2, 2015 Weill Cornell Medical College and Cellectis reported they have entered into a strategic translational research alliance to accelerate the development of a targeted immunotherapy for patients with acute myelogenous leukemia (AML), a deadly blood cancer (Filing, 6-K, Cellectis, JUN 2, 2015, View Source [SID:1234505216]). The alliance will foster the development of Cellectis’ lead product candidate in AML, called UCART123.

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The collaboration combines Weill Cornell’s broad expertise and resources in translational stem cell science and developmental therapeutics with Cellectis’ work in development and manufacturing of gene edited CAR-T cell product candidates, a special kind of immune cell that includes an antibody-derived receptor.

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The research will be led by co-principal investigators Dr. Gail J. Roboz, director of the leukemia program and an associate professor of medicine at Weill Cornell, and Dr. Monica Guzman, an assistant professor of pharmacology in medicine at Weill Cornell. Dr. Roboz is an internationally recognized leader in the field of acute leukemia and will design and implement clinical testing of UCART123 in patients with AML. Dr. Guzman is a renowned leukemia stem cell biologist who specializes in preclinical and early-stage testing to optimize the development of stem cell-targeted cancer drugs.

The alliance will seek to accelerate the development of Cellectis’ UCART123 in AML. Cellectis’ proprietary allogeneic CAR T-cell platform utilizes T-cells (immune cells) from healthy donors. The T-cells are engineered with a Chimeric Antigen Receptor (CAR), which enables them to detect specific proteins (antigens) expressed on malignant tumors. Large numbers of allogeneic CAR-modified T-cells are grown in the laboratory and then infused into a patient. The enhanced cells are designed to recognize and attack stem cells harboring the CD123 antigen, which is present on AML blast and stem cells. To enhance safety and minimize toxicity for patients, the company’s gene-editing process features customized control properties that seek to prevent the T cells from inappropriately attacking healthy tissues. Cellectis hopes to develop a cost-effective, "off-the-shelf" allogeneic CAR T-cell product, designed for efficient storage and distribution to patients around the globe.

Cellectis in April opened a new research and development facility in New York City, located in close proximity to the Weill Cornell campus.

"We are pleased to collaborate with Cellectis to develop and advance next-generation treatments for patients with this devastating form of leukemia," said Dr. Laurie H. Glimcher, the Stephen and Suzanne Weiss Dean of Weill Cornell Medical College. "Cellectis’ proficiency in genome engineering and our complementary expertise in translational research will help us realize our common goal of improving human health in New York and around the globe."

"CAR-T cells have shown remarkable promise in the treatment of acute lymphoblastic leukemia," Dr. Roboz said. "Cellectis has interesting preclinical data on UCART123 and our alliance will seek to build on these findings to better understand the clinical potential of this therapy. Our patients are anxiously awaiting the start of clinical trials."

"Weill Cornell offers unsurpassed expertise in translational research, with a wealth of leading-edge technologies and resources to help advance our pipeline of unique CAR-T product candidates," said Dr. Mathieu Simon, executive vice president and chief operating officer at Cellectis. "We are excited by the prospect of working with Dr. Roboz, Dr. Guzman and other premier investigators in leukemia stem cell research."

Weill Cornell’s Office of BioPharma Alliances and Research Collaborations negotiated the three-year alliance. In the program’s pre-clinical phase, Weill Cornell researchers will perform multiple analyses, including data mining of primary AML samples, immune profiling of AML patients and in vitro evaluation of allogeneically derived anti-CD123 CAR-T cells. In the alliance’s second phase, Weill Cornell and Cellectis will jointly develop protocols to facilitate early-phase testing, including phase 1 clinical trials.

"Cellectis believes the CAR-T platform has the potential to transform the way cancer patients are treated. We are confident that our broad, cross-discipline collaboration with Weill Cornell will foster creativity and speed in drug development for the benefit of clinicians and patients living with AML," said Dr. André Choulika, chief executive officer of Cellectis.

On June 2, 2015 Kite Pharma reported clinical biomarker data from patients with relapsed/refractory B cell malignancies treated with anti-CD19 chimeric antigen receptor (CAR) T-cell therapy in a poster presentation during the 51st Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper), which is taking place in Chicago (Press release, Kite Pharma, JUN 2, 2015, View Source [SID:1234505213]).

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In an ongoing Phase 1 clinical trial at the National Cancer Institute (NCI), being conducted under a Cooperative Research and Development Agreement (CRADA) between Kite Pharma and the NCI, patients with diverse B cell tumors are conditioned with cyclophosphamide and fludarabine, then dosed with their own T cells genetically modified to express a CAR designed to target the antigen CD19, a protein expressed on the cell surface of B-cell lymphomas and leukemias. As reported at last year’s ASCO (Free ASCO Whitepaper) meeting, 76% of evaluable patients (N=29) achieved an overall response rate in this study. In this updated biomarker analysis, conditioning chemotherapy was associated with a significant rise in homeostatic cytokines and chemokines, which could favor expansion, activation, and trafficking of CAR T cells. In addition, the recovery of B cells was seen in 7 of 12 patients with ongoing response duration greater than 12 months.

David Chang, M.D., Ph.D., Kite Pharma’s Executive Vice President, Research and Development, and Chief Medical Officer, and an author on the poster, commented, "The results being reported at ASCO (Free ASCO Whitepaper) provide additional key insights and further deepen our understanding of CAR T-cell therapy. We will continue to investigate biomarkers that may predict the clinical outcome in our ongoing KTE-C19 (anti-CD19 CAR T) clinical program which initiated patient dosing last month."

The ASCO (Free ASCO Whitepaper) meeting poster, titled "Biomarker Analysis of Patients Treated with Anti-CD19 Chimeric Antigen Receptor (CAR) T Cells" (Abstract # 3028), is available on the Kite Pharma website at View Source Further information on the NCI clinical trial protocols can be found at ClinicalTrials.gov, using Identifier NCT: 00924326.

On June 2, 2015 Nektar Therapeutics and The University of Texas MD Anderson Cancer Center reported a research collaboration that includes a Phase 1/2 clinical study to evaluate NKTR-214, a CD122-biased cytokine designed to preferentially stimulate production of CD8-positive T cells, which are tumor killing cells found naturally in the body (Press release, Nektar Therapeutics, JUN 2, 2015, View Source [SID:1234505210]). CD122, which is also known as the Interleukin-2 receptor beta sub-unit, is a key signaling receptor that is known to increase proliferation of these effector T cells.1

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"We are certain that cytokines are an essential pillar of immunotherapy, along with checkpoint inhibitors, adoptive T cell therapy and cancer vaccines," said Patrick Hwu, M.D., Division Head of Cancer Medicine at MD Anderson. "Through clinical studies, we will explore this new cytokine’s potential to preferentially activate an established target, the IL-2 receptor beta or CD122, in order to stimulate tumor cell killing within the tumor microenvironment. Collaborations with industry allow MD Anderson to pursue new treatment regimens that could dramatically improve patient treatment in the future."

The agreement covers a Phase 1/2 study to evaluate NKTR-214 in a variety of tumor types as a monotherapy and in combination with other therapies, including PD-1 pathway inhibitors. Nektar and MD Anderson expect to initiate the first dose-escalation clinical study later this year. The two organizations will also conduct translational research to identify predictive biomarkers that can be used in the future development of NKTR-214.

"Nektar is pleased to collaborate with MD Anderson, a recognized leader in immuno-oncology, for clinical development of our lead immunotherapy candidate, NKTR-214," said Ivan Gergel, M.D., Senior Vice President and Chief Medical Officer of Nektar. "We believe NKTR-214 has great potential in different tumor types, both as a single agent and in combination with checkpoint inhibitors and other inhibiting agents. This new alliance with MD Anderson will significantly advance the development of NKTR-214 and help us to potentially offer a new and important therapeutic option for cancer patients."

In preclinical studies, NKTR-214 demonstrated a mean ratio of 450:1 within the tumor micro-environment of CD8-positive effector T-cells, which promote tumor killing, compared with CD4-positive regulatory T-cells, which are a type of cell that can suppress tumor killing.2 Furthermore, although NKTR-214 is a cytokine, it is designed to be dosed on an antibody-like schedule similar to the dosing schedules for PD-1 and CTLA-4 agents.

About NKTR-214
NKTR-214 is a CD122-biased immune-stimulatory cytokine, which is designed to stimulate the patient’s own immune system to kill tumor cells. By biasing activation to the CD122 receptor, NKTR-214 enhances CD8+ memory effector T cells (tumor-killing cells) in the tumor. In preclinical studies, a single dose of NKTR-214 resulted in a 400-fold AUC exposure within the tumor compared with an equivalent dose of the existing IL-2 therapy, enabling, for the first time, an antibody-like dosing regimen for a cytokine.3 In dosing studies in non-human primates, there was no evidence of low blood pressure or vascular leak syndrome with NKTR-214 at predicted clinical therapeutic doses.4 NKTR-214 is currently completing final IND-enabling studies and is expected to begin clinical testing in the second half of 2015.

On June 2, 2015 Genmab reported it has entered into an agreement for an exclusive license from Bristol-Myers Squibb to a panel of human antibodies targeting CD19 together with associated intellectual property (Press release, Genmab, JUN 2, 2015, View Source [SID:1234505192]).

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The CD19 protein expressed on certain hematologic cancer cells is seen as a promising target for the treatment of these cancers. Genmab will make a one-time USD 4 million licensing payment to Bristol-Myers Squibb upon execution of the license. Other financial terms of the agreement were not disclosed. The deal is part of Genmab’s strategy to create a broad pipeline of innovative therapeutic products, using the company’s in house know-how and antibody expertise to create truly differentiated cancer therapeutics.

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"CD19 is a clinically-validated target for therapy of certain blood cancers and this exclusive license allows us to create truly differentiated next-generation antibody drugs using our deep understanding of antibody biology, which could lead to new ways of treating cancer. Genmab’s strength lies in our world-class antibody capabilities and our ability to turn science into medicine, which allows us to help patients whilst building a sustainably profitable business," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.

On June 2, 2015 Amgen reported a collaboration with Roche on a Phase 1b study to evaluate the safety and efficacy of talimogene laherparepvec, Amgen’s investigational oncolytic immunotherapy, in combination with Roche’s investigational anti-PDL1 therapy, atezolizumab (also known as MPDL3280A), in patients with triple-negative breast cancer and colorectal cancer with liver metastases (Press release, Amgen, JUN 2, 2015, View Source [SID:1234505188]).

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Talimogene laherparepvec is an investigational oncolytic immunotherapy designed to selectively replicate in tumors (but not normal tissue) and to initiate an immune response to target cancer cells. Atezolizumab is an investigational monoclonal antibody designed to interfere with the PD-L1 protein.

The rationale for combining these two investigational agents is to activate an anti-tumor immune response with talimogene laherparepvec and to block inhibitory T cell checkpoints with atezolizumab, to potentially increase the anti-tumor activity relative to each agent alone.

"We believe that talimogene laherparepvec has potential to help patients in several cancer types based on its mechanism of action to promote tumor antigen release and presentation, important steps in activating a systemic immune response," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "This further builds our alliance network in oncology and we look forward to collaborating with Roche on this study as part of our increasing efforts in immuno-oncology."

"Atezolizumab is our most advanced cancer immunotherapy with 10 ongoing Phase 3 pivotal trials across lung, bladder, breast and kidney cancers," said Sandra Horning, M.D., chief medical officer and head of Global Product Development at Roche. "We are looking forward to working with Amgen on this trial, which can inform potential future treatment options for patients affected by very difficult-to-treat tumor types."

About Talimogene Laherparepvec
Talimogene laherparepvec is an investigational oncolytic immunotherapy designed to selectively replicate in tumors (but not normal tissue) and to initiate an immune response to target cancer cells that have metastasized. Talimogene laherparepvec was designed to work in two important and complementary ways. First, it is injected directly into tumors where it replicates inside the tumor’s cells causing the cell to rupture and die in a process called lysis. Then, the rupture of the cancer cells can release tumor-derived antigens, along with GM-CSF, that can stimulate a system-wide immune response where white blood cells are able to seek out and target cancer that has spread throughout the body.

Amgen has initiated a comprehensive clinical development program for talimogene laherparepvec in metastatic melanoma, which includes combination studies with checkpoint inhibitors in patients with late-stage disease and monotherapy prior to surgery (neoadjuvant) in patients with resectable disease. Additionally, based on its clinical profile, talimogene laherparepvec has the potential to be studied in a variety of solid tumor types.

About Atezolizumab (also known as MPDL3280A)
Atezolizumab is an investigational monoclonal antibody designed to interfere with a protein called PD-L1. Atezolizumab is designed to target PD-L1 expressed on tumor cells and tumor-infiltrating immune cells, preventing it from binding to PD-1 and B7.1 on the surface of T cells. By inhibiting PD-L1, atezolizumab may enable the activation of T cells, restoring their ability to effectively detect and attack tumor cells.