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Kite Pharma Presents Clinical Biomarker Results in Patients Treated With Anti-CD19 Chimeric Antigen Receptor T-Cell Therapy at the 2015 ASCO Annual Meeting

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.

Nektar and MD Anderson Cancer Center Announce Phase 1/2 Clinical Research Collaboration for NKTR-214, a CD122-Biased Immuno-Stimulatory Cytokine

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

"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.

Genmab Gains License to Antibody Panel Targeting CD19

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]).

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.

Amgen Announces Collaboration With Roche On Cancer Immunotherapy Study With Investigational Medicines Talimogene Laherparepvec And Atezolizumab

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]).

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.

Amphivena Therapeutics Presents Positive Data on Novel Acute Myeloid Leukemia (AML) Immunotherapy at 2015 ASCO Annual Meeting

On Jun 1, 2015 Amphivena Therapeutics, Inc., a developer of cancer immunotherapies, reported positive data from several preclinical studies characterizing the company’s proprietary T-cell redirecting bispecific CD33/CD3-targeting antibodies as potential immunotherapeutics for the treatment of acute myeloid leukemia (AML) (Press release, Amphivena Therapeutics, JUN 1/, 2015, View Source [SID:SID1234515580]). Study findings, which demonstrated potent and specific anti-AML activity for the novel antibodies, were presented at the 2015 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. Amphivena also announced selection of a development candidate, AMV-564, based on these compelling preclinical data.

A diverse collection of Amphivena’s novel T-cell redirecting, tetravalent, bispecific CD33/CD3-targeting antibodies were evaluated across a rigorous panel of in vitro and in vivo systems in order to identify an optimal candidate for clinical development. The studies, conducted in collaboration with leading researchers at the Fred Hutchinson Cancer Research Center and the Washington University School of Medicine, were designed to examine the antibodies’ stability properties, affinity for CD33 and CD3, and impact on T-cell activation and cytotoxicity against CD33+ AML cells. The ASCO (Free ASCO Whitepaper) poster presentations (abstracts: 3057, 7067 and 7071) can be found on Amphivena’s website at www.amphivena.com.

Key study findings for Amphivena’s CD33/CD3-targeting antibodies included:

Mechanism-based, T-cell activation and proliferation was induced by the tetravalent, bispecific CD33/CD3-targeting antibodies. Importantly, the presence of CD33+ target cells was required for the T-cell activities, demonstrating the potential for minimal off-target safety issues for this antibody platform.

Potent and selective cytotoxic activity against CD33+ AML cell lines and 27 primary CD33+ AML specimens was observed at pM antibody concentrations. This activity was observed in newly diagnosed and relapsed or refractory AML samples, and was independent of disease stage. For the most potent CD33/CD3 antibodies, activity was independent of the level of CD33 expression.

Robust tumor growth inhibition and delay in prophylactic and established AML xenograft models using human cancer cell lines and donor T-cells.

Impressive activity in an AML patient-derived xenograft model with nearly complete elimination of leukemic blasts from all compartments, including bone marrow and spleen, despite the very low number of T-cells present in the patient sample.

"These preclinical studies identified T-cell redirecting bispecific CD33/CD3-targeting antibodies that meet our initial, pre-specified activity and safety profile for an immunotherapeutic clinical candidate for treating AML. Particularly exciting is the breadth and potency of the activity seen in AML patient samples from work done under the direction of Roland B Walter, M.D., Ph.D. at the Fred Hutchinson Cancer Research Center and the impressive level of activity observed in the AML patient-derived xenograft model in research conducted under the direction of John DiPersio, M.D., Ph.D., at the Washington University School of Medicine. Drs. DiPersio and Walter are two prominent, highly-regarded key opinion leaders in the area of hematologic oncology research and having their work support and validate our internal efforts is gratifying," said Jeanmarie Guenot, Ph.D., president and chief executive officer of Amphivena Therapeutics. "These positive preclinical results represent a key milestone for Amphivena, and we are happy to announce selection of a therapeutic candidate, AMV-564, for clinical development. While these studies highlighted promising therapeutic profiles for a number of our novel antibodies, we believe that AMV-564 provides the most rapid opportunity for successful development."

"The potent in vitro and in vivo activity of AMV-564 suggests this tetravalent, bispecific antibody may soon be ready for early phase clinical trials," said Dr. DiPersio, M.D., Ph.D., Chief, Division of Oncology, Deputy Director, Siteman Cancer Center, Washington University School of Medicine.

Dr. Walter, M.D., Ph.D., is Assistant Member, Clinical Research Division at the Fred Hutchinson Cancer Research Center and Associate Professor Medicine, Division of Hematology at the University of Washington.
Under terms of Amphivena’s ongoing agreement with Janssen Biotech, Inc. (Janssen), Janssen has the exclusive right to acquire Amphivena following approval of an Investigational New Drug (IND) application. As part of the agreement, Janssen has provided Amphivena with an initial upfront payment, as well as contingent payments to Amphivena based on achievement of predetermined milestones.

About AMV-564

AMV-564 is one of Amphivena’s proprietary first-in-class, tetravalent, bispecific TandAb antibodies. The novel immunotherapy recruits T-cells to eliminate cancer cells that express CD33, a receptor that is expressed on the majority of acute myeloid leukemias (AMLs) and is present on other hematologic malignancies. AMV-564 is bivalent for both CD33 on AML cells and CD3 on T-cells, forming a T-cell activating complex in the presence of target cancer cells. By maintaining the avidity for antigen as found in typical monoclonal antibodies, AMV-564 mediates potent and efficient tumor cell lysis. AMV-564 also offers pharmacokinetic advantages over smaller, monovalent bispecific constructs due to a molecule size that exceeds renal clearance limits. Amphivena is currently completing IND-enabling studies to advance AMV-564 into clinical development as a treatment for AML.