On April 18, 2016 Agenus Inc. (NASDAQ: AGEN), an immuno-oncology company developing checkpoint modulator antibodies and cancer vaccines, reported that three abstracts on the Company’s checkpoint modulator product candidates were accepted for poster presentations at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2016 Annual Meeting (Press release, Agenus, APR 18, 2016, View Source [SID:1234510982]). The conference is taking place in New Orleans from April 16-20, 2016.

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Poster Details:

OX40
Poster Title: INCAGN01949: A Novel Anti-OX40 Agonist Antibody with the Potential to Enhance Tumor Specific T-cell Responsiveness, while Selectively Depleting Intratumoral Regulatory T Cells
Poster Number: #3204
Session Date: Tuesday, April 19, 2016
Session Time: 8:00 AM -12:00 PM CDT

GITR
Poster Title: A Novel Agonist Antibody (INCAGN01876) that Targets the Costimulatory Receptor GITR
Poster Number: #3220
Session Date: Tuesday, April 19, 2016
Session Time: 8:00 AM -12:00 PM CDT

CTLA-4
Poster Title: AGEN1884 and AGEN2041: Two Functionally Distinct Anti-CTLA-4 Antagonist Antibodies
Poster Number: #5005
Session Date: Wednesday, April 20, 2016
Session Time: 7:30 AM -11:00 AM CDT

Agenus is partnered with Incyte Corporation for the development of INCAGN1949 and INCAGN1876, and is partnered with Recepta Biopharma SA for certain South American rights for AGEN1884 and AGEN2041. Abstracts and posters will become available on the Company’s website at View Source following the poster sessions.

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Glioblastoma multiforme (GBM) is the most common brain and central nervous system (CNS) cancer, accounting for 15.1% of all primary brain tumors, and 55.1% of all gliomas. There are an estimated 12,120 new glioblastoma cases predicted in 2016 in the U.S. Malignant brain tumors are the most common cause of cancer-related deaths in adolescents and young adults aged 15-39 and the most common cancer occurring among 15-19 year olds in the U.S. While GBM is a rare disease (2-3 cases per 100,000 person life years in U.S. and E.U.), it is quite lethal with 5-year survival rates historically less than 10%. Chemotherapy with temozolomide and radiation are shown to extend mean overall survival from 4.5 to 15 months, while surgery remains the standard of care. GBM remains difficult to treat due to the inherent resistance of the tumor to conventional therapies.

Immunotherapy approaches targeting brain tumors offer promise over conventional treatments. IL13Rα2 is an attractive target for CAR-T therapy as it has limited expression in normal tissue but is over-expressed on the surface of greater than 50% of GBM’s. CAR-T cells are designed to express membrane-tethered IL-13 receptor ligand (IL-13) with high affinity for IL13Rα2 and reduced binding to IL13Rα1 in order to reduce healthy tissue targeting.

We are developing an optimized CAR-T product incorporating enhancements in CAR design and T-cell engineering to improve antitumor potency and T-cell persistence. We include a second generation hinge optimized CAR containing mutations in the IgG4 linker to reduce off target Fc interactions as well as the 41BB (CD137) co-stimulatory signaling domain for improved survival and maintenance of memory T-cells as well as extracellular domain of CD20 as a selection/safety marker. In order to further improve persistence, central memory T-cells (TCM) are isolated and enriched. The manufacturing process limits ex vivo expansion in order to reduce T-cell exhaustion and maintain a TCM phenotype.

In collaboration with the COH, we have an on-going phase I clinical study to assess the feasibility and safety of using TCM enriched IL13Rα2-specific CAR engineered T-cells and are currently treating patients with recurrent/refractory GBM. We will assess the T-cell persistence and determine the potential immunogenicity of the cells to determine a recommended phase II dose.

On April 18, 2016 Heptares Therapeutics ("Heptares"), the wholly-owned subsidiary of Sosei Group Corporation (TSE Mothers Index: 4565), and Kymab Limited, a leading human monoclonal antibody biopharmaceutical company, reported that they have entered into a strategic collaboration to discover, develop and commercialise novel antibody therapeutics targeting a number of G protein-coupled receptors (GPCR) with an initial focus on immuno-oncology (Press release, Heptares, APR 18, 2016, View Source [SID:1234514761]).

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Immuno-oncology is an exciting new area in the treatment of cancer where the body’s immune system is activated to produce an immune response targeted at tumour cells. Immunotherapy drugs are poised to revolutionise the way cancer is treated and a number of immunotherapy antibody treatments have recently been approved. GPCRs are widely expressed on cells of the innate and adaptive immune system and play key roles in modulating cell migration and recruitment to the tumour environment, activation, survival, proliferation and differentiation. GPCRs act at critical checkpoints that can be targeted by novel immunotherapy antibodies.

Under the agreement, Heptares will apply its StaR platform to create stable antigens based on multiple GPCR targets chosen by the companies. Kymab will then use its Kymouse human antibody discovery platform to generate antibodies in response to immunisation with these antigens. The Kymouse platform will assure the highest probability of finding the best-in-class antibodies with highly attractive drug properties. Promising leads will be progressed using the partners’ complementary skills, resources and development capabilities in order to bring innovative products into the clinic. Under the agreement, the companies will jointly conduct and share the costs of each antibody discovery and development programme.

Malcolm Weir, Chairman and CEO of Heptares, said: "GPCRs have long been intractable targets for antibody discovery resulting in dearth of products. We believe that our proven StaR technology can unlock this substantial opportunity, not just in immuno-oncology but also across other therapeutic areas where GPCR-targeted biologics could have a significant impact. By entering into strategic collaborations with companies with world-leading antibody discovery technologies, such as Kymab, we have the potential to discover, develop and commercialise a highly valuable pipeline of new biologic products."

David Chiswell, CEO of Kymab, said: "Antibodies are important therapeutic agents for cancer and other indications. Our collaboration with Heptares will allow us to combine stable antigens based on multiple GPCR targets with our world-class Kymouse platform, which has unparalleled diversity and will therefore rapidly identify and yield highly selective potent human monoclonal antibodies for unmet medical needs."

On April 18, 2016 Varian Medical Systems (NYSE: VAR) reported it is supporting a phase III trial comparing outcomes of radiosurgery versus surgical resection for the treatment of early-stage, high-risk, operable non-small cell lung cancer (NSCLC) (Press release, InfiMed, APR 18, 2016, View Source [SID:1234510962]).

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Known as the "Stablemates Trial," the randomized study will test the hypothesis that the 3-year overall survival in high risk operable patients with stage I NSCLC is equivalent or greater in patients who undergo stereotactic ablative radiotherapy (SAbR) as compared with conventional sublobar resection (SR) surgery. Led by co-chairs Hiran Fernando, MD, Boston Medical Center, and Robert Timmerman, MD, University of Texas Southwestern Medical Center, the study currently involves 34 institutions and 258 patients.

"In addition to a potentially longer survival rate, SAbR may benefit some lung cancer patients by offering them a noninvasive, outpatient treatment option that is easier to tolerate and that doesn’t interfere greatly with their normal, everyday living activities," said Dr. Timmerman.

Sponsored by the Joint Lung Cancer Trialist’s Coalition, the study is being administered by the Department of Radiation Oncology at the University of Texas Southwestern Medical Center. Over the next five years, the study will examine patients’ overall, disease-free, and regional recurrence-free survival rates three years after treatment, as well as adverse events and post-treatment quality of life measures.

"Varian believes in supporting high quality clinical research," said Kolleen Kennedy, president of Varian’s Oncology Systems business. "This clinical trial presents the opportunity to advance radiation oncology and enhance the standard of patient care by giving clinicians a noninvasive treatment option in determining the appropriate therapy for patients."

Learn more about the Stablemates Trial at View Source

Lenalidomide and bevacizumab have antitumor activity in various tumor types. We conducted a phase I study of this combination in patients with advanced cancer.
A "3 + 3" study design was used. Lenalidomide 10 or 20 mg (orally, days 1-21) and bevacizumab 5, 7.5, or 10 mg/kg, (intravenously, every 2 weeks) were given at four escalating dose levels, followed by an expansion phase at the highest maximum tolerated dose (MTD) (1 cycle = 4 weeks). Dose-limiting toxicity (DLT), MTD, adverse events, and clinical outcomes were assessed.
Thirty-one patients were enrolled (median age, 60 years; men, 52 %). The most common tumor types were colorectal carcinoma (n = 11) and melanoma (n = 5). Overall, 105 cycles (median, 2) were administered. No DLTs were observed. The maximum tested dose (level 4) was used in the expansion phase. The most common toxicities were fatigue (n = 7, 23 %) and skin rash (n = 4, 13 %). One patient developed a transient ischemic attack (3.2 %); prophylactic anticoagulation became mandatory in the subsequent 17 treated patients. Of 31 patients, 27 were evaluable for response. Stable disease (SD) was noted in 10 (37 %) patients, including five patients with SD for ≥6 months (tumor types: clear cell sarcoma, germ cell tumor, colorectal carcinoma, and melanoma). The median progression-free survival and overall survival were 2.8 and 5.5 months, respectively.
The combination of lenalidomide with bevacizumab in patients with advanced solid tumors was safe. Prolonged stable disease was noted in selected tumor types, warranting further clinical evaluation.

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