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Review Of Delcath’s CHEMOSAT Accepted For Publication In Advances In Therapy

On October 17, 2016 Delcath Systems, Inc. (NASDAQ: DCTH), an interventional oncology Company focused on the treatment of primary and metastatic liver cancers, reported that a review of research conducted with the Delcath Hepatic CHEMOSAT Delivery System (CHEMOSAT) has been accepted for publication by the prestigious medical journal, Advances in Therapy (Press release, Delcath Systems, OCT 17, 2016, View Source;p=RssLanding&cat=news&id=2212191 [SID1234515872]). The retrospective study, "Chemosaturation Percutaneous Hepatic Perfusion: A Systemic Review," was conducted by a team led by Dr. Arndt Vogel of the University of Hanover in Germany, and resulted from a CHEMOSAT Experts Forum convened by Delcath in February 2015.

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"This retrospective study originated as a white paper produced by our Experts Panel in 2015 as a means of sharing information, recent research results, and clinical experiences using CHEMOSAT to treat primary and metastatic liver cancers," said Jennifer K. Simpson, Ph.D., MSN, CRNP, President and Chief Executive Officer of Delcath. "We are pleased that Dr. Vogel and his teams’ work has been accepted for publication in such a prestigious journal as Advances in Therapy, and that the potential for CHEMOSAT to treat primary and metastatic liver cancers as identified by our experts will reach a wider audience."

DelMar Pharmaceuticals Presents Overview of VAL-083’s Unique Anticancer Mechanism at the European Association of Neuro-Oncology (EANO) Annual Meeting

On October 17, 2016 DelMar Pharmaceuticals, Inc. (NASDAQ: DMPI) ("DelMar" and the "Company"), a biopharmaceutical company focused on the development and commercialization of new cancer therapies, reported that the Company presented additional data regarding VAL-083’s unique anti-cancer mechanism on Saturday October 15, 2016 at the 12th Meeting of the European Association of Neuro-Oncology (EANO) in Mannheim, Germany (Press release, DelMar Pharmaceuticals, OCT 17, 2016, View Source [SID1234515856]).

DelMar’s poster presentation can be viewed at View Source

"These data further differentiate VAL-083’s mechanism of action against cancer from the current standard of care in the treatment of glioblastoma multiforme (GBM), the most common and aggressive form of brain cancer," said Dr. Dennis Brown, DelMar’s Chief Scientific Officer.

Temozolomide, the current front-line therapy generates its anti-tumor activity by methylation of the O6-position of guanine, resulting in a base-pair mismatch which can be lethal to the tumor cell if not repaired. The majority of patients exhibit a high expression of the DNA repair enzyme "MGMT", which readily repairs temozolomide-derived DNA damage leading to tumor resistance and treatment failure. GBM patients failing temozolomide have a very poor prognosis with median survival of 6 – 9 months.

VAL-083 attacks the tumor’s DNA at a different location and in a different way, rapidly forming durable cross links at the N7-position of guanine. These cross-links are not repaired by MGMT.

"These cross-links result in double-strand breaks during DNA replication which are more potent and more difficult for the cell to repair in comparison to the DNA damage conferred by temozolomide. In particular, MGMT does not act against the type of DNA damage resulting from VAL-083 treatment," added Dr. Brown.

"The EANO meeting provided an opportunity to introduce our VAL-083 to European neuro-oncology thought-leaders," said Jeffrey Bacha chairman & CEO of DelMar. Expanding our relationships with key opinion leaders on a global basis will provide opportunities for collaboration as we expand the development of VAL-083 beyond our current focus in the refractory, Avastin-failed population.

"Importantly, poor patient outcomes due to MGMT-mediated chemo-resistance were a consistent theme throughout the conference. Based on our research, we believe VAL-083’s unique mechanism and ability to circumvent the tumor’s MGMT resistance mechanism may provide a foundational opportunity as a new treatment paradigm," stated Mr. Bacha.

About VAL-083
VAL-083 is a "first-in-class," small-molecule chemotherapeutic. In more than 40 Phase I and II clinical studies sponsored by the U.S. National Cancer Institute, VAL-083 demonstrated clinical activity against a range of cancers including lung, brain, cervical, ovarian tumors and leukemia both as a single-agent and in combination with other treatments.

VAL-083 has received an orphan drug designation in Europe for the treatment of malignant gliomas and the U.S. FDA Office of Orphan Products has granted an orphan designation to VAL-083 for the treatment of glioma, medulloblastoma and ovarian cancer.

The Company has completed a successful end of Phase II meeting with the US FDA and plans to advance VAL-083 into a pivotal clinical trial for GBM patients following bevacizumab failure. DelMar presented data from its Phase I/II clinical trial in refractory GBM at the 2016 American Association of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual meeting demonstrating that the median survival of 22 patients receiving an assumed therapeutic dose of VAL-083 (≥20mg/m2) was 8.35 months following bevacizumab (Avastin) failure compared to published literature where survival of approximately two to five months has been reported.

DelMar’s advanced development program will feature a single multi-center randomized Phase III study measuring survival outcomes compared to a "physicians’ choice" control, which, if successful, would serve as the basis for a New Drug Application (NDA) submission for VAL-083. The control arm will consist of a limited number of salvage chemotherapies currently utilized in the treatment of Avastin-failed GBM. The final pivotal trial design will be confirmed with the FDA following further discussions with the Company’s clinical advisors.

In addition to the pivotal trial, DelMar also plans to initiate two separate Phase II clinical trials in earlier-stage GBM patients.

In collaboration with the University of Texas MD Anderson Cancer Center: A non-comparative, biomarker-driven, Phase II study to determine if treatment of MGMT-unmethylated recurrent GBM with VAL-083 or CCNU improves overall survival at 9 months, compared to historical control in bevacizumab naïve patients. (clinicaltrials.gov identifier: NCT02717962)
In collaboration with Sun-Yat Sen University and Guangxi Wuzhou Pharmaceutical (Group) Co.: A single arm Phase II clinical trial to confirm the tolerability of DelMar’s dosing regimen in combination with radiotherapy (XRT) and to explore the activity of VAL-083 in newly diagnosed MGMT-unmethylated GBM patients whose tumors are known to express high levels of MGMT.
DelMar believes that data from these clinical trials, if successful, will form the basis of a new paradigm in the treatment for all GBM patients who fail, or whose tumors exhibit features that make them unlikely to respond to, currently available chemotherapy.

In addition to its clinical research in GBM, DelMar believes that its research supports a unique mechanism of action for VAL-083 and that these data support the potential of VAL-083 as a new chemotherapy that may offer improved outcomes in the treatment of GBM and other solid tumors in patients whose tumors have failed or exhibit features that make them resistant to or unlikely to respond to current standard-of-care chemotherapy.

Myriad Will Present New Data on Its Variant Classification Program at the ASHG Annual Meeting

On October 17, 2016 Myriad Genetics, Inc. (MYGN), a leader in molecular diagnostics and personalized medicine, reported it will present four new studies at the American Society of Human Genetics Annual Meeting being held Oct. 18-22, 2016 in Vancouver, British Columbia (Press release, Myriad Genetics, OCT 17, 2016, View Source [SID:SID1234515854]). The research being presented highlights the clinical utility of Myriad’s myVision Variant Classification Program and myRisk Hereditary Cancer gene panel test.

"Precision medicine is dependent on the accuracy of the information being provided to patients, and Myriad’s myVision is the most advanced variant classification program available to determine whether a patient’s genetic mutation is benign or deleterious," said Johnathan Lancaster, M.D., Ph.D, chief medical officer, Myriad Genetic Laboratories. "At ASH (Free ASH Whitepaper)G, we are excited to present four new studies, which advance the state of the art of genetic testing and meet the scientific needs of researchers and clinicians."

Below is a list of the featured presentations at ASH (Free ASH Whitepaper)G (#ASHG2016):

Platform Presentations

Title: PMS2CL-hybrid Alleles Containing PMS2 Sequence and Other PMS2CL-derived Large Rearrangements: The Importance of Correct Interpretation of Dosage Alteration Analysis in PMS2.
Presenter: Nanda Singh.
Date: Thursday, October 20, 2016: 12:00 p.m. PT.
Platform: 137, Ballroom C.
Title: NGS Facilitates Identification of Retrotransposon Insertional Mutations in Hereditary Cancer Genes.
Presenter: Yaping Qian.
Date: Thursday, October 20, 2016: 12:45 p.m. PT.
Platform: 156, Room 115.
Poster Presentations

Title: Characterization of TP53 Sequencing Variants Initially Detected in Peripheral Blood Using Next Generation Sequencing Analysis.
Presenter: Debora Mancini-DiNardo.
Date: Wednesday, October 19, 2016: 2:00 – 3:00 p.m. PT.
Poster: 781W, Exhibit Hall B.
Title: Diagnostic Detection, Characterization & Classification of Partial Single Exon Deletions in Hereditary Cancer Genes.
Presenter: Benjamin Roa.
Date: Wednesday, October 19, 2016: 2:00 – 3:00 p.m. PT.
Poster: 763W, Exhibit Hall B.
For more information about these presentations, including a complete list of abstracts and presentations, please visit the ASH (Free ASH Whitepaper)G website at View Source

Shire Granted EU Marketing Authorization of ONIVYDE®, In Combination With 5-Fluorouracil (5-FU) And Leucovorin (LV), For The Treatment of Metastatic Adenocarcinoma Of The Pancreas in Adult Patients Who Have Progressed Following Gemcitabine-Based Therapy

On October 18, 2016 Shire plc (LSE: SHP, NASDAQ: SHPG) reported that the European Commission (EC) has granted Marketing Authorization of ONIVYDE (pegylated liposomal irinotecan hydrochloride trihydrate), also known as nal-IRI or MM-398, for the treatment of metastatic adenocarcinoma of the pancreas, in combination with 5-fluorouracil (5-FU) and leucovorin (LV), in adult patients who have progressed following gemcitabine-based therapy (Press release, Shire, OCT 18, 2016, View Source [SID1234515897]). ONIVYDE is the first and only approved treatment option for this patient population.

With this approval, Shire is authorized to market ONIVYDE in the 28 Member States of the European Union (EU), as well as in Iceland, Liechtenstein and Norway. ONIVYDE was previously approved in the U.S. by the Food and Drug Administration (FDA), in October 2015.

"As the only treatment for metastatic pancreatic cancer following gemcitabine-based therapy that may improve patient survival, ONIVYDE is the first innovation that offers the potential to improve outcomes for this challenging patient population," said Philip J. Vickers, Ph.D., Global Head of Research and Development at Shire. "The approval of ONIVYDE marks a significant step forward in Shire’s focus to develop and commercialize treatments that represent the most promising science in oncology."

Pancreatic cancer is the fourth leading cause of cancer death in the regioniii and there are limited treatment options available.iv In September 2015, the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) stated that use of MM-398 (ONIVYDE) when available in all countries, may be the best option for patients following gemcitabine-based therapy.v Gemcitabine-based therapy is commonly used as a first-line treatment for patients with metastatic disease or locally advanced disease that cannot be treated with surgery, or as adjuvant therapy.vi

"The burden of pancreatic cancer for patients, their families and healthcare providers is profound and the treatment options available, especially to those with metastatic disease, have not substantially evolved for decades," said Alfredo Carrato, M.D., Professor of Medical Oncology at Alcala University and Director of the Medical Oncology Department at Ramon y Cajal University Hospital in Madrid, Spain. "With the approval of ONIVYDE, we have the first and only treatment approved for metastatic adenocarcinoma following gemcitabine-based therapy, and an option that may improve patient survival. This is an important advance for the field of oncology and the lives of those impacted by pancreatic cancer."

The Marketing Authorization is based on the data from the pivotal, Phase 3 NAPOLI-1 study that demonstrated ONIVYDE combined with 5-FU/LV significantly improved overall survival (OS) (primary endpoint), as well as progression-free survival (PFS) and objective response rate (ORR) relative to the 5-FU/LV control arm (secondary endpoints). In the trial, the most common Grade 3 or higher adverse events with greater than five percent difference in patients receiving ONIVYDE and 5-FU/LV, versus 5-FU/LV alone, were neutropenia, fatigue, diarrhoea, and vomiting.ii

About Pancreatic Cancer
Pancreatic cancer is a significantly underserved disease in Europe and is almost always fatal.vi At the time of diagnosis, more than 80 percent of people diagnosed with pancreatic cancer have metastatic disease or locally advanced disease that cannot be removed with surgery.vii The disease has a median five-year survival rate of about 5 percent,v and an overall median survival of typically less than a year, as supported by real-world European systematic review.vi The only curative treatment for pancreatic cancer is surgical resection in the primary stage, which can improve five-year survival to 10 percent.viii

The signs and symptoms of pancreatic cancer are non-specific (common presenting symptoms include jaundice, abdominal pain, weight loss, steatorrhoea, and new-onset diabetes)v and may not appear until the disease has spread locally or metastasized.vii Therefore, most patients are not candidates for surgery upon diagnosis.vii

Even though it accounts for less than three percent of all cancer cases,ix pancreatic cancer is the seventh leading cause of cancer death worldwide,x and the fourth in Europe.iv Worldwide, pancreatic cancer prognosis is typically poor, with an estimated 337,900 new cases and 330,400 deaths each year.xi

About ONIVYDE (nal-IRI)
ONIVYDE is a first-of-its-kind formulation (encapsulation) of irinotecan in a long-circulating liposomal form designed to improve delivery of length of tumor exposure to irinotecan and its active metabolite SN-38. Studies have suggested that encapsulation helps to improve delivery of irinotecan to tumors, such as metastatic pancreatic cancer.xii

In the pivotal Phase 3 NAPOLI-1 study, ONIVYDE demonstrated significantly improved overall survival in adult patients with metastatic ADENOCARCINOMA of the pancreas who have progressed following gemcitabine-based therapy.ii Gemcitabine, both as monotherapy as well as in combination, is commonly used in the first-line treatment of locally advanced and/or metastatic pancreatic adenocarcinoma, as well as in the adjuvant (treatment after surgery) and neo-adjuvant (treatment before surgery) settings.ii

Shire is responsible for the development and commercialization of ONIVYDE outside of the United States and Taiwan under an exclusive licensing agreement with Merrimack Pharmaceuticals, Inc. (NASDAQ: MACK). Merrimack markets ONIVYDE in the United States after having received US Food and Drug Administration (FDA) approval in October 2015 for the treatment of patients with metastatic adenocarcinoma of the pancreas who have progressed following treatment with gemcitabine-based therapy. ONIVYDE product license was granted in Taiwan in March 2016, where PharmaEngine holds the commercialization rights.

About NAPOLI-1ii
NAPOLI-1 is the first global, randomized open-label Phase 3 trial to show extended overall survival in metastatic pancreatic adenocarcinoma after gemcitabine-based therapy through treatment with ONIVYDE combined with 5-FU and LV. NAPOLI-1 is the largest Phase 3 study in this setting to date showing overall survival benefit. Patients were enrolled at 76 sites in 14 countries across North America, Europe, Asia, South America, and Australia. The study evaluated ONIVYDE (80mg/m2) in combination with 5-FU/LV administered intravenously every two weeks and as a monotherapy (120 mg/m2) administered every three weeks. Each ONIVYDE containing arm was compared to a control arm of 5-FU/LV.

NAPOLI-1 met the following primary and secondary endpoints by demonstrating that ONIVYDE combined with 5-FU/LV significantly improved OS, progression-free survival (PFS) and objective response (OR) compared to 5-FU/LV alone in patients with metastatic pancreatic cancer.i ONIVYDE plus 5-FU/LV demonstrated a significant increase in median overall survival versus 5-FU/LV alone: 6.1 months vs 4.2 months (based on a non-stratified hazard ratio [HR] of 0.67; 95% CI 0.49-0.92, p=0.012).i, ii

Grade 3 or 4 adverse events that occurred most frequently in the 117 patients assigned ONIVYDE plus 5-FU/LV were neutropenia (32 [27%]), diarrhoea (15 [13%]), vomiting (13 [11%]), and fatigue (16 [14%]).ii

Important Safety Information
The most common adverse reactions (incidence ≥20 percent) seen with ONIVYDE in combination with 5-FU/LV were: diarrhoea, nausea, vomiting, decreased appetite, neutropenia, fatigue, asthenia, anaemia, stomatitis, and pyrexia.i Early-onset (within 1 day of treatment) diarrhoea occurred in 30 percent of patients on ONIVYDE combined with 5-FU/LV and was usually transient.i Early-onset diarrhoea was accompanied by cholinergic symptoms in 3.4 percent of patients taking ONIVYDE in combination with 5-FU/LV.i Median time to late-onset diarrhoea was 8 days following the ONIVYDE dose.i Of patients taking ONIVYDE combined with 5-FU/LV, 11 percent of patients discontinued treatment.i

Lilly Partners with the National Cancer Institute to Accelerate Cancer Research through New Program under Cancer Moonshot Initiative

On October 17, 2016 Eli Lilly and Company (NYSE: LLY) reported it will contribute cancer research data to the National Cancer Institute’s Blood Profiling Atlas, an open access liquid biopsy database being created in response to Vice President Joe Biden’s call to action and in alignment with the goals of the Cancer Moonshot initiative (Press release, Eli Lilly, OCT 17, 2016, View Source [SID1234515873]). The database is an effort to reduce the development time of effective and safe blood profiling diagnostic technologies.

"We are honored to be a part of this unique partnership," said Andrew Schade, M.D., Ph.D., a distinguished medical fellow in Lilly’s clinical diagnostics laboratory. "Liquid biopsies are going to be critical in the future to both identify specific patients for targeted therapies and to follow their treatment to better determine response to therapy. We hope knowledge gained from our research efforts in this area will help to accelerate the development of safe and effective blood profiling diagnostic technologies that help people with cancer."

In support of this overarching mission, Lilly is studying approaches for the profiling of exosomes for mRNA and non-coding RNA expression and will share sample preparation methods, next-generation quantitative PCR-based methods, and next generation sequencing-based methods along with data related to disease characterization through gene expression analysis.

"Our scientists are dedicated to discovering and developing new cancer treatments to help people living with this disease," said Jan Lundberg, Ph.D., executive vice president of science and technology and president of Lilly Research Laboratories. "In addition to our own research, external partnerships are paramount, and we look forward to collaborating with other experts as part of the Cancer Moonshot initiative."

The Blood Profiling Atlas is part of the Cancer Moonshot initiative, which was established to improve the way research is conducted and expedite the delivery of medicines to patients. Allowing approved researchers access to raw unprocessed datasets in a scalable and reproducible manner, the open database will feature the following data: raw data sets from circulating tumor cells, circulating tumor DNA, and exosome assays, as well as relevant clinical data, sample preparation, and handling protocols from 12 different studies. The Blood Profiling Atlas pilot will be curated by a partnership between the University of Chicago and Seven Bridges, a biomedical data analysis company. For more information about the Blood Profiling Atlas, please click here.