On October 17, 2017 Syndax Pharmaceuticals, Inc. (“Syndax,” the “Company” or “we”) (Nasdaq:SNDX), a clinical stage biopharmaceutical company developing entinostat and SNDX-6352 in multiple cancer indications, reported that it has entered into an exclusive worldwide license agreement with Vitae Pharmaceuticals, Inc., a subsidiary of Allergan plc, for a portfolio of preclinical, orally-available small molecule inhibitors of the interaction of Menin with the Mixed Lineage Leukemia (“MLL”) protein (Press release, Syndax, OCT 17, 2017, View Source [SID1234520984]). These compounds have potential application in the treatment of a genetically-defined subset of acute leukemias with chromosomal rearrangements in the MLL gene (“MLL-r”). Syndax expects to initiate clinical studies in 2019.

“This agreement represents another strategic addition to our pipeline that we believe will enhance the long-term value of Syndax,” said Briggs W. Morrison, M.D., Chief Executive Officer of Syndax. “Syndax is well positioned to develop this unique product portfolio which holds the potential to significantly change the treatment paradigm for acute leukemic patients harboring MLL translocations, a disease that may meet the guidelines for orphan designation.”

“The Menin-MLL-r interaction is thought to play a central role in the pathology of acute leukemia patients with MLL translocations, a patient population routinely identified in clinical practice today,” said Michael L. Meyers, M.D., Ph.D., Chief Medical Officer of Syndax. “While intensive chemotherapy regimens are often employed in these patients, the 5-year survival rate remains significantly below 50% due to the lack of effective treatment options. We believe that this portfolio of compounds holds the potential to serve as an effective oral therapeutic option for pediatric and adult patients with MLL-r-driven leukemias.”

Under the terms of the license agreement, Syndax will make a one-time upfront payment to Allergan and will be responsible for development, manufacturing and global commercialization of the portfolio. Allergan will receive development and commercial stage milestones and tiered royalties on net sales of commercialized products.
About MLL Rearranged (MLL-r) Leukemias

Rearrangements of the MLL gene occur in 70-80% of infant acute leukemias and up to 10% of adult acute leukemias and are associated with a poor prognosis, with less than 40% of infants with MLL-r surviving past 5 years. The protein products of MLL gene rearrangements require interaction with a protein called Menin in order to drive leukemic cancer growth. Disruption of the Menin-MLL-r interaction has been shown to halt the growth of MLL-r leukemic cells. MLL-r leukemias are routinely diagnosed through currently available genetic screening techniques in leukemic cells, but there are currently no approved therapies indicated for MLL-r leukemias.

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.