On October 17, 2017 Ignyta, Inc. (Nasdaq: RXDX), a biotechnology company focused on precision medicine in oncology, reported updated results from its clinical trials, including the STARTRK-2 trial, of entrectinib – an investigational, CNS-active, potent, and selective tyrosine kinase inhibitor being developed for tumors that harbor NTRK fusions or ROS1 fusions (Press release, Ignyta, OCT 17, 2017, View Source [SID1234520990]). In this interim analysis, entrectinib demonstrated a 78% confirmed ORR (by Investigator; 95% CI: 60.0, 90.7) and a 69% confirmed ORR (by Blinded Independent Central Review, or BICR; 95% CI: 50.0, 83.9) in 32 patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) that harbored ROS1 fusions.

Entrectinib demonstrated compelling durability in these patients, with a median duration of response (mDOR) of 28.6 months (by BICR; 95% CI: 6.8, 34.8; median follow-up of 12.9 months) and a median progression free survival (mPFS) of 29.6 months (by BICR; 95% CI: 7.7, 36.6; median follow-up of 8.5 months). Of the patients evaluated, 11 had CNS metastases at baseline as assessed by Investigator, and 83 percent (5 out of 6; by BICR) of the patients with measurable CNS metastases at presentation had confirmed intracranial RECIST responses to treatment with entrectinib. The data were presented today in an oral presentation at the International Association for the Study of Lung Cancer (IASLC) 18th World Conference on Lung Cancer (WCLC) in Yokohama, Japan.

“Based on these data, we believe that entrectinib has the potential to be a best-in-class therapeutic option as a first-line targeted therapy for patients with ROS1-positive NSCLC”
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“Based on these data, we believe that entrectinib has the potential to be a best-in-class therapeutic option as a first-line targeted therapy for patients with ROS1-positive NSCLC,” said Jonathan Lim, M.D., chairman and CEO of Ignyta. “The extended duration of response and progression free survival times observed in these interim data are particularly compelling, and we believe may be driven by entrectinib’s CNS activity. Entrectinib was designed to cross the blood-brain barrier, allowing it to both address preexisting CNS lesions and have the potential to prevent or delay the onset of metastases to the brain, a common site of progression, particularly in NSCLC.”

Safety was consistent with previous studies of entrectinib. With over 200 patients treated at the recommended phase 2 dose, most adverse events (AEs) were Grade 1-2 and reversible, and only 3 percent of patients discontinued from the study due to treatment-related AEs (TRAEs). The most common TRAEs were dysgeusia (38%), fatigue (29%), constipation (23%), dizziness (23%), and increased weight (19%). The most common Grade 3 TRAEs were increased weight (5%), anemia (4%), and fatigue (3%). There were no Grade 4 events occurring in greater than one percent of patients and no Grade 5 TRAEs.

“ROS1 fusions occur in approximately two percent of all cases of NSCLC and, given the propensity for these tumors to metastasize to the brain, the CNS activity of entrectinib is a critical differentiating feature of the compound and may be contributing to the impressive duration and progression free survival it has demonstrated thus far,” said Myung-Ju Ahn, Professor in the Department of Hematology and Oncology at the Samsung Medical Center in Seoul Korea and study author.

In addition to these data in ROS1-positive NSCLC, entrectinib has demonstrated promising preliminary antitumor activity across NTRK-positive solid tumors, an indication for which entrectinib has received breakthrough therapy designation (BTD) from the U.S. Food and Drug Administration (FDA) and PRIME designation from the European Medicines Agency (EMA). Based on recent guidance from the FDA, the company is on track for dual NDA submissions in both the NTRK tissue-agnostic and the ROS1-positive NSCLC indications in 2018.

A conference call and live webcast will be held on October 18, 2017, at 8:00 a.m. Eastern Time to discuss the data presented, as well as the comprehensive entrectinib program. To participate in the conference call, please dial 800-946-0716 (U.S.) or 719-325-4934 (international) and provide Conference ID 7994148. To access the live webcast, go to View Source

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, TRKB and TRKC) 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.

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 gene 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.

About Ignyta, Inc.

Blazing a New Future for Patients with Cancer

At Ignyta, we work tirelessly on behalf of patients with cancer to offer potentially life-saving, precisely targeted therapeutics (Rx) guided by diagnostic (Dx) tests. Our integrated Rx/Dx strategy allows us to enter uncharted territory, illuminating the molecular and immunological drivers of cancer and quickly advancing treatments to address them. This approach embraces even those patients with rare cancers, who have the highest unmet need and who may otherwise not have access to effective treatment options. With our pipeline of potentially first-in-class or best-in-class precision medicines, we are pursuing the ultimate goal of not just shrinking tumors, but eradicating cancer relapse and recurrence in precisely defined patient populations.

For more information, please visit: www.ignyta.com.

About the WCLC

The World Conference on Lung Cancer (WCLC) is the world’s largest meeting dedicated to lung cancer and other thoracic malignancies, attracting over 6,000 researchers, physicians and specialists from more than 100 countries. The goal is to disseminate the latest scientific achievements; increase awareness, collaboration and understanding of lung cancer; and to help participants implement the latest developments across the globe. Organized under the theme of “Synergy to Conquer Lung Cancer,” the conference will cover a wide range of disciplines and unveil several research studies and clinical trial results. For more information, visit View Source

On October 17, 2017 Prima BioMed Ltd (ASX: PRR; NASDAQ: PBMD) (“Prima”) reported that new data investigating the use of eftilagimod alpha (IMP321), the Company’s lead product candidate, in combination with pembrolizumab in metastatic melanoma patients in Australia that have had either no response or a suboptimal response to pembrolizumab, will be presented in a poster presentation for the first time at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 2017 Annual Meeting (Press release, Prima Biomed, OCT 17, 2017, View Source [SID1234520988]).

Pushing the accelerator and releasing the break: testing the soluble LAG-3 protein (IMP321), an antigen presenting cell activator, together with pembrolizumab in unresectable or metastatic melanoma. Poster Number P259
Authors: Victoria Atkinson, Andrew Haydon, Melissa Eastgate, Amitesh Roy, Adnan Khattak, Christian Mueller, Tina Dunkelmann, Chrystelle Brignone, Frederic Triebel
The SITC (Free SITC Whitepaper) 2017 Annual Meeting is being held on November 10-12, 2017 at the Gaylord National Hotel & Convention Center in National Harbor, Maryland.

On October 17, 2017 Cellectar Biosciences, Inc. (Nasdaq: CLRB) (the “company”), an oncology-focused, clinical stage biotechnology company, reported the Japanese Patent Office has granted it a patent covering both composition of matter and method of use for CLR 131 and CLR 125, two of the company’s phospholipid drug conjugates (PDCs) (Press release, Cellectar Biosciences, OCT 17, 2017, View Source [SID1234520987]). Both compounds are composed of radio isotopes conjugated to the company’s proprietary PDC delivery platform. CLR 131 is the company’s lead compound and is currently in a Phase 1 trial for multiple myeloma and a Phase 2 trial for multiple blood cancers. CLR 125 was part of a National Cancer Institute (NCI)-sponsored study showing potential effect against triple-negative breast cancer.

The recently issued patent, JP 2014-147869 (Phospholipid Analogs as Diapeutic Agents) provides intellectual property protection for both diagnostic and therapeutic applications. Most significantly, the patent includes five claims for CLR 131 and CLR 125 in treating multiple solid tumor cancer types, including brain (glioma), colorectal, intestinal, ovarian, cervical, pancreatic, lung, adrenal, retinoblastoma and skin cancers, as well as squamous cell cancers (cancers of the lining of hollow organs, i.e., head and neck cancer, bladder cancer, etc.). Cellectar Biosciences holds the exclusive, worldwide rights to develop and commercialize both CLR 131 and CLR 125.

“The issuance of this Japanese patent enhances our growing intellectual property portfolio in this strategically important market and underscores the novelty of our delivery platform and the potential of these compounds. Certain cancers such as head and neck and gastric are more prevalent in Asia and represent high unmet medical need both within and outside the region,” said Jim Caruso, president and CEO of Cellectar. “The increased market protection provided by this patent combined with the ongoing NCI supported research in head and neck cancer and the early clinical benefits seen to date with CLR 131, affords us the opportunity to initiate a more global development program.”

About CLR 131
CLR 131 is an investigational compound under development for a range of hematologic malignancies. It is currently being evaluated as a single-dose treatment in a Phase 1 clinical trial in patients with relapsed or refractory (R/R) multiple myeloma (MM) as well as in a Phase 2 clinical trial for R/R MM and select R/R lymphomas as either a one- or two-dose treatment. CLR 131 represents a novel approach to treating hematological diseases and based upon preclinical and interim Phase 1 study data, may provide patients with therapeutic benefits including, overall survival, an improvement in progression-free survival, and overall quality of life. CLR 131 utilizes the company’s patented PDC tumor targeting delivery platform to deliver a cytotoxic radioisotope, iodine-131, directly to tumor cells. The FDA has granted Cellectar an orphan drug designation for CLR 131 in the treatment of multiple myeloma.

About CLR 125
CLR 125 utilizes the company’s patented PDC tumor targeting delivery platform to deliver a radiotherapeutic isotope, iodine-125, directly to tumor cells. This compound may be uniquely suited to treat select cancers, such as triple negative breast cancer, and micro-metastatic disease. Iodine-125 is a low energy gamma emitting isotope that when selectively delivered to tumor cells can result in improved outcomes.

About Phospholipid Drug Conjugates (PDCs)
Cellectar’s product candidates are built upon its patented cancer cell-targeting delivery and retention platform of optimized phospholipid ether-drug conjugates (PDCs). The company designed its phospholipid ether (PLE) carrier platform to be coupled with a variety of payloads to facilitate the discovery and development of improved targeted novel therapeutic compounds. The basis for selective tumor targeting of our PDC compounds lies in the differences between the plasma membranes of cancer cells compared to those of normal cells. Cancer cell membranes are highly enriched in lipid rafts, which are glycolipoprotein microdomains of the plasma membrane of cells that contain high concentrations of cholesterol and sphingolipids, and serve to organize cell surface and intracellular signaling molecules. PDCs have been tested in more than 80 different xenograft models of cancer.

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.