On December 11, 2018 PharmaCyte Biotech, Inc. (OTCQB: PMCB), reported a biotechnology company focused on developing targeted treatments for cancer and diabetes using its signature live-cell encapsulation technology, Cell-in-a-Box, released an interview with Lyon Gleich, M.D., of Medpace, a global full-service clinical contract research organization (CRO) (Press release, PharmaCyte Biotech, DEC 11, 2018, View Source [SID1234532010]). Dr. Gleich serves as the Medical Monitor and key team member of PharmaCyte’s planned clinical trial in locally advanced, inoperable pancreatic cancer (LAPC).

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Dr. Gleich is Vice President, Medical Oncology, at Medpace headquartered in Cincinnati, Ohio. Dr. Gleich has provided medical leadership over oncology trials at Medpace for nearly 15 years. He has extensive expertise in new drug development in oncology—specifically, pancreatic cancer.

Why is Medpace well suited to conduct PharmaCyte’s clinical trial in locally advanced, non-metastatic, inoperable pancreatic cancer?

Dr. Lyon Gleich: "Medpace is experienced in managing oncology trials of new molecular entities for our biotech partners and our full-service, scientific-model aligns well with innovative companies such as PharmaCyte. Oncology is a clear and well-established focus of Medpace with multiple recent trials in pancreatic cancer. We have strong relationships with oncology sites and site investigators who will help us recruit the best site investigators for this trial. This will also provide patients access to the trial by having multiple sites throughout the United States. Medpace will work with the Principle Investigator and site investigators to maximize their regional referral networks, as well as to support recruitment for PharmaCyte’s study.

"Conducting a pancreatic cancer study is not like managing a study in more benign conditions, where you can advertise for patients. Working with established cancer centers of excellence that have access to pancreatic cancer patients will be critical to the trial’s success. Our relationships with these sites and site investigators, as well as our processes, will enable us to support the site relationships while making sure that the data quality is high and that the trial is run correctly. Medpace will also support the site’s recruitment efforts and trial management to make it as easy as possible for each site and its patients to participate in the trial."

What is unique about PharmaCyte’s signature live-cell encapsulation technology, Cell-in-a-Box?

Dr. Lyon Gleich: "Given the severe mortality rate associated with pancreatic cancer as well as the morbidity of the locally advanced disease, we are eager to work with PharmaCyte to advance their live-cell encapsulation therapy that can potentially improve local morbidity as well as impact survival for patients suffering from this aggressive disease. The Cell-in-a-Box or ‘CypCaps’ capsules that are implanted into each patient will activate the chemotherapy agent ifosfamide in the pancreatic tumor bed specifically, which will permit an infusion of only a low dose of the chemotherapeutic agent PharmaCyte uses for its pancreatic cancer therapy. This is a novel way to take an older and effective chemotherapeutic product and make it even more efficacious. PharmaCyte’s therapy offers LAPC patients a drug with proven anti-cancer activity that is delivered locally to their advanced cancer.

"The CypCaps will require angiographic administration into the pancreatic cancer feeding vessel. Medpace will train each trial site regarding the implantation of the capsules into the patient to ensure proper and consistent methodologies across the study. This will help ensure that the implantation is done without any adverse events and maximize the potential for efficacy of the chemotherapy agent ifosfamide."

What are your thoughts about PharmaCyte and Medpace teaming up with well-known and respected pancreatic cancer experts such as Dr. Manuel Hidalgo?

Dr. Lyon Gleich: "PharmaCyte and the experience of Medpace with pancreatic cancer experts will be key to driving success in this trial. It is important to have the support of the thought leaders in pancreatic cancer that have already been involved with PharmaCyte so that the best sites are recruiting appropriate patients for the study and the quality of the CypCaps administration is done consistently.

"Manuel Hidalgo, M.D., of Beth Israel Deaconess Medical Center, is the Principal Investigator and a well-known expert in pancreatic cancer with whom Medpace is experienced. This is an excellent example of teaming and collaborating with the best resources in treating pancreatic cancer."

How do the CRO and the PI work together during clinical trials?

Dr. Lyon Gleich: "Medpace works to be as supportive and transparent as possible with the Principle Investigator and the site investigators alike. This includes providing training on all protocol procedures and helping sites understand the purpose and details of the study to present it accurately to potential patients. Medpace physicians and staff are readily available to the sites to support and answer trial-related questions and concerns, and thereby help continuously with enrollment and patient treatment in accordance with the protocol. Of course, one of our main responsibilities is also site monitoring to ensure that data is entered in a timely manner and supported at all times by proper site documentation to support any future applications for Marketing Authorization."

What are some of the biggest challenges you anticipate and are planning for in this trial?

Dr. Lyon Gleich: "Any trial in pancreatic cancer is a difficult trial because of the severity and morbidity of the disease. Many patients enrolled in these studies, even if they have a good performance status and high activity level, are patients with advanced cancer with a very high mortality rate. Patients can turn the corner at any moment, in a very negative way, in terms of having a severe worsening of their disease such as an increase in ascites, a blockage of their biliary duct, and even in some cases, a quick descent to death. This is a huge hurdle for any trial in pancreatic cancer. Even during the couple of weeks during the screening period, LAPC patients can see a rapid progression of the disease and are no longer able to respond to any therapy.

"In this trial, we are hopeful that we won’t experience too much of that. The trial is designed for patients with locally advanced non-metastatic unresectable pancreatic cancer. Many patients with pancreatic cancer do have metastatic disease, meaning the spread of the cancer elsewhere in the body, not just a locally advanced disease. This therapy won’t offer a benefit to those patients and is designed for the non-metastatic locally advanced patient. We need to find locally advanced patients without metastases who still have an acceptable performance status and haven’t, so to speak, gone over the precipice where the disease takes off in a way that therapies can no longer help.

"The support of the patients by the treating physicians, their teams and nurses are key to this. Medpace will work closely with PharmaCyte to provide support and education to the teams so that they can provide that needed support and education to the patients to help them through this terrible disease.

"Based on Medpace’s experience in trials with pancreatic cancer and our experience in working with sites in similar difficult studies for late stage advanced pancreatic cancer, we are well positioned to know what the sites expect from us regarding support. Through this important trial, our hope is being able to advance the treatment of pancreatic cancer, which is greatly needed."

About Medpace

Medpace is a scientifically-driven, global, full-service clinical contract research organization (CRO) providing Phase I-IV clinical development services to the biotechnology, pharmaceutical, and medical device industries. The mission of Medpace is to accelerate the global development of safe and effective medical therapeutics through its high-science and disciplined operating approach that leverages local regulatory and deep therapeutic expertise across all major areas including oncology, cardiology, metabolic disease, endocrinology, central nervous system and anti-viral and anti-infective

On December 10, 2018 AstraZeneca reported a new collaboration with Cancer Research UK to launch a centre of excellence in genetic screening, cancer modelling and big data processing aimed at accelerating the discovery of new cancer medicines (Press release, AstraZeneca, DEC 10, 2018, View Source [SID1234531979]). The Functional Genomics Centre will further develop CRISPR technology to better understand the biology of cancer, creating biological models that may be more reflective of human disease, and advancing computational approaches to better analyse big datasets. These approaches are designed to inform new druggable targets in oncology by using clinical insights to better understand tumour disease and resistance mechanisms.

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Functional genomics aims to understand the complex relationship between genetic changes happening within DNA and how these translate to cellular changes in disease. Knowing the functional genomic drivers of disease enables scientists to more accurately select the right drug targets and increases the probability of success in the clinic.

Mene Pangalos, Executive Vice President, Innovative Medicines & Early Development, AstraZeneca, said: "The best science doesn’t happen in isolation which is why AstraZeneca is committed to advancing innovative science through collaboration. This new centre of excellence with Cancer Research UK will combine our expertise in functional genomics and CRISPR technology to identify new biological pathways driving disease and will accelerate the development of new cancer medicines for patients."

Dr Iain Foulkes, Cancer Research UK’s Executive Director of Research and Innovation, said: "We’re delighted to collaborate with AstraZeneca on this exciting new initiative which will give leading Cancer Research UK scientists and our alliance partners access to the latest in CRISPR technology. As we move into an era of personalised medicine, we’ve reached a turning point in our ability to harness powerful technologies in the pursuit of targeted cancer therapies. We hope that this will translate into urgently needed new therapies for patients with hard to treat cancers such as lung, pancreatic, oesophageal and brain tumours."

The Functional Genomics Centre will be located at the Milner Therapeutics Institute at the University of Cambridge. AstraZeneca and Cancer Research UK will have independent use of the Centre’s facilities, and their scientists will work alongside each other to facilitate collaboration, technical innovation and scientific progress.

At the Centre, scientists will have access to the next generation of CRISPR libraries for silencing or activating every gene in the genome, accessed through an extension of the existing collaboration between AstraZeneca and the Wellcome Sanger Institute. This collaboration includes access to the Wellcome Sanger Institute’s most recent versions of human and mouse genome-wide CRISPR/Cas9 knockout libraries, as well as Cas9 and dual gRNA expression vectors. This extends the application of CRISPR technology with vectors, providing enhanced sensitivity and specificity in gene editing, leading to easier targeting and identification.

A separate collaboration between AstraZeneca and the California-based Innovative Genomics Institute (IGI) will aim to use CRISPR to uncover genes and disease pathway mechanisms involved in DNA Damage Response (DDR), a key process involved in many cancers and one of AstraZeneca’s four key platforms in oncology. Research will focus on identifying potential therapeutic strategies for DDR inhibitors, including combinations, in oncology.

On December 10, 2018 Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D. "Astellas") reported that XOSPATA (generic name: gilteritinib) is now available for prescription in the United States for the treatment of adult patients who have relapsed or refractory (resistant to treatment) Acute Myeloid Leukemia (AML) with a FLT3 mutation as detected by an FDA-approved test (Press release, Astellas, DEC 10, 2018, View Source [SID1234531995]).1 An oral monotherapy, XOSPATA is the first and only FLT3-targeting agent approved by the FDA for the treatment of relapsed or refractory FLT3 mutation-positive (FLT3mut+) AML.

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XOSPATA was approved by the U.S. Food and Drug Administration (FDA) on November 28, 2018. Health professionals, patients and their caregivers can learn more about XOSPATA and support services provided through Astellas at View Source

"Astellas aims to pursue cutting-edge science that provides value to patients," said Mark Reisenauer, senior vice president, oncology business unit, Astellas. "XOSPATA is an excellent example of how we are continuing to advance on this promise to patients."

Astellas is providing a full range of patient support services for XOSPATA in the U.S. XOSPATA Support SolutionsSM offers access and reimbursement support to help patients access XOSPATA as prescribed by their healthcare providers . XOSPATA Support SolutionsSM also provides information regarding patient healthcare coverage options and financial assistance programs that may be available to help eligible patients with financial needs. Patients, caregivers and healthcare providers can visit www.xospatasupportsolutions.com or call 844-632-9272 to learn more.

Astellas reflected the impact from this launch in its financial forecasts of the current fiscal year ending March 31, 2019.

About Acute Myeloid Leukemia
Acute Myeloid Leukemia (AML) is a cancer that impacts the blood and bone marrow,2 and its incidence increases with age.3 The American Cancer Society estimates that in 2018, approximately 19,000 people will be diagnosed with AML in the U.S.3

About XOSPATA (gilteritinib)
XOSPATA is indicated for the treatment of adult patients who have relapsed or refractory Acute Myeloid Leukemia (AML) with a FMS-like tyrosine kinase 3 (FLT3) mutation as detected by an FDA-approved test.1 XOSPATA is also approved by the Japan Ministry of Health, Labor and Welfare (MHLW) for relapsed or refractory AML with FLT3 mutations. It is launched as XOSPATA 40 mg Tablets in Japan.

Gilteritinib was discovered through a research collaboration with Kotobuki Pharmaceutical Co., Ltd., and Astellas has exclusive global rights to develop, manufacture and commercialize gilteritinib.

Astellas is currently investigating gilteritinib in various FLT3 mutation-positive AML patient populations through several Phase 3 trials. Visit AstellasAMLTrials.com to learn more about ongoing gilteritinib clinical trials.

Important Safety Information

Contraindications
XOSPATA is contraindicated in patients with hypersensitivity to gilteritinib or any of the excipients. Anaphylactic reactions have been observed in clinical trials.

Warnings and Precautions
Posterior Reversible Encephalopathy Syndrome (PRES) There have been rare reports of PRES with symptoms including seizure and altered mental status with XOSPATA. Symptoms have resolved after discontinuation of XOSPATA. A diagnosis of PRES requires confirmation by brain imaging, preferably MRI. Discontinue XOSPATA in patients who develop PRES.

Prolonged QT Interval XOSPATA has been associated with prolonged cardiac ventricular repolarization (QT interval). Of the 292 patients treated with XOSPATA in the clinical trial, 1.4% were found to have a QTc interval greater than 500 msec and 7% of patients had an increase from baseline QTc greater than 60 msec. Perform electrocardiogram (ECG) prior to initiation of treatment with XOSPATA, on days 8 and 15 of cycle 1, and prior to the start of the next two subsequent cycles. Interrupt and reduce XOSPATA dosage in patients who have a QTcF >500 msec. Hypokalemia or hypomagnesemia may increase the QT prolongation risk. Correct hypokalemia or hypomagnesemia prior to and during XOSPATA administration.

Pancreatitis There have been rare reports of pancreatitis in patients receiving XOSPATA in clinical studies. Evaluate patients who develop signs and symptoms of pancreatitis. Interrupt and reduce the dose of XOSPATA in patients who develop pancreatitis.

Embryo-Fetal Toxicity Based on findings in animals and its mechanism of action, XOSPATA can cause embryo-fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during treatment with XOSPATA and for at least 6 months after the last dose of XOSPATA. Advise males with female partners of reproductive potential to use effective contraception during treatment with XOSPATA and for at least 4 months after the last dose of XOSPATA. Pregnant women, patients becoming pregnant while receiving XOSPATA or male patients with pregnant female partners should be apprised of the potential risk to the fetus.

Adverse Reactions
The most frequent non-hematological serious adverse reactions (≥5%) reported in patients were pneumonia (19%), sepsis (13%), fever (13%), dyspnea (7%) and renal impairment (5%).

Overall, 22 of 292 patients (8%) discontinued XOSPATA treatment permanently due to an adverse reaction. The most common adverse reactions (>1%) leading to discontinuation were pneumonia (2%), sepsis (2%) and dyspnea (1%). The most common adverse reactions (≥20%) were myalgia/arthralgia (42%), transaminase increased (41%), fatigue/malaise (40%), fever (35%), non-infectious diarrhea (34%), dyspnea (34%), edema (34%), rash (30%), pneumonia (30%), nausea (27%), stomatitis (26%), cough (25%), headache (21%), hypotension (21%), dizziness (20%) and vomiting (20%).

Other clinically significant adverse reactions occurring in ≤10% of patients included: electrocardiogram QT prolonged (7%), cardiac failure (grouped terms) (4%), pericardial effusion (3%), pericarditis (2%), differentiation syndrome (1%), anaphylactic reaction (1%) and posterior reversible encephalopathy syndrome (1%).

Lab Abnormalities: The most common lab abnormalities (>20%) that were Grade ≥3 that occurred ≥10% were: hypophosphatemia (12%), alanine aminotransferase increased (12%), hyponatremia (12%), aspartate aminotransferase increased (10%).

Drug Interactions
Combined P-gp and Strong CYP3A Inducers: Concomitant use of XOSPATA with a combined P-gp and strong CYP3A inducer decreases XOSPATA exposure which may decrease XOSPATA efficacy. Avoid concomitant use of XOSPATA with combined P-gp and strong CYP3A inducers.

Strong CYP3A inhibitors: Concomitant use of XOSPATA with a strong CYP3A inhibitor increases XOSPATA exposure. Consider alternative therapies that are not strong CYP3A inhibitors. If the concomitant use of these inhibitors is considered essential for the care of the patient, monitor patient more frequently for XOSPATA adverse reactions. Interrupt and reduce XOSPATA dosage in patients with serious or life-threatening toxicity.

Drugs that Target 5HT2B Receptor or Sigma Nonspecific Receptor: Concomitant use of XOSPATA may reduce the effects of drugs that target the 5HT2B receptor or the sigma nonspecific receptor (e.g., escitalopram, fluoxetine, sertraline). Avoid concomitant use of these drugs with XOSPATA unless their use is considered essential for the care of the patient.

Specific Populations
Lactation: Advise women not to breastfeed during treatment with XOSPATA and for 2 months after the last dose.

On December 10, 2018 OncoSec Medical Incorporated (OncoSec) (NASDAQ: ONCS), a company developing intratumoral cancer immunotherapies, reported that the Company has received a $7.0 million investment at $1.50 per share from Alpha Holdings, Inc. (kosdaq:117670) as part of a fundamental strategic investment centered on the clinical development of OncoSec’s lead immunotherapy product candidate, TAVO (tavokinogene telseplasmid) (Press release, OncoSec Medical, DEC 10, 2018, View Source [SID1234531980]).

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Under the terms of the stock purchase agreement, Alpha Holdings purchased $7 million worth of shares of common stock from OncoSec at $1.50 per share. The investment was executed on December 6 and completes a commitment to OncoSec by Alpha Holdings to purchase a total value of $15 million shares of common stock priced at $1.50 per share. Further details of the transaction can be found in the Form 8-K filed by the Company describing the agreement.

"We have identified the biotechnology sector and the immunotherapy space in particular as a significant value driver for us moving forward. Specifically, we see tremendous potential in OncoSec’s strategy to turn good drugs into great drugs," said Hee Do Koo, President and Chief Executive Officer of Alpha Holdings. "OncoSec recently released positive preliminary data on TAVO demonstrating significant potential when combined with a checkpoint inhibitor, and we believe their platform has broad applicability to improve patient outcomes by expanding the utility of checkpoint inhibitors across a variety of tumor types."

Alpha Holdings is a leading Korean technology company engaged in the design, development, service and manufacture of system semiconductors, as well as the development of biotechnologies and thermal compound materials. Since 2002, Alpha Holdings has successfully carried out many projects as a major partner of Samsung Advanced Foundry Eco-system (SAFE) of Samsung Electronics. Alpha Holdings, a listed company in the KOSDAQ Market, was founded in 2002 and is headquartered in Seongnam, South Korea.

"Alpha Holdings shares our vision for the potential of our platform and their continued support will be an asset for us as we advance TAVO and our robust pipeline of compounds focused on intratumoral treatment of cancer," said Daniel J. O’Connor, President and Chief Executive Officer of OncoSec. "Having Alpha Holdings as a partner also strengthens our presence in Korea and Asia, important markets for potential opportunities as we move forward."

On December 10, 2018 Varian (NYSE: VAR) reported that it will report results for the first quarter of fiscal year 2019 after market close on Wednesday, January 23, 2019 (Press release, Varian Medical Systems, DEC 10, 2018, View Source [SID1234531996]). The news release will be followed by a teleconference available to all interested at 1:30 p.m. Pacific Time. To access the teleconference call and replay:

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Teleconference: Access from within the U.S. by dialing 1-877-869-3847, and from outside the U.S. by dialing 1-201-689-8261.

Replay: Access from within the U.S. by dialing 1-877-660-6853 and from outside the U.S. by dialing 1-201-612-7415, and enter conference ID 13685671. The teleconference replay will be available until 5:00 p.m. Pacific Time, Friday, January 25, 2019.

Webcast: To access the live webcast and replay, visit the company website at: www.varian.com/investors and click on the link for First Quarter Earnings Results.

For automatic e-mail alerts regarding Varian news and events, investors can subscribe on the company website: View Source