On April 27, 2018 The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency reported that it has adopted a positive opinion, recommending a change to the terms of the Marketing Authorisation for Tagrisso (osimertinib) to include the 1st-line treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with activating epidermal growth factor receptor (EGFR) mutations (Press release, AstraZeneca, APR 27, 2018, View Source [SID1234525785]). The recommendation is based on results from the Phase III FLAURA trial, which were presented at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) 2017 Congress and published in the New England Journal of Medicine.

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Sean Bohen, Executive Vice President, Global Medicines Development and Chief Medical Officer at AstraZeneca, said: "This positive recommendation acknowledges Tagrisso’s potential as a new 1st-line standard of care for patients with EGFR-mutated NSCLC in Europe. It reflects the strength of the FLAURA data that show Tagrisso delivered a statistically-significant and clinically-meaningful improvement in progression-free survival over the EGFR-TKI comparator arm across all pre-specified patient subgroups, including those with or without central nervous system metastases."

Safety data for Tagrisso were in line with those observed in prior clinical trials. Tagrisso was well tolerated, with fewer Grade 3 or higher adverse events (AEs) than with standard EGFR-TKIs (34% vs. 45%). In all patients, the most common adverse reactions were rash (58% [1.1% Grade ≥3] for Tagrisso vs. 78% [6.9% Grade ≥3] for the comparator arm), diarrhoea (58% [2.2% Grade ≥3] for Tagrisso vs. 57% [2.5% Grade ≥3] for the comparator arm) and dry skin (36% [<1% Grade ≥3] for Tagrisso vs. 36% [1.1% Grade ≥3] for the comparator arm).

The positive opinion from the CHMP will now be reviewed by the European Commission, which has the authority to approve medicines for the 28 EU member countries plus Iceland, Norway and Liechtenstein. Earlier this month, Tagrisso was approved in the US for the 1st-line treatment of patients with metastatic NSCLC whose tumours have EGFR mutations (exon 19 deletions or exon 21 L858R mutations). In addition to the EU, Tagrisso is under regulatory review in Japan for use in the 1st-line treatment setting with a decision anticipated in the second half of 2018. Other global health authority reviews and submissions are also ongoing.

Notes to Editors
About NSCLC

Lung cancer is the leading cause of cancer death among both men and women, accounting for about one-fifth 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 EGFR-mutated (EGFRm) NSCLC. These patients are particularly sensitive to treatment with EGFR-TKIs, which block the cell-signalling pathways that drive the growth of tumour cells. Tumours almost always develop resistance to EGFR-TKI treatment, however, leading to disease progression. Approximately half of patients develop resistance to approved EGFR-TKIs such as gefitinib, erlotinib and afatinib due to the EGFR T790M resistance mutation. There is also a need for medicines with improved CNS efficacy, since approximately 25% of patients with EGFRm 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 the US and Brazil for 1st-line EGFRm advanced NSCLC, and in more than 75 countries, including the US, EU, Japan and China for patients with EGFR T790M mutation-positive advanced NSCLC. Tagrisso is also being tested 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 EGFRm NSCLC. The trial was double-blinded and randomised, 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 three 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 Oncology as a key 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.

On April 27, 2018 Sanofi reported financial results for the first quarter ended March 31, 2018 (Press release, Sanofi, APR 27, 2018, View Source [SID1234525827]).

First-quarter 2018 reflected strong Specialty Care sales offset by U.S. Lantus and sevelamer exclusivity losses

Net sales were €7,898 million, down 8.7% on a reported basis, down 0.4%(3) at CER and down 1.1% at CS/CER(4).
Sanofi Genzyme sales grew strongly, up 16.2%(5), driven by contribution from the new immunology franchise.
Vaccines sales (-0.9%) reflected strong performance in EU, offset by expected Pentaxim supply constraint in China.
CHC sales grew 2.0% supported by double-digit growth in Emerging Markets(6).
Diabetes and Cardiovascular GBU sales down 15.7%; global Diabetes franchise sales declined 10.0%.
Emerging Markets sales(6) increased 8.3%, driven by double-digit growth in China and Latin America.
2018 guidance confirmed

First-quarter 2018 business EPS(1) increased 1.4% at CER to €1.28.
First-quarter 2018 IFRS EPS was €0.81 (-82.0%) due to a gain on disposal of the Animal Health business in 2017.
Sanofi continues to expect 2018 Business EPS to grow between 2% and 5% at CER(7) barring unforeseen major adverse events. Applying the average April 2018 exchange rates, the currency impact on 2018 Business EPS is estimated to be around -7%.
Announcement of a €1.5bn share buyback program(8) expected to be completed in mid-2019

Sanofi strengthens leadership in Specialty Care through the addition of a Rare Blood Disorder franchise

Sanofi completed the acquisition of Bioverativ and consolidated its financial results from March 9.
First patient dosed with fitusiran, a novel RNAi therapeutic for hemophilia, in phase 3 ATLAS program.
Ablynx acquisition(9) will add caplacizumab for aTTP(10) (submitted in EU) and innovative Nanobody platform.
Sustaining innovation in R&D

Praluent significantly reduced the risk of cardiovascular events in high risk patients in the ODYSSEY OUTCOMES study and was associated with a lower death rate.
Dupixent supplemental BLA filed in the U.S., Japan and EU for moderate-to-severe asthma in adults and adolescents.
Cemiplimab filed in EU for metastatic cutaneous squamous cell carcinoma.
Sotagliflozin submitted in the U.S. and EU for type 1 diabetes.

On April 27, 2018 Sterias Biotherapeutics, Inc. (NYSE MKT:AST), a biotechnology company dedicated to developing cell-based therapeutics to treat neurological conditions associated with demyelination and cellular immunotherapies to treat cancer, reported that Nate Manley, Asterias’ Associate Director of Neurobiology, will present an AST-OPC1 program update at the American Society for Neural Therapy and Repair INTR-15 Conference, which is being held during April 25-28, 2018 in Clearwater Beach, Florida (Press release, Asterias Biotherapeutics, APR 27, 2018, View Source;date=April+27%2C+2018&title=Asterias+Biotherapeutics+to+Present+AST-OPC1+Program+Update+at+the+Upcoming+American+Society+for+Neural+Therapy+and+Repair+Conference [SID1234525789]).

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The details of the presentation are as follows:

Title: ESC-Derived Oligodendrocyte Progenitor Cells (AST-OPC1): Clinical Update and Preclinical Progress in Spinal Cord Injury
Date: Saturday, April 28, 2018
Time: 10:00 am – 11:15 am Eastern Time

On April 27, 2018 Bolder BioTechnology, Inc. reported that it has completed a Phase 1 clinical trial of BBT-015, a proprietary long-acting granulocyte colony-stimulating factor (G-CSF) analog, in healthy human volunteers (Press release, Bolder BioTechnology, APR 27, 2018, View Source [SID1234525790]). BBT-015 is being developed as a treatment for chemotherapy-related neutropenia in cancer patients and for Acute Radiation Syndrome. Demonstration that the drug is safe in healthy volunteers is one of the requirements for Food and Drug Administration approval of the drug to treat Acute Radiation Syndrome.

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Joe Cox, Ph.D., Bolder BioTechnology’s President said, "We are very pleased with the results of this trial, which appear to confirm the increased potency of BBT-015 compared to other approved G-CSF products. The trial studied the pharmacokinetics, pharmacodynamics, safety and tolerability of single subcutaneous administrations of three different dose levels of BBT-015 (0.01, 0.04, and 0.1 mg/kg), and a single dose level (0.1 mg/kg) of a comparator drug, pegfilgrastim (Neulastaâ, Amgen, Inc.). There were 5 male subjects per treatment group. The clinical trial was conducted by Celerion, Inc. (Lincoln, NE), and we are grateful for their rapid patient recruitment and excellent study performance."

"BBT-015 plasma levels were dose-dependent, being highest in subjects receiving the 0.1 mg/kg dose; at this dose, mean peak BBT-015 plasma levels were about two-fold higher than mean peak pegfilgrastim plasma levels. All BBT-015 doses stimulated long-lasting increases in circulating neutrophils. Mean peak neutrophil levels reached a maximum in subjects treated with 0.04 mg/kg and 0.1 mg/kg BBT-015, and were higher in these subjects than in subjects treated with 0.1 mg/kg pegfilgrastim."

"BBT-015 also stimulated dose-dependent increases in circulating peripheral blood progenitor cells (CD34+ cells), which are used in hematopoietic stem cell transplants. Mean peak CD34+ cell numbers were about 50% higher in subjects treated with 0.1 mg/kg BBT-015 compared to subjects treated with the 0.1 mg/kg pegfilgrastim."

"All BBT-015 doses were well tolerated and all subjects completed the trial. All adverse events attributed to BBT-015 were rated as mild, while adverse events attributed to pegfilgrastim were rated as mostly mild, with a couple moderate. Musculoskeletal pain and headaches were the most frequent adverse events for both drugs. Subjects treated with the 0.01 and 0.04 mg/kg BBT-015 experienced fewer than half as many adverse events as subjects treated with 0.1 mg/kg BBT-015 or 0.1 mg/kg pegfilgrastim. None of the 15 subjects treated with BBT-015 reported feeling nauseous or vomiting, which are common side effects of other G-CSF drugs. None of the subjects developed antibodies to BBT-015 or pegfilgrastim."

"Although subject numbers in this trial are small, the data are very promising and warrant further study of BBT-015 in additional clinical trials."

About BBT-015

BBT-015 is a long-acting G-CSF analog that stimulates production of neutrophils, a type of white blood cell important for fighting infections. G-CSF has a short half-life in humans and typically is administered to patients by daily injection. BBT-015 has been selectively modified with the polymer polyethylene glycol at a unique site in the protein, which allows the protein to last longer in patients, reducing the need for frequent administration and increasing the protein’s ability to stimulate long-lasting production of neutrophils.

On April 26, 2018 Corvus Pharmaceuticals, Inc. (NASDAQ:CRVS), a clinical-stage biopharmaceutical company focused on the development and commercialization of precisely targeted oncology therapies, reported that it is enrolling patients in a multicenter Phase 1/1b clinical trial of CPI-006, a humanized monoclonal antibody directed against CD73 (Press release, Corvus Pharmaceuticals, APR 26, 2018, View Source;p=RssLanding&cat=news&id=2344945 [SID1234525734]). The three-arm study in patients with a variety of solid tumors is evaluating CPI-006 administered as a single agent, in combination with Corvus’ CPI-444, a selective and potent inhibitor of the adenosine A2A receptor, and in combination with pembrolizumab, an anti-PD-1 antibody.

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"CPI-006 is an antibody engineered to completely inhibit the CD73 enzyme by binding to its active site. We look forward to evaluating this anti-CD73 antibody in our comprehensive Phase 1/1b trial, which we believe is the first human clinical trial in oncology to evaluate the effect of dual-blockade of the adenosine pathway by inhibiting both CD73 and the A2A receptor," said Richard A. Miller, M.D., an oncologist and co-founder, president and chief executive officer of Corvus. "This trial is designed to answer multiple important questions regarding the role of CD73 blockade and the adenosine pathway in patients with advanced cancer. With the initiation of this new trial and our ongoing Phase 1/1b clinical trial of CPI-444, we continue to reinforce our leadership position in this new therapeutic area."

ABOUT THE PHASE 1/1B TRIAL DESIGN
The Phase 1/1b trial is designed to select the dose and evaluate the safety, pharmacokinetics, immune biomarkers and efficacy of CPI-006 as a single agent, in combination with CPI-444 and in combination with pembrolizumab. Patients with non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC), and other cancers who have failed standard therapies are eligible. The efficacy endpoints are complete response (CR), partial response (PR), disease control rate, duration of response, progression-free survival and overall survival.

In the dose-selection part of the trial, doses of CPI-006 will be escalated in the single-agent arm and in the two combination arms to determine the maximally tolerated dose or the dose that saturates the CD73 enzyme. Fixed doses of CPI-444 and pembrolizumab will be used. Once an optimum dose of CPI-006 is determined, the second part of the trial will enroll patients in nine cohorts: three will receive CPI-006 alone, three will receive CPI-006 in combination with CPI-444, and three will receive CPI-006 with pembrolizumab. Patients with NSCLC, RCC and the group of other cancers will be enrolled into each of the three disease-specific arms. Each of the nine cohorts may initially enroll up to 11 patients. However, if there is one or more objective responses (CR or PR) in the 11 patients, the cohort may be expanded to 28 patients. The trial may enroll up to 350 patients in total.

ABOUT CD73 AND ADENOSINE
CD73 is a cell surface enzyme whose function is to convert adenosine monophosphate (AMP) to adenosine by removing phosphate from AMP. CD73 is expressed on cells of the immune system, including T-cells and B-cells. CD73 is also present on many tumors, including lung, renal, melanoma, colon, prostate, breast and others. In the tumor microenvironment, CD73 produces adenosine, which binds to the adenosine A2A receptor on immune cells and inhibits various immune responses including those directed against the tumor. Tumors utilize this immunosuppressive mechanism to escape attack by the immune system.

ABOUT CPI-006
CPI-006 is a potent humanized monoclonal antibody that reacts with the active site of CD73, blocking the conversion of AMP to adenosine. In vitro studies of CPI-006 have shown it is capable of substantially inhibiting the production of adenosine by blocking the CD73 enzyme.

ABOUT CPI-444
CPI-444 is a small molecule, oral, checkpoint inhibitor designed to disable a tumor’s ability to subvert attack by the immune system by blocking the binding of adenosine in the tumor microenvironment to the A2A receptor. Adenosine, a metabolite of ATP (adenosine tri-phosphate), is produced within the tumor microenvironment where it may bind to the adenosine A2A receptor present on immune cells and block their activity. CD39 and CD73 are enzymes on the surface of tumor cells and immune cells. These enzymes work in concert to convert ATP to adenosine. In vitro and preclinical studies have shown that dual blockade of CD73 and the A2A receptor may be synergistic