On November 21, 2016 Ruga Corporation reported the company’s name change to Aravive Biologics, Inc., and the relocation of its business operations to Houston, Texas (Press release, Aravive Biologics, NOV 21, 2016, View Source [SID1234516733]). The move follows the company’s award of a $20 million grant from the Cancer Prevention & Research Institute of Texas (CPRIT), which is supporting the development of a novel drug candidate, Aravive-S6, as a potential treatment for acute myelogenous leukemia (AML) and solid tumors including ovarian, pancreatic, and breast cancers.

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"We are very pleased to be selected to receive this significant funding from CPRIT and look forward to building our business in Houston’s Texas Medical Center," said Ray Tabibiazar, M.D., President and Chief Executive Officer of Aravive Biologics. "Houston’s vibrant biomedical community is home to many of the top cancer researchers in the United States, including noted experts on AML, our lead hematologic cancer indication. We look forward to accessing this outstanding expertise and growing our presence within the local biomedical community as we advance Aravive-S6 into clinical trials."

"Investing in Aravive Biologics’ clinical development program was an easy decision for CPRIT," said Michael Lang, Chief Product Development Officer of CPRIT. "Aravive-S6 is an innovative compound that has exhibited strong preclinical proof-of-principal, and it addresses a critical unmet medical need. The company also has experienced management with an excellent track record in oncology drug development. Aravive team members are well positioned for success, and we welcome them to the Houston biomedical community."

Aravive-S6 is a novel high-affinity, soluble Fc-fusion protein designed to block the activation of the GAS6- AXL signaling pathway by serving as a decoy that prevents the binding of GAS6 to the AXL receptor on the surface of tumor cells. The AXL receptor, when activated through GAS6 binding, has been shown to act as a "survival switch," a key driver of invasiveness and metastasis, and a critical regulator of therapeutic resistance to cytotoxic chemotherapeutic drugs.

Aravive Biologics has robust and compelling data demonstrating the in vivo efficacy and tolerability of its lead drug candidate in preclinical models of ovarian, renal, breast, and pancreatic cancer, and AML. Aravive-S6 provides high specificity and selectivity for the AXL/GAS6 pathway that other anti-AXL and anti-GAS6 inhibitors have been unable to match; it has greater than 100-fold tighter affinity for GAS6 compared to other anti-AXL and anti-GAS6 antibody candidates in development. Aravive Biologics has also developed a proprietary complementary diagnostic tool that may enable the identification of patients with cancers exhibiting elevated GAS6 levels, which would allow the company to match its drug candidate to those patients most likely to benefit from therapy.

AML is a cancer that begins in bone marrow and affects cells intended to mature into different types of blood cells. Research shows that interaction between the AXL receptor and its GAS6 ligand leads to more severe and invasive cases of AML.

"As patients with AML tend to be older (over 60 years of age) and possibly also in poorer health, they are often unable to tolerate standard, intensive chemotherapy regimens and thus must undergo less rigorous treatment, said Amato Giaccia, Ph.D., Chief Scientific Officer and co-founder of Aravive. "We envision that Aravive-S6 might be administered either as a single agent or as a complement to standard chemotherapy that assists in reducing the survival of cancer cells, which have become "addicted" to AXL/GAS6 signaling, while attempting to achieve or maintain remission."

Each year, approximately 19,950 new cases of AML are diagnosed, primarily in adults, and about 10,430 deaths from the disease, nearly all in adults. About 35% of AML cases exhibit active GAS6/AXL signaling, an incidence which may potentially qualify Aravive-S6 for Orphan Drug Designation.

On November 21, 2016 ImmunoCellular Therapeutics, Ltd. ("ImmunoCellular") (NYSE MKT:IMUC) reported the presentation of updated immune monitoring data from the phase 2 trial of ICT-107 in patients with newly diagnosed glioblastoma (Press release, ImmunoCellular Therapeutics, NOV 21, 2016, View Source [SID1234516718]). Also presented were updated long-term survival data from the phase 1 trial of ICT-107. ICT-107 is a dendritic cell-based immunotherapy targeting multiple tumor-associated antigens on glioblastoma stem cells. ICT-107 is currently being tested in a phase 3 registration trial in patients with newly diagnosed glioblastoma. The updated phase 1 and phase 2 data were presented in two oral sessions on Friday, November 18th, at the 21st Annual Scientific Meeting and Education Day of the Society for Neuro-Oncology, held in Scottsdale, AZ.

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The ICT-107 phase 2 trial was a randomized, double-blind, placebo-controlled phase 2 study of the safety and efficacy of ICT-107 in patients with newly diagnosed glioblastoma following resection and chemoradiation. ICT-107 is an intradermally administered autologous immunotherapy consisting of the patient’s own dendritic cells pulsed with six synthetic tumor-associated antigens: AIM-2, MAGE-1, TRP-2, gp100, HER-2, IL-13Rα2. The placebo control consisted of the patient’s unpulsed dendritic cells. The data from the phase 2 trial indicated a survival advantage in the ICT-107 treated group compared to the control group. The data also showed an association between immune response and survival, especially in HLA-A2 positive (HLA-A2+) patients, which is the target patient population for the ongoing phase 3 registration trial.

The updated immune response data from the phase 2 trial showed that treatment with ICT-107 resulted in the development of a measurable anti-tumor T cell response in some patients, which was associated with survival. Patients that developed the anti-tumor T cell response which was measurable by both ELISpot (to detect viable T cells capable of binding to a target antigen) and multimer testing (to detect T cell binding with higher sensitivity than ELISpot) had improved survival. The data demonstrated that immuno-monitoring can provide an early indication of patients responding to immunotherapy. In the current ongoing phase 3 registration trial of ICT-107, ImmunoCellular plans to perform immuno-monitoring to support the trial.

The data were presented at SNO by Steven J. Swanson, PhD, Senior Vice President, Research, ImmunoCellular Therapeutics, in a presentation titled, "Categorizing immune responders with fusion metrics and simulation for association to survival and progression-free survival with immune response in HLA-A2+ patients with GBM from a phase 2 trial of dendritic cell (DC) immunotherapy (ICT-107)."

Dr. Swanson commented: "ICT-107 is designed to deliver therapeutic benefit by stimulating the patient’s immune system to attack tumor tissue. A first indicator that the immunotherapeutic is active is the production of tumor-specific T cells by the patient. In our SNO presentation, we described our ability to more clearly interpret the immune-monitoring data from the phase 2 trial. The ability to accurately identify negative and positive responses enabled us to better understand which of the patients in our trial generated T cells capable of attacking the tumor. We determined that patients with a T cell response measureable in both the ELIspot assay and through multimer analysis achieved longer survival as compared with patients who did not show a positive response. These data should enable us to better interpret the results of our ongoing phase 3 trial."

Andrew Gengos, ImmunoCellular Chief Executive Officer, said: "The phase 2 trial immune monitoring results indicate that patients who mount a T cell response appear to have improved survival over those without a detectable response. In designing the phase 3 trial, we have made important changes in the protocol to potentially enhance the immune response in ICT-107 treated patients with the goal of optimizing the potential survival outcomes in the trial."

Data from the phase 1 trial of ICT-107 were presented by Surasak Phuphanich, MD, Department of Neurology, Cedars-Sinai in Los Angeles, in a presentation titled "Ten-year follow up with long term remission in patients with newly diagnosed glioblastoma (GBM) treated with ICT-107 vaccine (phase 1)." The phase 1 open-label, single institution trial, which was completed in 2010, included 16 evaluable patients with newly diagnosed glioblastoma. Results of the study were initially published in 2012 (Cancer Immunol Immunother).

Updated survival data presented by Dr. Phuphanich at the 2016 SNO meeting showed that 19% of patients had long-term remission of greater than 8 years, with the longest remission being 9.6 years. Also, 38% of patients demonstrated long-term survival of greater than 8 years, with the longest survivor greater than 10.2 years. Immune response data showed a correlation between survival and cancer-stem-associated expression, and a trend toward greater CD8 T cell cytokine responses in long-term survivors.

ICT-107 Phase 3 Registration Trial Underway

The ongoing phase 3 registrational trial of ICT-107 is designed as a randomized, double-blind, placebo-controlled study of HLA-A2+ subjects, which is being conducted at about 120 sites in the US, Canada and the EU, with plans to randomize at least 500 patients with newly diagnosed glioblastoma. The primary endpoint in the trial is overall survival. Secondary endpoints include progression-free survival and safety, as well as overall survival in the two pre-specified MGMT subgroups.

For patients, families and physicians seeking additional information about the ICT-107 phase 3 trial, please consult www.clinicaltrials.gov.

About ImmunoCellular Therapeutics, Ltd.

On November 21, 2016 RedHill Biopharma Ltd. (NASDAQ:RDHL) (TASE:RDHL) ("RedHill" or the "Company"), a biopharmaceutical company primarily focused on development and commercialization of late clinical-stage, proprietary, orally-administered, small molecule drugs for gastrointestinal and inflammatory diseases and cancer, reported the presentation of a poster relating to YELIVA (ABC294640), the Company’s proprietary, first-in-class, orally-administered sphingosine kinase-2 (SK2) selective inhibitor, at the 2016 EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Molecular Targets and Cancer Therapeutics Symposium, on November 29, 2016, in Munich, Germany (Press release, RedHill Biopharma, NOV 21, 2016, View Source [SID1234516722]).

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The poster, entitled ‘Antitumor and Anti-Inflammatory Effects of the Sphingosine Kinase-2 Inhibitor ABC294640 in Combination with Radiation,’ was authored by scientists from Apogee Biotechnology Corporation ("Apogee"), the original developers of YELIVA.

By inhibiting the SK2 enzyme, YELIVA blocks the synthesis of sphingosine 1-phosphate (S1P), a lipid signaling molecule that promotes cancer growth and pathological inflammation.

RedHill is pursuing and evaluating, with YELIVA, multiple clinical programs in oncology, inflammatory and gastrointestinal indications, as well as potential collaboration opportunities with larger pharmaceutical companies to evaluate YELIVA as an add-on therapy to their existing oncology treatments.

Results from a Phase I study with YELIVA in patients with advanced solid tumors confirmed that the study, conducted at the Medical University of South Carolina Hollings Cancer Center (MUSC), successfully met its primary and secondary endpoints, demonstrating that the drug is well-tolerated and can be safely administered to cancer patients at doses that provide circulating drug levels that are predicted to have therapeutic activity.

A Phase II study with YELIVA for the treatment of advanced hepatocellular carcinoma (HCC) was initiated at MUSC Hollings Cancer Center. The study protocol is under FDA review and enrolment is expected to begin by year end 2016. The study is supported by a $1.8 million grant from the National Cancer Institute (NCI) awarded to MUSC and is intended to fund a broad range of studies on the feasibility of targeting sphingolipid metabolism for the treatment of a variety of solid tumor cancers, with additional funding from RedHill.

A Phase Ib/II study with YELIVA for the treatment of refractory or relapsed multiple myeloma was initiated at Duke University Medical Center. The study is supported by a $2 million grant from the NCI Small Business Innovation Research Program (SBIR) awarded to Apogee, in conjunction with Duke University, with additional support from RedHill.

A Phase I/II clinical study evaluating YELIVA in patients with refractory/relapsed diffuse large B-cell lymphoma was initiated at the Louisiana State University Health Sciences Center in New Orleans in June 2015 and was recently amended to address overall recruitment prospects. The study, which will now also include Kaposi sarcoma patients, is expected to resume by the end of 2016, pending regulatory approval. The study is supported by a grant from the NCI, as well as additional support from RedHill.

A Phase Ib study to evaluate YELIVA as a radioprotectant for prevention of mucositis in head and neck cancer patients undergoing therapeutic radiotherapy is planned to be initiated in the first quarter of 2017.

The ongoing studies with YELIVA (ABC294640) are registered on www.ClinicalTrials.gov, a web-based service by the U.S. National Institute of Health, which provides public access to information on publicly and privately supported clinical studies.

About YELIVA (ABC294640):
YELIVA (ABC294640) is a Phase II-stage, proprietary, first-in-class, orally-administered, sphingosine kinase-2 (SK2) selective inhibitor with anti-cancer and anti-inflammatory activities. RedHill is pursuing with YELIVA multiple clinical programs in oncology, inflammatory and gastrointestinal indications. By inhibiting the SK2 enzyme, YELIVA blocks the synthesis of sphingosine 1-phosphate (S1P), a lipid signaling molecule that promotes cancer growth and pathological inflammation. SK2 is an innovative molecular target for anticancer therapy because of its critical role in catalyzing the formation of S1P, which is known to regulate cell proliferation and activation of inflammatory pathways. YELIVA was originally developed by U.S.-based Apogee Biotechnology Corp. and completed multiple successful pre-clinical studies in oncology, inflammation, GI and radioprotection models, as well as the ABC-101 Phase I clinical study in cancer patients with advanced solid tumors. The development of YELIVA was funded to date primarily by grants and contracts from U.S. federal and state government agencies awarded to Apogee Biotechnology Corp., including the U.S. National Cancer Institute, the U.S. Department of Health and Human Services’ Biomedical Advanced Research and Development Authority (BARDA), the U.S. Department of Defense and the FDA Office of Orphan Products Development.

On November 18, 2016 Argos Therapeutics Inc. (Nasdaq:ARGS) ("Argos"), an immuno-oncology company focused on the development and commercialization of individualized immunotherapies based on the Arcelis technology platform, and its partner Cellthera Pharm ("Cellthera"), a subsidiary of Pharmstandard focused on personalized therapeutics, reported the presentation of data on a murine ("mouse") model developed by Cellthera to determine functional activity of a therapy modeled after Argos’ AGS-003 individualized immunotherapy (Press release, Argos Therapeutics, NOV 18, 2016, View Source [SID1234516678]). The data were presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 31st Annual Meeting, which was held November 11-13 in National Harbor, Maryland.

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The data presented demonstrated the favorable effects of the AGS-003-like therapy as a single agent and in combination with sunitinib and a PD-1 checkpoint inhibitor in a murine model of renal cell carcinoma (RCC). "Our model provides some exciting survival data using an AGS-003-like therapy in a murine kidney cancer model that has proven useful in exploring combinations with other agents in a relevant preclinical setting," said Dr. Alexander Shuster, chairman of Cellthera. In this experiment the agents were administered alone or together 7 days prior to the inoculation of tumor cells and then each group was followed for tumor reduction and survival. Dr. Shuster continued, "The prophylactic mouse data show the superiority of the AGS-003-like therapy as a single agent versus control in both survival and enhanced control of tumor growth. Furthermore, the AGS-003-like therapy when combined with sunitinib or a PD-1 checkpoint inhibitor outperformed each agent alone, and the combination of all three therapies demonstrated the strongest survival advantage."

Argos is currently evaluating AGS-003 in combination with standard of care agents in the pivotal ADAPT Phase 3 clinical trial for the treatment of metastatic renal cell carcinoma (mRCC). Enrollment in this 462-patient study was initiated in February 2013 and completed in July 2015. The Independent Data Monitoring Committee (IDMC) for this study most recently recommended continuation of the study following a meeting in June 2016, with the next IDMC meeting planned for February 2017. In addition, AGS-003 is being studied in Phase 2 investigator-initiated clinical trials as neoadjuvant therapy for RCC and for the treatment of non-small cell lung cancer (NSCLC).

"These mouse data support the expectation of enhanced clinical benefit for the combination of AGS-003 with checkpoint inhibitors and, importantly, also show that amplified total tumor RNA is essential to the anti-tumor activity of Arcelis-derived dendritic cells," noted Dr. Charles Nicolette, chief scientific officer and vice president of research and development at Argos. "Additionally, the observation in mice that the AGS-003-like therapy and sunitinib are each active separately and lead to improved control of tumor growth when combined bodes well for our ongoing Phase 3 ADAPT trial in advanced renal cell carcinoma where AGS-003 is initially being combined with sunitinib."

A copy of this and other Argos-related publications can be found at:
View Source

About the Arcelis Technology Platform
Arcelis is a precision immunotherapy technology that captures both mutated and variant antigens that are specific to each patient’s individual disease. It is designed to overcome immunosuppression by producing a specifically targeted, durable memory T-cell response without adjuvants that may be associated with toxicity. The technology is potentially applicable to the treatment of a wide range of different cancers and infectious diseases and is designed to overcome many of the manufacturing and commercialization challenges that have impeded other personalized immunotherapies. The Arcelis process uses only a small disease sample or biopsy as the source of disease-specific antigens and the patient’s own dendritic cells, which are optimized from cells collected by a leukapheresis procedure. The proprietary process uses RNA isolated from the patient’s disease sample to program dendritic cells to target disease-specific antigens. These activated, antigen-loaded dendritic cells are then formulated with the patient’s plasma and administered via intradermal injection as an individualized immunotherapy.

On November 17, 2016 Triphase Accelerator Corporation, a private drug development company dedicated to advancing novel compounds through Phase 2 proof-of-concept, reported that Celgene Corporation, through an affiliate, has acquired the company’s assets related to its proteasome inhibitor, marizomib (MRZ), which is in development for glioblastoma and relapsed and/or refractory multiple myeloma (Press release, Celgene, NOV 17, 2016, View Source [SID1234527214]).

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Under the terms of the agreement, Celgene will make an upfront payment plus additional regulatory, approval and sales milestone payments. Specific financial terms were not disclosed. "This acquisition validates the potential of marizomib based on early clinical results. Our vision is to become a leading early stage oncology drug development company, and this first opt-in by Celgene brings us a step closer to achieving that goal," said Mohit Trikha, Ph.D., chief scientific officer, Triphase Accelerator Corporation. "Just as importantly, this transaction affords us the opportunity to accelerate our efforts on advancing other assets in our pipeline."

"Consistent with our deep commitment and passion for the patients, glioblastoma is an area of significant unmet medical need, and Celgene is committed to helping these patients. We are pleased with Triphase Accelerator’s rapid and high quality work to date, and we value the exceptional collaboration we have with them to advance marizomib," said Celgene’s President of Hematology Oncology, Michael Pehl.

Going forward Celgene has full responsibility for the development of marizomib and will pay Triphase to complete the ongoing clinical studies with marizomib, including a Phase 1 study in relapsed refractory multiple myeloma, a Phase 2 study in recurrent glioma and a Phase 1 study in newly diagnosed glioma.

About Marizomib
Marizomib is a novel, brain-penetrant proteasome inhibitor, which inhibits all three proteasome subunits.

Triphase Accelerator is developing marizomib in both intravenous (IV) and oral formulations as a proteasome inhibitor for hematologic malignancies and solid tumors. The IV formulation has been evaluated in more than 300 patients in multiple clinical studies in patients with solid and hematologic malignancies, either as a single agent or in combination with dexamethasone, a histone deacetylase inhibitor, or an immunomodulatory drug.

The company is currently evaluating marizomib in a proof-of-concept clinical study in combination with bevacizumab (Avastin) in patients with Grade IV malignant glioma (glioblastoma), and has received Orphan Drug designation for marizomib in glioblastoma in the United States from the FDA. In addition, Triphase Accelerator is currently developing marizomib in combination with pomalidomide and dexamethasone in patients with relapsed and refractory multiple myeloma, and has received Orphan Drug designation for marizomib in multiple myeloma in the United States and the European Union. Triphase Accelerator is also evaluating an oral formulation in preclinical studies.

Marizomib has not been approved for any use in any country.