Genprex has filed a 10-Q – Quarterly report [Sections 13 or 15(d)] with the U.S. Securities and Exchange Commission (Filing, 10-Q, Genprex, 2018, NOV 27, 2017, View Source [SID1234527530]).

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Varian Medical Systems has filed a 10-K – Annual report [Section 13 and 15(d), not S-K Item 405] with the U.S. Securities and Exchange Commission (Filing, 10-K, Varian Medical Systems, 2017, NOV 27, 2017, View Source [SID1234522258]).

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On November 27, 2017 Medigene AG (FSE: MDG1, Prime Standard, TecDAX) reported that all planned patients have been enrolled in the Company’s ongoing Phase I/II study with dendritic cell (DC) vaccines in acute myeloid leukaemia (AML) (Press release, MediGene, NOV 27, 2017, https://www.medigene.com/investors-media/press-releases/detail/article/patient-recruitment-completed-for-phase-iii-dc-vaccine-trial-in-aml/ [SID1234522264]). The completion of the study, as previously announced, is expected in 2019 after a treatment period of two years for all patients.

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Medigene’s Phase I/II trial (NCT02405338) includes 20 AML patients who show complete remission after standard chemotherapy, but who are not eligible for stem cell transplantation that would reduce the risk of a relapse. All patients will be vaccinated with Medigene’s DC vaccines for two years. The primary objective is to assess safety and feasibility of the active immunotherapy with Medigene’s dendritic cells. Secondary objectives of the study are induction of immune responses, overall survival (OS), progression free survival (PFS), control of minimal residual disease (MRD) and time to progression (TTP).

Dr. Kai Pinkernell, SVP Clinical Affairs and Chief Medical Officer of Medigene AG, comments: "With this study we aim to improve the outcome of the patients and show that vaccination with dendritic cells can help to control AML, a leukemia with normally high relapse rates. We are glad to announce the complete enrollment of our phase I/II trial as projected, which puts us on track for a study end in 2019. We intend to provide preliminary data on certain aspects of the trial at scientific conferences once a large part of the patients has been treated for more than a year."

About Medigene’s DC vaccines: The platform for the development of antigen-tailored DC vaccines is the most advanced of Medigene’s highly innovative and complementary immunotherapy platforms. Currently Medigene evaluates its DC vaccines in a company-sponsored Phase I/II clinical trial in acute myeloid leukaemia (AML).

Dendritic cells (DCs) are the most potent antigen-presenting cells of our immune system. Their task is to take up, process and present antigens on their cell surface, which enables them to activate antigen-specific T cells for maturation and proliferation. This way T cells can recognize and eliminate antigen-bearing tumor cells. Dendritic cells can also induce natural killer cells (NK cells) to attack tumor cells. The team of Medigene Immunotherapies scientists has developed new, fast and effective methods for generating dendritic cells ex-vivo, which are able to activate both T cells and NK cells. The DC vaccines are developed from autologous (patient-derived) precursor cells, isolated from the patient’s blood, and can be loaded with tumor-specific antigens to treat different types of cancer. Medigene’s DC vaccines are in development for the treatment of minimal residual disease or for use in combination therapies.

About acute myeloid leukaemia (AML): Acute myeloid leukaemia is a malignant disease of the hematopoietic system, affecting mainly adults above 60 years of age. In Germany, about 3,600 incidences are registered annually.
AML is caused by uncontrolled growth of dysfunctional hematopoietic precursor cells in the bone marrow. These cells prevent the generation of normal blood cells, causing a drop in erythrocytes and platelets, for example. Typical symptoms of AML include anemia, fever, increased risk of infection, and blood coagulation disorder. AML progresses rapidly and may be fatal within a few weeks if untreated.
AML is treated initially with intensive chemotherapy. Another treatment option is allogeneic hematopoietic stem cell transplantation. Unfortunately, the majority of patients suffer a relapse. Only about 15 – 20% of the patients show long-term remission after conventional chemotherapy. Allogeneic hematopoietic stem cell transplantation is the only treatment option that offers a more positive prognosis.

On November 27, 2017 Inovio Pharmaceuticals, Inc. (NASDAQ:INO) reported the synergistic effect of combining Inovio’s TERT (telomerase reverse transcriptase) cancer immunotherapy in combination with a checkpoint inhibitor in preclinical tumor model (Press release, Inovio, NOV 27, 2017, View Source [SID1234522244]). The combination therapies resulted in robust anti-tumor effects and showed significant improvement in survival compared to either therapy alone. Preclinical TERT study results were detailed in a paper published in the most recent edition of Molecular Therapy entitled, "Synergy of Immune Checkpoint Blockade with a Novel Synthetic Consensus DNA Vaccine Targeting TERT," by Inovio and its collaborators at the Wistar Institute.

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Dr. J. Joseph Kim, President and CEO, said, "The synergistic anti-tumor effect observed in this published preclinical study provides Inovio with added confidence in the company’s recently initiated efficacy studies combining checkpoint inhibitors and INO-5401, Inovio’s cancer immunotherapy which includes three of Inovio’s top SynCon cancer antigens – hTERT, WT1, and PSMA, which are over-expressed in multiple tumor types. MedImmune, Regeneron and Genentech have all turned to Inovio’s DNA-based immunotherapy products to evaluate increased response rates in combination with their checkpoint inhibitors. We look forward in sharing combination data from these efficacy trials when they become available."

Inovio is currently evaluating its human TERT (hTERT) immunotherapy, INO-1400, as a mono-therapy, in nine different solid tumors including breast, lung and pancreatic cancers. A recent poster presentation at the SITC (Free SITC Whitepaper) annual conference demonstrated that INO-1400 generated hTERT-specific T cell immune responses in patients. Furthermore, hTERT along with WT1 and PSMA antigens also comprise the new multi-antigen immunotherapy INO-5401, which is being evaluated in two separate phase 1/2 efficacy trials in combinations PD-L1 (with Genentech) and PD-1 (with Regeneron) checkpoint inhibitors in metastatic bladder cancer and in newly diagnosed Glioblastoma multiforme (GBM), respectively.

INO-5401 is being tested in combination with PD-1/PD-L1 inhibitors to bring about better anti-tumor effects in metastatic bladder and GBM. Nearly 430,000 new cases of urinary bladder cancer are diagnosed each year worldwide; it accounts for about 165,000 deaths worldwide annually. Advanced unresectable or metastatic UC remains a high unmet medical need as survival remains poor for most patients. The approval of several checkpoint inhibitors for advanced unresectable or metastatic UC has improved response and survival rates for some patients, however, the majority (~80%) of patients do not experience meaningful clinical responses to checkpoint inhibitor monotherapy. GBM is the most aggressive brain cancer and its prognosis is extremely poor. The median overall survival for patients receiving standard of care therapy is approximately 15 months and the average five-year survival rate is less than three percent. Clinical responses to checkpoint inhibitors in GBM patients have been poor overall (ORR<10%). Both of these INO-5401 combination studies are designed to test the synergistic anti-tumor effects of the combination therapies.

Significant early checkpoint combination effects were seen in a clinical study of another Inovio T-cell generating product, INO-3112 (licensed to MedImmune and now called MEDI0457). In a phase 1 study of MEDI0457 in 22 HPV-positive patients with squamous cell carcinoma of the head and neck, Inovio has previously demonstrated that this cancer immunotherapy generated robust antigen-specific CD8+ killer T cell responses measured in both tumor tissue and peripheral blood. One patient who initially displayed a slight increase in T cell immune responses developed progressive disease at 11 months into the study. The patient subsequently received nivolumab, a PD-1 checkpoint inhibitor and sustained complete response after only four doses of nivolumab. This patient continues on therapy with no evidence of disease, 16 months after initiation of nivolumab. Medimmune is currently conducting a separate phase 1/2 efficacy trial combining its PD-L1 inhibitor (durvalumab) with MEDI0457 in 50 metastatic HPV-associated head and neck cancer patients to evaluate the clinical efficacy of the combination treatment. Head and neck cancer caused by HPV is the fastest growing cancer in men today, and the checkpoint inhibitor therapies alone have only been positive in limited percentage (ORR<20%) of treated patients.

This published paper highlights the potential benefits of DNA immunotherapy/immune checkpoint blockade combinations using PD-1 or CTLA4 checkpoint inhibitors in patients that respond poorly to immune checkpoint blockade alone, and allow for better rational design of combination therapies. Furthermore, these results suggest that this synergistic anti-tumor effect is due to the effect of immune checkpoint blockade on expanding effector T cells generated from the TERT therapy in the tumor microenvironment rather than boosting vaccine responses in the periphery.

On November 27, 2017 AstraZeneca reported the submission of a supplemental new drug application (sNDA) to Japan’s Pharmaceuticals and Medical Devices Agency for the use of Tagrisso (osimertinib), a third-generation, irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) with clinical activity against central nervous system (CNS) metastases, for the 1st-line treatment of patients with inoperable or recurrent EGFR mutation-positive (EGFRm) non-small cell lung cancer (NSCLC) (Press release, AstraZeneca, NOV 27, 2017, View Source [SID1234522242]).

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The Japan sNDA is based on data from the Phase III FLAURA trial, in which Tagrisso significantly improved progression-free survival (PFS) compared to current 1st-line EGFR-TKIs, erlotinib or gefitinib, in previously-untreated patients with locally-advanced or metastatic EGFRm NSCLC.

NOTES TO EDITORS

About NSCLC

Lung cancer is the leading cause of cancer death among both men and women, accounting for about one-quarter of all cancer deaths, more than breast, prostate and colorectal cancers combined. Approximately 10-15% of patients in the US and Europe, and 30-40% of patients in Asia have EGFRm NSCLC. These patients are particularly sensitive to treatment with currently-available EGFR-TKIs, which block the cell-signalling pathways that drive the growth of tumour cells. However, tumours almost always develop resistance to EGFR-TKI treatment, leading to disease progression. Approximately half of patients develop resistance to approved EGFR-TKIs such as gefitinib and erlotinib due to the resistance mutation, EGFR T790M.Tagrisso also targets this secondary mutation that leads to disease progression. There is also a need for medicines with improved CNS efficacy, since approximately 25% of patients with EGFR-mutated NSCLC have brain metastases at diagnosis, increasing to approximately 40% within two years of diagnosis.

About Tagrisso

Tagrisso (osimertinib) is a third-generation, irreversible EGFR-TKI designed to inhibit both EGFR-sensitising and EGFR T790M-resistance mutations, with clinical activity against CNS metastases. Tagrisso 40mg and 80mg once-daily oral tablets have been approved in more than 60 countries, including the US, EU, Japan and China, for patients with EGFR T790M mutation-positive advanced NSCLC. Tagrisso is also being investigated in the adjuvant setting and in combination with other treatments.

About the FLAURA trial

The FLAURA trial assessed the efficacy and safety of Tagrisso 80mg once daily vs standard-of-care EGFR-TKIs (either erlotinib [150mg orally, once daily] or gefitinib [250mg orally, once daily]) in previously-untreated patients with locally-advanced or metastatic EGFR-mutated NSCLC. The trial was a double-blinded, randomised trial, with 556 patients across 29 countries.

About AstraZeneca in Lung Cancer

AstraZeneca is committed to developing medicines to help every patient with lung cancer. We have two approved medicines and a growing pipeline that targets genetic changes in tumour cells and boosts the power of the immune response against cancer. Our unrelenting pursuit of science aims to deliver more breakthrough therapies with the goal of extending and improving the lives of patients across all stages of disease and lines of therapy.

About AstraZeneca in Oncology

AstraZeneca has a deep-rooted heritage in Oncology and offers a quickly-growing portfolio of new medicines that has the potential to transform patients’ lives and the Company’s future. With at least six new medicines to be launched between 2014 and 2020, and a broad pipeline of small molecules and biologics in development, we are committed to advance New Oncology as one of AstraZeneca’s five Growth Platforms focused on lung, ovarian, breast and blood cancers. In addition to our core capabilities, we actively pursue innovative partnerships and investments that accelerate the delivery of our strategy, as illustrated by our investment in Acerta Pharma in haematology.

By harnessing the power of four scientific platforms – Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response and Antibody Drug Conjugates – and by championing the development of personalised combinations, AstraZeneca has the vision to redefine cancer treatment and one day eliminate cancer as a cause of death.