On October 17, 2017 PharmaCyte Biotech, Inc. (OTCQB: PMCB), a clinical stage biotechnology company focused on developing targeted cellular therapies for cancer and diabetes using its signature live-cell encapsulation technology, Cell-in-a-Box, reported that its research partner, the University of Northern Colorado (UNC), has identified an organism whose genome contains the genetic code for production of an enzyme capable of activating a cannabinoid prodrug into its active cancer-killing form (Press release, PharmaCyte Biotech, OCT 17, 2017, View Source [SID1234520983]).

“We are pleased that UNC has taken us one step closer to developing cannabinoid-based therapies to combat cancer utilizing our proprietary Cell-in-a-Box live-cell encapsulation technology,” commented PharmaCyte’s Chief Executive Officer, Kenneth L. Waggoner. “PharmaCyte’s innovative Cannabis Program has established PharmaCyte as a serious player in the medical Cannabis sector, and we are exploring additional strategic relationships to advance product development and commercialization.”

PharmaCyte’s Cannabis Program has had two primary areas of focus. The first is confirming the anti-cancer activity of cannabinoids (constituents of the Cannabis plant), such as tetrahydrocannabinol (THC) and cannabidiol (CBD). UNC’s research has confirmed that a purified cannabinoid showed a potent dose-dependent decrease in cell viability for various cancers, suggesting that this cannabinoid exhibits significant anti-proliferative effects (stops the growth of cancer cells). This activity has been demonstrated in glioblastoma (brain), pancreatic, breast, lung, colon and melanoma cancer cell lines.

The second area of focus is in finding an enzyme capable of converting an inactive, side-effect-free, cannabinoid prodrug into its active cancer-killing form. The research team at UNC has screened numerous cell lines and numerous enzymes. As result of this extensive work, an organism has been identified that has been confirmed to produce an enzyme capable of catalyzing the desired cannabinoid-prodrug-activating reaction. Work is now underway to locate the enzyme’s gene.

Dr. Mark L. Rabe, PharmaCyte’s Director of Cannabis Program Development, commented, “Our work at UNC continues to bear fruit. The work with cancer cell lines not only confirmed cannabinoid anti-cancer activity, it generated important dosing data. The work to identify the needed activating enzyme has been intensive and time-consuming, and we are pleased to have identified a front-running candidate that has exhibited the desired activity.”

Once the location of the activating enzyme gene has been determined within the organism’s genome, a series of steps will occur to amplify and clone the gene and confirm its activity. The gene will then be used to bio-engineer a human cell line that will then become a cannabinoid-prodrug-activating enzyme “factory.” Importantly, the parental human cell line that will be utilized is the same cell line being utilized in PharmaCyte’s therapy for pancreatic cancer. Upon confirmation of the desired activity by the bio-engineered cell line, the final steps include live-cell encapsulation with the Cell-in-a-Box technology and validation.

Clinically, targeted cannabinoid-based chemotherapy would be accomplished by implanting the encapsulated bio-engineered cells near the site of a tumor, along with administration of a cannabinoid prodrug which would become activated at the site of the tumor by an enzyme produced by the encapsulated cells. The end goal is better efficacy than existing therapies with few, if any, side effects.

On October 17, 2017 Varian (NYSE: VAR) reported an 80-year-old male with head & neck cancer became the first patient in Europe to be treated on the Halcyon system at University Hospitals Leuven (UZ Leuven) in Belgium (Press release, InfiMed, OCT 17, 2017, View Source [SID1234520980]). Halcyon is an advanced cancer treatment system that is more comfortable for the patient while delivering ease-of-use for healthcare providers, accelerated installation timeframes, expedited commissioning, simplified training, and automated treatment.

Halcyon simplifies and enhances virtually every aspect of image-guided volumetric intensity modulated radiotherapy (IMRT), and is designed to expand the availability of high-quality cancer care globally and help save the lives of millions more cancer patients. It is well suited to handle the majority of cancer patients, offering advanced treatments for lung, esophagus, brain, head & neck, and many other forms of cancer.

“We selected the Halcyon system because of its potential to accelerate the treatment workflow and allow for a much closer connection between the patient and therapist,” said professor Karin Haustermans, MD, chair of the department, UZ Leuven. “Having now completed our first treatments I can say that Halcyon lived up to its promise of a more efficient workflow and better integration of imaging and treatment, which resulted in a much faster overall treatment time.”

“We are very proud to have partnered with UZ Leuven on making Halcyon treatments available to patients in Europe just two months after the hospital ordered this new system,” said Kolleen Kennedy, president of Varian’s Oncology Systems business. “The treatments beginning at UZ Leuven are another important step in continuing our efforts of advancing cost-effective cancer care worldwide.”

For more information on Halcyon, visit www.varian.com/halcyon

On October 17, 2017 Ignyta, Inc. (Nasdaq: RXDX), a biotechnology company focused on precision medicine in oncology, reported that the European Medicines Agency (EMA) has granted Priority Medicines (PRIME) designation for entrectinib in the treatment of NTRK fusion-positive, locally advanced or metastatic solid tumours in adult and paediatric patients who have either progressed following prior therapies or who have no acceptable standard therapy (Press release, Ignyta, OCT 17, 2017, View Source [SID1234520979]). Through the PRIME initiative, Ignyta will have enhanced EMA support, including optimizing the entrectinib development pathway, potentially accelerating assessment of the Marketing Authorisation Application (MAA), and engaging in early discussion with EMA and health technology assessments (HTAs) regarding reimbursement pathways. PRIME designation for entrectinib was substantially based on data from the Phase 2 global study, STARTRK-2.

“We are pleased and grateful that the EMA has accepted entrectinib into its PRIME program, which is analogous to the Breakthrough Therapy Designation from the U.S. FDA that entrectinib received earlier this year. This PRIME designation recognition is the result of the efforts of Ignyta’s team to ensure that entrectinib development was global in nature from its earliest days, and further validates the broad potential of entrectinib as a novel treatment for patients, regardless of age, with NTRK-positive tumors, a group of cancers for which there currently is no approved treatment,” said Jonathan Lim, M.D., chairman and CEO of Ignyta. “We look forward to collaborating with the EMA, as well as other global regulatory authorities, on the accelerated assessment of entrectinib with the goal to provide a new therapy for patients in need.”

Entrectinib is an investigational, orally available, CNS-active tyrosine kinase inhibitor targeting tumors that harbor NTRK1/2/3 or ROS1 gene fusions. Entrectinib was previously granted Breakthrough Therapy Designation by the U.S. Food and Drug Administration (FDA) for the treatment of NTRK fusion-positive, locally advanced or metastatic solid tumors in adult and pediatric patients who have either progressed following prior therapies or who have no acceptable standard therapies in May 2017.

About the Priority Medicines (PRIME) Initiative
The PRIME initiative was launched in 2016 by the EMA to support the development and accelerate the review of new therapies to treat patients with unmet medical need. The criteria for the PRIME initiative require early clinical evidence that the therapy offers a therapeutic advantage over existing treatments or benefits patients without treatment options. This designation provides appointment of a rapporteur, early dialogue and scientific advice at key development milestones, and the potential to qualify products for accelerated review earlier in the application process.

About Entrectinib
Entrectinib is an investigational, CNS-active, potent, and selective small molecule tyrosine kinase inhibitor of the TRK (tropomyosin receptor kinase) family of tyrosine kinase receptors (TRKA/B/C) and ROS1 proteins, which is in a Phase 2 clinical study and two Phase 1 clinical studies in molecularly defined adult patient populations for the treatment of solid tumors, and a Phase 1/1b clinical study in pediatric patients with advanced solid tumor malignancies.
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About STARTRK-2
STARTRK-2 is an open-label, multicenter, global Phase 2 basket study of entrectinib for the treatment of patients with locally advanced or metastatic solid tumors that harbor NTRK1/2/3, ROS1, or ALK rearrangements. The basket design screens patient tumor samples for the relevant targets to take full advantage of entrectinib’s demonstrated preliminary clinical activity across a range of different tumor types and molecular targets.

On October 17, 2017 Diffusion Pharmaceuticals Inc. (NASDAQ:DFFN) (“Diffusion” or “the Company”), a clinical-stage biotechnology company focused on extending the life expectancy of cancer patients, reported that it has received final protocol guidance from the U.S. Food and Drug Administration (FDA) for a Phase 3 clinical trial with the Company’s lead compound trans sodium crocetinate (TSC) in patients newly diagnosed with inoperable glioblastoma multiforme (GBM), a type of brain cancer (Press release, Diffusion Pharmaceuticals, OCT 17, 2017, View Source [SID1234520978]). The Company has responded to all outstanding points raised by the FDA and plans to begin the trial under the protocol agreed to by the FDA by the end of 2017. The trial will compare survival at two years of patients receiving TSC concurrent with chemotherapy and radiation (standard of care, or SOC), with patients receiving SOC alone.

“Following a series of interactions with the FDA, we are gratified to have an agreed-upon protocol and to be preparing to start our TSC Phase 3 trial in patients newly diagnosed with inoperable GBM,” said David Kalergis, Chief Executive Officer of Diffusion Pharmaceuticals. “As previously announced, we have engaged the contract research organization to oversee this trial and have completed the Phase 3 TSC drug production run to FDA standards. On our way to opening an anticipated total of 100 sites across the U.S. and Europe, we have 17 initial sites selected in the U.S., all under one Institutional Review Board, and first patients are expected to be enrolled this year.”

Mr. Kalergis continued, “This Phase 3 study will focus on treating newly diagnosed GBM patients who have been judged by their medical team to be inoperable because of the size or location of the tumor. In Diffusion’s Phase 2 proof-of-concept trial, the inoperable GBM patients who were treated with TSC plus standard of care showed a nearly four-fold increase in survival at two years compared with standard of care patients only. Due to their poor prognoses, inoperable patients are often excluded from GBM clinical trials and have usually been treated with radiation and chemotherapy only. We are excited to bring a new treatment possibility to patients with inoperable GBM, and look forward to beginning the trial.”

About the Glioblastoma Multiforme Phase 3 Trial

The Phase 3 trial is a randomized, controlled registration trial with TSC and SOC chemotherapy and radiation, compared with SOC alone in newly diagnosed inoperable GBM patients. The primary endpoint is overall survival, either after a predetermined number of patient deaths or following successful results of an optional interim analysis. Secondary endpoints include progression-free survival (PFS) and objective response rate (ORR; tumor response) using RANO criteria, as well as patient performance scoring (Karnofsky Performance Scale; KPS), Quality of Life (EQ-5D-5L questionnaire) and corticosteroid and anticonvulsant usage.

A total of 236 patients will be randomized 1:1 at 100 clinical sites (54 U.S., 46 EU). TSC will be dosed three times each week for six weeks concurrent with standard radiation and chemotherapy as initial treatment. This will be followed by one month of rest and then adjuvant chemotherapy consisting of six monthly cycles of TSC and temozolomide given for the first week of each cycle. As such, 18 doses of TSC will be administered during initial treatment and another 18 doses will be administered during adjuvant treatment to those so randomized.

About Treatment-Resistant Cancers and TSC

Oxygen deprivation at the cellular level (hypoxia) is the result of rapid tumor growth, causing the tumor to outgrow its blood supply. Cancerous tumor cells thrive with hypoxia and the resultant changes in the tumor microenvironment cause the tumor to become resistant to radiation therapy and chemotherapy. Using a novel, proprietary mechanism of action, Diffusion’s lead drug TSC counteracts tumor hypoxia – and therefore treatment-resistance – by safely re-oxygenating tumor tissue, thus enhancing tumor kill and potentially prolonging patient life expectancy. Oxygen levels of normal tissue remain unaffected upon administration of TSC, thereby avoiding the introduction of harmful side effects.

On October 17, 2017 Celsion Corporation (NASDAQ:CLSN), an oncology development company, reported a summary of ThermoDox related presentations made during the Company’s Research and Development (R&D) Day held on Thursday, October 12, 2017 (Press release, Celsion, OCT 17, 2017, View Source [SID1234520977]). This summary is intended to provide easy access to pertinent, top line information discussed during the conference. A complete webcast of the presentations is available on Celsion’s website at www.celsion.com under the heading News & Investors / Financial Events / Featured Events – October 12, 2017 – Celsion to Host Research and Development Update.

The presentations focused on the Company’s research and development program using ThermoDox, Celsion’s proprietary heat-activated liposomal encapsulation of doxorubicin, for the treatment of primary liver cancer, also known as hepatocellular carcinoma or HCC. Leading OPTIMA Study clinical investigators representing various geographical regions (Asia-Pacific and Europe) and multiple medical disciplines (hepatology, interventional radiology and surgery) presented their past and current experiences with ThermoDox for the treatment of primary liver cancer.

— Nicholas Borys, M.D., Celsion’s Senior Vice President & Chief Medical Officer, presented the following:
ThermoDox’s mechanism of action and how it utilizes tumor biology to deliver high concentrations of drug (Doxorubicin) directly to the tumor site and the importance of heating time.

Key learnings from the Company’s 701 patient HEAT Study including results from (i) computer simulation studies, (ii) preclinical animal studies and (iii) a post hoc subgroup analysis, all of which establishes a clear understanding of a key ThermoDox heat-based mechanism of action: the longer the target tissue is heated, the greater the doxorubicin tissue concentration.

Hypothesis prompted by the HEAT Study post-hoc findings: ThermoDox, when used in combination with Radiofrequency Ablation (RFA) standardized to a minimum dwell time of 45 minutes (sRFA > 45 min), appears to increase the overall survival (OS) of patients with HCC.

Results from an independent retrospective analysis conducted by the National Institutes of Health on the intent-to-treat population of the HEAT Study which sought to evaluate the correlation between RFA burn time per tumor volume (min/ml) and clinical outcome. The analysis concluded that increased RFA “burn time” per tumor volume significantly improved overall survival (OS) in patients with solitary lesions treated with sRFA + ThermoDox compared to patients treated with sRFA alone.

Update on the current enrollment status of the OPTIMA Study which is approaching 70% of the 550 patients necessary to ensure that its primary end point, overall survival, can be evaluated with statistical significance. The statistical plan for the OPTIMA Study calls for two interim efficacy analyses by the IDMC. The Company projects full patient enrollment by mid-2018 and the first pre-planned efficacy analysis after 118 overall survival events by the first quarter of 2019.

— Won Young Tak, M.D., Ph.D., Professor Internal Medicine, GI & Hepatology Kyungpook National University Hospital Daegu, Republic of Korea presented the following:

RFA has limited efficacy in larger tumors due to microsatellite nodules or viable tumors.
Patients treated with ThermoDox in the HEAT Study had excellent survival outcome. Two cases presented for the HEAT Study showed five and nine year survival benefit for patients treated with ThermoDox plus sRFA.

— Stephen N. Wong, M.D., Principal Investigator OPTIMA, Chinese General Hospital, Philippines presented the following:

HEAT Study patients treated with ThermoDox demonstrated a high complete response rate compared to other studies

A strong correlation exists between complete response and better survival.

— Robert M. Eisele, M.D., Deputy Head of Department, Dept. of General, Visceral, Vascular and Pediatric Surgery, Medical Faculty of the University of Saarland, Homburg, Germany presented the following:
HCC is a worldwide problem with high incidence that continues to rise.

Treatment strategies for treating HCC should be tailored.

Until ThermoDox, RFA was insufficient in treating intermediate to large tumors.
Data from the HEAT Study suggests a new role for RFA plus ThermoDox in HCC – a “promising option.”

About the OPTIMA Study
The Phase III OPTIMA Study is expected to enroll up to 550 patients in up to 70 clinical sites in the United States, Europe, China and Asia Pacific, and will evaluate ThermoDox in combination with optimized RFA, which will be standardized to a minimum of 45 minutes across all investigators and clinical sites for treating lesions three to seven centimeters, versus optimized RFA alone. The primary endpoint for the trial is Overall Survival, which is supported by post-hoc analysis of data from the Company’s 701 patient HEAT Study, where optimized RFA has demonstrated the potential to significantly improve survival when combined with ThermoDox. The statistical plan calls for two interim efficacy analyses by an independent Data Monitoring Committee.

ThermoDox has received U.S. FDA Fast Track Designation and has been granted orphan drug designation for primary liver cancer in both the U.S. and Europe. Further, the U.S. FDA has provided ThermoDox with a 505(b)(2) registration pathway. Subject to a successful trial, the OPTIMA Study has been designed to support registration in all key primary liver cancer markets. Celsion fully expects to submit registrational applications in the USA, Europe and China. The Company believes that applications will be accepted in South Korea, Taiwan and Vietnam, three other large and important markets for ThermoDox subject to approval in Europe, China or the USA.