On September 24, 2015 TESARO, Inc. (NASDAQ:TSRO), an oncology-focused biopharmaceutical company, reported the decision of the National Comprehensive Cancer Network (NCCN) to include VARUBI (rolapitant) in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) Antiemesis Version 2.2015, as a recommended option in combination with other antiemetic agents for patients receiving both high emetic risk intravenous chemotherapy (HEC) and moderate emetic risk intravenous chemotherapy (MEC) (Press release, TESARO, SEP 24, 2015, View Source [SID:1234507537]). Category 1, the highest level category of evidence and consensus, was granted to rolapitant for both HEC and MEC chemotherapy.

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VARUBI is a selective and competitive antagonist of human substance P/neurokinin 1 (NK-1) receptors, with a plasma half-life of approximately seven days. Results from three Phase 3 trials of VARUBI demonstrated a significant reduction in episodes of vomiting or use of rescue medication during the 25 to 120 hour period following administration of highly emetogenic and moderately emetogenic chemotherapy regimens.

"Patients are at the center of all that we do, and are the reason we act with a sense of urgency and passion. We are grateful that NCCN has included VARUBI in their Antiemesis Guidelines so soon after our FDA approval, and we look forward to making VARUBI available to the patients who are at risk for delayed CINV later this fall," said Mary Lynne Hedley, Ph.D., President and COO of TESARO. "The prevention of delayed CINV represents a substantial opportunity for improving the care of patients who receive HEC and MEC."

TESARO plans to launch VARUBI in the U.S. in Q4 of 2015.

The NCCN Guidelines are a comprehensive set of guidelines detailing the sequential management decisions and interventions that currently apply to 97 percent of cancers affecting patients in the United States. The intent of the NCCN Guidelines is to assist in the decision-making process of individuals involved in cancer care—including physicians, nurses, pharmacists, payers, patients and their families—with the ultimate goal of advancing patient care in the fight against cancer.

VARUBI was approved by the U.S. Food and Drug Administration (FDA) on Sept. 2, 2015 in combination with other antiemetic agents in adults for the prevention of delayed nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy, including, but not limited to, highly emetogenic chemotherapy.

About Chemotherapy-Induced Nausea and Vomiting

Chemotherapy-induced nausea and vomiting can be a debilitating, yet often preventable, side effect of chemotherapy. Up to 50% of patients undergoing highly or moderately emetogenic chemotherapy experience delayed CINV (25 to 120 hours post chemotherapy)—even when prescribed a 5-HT3 receptor antagonist and corticosteroid.

Blocking both 5-HT3 and NK-1 receptors has been shown to offer better control of nausea and vomiting than inhibiting 5-HT3 receptors alone. Because NK-1 receptors are key drivers of CINV, especially in the delayed Phase, NK-1 receptor antagonists such as VARUBI, when combined with a 5-HT3 receptor antagonist and a corticosteroid, provide enhanced protection from CINV.

About VARUBI

VARUBI is a substance P/neurokinin-1 (NK-1) receptor antagonist indicated in combination with other antiemetic agents in adults for the prevention of delayed nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy, including, but not limited to, highly emetogenic chemotherapy. NK-1 receptors are highly concentrated in the brain and bind neurokinin substance P. Activation of NK-1 receptors plays a central role in nausea and vomiting induced by emetogenic stimuli, including certain cancer chemotherapies. A Positron Emission Tomography (PET) study with rolapitant in normal, healthy volunteers demonstrated that rolapitant crosses the blood brain barrier and occupies brain NK-1 receptors at high levels for up to 120 hours. VARUBI has a half-life of approximately 7 days, which may contribute to the ability of a single dose of VARUBI to cover the entire delayed CINV Phase (25-120 hours).

An intravenous formulation of rolapitant is also being developed. TESARO licensed exclusive rights for the development, manufacture, commercialization and distribution of VARUBI (rolapitant) from OPKO Health, Inc.

The full prescribing information for VARUBI is available at www.VarubiRx.com.

VARUBI Additional Safety Information

VARUBI is contraindicated in patients receiving thioridazine, a CYP2D6 substrate with a narrow therapeutic index.

Use of VARUBI should be avoided in patients who are receiving pimozide, a CYP2D6 substrate with a narrow therapeutic index. Adverse reactions should be monitored if concomitant use of VARUBI and other CYP2D6 substrates with a narrow therapeutic index cannot be avoided. The inhibitory effect of VARUBI on CYP2D6 lasts for at least 7 days and may last longer after administration of a single dose of VARUBI.

The most common adverse reactions (≥5%) in clinical trials were decreased appetite, neutropenia, hiccups and dizziness.

VARUBI is available by prescription only.

On September 24, 2015 Celator Pharmaceuticals, Inc. (Nasdaq: CPXX), a biopharmaceutical company that is transforming the science of combination therapy and developing products to improve patient outcomes in cancer, reported their successful R&D efforts to apply the CombiPlex technology platform to optimize the efficacy of anticancer drug combinations incorporating molecularly targeted agents (MTAs) (Press release, Celator Pharmaceuticals, SEP 24, 2015, View Source [SID:1234507532]).

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CombiPlex is Celator’s proprietary technology that aims to address several of the fundamental shortcomings of conventional combination regimens, as well as the inherent challenges in combination drug development. Celator is applying this technology to create new drug combinations that target pathways associated with tumor cell growth and/or resistance to treatment. Such MTAs are being widely pursued with an increasing focus on combining agents that target multiple cellular pathways in order to improve therapeutic responses.

"While there have been promising signs of activity for certain molecularly targeted agents, it is clear that combinations will be required for optimal efficacy," said Dr. Joseph Bertino, chief scientific officer at Rutgers Cancer Institute of New Jersey and chairman of Celator’s Scientific Advisory Board. "In addition, many combinations will require simultaneous exposure and attempts to accomplish this to date have often led to toxicity problems."

CombiPlex is well positioned to address the challenges with the development of combination drug candidates. Nano-scale delivery systems coordinate the pharmacokinetics (PK) of drug combinations after administration so that the optimal ratio of the two drugs is exposed to tumor cells for prolonged times while reducing drug exposure and toxicity to normal tissues.

Recent results from preclinical studies conducted by Celator suggest the technology may significantly improve the therapeutic index of combinations containing MTAs. Celator’s efforts have focused on two combinations: the heat shock protein 90 inhibitor AUY922 combined with docetaxel and the MEK inhibitor selumetinib combined with the Akt inhibitor ipatasertib. In both cases, the drug combinations were stably co-formulated in Celator’s proprietary hydrophobic prodrug nanoparticle delivery systems which provided well-coordinated plasma concentrations over 24 hours that were orders of magnitude higher than observed for the free drug combinations. Free drug combinations refer to the drugs as they are currently administered; individual drugs administered in combination without regard to their ratio dependent interaction. In addition, whereas combined treatment with the free drugs required marked dose reductions due to toxicity, the nanoparticle formulations could be administered at higher doses.

For both combinations, the CombiPlex formulations provided significant improvements in efficacy over the free drugs in human xenograft tumor models including breast, colorectal and ovarian. Furthermore, there was evidence of strong drug ratio-dependent efficacy and in vivo synergy.

Another benefit observed during this research was the versatility and modular nature of the nanoparticle technology. Once formulation conditions were optimized for the two initial combinations, the drug components could be "mixed and matched," rapidly generating additional CombiPlex products with coordinated PK. This versatility was then taken one step further by generating a 3-drug combination, co-formulating selumetinib, AUY922 and docetaxel into a single hydrophobic prodrug nanoparticle.

The data have been accepted for presentation at the 2015 AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper) being held in Boston, MA November 5-9.

"We are very pleased with the data packages generated on the CombiPlex formulations containing molecularly targeted agents," said Dr. Lawrence Mayer, president and chief scientific officer at Celator. "CombiPlex appears to address difficulties associated with the free drugs, resulting in important efficacy improvements. We achieved this milestone on time, and believe these data may help Celator establish collaborative R&D programs with pharma partners where CombiPlex can provide a strategic advantage for their agents."

On September 24, 2015 BIND Therapeutics, Inc. (NASDAQ: BIND), a clinical-stage nanomedicine company developing targeted and programmable therapeutics called AccurinsTM, reported that Pfizer Inc. exercised its option to obtain an exclusive license to develop and commercialize an Accurin drug candidate for the treatment of solid tumors under the companies’ global collaboration agreement (Press release, BIND Therapeutics, SEP 24, 2015, View Source [SID:1234507531]).

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The actively targeted Accurin is designed to impart cellular targeting capability and was engineered by BIND using one of Pfizer’s proprietary kinase inhibitors and one of BIND’s proprietary ligands. As a result of the option exercise, BIND will receive a $2.5 million option exercise fee from Pfizer. In parallel with exercising its first option, Pfizer informed BIND that it will not exercise its option for the second compound in the collaboration.

"Pfizer’s decision to obtain an exclusive license to our actively targeted Accurin further validates what we believe is the unique ability of our platform to optimize the therapeutic potential of potent pathway inhibitors," said Andrew Hirsch, president and chief executive officer at BIND Therapeutics. "This milestone with Pfizer is an important step toward our goal of advancing this innovative Accurin drug candidate into clinical testing. Working closely with Pfizer has allowed us to identify the Accurin candidate with the greatest potential in the collaboration. We now have the potential to have at least four Accurins in clinical development over the next two years, both through collaborations and with internal product candidates. With our belief in the ability of Accurins to deliver the right concentration of the right drug to the right place for the right amount of time, combined with Pfizer’s experience and expertise, we are pleased to move to the next stage in this collaboration."

"Our experiments to date have resulted in data that we believe justify advancing this candidate to the next stage of research," said Robert Abraham, Ph.D., senior vice president, Oncology-Rinat Research & Development Group, Pfizer. "BIND’s Accurin technology may help us to achieve an optimal efficacy-safety ratio for this investigational drug. We look forward to further exploring this potential in our ongoing collaboration with BIND."

Under terms of the original collaboration agreement, which was established in April 2013, Pfizer was granted options to obtain exclusive licenses to pursue development and commercialization of two Accurins that incorporate specified Pfizer small molecular targeted therapies. For the Accurin that has been selected, both companies will work together on preclinical research; Pfizer will have responsibility for development and commercialization, and BIND will conduct chemistry, manufacturing and control activities.

In addition to the $2.5 million option exercise fee, BIND received an upfront payment of $4.0 million in 2013 and achieved a $1.0 million preclinical development milestone for the selected Accurin in December 2014. BIND has the potential to receive additional milestone payments for the selected Accurin of up to $86.0 million in aggregate upon the achievement of additional specified development and regulatory events under the Pfizer collaboration agreement. BIND may also receive additional milestone payments for the selected Accurin of up to $110 million in aggregate for specified commercial events as well as royalties in the low single to high single digit percentages on potential future sales of the selected Accurin, if any.