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Verastem Announces New Research Published in the Journal Cell That Highlights the Potential of FAK Inhibition to Enhance the Efficacy of Anti-Tumor Immunotherapy

On September 24, 2015 Verastem, Inc. (NASDAQ:VSTM), focused on discovering and developing drugs to treat cancer by the targeted killing of cancer stem cells, reported that researchers from the University of Edinburgh have published a study in the journal Cell which highlights the potential of FAK inhibition to enable the body’s immune system to fight cancer (Press release, Verastem, SEP 24, 2015, View Source [SID:1234507543]).

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The paper discusses results from preclinical research showing that focal adhesion kinase (FAK), a protein which is often overproduced in tumors, enables cancer cells to evade attack by the immune system. In this study, researchers discovered that FAK inhibition can modulate the balance of immune cells in the tumor enabling an immune response to destroy the cancer cells.

Dr. Alan Serrels, one of the lead authors, at the Edinburgh Cancer Research UK Centre at the University of Edinburgh, said: "FAK is hi-jacked by cancer cells to protect them from the immune system. This exciting research reveals that by blocking FAK, we’ve now found a promising new way to help the immune system recognise the cancer and fight it. FAK inhibitors are already in clinical trials and have generally been well tolerated, so could potentially be an excellent complement to existing immunotherapy treatments."

The research, which was carried out in mice with squamous cell carcinoma, showed complete T-cell mediated tumor regression when the mice were administered the FAK inhibitor. This research is the first to demonstrate that FAK inhibition increases the presence of cytotoxic T cells in the tumor and decreases the presence of immunosuppressive T regulatory cells.

"This is a ground-breaking paper which shows that FAK inhibitors can induce tumor regression through a T cell-mediated mechanism," said Jonathan Pachter, Ph.D., Verastem Head of Research and co-author of the study. "These early data are encouraging and provide important support for the thesis that FAK inhibitors such as defactinib may be useful in combination with immuno-oncology agents with the goal of yielding more durable responses for a greater number of cancer patients."
The research was funded by Cancer Research UK, European Research Council, and Medical Research Council.
The full press release from Cancer Research UK can be accessed here: http://bit.ly/1gRLBC0

The paper, titled "Nuclear FAK controls chemokine transcription, Tregs and evasion of anti-tumor immunity," can be accessed at http://bit.ly/1KTb3mW.

About VS-6063
VS-6063 (defactinib) is an orally available compound designed to target cancer stem cells through the potent inhibition of focal adhesion kinase (FAK). Cancer stem cells are an underlying cause of tumor resistance to chemotherapy, recurrence and ultimate disease progression. Research has demonstrated that FAK activity is critical for the growth and survival of cancer stem cells. VS-6063 is currently being studied in the registration-directed COMMAND trial in mesothelioma (www.COMMANDmeso.com), a "Window of Opportunity" study in patients with mesothelioma prior to surgery, a Phase 1/1b study in combination with paclitaxel in patients with ovarian cancer, a trial in patients with KRAS-mutated non-small cell lung cancer and a trial evaluating the combination of VS-6063 and VS-5584 in patients with relapsed mesothelioma. VS-6063 has been granted orphan drug designation for use in mesothelioma in the U.S. and EU.

About VS-4718
VS-4718 is an orally available compound designed to target cancer stem cells through the potent inhibition of focal adhesion kinase (FAK). VS-4718 is currently being studied in a Phase 1 dose escalation study in patients with advanced cancers.

ImmunoCellular Therapeutics Awarded $19.9 Million Grant from California Institute for Regenerative Medicine (CIRM) to Fund ICT-107 Phase 3 Registration Program in Glioblastoma

On September 24, 2015 ImmunoCellular Therapeutics, Ltd. ("ImmunoCellular") (NYSE MKT: IMUC) reported that the governing Board of the California Institute for Regenerative Medicine (CIRM), California’s stem cell agency, has awarded the Company $19.9 million to support the ICT-107 phase 3 registration trial in patients with newly diagnosed glioblastoma (Press release, ImmunoCellular Therapeutics, SEP 24, 2015, View Source [SID:1234507542]). The $19.9 million was granted under the CIRM 2.0 program, a comprehensive collaborative initiative designed to accelerate the development of stem cell-based treatments for people with unmet medical needs. ICT-107 qualified for grant consideration on the basis of being specifically engineered as an immunotherapy that preferentially targets and kills cancer tumor stem cells with the goal of preventing tumor recurrence following standard-of-care treatment.

ImmunoCellular is on track to initiate the phase 3 ICT-107 trial in the fourth quarter of 2015, which will include approximately 120 clinical sites in the US, Europe and Canada, and will recruit about 400 patients. ImmunoCellular has reached agreement with the US FDA on a Special Protocol Assessment (SPA) relative to the primary and secondary endpoints as well as the statistical plan for the phase 3 trial. The $19.9 million CIRM grant funds will be received by the Company over the duration of the trial as specified milestones are achieved.

"We are deeply appreciative to CIRM for their generous support and validation of the therapeutic potential of our ICT-107 dendritic cell-based immunotherapy. We share CIRM’s commitment to advancing potential breakthrough stem cell-based therapies to patients with unmet medical needs," said Andrew Gengos, ImmunoCellular President and Chief Executive Officer. "We are excited to be close to initiating our phase 3 registration trial. With this important grant of non-dilutive capital and our current cash, we are in position to cover the full external cost of conducting the trial and ensure high quality trial execution. Our strategic focus going forward will be on advancing our Stem-to-T-cell immunotherapy platform and pursuing additional related technologies to grow our pipeline – strategies that are key to achieving our goal of building a leading cancer immunotherapy company."

Aduro Biotech Enters Into Definitive Agreement to Acquire Premier Antibody Portfolio and Engineering Capabilities Through Purchase of BioNovion

On September 24, 2015 Aduro Biotech, Inc. (Nasdaq:ADRO) and BioNovion Holding B.V. reported that they have entered into a definitive agreement for Aduro to acquire BioNovion, a privately held monoclonal antibody discovery and development company based in The Netherlands (Press release, Aduro BioTech, SEP 24, 2015, View Source [SID:1234507538]).

The acquisition will further strengthen and expand Aduro’s immunotherapy capabilities to now encompass monoclonal antibodies, including preclinical assets that inhibit clinically validated immune checkpoint pathways. Such immune checkpoint inhibitors could potentially be used alone or in combination with Aduro’s LADD and CDN platforms to increase immunotherapy potency and durability. In addition, BioNovion has a rich pipeline of novel preclinical monoclonal antibodies which inhibit or activate unique immune response pathways that have a role in controlling the progression of diverse malignancies. BioNovion has developed a proprietary technology to rapidly produce a broad library of therapeutic antibodies against validated targets, including PD1 and CTLA-4, as well as several undisclosed novel targets. Also, BioNovion’s pipeline includes an APRIL antagonist and five bispecific antibody programs against immune-oncology targets under collaboration with Genmab using Genmab’s proprietary DuoBody Technology.

"Through this acquisition, we gain access to another immunotherapy platform to enhance our portfolio and potential offerings to patients," said Stephen T. Isaacs, chairman and chief executive officer of Aduro. "Antibodies, particularly immune checkpoint inhibitors, are complementary to our existing immune stimulating technologies with LADD and CDNs. Having these capabilities provides another dimension to our company and uniquely positions us in the immunotherapy field. We are especially pleased to gain the expertise of the founding scientists at BioNovion who have a proven track record in the field of antibody discovery and development, including the discovery of anti PD-1 immune checkpoint inhibitor pembrolizumab earlier in their careers."

"We believe the cutting edge immuno-oncology research and development at Aduro is a perfect complement to our efforts at BioNovion. We envision the blend of our culture and technologies will produce new and powerful combination approaches to treat cancer and other diseases," said Andrea van Elsas, chief scientific officer of BioNovion.

Hans van Eenennaam, chief operating office of BioNovion added, "Both companies operate in a strong academic network in an entrepreneurial culture. We are excited to become a part of their team, to broaden our impact and to accelerate our efforts of getting new compounds into the clinic."

BioNovion specializes in immune oncology antibody discovery. The company’s B-cell selection platform enables full and highly effective exploration of immunoglobulin diversity. In a unique combination with functional screening, the platform has successfully developed leading antibody candidates. In close collaboration with world-class cancer institutes, such as the Dutch Cancer Institute, NKI-AVL in Amsterdam, and the Dana-Farber Cancer Institute in Boston, MA, BioNovion is validating the therapeutic potential of its innovative antibodies in immune oncology.

Upon close of the transaction, Aduro plans to maintain BioNovion’s current 24-person operations as a subsidiary of Aduro in Pivot Park, Oss, the Netherlands, Drs. Andrea van Elsas and Hans van Eenennaam, BioNovion’s chief scientific officer and chief operating officer respectively, will retain the same titles of the subsidiary.

Under the terms of the agreement, Aduro will pay BioNovion 14.5 million Euro in cash and 14.5 million Euro in Aduro stock. In addition, BioNovion shareholders are eligible to receive payments upon the completion of specific regulatory milestones. The transaction is subject to certain closing conditions, which are expected to conclude in October 2015.

Aduro will discuss the transaction on a conference call today at 1:30 p.m. Pacific Time. To participate in the conference call, please dial (855) 283-3941 (domestic) or (330) 863-3274 (international) and refer to conference ID 78990127. Live audio of the conference call will be simultaneously webcast and will be available to members of the news media, investors and the general public under the Investors section of the company’s website at www.aduro.com.

TESARO Announces Inclusion of VARUBI(TM) (rolapitant) in NCCN(R) Antiemesis Guidelines

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.

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.

Celator® Pharmaceuticals Announces Positive Results from R&D Programs

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]).

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."