On September 18, 2017 DelMar Pharmaceuticals, Inc. (Nasdaq: DMPI) ("DelMar" and "the Company"), a biopharmaceutical company focused on the development of new cancer therapies, reported that the U.S. Food and Drug Administration ("FDA") has allowed an additional Investigational New Drug Application ("IND") to study its lead drug candidate VAL-083 as a potential treatment for ovarian cancer (Press release, DelMar Pharmaceuticals, SEP 18, 2017, View Source [SID1234520541]).

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"The opening of this new IND to study VAL-083 in ovarian cancer marks a major milestone for our Company as we continue to investigate this agent as an important potential therapy for the treatment of multiple cancers," said Jeffrey Bacha, DelMar’s president and chief executive officer.

VAL-083 is a first-in-class, DNA targeting agent that demonstrated clinical activity against a range of tumor-types in prior clinical trials sponsored by the U. S. National Cancer Institute ("NCI"). Published results from NCI studies include recommendations for further study of VAL-083 in advanced clinical trials for ovarian cancer and other gynecologic malignancies.

DelMar’s clinical trial will be a multi-center, Phase 1/2 Study of VAL-083 in patients with Recurrent Platinum Resistant Ovarian Cancer ("VAL-083 REPROVe Trial"). DelMar’s research demonstrates that VAL-083’s unique mechanism of action has the potential to overcome chemo-resistance to platinum-based chemotherapy in ovarian, lung and other solid tumors.

Ovarian cancer remains the leading cause of death among women with gynecological cancers and the fifth most frequent cause of cancer deaths in women overall. The American Cancer Society estimates that in 2017, approximately 22,440 women in the US will be diagnosed with ovarian cancer and approximately 14,080 will die from their disease. The majority of these deaths were patients whose tumors had become resistant to platinum-based chemotherapy regimens. Currently, there are no high-efficacy therapeutic options for platinum-resistant ovarian cancer, leaving these cancer patients with very poor prognosis. According to published literature, the overall response rate ("ORR") to second line therapy is in the 10-15% range and overall survival is approximately 12-months.

"The development of new treatments to overcome platinum resistance represents the largest unmet medical need in the treatment of ovarian cancer," stated Dr. Bradley J. Monk, MD, principal investigator of the VAL-083 REPROVe Trial and director of the Division of Gynecologic Oncology Research at Arizona Oncology. "Based on DelMar’s recent presentation of pre-clinical data demonstrating activity of VAL-083 against platinum-resistant ovarian cancer, we are enthusiastic about exploring the drug’s potential in this important clinical setting."

About the VAL-083 REPROVe Trial

The VAL-083 REPROVe Trial is an open label, multi-center, Phase 1/2 clinical trial to evaluate the safety and efficacy of VAL-083 in patients with recurrent adenocarcinoma of the ovary, who have been previously treated with a minimum of two courses of platinum-based chemotherapy, and whose cancer has recurred within six months of the most recent platinum-based chemotherapy. Patients enrolled in the trial will receive VAL-083 intravenously once per week for 16 weeks or until disease progression.

VAL-083 activity against platinum-resistant ovarian cancer will be measured based on ORR using the Response Evaluation Criteria in Solid Tumors ("RECIST") version 1.1 criteria as well as response duration, progression free survival, and a measurement of CA-125 biomarker levels in the blood. The study’s primary endpoint is to demonstrate an ORR benefit compared to historical control of 12-15%.

Twenty-four patients will be enrolled under the first phase of the VAL-083 REPROVe Trial with top line results expected within 18-24 months from trial initiation of patient treatment. DelMar plans to request a meeting with the FDA following the completion of Phase 1. If successful, DelMar expects that data from Phase 1 will lead to a Phase 2 expansion study. If Phase 2 is successful, and subject to FDA feedback, DelMar may be positioned to file an application for accelerated approval or, alternatively, to advance VAL-083 to a pivotal Phase 3 trial.

"Our planned work in ovarian cancer will be complementary to our ongoing Phase 2 and 3 clinical trials with VAL-083 as a potential treatment for refractory and MGMT-unmethylated glioblastoma multiforme ("GBM"). Based on our research, we believe that the REPROVe Trial has the potential to provide significantly improved outcomes for patients suffering from platinum-resistant ovarian cancer," added Mr. Bacha. Subject to availability of funding, DelMar anticipates opening the VAL-083 REPROVe Trial for patient enrollment in early 2018.

Further details on the VAL-083 REPROVe Trial and other VAL-083 clinical trials can be found at View Source

About VAL-083

VAL-083 (dianhydrogalactitol) is a "first-in-class", DNA-targeting agent that introduces interstrand DNA cross-links at the N7-position of guanine leading to DNA double-strand breaks and cancer cell death. VAL-083 has demonstrated clinical activity against a range of cancers including GBM in historical clinical trials sponsored by the U.S. National Cancer Institutes.

VAL-083 has been granted an orphan drug designation by the U.S. FDA Office of Orphan Products for the treatment of glioma, medulloblastoma and ovarian cancer, and in Europe for the treatment of malignant gliomas. VAL-083 is currently being studied in multiple clinical trials as a potential new treatment for GBM, the most common and aggressive form of brain cancer.

DelMar has demonstrated that VAL-083’s mechanism of action is distinct from multiple chemotherapies widely used in the treatment of cancer and that this unique mechanism may offer opportunities to overcome treatment resistance thereby offering new treatment options to cancer patients. Further details regarding these studies can be found at View Source

On September 15, 2017 H3 Biomedicine Inc., a clinical stage biopharmaceutical company specializing in the discovery and development of precision medicines for oncology and a member of Eisai’s global Oncology Business Group, reported that company scientists will present data from pre-clinical studies involving one of its oncology drug candidates, H3B-6527 (Press release, H3 Biomedicine, SEP 15, 2017, View Source [SID1234520544]). This data was accepted as an oral presentation at the 2017 International Liver Cancer Association (ILCA) annual meeting taking place September 15-17, 2017 in Seoul, Republic of Korea.

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H3 Biomedicine’s oral presentation is scheduled at 3:30 p.m. on Friday September 15, in Grand Ballroom 1 & 2, Lobby Level. The presentation will overview H3B-6527, an orally bioavailable, highly selective and potent inhibitor of fibroblast growth factor receptor 4 (FGFR4), which is currently in an ongoing Phase I clinical study in advanced hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (IHCC). The presentation will be given by H3 scientist and lead author, Anand Selvaraj, Ph.D.

"The data being presented at ILCA highlight the excellent progress H3’s scientists have made within this program and demonstrate that FGF19 expression is a predictive biomarker for response to H3B-6527 therapy in non-clinical studies," said Markus Warmuth, M.D., President and CEO of H3 Biomedicine. "These results highlight the potential for FGFR4 inhibition with H3B-6527, and we are excited to continue with our research to determine if it may provide clinical benefit to patients who have been diagnosed with HCC and IHCC."

The study revealed that biochemical and cellular selectivity assays showed that H3B-6527 is >250 fold selective towards FGFR4 compared to other FGFR isoforms. Addition of H3B-6527 to FGF19 amplified HCC cell lines led to dose dependent inhibition of FGF19/FGFR4 signaling and concomitant reduction in cell viability. In a panel of 40 HCC cell lines, H3B-6527 selectively reduced the viability of cells that harbor FGF19 amplification and showed no effect in FGF19 non-amplified HCC cell line models. Oral dosing of H3B-6527 to mice led to dose-dependent pharmacodynamic modulation of FGFR4 signaling and tumor regression in FGF19 altered HCC cell line derived xenograft models. H3B-6527 demonstrated inhibition of tumor growth in an orthotopic liver xenograft model of FGF19 altered HCC grown in nude mice. Importantly, the inhibition of tumor growth occurred at doses that were well tolerated in mice and no evidence of FGFR1-3 related toxicities were observed at efficacious doses.

"We are extremely pleased with the results of this work and the progress the program has made, to date," said Pete Smith, Ph.D., Chief Scientific Officer, H3 Biomedicine. "H3B-6527 demonstrated tumor regressions in multiple patient-derived xenograft models with high FGF19 expression and has shown excellent combination potential with standard-of-care and experimental agents. The data described in the presentation support the ongoing clinical development of H3B-6527 and highlight our aim to select patients most likely to respond to H3B-6527 treatment."

About H3B-6527

H3B-6527 is a selective, orally bioavailable, and potent inhibitor of fibroblast growth factor receptor 4 (FGFR4) that is being investigated for the treatment of advanced hepatocellular carcinoma (HCC). Aberrant signaling through the FGF19-FGFR4 axis has been shown to drive tumor development and dependency in pre-clinical models of HCC. H3B-6527 has shown sustained tumor regressions in several preclinical models of HCC where FGF19-FGFR4 signaling is aberrantly activated. The safety and preliminary efficacy of H3B-6527 will be explored in patients that are selected using a companion diagnostic that identifies HCC with activated FGF19-FGFR4 pathway activity. H3B-6527 is currently in Phase 1 clinical trials. For more information on the clinical trial, please click here.

On September 15, 2017 TESARO, Inc. (NASDAQ:TSRO), an oncology-focused biopharmaceutical company, reported that the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion for the Company’s marketing authorization application (MAA) for ZEJULA (niraparib) as a monotherapy for the maintenance treatment of adult patients with platinum-sensitive relapsed high grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete response (CR) or partial response (PR) to platinum-based chemotherapy (Press release, TESARO, SEP 15, 2017, View Source [SID1234520538]). This opinion will now be referred to the European Commission (EC), which grants marketing authorization for medicines in the European Union. Pending the decision by the EC, ZEJULA would be the first oral, once-daily poly (ADP-ribose) polymerase (PARP) 1/2 inhibitor approved in Europe for use in patients regardless of BRCA mutation or biomarker status.

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ZEJULA was approved by the Food and Drug Administration (FDA) on March 27, 2017 and is marketed by TESARO in the United States, where it is the most frequently prescribed PARP inhibitor.

"ZEJULA was studied with the highest level of clinical rigor, and the Phase 3 NOVA trial generated unsurpassed efficacy results in patients with recurrent ovarian cancer, including women without germline BRCA mutations who have the most challenging prognosis and few treatment options," said Mary Lynne Hedley, Ph.D., President and COO of TESARO. "Today’s positive CHMP opinion brings us one step closer to providing this important new medicine to a broad population of patients with recurrent ovarian cancer in Europe."

The ZEJULA marketing authorization application is supported by data from the ENGOT-OV16/NOVA trial, a double-blind, placebo-controlled, international Phase 3 study of ZEJULA that enrolled 553 patients with recurrent ovarian cancer who had achieved either a PR or CR to their most recent platinum-based chemotherapy. Approximately two-thirds of study participants did not have germline BRCA mutations. Progression in the NOVA study was determined by robust, unbiased, blinded central review to be the earlier of radiographic or clinical progression. ZEJULA significantly increased progression free survival (PFS) in patients with and without germline BRCA mutations as compared to the control arm. Treatment with ZEJULA reduced the risk of disease progression or death by 73% in patients with germline BRCA mutations (HR 0.27) and by 55% in patients without germline BRCA mutations (HR 0.45). The magnitude of benefit was similar for patients entering the trial with a PR or a CR.

The most common grade 3/4 adverse reactions to ZEJULA in the NOVA trial included thrombocytopenia (34%), anemia (25%), neutropenia (20%), and hypertension (9%). Following dose adjustment based on individual tolerability, the incidence of grade 3/4 thrombocytopenia was low; approximately 1% after month two. The majority of hematologic adverse events were successfully managed via dose modification, and discontinuation of therapy due to thrombocytopenia, neutropenia and anemia occurred in 3.3%, 1.9% and 1.4% of patients, respectively.

"This is an important milestone for TESARO, marking our second positive CHMP opinion for our portfolio in 2017. We are rapidly globalizing the Company’s mission of providing transformative oncology therapies to those who need them most," said Orlando Oliveira, Senior Vice President and General Manager of TESARO International. "Upon final approval by the EC, we intend to launch ZEJULA across multiple countries in Europe where we already have an established, direct presence, beginning in the fourth quarter."

About Ovarian Cancer in Europe
Europe has one of the highest incidences of ovarian cancer in the world with approximately 45,000 women diagnosed there every year1,[2]. Ovarian cancer affects approximately 1.3 in 10,000 people in the European Union, where it is the sixth-most common cancer among women and the fifth-most frequent cause of cancer death among women3,[4]. Despite high initial response rates to platinum-based chemotherapy, approximately 85% of women with advanced ovarian cancer will experience a recurrence of the disease after first-line treatment. The efficacy of chemotherapy also diminishes over time.