On July 30, 2018 Astex Pharmaceuticals, a member of the Otsuka group of companies, and Otsuka Pharmaceutical Co. Ltd., reported that top-line results from the ASTRAL-1 study evaluating the efficacy and safety of guadecitabine (SGI-110) in adults with previously untreated AML who are not eligible for intensive induction chemotherapy (Press release, Astex Pharmaceuticals, JUL 30, 2018, View Source [SID1234527955]). The study did not meet its co-primary endpoints: complete response (CR) rate (p>0.04), and overall survival (OS) (p>0.01) as per the protocol analysis plan, compared with the control arm of physician’s choice of azacitidine, decitabine, or low dose cytarabine. Evaluation of the study’s secondary endpoints and safety data is ongoing. The full data will be presented at an upcoming scientific meeting.

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The company continues to focus on completing the ongoing global phase 3 ASTRAL-2 and ASTRAL-3 studies evaluating guadecitabine in the treatment of relapsed and refractory AML and relapsed and refractory MDS and CMML.

"We are disappointed in the outcome of the ASTRAL-1 study," said Mohammad Azab, Astex’s president and chief medical officer. "The study used very strict criteria of ineligibility to receive intensive chemotherapy based on age (over 75 years) or poor performance status (ECOG PS of 2 or 3) or comorbidities, which made it a difficult population to show superior benefit of guadecitabine." Dr. Azab also added, "ASTRAL-1 is the largest global prospective study ever conducted in this specific patient population with low intensity therapy, with 815 patients randomized, of whom about 90% were treated with hypomethylating agents or HMAs (guadecitabine, azacitidine, or decitabine). The large body of clinical and genetic data will still provide the medical community with very valuable insights into the role of several prognostic clinical and genetic markers that may influence outcome with HMA treatment. We are extremely grateful to all the patients, physicians and other healthcare professionals, and partner research and manufacturing organizations who contributed to this global effort. We are now looking forward to the completion of the ASTRAL-2 and ASTRAL-3 studies currently actively recruiting in two different indications."

About Guadecitabine (formerly SGI-110)

Guadecitabine is a next-generation DNA hypomethylating agent.1,2 Guadecitabine was rationally designed to be resistant to degradation by cytidine deaminase, prolonging the exposure of tumor cells to the active metabolite, decitabine, thus ensuring greater uptake of decitabine into the DNA of rapidly dividing cancer cells.3 Guadecitabine, through the action of decitabine, inhibits DNA methyl transferase (DNMT), with the potential to reverse aberrant DNA methylation, an epigenetic change characteristic of many cancer cells that results in silencing of critical genes. This action may restore the expression of silenced tumor suppressor genes and tumor-associated antigens.4 Through this re-expression of silenced genes, guadecitabine may have the potential to sensitize tumor cells to other anticancer agents,5,6,7 including immunotherapeutics,8 as well as re-sensitizing cancer cells previously resistant to chemotherapeutics.7

Guadecitabine is currently being studied in two additional phase 3 studies:

ASTRAL-2: A randomized, open-label study in leukemia patients with relapsed or refractory acute myeloid leukemia (AML) following intensive chemotherapy. See www.clinicaltrials.gov NCT02920008.
ASTRAL-3: A randomized, open-label study in myelodysplastic syndromes (MDS) or chronic myelomonocytic leukemia (CMML) after failure of treatment with azacitidine, decitabine, or both. See www.clinicaltrials.gov NCT02907359.
In addition, guadecitabine is being evaluated in over twenty investigator and company-sponsored trials in other hematological malignancies and in solid tumors, both as a single agent, and in combination with chemotherapy or immunotherapy.

Guadecitabine was designed to be administered subcutaneously as a low-volume, stable formulation.

About the ASTRAL-1 Study

The ASTRAL-1 study evaluated the efficacy and safety of guadecitabine (formerly SGI-110) in adults with previously untreated AML who are not eligible for intensive induction chemotherapy (see www.clinicaltrials.gov NCT02348489). The study is the largest global prospective study ever conducted in this specific patient population, with 815 patients randomized from 163 investigator sites in 24 countries worldwide. The study compared guadecitabine, delivered subcutaneously (SC) 60mg/m2/day for 5 days, with physicians’ choice of azacitidine IV or SC 75 mg/m2/day for 7 days, decitabine IV 20 mg/m2/day for 5 days, or low dose cytarabine SC 20 mg bid for 10 days, all administered in 28-day cycles. In addition to the co-primary endpoints of OS and CR, the study evaluated multiple secondary endpoints including progression-free survival; composite CR or CRc (CR + CRi + CRp); overnight stays in hospital; red cell / platelet transfusions; QOL (EQ-5D-5L); duration of response and safety.

About Acute Myeloid Leukemia

AML is the most common form of acute leukemia in adults.9 There were an estimated 21,380 new cases of AML diagnosed in the US in 2017,10 and an estimate of 10,590 patients were projected to have died from AML in the US in 2017.11 Although 60 to 80 percent of AML patients less than 60 years of age may achieve a complete response (CR) with standard intensive induction chemotherapy,12 the outlook for patients 60 years of age or more is significantly worse, with response rates less than 50 percent, cure rates following transplant remaining at less than 10 percent and a median survival of less than one year.12,13,14 These figures have not significantly improved during the last three decades. These patients have few therapeutic options available.15,16 Effective, less toxic therapies are needed for the treatment of AML, particularly for elderly patients where comorbidities and other consequences of aging may often render them ineligible to receive intensive induction chemotherapy, thus denying them a potentially curative transplant.14

On July 27, 2018 AstraZeneca and MedImmune, its global biologics research and development arm, reported that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency has adopted a positive opinion, recommending a marketing authorisation of Imfinzi (durvalumab) for the treatment of locally-advanced, unresectable non-small cell lung cancer (NSCLC) in adults whose tumours express PD-L1 on ≥1% of tumour cells and whose disease has not progressed following platinum-based chemotherapy and radiation therapy (CRT) (Press release, AstraZeneca, JUL 27, 2018, View Source [SID1234527927]). The recommendation is based on the progression-free survival (PFS) and overall survival (OS) primary endpoints of the Phase III PACIFIC trial, and post-hoc subgroup analyses by PD-L1 expression requested by the CHMP.

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Sean Bohen, Executive Vice President, Global Medicines Development and Chief Medical Officer at AstraZeneca, said: "The CHMP positive opinion brings European patients closer to having a treatment following chemoradiation therapy. There have been no new treatments in this setting for decades. With approximately a third of European non-small cell lung cancer patients presenting with this stage of disease, we are excited by this potential new standard of care in this curative-intent setting."

In the PACIFIC trial, Imfinzi demonstrated a statistically-significant and clinically-meaningful improvement in PFS and OS in "all-comer" patients. The recommended label reflects most of the patients in the trial with a known PD-L1 status.

Overall survival results from the PACIFIC trial will be presented at a forthcoming medical meeting.

The positive opinion from the CHMP will now be reviewed by the European Commission, which has the authority to approve medicines for the 28 European Union member countries plus Iceland, Norway and Liechtenstein. Earlier this year, Imfinzi was approved for unresectable, Stage III NSCLC in the US, Canada, Switzerland, India, Japan and Brazil based on the Phase III PACIFIC trial. In addition to the EU, other global health authority reviews and submissions are ongoing.

About Stage III NSCLC

Stage III (locally advanced) NSCLC is commonly divided into three sub-categories (IIIA, IIIB and IIIC), defined by how much the cancer has spread locally and the possibility of surgery. Stage III disease is different from Stage IV disease, when the cancer has spread (metastasised) to distant organs, as Stage III is currently treated with curative intent.

Stage III NSCLC represents approximately one-third of NSCLC incidence and was estimated to affect around 105,000 patients in the top-eight countries (China, France, Germany, Italy, Japan, Spain, UK, US) in 2017. The majority of Stage III NSCLC patients are diagnosed with unresectable tumours. No new treatments beyond chemoradiation therapy, followed by active surveillance to monitor for progression, have been available to patients for decades.

About PACIFIC

The PACIFIC trial is a randomised, double-blinded, placebo-controlled, multi-centre trial of Imfinzi as treatment in ‘all-comer’ patients (i.e. regardless of PD-L1 status) with unresectable, Stage III NSCLC whose disease has not progressed following platinum-based chemotherapy and radiation therapy (CRT).

The trial is being conducted in 235 centres across 26 countries involving 713 patients. The primary endpoints of the trial are PFS and OS, and secondary endpoints include landmark PFS and OS, objective response rate, and duration of response.

About Imfinzi

Imfinzi (durvalumab) 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.

Imfinzi is approved for unresectable, Stage III NSCLC in the US, Canada, Switzerland, India, and Japan based on the Phase III PACIFIC trial.

As part of a broad development programme, Imfinzi is also being tested as a monotherapy and in combination with chemotherapy, radiation therapy, small molecules, and tremelimumab, an anti-CTLA4 monoclonal antibody, as a first or second-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 AstraZeneca in Lung Cancer

Lung cancer is the leading cause of cancer death among both men and women, accounting for about one-third of all cancer deaths.

AstraZeneca has a comprehensive portfolio of approved and potential new medicines in late-stage clinical development for the treatment of different forms of lung cancer across all stages of disease and lines of therapy. We aim to address the 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, ADAURA and LAURA Phase III trials. Our extensive late-stage immuno-oncology programme focuses on 75-80% of patients with lung cancer without a known genetic mutation. The portfolio includes Imfinzi, an anti-PDL1 antibody, which is in development as monotherapy (ADJUVANT BR.31, PACIFIC2, MYSTIC and PEARL Phase III trials) and in combination with tremelimumab and/or chemotherapy (MYSTIC, NEPTUNE, POSEIDON and CASPIAN Phase III trials).

About AstraZeneca’s Approach to Immuno-Oncology (IO)

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-PDL1) as monotherapy and in combination with tremelimumab (anti-CTLA4) 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

On July 27, 2018 BeiGene, Ltd. (NASDAQ:BGNE), a commercial-stage biopharmaceutical company focused on developing and commercializing innovative molecularly-targeted and immuno-oncology drugs for the treatment of cancer, reported a Hong Kong initial public offering and a global offering (the "Offering") of 65,600,000 of its ordinary shares, par value $0.0001 per share (the "Shares"), and the proposed listing of the Shares on the Main Board of The Stock Exchange of Hong Kong Limited (the "SEHK") (Press release, BeiGene, JUL 27, 2018, View Source [SID1234528781]). BeiGene’s American Depositary Shares ("ADS") are currently listed on the Nasdaq Global Select Market under the symbol "BGNE." Each ADS represents the right to receive 13 ordinary shares.

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The Offering initially comprises 5,904,000 Shares for subscription by the public in Hong Kong and 59,696,000 Shares for subscription globally, representing 9% and 91% of the total number of Shares, respectively, subject to reallocation. In addition, BeiGene expects to grant the joint global coordinators a 30-day option to purchase up to an additional 9,840,000 Shares. The Offering is subject to market and other conditions, and there can be no assurance as to whether or when the Offering may be completed, or as to the actual size or terms of the Offering.

Morgan Stanley & Co. International plc, Goldman Sachs (Asia) L.L.C., Credit Suisse (Hong Kong) Limited and CLSA Limited are acting as joint global coordinators for the Offering.

Sales of Shares outside of Hong Kong, initially offered in the United States and sold outside the United States that may be resold from time to time in the United States, are being offered pursuant to an automatically effective shelf registration statement that was previously filed with the U.S. Securities and Exchange Commission (the "SEC"). A preliminary prospectus supplement relating to and describing the terms of the Offering will be filed with the SEC and will be available on the SEC’s website at www.sec.gov. When available, copies of the preliminary prospectus supplement and the accompanying prospectus relating to these securities may also be obtained for free from the offices of Morgan Stanley & Co. LLC, Attention: Prospectus Department, 180 Varick Street, 2nd Floor, New York, NY 10014; and Goldman Sachs & Co. LLC, Attention: Prospectus Department, 200 West Street, New York, NY 10282, telephone: 1-866-471-2526, or email:[email protected]; and Credit Suisse Securities (USA) LLC, Attention: Prospectus Department, One Madison Avenue, New York, New York 10010, or by email at [email protected].

This press release shall not constitute an offer to sell or the solicitation of an offer to buy, nor shall there be any sale of, these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of such state or jurisdiction.

On July 27, 2018 BioCryst Pharmaceuticals, Inc. (NASDAQ:BCRX) reported that its second quarter 2018 financial results will be reported on Tuesday, August 7, 2018 (Press release, BioCryst Pharmaceuticalsa, JUL 27, 2018, View Source [SID1234527928]).

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BioCryst will host a conference call and webcast at 11:00 a.m. Eastern Time to discuss financial results and to provide an update regarding the Company’s clinical development programs. The call will be led by Jon P. Stonehouse, President & Chief Executive Officer, Thomas R. Staab II, Senior Vice President & Chief Financial Officer, Lynne Powell, Senior Vice President & Chief Commercial Officer, and Dr. Bill Sheridan, Senior Vice President and Chief Medical Officer.

Links to a live audio webcast and replay of the presentation may be accessed on the BioCryst website events page at View Source

On July 27, 2018 Cambrex Corporation (NYSE:CBM), a leading manufacturer of small molecule innovator and generic Active Pharmaceutical Ingredients (APIs), reported that second quarter 2018 financial results will be released on Thursday, August 2, 2018 before the market opens (Press release, Cambrex, JUL 27, 2018, View Source [SID1234527929]).

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The Company will host a conference call to discuss the financial results.

Second Quarter 2018 Earnings Conference Call
When: Thursday, August 2, 2018 at 8:30 a.m. Eastern Time
Dial-in: 1-888-208-1711 for U.S.
+1-323-794-2575 for International
Passcode: 3913181
Dial-in Replay: 1-888-203-1112 for U.S.
+1-719-457-0820 for International
Passcode: 3913181
Available through Thursday, August 9, 2018
Webcast: www.cambrex.com