On September 28, 2016 Mirna Therapeutics, Inc. (the "Company") reported that it received verbal notice from the U.S. Food and Drug Administration (the "FDA") that the Company’s Investigational New Drug ("IND") for MRX34, its investigational microRNA therapy for multiple cancers, has been placed on full clinical hold ((Press release, Mirna Therapeutics, SEP 28, 2016, View Source [SID1234515521]). The Company anticipates that it will receive a formal clinical hold letter from the FDA within 30 days. This follows the Company’s announcement on September 20, 2016 that it was voluntarily stopping its Phase 1 trial for MRX34

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On September 28, 2016 Otsuka Pharmaceutical Co., Ltd. reported that it has received regulatory approval in Japan for manufacture and sales of ICLUSIG Tablets 15 mg (ponatinib hydrochloride), a tyrosine kinase inhibitor (TKI) indicated to treat patients with chronic myeloid leukemia (CML) who are resistant or intolerant to previous treatments and patients with recurrent or refractory Philadelphia-chromosome positive acute lymphoblastic leukemia (Ph+ ALL) (Press release, Otsuka, SEP 28, 2016, View Source;date=2016-09-28 [SID:SID1234515492]).*2

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Although TKIs are used as a first-line treatment for CML and Ph+ ALL, mutation of BCR-ABL genes can develop during the treatment period and indicates resistance to the currently used TKI. In addition, intolerance to the side effects of existing TKI treatments can lead to a discontinuation of treatment.

ICLUSIG, discovered in the U.S. by ARIAD Pharmaceuticals, Inc., is a TKI that targets BCR-ABL expressed in CML and Ph+ ALL. This drug is a new chemically synthesized oral TKI, and is specifically designed to inhibit mutated TK caused by a T315I mutation which induces resistance to the currently used TKI. ICLUSIG demonstrates efficacy in CML patients with resistance to or with intolerance to currently available TKIs. ICLUSIG was approved in the U.S. in 2012, in Europe in 2013, and in 2014 Otsuka obtained the rights to commercialize and develop ICLUSIG in ten Asian countries and regions.*1 ICLUSIG was designated as an orphan drug in Japan and a new drug application (NDA) was submitted in January 2016. NDAs have been submitted in Korea and Taiwan as well.

On September 28, 2016 Cascadian Therapeutics (NASDAQ:CASC), a clinical-stage biopharmaceutical company, reported two upcoming poster presentations on tucatinib (ONT-380), the Company’s lead product candidate for the treatment of HER2+ breast cancer, at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) 2016 Congress being held October 7 -11, 2016 in Copenhagen, Denmark (Press release, Cascadian Therapeutics, SEP 28, 2016, View Source [SID:SID1234515460]).

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Details of Poster Presentations:

Title: Cutaneous responses in Her-2+ metastatic breast cancer (MBC) on phase 1b study of ONT-380, an oral HER2-specific inhibitor in combination with capecitabine (C) and/or trastuzumab (T) in third line or later treatment
Poster Number: 278
Date: Monday, October 10, 2016
Time: 1:00pm — 2:00pm (CEST)

Title: A phase 2 randomized, double-blinded, controlled study of ONT-380 vs. placebo in combination with capecitabine (C) and trastuzumab (T) in patients with pretreated HER2+ unresectable locally advanced or metastatic breast carcinoma (MBC)
Poster Number: 312 (trial in progress)
Date: Monday, October 10, 2016
Time: 1:00pm — 2:00pm (CEST)

On September 28, 2016 AbbVie (NYSE: ABBV), a global biopharmaceutical company, reported that it has strengthened its manufacturing capabilities by opening the small molecule active pharmaceutical ingredient (API) facility of its Singapore manufacturing site (Press release, AbbVie, SEP 28, 2016, View Source [SID:SID1234515496]). This facility supports the growth of AbbVie’s oncology and women’s health pipeline and reflects progress from AbbVie’s two previous announcements for manufacturing investment in Asia in 2014.

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The new 120,000 square-meter site – located in the Tuas Biomedical Park – is AbbVie’s first manufacturing facility in Asia and will also include a biologics manufacturing facility that is expected to be fully operational by the end of 2018. Combined, the API and biologics facilities represent a $320 million (more than S$400 million) investment in Singapore that will employ more than 250 new employees, the majority of whom will be hired locally in Singapore, including skilled positions across manufacturing, technical operations, administration, quality, information technology and supply chain.

"Our goal as AbbVie is to assure patients around the world have access to new and innovative medicines when they need them and where they need them," said Azita Saleki-Gerhardt, Ph.D., senior vice president, operations, AbbVie. "Today, with the opening of the first phase of our Singapore facility, we will further strengthen our manufacturing capabilities and continue to enhance our support of AbbVie’s pipeline in the therapeutic areas of oncology and women’s health for patients around the world."

Speaking at the opening ceremony, Site Director Marc O’Donoghue, Ph.D., added, "Singapore is recognized as a leader in the biopharmaceutical industry and AbbVie is excited to open its facility and begin operations. Singapore has a robust infrastructure, a highly educated and skilled workforce and provides a supportive environment for manufacturing. Our presence in Singapore establishes AbbVie’s footprint in Asia and provides geographic balance in AbbVie’s manufacturing network to ensure continuity of supply."

"AbbVie’s choice of Singapore for its first in Asia manufacturing facility is testament to our capabilities as a high-quality, global biopharmaceutical manufacturing hub. Given our track record of providing a world-class business environment and skilled talent pool to companies, we enable companies such as AbbVie to develop and manufacture innovative products to deliver value for patients worldwide," said Ms. Weng Si Ho, director, biomedical sciences, Singapore Economic Development Board (EDB). "EDB will continue to commit strong investments in talent, infrastructure and technology to support the strong growth in the biopharmaceutical industry."

AbbVie’s manufacturing network now includes 13 locations across the United States, Europe, Asia and Puerto Rico, as well as strategic partnerships with third-party manufacturers.

On September 27, 2016 (GLOBE NEWSWIRE) Peregrine Pharmaceuticals, Inc. (NASDAQ:PPHM) (NASDAQ:PPHMP), a biopharmaceutical company committed to improving patient lives by manufacturing high quality products for biotechnology and pharmaceutical companies and advancing its proprietary R&D pipeline, reported the presentation of preclinical study data demonstrating that phosphatidylserine (PS)-targeting antibodies similar to bavituximab are able to enhance the anti-tumor activity of multiple checkpoint targeting agents including anti-PD-1 and anti-LAG3 therapies in a model of triple negative breast cancer (TNBC) (Press release, Peregrine Pharmaceuticals, SEP 27, 2016, View Source [SID:SID1234515466]). Data showed that eight of the ten (80%) animals receiving the preclinical bavituximab equivalent (ch1N11) combined with anti-PD-1 and anti-LAG3 therapies ("Triple Combination") experienced complete tumor regressions, whereas there were no animals (0/10) in the anti-PD-1 and anti-LAG3 combination treatment arm that had a complete regression.

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Additional data demonstrated that the Triple Combination featuring ch1N11 led to a 99% reduction in total tumor volume at the interim analysis point (Day 25) across all animals as compared to the control arm. In addition, the Triple Combination showed a statistically significant increase in tumor growth inhibition (TGI) as compared to the anti-PD-1 and anti-LAG3 combination treatment (99% vs. 62%; p < 0.05). Peregrine’s Michael J. Gray, Ph.D., the study’s lead scientist, presented the study findings at the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference (CIMT) (Free CIMT Whitepaper) September 25-28, 2016, in New York City.

The presented study evaluated various combinations of ch1N11, anti-PD-1 and anti-LAG3 therapy in the well-characterized E0771 murine model of TNBC. Other key study findings included:
Treatment with Triple Combination therapy (ch1N11/anti-PD-1/anti-LAG3) led to a significant increase in tumor infiltrating lymphocytes (TILs), particularly CD8+ T cells, as compared with anti-PD-1 and anti-LAG3 combination treatments.

Treatment with Triple Combination therapy (ch1N11/anti-PD-1/anti-LAG3) resulted in a reduction in immunosuppressive cell types, including CD4+ cells, regulatory T cells (Tregs) and myeloid derived suppressor cells (MDSCs). These results show that the Triple Combination therapy is capable of significantly altering the tumor microenvironment from highly immunosuppressive to highly immuno-stimulatory. Other treatment combinations evaluated in the study lacked a statistically significant reduction in immunosuppressive cells.

"These data offer compelling evidence for the therapeutic potential of including PS-targeted therapies in combination with multiple checkpoint inhibitors in the treatment of TNBC. This is highlighted by the dramatic distinction in complete tumor regression rates seen between the Triple Combination and anti-PD-1/anti-LAG3 treatment arms, combined with the significant difference in tumor growth inhibition percentages witnessed for these groups," stated Jeff T. Hutchins, Ph.D., Peregrine’s vice president, preclinical research. "In addition to its impact on tumor growth, we saw very important changes in the tumor microenvironment with the Triple Combination treatment with a significant reduction in cell types that contribute to immune suppression such as CD4+ cells, Tregs and MDSCs coupled with the expansion of tumor fighting cells such as CD8+ T cells. These data offer mechanistic evidence that highlight the manner by which the combination of ch1N11/anti-PD-1/anti-LAG3 may be eliciting such anti-tumor responses."
Bavituximab is an investigational monoclonal antibody that targets PS. Signals from PS inhibit the ability of immune cells to recognize and fight tumors. Bavituximab is believed to override PS mediated immunosuppressive signaling by blocking the engagement of PS with its receptors as well as by sending an alternate immune activating signal. Previous studies demonstrated PS-targeting antibodies shift the functions of immune cells in tumors, resulting in multiple signs of immune activation and anti-tumor responses. Peregrine evaluates the preclinical equivalent of bavituximab, ch1N11, in animal model studies to guide clinical development.
Peregrine’s clinical development strategy for bavituximab currently focuses on small, early-stage, proof-of-concept trials evaluating the drug in combination with other cancer treatments. This approach includes the recently announced grants by the National Comprehensive Cancer Network (NCCN) to support three different clinical trials of bavituximab treatment combinations. Those trials will evaluate novel bavituximab combinations in glioblastoma, head and neck cancer, and hepatocellular carcinoma including an immunotherapy combination. Additionally, Peregrine continues to advance its pre-clinical collaboration with Memorial Sloan Kettering Cancer Center with the goal of evaluating combinations of bavituximab with other checkpoint inhibitors and immune stimulatory agents. The intent behind this strategy is to focus our research and development spending to further validate bavituximab’s combination potential as we seek to advance the program though a pharmaceutical or biotechnology partner.