On December 13, 2017 Bristol-Myers Squibb Company (NYSE:BMY) and Ono Pharmaceutical Co., Ltd. (Osaka, Japan; President, Representative Director, Gyo Sagara; "Ono") reported an agreement that grants Bristol-Myers Squibb an exclusive license for the development and commercialization of ONO-4578, Ono’s selective Prostaglandin E2 (PGE2) receptor 4 (EP4) antagonist (Press release, Bristol-Myers Squibb, DEC 13, 2017, View Source [SID1234522637]). The companies will also collaborate on discovery efforts to identify additional compounds from Ono’s PGE2 receptor antagonist programs.

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"To improve long-term outcomes for more patients with cancer, we believe more Immuno-Oncology based combinations may be required, and we are pleased to continue our long-standing collaboration with Ono with this focus in mind," said Fouad Namouni, M.D., head of Development, Oncology, Bristol-Myers Squibb. "Ono’s Prostaglandin E2 receptor antagonist programs offer the potential to develop targeted therapies that counteract the effects of an immunosuppressive tumor microenvironment. Researching Prostaglandin E2 receptor antagonists in combination with our oncology portfolio has the potential to result in an enhanced response in a broad range of tumors."

"We are very pleased to collaborate with Bristol-Myers Squibb on ONO-4578, an innovative Immuno-Oncology therapy candidate derived from our long-standing Prostaglandin projects, and to further work with Bristol-Myers Squibb on other Prostaglandin E2 receptor antagonist programs," said Hiroshi Awata, Vice President Executive Officer and Executive Director, Clinical Development, Ono Pharmaceutical Co., Ltd. "We are committed to further pursuing the worldwide development of ONO-4578 with Bristol-Myers Squibb with the goal of improving outcomes of patients suffering from cancer around the world as promptly as possible."

Under the terms of the agreement, Bristol-Myers Squibb will make an upfront payment of $40 million to Ono. Bristol-Myers Squibb will be solely responsible for the development, manufacturing and commercialization of ONO-4578 as well as other PGE2 receptor antagonist products in all countries of the world except Japan, South Korea, Taiwan, China and Association of Southeast Asian Nations (ASEAN) countries. Ono is eligible to receive subsequent clinical, regulatory and sales-based milestone payments, as well as royalties in these countries where Bristol-Myers Squibb has exclusive license. In Japan, South Korea and Taiwan, Bristol-Myers Squibb and Ono will partner on the development and commercialization under the companies’ existing collaboration agreement, while in China and ASEAN countries, Ono will retain exclusive rights.

About Prostaglandin E 2 and Immuno-Oncology

Prostaglandin E2 (PGE2), a major immunosuppressive factor in the tumor microenvironment, is believed to suppress tumor immunity and promote tumor progression. Preclinical data suggests that modulation of PGE2 through any PGE2 receptor antagonists may complement Immuno-Oncology therapies, including anti-PD-1 and anti-CTLA-4, and potentially increase both the rate and durability of response in tumors that are refractory to immunotherapy. Certain patients and tumor types have higher expression of PGE2-related molecules and/or immune characteristics that are more likely to respond to PGE2 receptor blockade, presenting an opportunity for patient stratification to improve outcomes.

About ONO-4578

ONO-4578 is a selective, oral antagonist of EP4, which is a Prostaglandin E2 receptor. In results from experiments using mouse models, ONO-4578 showed an anti-tumor effect by improving immunosuppressive tumor microenvironment. Ono has already commenced Phase I clinical study of ONO-4578 in Japan.

About the Bristol-Myers Squibb and Ono Pharmaceutical Collaboration

In 2011, through a collaboration agreement with Ono Pharmaceutical Co., Ltd., Bristol-Myers Squibb expanded its territorial rights to develop and commercialize Opdivo globally except in Japan, South Korea and Taiwan, where Ono had retained all rights to the compound at the time. On July 23, 2014, Ono and Bristol-Myers Squibb further expanded the companies’ strategic collaboration agreement to jointly develop and commercialize multiple immunotherapies – as single agents and combination regimens – for patients with cancer in Japan, South Korea and Taiwan.

On December 13, 2017 MabVax Therapeutics Holdings, Inc. (Nasdaq: MBVX), a clinical-stage biotechnology company focused on the development of antibody-based products to address unmet medical needs in the treatment of cancer, reported the completion of enrollment and dosing of all patients in the initial cohort of the Phase 1 clinical trial evaluating the Company’s new human antibody-based radioimmunotherapy ("RIT") product MVT-1075 for the treatment of pancreatic, colon and lung cancer (Press release, MabVax, DEC 13, 2017, View Source [SID1234522631]).

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This Phase 1 first-in-human clinical trial is an open-label, multi-center study evaluating the safety and efficacy of MVT-1075 in approximately 22 patients with CA19-9 positive malignancies in the U.S. The primary objective is to determine the maximum tolerated dose and safety profile in patients with recurring disease who have failed prior therapies. Secondary endpoints are to evaluate tumor response rate and duration of response by RECIST 1.1, and to determine dosimetry and pharmacokinetics. This dose-escalation study utilizes a traditional 3+3 design. The investigative sites include Honor Health in Scottsdale, Arizona and Memorial Sloan Kettering Cancer Center in New York City. The Company plans to report interim results from this study early in the first quarter of 2018 and continue the dose escalation phase of the program.

In April, the Company reported preclinical results for MVT-1075 at the American Association of Clinical Research (AACR) (Free AACR Whitepaper) Annual Meeting, demonstrating marked suppression, and in some instances, regression of tumor growth in xenograft animal models of pancreatic cancer, potentially making this product an important new therapeutic agent in the treatment of pancreatic, colon and lung cancers. Supporting the MVT-1075 RIT clinical investigation are the Company’s successful Phase 1a safety and target specificity data which were reported earlier this year at the annual meetings of the American Society for Clinical Oncology (ASCO) (Free ASCO Whitepaper) and the Society for Nuclear Medicine and Molecular Imaging (SNMMI), including the clinical results for the Company’s MVT-5873 single agent therapeutic antibody and MVT-2163, an immuno-PET imaging agent. The combined results from 50 patients in the Phase 1a MVT-5873 and MVT-2163 studies, established safety and provided significant insight into drug biodistribution and an optimal dosing strategy, which the Company has incorporated into the MVT-1075 program.

MVT-1075 combines the clinically demonstrated tumor targeting characteristics of the Company’s fully human HuMab-5B1 antibody and the commercially validated radionuclide, 177Lutetium, for the purpose of delivering a lethal dose of radiation to the targeted cancer cells.

For additional information about the Phase 1 MVT-1075 clinical trial, please visit clinicaltrials.gov, and reference Identifier NCT03118349.

About MVT-1075

MVT-1075 is a radioimmunotherapy product that combines established efficacy of radiation therapy with tumor specific targeting. It has the potential to deliver a more potent HuMab-5B1 based product. MVT-1075 uses small doses of the Company’s MVT-5873 antibody, coupled to a radioisotope to target pancreatic cancer cells and kill them.

On December 13, 2017 Cascadian Therapeutics, Inc. (Nasdaq:CASC), a clinical-stage biopharmaceutical company, reported that it has been selected for addition to the Nasdaq Biotechnology Index (Nasdaq:NBI), which will become effective prior to U.S. market open on Monday, December 18, 2017 (Press release, Cascadian Therapeutics, DEC 13, 2017, View Source [SID1234522627]).

The Nasdaq Biotechnology Index is designed to track the performance of a set of securities listed on the Nasdaq Stock Market (Nasdaq) that are classified as either biotechnology or pharmaceutical according to the Industry Classification Benchmark (ICB). The Nasdaq Biotechnology Index is re-ranked annually and all securities in the index are listed on the Nasdaq Global Market or the Nasdaq Global Select Market, and meet minimum market value and share volume requirements among other criteria. For more information about the Nasdaq Biotechnology Index, including eligibility criteria, visit www.nasdaq.com.

On December 13, 2017 Shire plc (LSE: SHP, NASDAQ: SHPG), the global leader in rare diseases, reported that the European Commission (EC) granted Marketing Authorization for lyophilized ONCASPAR (pegaspargase), as a component of antineoplastic combination therapy in acute lymphoblastic leukemia (ALL) in pediatric patients from birth to 18 years, and in adult patients (Press release, Shire, DEC 13, 2017, View Source [SID1234522624]).1 The approval – which authorizes Shire to market lyophilized ONCASPAR in the 28 member states of the European Union (EU), as well as Iceland, Liechtenstein and Norway – follows a positive opinion adopted by the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) on October 12.

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"This approval underscores Shire’s commitment to patients with acute lymphoblastic leukemia through continued research and evolution of asparaginase therapy," said Howard B. Mayer, M.D., SVP and ad-interim Head, Global Research and Development, Shire. "With this lyophilized formulation, we aim to make pegylated asparaginase, part of the pediatric standard therapy in acute lymphoblastic leukemia, available to patients in countries where liquid ONCASPAR is not currently offered. Additionally, with extended shelf life up to 24 months, treatment centers will have flexibility in inventory management to help ensure continuous treatment supply for patients."

Lyophilized ONCASPAR builds on more than a decade of data and research with liquid ONCASPAR, a pegylated asparaginase, and works the same way as the liquid formulation. By depleting serum L-asparagine levels and thereby interfering with protein synthesis, ONCASPAR deprives lymphoblasts of L-asparagine, resulting in cell death.2,3,4

The new lyophilized formulation offers the same dosing regimen as liquid ONCASPAR, but with a three-times longer shelf life than the liquid formulation.1 Asparaginase is a critical component of the treatment regimen for ALL patients as it is a proven approach to inducing leukemic cell death.2,3,4

Shire expects lyophilized ONCASPAR to be available in European markets beginning in the first half of 2018.

About Acute Lymphoblastic Leukemia
Acute lymphoblastic leukemia (ALL) is a cancer of the white blood cells and is characterized by an overproduction and accumulation of lymphoblasts, immature white blood cells. ALL is the most common type (~75%) of cancer among children diagnosed with leukemia5. ALL can be curable within certain pediatric patient populations, with a five-year overall survival rate of 96% in children treated with regimens including ONCASPAR6.

On December 13, 2017 Iovance Biotherapeutics, Inc. (NASDAQ:IOVA), a biotechnology company developing novel cancer immunotherapies based on tumor-infiltrating lymphocyte (TIL) technology, reported that patient enrollment has begun in a study combining TIL and nivolumab in advanced non-small cell lung cancer (NSCLC) patients in collaboration with researchers at H. Lee Moffitt Cancer Center and Research Institute (Moffitt), Stand Up to Cancer and other partners (Press release, Iovance Biotherapeutics, DEC 13, 2017, View Source;p=RssLanding&cat=news&id=2322489 [SID1234522622]). The company also announced that a Phase 2 study in PD-1/PDL-1 naïve NSCLC patients, sponsored by Iovance, in collaboration with MedImmune, the global biologics research and development arm of AstraZeneca, will initiate in the first half of 2018. The study with MedImmune will allow for enrollment of NSCLC patients for treatment with LN-145 alone or in combination with durvalumab.

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"Lung cancer is the leading cause of death in cancer and the second most common cancer in the United States. Five-year survival for NSCLC remain under 20% despite recent advances in the field," said Dr. Maria Fardis, PhD, MBA, President and Chief Executive Officer of Iovance Biotherapeutics. "The Phase 1 TIL and nivolumab combination study is being conducted in collaboration with the Moffitt Cancer Center, Stand Up To Cancer, as well as support from Bristol-Myers Squibb and Prometheus Laboratories,1 and speaks to the potential application of TIL technology in lung cancer. MedImmune is a leader in development of immuno-oncology therapy and we look forward to initiating our clinical collaboration with them for this unique combination therapy in the first half of next year."

The initiated Phase 1 study (NCT03215810) is designed to enroll up to 18 patients with advanced NSCLC.

NSCLC is associated with high mutational load in the tumor. Results of TIL growth from this tumor type has been reported by Iovance at the SITC (Free SITC Whitepaper) 31st Annual Meeting in 2016. Impact of treatment of NSCLC with TIL alone, as well as in combination with durvalumab, will be explored in PD-1/PDL-1 naïve patients in the Iovance Phase 2 study to be conducted in collaboration with MedImmune. The Phase 2 multicenter study will enroll up to 24 patients and be composed of two cohorts to assess the efficacy and safety of LN-145 alone and in combination with anti-PD-L1 inhibitor durvalumab in patients with locally advanced or metastatic NSCLC.

About Lung Cancer
Lung cancer is the leading cause of human cancer deaths worldwide, with approximately 1.7 million deaths reported in 2015, of which 80% to 85% were attributed to non-small cell lung cancer (NSCLC). In 2017, there were an estimated 222,500 new cases and 155,870 deaths due to lung and bronchus cancer in the United States. In men and women, the lifetime risk of developing lung cancer is about 1 in 14 and 1 in 17, respectively, including both smokers and nonsmokers.

Forward-Looking Statements
Certain matters discussed in this press release are "forward-looking statements". The Company may, in some cases, use terms such as "predicts," "believes," "potential," "continue," "estimates," "anticipates," "expects," "plans," "intends," "may," "could," "might," "will," "should" or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. In particular, the Company’s statements regarding trends and potential future results are examples of such forward-looking statements. The forward-looking statements include risks and uncertainties, including, but not limited to, the success, timing and cost of the Company’s ongoing clinical trials and anticipated clinical trials for its current product candidates, including statements regarding the timing of initiation and completion of the trials; the timing of and its ability to obtain and maintain U.S. Food and Drug Administration or other regulatory authority approval of, or other action with respect to, its product candidates; the strength of Company’s product pipeline; the successful implementation of the Company’s research and development programs and collaborations; the success of the Company’s license or development agreements; the acceptance by the market of the Company’s product candidates, if approved; and other factors, including general economic conditions and regulatory developments, not within the Company’s control. The factors discussed herein could cause actual results and developments to be materially different from those expressed in or implied by such statements. A further list and description of the Company’s risks, uncertainties and other factors can be found in the Company’s most recent Annual Report on Form 10-K and the Company’s subsequent filings with the Securities and Exchange Commission. Copies of these filings are available online at www.sec.gov or www.iovance.com. The forward-looking statements are made only as of the date of this press release and the Company undertakes no obligation to publicly update such forward-looking statements to reflect subsequent events or circumstance.