On April 3, 2017 SignalRx Pharmaceuticals Inc., focused on developing novel small-molecule cancer therapeutics targeting key orthogonal and synergistic oncotargets, reported the upcoming presentation of scientific data on the company’s triple PI3K/CDK4-6/BRD4 inhibitor program and first-in-class triple inhibitor SRX3177 (Press release, SignalRx, APR 3, 2017, http://www.ireachcontent.com/news-releases/signalrx-to-present-at-the-aacr-annual-meeting-on-its-first-in-class-triple-pi3kcdk4-6brd4-inhibitor-srx3177-for-treating-cancer-617971313.html [SID1234527324]). The poster presentation by Dr. Donald L. Durden, MD, PhD, senior scientific advisor for SignalRx, will be poster #LB-298 at the April 5th late breaking poster session at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in Washington, DC.

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SRX3177 is developed on the rationale that concurrent PI3K inhibition can prevent resistance to CDK4/6 inhibition, and combined CDK4/6 and PI3K inhibition leads to synthetic lethality reported in a number of cancer types, including breast cancer and mantle cell lymphoma, and blocking the chromatin reader protein BRD4 downregulates MYC and cyclin D1 transcription, further promoting cell cycle arrest in G1.

The presentation will describe the discovery and early development of the molecularly designed small-molecule triple inhibitor SRX3177. Key highlights to be presented include:

SRX3177’s potent in vitro enzymatic inhibition profile (IC50: CDK4 = 2.54 nM, CDK6 = 3.26 nM; PI3Kα = 79.3 nM, PI3Kδ = 83.4 nM; BRD4-BD1 = 32.9 nM, BRD4-BD2 = 88.8 nM).
SRX3177 rational design based on thieno-pyranone scaffold and target modeling.
Up to 82-fold more potent than palbociclib in a panel of mantle cell lymphoma, neuroblastoma, and hepatocellular carcinoma cell lines.
5-Fold more potent in cancer cells than combination of BKM120 (PI3K inhibitor) + palbociclib (CDK4/6 inhibitor) + JQ1 (BRD4 inhibitor).
40-Fold less toxic to normal epithelial cells than combination of BKM120 + palbociclib + JQ1.
Cell cycle arrest and apoptosis induction with proven mode of action (p-AKT, p-Rb, chromatin release).
SignalRx is also announcing that it is seeking partnering opportunities to accelerate the development of this program and its PI3K-BRD4 program to advance novel small molecules into first-in-man clinical trials based on the promising profile of its inhibitors shown so far. Since these are single molecules with a single PK/PD and toxicity profile, there is a great opportunity to develop them as single therapeutics and streamline their development in combination therapies focused on companion diagnostics built around synthetic lethality discoveries in human cancers.

On April 3, 2016-Bristol-Myers Squibb Company (NYSE:BMY) reported that CheckMate -143, a randomized Phase 3 clinical trial evaluating the efficacy and safety of Opdivo in patients with first recurrence of glioblastoma multiforme (GBM), did not meet its primary endpoint of improved overall survival over bevacizumab monotherapy (Press release, Bristol-Myers Squibb, APR 3, 2017, View Source [SID1234518425]). These data will be presented on May 7, 2017 at the World Federation of Neuro-Oncology Societies (WFNOS) meeting in Zurich, Switzerland.

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"GBM is a historically difficult disease to treat and conventional treatment options have demonstrated limited responses," said Fouad Namouni, M.D., head of Oncology Development and head of Medical, Bristol-Myers Squibb. "We remain steadfast in our pursuit of treatments for diseases with the highest unmet need and continue our work to determine how our Immuno-Oncology agents can potentially improve outcomes for these patients."

CheckMate -143 was the first randomized clinical trial in GBM with a PD-1 checkpoint inhibitor. BMS has two first-line GBM clinical trials, CheckMate -498 and CheckMate -548, evaluating the combination of Opdivo with radiation therapy with or without temozolomide in O6-methylguanine-DNA methyltransferase (MGMT)-unmethylated and methylated patients. These trials are moving forward as planned.

Bristol-Myers Squibb & Immuno-Oncology: Advancing Oncology Research

At Bristol-Myers Squibb, patients are at the center of everything we do. Our vision for the future of cancer care is focused on researching and developing transformational Immuno-Oncology (I-O) medicines that will raise survival expectations in hard-to-treat cancers and will change the way patients live with cancer.

We are leading the scientific understanding of I-O through our extensive portfolio of investigational and approved agents, including the first combination of two I-O agents in metastatic melanoma, and our differentiated clinical development program, which is studying broad patient populations across more than 35 types of cancers with 13 clinical-stage molecules designed to target different immune system pathways. Our deep expertise and innovative clinical trial designs uniquely position us to advance the science of combinations across multiple tumors and potentially deliver the next wave of I-O combination regimens with a sense of urgency. We also continue to pioneer research that will help facilitate a deeper understanding of the role of immune biomarkers and inform which patients will benefit most from I-O therapies.

We understand making the promise of I-O a reality for the many patients who may benefit from these therapies requires not only innovation on our part but also close collaboration with leading experts in the field. Our partnerships with academia, government, advocacy and biotech companies support our collective goal of providing new treatment options to advance the standards of clinical practice.

About Opdivo

Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor that is designed to uniquely harness the body’s own immune system to help restore anti-tumor immune response. By harnessing the body’s own immune system to fight cancer, Opdivo has become an important treatment option across multiple cancers.

Opdivo’s leading global development program is based on Bristol-Myers Squibb’s scientific expertise in the field of Immuno-Oncology and includes a broad range of clinical trials across all phases, including Phase 3, in a variety of tumor types. To date, the Opdivo clinical development program has enrolled more than 25,000 patients. The Opdivo trials have contributed to gaining a deeper understanding of the potential role of biomarkers in patient care, particularly regarding how patients may benefit from Opdivo across the continuum of PD-L1 expression.

In July 2014, Opdivo was the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world. Opdivo is currently approved in more than 60 countries, including the United States, the European Union and Japan. In October 2015, the company’s Opdivo and Yervoy combination regimen was the first Immuno-Oncology combination to receive regulatory approval for the treatment of metastatic melanoma and is currently approved in more than 50 countries, including the United States and the European Union.

On April 3, 2017 Insys Therapeutics, Inc. (NASDAQ:INSY) ("Insys" or "the Company") reported financial results for the three- and twelve-month periods ended December 31, 2016 (Press release, Insys Therapeutics, APR 3, 2017, View Source;p=RssLanding&cat=news&id=2259151 [SID1234518439]).

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Highlights of and subsequent to the fourth quarter of 2016 include:

Total net revenue decreased to $54.9 million, compared to $93.9 million for the fourth quarter of 2015;

Net loss was $3.7 million, or $(0.05) per basic and diluted share, compared to net income of $18.1 million, or $0.25 per basic and $0.24 diluted share, for the fourth quarter of 2015;

Cash, cash equivalents and investments were $236.7 million as of December 31, 2016;

Announced that the Company is providing for the use of Cannabidiol Oral Solution at doses up to 40 mg/kg/day in compassionate use studies in subjects with refractory pediatric epilepsy following completion of 48 weeks of treatment in the ongoing long-term safety study;

Targeting an NDA filing by end-2017 for Buprenorphine Sublingual Spray for the treatment of moderate to severe acute pain;

The DEA issued an interim final rule that would result in Syndros (dronabinol oral solution) being placed in Schedule II of the Controlled Substances Act;

Saeed Motahari will become President and Chief Executive Officer and be appointed to the Board of Directors, effective April 17, 2017; and

For the first quarter of 2017, the Company experienced an approximate 32% decline in Subsys scripts as compared the fourth quarter of 2016. As a result, Insys anticipates a commensurate impact on net revenue for the first quarter of 2017.
"During 2016 we continued to make progress in our product pipeline across both our sublingual and cannabidiol platforms, and expect to advance our pipeline candidates in 2017. With recent clarity on the scheduling of Syndros, we are targeting a launch in the second half of 2017 and believe the differentiating attributes of this product will provide an important new treatment option for prescribers and patients," said Dr. Santosh Vetticaden, Interim Chief Executive Officer, and Chief Medical Officer of Insys.

Fourth Quarter 2016 Financial Results

Net revenue for the fourth quarter of 2016 was $54.9 million compared to $93.9 million for the fourth quarter of 2015.

Gross margin was 82% for the fourth quarter of 2016 compared with 93% for the fourth quarter of 2015, which was impacted by a $5.8 million charge for excess and obsolete inventory.

Sales and marketing expense was $13.5 million during the fourth quarter of 2016, or 25% of net revenue, compared to $18.5 million, or 20% of net revenue, for the fourth quarter of 2015.

Research and development expense decreased to $15.5 million for the fourth quarter of 2016, compared to $16.1 million for the fourth quarter of 2015.

General and administrative expense decreased to $15.8 million for the fourth quarter of 2016, compared to $21.8 million for the fourth quarter of 2015. Insys recorded a $3.9 million charge related to litigation award and government settlements during the fourth quarter of 2016.

Income tax expense was $0.3 million for the fourth quarter of 2016.

Net loss for the fourth quarter of 2016 was $3.7 million, or $(0.05) per basic and per diluted share, compared to net income of $18.2 million, or $0.25 per basic and $0.24 per diluted share, for the fourth quarter of 2015. Non-GAAP adjusted net income for the fourth quarter of 2016 was $2.1 million, or $0.03 per diluted share, compared to non-GAAP adjusted net income of $32.1 million, or $0.42 per diluted share, in the prior year quarter. The reconciliation of net income to non-GAAP adjusted net income is included at the end of this press release.

2016 Financial Results

Net revenue for the year ended December 31, 2016 was $242.3 million compared to $330.3 million for the year ended December 31, 2015, a decrease of 26.7%.

Gross margin for 2016 was 90%, compared with 91% for 2015.

Sales and marketing expense was $69.7 million during 2016, or 29% of net revenue, compared to $80.7 million, or 25% of net revenue, for 2015.

Research and development expense increased to $73.9 million for 2016, or 31% of net revenue, compared to $56.8 million, or 17% of revenue, for 2015, mainly as a result of Insys’ continued pipeline development investments during 2016.

General and administrative expense decreased to $62.1 million for 2016, or 26% of net revenue, compared to $63.0 million, or 19% of net revenue, for 2015. Insys recorded a $3.9 million charge related to litigation award and government settlements during 2016.

Income tax expense was $0.8 million for 2016.

Net income for 2016 was $7.6 million, or $0.11 per basic and $0.10 per diluted share, compared to net income of $58.1 million, or $0.81 per basic and $0.77 per diluted share, for 2015. Non-GAAP adjusted net income, which adjusts for non-cash stock compensation expense and non-cash income tax expense, was $27.9 million, or $0.38 per diluted share, compared to $105.0 million, or $1.39 per diluted share, in the prior year. The reconciliation of net income to Non-GAAP adjusted net income is included at the end of this press release.

Liquidity

The Company had $236.7 million in cash, cash equivalents, and short-term and long-term investments, no debt, and $269.6 million in stockholders’ equity as of December 31, 2016.

On April 3, 2017 Intrexon Corporation (NYSE:XON), a leader in the engineering and industrialization of biology to improve the quality of life and health of the planet, ZIOPHARM Oncology (NASDAQ:ZIOP), a biopharmaceutical company focused on new immunotherapies, and Merck KGaA, Darmstadt, Germany, a leading science and technology company, reported an update on the development of next-generation chimeric antigen receptor T cell (CAR-T) therapy for cancer as part of their strategic collaboration and license agreement (Press release, Ziopharm, APR 3, 2017, View Source [SID1234518449]).

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Intrexon and ZIOPHARM Oncology, in an exclusive partnership with Merck KGaA, Darmstadt, Germany, are advancing a unique approach to develop therapeutic candidates for two CAR-T targets expressed on a wide range of tumor types, including hematologic malignancies and solid tumors.

The distinctive methodology centers on two technologies: the proprietary RheoSwitch Therapeutic System (RTS) platform to regulate expression of membrane-bound interleukin-15 (mbIL15) co-expressed with CARs and Sleeping Beauty non-viral gene integration.

"Sleeping Beauty and the RTS approach are a powerful combination to improve the manufacturing process and instill control over CAR-modified T cells co-expressing cytokines such as membrane-bound IL-15. The collaboration with Intrexon and Merck KGaA, Darmstadt, Germany, has been a catalyst to progress these next-generation gene therapy technologies. We are excited by the progress and look forward to advancing this innovative approach toward the clinic in mid-2018," said Laurence Cooper, M.D., Ph.D., Chief Executive Officer of ZIOPHARM.

The interleukin-15 (IL-15) cytokine is increasingly recognized as a key driver of therapeutic effect in CAR-T therapy, including in a recent Journal of Clinical Oncology publication which correlated lymphoma remissions with elevated IL-15 levels. Through the RTS gene switch, the expression of mbIL15 can be regulated to help CARs target cancers in a controlled manner, thus providing a new paradigm in T-cell therapy.

Additionally, the non-viral Sleeping Beauty transposon-transposase is an exceptional system for introducing genes encoding CARs and TCRs into T cells that holds multiple advantages over viral-based delivery systems. It simplifies genetic modification, and when coupled with reduced ex vivo processing, offers a pathway to shortened manufacturing and personalized T-cell therapies.

On March 31, 2017 Oncolytics Biotech Inc. (Oncolytics or the Company) (TSX:ONC) (OTCQX:ONCYF) reported the presentation of positive overall survival data from an open-label, randomized, Phase 2 study designed by the Canadian Cancer Trials Group (CCTG, formerly known as the National Cancer Institute of Canada – NCIC) (Press release, Oncolytics Biotech, MAR 31, 2017, View Source [SID1234518366]). The 74-patient study, powered to 90 percent, assesses the therapeutic combination of intravenously-administered REOLYSIN given in combination with paclitaxel versus paclitaxel alone in patients with advanced or metastatic breast cancer. Data from the study (IND 213), will be presented during the American Academy of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, April 1-5, in Washington, DC.

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The abstract reports that in the intention-to-treat (ITT) patient population there was an improvement in median OS (secondary endpoint) from 10.4 months on the control arm to 17.4 months on the test arm (Hazard ratio 0.65, 80% CI 0.46-0.91, p=0.1), meeting the pre-specified significance level for the 90 percent powered study. Consistent with REOLYSIN acting as an immune therapy agent, there was no meaningful improvement in either progression free survival (the primary endpoint), or response rate (secondary endpoint). The Company is now planning a registration study in metastatic breast cancer with overall survival as the primary endpoint.

"This is the first controlled, randomized study where the systemic administration of an immuno-oncology viral agent (REOLYSIN), was well tolerated and had a significant impact on the overall survival of relapsed metastatic breast cancer patients when used in combination with paclitaxel," said Dr. Karen Gelmon, Head, Investigational Drug Program, Experimental Therapeutics, Department of Medical Oncology, British Columbia Cancer Agency.

"There is an emerging pattern, from this and other studies with REOLYSIN, where patients obtain significant benefit in overall survival, despite limited impact on response rates and/or progression-free survival," said Dr. Andres Gutierrez, Chief Medical Officer of Oncolytics. "This is a well-established pattern for other immunotherapies, like checkpoint inhibitors, which have been approved on an overall survival primary endpoint in melanoma, NSCLC and head and neck cancers. These phase 2 data also support the established mode of activity of REOLYSIN where selective cell lysis of permissive cancer cells is followed by an anti-tumor immune response, which may be responsible for the meaningful survival benefit for patients. Taking into account the specific findings from this study, we continue to believe that REOLYSIN is not solely an oncolytic agent, but has key attributes of an immuno-oncology agent as well."

The abstract, authored by Bernstein et al, "A randomized (RCT) phase II study of oncolytic reovirus (pelareorep) plus standard weekly paclitaxel (P) as therapy for metastatic breast cancer (mBC)" is now available on the AACR (Free AACR Whitepaper) website. CCTG will be making a poster presentation, #8466, at the AACR (Free AACR Whitepaper) Annual Meeting, on Tuesday Apr 4, 2017 from 1:00 PM – 5:00 PM, in Washington, DC.

Oncolytics would like to thank the patients that participated in this study, the CCTG and all the physicians and nurses involved.

About Breast Cancer
The American Cancer Society estimates there will be 255,180 new cases of breast cancer diagnosed in the United States and 41,070 deaths from the disease in 2017.