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:

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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.

On October 10, 2018 Vaccibody AS, a clinical stage immunotherapy company focused on developing personalized neoantigen cancer vaccines to target solid tumors, reported that the first 10 patients have been enrolled in its phase I/IIa cancer neoantigen vaccine trial and that vaccinations with VB10.NEO have started (Press release, Vaccibody, OCT 10, 2018, View Source [SID1234529872]). The trial is planned to enroll up to 40 patients with locally advanced or metastatic melanoma, non-small cell lung carcinoma, clear renal cell carcinoma as well as urothelial cancer or squamous cell carcinoma of the head and neck. The VB10.NEO vaccine is given in combination with standard of care checkpoint inhibitors.

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Mads Axelsen, MD, Chief Medical Officer in Vaccibody, said "We are very pleased with the enrolment in the neoantigen trial and with the interest we are experiencing from clinical investigator and from patients. To that end I would like to thank the experienced cancer experts and investigators in this trial namely Prof. Jürgen Krauss from Heidelberg, Prof. Angela Krackhardt from Munich and Prof. Elke Jäger from Frankfurt. Together with their dedicated teams they are doing an outstanding job with the neoantigen trial"

On October 10, 2018 Halozyme Therapeutics, Inc. (NASDAQ: HALO), a biotechnology company developing novel oncology and drug-delivery therapies, reported that it will webcast its Quarterly Update Conference Call for the third quarter 2018 on Tues., Nov. 6 at 4:30 p.m. ET/1:30 p.m. PT. Dr. Helen Torley, president and chief executive officer, will lead the call (Press release, Halozyme, OCT 10, 2018, View Source [SID1234529865]). On the same date, Halozyme will release financial results for the third quarter ended September 30, 2018 following the close of trading.

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The call will be webcast live through the "Investors" section of Halozyme’s corporate website and a replay will be available following the close of the call. The live call may be accessed by dialing (877) 410-5657 (domestic callers) or (334) 323-7224 (international callers) using passcode 387156. A telephone replay will be available after the call by dialing (877) 919-4059 (domestic callers) or (334) 323-0140 (international callers) using replay ID number 55575898.