On June 6, 2019 SillaJen, Inc., (KOSDAQ:215600), a clinical-stage, biotherapeutics company focused on the development of oncolytic immunotherapy products for cancer, reported the first patient has been enrolled in Part 2 of JX594-REN026, a Phase 1b clinical trial of Pexa-Vec (pexastimogene devacirepvec) in combination with Libtayo(cemiplimab-rwlc), for the treatment of renal cell cancer (RCC) (Press release, SillaJen, JUN 6, 2019, View Source [SID1234536937]). Enrollment of Part 1 (dose-escalation phase) of the trial was completed in March 2019 without significant safety concerns, and the first seven patients in Part 2 were enrolled in South Korea, with expansion to sites in the United States and Australia anticipated over the coming weeks.

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SillaJen is collaborating with Regeneron to evaluate Pexa-Vec, SillaJen’s lead clinical candidate, in combination with Regeneron’s Libtayo, an anti-PD1 monoclonal antibody Regeneron is developing in collaboration with Sanofi. The aim of the trial is to assess the safety and efficacy of the combination in patients with unresectable or metastatic renal cell carcinoma. The study will also investigate the immune modulating potential of Pexa-Vec given concurrently with checkpoint inhibitor therapy by evaluating multiple blood and tissue biomarkers.

"We are encouraged to see positive safety data from the dose escalation phase of the REN026 study. Part 2 of this study is designed to reinforce the rationale of Pexa-Vec in combination with Libtayo," stated Francis Hyukchan Kwon, M.D, Ph.D., chief medical officer at Sillajen.

About Pexa-Vec and the SOLVE Platform
Pexa-Vec is the most advanced product candidate from SillaJen’s proprietary SOLVE (Selective Oncolytic Vaccinia Engineering) platform. The vaccinia strain backbone of Pexa-Vec has been used safely in millions of people as part of a worldwide vaccination program, and over 300 cancer patients have been treated with Pexa-Vec to date. Pexa-Vec was engineered to target common genetic defects in cancer cells by deleting their thymidine kinase (TK) gene, thus making Pexa-Vec dependent on the cellular TK expressed at persistently high levels in cancer cells. Pexa-Vec is also engineered to express granulocyte-macrophage colony stimulating factor (GM-CSF) protein. GM-CSF complements the cancer cell lysis of the product candidate, leading to a cascade of events resulting in tumor necrosis, tumor vasculature shutdown and sustained anti-tumoral immune attack. Pexa-Vec has been shown to be effective when delivered both intratumorally and systemically by intravenous administration. Pexastimogene devacirepvec (Pexa-Vec) is currently being evaluated in a worldwide Phase 3 clinical trial for advanced primary liver cancer, and more information can be found at: View Source

On June 6, 2019 Boston Biomedical, Inc. reported the continuation of the CanStem303C study evaluating the safety and efficacy of investigational agent napabucasin when given in combination with FOLFIRI with or without bevacizumab in patients with advanced colorectal cancer (Press release, Boston Biomedical, JUN 6, 2019, View Source [SID1234536936]). This decision is based on a recommendation by the independent Data and Safety Monitoring Board (DSMB) to continue the study without modification following a pre-specified interim analysis of 50 percent of the total planned events. Boston Biomedical, Inc. has accepted this recommendation.

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About Napabucasin
Napabucasin is an orally-administered investigational agent that is bioactivated by NQO1, which generates reactive oxygen species (ROS) to affect multiple oncogenic cellular pathways, including the STAT3 pathway, which is expected to result in cancer cell death.1

Napabucasin is currently being investigated in CanStem303C, a phase 3 trial for metastatic colorectal cancer (NCT02753127) and CanStem111P, a phase 3 trial for metastatic pancreatic cancer (NCT02993731). It is also being investigated in earlier phase trials in multiple solid malignancies. In 2016, the U.S. Food and Drug Administration granted Orphan Drug Designation for napabucasin in pancreatic cancer.

On June 6, 2019 Astex Pharmaceuticals, Inc. a member of the Otsuka group of companies, and Otsuka Pharmaceutical Co. Ltd., reported top-line results from the ASCERTAIN phase 3 study evaluating cedazuridine and decitabine fixed-dose combination (ASTX727) vs decitabine IV in adults with intermediate and high-risk MDS or CMML (Press release, Astex Pharmaceuticals, JUN 6, 2019, View Source [SID1234536935]).

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The study met its primary endpoint of decitabine exposure equivalence of 5-day dosing between orally administered ASTX727 and IV decitabine as per the protocol analysis plan. Safety and clinical activity were similar to that observed in a previous phase 1/2 study. The full data will be presented at an upcoming scientific meeting.

Astex plans to file an NDA with the US FDA by the end of 2019.

"We are delighted with the outcome of the ASCERTAIN trial, and the demonstration that the fixed dose combination of cedazuridine with decitabine enables successful oral delivery of decitabine, alleviating the significant burden of five days of monthly IV infusions for patients who may continue to benefit from the drug for several months or even years," said Mohammad Azab, Astex Pharmaceuticals’ president and chief medical officer. "Subject to regulatory review and approvals, ASTX727 could bring a new treatment option to patients with these deadly diseases. We are extremely grateful to all the patients, caregivers, partner research and manufacturing organizations, as well as the healthcare professionals who contributed to this effort."

About Cedazuridine and Decitabine Fixed-Dose Combination (ASTX727)

ASTX727 is a novel, orally administered fixed dose combination of cedazuridine, an inhibitor of cytidine deaminase, with the anti-cancer DNA hypomethylating agent, decitabine.1 By inhibiting cytidine deaminase in the gut and the liver, ASTX727 allows for oral delivery of the approved DNA hypomethylating agent, decitabine at exposures which are equivalent to the approved intravenous form of decitabine administered over 5 days.

ASTX727 has been evaluated in a phase 1/2 pharmacokinetics-guided dose escalation and dose confirmation study in patients with MDS and CMML to define appropriate doses of the individual components of ASTX727 (cedazuridine and decitabine) so that decitabine exposure after oral administration of ASTX727 is similar to exposure after IV decitabine at the approved daily dose of a 1-hour infusion at 20 mg/m2 (see View Source NCT02103478). This study demonstrated that ASTX727 allowed decitabine to be delivered orally at a dose that emulates parenteral pharmacokinetics, as measured by 5-day area-under-the-curve (AUC).3 The drug’s safety profile was similar to that of IV decitabine. Of particular note was the low level of gastrointestinal adverse events.3

The concept of using cedazuridine to block the action of cytidine deaminase is also being evaluated in a low dose formulation of cedazuridine and decitabine for the treatment of lower risk MDS (see View Source NCT03502668). ASTX727 may also have potential in all-oral combination regimes for the treatment of a range of different tumor types.

Astex is also expanding the evaluation of cedazuridine – decitabine combinations through a program of investigator-sponsored trials.

ASTX727 is an investigational compound and is not currently approved in any country.

About the ASCERTAIN Study

The ASCERTAIN study was designed to demonstrate that the cedazuridine and decitabine fixed-dose combination (ASTX727) could deliver orally a pharmacokinetically equivalent exposure of decitabine compared to IV decitabine in adults with previously untreated or treated MDS, including all French-American-British subtypes (refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, and CMML), and subjects with MDS International Prognostic Scoring System (IPSS) int-1, int-2, or high-risk MDS. (see View Source NCT03306264). The study was designed as a randomized, open-label cross-over study in which patients were randomized in a 1:1 ratio to receive ASTX727 daily x 5 in the first 28-day cycle followed by IV decitabine daily x 5 in the second 28-day cycle, or the converse order. Following completion of the first two cycles, patients continued to receive treatment with ASTX727 in 28-day cycles until disease progression, unacceptable toxicity, or the subject decided to discontinue treatment or withdrew from the study. The primary endpoint of the study was total 5-day AUC exposures of decitabine after treatment with ASTX727 versus IV decitabine as measured across the first two cycles. Secondary endpoints included safety assessments, pharmacodynamic measurements, secondary PK parameters, clinical responses, red blood cell transfusion independence, leukemia-free survival, and overall survival. The study was conducted in 138 patients at 46 sites in the US and Canada.

About Myelodysplastic Syndromes (MDS) and Chronic Myelomonocytic Leukemia (CMML)

Myelodysplastic syndromes are a heterogeneous group of hematopoietic stem cell disorders characterized by dysplastic changes in myeloid, erythroid, and megakaryocytic progenitor cells, and associated with cytopenias affecting one or more of the three lineages. US incidence of MDS is estimated to be 10,000 cases per year, although the condition is thought to be under-diagnosed.4,5 The prevalence has been estimated to be from 60,000 to 170,000 in the US.6 MDS may evolve into acute myeloid leukemia (AML) in one-third of patients.7 The prognosis for MDS patients is poor; patients die from complications associated with cytopenias (infections and bleeding) or from transformation to AML. CMML is a clonal hematopoietic malignancy characterized by accumulation of abnormal monocytes in the bone marrow and in blood. The incidence of CMML in the US is approximately 1,100 new cases per year,8 and CMML may transform into AML in 15% to 30% of patients.9 The hypomethylating agents decitabine and azacitidine are effective treatment modalities for hematologic cancers and are FDA-approved for the treatment of higher risk MDS and CMML. These agents are administered by IV infusion, or by large-volume subcutaneous injections.

On June 6, 2019 bluebird bio, Inc. (Nasdaq: BLUE) reported that the company will host a live webcast to review new data presented at the European Hematology Association (EHA) (Free EHA Whitepaper) Annual Meeting, and to discuss the approval of ZYNTEGLO (autologous CD34+ cells encoding βA-T87Q-globin gene) on Friday, June 14 at 8:00 a.m. ET (Press release, bluebird bio, JUN 6, 2019, View Source [SID1234536934]).

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Investors may listen to the call by dialing (844) 825-4408 from locations in the United States or +1 (315) 625-3227 from outside the United States. Please refer to conference ID number 2189283.

To access the live webcast of bluebird bio’s presentation, please visit the "Events & Presentations" page within the Investors & Media section of the bluebird bio website at View Source Replays of the webcast will be available on the bluebird bio website for 90 days following the event.

On June 6, 2019 GRAIL, Inc., a healthcare company whose mission is to detect cancer early, when it can be cured, reported that Hans Bishop has been appointed as Chief Executive Officer, effective immediately (Press release, Grail, JUN 6, 2019, View Source [SID1234536933]). He succeeds Jennifer Cook, who has stepped down from the Board and her role as Chief Executive Officer for family health reasons. Mr. Bishop has served on GRAIL’s Board of Directors since August 2018 and will continue to serve as a Director on the GRAIL Board.

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GRAIL also announced the appointment of Joshua Ofman as Chief of Corporate Strategy and External Affairs. In addition, Maykin Ho has joined GRAIL’s Board as an Independent Director. The company also announced that Renée Galá has decided to step down from her role as Chief Financial Officer.

During her tenure as Chief Executive Officer, Ms. Cook led the company through the transition from discovery-stage research to advancing an investigational multi-cancer early detection test into clinical development and toward commercialization. In addition, the company has fully enrolled two of its population-scale clinical studies with approximately 115,000 participants, and initiated a third 50,000-participant clinical study.

"We are very grateful to Jennifer for her important contributions to the company, resulting in the pivotal milestone of the recently presented impressive data from CCGA that support advancement of GRAIL’s investigational multi-cancer early detection test toward commercialization. While we are disappointed to see Jennifer go, we respect and support her decision," said Catherine Friedman, Chair of the GRAIL Board of Directors. "We are thrilled that Hans is stepping into the CEO role to continue building upon this positive trajectory. Hans is a widely respected corporate leader with significant experience building successful companies and guiding novel products through commercialization."

Ms. Friedman continued: "In addition, we are delighted to welcome Josh, an accomplished industry expert in health economics, market access, and health policy with deep experience integrating innovation into healthcare systems, and Maykin, a distinguished biotech leader with unparalleled expertise in healthcare strategy and finance, to GRAIL."

"GRAIL is guided by its bold vision to improve cancer survival rates by creating a single blood test that can detect multiple deadly cancer types at one time," said Mr. Bishop. "For much of my career, I’ve been involved in the fight against cancer, and during that time, I have seen real progress for patients. However, cancer is still the second leading cause of death globally, and I believe early detection is key to changing that. I’m excited to step into the CEO role at a time where the team at GRAIL has delivered such exciting results. I look forward to working with the Board and the entire GRAIL team in this new role to ensure a smooth transition as we advance our test toward commercialization."

Mr. Bishop has more than 30 years of experience in the biotechnology industry. He will continue to serve as the Executive Chair of the Sana Board of Directors and as a Director of Celgene, Agilent Technologies, and Lyell Immunopharma. Mr. Bishop founded Juno Therapeutics in 2013 and served as its President and Chief Executive Officer until the company was acquired by Celgene in March 2018. Prior to this, he served as an Executive in Residence at Warburg Pincus. Earlier, he was Executive Vice President and Chief Operating Officer for Dendreon, Inc. He also previously served as President of Specialty Medicine at Bayer Healthcare, Senior Vice President of Global Commercial Operations at Chiron Corporation, and Vice President and General Manager of European Biopharmaceuticals. Mr. Bishop holds a bachelor’s degree in chemistry from Brunel University in London.

Joshua Ofman, MD, MSHS, joins GRAIL from Amgen where he spent 16 years in several roles, most recently as Senior Vice President, Global Health Policy. Prior to joining Amgen in 2003, Dr. Ofman was a member of the academic faculty in the Department of Medicine and Health Services Research, University of California, Los Angeles (UCLA) School of Medicine, Cedars-Sinai Medical Center. Dr. Ofman also served as Senior Vice President of Zynx Health Inc., a healthcare IT company and subsidiary of the Cerner Corp. Dr. Ofman obtained his undergraduate degree from the University of California, Berkeley and his MD from the University of California, Irvine, School of Medicine. He conducted his internship and residency in internal medicine and fellowship in digestive diseases at the UCLA Department of Medicine. In addition, Dr. Ofman completed a RAND/VA/UCLA fellowship in ambulatory care and health services research, specializing in technology assessment, and obtained his MSHS from the UCLA School of Public Health. He is widely published in health economics and technology assessment, public health program evaluation, and health policy analysis.

Maykin Ho, PhD, has more than 30 years of experience in the healthcare and finance industries. She is a venture partner of Qiming Venture Partners and a member of the Biotech Advisory Panel of the Stock Exchange of Hong Kong. She is also a retired partner of the Goldman Sachs Group, where she served as senior biotechnology analyst, co-head of healthcare for global investment research, and advisory director for healthcare investment banking. Prior to Goldman Sachs, Dr. Ho held various managerial positions in licensing, strategic planning, marketing, and research at DuPont-Merck Pharmaceuticals and DuPont de Nemours & Company. Dr. Ho serves on the Board of Directors for FibroGen, Agios Pharmaceuticals, Parexel International Corporation, the Aaron Diamond AIDS Research Center, and the Institute for Protein Innovation. She was a postdoctoral fellow at Harvard Medical School. Dr. Ho received a PhD in Microbiology and Immunology and a BS from the State University of New York, Downstate Medical Center.