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 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.

On November 15, 2016 Cellectar Biosciences, Inc. (Nasdaq: CLRB) (the "company"), an oncology-focused, clinical stage biotechnology company, reported it has selected INC Research (Nasdaq: INCR), a leading, global Phase I to IV contract research organization, to oversee its NCI-supported Phase II clinical trial of CLR 131 in patients with multiple myeloma and select hematologic malignancies (Filing, 8-K, Cellectar Biosciences, NOV 17, 2016, View Source [SID1234516654]). The company anticipates that its $2M NCI grant will cover approximately 50 percent of the study’s cost, and the terms of the grant allow Cellectar to pursue an additional $3M for a pivotal Phase III trial of the company’s lead radiotherapeutic compound.

Cellectar plans to leverage the results of its 80-patient, Phase II study to optimally design its pivotal trial of CLR 131 in multiple myeloma and other hematologic malignancies. The multi-armed study will include relapse/refractory patients with multiple myeloma (MM), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), lymphoplasmacytic lymphoma (LPL), marginal zone lymphoma (MZL), mantle cell lymphoma (MCL), and potentially diffuse large B-cell lymphoma (DLBCL), who have been treated with standard therapy for their underlying malignancies. The company recently accelerated its guidance and announced plans to initiate the trial during the first quarter of 2017.

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"INC Research has outstanding experience in cancer clinical research and a strong reputation within the hematology community. With strong investigator relationships, proven operational expertise and a commitment to high-quality data, they are the ideal partner for this important trial," said Jim Caruso, president and CEO of Cellectar. "Given the accelerated initiation of our Phase II study to the first quarter of 2017 and that we will utilize as many as 15 participating sites, we can confidently plan on providing initial efficacy data in the second half of 2017."

About CLR 131
CLR 131 is an investigational compound under development for a range of hematologic malignancies. It is currently being evaluated in a Phase I clinical trial in patients with relapsed or refractory multiple myeloma. The company plans to initiate a Phase II clinical study to assess efficacy in a range of B-cell malignancies in the first quarter of 2017. Based upon preclinical and interim Phase I study data, treatment with CLR 131 provides a novel approach to treating hematological diseases and may provide patients with therapeutic benefits, including overall response rate (ORR), an improvement in progression-free survival (PFS) and overall quality of life. CLR 131 utilizes the company’s patented PDC tumor targeting delivery platform to deliver a cytotoxic radioisotope, iodine-131 directly to tumor cells. The FDA has granted Cellectar an orphan drug designation for CLR 131 in the treatment of multiple myeloma.

About Phospholipid Drug Conjugates (PDCs)
Cellectar’s product candidates are built upon its patented cancer cell-targeting delivery and retention platform of optimized phospholipid ether-drug conjugates (PDCs). The company deliberately designed its phospholipid ether (PLE) carrier platform to be coupled with a variety of payloads to facilitate both therapeutic and diagnostic applications. The basis for selective tumor targeting of our PDC compounds lies in the differences between the plasma membranes of cancer cells compared to those of normal cells. Cancer cell membranes are highly enriched in lipid rafts, which are glycolipoprotein microdomains of the plasma membrane of cells that contain high concentrations of cholesterol and sphingolipids, and serve to organize cell surface and intracellular signaling molecules. PDCs have been tested in over 70 different xenograft models of cancer.

About Relapsed or Refractory Multiple Myeloma
Multiple myeloma is the second most common blood or hematologic cancer with approximately 30,000 new cases in the United States every year. It affects a specific type of blood cells known as plasma cells. Plasma cells are white blood cells that produce antibodies to help fight infections. While treatable for a time, multiple myeloma is incurable and almost all patients will relapse or the cancer will become resistant/refractory to current therapies.

On November 17, 2016 Spectrum Pharmaceuticals (NasdaqGS: SPPI), a biotechnology company with fully integrated commercial and drug development operations with a primary focus in Hematology and Oncology, reported that scientists from MD Anderson Cancer Center will be presenting data from a preclinical study evaluating poziotinib in lung cancer at the 17th International Association for the Study of Lung Cancer (IASLC) World Conference on Lung Cancer taking place in Vienna, Austria, December 4-7, 2016 (Press release, Spectrum Pharmaceuticals, NOV 17, 2016, View Source [SID1234516662]).

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"Poziotinib has shown promising efficacy in preclinical models of non-small cell lung cancer (NSCLC) with exon 20 insertion mutations," said John Heymach, MD, PhD, Chairman, Professor, and David Bruton Junior Chair in Cancer Research, Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center. "Tumors with these mutations have generally not been responsive to approved EGFR inhibitors, and there is an unmet need for better therapies for these patients. Computational modeling suggests that poziotinib may overcome steric hindrance of the drug binding pocket induced by the exon 20 insertion mutations. Based on these results, we are in the process of initiating a Phase 2 study in lung cancer that we plan to start in the near future."

"Poziotinib has already shown promising data in breast cancer, and we are excited that it may now have application in lung cancer as well," said Rajesh C. Shrotriya, MD, Chairman and Chief Executive Officer of Spectrum Pharmaceuticals. "Lung cancer is the leading cause of cancer deaths in the world. Due to the mutations in the genes, lung cancer often becomes unresponsive to treatments. Patients who have exon 20 insertion mutations have few options, if any. We look forward to working closely with MD Anderson Cancer Center to continue development of this drug in this area of unmet medical need."

17th IASLC World Conference on Lung Cancer

Abstract Title:
Poziotinib overcomes de novo resistance of EGFR exon 20 insertion mutations in NSCLC
Oral Presentation Schedule:
December 7, 2016 Session "Novel Strategies in Targeted Therapies"
Abstract Link:
View Source

About Poziotinib

Poziotinib is a novel, oral pan-HER inhibitor that irreversibly blocks signaling through the Epidermal Growth Factor Receptor (EGFR, HER) Family of tyrosine-kinase receptors, including HER1 (erbB1; EGFR), HER2 (erbB2), and HER4 (erbB4), and importantly, also HER receptor mutations; this, in turn, leads to the inhibition of the proliferation of tumor cells that overexpress these receptors. Mutations or overexpression/amplification of EGFR family receptors have been associated with a number of different cancers, including non-small cell lung cancer (NSCLC), breast cancer, and gastric cancer.