On December 18, 2017 AstraZeneca reported that the US Food and Drug Administration (FDA) has accepted a supplemental New Drug Application (sNDA) 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, in the 1st-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumours have EGFR mutations (exon 19 deletions or exon 21 (L858R) substitution mutations) (Press release, AstraZeneca, DEC 18, 2017, View Source [SID1234522687]). The FDA has granted Tagrisso Priority Review status and previously granted Breakthrough Therapy Designation in the 1st-line treatment of patients with metastatic EGFR mutation-positive (EGFRm) NSCLC.

The submission acceptance 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.

On 28 September 2017, the US National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology were updated to include the use of Tagrisso in the 1st-line treatment of patients with metastatic EGFRm NSCLC. The use of Tagrisso in this indication is not yet approved by the FDA.

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.

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On December 18, 2017 Transgene (Paris:TNG) (Euronext Paris: TNG) reported that Management will participate in the upcoming investor events set out below (Press release, Transgene, DEC 18, 2017, View Source [SID1234522690]).

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Transgene will meet institutional investors from January 7 to 11, 2018, in San Francisco, USA, concurrent with the J.P. Morgan Healthcare conference.

The Company will also attend:

Oddo Forum: January 11 & 12, 2018 – Lyon, France
Portzamparc MidCap Conference: April 4, 2018 – Paris, France
Small Cap Event: April 16 & 17, 2018 – Paris, France
Kempen Life Sciences Conference: April 18 & 19, 2018 – Amsterdam, Netherlands

On December 18, 2017 Can-Fite BioPharma Ltd. (NYSE American: CANF) (TASE:CFBI), a biotechnology company advancing a pipeline of proprietary small molecule drugs that address cancer, liver and inflammatory diseases, reported an update on its Phase II clinical trial with drug candidate Namodenoson (CF102) in the treatment of advanced hepatocellular carcinoma (HCC). Ongoing close observation of enrolled subjects indicates a potentially favorable drug safety profile (Press release, Can-Fite BioPharma, DEC 18, 2017, View Source [SID1234522681]). The Company previously announced in August that it had successfully completed enrollment of 78 patients.

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The global Phase II study is being conducted in the U.S., Europe and Israel. Patients with advanced HCC, Child Pugh B, who failed Nexavar (sorafenib) as a first line treatment are treated twice daily with 25 mg of oral Namodenoson or placebo using a 2:1 randomization. The primary endpoint of the Phase II study is Overall Survival (OS). Secondary endpoints include Progression Free Survival (PFS), safety, and the relationship between outcomes and A3AR expression.

Although the trial remains blinded to the Company, accumulated safety data to date indicates a potentially favorable drug safety profile without hepatotoxicity and possible positive clinical effects. There are now subjects treated for more than one year and in some cases, two years. To date, 15 subjects have completed at least 12 cycles of treatment (each cycle is 28 days of treatment) of which two completed 24 cycles. The Company anticipates data release to occur in 2H2018.

Can-Fite CEO Dr. Pnina Fishman commented, "We are pleased with the progress so far in our clinical trial for Namodenoson for the treatment of advanced HCC, the third leading cause of cancer deaths worldwide, and look forward to data release later in 2018."

Can-Fite received Orphan Drug Designation for Namodenoson in Europe and the U.S., as well as Fast Track Status in the U.S. as a second line treatment for HCC.

About Namodenoson

Namodenoson is a small orally bioavailable drug that binds with high affinity and selectivity to the A3 adenosine receptor (A3AR). Namodenoson is being evaluated in Phase II trials for two indications, as a second line treatment for hepatocellular carcinoma, and as a treatment for non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). A3AR is highly expressed in diseased cells whereas low expression is found in normal cells. This differential effect accounts for the excellent safety profile of the drug.

On December 18, 2017 Intellia Therapeutics, Inc. (NASDAQ:NTLA), a leading genome editing company focused on developing curative therapeutics using CRISPR/Cas9 technology, reported that it has named John Leonard, M.D., President and Chief Executive Officer (CEO), effective January 1, 2018 (Press release, Intellia Therapeutics, DEC 18, 2017, View Source [SID1234522683]). Dr. Leonard succeeds Nessan Bermingham, Ph.D., Intellia’s founding President and CEO, who is returning to the venture capital industry. In recognition of the company’s growth and expanding pipeline, the Board of Directors and Dr. Bermingham agreed that Dr. Leonard should lead the Company as it progresses toward clinical development, given his experience in successfully developing biopharmaceutical products and leading large scientific organizations.

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Dr. Leonard joined Intellia in 2014 as the Company was being formed. He initially served as Intellia’s Chief Medical Officer and as a member of its Board of Directors, and together with Dr. Bermingham, set the strategic direction of the Company. In 2016, Dr. Leonard became Intellia’s Executive Vice President of Research & Development (R&D). Prior to Intellia, Dr. Leonard was Chief Scientific Officer and Senior Vice President of Research and Development at AbbVie, Inc., a global biopharmaceutical company, which was spun off from Abbott Laboratories in 2013. At Abbott, Dr. Leonard served as Senior Vice President of Global Pharmaceutical Research & Development from 2008 to 2012.

His combined tenure at Abbott and AbbVie spanned 22 years from 1992, until his retirement from AbbVie in 2013. Dr. Leonard was responsible for the development of the groundbreaking HIV protease inhibitors Norvir and Kaletra, which led to new treatment paradigms for HIV/AIDS.

He also led AbbVie’s HCV programs, laid the foundation for its Oncology effort and guided the development of HUMIRA, the all-time, top-selling pharmaceutical product worldwide.

"After nearly four years of building Intellia and this exceptional team, the Company is now poised to begin development of CRISPR/Cas9-based therapies," says Nessan Bermingham, Ph.D. "At this stage, Intellia requires a CEO with a track record of successful drug development. John was the first to join me in starting Intellia, and was an ideal partner because of his unmatched R&D expertise and biopharmaceutical leadership experience. As I return to my roots in biotech venture capital, I am confident that Intellia, the science and our employees are in great hands."

"With more than a 30-year career in biopharmaceutical R&D, John is well recognized as a premier R&D leader, having developed many breakthrough medicines that turned into life-improving therapies for patients. As Intellia progresses towards clinical development, we are fortunate that he will lead the company," says Intellia’s Chairman Perry Karsen. "We thank Nessan for his passion and leadership in taking Intellia from an idea through preclinical science, initial public offering and the path to the clinic. As Intellia’s founder, Nessan had great vision for what was possible with the CRISPR/Cas9 technology and its application in human therapeutics."

"Intellia has made significant progress in advancing the CRISPR/Cas9 technology and in applying it in our pre-clinical programs, as well as in those of our partners Novartis and Regeneron," says John Leonard, M.D. "As we enter the next phase, our ambition and business strategy remains the same. We will build on Nessan’s vision, and advance our mission of developing curative genome editing treatments that can positively transform the lives of people living with severe and life-threatening diseases."

On December 18, 2017 Aduro Biotech, Inc. (Nasdaq:ADRO), a biopharmaceutical company with three distinct immunotherapy technologies, reported that the first patient in its Phase 1/2 dose escalation and dose expansion clinical trial (see www.clinicaltrials.gov, identifier NCT03340883) has been dosed at Virginia Cancer Specialists in Fairfax, Virginia, the first site in this multi-center trial (Press release, Aduro Biotech, DEC 18, 2017, View Source;p=RssLanding&cat=news&id=2323132 [SID1234522686]). The study is designed to evaluate the safety and activity of BION-1301, a humanized anti-APRIL (A PRoliferation-Inducing Ligand) antibody, for adults with relapsed or refractory multiple myeloma.

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"Neutralizing APRIL is a differentiated approach in the treatment of multiple myeloma, and it has been shown to inhibit tumor growth and overcome drug resistance in preclinical studies," said Natalie Sacks, M.D., chief medical officer of Aduro Biotech. "BION-1301 is our wholly-owned novel antibody that has been shown in non-clinical studies to fully block the APRIL-induced signaling cascade at a critical juncture, and we are eager to further characterize its potential activity in the clinic. Until there is a cure for multiple myeloma which remains a debilitating disease, alternative treatments are needed."

Recently, two datasets on anti-APRIL were presented at the 59TH American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in Atlanta, Georgia. Data presented by Yu-Tzu Tai, Ph.D., of the Dana Farber Cancer Institute in an oral session at ASH (Free ASH Whitepaper) demonstrate that BION-1301 and its parental antibody blocked APRIL binding to both its receptors BCMA and TACI. Blocking APRIL with BION-1301 (or its parental antibody) not only inhibited proliferation and survival of multiple myeloma cells but it also alleviated drug resistance and immune suppression in preclinical models and cell culture, leading to enhanced anti-BCMA and daratumumab-mediated myeloma cell killing. Additionally, Dr. Tai and her colleagues demonstrated that regulatory T cells in the blood and bone marrow expressed TACI, and that APRIL blockade inhibited their function. Also, John Dulos, Ph.D., director and project team leader at Aduro Biotech, and his team conducted preclinical pharmacokinetic and pharmacodynamic studies indicating BION-1301 was well tolerated and binding of APRIL in preclinical models resulted in decreased IgA, IgG and IgM production in a dose-dependent fashion.

"We know that APRIL sets off a cascade of events that hinders the immune response to multiple myeloma cells, helping the disease escape immune attack. The data presented at ASH (Free ASH Whitepaper) indicate that blocking APRIL by targeting BCMA alone may not be sufficient for the treatment of multiple myeloma, as APRIL critically modulates regulatory T cell function via TACI, not BCMA," said Dr. Tai. "Importantly, BION-1301, as a fully-blocking monoclonal antibody, may have unique efficacy by inhibiting APRIL-induced proliferation of immune system components linked to multiple myeloma progression."

About Phase 1/2 Trial
The Phase 1/2 multi-center, open-label study is designed to evaluate the safety and activity of BION-1301 in patients with relapsed or refractory multiple myeloma whose disease has progressed after at least 3 prior systemic therapies, including immunomodulatory drugs (IMiDs), proteasome inhibitors, chemotherapies, or monoclonal antibodies. The Phase 1 part of the study will evaluate the safety, pharmacokinetics and pharmacodynamics of escalating doses of BION-1301 administered once every two weeks in a 28-day cycle. Once the recommended Phase 2 dose is determined, the Phase 2 part of the study will begin. It will assess safety and preliminary activity of BION-1301 at the selected dose, with a primary activity endpoint of objective response rate.

About APRIL and BION-1301
APRIL (A PRoliferation-Inducing Ligand) is a member of the tumor necrosis factor (TNF) superfamily and is primarily secreted by bone marrow and/or myeloid cells. APRIL is overproduced in patients with multiple myeloma and binds to BCMA (B cell maturation antigen) and TACI (Transmembrane Activator and CAML Interactor) to stimulate a wide variety of responses that promote multiple myeloma growth and suppress the immune system so that the tumor cells are allowed to proliferate. BION-1301 is a humanized anti-APRIL antibody that has been shown in preclinical studies to effectively neutralize APRIL, eliminate malignant cells and reduce resistance to therapy in models of multiple myeloma. In addition to multiple myeloma, APRIL’s role in other cancers and in B cell dependent autoimmune and inflammatory diseases indicate that BION-1301 may also be useful in treating chronic lymphocytic leukemia, colorectal cancer and Berger’s disease (caused by IgA antibody deposits in the kidneys).

About Multiple Myeloma
Lymphocytes (B cells and T cells) are the primary cell types within the immune system that work together to fight infection and disease. As B cells respond to normal infection in the body, they mature and change into plasma cells, which in turn make antibodies that help the body attack infection. While lymphocytes circulate throughout the body, plasma cells remain primarily in the bone marrow. Multiple myeloma is a blood cancer that occurs when malignant plasma cells proliferate uncontrollably. Approximately 50,000 new cases of multiple myeloma are expected to be diagnosed in the United States and Europe each year. While many new therapies have become available in recent years, multiple myeloma remains incurable and significant unmet needs exist among patients who relapse following, are resistant to, or cannot tolerate currently available agents.