On June 1, 2016 Xcovery, a developer of targeted therapeutics for cancer, reported that data on the plasma genotyping of patients enrolled in its expansion Phase I/II trial of ensartinib (X-396), the Company’s lead ALK inhibitor drug candidate, in patients with anaplastic lymphoma kinase (ALK) positive non-small cell lung cancer (NSCLC) will be presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting 2016, which is being held from June 3 – 7, 2016 in Chicago, Illinois (Press release, Xcovery, JUN 1, 2016, View Source [SID:1234512947]). The presentation details are as follows:

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Poster Title: Plasma genotyping of patients enrolled on the expansion phase I/II trial of X-396 in patients (pts) with ALK+ non-small cell lung cancer (NSCLC)
Poster Session: Lung Cancer – Non-Small Cell Metastatic
Poster Time: Sunday, June 5, 2016 from 8:00am – 11:30am CDT
Session Location: McCormick Place, Hall A
Poster Board Number: 379
Abstract Number: 9056
Presented by: Leora Horn, MD, MSc, Vanderbilt University Medical Center
Additional abstract details can be found at abstracts.asco.org.

About Ensartinib (X-396)

Xcovery’s lead asset is Ensartinib (X-396), a small molecule, anaplastic lymphoma kinase (ALK) inhibitor. It is being studied in the eXalt2 Study, a Phase II trial for the treatment of ALK-positive non-small cell lung cancer (NSCLC). The eXalt2 Study is currently enrolling patients. To learn more, visit: www.xalt2study.com or ClinicalTrials.gov under trial identifier NCT01625234.

About NSCLC and ALK

Lung cancer is the second most common type of cancer identified in the United States with an estimated 221,000 new diagnoses expected in 2015. Non‐small cell lung cancer (NSCLC) is the most common type of lung cancer, accounting for an estimated 85‐90% of the lung cancer cases. The anaplastic lymphoma kinase (ALK) gene is located on chromosome 2 and rearrangement of the ALK gene can lead to its activation or expression, therefore increasing a person’s chance of developing certain types of cancer, including NSCLC. Between three and seven percent of patients with NSCLC have the ALK rearrangement, making this a molecular target warranting investigation for NSCLC patients.

On June 1, 2016 CEL-SCI Corporation (NYSE MKT: CVM) ("CEL SCI" or the "Company") reported that during the month of May it has enrolled 19 patients in its ongoing Phase 3 trial of its investigational immunotherapy Multikine* (Leukocyte Interleukin, Injection) in patients with advanced primary head and neck cancer (Press release, Cel-Sci, JUN 1, 2016, View Source [SID:1234512946]). Total patient enrollment for the trial is now 816 as of May 31, 2016.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

About the Multikine Phase 3 Study

The Multikine Phase 3 study is enrolling patients with advanced primary (not yet treated) squamous cell carcinoma of the head and neck. The objective of the study is to demonstrate a statistically significant improvement in the overall survival of enrolled patients who are treated with the Multikine treatment regimen plus standard of care ("SOC") vs. subjects who are treated with SOC only.

About Multikine

Multikine is an investigational immunotherapeutic agent that is being tested in an open-label, randomized, controlled, global pivotal Phase 3 clinical trial as a potential first-line treatment for advanced primary squamous cell carcinoma of the head and neck. Multikine is designed to be a different type of therapy in the fight against cancer: one that appears to have the potential to work with the body’s natural immune system in the fight against tumors.

Multikine is also being tested in a Phase 1 study under a Cooperative Research and Development Agreement ("CRADA") with the U.S. Naval Medical Center, San Diego, and at University of California, San Francisco (UCSF), as a potential treatment for peri-anal warts in HIV/HPV co-infected men and women. Dr. Joel Palefsky, a world-renowned scientist and Key Opinion Leader (KOL) in human papilloma virus (HPV) research and the prevention of anal cancer, is the Principal Investigator at UCSF, which was added to the study in July 2015.

CEL-SCI has also entered into two additional co-development agreements for up to $3 million each with Ergomed Clinical Research Limited to further the development of Multikine for cervical dysplasia/neoplasia in women who are co-infected with HIV and HPV and for peri-anal warts in men and women who are co-infected with HIV and HPV.

On June 1, 2016 BRCA Share, a public-private BRCA gene datashare initiative, reported the public release of a large collection of new data on genetic variants in the BRCA1 and BRCA2 genes (Filing, 8-K, LabCorp, JUN 1, 2016, View Source [SID:1234512944]). Mutations of these genes raise the risk of breast, ovarian and other cancers. The findings are to be presented today at the 6th International Biennial Meeting of Human Variome Project Consortium (HVP6) held at UNESCO headquarters in Paris.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

BRCA Share was co-founded by Quest Diagnostics and the French National Institute of Health and Medical Research (Inserm) in April 2015, with Laboratory Corporation of America Holdings (LabCorp) as the first commercial participant. The goal of the initiative is to share clinical, genetic, epidemiological and biological data on BRCA variants, particularly variants of uncertain significance, in order to improve the quality of laboratory diagnostics to better predict which individuals are at risk of developing hereditary breast and ovarian cancers, and to accelerate research on BRCA gene mutations. BRCA Share builds on a BRCA gene-data curation process developed by Inserm, Institut Curie, and Unicancer Genetic Group (UGG) with associated University Hospital Centers, using data developed over a decade of BRCA patient testing by the 16 UGG laboratories in France together with the same associated University Hospital Centers.

This new release adds variants from Quest Diagnostics and LabCorp, two clinical testing laboratory companies operating primarily in the United States, to the collection previously developed by Inserm through the Universal Mutation Database (UMD) project in France. The BRCA Share database now contains over 6,200 total BRCA variants, an increase of nearly 30% compared to the previous Inserm UMD database. Of these variants, 334 are newly identified pathogenic or likely pathogenic, increasing by about 20% the total number of pathogenic or likely pathogenic variants to 1,826.

The data include 375 BRCA gene variants whose role in cancer risk was previously uncertain. Of these, 93% are now classified as neutral or likely neutral, while the remaining 7% are now classified as pathogenic or likely pathogenic. Neutral gene variants are generally considered benign, or non-disease-causing, while pathogenic variants are gene mutations that increase an individual’s cancer risk.

The findings are significant because they will contribute to well-informed patient management strategies. A patient with a pathogenic BRCA gene test result may consider options to reduce the risk of developing cancer in the future, including increased screening or prophylactic mastectomy or oophorectomy (removal of breasts or ovaries). Participating commercial laboratories notify physicians of changes in classifications for affected patients.

The BRCA Share Initiative is intended to help scientists, physicians and laboratory experts improve the interpretation of BRCA gene mutations for patient testing and cancer research. With the release of the new set of variants and clinical data, BRCA Share is the largest database providing access to high-quality BRCA genetic data that has been researched and curated to determine clinical significance. Other public BRCA data initiatives collect a mix of curated and uncurated BRCA variant information from participating laboratories. Data curation is an essential step in maximizing the likelihood that data is clinically appropriate and actionable. Variants that are curated have been individually researched and categorized to determine the likelihood that they confer increased cancer risk. Advances in scientific knowledge may lead to new variant discoveries and reclassifications.

"We created BRCA Share to accelerate BRCA science and bring clarity to BRCA patient testing, and in short order, that’s exactly what this initiative has done," said Charles (Buck) Strom, M.D., Ph.D., FAAP, FACMG, HCLD, vice president, genetics and genomics, Quest Diagnostics. "This doesn’t just benefit patients of Quest, or LabCorp, or Inserm’s participating labs. This initiative benefits anyone in the global medical community seeking robust analysis of BRCA genetics based on shared pooling of clinical-grade data and expertise."

"The promise of BRCA Share was to significantly improve BRCA diagnostics and enhance patient care and treatment," said Marcia Eisenberg, Ph.D., chief scientific officer of LabCorp Diagnostics. "BRCA Share has already delivered on that promise, and it will help physicians and patients make more informed monitoring and treatment decisions that can improve health and improve lives."

"BRCA Share demonstrates that public-private data sharing collaborations, funded by commercial parties, can hasten advances in medical research that will benefit patients. This first experience encourages Inserm Transfert to continue its development strategy on health databases whenever it is relevant with industrial partners," said Pascale Augé, Ph.D., CEO, Inserm Transfert.

"In little more than a year, this initiative has provided more than 1,300 new variants and has lifted the veil of uncertainty from 375 variants and identified 334 likely cancer risk variants," added Prof. Christophe Béroud, Pharm.D., Ph.D., leader of the "Genetics and Bioinformatics" research team, Inserm/Aix Marseille University (AMU) UMR_S910.

Research entities and individuals with a research-only focus on BRCA — including physicians and patients — can participate in BRCA Share at no charge. The new data is available, beginning today, at View Source and View Source . Commercial laboratories may participate in BRCA Share by paying an annual fee to Inserm determined on a sliding scale to fund research and administrative expenses.

Since the launch of BRCA Share, nearly 1,000 scientists from 49 countries have registered to access BRCA Share for research purposes.

To participate, BRCA Share commercial laboratory members must submit their BRCA variant data, which Inserm’s variant team then researches and curates. When a variant is curated and/or reclassified, Inserm notifies BRCA Share members and uploads the new data into BRCA Share. BRCA Share’s participating laboratories may then begin to use the new data to inform decisions about patient test results.

Members of BRCA Share are free to also share their BRCA data with other datashare initiatives.

On June 1, 2016 Regulus Therapeutics Inc. (NASDAQ: RGLS), a biopharmaceutical company leading the discovery and development of innovative medicines targeting microRNAs (miR), reported that it has expanded its clinical trial collaboration agreement with GSK (NYSE: GSK) for the development of RG-101, Regulus’ wholly-owned, GalNAc-conjugated anti-miR that targets miR-122 (Press release, Regulus, JUN 1, 2016, View Source [SID:1234512943]). In the expanded collaboration, the companies plan to conduct a multi-centered, randomized, dose-ranging Phase II study evaluating the combination of RG-101 and GSK’s long-acting parenteral ("LAP") formulation of GSK2878175 as a potential single-visit cure in patients chronically infected with HCV. This study will be conducted outside the United States and is planned to begin in the fourth quarter of 2016. Based on predicted enrollment rates, interim results from this expanded collaboration should be available in the second half of 2017, enabling a potential initiation of a pivotal study in late 2017. As with the initial collaboration, both parties will share equally in the costs associated with the study. Neither Regulus nor GSK has any further obligations or commitments to each other beyond this expanded clinical collaboration agreement.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We are very pleased to expand our working collaboration with GSK. This is an important next step to advance the scientific understanding of the potential for a combination therapy to achieve a single-visit cure for HCV," said Paul Grint, M.D., President and CEO of Regulus. "The market research conducted to date indicates that a potential single visit cure would be a highly preferred product profile to existing regimens."

Zhi Hong, Senior Vice President and Head of the Infectious Diseases Therapy Area, GSK, commented, "We are excited about the potential of this combination to provide people living with HCV a new treatment option that could be delivered in a single visit. Together with Regulus, we are taking another step forward to proving this novel concept."

Earlier this year, pursuant to the initial GSK-Regulus clinical trial collaboration agreement, Regulus began enrolling patients in an open-label Phase II clinical trial combining RG-101 and GSK2878175 for the treatment of HCV to evaluate the potential to achieve sustained viral responses post treatment with a single subcutaneous administration of 4 mg/kg of RG-101 in combination with daily oral administrations of 20 mg of GSK2878175 for up to 12 weeks in treatment-naïve patients chronically infected with HCV genotypes 1 and 3. Regulus and GSK anticipate reporting interim results from this study by year-end.

About microRNAs

The discovery of microRNAs in humans during the last decade is one of the most exciting scientific breakthroughs in recent history. microRNAs are small RNA molecules, typically 20 to 25 nucleotides in length, that do not encode proteins but instead regulate gene expression. More than 800 microRNAs have been identified in the human genome, and over two-thirds of all human genes are believed to be regulated by microRNAs. A single microRNA can regulate entire networks of genes. As such, these molecules are considered master regulators of the human genome. microRNA expression, or function, has been shown to be significantly altered or dysregulated in many disease states, including oncology, fibrosis, metabolic diseases, immune-inflammatory diseases and HCV. Targeting microRNAs with anti-miRs, chemically modified, single-stranded oligonucleotides, offers a unique approach to treating disease by modulating entire biological pathways and may become a new and major class of drugs with broad therapeutic application.

On June 1, 2016 Nektar Therapeutics (Nasdaq: NKTR) reported that it has entered into an agreement with Daiichi Sankyo Europe for Nektar’s investigational drug therapy, ONZEALD (etirinotecan pegol, NKTR-102), which has completed a Phase 3 clinical trial (the BEACON study) in patients with advanced breast cancer (Filing, 8-K, Nektar Therapeutics, JUN 1, 2016, View Source [SID:1234512942]). The agreement grants Daiichi Sankyo Europe exclusive rights to market ONZEALD in Europe (EEA), Switzerland and Turkey. Nektar Therapeutics will retain rights to ONZEALD in the United States and the rest of the world.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Under the terms of the agreement, Nektar Therapeutics is entitled to an upfront payment of $20 million as well as an additional $60 million in milestone payments, based upon the achievement of European regulatory milestones and European sales of ONZEALD. Nektar is also entitled to significant double-digit royalties on net sales in Europe.

"This new collaboration with Daiichi Sankyo Europe allows Nektar to advance ONZEALD to a potential conditional approval and availability in Europe as early as next year, and also enables us to retain ownership of the drug in the U.S. and rest of world," said Howard W. Robin, President and Chief Executive Officer of Nektar Therapeutics. "We are pursuing conditional approval for ONZEALD based on highly promising data from our Phase 3 BEACON clinical trial in the pre-specified subgroup of patients with advanced breast cancer who have a history of brain metastases. A diagnosis of brain metastases in women with advanced breast cancer is devastating and there are no therapies approved to treat this specific patient population."

Nektar plans to submit an MAA filing in June 2016 seeking conditional approval from the European Medicines Agency (EMA) for the use of ONZEALD in the treatment of patients with advanced breast cancer and brain metastases. On May 26, 2016, the Committee for Medicinal Products for Human Use (CHMP) granted an accelerated assessment procedure for the planned ONZEALD filing, which provides for an accelerated MAA review timeline.

Nektar will be responsible for sponsoring and funding the confirmatory trial which will support the Marketing Authorization Application (MAA) filing for ONZEALD in Europe. The data from the confirmatory trial can be used by Nektar for a potential U.S. new drug application (NDA) filing for ONZEALD.

Breast cancer is the most frequently diagnosed cancer in women worldwide with nearly 1.7 million new cases diagnosed in 2012.1 There are approximately 250,000 newly-diagnosed cases of breast cancer in the United States and 470,000 in Europe each year. 1 Approximately 10-30 percent of patients with advanced breast cancer are also diagnosed with brain metastases. 2

Nektar’s planned MAA filing is based upon data from a subgroup of patients from the completed BEACON study of single-agent ONZEALD in patients with advanced breast cancer. In this subgroup of 67 patients who also had a history of brain metastases, treatment with single-agent ONZEALD resulted in an improvement in median overall survival (OS) of 5.2 months compared to treatment with a single-agent chemotherapy of physician’s choice (TPC) (10 months vs. 4.8 months, P < 0.01). TPC included a choice of ixabepilone, vinorelbine, gemcitabine, eribulin or a taxane. In the planned primary analysis for the overall patient population in the BEACON study, ONZEALD median OS was 2.2 months longer than TPC (12.4 months vs. 10.3 months, P= 0.08).3 In the overall patient population in the BEACON study, fewer patients in the ONZEALD arm had grade 3 or worse adverse events (AEs) than those in the TPC arm (204 [48%] vs. 256 [63%]; p<0·0001).3 The most common grade 3 and above AEs observed with ONZEALD were diarrhea (9.6%), neutropenia (9.6%), anemia (4.7%) and fatigue (4.5%). The most common grade 3 and above AEs observed with TPC were neutropenia (30.8%), anemia (4.7%), and dyspnea (4.4%).

In order to satisfy the EMA’s requirement for additional controlled data with the MAA for conditional approval, Nektar will sponsor a global, randomized Phase 3 trial of ONZEALD in approximately 350 patients with advanced breast cancer and brain metastases. The trial will compare ONZEALD to TPC and the primary endpoint in the trial will be OS. The trial will include a pre-specified interim analysis for OS which is to be conducted after 130 events have been observed in the trial. The U.S. Food and Drug Administration has also reviewed the Phase 3 study design with the Statistical Analysis Plan, and indicated the trial could serve as a potential registrational study by Nektar for purposes of seeking approval of ONZEALD to treat this patient population in the U.S.
The EMA may grant conditional marketing authorization when the potential treatment addresses a severely debilitating disease with an unmet medical need, has a positive benefit to risk profile, and the benefits to public health of its immediate availability outweigh the risks inherent in the fact that additional data are still required. Ongoing or new studies must be completed with the objective of confirming that the benefit to risk balance is positive. A conditional approval granted by the EMA is renewed on an annual basis until all obligations have been fulfilled, at which point a full approval may be granted by the EMA.

For additional terms and conditions of the licensing agreement between Nektar and Daiichi Sankyo Europe, please refer to the Current Report on Form 8-K filed today with the Securities and Exchange Commission.

About ONZEALD (etirinotecan pegol) (formerly NKTR-102)

ONZEALD is the first long-acting topoisomerase I inhibitor with an extended half-life and a unique structure that is designed to concentrate the drug in tumors. In patients, ONZEALD leads to greatly prolonged plasma SN38 exposure compared with irinotecan (elimination half-life of 37 days compared with 2 days) yet peak SN38 concentrations are at least 5- to 10-times less, which may also result in a favorable tolerability profile. ONZEALD was evaluated in a Phase 3, open-label, randomized, multicenter study (the BEACON study) that enrolled 852 women with locally recurrent or metastatic breast cancer, who have previously been treated with an anthracycline, taxane and capecitabine therapies.