On January 7, 2016 CANbridge Life Sciences reported that it has completed a biomarker study in Chinese patients with glioblastoma multiforme (GBM) for expression of CD95 ligand, the target of its first candidate for clinical development, CAN008, also known as APG101 (Press release, CANbridge Life Sciences, JAN 7, 2016, View Source [SID:1234510067]). The study demonstrated a high degree of CD95 ligand expression consistency between geographically-diverse Chinese and Western GBM patients. CAN008 is a fully-human fusion protein that inhibits the CD95 ligand, a member of the tumor necrosis factor (TNF) superfamily. By blocking the CD95 ligand, CAN008 restores the immune response against tumors and inhibits invasive tumor cell growth.

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Based on this confirmatory biomarker study, CANbridge plans to initiate a CAN008 Phase I/II study in newly-diagnosed GBM in Taiwan and expects to dose the first patient in the second half of 2016. In other news, CANbridge announced that it has expanded the licensed territories from Germany’s Apogenix (www.apogenix.com), which is developing APG101 in all other territories, to include Taiwan. In July, CANbridge entered into an exclusive license agreement with Apogenix to develop, manufacture and commercialize APG101 in GBM, with options for other indications, in China, Hong Kong and Macao. Both companies are privately-held.

"The study showing the correlation between Western and Chinese biomarker expression validates our belief that CAN008 is a strong candidate for glioblastoma treatment development in Taiwan and other Chinese territories," said Mark Goldberg, MD, CANbridge Chief Medical Officer and practicing hematologist and oncologist at Brigham and Women’s Hospital and Dana Farber Cancer Institute. "In a Phase II study conducted in Europe, CAN008 showed an improved overall survival benefit in patients with relapsed glioblastoma, especially among patients who expressed the CD95 ligand."

"The results from the biomarker study pave the way for us to advance to our first clinical trial in Asia, executing on our mission to bring promising Western drug candidates to underserved Chinese markets," said James Xue, CANbridge Chairman and CEO. "Brain cancer mortality rates are among the ten highest cancer death rates in China, where the treatment options are even more limited than in the West. We look forward to initiating one of the first immuno-oncology clinical treatment programs in China for this deadly cancer.

On January 7, 2016 BioInvent International (OMXS: BINV) reported that the FDA has completed the safety review of its Investigational New Drug (IND) application and have concluded that the proposed pediatric clinical investigation can proceed (Press release, BioInvent, JAN 7, 2016, http://www.bioinvent.com/media-centre/press-releases/release/?ReleaseID=9BA3A7EAD4A9883F [SID:1234508694]). The IND application is for a Phase I/IIa study that will evaluate the efficacy and safety of TB-403 for the treatment of relapsed or refractory medulloblastoma. This is a rare, life-threatening brain tumor that mainly affects children.

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The study, which is planned to commence in Q1 2016, will be conducted at a number of specialist centers in the United States. Initial results from the study are expected by early 2017.

TB-403 is a humanized monoclonal antibody against placental growth factor (PlGF) which is expressed in several types of cancer, including medulloblastoma. High expression of the PlGF receptor neuropilin 1 has been shown to correlate with poor overall survival. Treatment with TB-403 in pre-clinical models for medulloblastoma has demonstrated beneficial effects on tumor growth and survival. The antibody can potentially be used in other pediatric cancer indications, including neuroblastoma, Ewing sarcoma or alveolar rhabdomysarcoma.

A favourable safety profile of TB-403 has been demonstrated in previous clinical trials in healthy volunteers and adult patients with various types of solid tumors.

"We are delighted that the FDA has accepted our IND for TB-403. This is a milestone for commencing the phase I/IIa study evaluating TB-403 in rare pediatric brain cancers according to plans communicated in December 2015. The study will be conducted at an attractive cost and efficacy signals in patients will provide opportunities to approach the FDA regarding expedited approval. TB-403 may in this scenario get a rapid pathway to launch," says Michael Oredsson, CEO of BioInvent.

The TB-403 drug project is conducted in cooperation with Oncurious, a subsidiary of the Belgian biopharma company ThromboGenics. BioInvent is paying half of the development costs and has the right to 40 percent of all future revenue from the project.

On January 07, 2016 Merck, a leading science and technology company reported that it has signed a collaboration agreement with Biocartis for the development and commercialization of a new liquid biopsy RAS biomarker test for patients with metastatic colorectal cancer (mCRC) (Press release, Merck KGaA, JAN 7, 2016, View Source [SID:1234508693]). The test will be developed on Biocartis’ innovative, fully automated molecular diagnostics system, Idylla, which is designed to offer accurate and reliable molecular information from virtually any biological sample in virtually any setting. The new test aims to support clinical practice in performing integrated liquid biopsy RAS biomarker tests, independently of the laboratories’ volume of testing or level of expertise.

Understanding metastatic colorectal cancer (mCRC) patients’ individual biomarker status is key to support timely treatment decision-making.

"Through this collaboration, our desire is to have more metastatic colorectal cancer patients gain access to liquid biopsy RAS testing, regardless of their geographical location," said Rehan Verjee, Chief Marketing and Strategy Officer of Merck’s biopharma business. "As the first pharmaceutical company to collaborate with multiple diagnostic providers of liquid biopsy RAS testing, we are living our commitment to supporting patients and physicians by going beyond treatment. The Biocartis technology will be complementary to other technology previously developed, and will allow for liquid biopsy RAS offerings to a wide range of lab segments, regardless of size and expertise levels."

The Idylla system is a fully automated sample-to-result PCR-based (polymerase chain reaction) molecular diagnostics system. It is designed to offer real-time, reliable and sensitive molecular diagnostic tests. Whereas most of today’s solutions only look for the most prevalent RAS mutations, the Idylla RAS test, comprising two Idylla cartridges, will be designed to detect an extended panel of RAS mutations. In addition, the new test will also provide a BRAF V600 mutation analysis directly integrated with the Idylla RAS test, to allow clinicians to evaluate BRAF and RAS mutation status simultaneously. Based on a direct sample of only 2 ml of blood plasma, the test aims to provide high sensitivity and ease-of-use. The test will be designed to require less than 2 minutes of hands-on time and a turnaround time of approximately 2 hours, enabling clinical decision-making in a timely manner.

"Today, complex diagnostic laboratory infrastructure and specialized expertise requirements are important barriers when it comes to the implementation of personalized medicine on a global scale." said Rudi Pauwels, CEO Biocartis. "We are pleased to partner with Merck, who supports us in putting personalized medicine into daily practice with this collaboration, through the development of rapid and accurate tests on the Idylla system. After having already launched solid biopsy RAS tests, the Idylla liquid biopsy RAS test is a logical next step in our rapidly expanding menu of oncology tests."

Merck and Biocartis plan to implement the Idylla liquid biopsy RAS test in numerous medical centers across the world, excluding the U.S., China and Japan. The test will be available for Research Use Only (RUO) in H2 2016 and is shortly thereafter planned to be submitted for a CE Mark. A concordance study is currently also being undertaken to substantiate the value of the test.

About mCRC
Approximately half of patients with mCRC have RAS wild-type tumors and half have RAS mutant tumors.1 Results from studies assessing RAS mutation status in patients with mCRC have shown that anti-epidermal growth factor receptor (EGFR) monoclonal antibody therapies, such as Erbitux (cetuximab), can improve outcomes in patients with RAS wild-type mCRC.2-6 Colorectal cancer (CRC) is the third most common cancer worldwide, with an estimated incidence of more than 1.36 million new cases annually.7 An estimated 694,000 deaths from CRC occur worldwide every year, accounting for 8.5% of all cancer deaths and making it the fourth most common cause of death from cancer.7 Almost 55% of CRC cases are diagnosed in developed regions of the world, and incidence and mortality rates are substantially higher in men than in women.7

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On January 7, 2016 Tokai Pharmaceuticals Inc. (NASDAQ: TKAI) reported an update on its clinical development program evaluating galeterone in the treatment of men with metastatic castration-resistant prostate cancer (mCRPC) (Press release, Tokai Pharmaceuticals, JAN 7, 2016, View Source;p=RssLanding&cat=news&id=2127152 [SID:1234508690]).

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ARMOR3-SV Update
Tokai is enrolling patients in its ARMOR3-SV study, a Phase 3 registration clinical trial of galeterone in AR-V7+ mCRPC. The company now expects to complete enrollment in this trial during the second half of 2016 and to have top-line data available by mid-2017. This change in guidance reflects the timing for implementation of the AR-V7 clinical trial assay as well as a delay in initiating clinical sites in Western Europe and Australia during the fourth quarter of 2015. The AR-V7 assay has now been implemented in all regions. Patients are being screened at more than 85 clinical sites globally, and the number of clinical sites is expected to exceed 100 by the end of the first quarter. Notably, AR-V7 prevalence observed in ARMOR3-SV to date has been consistent with the company’s expectations and is in line with the published literature.

"With our rapidly growing number of open ARMOR3-SV clinical sites globally and the implementation of new recruitment initiatives, we believe in our ability to recruit to our revised guidance," said Jodie Morrison, President and Chief Executive Officer of Tokai. "Interest in AR-V7 as a marker for resistance to other therapies continues to increase throughout the prostate cancer community, and we remain focused on our goal of completing ARMOR3-SV as rapidly as possible."

2016 Galeterone Expansion Plans
With the ARMOR3-SV trial building momentum, Tokai now plans to expand galeterone development into broader mCRPC populations, including the initiation of two additional studies during the first half of 2016 in patients who have shown resistance following treatment with either abiraterone or enzalutamide.

The first of these studies is an open-label, two-part Phase 2 clinical trial designed to evaluate galeterone in men whose mCRPC rapidly progressed following treatment with either abiraterone or enzalutamide. The first part of the study will evaluate the rates of prostate-specific antigen (PSA) decline in approximately 36 patients. Following completion of the first part of the study, Tokai may then expand the study to a second, randomized phase that will compare galeterone to the next alternate androgen signaling inhibitor, with efficacy endpoints to include time to PSA progression and rPFS. Tokai plans to evaluate all patients enrolled in this open-label study for the presence of AR-V7, but AR-V7+ status is not a criterion for inclusion in the trial.

The second study is an expansion of an arm of the ongoing Phase 2 clinical trial of galeterone (ARMOR2) in mCRPC patients who have progressed following an initial response to enzalutamide. The expansion of the cohort from nine to 30 patients follows a compelling response seen in a post-enzalutamide patient. This patient did not initially show a PSA response until after seven months of galeterone treatment, at which time the patient’s PSA level rapidly dropped by over 90 percent and has remained at less than 0.1µg/L for over a year. This expanded post-enzalutamide cohort will assess reduction in PSA levels and safety.

About ARMOR3-SV
ARMOR3-SV is Tokai’s pivotal Phase 3 clinical trial of galeterone in men with metastatic castration-resistant prostate cancer (mCRPC) whose tumor cells express the AR-V7 splice variant, a truncated form of the androgen receptor that has been associated with non-responsiveness to commonly-used oral therapies for mCRPC. ARMOR3-SV is designed to evaluate whether administration of galeterone results in a statistically significant increase in radiographic progression free survival as compared to Xtandi (enzalutamide) in 148 treatment-naive mCRPC patients whose prostate tumor cells express the AR-V7 splice variant. ARMOR3-SV is the first pivotal trial in prostate cancer to employ a precision medicine approach for patient selection. Top-line results from ARMOR3-SV are anticipated by mid-2017.

On January 7, 2016 Teva Pharmaceutical Industries Ltd. (NYSE and TASE: TEVA) and Checkpoint Therapeutics, Inc. ("Checkpoint"), a Fortress Biotech (NASDAQ: FBIO) Company reported a license agreement in which Checkpoint will obtain the exclusive worldwide rights to develop and commercialize CEP-8983 and its small molecule prodrug, CEP-9722, an oral poly (ADP-ribose) polymerase (PARP) inhibitor in early clinical development for solid tumors (Press release, Teva, JAN 7, 2016, View Source;p=RssLanding&cat=news&id=2127237 [SID:1234508689]). CEP-9722 is a novel, orally active, small molecule selective inhibitor of PARP-1 and PARP-2 enzymes that will be developed by Checkpoint as both a monotherapy and in combination with other anti-cancer agents, including Checkpoint’s novel immuno-oncology and checkpoint inhibitor antibodies currently in development.

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"Teva is committed to facilitating the development of its early clinical stage oncology programs, which hold promise for the oncology community, by identifying targeted opportunities with companies who have unique R&D capabilities in this therapeutic area," said Michael Hayden, MD, PhD, President of Global R&D and Chief Scientific Officer at Teva. "We believe Checkpoint’s development capabilities, in combination with its immuno-oncology antibodies already under development, will enable these molecules to move forward with future potential for patients."

James F. Oliviero, III, President and CEO of Checkpoint Therapeutics stated, "The acquisition of worldwide rights to CEP-9722 immediately transforms Checkpoint Therapeutics into a clinical-stage biopharmaceutical company, expanding our proprietary portfolio with an exciting targeted therapy that, when combined with our immuno-oncology antibodies under development, can potentially create wholly-owned proprietary combinations that leverage the immune system and other complimentary mechanisms with the goal of providing significant benefit to patients. PARP inhibitors have been associated with promising activity across multiple tumor types, including breast, ovarian and prostate cancer." Mr. Oliviero, continued, "We appreciate Teva’s belief in our organization and our development strategy for this drug candidate in multiple strategic indications."

About PARP
Poly (ADP-ribose) polymerase (PARP) enzymes are involved in normal cellular homeostasis, such as DNA transcription, cell cycle regulation, and DNA repair. DNA repair enzymes such as PARP, whose activity and expression are up-regulated in tumor cells, are believed to contribute to resistance and dampen the effects of chemotherapy and radiation. By inhibiting PARP, certain cancer cells may be rendered unable to repair single strand DNA breaks, which in turn causes double strand DNA breaks and can lead to cancer cell death. Across multiple tumor types, including breast, ovarian and prostate cancer, PARP inhibitors have shown promising activity as a monotherapy against tumors with existing DNA repair defects, such as BRCA1 and BRCA2, and as a combination therapy when administered together with anti-cancer agents that induce DNA damage.

About Checkpoint Therapeutics
Checkpoint Therapeutics, Inc. ("Checkpoint"), a Fortress Biotech Company, is an innovative, immuno-oncology biopharmaceutical company focused on the acquisition, development and commercialization of novel, non-chemotherapy, immune-enhanced combination treatments for patients with solid tumor cancers. Checkpoint aims to acquire rights to these technologies by licensing the rights or otherwise acquiring an ownership interest in the technologies, funding their research and development and eventually either out-licensing or bringing the technologies to market. Currently, Checkpoint is developing a portfolio of fully human immuno-oncology targeted antibodies generated in the laboratory of Dr. Wayne Marasco, MD, PhD, a professor in the Department of Cancer Immunology and AIDS at the Dana-Farber Cancer Institute. The portfolio of antibodies Checkpoint licensed from Dana-Farber includes antibodies targeting Programmed death-ligand 1 ("PD-L1"), Glucocorticoid-induced TNFR related protein ("GITR") and carbonic anhydrase IX ("CAIX"). Checkpoint plans to develop these novel immune-oncology and checkpoint inhibitor antibodies on their own and in combination with each other, as data suggests that combinations of these targets may work synergistically together. Checkpoint has also licensed a small molecule inhibitor of epidermal growth factor receptor ("EGFR") mutations from NeuPharma, Inc. Clinical trials are expected to start in the first half of 2016 for the EGFR inhibitor and the second half of 2016 for one or more of the Dana-Farber antibodies. Additionally, Checkpoint will seek to add additional immuno-oncology drugs as well as other targeted therapies to create wholly-owned proprietary combinations that leverage the immune system and other complimentary mechanisms. Checkpoint is headquartered in New York City. For more information, visit www.checkpointtx.com.