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CANbridge’s CAN-008 Approved for Phase I/II Trial in Newly-Diagnosed Glioblastoma Multiforme in Taiwan

On July 25, 2016 CANbridge Life Sciences, a biopharmaceutical company focused on developing Western drug candidates in China and North Asia, reported that the Taiwan Food and Drug Administration (TFDA) has approved the Investigational New Drug (IND) application for a Phase I/II clinical study of CAN-008, plus temozolomide (TMZ), during and after radiation therapy, in patients with newly-diagnosed glioblastoma multiforme (GBM) (Press release, CANbridge Life Sciences, JUL 26, 2016, View Source [SID:1234514049]).

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The study design consists of an open-label, dose-escalation Phase I trial, and a multi-center, double-blind, randomized, placebo-controlled Phase II trial. The Phase I trial will evaluate safety, tolerability, pharmacokinetics and preliminary efficacy. The Phase II trial will evaluate efficacy and safety. The combined Phase I/II trial will enroll a total of approximately 55 patients. The Phase I portion of the trial will commence in August 2016.
"The approval of our first human clinical trial marks CANbridge’s transition to a clinical stage company, validating our business strategy and regulatory approach to develop promising Western drug candidates for underserved conditions in the Asian market, " said James Xue PhD, CANbridge Chairman and CEO. "That we will be moving forward in a front-line setting is also good news for glioblastoma patients in Taiwan, and the rest of Asia, who have very few treatment options."
"This approval by the TFDA is a very important step in the development of CAN008 for patients with glioblastoma multiforme (GBM) brain tumors," said Mark Goldberg, MD, CANbridge Acting Chief Medical Officer. "Glioblastoma multiforme is a devastating type of brain tumor. Better therapies are desperately needed. We are pleased to be able to move the clinical program forward and hope that CAN008 will prove to be an important advance, improving outcomes for patients with GBM. "

About CAN-008
CAN-008 is a fully human fusion protein consisting of the extracellular domain of CD95 fused to the Fc region of human IgG that inhibits the CD95 ligand, a member of the tumor necrosis factor (TNF) family. By blocking it, CAN-008 restores the immune system’s anti-tumor response and inhibits invasive tumor cell growth. In a European Phase II trial in patients with recurrent glioblastoma, conducted by the drug’s developer, privately-held Apogenix, patients with biomarkers for the CD95 ligand experienced the greatest benefits. In July 2015, CANbridge acquired an exclusive license to develop, manufacture and commercialize CAN-008 for GBM and other indications, in China, Hong Kong and Macau, which was recently expanded to include Taiwan.

Transgenomic Launches First Commercially Available CLIA Test for Detection of EGFR C797S Mutations That Predict Resistance to 3rd Generation Kinase Therapies for Lung Cancer

On July 25, 2016 Transgenomic, Inc. (TBIO), (NASDAQ: TBIO) reported the launch of its new CLIA assays that detect the presence of the EGFR C797S mutation, a novel mechanism of acquired resistance to third-generation tyrosine kinase inhibitor (TKI) drugs for non-small cell lung cancer (NSCLC) (Press release, Transgenomic, JUL 26, 2016, http://www.transgenomic.com/2016/07/25/transgenomic-launches-first-commercially-available-clia-test-for-detection-of-egfr-c797s-mutations-that-predict-resistance-to-3rd-generation-kinase-therapies-for-lung-cancer/ [SID:1234514048]). The C797S detection test is available as a solo assay and in three panels–TBIO’s EGFR-TKI resistance panel that also tests for the EGFR T790M mutation, its MX-ICP EGFR NSCLC panel and its MX-ICP EGFR Analysis panel, which also test for other actionable EGFR mutations relevant to the treatment of lung cancer.

These ultra-high sensitivity assays use TBIO’s Multiplexed ICE COLD-PCR (MX-ICP) enrichment technology to generate accurate results from tissue, blood or serum samples, making it feasible to test patients for resistance as treatment proceeds. The EGFR tests are currently available for clinical use through the company’s Oncology CLIA laboratory in Omaha, Nebraska.

TBIO President and CEO Paul Kinnon commented, "We are proud to be the first to offer testing for the EGFR C797S mutation and to do so in flexible formats designed to maximize their utility. This is our 10th CLIA-certified ICP assay for the detection of actionable cancer mutations, with many more slated for commercial release in the coming months. Our ICP technology is an ideal solution for the repeat DNA testing needed to capitalize on new cancer treatments–it has high sensitivity and requires very small amounts of sample, thereby enabling the liquid biopsies needed for ongoing patient monitoring. These unique ICP CLIA assays provide potentially lifesaving information by enabling the ongoing testing and optimal treatment of lung cancer patients."

The EGFR C797S assay is intended for NSCLC patients potentially eligible for treatment with third generation EGFR-TKI drugs. The combination of EGFR C797S and T790M markers comprise an acquired resistance panel for EGFR-TKI therapy. EGFR C797S has also been added to the MX-ICP NSCLC (EGFR exons 18 – 21, EGFR C797S, KRAS exons 2 and 3, BRAF exon 15, PIK3CA exons 9 and 20) and the MX-ICP EGFR Analysis (EGFR exons 18 – 21, EGFR C797S) panels to provide comprehensive testing of genetic markers that are key actionable mutations relevant to the treatment of NSCLC. NSCLC is one of the most common types of cancer in the US and is the leading cause of cancer deaths.

ICE COLD-PCR achieves its ultra-high sensitivity through selective amplification of mutant DNA. The result is up to a 500-fold increase in sensitivity in identifying mutations with the most precise sequence alteration detection rates available. ICP was originally developed by the laboratory of Dr. Mike Makrigiorgos at the Dana-Farber Cancer Institute, which has exclusively licensed rights to the technology to Transgenomic.

AstraZeneca files first clinical trial application in Moderna messenger RNA collaboration

On July 26, 2016 AstraZeneca reported that it has filed a Clinical Trial Application (CTA) with the Paul Ehrlich Institute and the German Federal Ministry of Health to initiate a Phase I clinical trial of AZD8601 (Press release, AstraZeneca, JUL 26, 2016, View Source [SID:1234514046]). The programme is part of a collaboration between AstraZeneca and Moderna to discover, develop and commercialise messenger mRNA (mRNA) TherapeuticsTM to treat serious cardiovascular, metabolic and renal diseases as well as cancer. It marks the first programme resulting from the collaboration to progress towards clinical trials.

AZD8601 is an investigational mRNA-based therapy that encodes for vascular endothelial growth factor-A (VEGF-A). It was discovered and developed in collaboration with Kenneth Chien, M.D., Ph.D., Professor of Cellular and Molecular Biology and Medicine and his team at the Integrated Cardio-Metabolic Centre at Karolinska Institutet in Stockholm, Sweden.

Marcus Schindler, Vice President, Innovative Medicines & Early Development at AstraZeneca said, "Development of regenerative therapies for the treatment of cardiometabolic disease is a hugely exciting and innovative area. We believe that using modified mRNA to initiate a strong, local and transient surge of VEGF-A expression could help us overcome challenges associated with previous approaches to regulate this protein in tissues. AZD8601 could one day provide a unique regenerative treatment option for patients with heart failure, diabetic wound healing and other ischemic vascular diseases."

Stéphane Bancel, Chief Executive Officer, Moderna said, "This marks a significant milestone for both Moderna and AstraZeneca as our first partnered mRNA programme reaches the clinic. It is a validation of our shared vision to harness the potential of mRNA Therapeutics to address serious unmet needs with the goal of improving patients’ lives." This has been a highly collaborative partnership since its inception, and I want to recognise the tremendous work of all involved, including the AstraZeneca team, my Moderna colleagues and Dr. Chien and his team. Together, I believe we will continue to make significant strides that will push new boundaries in the treatment of cardiovascular and metabolic diseases."

Dr. Chien said, "It has been rewarding working as an integrated academic partner with AstraZeneca and Moderna to generate a complete package of strong pre-clinical data over the past three years since our initial publication in mouse studies and we are thrilled that the clinical trial application has been filed."

About AZD8601
mRNA is responsible for carrying genetic instructions transcribed from DNA, which cells then translate to produce proteins. Proteins are responsible for directing the body’s biological functions. Moderna’s pioneering mRNA Therapeutics are designed to trigger the cellular machinery to produce specific proteins. In this application, AZD-8601 may enable the delivery of genetic instructions to spur the production of VEGF-A.

The AZD8601 program is built upon a decade of pioneering research on heart stem cells in cardiovascular development conducted by Dr. Chien, including the finding that VEGF-A can act as a cell fate switch for cardiac progenitors.[i]

Tokai Pharmaceuticals Announces Clinical Update

On July 26, 2016 Tokai Pharmaceuticals Inc. (NASDAQ:TKAI), a biopharmaceutical company focused on developing and commercializing innovative therapies for prostate cancer and other hormonally driven diseases, reported that it plans to discontinue the ARMOR3-SV clinical trial, the company’s pivotal Phase 3 study comparing galeterone to enzalutamide in treatment-naïve metastatic castration-resistant prostate cancer (mCRPC) patients whose prostate tumors express AR-V7, following the recommendation made yesterday by the trial’s independent Data Monitoring Committee (DMC) (Press release, Tokai Pharmaceuticals, JUL 26, 2016, View Source [SID:1234514045]).

Based on a review of all safety and efficacy data, the DMC determined that the ARMOR3-SV trial will likely not succeed in meeting its primary endpoint of demonstrating an improvement in radiographic progression-free survival (rPFS) for galeterone versus enzalutamide in AR-V7 positive mCRPC. In making its recommendation, the DMC did not cite any safety concerns with galeterone in the trial. ARMOR3-SV is the first pivotal clinical trial in mCRPC to prospectively select AR-V7 positive patients, a population with an unmet medical need and aggressive disease course. The company plans to present data from the trial in a scientific forum once fully available and analyzed.

"We are very disappointed by this outcome. An immediate priority is to analyze the unblinded study data in detail as we evaluate potential paths forward for galeterone and our pipeline," said Jodie Morrison, President and Chief Executive Officer of Tokai. "We are deeply grateful for the support and commitment from the patients participating in the study, their caregivers, and the study investigators and their staff."

The company intends to evaluate its ongoing ARMOR2 expansion in mCRPC patients with acquired resistance to enzalutamide, and the planned study in patients who rapidly progress on either enzalutamide or abiraterone acetate. Tokai plans to allow all patients currently enrolled in the ARMOR2 and ARMOR3-SV trials to continue on therapy following consultation with their physicians and study investigators. The appropriate health authorities and clinical study investigators are being notified that ARMOR3-SV is being discontinued.

As of June 30, 2016, Tokai had approximately $43.9M in cash and cash equivalents.

About ARMOR3-SV
ARMOR3-SV was a pivotal Phase 3 trial comparing galeterone to Xtandi (enzalutamide) in mCRPC treatment-naïve patients whose prostate tumors express the AR-V7 splice variant. These truncated ARs are missing the C-terminal end of the AR that contains the ligand-binding domain, which is known as C-terminal loss. AR-V7 is the most common form of C-terminal loss. The trial employed a precision medicine approach for selection of patients with the AR-V7 splice variant by using an AR-V7 clinical trial assay successfully optimized for global use by Qiagen. The primary endpoint of ARMOR3-SV was radiographic progression-free survival assessed by blinded independent central review.

About Galeterone
Galeterone is an oral small molecule that utilizes the mechanistic pathways of current second-generation hormonal therapies, including abiraterone and enzalutamide, while also introducing a unique third mechanism – androgen receptor degradation – that impairs the function of androgen receptors, decreasing their sensitivity to androgen activity and reducing tumor growth. Tokai is developing galeterone for the treatment of patients with metastatic castration-resistant prostate cancer. Tokai has worldwide development and commercialization rights to galeterone.

Eisai And Halozyme Initiate Phase 1b/2 Clinical Trial With First Patient Dosing Of Eribulin In Combination With PEGPH20

On July 26, 2016 Halozyme Therapeutics, Inc. (NASDAQ: HALO) reported that Eisai Inc. has dosed the first patient in a collaborative phase 1b/2 clinical trial to assess whether Eisai’s eribulin mesylate (HALAVEN) in combination with Halozyme’s investigational drug PEGPH20 (PEGylated recombinant human hyaluronidase) can improve overall response rate (ORR) – the proportion of women that have a predefined reduction in tumor burden – as compared with eribulin alone as a therapy in women with advanced or metastatic, High-Hyaluronan (HA) HER2-negative breast cancer (Press release, Halozyme, JUL 26, 2016, View Source [SID:1234514042]).

"Initiation of this study is not only a major milestone in our collaboration with Eisai, it underscores our combined focus on advancing the treatment of metastatic breast cancer—one of the most common cancers in women worldwide," said Dr. Helen Torley, president and chief executive officer.

PEGPH20 is an investigational drug administered intravenously that targets the degradation of HA, a glycosaminoglycan – or chain of natural sugars throughout the body – that can accumulate around cancer cells to inhibit other therapies. Eribulin, a synthetic analog of halichondrin B, a natural product that was isolated from the marine sponge Halichondria okadai, is a microtubule dynamics inhibitor with a distinct binding profile that has been shown in in vitro studies to lead to apoptotic cell death after prolonged and irreversible mitotic blockage. In HA-high triple-negative breast preclinical animal models, the addition of PEGPH20 to eribulin showed a significant increase in tumor growth inhibition and overall tumor regression when compared to eribulin alone.

The collaborative study will seek to determine whether or not the combination therapy of eribulin and PEGPH20 can improve the overall response rate in patients with metastatic breast cancer with high levels of HA. The study protocol includes metastatic HER2-negative patients with HA-high breast cancer that were previously untreated and those that received one prior line of therapy.

About Advanced Breast Cancer

Advanced or metastatic breast cancer is a very difficult condition to treat and only 26.3 percent of women will survive beyond five years. (SEER 2016)

About PEGPH20

PEGPH20 is an investigational PEGylated form of Halozyme’s proprietary recombinant human hyaluronidase under clinical development for the potential systemic treatment of tumors that accumulate hyaluronan.

FDA granted orphan drug designation to PEGPH20 for treatment of pancreatic cancer and fast track for PEGPH20 in combination with gemcitabine and nab-paclitaxel for the treatment of metastatic pancreatic cancer. Additionally, the European Commission, acting on the recommendation from the Committee for Orphan Medicinal Products of the European Medicines Agency, designated investigational drug PEGPH20 an orphan medicinal product for the treatment of pancreatic cancer.

About Eribulin Mesylate Injection (Available as HALAVEN)

Halaven (eribulin mesylate) is a microtubule dynamics inhibitor indicated for the treatment of patients with:

Metastatic breast cancer who have previously received at least two chemotherapeutic regimens for the treatment of metastatic disease. Prior therapy should have included an anthracycline and a taxane in either the adjuvant or metastatic setting.
Unresectable or metastatic liposarcoma who have received a prior anthracycline-containing regimen.
Discovered and developed by Eisai, eribulin is a synthetic analog of halichondrin B, a natural product that was isolated from the marine sponge Halichondria okadai. First and only in the halichondrin class, eribulin is a microtubule dynamics inhibitor with a distinct binding profile. Eribulin is believed to work primarily via a tubulin-based mechanism that causes prolonged and irreversible mitotic blockage, ultimately leading to apoptotic cell death. Additionally, in preclinical studies of human breast cancer, eribulin demonstrated complex effects on the tumor biology of surviving cancer cells, including increases in vascular perfusion resulting in reduced tumor hypoxia, and changes in the expression of genes in tumor specimens associated with a change in phenotype, promoting the epithelial phenotype, opposing the mesenchymal phenotype. Eribulin has also been shown to decrease the migration and invasiveness of human breast cancer cells.