On April 24, 2018 AstraZeneca and MedImmune, reported its global biologics research and development arm, reported high-level results from the Phase III ARCTIC trial in patients with locally-advanced or metastatic non-small cell lung cancer (NSCLC) who have received at least two prior treatments (Press release, AstraZeneca, 24 24, 2018, View Source [SID1234525617]). This randomised, open-label, multi-centre trial assessed the efficacy and safety of the combination of Imfinzi (durvalumab) plus tremelimumab, as well as Imfinzi and tremelimumab monotherapies, versus standard-of-care chemotherapy (SoC) in patients with PDL1-low/negative NSCLC (sub-study B), and Imfinzi monotherapy versus SoC in patients with PDL1-high NSCLC (sub-study A).

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In sub-study B, the combination of Imfinzi plus tremelimumab in patients with PD-L1 low/negative NSCLC did not meet the primary endpoints of a statistically-significant and clinically-meaningful improvement in progression-free survival (PFS) and overall survival (OS) compared to SoC. Activity and safety of monotherapy arms of sub-study B were consistent with prior published data.

Sub-study A was not powered for statistical significance; however, Imfinzi monotherapy showed a clinically-meaningful reduction in the risk of death compared to chemotherapy.

Full data from the ARCTIC trial will be presented at a forthcoming medical meeting.

Sean Bohen, Executive Vice President, Global Medicines Development and Chief Medical Officer, said: "While we are disappointed that the combination of Imfinzi plus tremelimumab did not result in a statistically-significant survival benefit in this heavily pre-treated patient population, we are encouraged by the activity of Imfinzi monotherapy observed in this trial and look forward to presenting the full data from the ARCTIC trial at an upcoming medical meeting."

AstraZeneca recently received approval from the US FDA for Imfinzi for the treatment of patients with unresectable, Stage III NSCLC whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy.

NOTES TO EDITORS
About ARCTIC

The ARCTIC trial was a randomised, open-label, multi-centre, global Phase III trial containing two sub-studies: sub-study A (1:1 randomisation of patients with PDL1-high tumours to Imfinzi (durvalumab) vs. SoC) and sub-study B (2:3:1:2 randomisation of patients with PDL1-low/negative tumours to Imfinzi monotherapy, Imfinzi plus tremelimumab or tremelimumab vs SoC). Tumour PD-L1 expression was assessed with the Ventana PD-L1 (SP263) assay with PD-L1 high defined as ≥25% of tumour cells with membrane staining.

About Imfinzi

Imfinzi is a human monoclonal antibody that binds to PD-L1 and blocks the interaction of PD-L1 with PD-1 and CD80, countering the tumour’s immune-evading tactics and releasing the inhibition of immune responses.

In February 2018, Imfinzi received US FDA approval for the treatment of patients with unresectable, Stage III NSCLC whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy. Imfinzi also received accelerated approval in the US for the treatment of patients with locally-advanced or metastatic urothelial carcinoma, who have disease progression during or following platinum-containing chemotherapy, or whose disease has progressed within 12 months of receiving platinum-containing chemotherapy before (neoadjuvant) or after (adjuvant) surgery.

As part of a broad development programme, Imfinzi is also being tested as a monotherapy and in combination with tremelimumab, an anti-CTLA-4 monoclonal antibody and potential new medicine, as a first-line treatment for patients with NSCLC, small cell lung cancer, locally-advanced or metastatic urothelial carcinoma, head and neck cancer and other solid tumours.

About tremelimumab

Tremelimumab is a human monoclonal antibody and potential new medicines that targets the activity of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). Tremelimumab blocks the activity of CTLA-4, contributing to T cell activation and boosting the immune response to cancer. Tremelimumab is being tested in an extensive clinical-trial programme in combination with Imfinzi in NSCLC, locally-advanced or metastatic urothelial carcinoma, head and neck cancer, liver cancer and blood cancers.

About AstraZeneca in NSCLC

Lung cancer is the leading cause of cancer death among both men and women, accounting for about one-third of all cancer deaths and more than breast, prostate and colorectal cancers combined.

AstraZeneca has a comprehensive portfolio of approved and potential new medicines in late-stage clinical development for the treatment of NSCLC across all stages of disease and lines of therapy. We aim to address unmet needs of patients with EGFR-mutated tumours as a genetic driver of disease, which occur in 10-15% of NSCLC patients in the US and EU and 30-40% of NSCLC patients in Asia, with our approved medicines Iressa and Tagrisso and ongoing FLAURA and ADAURA trials. Our extensive late-stage immuno-oncology programme focuses on 75-80% of patients with NSCLC without a known genetic mutation. Our portfolio includes Imfinzi, an anti-PDL1 antibody, which is in development as monotherapy (ADJUVANT, PACIFIC, MYSTIC, PEARL and ARCTIC trials) and in combination with tremelimumab (MYSTIC, NEPTUNE, ARCTIC and POSEIDON trials).

About AstraZeneca’s Approach to Immuno-Oncology

Immuno-Oncology (IO) is a therapeutic approach designed to stimulate the body’s immune system to attack tumours. At AstraZeneca and MedImmune, our biologics research and development arm, our IO portfolio is anchored by immunotherapies that have been designed to overcome anti-tumour immune suppression. We believe that IO-based therapies will offer the potential for life-changing cancer treatments for the clear majority of patients.

We are pursuing a comprehensive clinical-trial programme that includes Imfinzi (anti-PD-L1) as monotherapy and in combination with tremelimumab (anti-CTLA-4) in multiple tumour types, stages of disease, and lines of therapy, using the PD-L1 biomarker as a decision-making tool to define the best potential treatment path for a patient. In addition, the ability to combine our IO portfolio with small, targeted molecules from across our Oncology pipeline, and with those of our research partners, may provide new treatment options across a broad range of tumours.

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 advancing Oncology as a growth driver for AstraZeneca, 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.

About MedImmune

MedImmune is the global biologics research and development arm of AstraZeneca, a global, innovation-driven biopharmaceutical business that focuses on the discovery, development and commercialisation of small-molecule and biologic prescription medicines. MedImmune is pioneering innovative research and exploring novel pathways across Oncology; Respiratory; Cardiovascular, Renal & Metabolic Diseases; and Infection and Vaccines. The MedImmune headquarters is located in Gaithersburg, MD, one of AstraZeneca’s three global R&D centres, with additional sites in Cambridge, UK, and Mountain View, CA. For more information, please visit www.medimmune.com.

On April 24, 2018 Takeda Pharmaceutical Company Limited ("Takeda") reported the statement made by Shire plc ("Shire") and confirms that it has made a revised proposal to the Board of Shire.

There can be no certainty that any firm offer for the Company will be made nor as to the terms on which any firm offer might be made.

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Other matters

In accordance with Rule 2.6(a) of the Code, Takeda must, by no later than 5.00 p.m. (London time) on 25 April 2018, either announce a firm intention to make an offer, subject to conditions or pre-conditions if relevant, for Shire in accordance with Rule 2.7 of the Code or announce that it does not intend to make an offer for Shire, in which case the announcement will be treated as a statement to which Rule 2.8 of the Code applies. This deadline will only be extended with the consent of the UK Panel on Takeovers and Mergers (the "Panel") in accordance with Rule 2.6(c) of the Code.

In accordance with Rule 26.1 of the Code, a copy of this announcement will be published on the Takeda website (View Source) by no later than 12 noon (London time) on April 25, 2018. The content of the websites referred to in this announcement is not incorporated into and does not form part of this announcement.

On April 24, 2018 Checkmate Pharmaceuticals (Checkmate)  reported that it had initiated treatment with CMP‐001 combined with atezolizumab (TECENTRIQ) in a Phase 1b clinical trial of patients with advanced non‐small cell lung cancer (NSCLC) and disease progression on prior anti‐PD‐1/PD‐L1 therapy (Press release, Checkmate Pharmaceuticals, APR 24, 2018, View Source [SID1234525653]).

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CMP-001 is designed to activate innate immunity to convert "uninflamed" tumors, which generally do not respond to anti-PD-1/L1 therapy, into "inflamed" tumors, which are responsive to PD-1 inhibition. When used in combination with PD-1/PD-L1 inhibitors, CMP-001 has the potential to increase the number of cancer patients who respond to checkpoint inhibitor therapies and to increase the magnitude and duration of the antitumor responses, possibly providing added clinical benefit.

"We are pleased to be advancing the clinical development of CMP-001 into a second tumor type," stated Art Krieg, founder and CEO of Checkmate Pharmaceuticals. "The mechanism of action of CMP-001 should apply across most or all tumor types, and so we expect CMP-001 to reverse PD-1 resistance in NSCLC, just as we reported for PD-1 resistant advanced melanoma last week at the 2018 American Association of Cancer Research Annual Meeting in Chicago," noted Dr. Krieg.

The trial is designed as a multi-center, open label, two-part Phase 1b study of CMP-001 administered in combination with atezolizumab with and without low-level radiation therapy. Part one of the study will evaluate CMP-001 (5 mg dose) administered subcutaneously (SC) weekly for two weeks and then intratumorally (IT) weekly for three weeks, followed by either SC or IT injection every three weeks.

In the second part of the trial, the combination of CMP-001 and atezolizumab therapy will be preceded by low-level radiation therapy to the target lesion. "In our ongoing melanoma trial we learned that patients whose tumors contain more plasmacytoid dendritic cells (pDC) appear to be more likely to respond to CMP-001 in combination with checkpoint inhibitor therapy. Low dose radiation therapy recruits pDC into tumors, and so we expect this triple combination regimen to increase the response rate to our therapy," explained Dr. Krieg. Patients will be monitored for safety and tolerability, as well as clinical response. Correlative studies will also be undertaken to characterize the immune effects of treatment in the blood and tumors.

About CMP-001

CMP-001, is a first-in-class CpG-A Toll-like receptor 9 (TLR9) agonist, that is encapsulated in a virus-like particle (VLP) and is designed to activate the innate immune system via TLR9 and mediate tumor control by the subsequent induction of both innate and adaptive anti-tumor immune responses, thereby converting immunologically "cold" tumors to immunologically "hot" tumors. It is the only CpG-A class TLR9 agonist in clinical trials and differs from other CpG classes in clinical development by having a native DNA backbone that induces the highest levels of type I IFN. Based on analysis of gene expression in human tumors showing that increased IFN gene expression is associated with better response to PD-1 inhibition, it is believed that this mechanism of action may restore, enable or improve responses to anti-PD-1/PD-L1 therapeutics.

CMP-001 is being evaluated in multiple tumor types to assess its safety, activity, alternative routes of administration and combination with other immunotherapies and modalities. For information on CMP-001 trials that are currently recruiting patients, please visit www.clinicaltrials.gov.

On April 24, 2018 Atossa Genetics Inc. (ATOS) ("Atossa" or the "Company"), a clinical-stage pharmaceutical company developing novel therapeutics and delivery methods to treat breast cancer and other breast conditions, reported that it has received a positive interim review on its Phase 1 study of topical endoxifen in men, which is being developed to address gynecomastia (or male breast enlargement), which is a common condition in patients being treated for prostate cancer (Press release, Atossa Genetics, APR 24, 2018, View Source [SID1234525619]). The Independent Safety Committee reviewed the blinded data generated from the first group in the study (eight subjects) and concluded that the study may advance to the next dosing level.

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"This positive safety determination is on the critical path for a successful outcome of this Phase 1 study in men," stated Dr. Steven Quay, Ph.D., MD, President and CEO of Atossa. "It is the first assessment of our clinical safety and tolerability data and it indicates that proceeding to the next dosing level with our proprietary topical endoxifen is warranted. We can now advance to the next level of the study which is to escalate the dosage in a new cohort of subjects as we continue to monitor safety and tolerability in the first cohort of the study." Dr. Quay added, "We believe this is the first clinical trial ever conducted of a topical pharmaceutical for the treatment of gynecomastia. There are no approved drugs, either topical or oral, for this important, unmet medical need which affects 25% of men ages 50-69."

The objectives of this double-blinded, placebo-controlled, repeat dose study of 24 healthy male subjects is to assess the pharmacokinetics of proprietary formulations of topical endoxifen dosage forms over 28 days, as well as to assess safety and tolerability. The study is being conducted on behalf of Atossa by CPR Pharma Services Pty Ltd., Thebarton, SA, Australia.

About Gynecomastia

Gynecomastia is male breast enlargement and accompanying pain. It is the most common male breast disorder and is caused by a hormone imbalance where testosterone is low compared to estrogen. In prostate cancer treatment, testosterone is suppressed resulting is higher estrogen levels that usually triggers gynecomastia. Prophylactic breast bud irradiation is commonly used in prostate cancer patients, but must often be repeated. One recent study indicates that up to 90% of men taking androgen deprivation therapy suffer from gynecomastia and breast pain (Handoo Rhee, et al., October 18, 2014, BJU International).

According to the Mayo Clinic, although it can affect men at almost any age, it is most prevalent in men ages 50-69, affecting at least 1 in 4 men in this age group. Gynecomastia is caused by, among other things, any number of commonly prescribed medications, such as androgen deprivation therapy to treat prostate enlargement and prostate cancer; anti-anxiety medications; cancer treatments (chemotherapy), and some heart medications. Gynecomastia is not only painful and embarrassing, it can also cause men to stop taking these important medications.

There are no FDA-approved therapeutics for gynecomastia. Breast-bud irradiation, use of compression garments and plastic surgery are the most common approaches used to treat gynecomastia.

On April 24, 2018 Five Prime Therapeutics, Inc. (NASDAQ: FPRX), a clinical-stage biotechnology company focused on discovering and developing innovative immuno-oncology protein therapeutics, reported that it will report its first quarter 2018 financial results on Tuesday, May 8, 2018, after the U.S. financial markets close (Press release, Five Prime Therapeutics, APR 24, 2018, View Source [SID1234525637]). Five Prime will host a conference call and live audio webcast on Tuesday, May 8, 2018, at 4:30 p.m. (ET)/1:30 p.m. (PT) to discuss the company’s financial results and provide a general business update.

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The live audio webcast may be accessed through the "Events & Presentations" page in the "Investors" section of the company’s website at www.fiveprime.com. Alternatively, participants may dial (877) 878-2269 (domestic) or (253) 237-1188 (international) and refer to conference ID 6585139.

The archived conference call will be available on Five Prime’s website beginning approximately two hours after the event and will be archived and available for replay for at least 30 days after the event. (Press release, Five Prime Therapeutics, APR 24, 2018, View Source [SID1234525637])