On October 10, 2018 Helix BioPharma Corp. (TSX: HBP), (FSE: HBP) ("Helix" or the "Company"), an immuno-oncology company developing innovative drug candidates for the prevention and treatment of cancer, reported that it has extended its collaboration agreement with Moffitt Cancer Center for an additional year (Press release, Helix BioPharma, OCT 10, 2018, View Source [SID1234530409]).

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During the first year of the collaboration, a new pancreatic adenocarcinoma mouse model suitable for testing L-DOS47 in combination with immunotherapy was developed. Preliminary studies in this model showed that L-DOS47 may increase the activity of a PD-1/PD-L1 inhibitor in treating pancreatic cancer. In addition, work was initiated to demonstrate that certain imaging techniques may be useful in directly measuring tumor acidity. Helix is hoping to use this non-invasive technique in the clinic soon.

In year two of the project, work will include not only the study of L-DOS47 in combination with PD-1/PDL1 inhibitors, but also in combination with other drugs in the pancreatic model. Analysis of the immune response that is occurring in the tumor upon L-DOS47 combination treatment will also be characterised. Results from these studies will add to the current understanding of how tumor acidity affects the tumor immune response. Data from these studies will also support Helix’s plan to increase the clinical application of L-DOS47 with various combination treatments, including immunotherapies with checkpoint inhibitors.

"We are strongly encouraged by our preliminary data that this may be an effective approach to improving outcomes to a variety of therapies" said Dr. Robert Gillies, Martin Silbiger Endowed Chair, Moffitt Cancer Center. "We know that tumor acidity is an important contributor to therapy resistance, and thus neutralizing acidity with L-DOS47 should have a positive effect in combination with chemotherapies and immune checkpoint blockade".

"This years’ Nobel prize in Physiology or Medicine was awarded for the discovery of cancer therapy by inhibition of negative immune regulation." said Heman Chao, Ph.D., Chief Executive & Scientific Officer of Helix. "We are very excited to work with the Moffitt team in applying L-DOS47 in immunotherapy and we look forward to using L-DOS47 with PD-1/PD-L1 inhibitors in the clinic which could result in significant benefits to patients."

On October 10, 2018 BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160), a commercial-stage biopharmaceutical company focused on developing and commercializing innovative molecularly-targeted and immuno-oncology drugs for the treatment of cancer, reported that China’s State Medical Insurance Administration (SMIA) has included VIDAZA (azacitidine for injection) on its national reimbursement drug list (NRDL) (Press release, BeiGene, OCT 10, 2018, View Source;p=RssLanding&cat=news&id=2370979 [SID1234530257]). VIDAZA is a nucleoside metabolic inhibitor and was approved in China for patients with intermediate-2 / high-risk myelodysplastic syndrome (MDS), acute myeloid leukemia (AML) with 20-30% bone marrow blasts and chronic myelomonocyte leukemia (CMML). It is marketed in China by BeiGene under an exclusive license from Celgene Corporation.

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"VIDAZA became commercially available in China in February and is the only approved hypomethylating agent shown to prolong survival for patients with MDS. With this national reimbursement coverage, we expect more patients to have an opportunity to benefit from VIDAZA in China," commented Dr. Xiaobin Wu, General Manager of China and President of BeiGene, Ltd. "BeiGene is committed to improving patient access to high-quality, innovative cancer treatments."

VIDAZA is recommended by National Comprehensive Cancer Network (NCCN) Guidelines in the US as a front-line treatment. In a global Phase 3 trial (AZA-001) involving intermediate-2 and high-risk MDS patients, VIDAZA significantly prolonged the median overall survival to 24.5 months compared with 15 months for the conventional care regimens (CCR- best supportive care, low-dose cytarabine or intensive chemotherapy) group. In the VIDAZA group, 45% of patients who were dependent on red blood cell transfusions at baseline became transfusion independent compared with 11% in the CCR group.There was a higher objective response rate among patients treated with VIDAZA (49%) as compared to the CCR arm (29%). VIDAZA also delayed the onset of AML for these patients (17.8 months vs.11.5 months). The most common grade 3-4 events were peripheral blood cytopenias for all treatments.

"We are pleased that patients in China will have improved access to VIDAZA and other cancer treatments listed on the 2018 NRDL," said Professor Wang Jianxiang, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences. "VIDAZA is an important treatment for MDS with demonstrated survival benefit. The broadening access to new treatments like VIDAZA could significantly improve the care of our patients."

About Myelodysplastic Syndrome, Acute Myeloid Leukemia and Chronic Myelomonocyte Leukemia

MDS is a group of conditions that can occur when the bloodforming cells in the bone marrow become abnormal. This leads to low numbers of one or more types of blood cells. In about one-third of patients with MDS, the disease can progress to a rapidly growing cancer of bone marrow cells called AML.i CMML is a type of cancer that starts in blood-forming cells of the bone marrow and invades the blood; it affects mainly older adults. CMML has features of both MDS and myeloproliferative disorder and is considered the most common disease among myelodysplastic/myeloproliferative diseases.ii

About VIDAZA (Azacitidine for Injection)

VIDAZA is a nucleoside metabolic inhibitor indicated in China for the treatment of patients with intermediate-2 / high-risk MDS, AML with 20-30% bone marrow blasts and CMML. It is marketed in China by BeiGene under an exclusive license from Celgene Corporation.

In the US, VIDAZA is indicated for the treatment of patients with the following FAB MDS subtypes: refractory anemia (RA) or refractory anemia with ringed sideroblasts (RARS) (if accompanied by neutropenia or thrombocytopenia or requiring transfusions), refractory anemia with excess blasts (RAEB), refractory anemia with excess blasts in transformation (RAEB-T), and CMML.

Important Safety Information

VIDAZA is contraindicated in patients with a known hypersensitivity to azacitidine or mannitol and in patients with advanced malignant hepatic tumors.

In Study 1 (a randomized, open-label, controlled trial carried out in 53 U.S. sites compared the safety and efficacy of subcutaneous VIDAZA plus supportive care with supportive care alone ("observation") in patients with any of the five FAB subtypes of myelodysplastic syndromes (MDS)) and Study 2 (a multi-center, open-label, single-arm study of 72 patients with RAEB, RAEB-T, CMMoL, or AML), most frequently observed adverse reactions occurring in at least 5% of patients by SC route were nausea (70.5%), anemia (69.5%), thrombocytopenia (65.5%), vomiting (54.1%), pyrexia (51.8%), leukopenia (48.2%), diarrhea (36.4%), injection site erythema (35.0%), constipation (33.6%), neutropenia (32.3%), and ecchymosis (30.5%). Other adverse reactions included dizziness (18.6%), chest pain (16.4%), febrile neutropenia (16.4%), myalgia (15.9%), injection site reaction (13.6%), and malaise (10.9%). In Study 3, the most common adverse reactions by IV route also included petechiae (45.8%), weakness (35.4%), rigors (35.4%), and hypokalemia (31.3%).

In Study 4 (the AZA-001 survival trial, an international, multicenter, open-label, randomized trial in MDS patients with RAEB, RAEB-T or modified CMMoL according to FAB classification and Intermediate-2 and High risk according to IPSS classification), most frequently observed adverse reactions occurring in at least 5% of patients were thrombocytopenia (69.7%), neutropenia (65.7%), anemia (51.4%), constipation (50.3%), nausea (48.0%), injection site erythema (42.9%), and pyrexia (30.3%). The most frequently observed adverse reactions in the percentage with NCI CTC Grade 3/4 reactions were neutropenia (61.1%), thrombocytopenia (58.3%), leukopenia (14.9%), anemia (13.7%), and febrile neutropenia (12.6%).

Because treatment with VIDAZA is associated with anemia, neutropenia and thrombocytopenia, complete blood counts should be performed as needed to monitor response and/or toxicity, but at a minimum, prior to each dosing cycle.

Because azacitidine is potentially hepatotoxic in patients with severe preexisting hepatic impairment, caution is needed in patients with liver disease. In addition, azacitidine and its metabolites are substantially excreted by the kidneys and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, it may be useful to monitor renal function.

VIDAZA may cause fetal harm when administered to a pregnant woman. Females of reproductive potential should be advised to avoid pregnancy during treatment with VIDAZA. Males with female sexual partners of reproductive potential should not father a child and should use effective contraception during treatment with VIDAZA.

The importance of the drug to the mother should be taken into consideration before the breastfeeding mothers decide to discontinue breastfeeding or the drug.

On October 10, 2018 DelMar Pharmaceuticals, Inc. (NASDAQ: DMPI) ("DelMar" or the "Company"), a biopharmaceutical company focused on the development and commercialization of new cancer therapies, reported the publication of a peer-reviewed scientific paper on the mechanism of action for VAL-083, the Company’s product candidate, in Cell Death and Disease by Nature Publishing Group (Press release, DelMar Pharmaceuticals, OCT 10, 2018, View Source [SID1234530251]).

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The paper, entitled "Dianhydrogalactitol induces replication-dependent DNA damage in tumor cells preferentially resolved by homologous recombination," details the mechanism of action for VAL-083 (dianhydrogalactitol) involving S-phase dependent DNA double stand breaks (DSB) and homologous recombination (HR) DNA repair. This peer-reviewed publication further validates VAL-083’s unique anti-tumor mechanism and differentiates it from the standard-of-care. In addition, this research supports the use of VAL-083 in combination with drugs targeting cancer cells in S-phase, including topoisomerase inhibitors. Furthermore, the results suggest VAL-083 as a potential treatment option for tumors with impaired HR DNA repair, such as high-grade ovarian carcinomas, or tumors treated with PARP inhibitors.

The research was conducted in the laboratory of Dr. Mads Daugaard at the Vancouver Prostate Center, one of the world’s most respected cancer research institutes. Using non-small cell lung cancer (NSCLC) as a model system for cancer cells, the research group showed that VAL-083-induced cytotoxicity materialized when the cells entered the S-phase of the cell cycle. The resulting DNA damage subsequently triggered irreversible cell cycle arrest and ultimately cancer cell death. Further analysis revealed that cancer cells attempted to use their HR DNA repair pathway to reverse VAL-083-induced DNA damage and cancer cells with an impaired HR repair pathway were therefore particularly sensitive to VAL-083.

DelMar is currently studying VAL-083 in two collaborator-supported, biomarker driven, Phase 2 clinical trials for MGMT-unmethylated glioblastoma multiforme (GBM). As demonstrated in prior publications, the DNA repair protein MGMT is overexpressed in over 60% of GBM patients which causes resistance to the standard-of-care (temozolomide). In contrast to temozolomide, which targets the O6-position of guanine vulnerable to MGMT repair, VAL-083 targets the N7-position of guanine. This distinct mechanism-of-action differentiates VAL-083 from temozolomide and nitrosoureas, allowing VAL-083 to overcome MGMT-related chemoresistance, thereby addressing a significant unmet medical need.

About VAL-083

VAL-083 (dianhydrogalactitol) is a "first-in-class," bifunctional 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 and ovarian cancer in historical clinical trials sponsored by the U.S. National Cancer Institute (NCI). DelMar has demonstrated that VAL-083’s anti-tumor activity is unaffected by common mechanisms of chemoresistance, including MGMT, in cancer cell models and animal studies. Further details regarding these studies can be found at:

View Source

VAL-083 has been granted orphan drug designations 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 has been granted fast-track status for the treatment of recurrent GBM by the US FDA.

On October 10, 2018 Chugai Pharmaceutical Co., Ltd. (TOKYO: 4519) reported that it obtained a supplemental approval from the Japanese Ministry of Health, Labour and Welfare (MHLW) on October 10, 2018, for the anti-cancer agent, pertuzumab (brand name: PERJETA I.V. Infusion 420 mg/14 mL) for the indication of "neoadjuvant and adjuvant therapy for HER2-positive early breast cancer (Press release, Chugai, OCT 10, 2018, View Source [SID1234529941])." In Japan, PERJETA is currently on the market and its approved indication is in "HER2-positive inoperable or recurrent breast cancer." With this supplemental approval, the indication of PERJETA has been broadened to "HER2-positive breast cancer."

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"The ultimate goal for early breast cancer treatment is to cure. Although treatment outcomes have improved over the years, unfortunately, some patients still have recurrence of cancer. By offering a new treatment option for HER2-positive early breast cancer with this approval, we hope that PERJETA can make an even greater contribution to the advancement of breast cancer treatments," said Dr. Yasushi Ito, Chugai’s Executive Vice President, Co-Head of Project & Lifecycle Management Unit. "Chugai will continue to focus on collecting and providing information for the proper use of PERJETA against the treatment of HER2-positive breast cancer."

This approval is based on the results from the APHINITY study (Adjuvant Pertuzumab and Herceptin IN Initial TherapY in Breast Cancer), a global phase III study, and several clinical studies. The APHINITY study is a global phase III study evaluating the efficacy and safety of PERJETA plus Herceptin and chemotherapy (anthracycline medicine followed by docetaxel or paclitaxel / docetaxel plus carboplatin) compared to Herceptin and chemotherapy as adjuvant (post-surgery) therapy in 4,805 patients (including 302 patients in Japan) with HER2-positive early breast cancer who have undergone curative surgery. The primary endpoint of the APHINITY study is invasive disease-free survival (IDFS), which is the time a patient lives without return of invasive breast cancer at any site or death from any cause after adjuvant therapy. PERJETA arm significantly reduced the risk of recurrence or death by 19% compared to control arm (HR=0.81, 95%CI 0.66-1.00, stratified log-rank test, p=0.0446). The safety profile of PERJETA was consistent with that seen in previous studies.

PERJETA was approved for neoadjuvant therapy for HER2-positive early breast cancer in September 2013 in the US and in July 2015 in Europe. In addition, PERJETA was approved for adjuvant therapy for HER2-positive early breast cancer in December 2017 in the US and in May 2018 in Europe.

As the leading pharmaceutical company in the field of oncology in Japan, Chugai believes that PERJETA will make a significant contribution to patients’ lives as a new treatment option for "HER2-positive early breast cancer."

Drug Information

The underlined descriptions are newly added and changed.

Product name: PERJETA I.V. Infusion 420 mg/14 mL

Generic name: pertuzumab (genetical recombination)

Indication: HER2-positive breast cancer

Dosage and administration: The usual adult dosage when used in combination with trastuzumab (genetical recombination) and other anticancer drugs is a loading dose of 840 mg of pertuzumab (genetical recombination) followed by 420 mg every three weeks given by intravenous infusion over 60 minutes. For neoadjuvant or adjuvant chemotherapy, however, treatment should be given for up to 12 months. The infusion time can be shortened to as little as 30 minutes from the second infusion onward if the first infusion is well tolerated.

On October 10, 2018 OSE Immunotherapeutics SA (ISIN: FR0012127173; Mnémo: OSE) reported the submission of a clinical trial application to initiate a Phase 2 clinical trial of Tedopi in advanced or metastatic pancreatic cancer (Press release, OSE Immunotherapeutics, OCT 10, 2018, View Source [SID1234529889]). The trial will compare Tedopi, 10 neoepitopes associated to activate cytotoxic T-lymphocytes, in combination with nivolumab, an immune checkpoint inhibitor releaving the brakes that prevent optimal T lymphocyte activation versus maintenance standard of care treatment with Folfiri.

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The clinical trial application has been submitted in France to the ANSM (the French National Agency for Medicines and Health Products Safety) and to the central Ethics Committee by the oncology cooperative group GERCOR, who is sponsoring the clinical trial as part of PRODIGE intergroup. The Company expects activation of the trial and opening of clinical centers in early 2019.

The Phase 2 clinical trial, named TEDOPaM, aims to evaluate Tedopi as a maintenance therapy, alone or in combination with immune checkpoint inhibitor nivolumab, and evaluated versus Folfiri, a combination chemotherapy with folinic acid, fluorouracil and irinotecan and the standard of care. The study will be completed in HLA-A2 positive patients with stable disease who have received four months of first line standard-of-care chemotherapy Folforinox, a combination chemotherapy with folinic acid, fluorouracil, irinotecan and oxaliplatin.

"This new step marks the expansion of the development of Tedopi, already under evaluation in a Phase 3 study in advanced lung cancer, to an additional oncology indication, a particularly aggressive cancer for which new therapeutic options are strongly needed. With this new clinical development program evaluating Tedopi in combination with the PD-1 inhibitor nivolumab, a checkpoint inhibitor, in advanced pancreatic cancer, we are broadening our exploration of new pathwaysin immuno-oncology," commented Alexis Peyroles, chief executive officer of OSE Immunotherapeutics.

"The study’s rationale is based on the interest of a combination of immunotherapies that stimulate cytotoxic T-cells with Tedopi, whose antigens are overexpressed in pancreatic tumor, and a PD-1 checkpoint inhibitor nivolumab, whose preclinical data available to date in this cancer plead in favor of a combination with a neoepitope-type immunotherapy, likely to potentiate its activity. Our network of clinicians is now mobilizing to start this Phase 2 trial," concluded Professor Christophe Louvet, president of GERCOR.

Tedopi is a combination of 10 neoepitopes selected and optimized from five tumor associated antigens able to generate a specific response against cytotoxic T-cells expressing at least one of these tumor associated antigens and an associated helper T-cell response.

ABOUT GERCOR
GERCOR is an association of physicians whose purpose is to improve the care of patients affected by cancer by developing clinical research in the scope of an independent, multidisciplinary and multi-focused group. GERCOR
concentrates its efforts on only one mission: clinical research. Thanks to its network, GERCOR offers patients easy
access to its up-to-date treatments. To achieve this goal, GERCOR stimulates the inclusion into its network of the
greatest number of physicians involved in the treatments it is conducting, offers vital logistical assistance to research
physicians whose job is to direct and monitor the application of the treatments to patients.