On January 4, 2018 CureVac AG, a leading clinical-stage biopharmaceutical company focused on the development of pioneering mRNA therapeutics, and Arcturus Therapeutics Ltd. (NASDAQ:ARCT), an RNA medicines company, reported they have entered into a broad strategic collaboration to jointly discover, develop and commercialize novel messenger RNA (mRNA) therapeutics (Press release, CureVac, JAN 4, 2018, View Source [SID1234522914]).

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Under the agreement, the companies will collaborate to develop up to four molecular therapy products for rare diseases using Curevac’s optimized natural mRNA sequence (RNAoptimizer) and Arcturus’s lipid-mediated nucleic acid delivery system (LUNAR). The agreement focuses on developing mRNA therapeutics for enzyme replacement and antibody generation. Development costs will be shared between the companies, with plans to co-commercialize products in the future under a profit sharing arrangement. The first mRNA therapy to be jointly developed and potentially commercialized by the companies will target ornithine transcarbamylase (OTC) deficiency, a genetic disease characterized by the accumulation of ammonia in the blood. The collaboration also grants CureVac access to the full suite of Arcturus’s lipid-mediated delivery intellectual property to enable the development of additional mRNA product candidates.

"This collaboration for up to four products establishes a sound relationship with Arcturus, which we believe is one of the leaders in developing lipid-mediated delivery systems for mRNA molecules," said Ingmar Hoerr, Ph.D., co-founder and CEO of CureVac. "Just as important, we are excited to have secured access to Arcturus’s leading intellectual property rights for future product development in molecular therapies. This partnership combines both companies’ technology platforms with the expertise necessary to develop the next generation of therapeutics based on the considerable potential of mRNA."

"We are thrilled to combine Arcturus’s platform technologies and expertise with CureVac’s recognized capabilities in mRNA construct optimization and GMP manufacturing to co-develop messenger RNA medicines for patients in need," said Joseph Payne, President and CEO of Arcturus. "We believe our collaboration with CureVac has the potential to help reduce costs, mitigate manufacturing risks, and accelerate our timelines for ushering quality mRNA medicines into the clinic."

On January 4, 2018 Cellectar Biosciences, Inc. (Nasdaq: CLRB), a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of drugs for the treatment of cancer, reported that company management will be participating in Biotech Showcase 2018 taking place January 8-10, 2018 at the Hilton San Francisco Union Square (Press release, Cellectar Biosciences, JAN 4, 2018, View Source [SID1234522906]). James Caruso, president and chief executive officer of Cellectar Biosciences, will present a company overview and update on January 10, 2018 at 10:00 a.m. Pacific time.

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Mr. Caruso’s presentation will be webcast live at View Source;tp_key=5c62464b98 and on the Events section of the company’s website where it will also be archived.

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 deliberately designed its phospholipid ether (PLE) carrier platform to be coupled with a variety of payloads to facilitate both therapeutic and diagnostic applications. 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 January 4, 2018 Onconova Therapeutics, Inc. (NASDAQ:ONTX), a Phase 3 stage biopharmaceutical company focused on discovering and developing novel small molecule drug candidates to treat cancer, with a primary focus on Myelodysplastic Syndromes (MDS), reported that it has entered into a Cooperative Research and Development Agreement (CRADA) with the National Cancer Institute (NCI), part of the National Institutes of Health (NIH) (Press release, Onconova, JAN 4, 2018, View Source [SID1234522892]). Under the terms of the CRADA, the NCI will conduct research, including preclinical laboratory studies and a clinical trial, on rigosertib in pediatric cancer associated RASopathies.

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The RASopathies are a group of rare diseases which share a well-defined molecular basis in expression or defects involving Ras Effector Pathways. They are usually caused by germline mutations in genes that alter the RAS subfamily and mitogen-activated protein kinases that control signal transduction, and are among the most common genetic syndromes. Together, this group of diseases can impact more than 1 in 1000 individuals, according to RASopathiesNet.

Dr. Steve Fruchtman, Chief Medical Officer of Onconova, noted: "We are excited about the potential of our collaboration with the Pediatric Oncology Branch at NCI’s Center for Cancer Research in the study of rigosertib in children with both hematological and solid tumors that are driven by the Ras pathway. This collaboration could lead to important advances in the treatment of these refractory tumors. This novel approach directed at a specific mechanism driving the underlying neoplasm is the basis of personalized medicine for these indications".

As part of the CRADA, Onconova will provide rigosertib supplies and initial funding towards non-clinical studies. The NCI will fund the majority of the research, including the cost of the clinical trial, which is expected to start in 2018. A clinical trial protocol has been developed and will be reviewed by the Institutional Review Board.

Onconova is also collaborating with academic researchers and patient advocacy groups interested in developing novel therapeutics to address the needs of these patients. In October 2017, Onconova held a Key Opinion Leader Breakfast Symposium in New York City to bring attention to this unmet medical need and the potential for rigosertib in RASopathies. The meeting featured presentations by Bruce D. Gelb, M.D. (Mount Sinai, New York) and Elliot Stieglitz, M.D. (University of California, San Francisco), alongside Dr. Fruchtman. In July 2017, Onconova also presented a summary of its targeted approach at a symposium organized by RASopathiesNet.org.

While the NCI will conduct a trial for RASopathy related cancers in pediatric patients, Onconova will focus on Juvenile Myelomonocytic Leukemia (JMML), a well-described RASopathy affecting children which is incurable without an allogenic hematopoietic stem cell transplant.

Additional information highlighting Onconova’s approach to studying rigosertib in RAS mediated diseases can be found in the presentation, "Strategies to RASopathies and JMML," located in the "Scientific Presentations" section of Onconova’s website.

For Patients

Patients interested in enrolling please contact NCI’s toll-free number 1-800-4-Cancer (1-800-422-6237) (TTY: 1-800-332-8615).

On January 4, 2018 Galera Therapeutics, Inc., a clinical-stage biotechnology company focused on the development of drugs targeting oxygen metabolic pathways with the potential to transform cancer radiotherapy, reported data from its Phase 2b clinical trial of lead product candidate GC4419 for the treatment of severe oral mucositis (SOM) in patients with head and neck cancer will be presented during an oral presentation at the 2018 Multidisciplinary Head and Neck Cancers Symposium being held February 15-17, 2018, at The Westin Kierland Resort & Spa in Scottsdale, Ariz (Press release, Galera Therapeutics, JAN 4, 2018, View Source [SID1234522908]).

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Details of the presentation are as follows:

Abstract ID: 20496
Title: GC4419, a small molecule superoxide dismutase (SOD) mimetic: Randomized, placebo (PBO)-controlled, double blind trial to reduce oral mucositis (OM) from chemoradiotherapy (CRT) in patients (pts) with oral cavity (OC) or oropharyngeal (OP) carcinoma (OCC)
Presentation #: LBA2
Session: Breakout Session II: Survivorship and Acute and Late Effects
Date/Time: Friday, February 16, 2018, 3-4:30 p.m. MT
Presenter: Carryn M. Anderson, M.D., Department of Radiation Oncology, University of Iowa

"We are very pleased with the robust results of this clinical trial, one of the largest ever conducted for this indication, and look forward to presenting the data at this important meeting for patients with head and neck cancer," said Mel Sorensen, M.D., President and CEO of Galera. "We believe GC4419, which leverages our dismutase mimetic platform, has the potential to represent an important new treatment approach for patients with chemoradiotherapy-related severe oral mucositis."

Co-sponsored by the American Society for Radiation Oncology (ASTRO), the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) and the American Head & Neck Society (AHNS), the Multidisciplinary Head and Neck Cancers Symposium brings researchers and clinicians together to discuss advances in research and treatments for head and neck cancers. For more information about the meeting, visit: View Source

About GC4419

GC4419 is a highly selective and potent small molecule dismutase mimetic that closely mimics the activity of human superoxide dismutase enzymes. GC4419 works to reduce elevated levels of superoxide free radical levels caused by radiation therapy by rapidly converting superoxide free radical molecules to hydrogen peroxide and oxygen. Left untreated, elevated superoxide free radicals can damage noncancerous tissues and lead to debilitating side effects, including oral mucositis (OM), which can limit the antitumor efficacy of radiation therapy.

GC4419 is initially being studied for its ability to reduce the incidence, duration and severity of radiation and chemotherapy-induced OM in patients with head and neck cancer. As reported in December 2017, top-line results from Galera’s 223-patient, double blind, randomized, placebo-controlled Phase 2b clinical trial demonstrate GC4419’s ability to dramatically reduce the duration of severe OM from 19 days to 1.5 days (92 percent), the incidence of severe OM through completion of radiation by 34 percent and the severity of patients’ OM by 47 percent, while preserving healthy tissue. In addition, in preclinical study GC4419 demonstrated an increased tumor response to radiation therapy while preventing toxicity in normal tissue.

The U.S. Food and Drug Administration granted Fast Track designation to GC4419 for the reduction and incidence of radiotherapy induced OM in patients with head and neck cancer. GC4419 also has potential in other indications in which mucosa is damaged by radiation.

About Oral Mucositis

Oral mucositis (OM) is a painful and problematic complication during cancer treatment, especially radiation therapy, caused by excessive superoxide generated during treatment that breaks down epithelial cells that line the mouth. Patients suffering from OM experience severe pain, inflammation, ulceration and bleeding of the mouth.

In the United States, more than 50 percent of patients with cancer receive radiotherapy at some time in their treatment. In patients with head and neck cancer, radiotherapy is a mainstay of treatment and approximately 70 percent of patients receiving chemoradiotherapy develop severe oral mucositis (SOM) as defined by the World Health Organization as Grade 3 or 4, which is the most debilitating side effect of the radiotherapy.

SOM can adversely affect cancer treatment outcomes by causing interruptions in radiotherapy, which may compromise the otherwise good prognosis for tumor control in many of these patients. SOM may also inhibit patients’ ability to eat solid food or even drink liquids, and can cause serious infections. Further, the costs of managing these side effects are substantial, particularly when hospitalization and/or surgical placement of PEG tubes to maintain nutrition and hydration are required. There is currently no drug approved to prevent or treat SOM in patients with head and neck cancer.

On January 4, 2018 SignalRx Pharmaceuticals Inc., a clinical-stage company developing novel small-molecules therapeutics to inhibit key orthogonal and synergistic oncotargets for the treatment of cancer, reported the in silico design and discovery of SRX3225, its first-in-class small-molecule potent inhibitor of three key cancer targets HDAC6, BRD4, and PI3K (Press release, SignalRx, JAN 4, 2018, http://www.ireachcontent.com/news-releases/signalrx-announces-in-silico-design-and-discovery-of-the-first-in-class-hdac6-brd4-pi3k-epigenetic-kinase-inhibitor-srx3225-668070373.html [SID1234527319]).

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SignalRx’s proprietary CRIMP technology platform led to the in silico design and identification of SRX3225 within its triple inhibitor program. SRX3225 is a novel picomolar potent HDAC6 inhibitor with high selectivity over HDAC1, HDAC2 and HDAC3 isoforms (31-35 times selective) and more so against isozymes HDAC4 through HDAC11 (up to 20,000 times selective). In addition, SRX3225 potently inhibits the epigenetic target BRD4-BD1 with >5X selectivity over BRD4-BD2, and it also potently inhibits PI3K alpha and delta isoforms. Importantly, because the design of SRX3225 is achieved in silico using cancer targets’ structural data, it is possible to independently dial in and out each of the three inhibitory components in a small molecule generating dual and single inhibitory chemotypes from SRX3225.

"This is a huge immuno-oncology breakthrough because it creates a synergistic synthetic lethality effect as a result of PI3K and BRD4 and HDAC inhibition delivered with a single molecule. While dual PI3K/BRD4, dual HDAC/PI3K, and dual BRD4/HDAC inhibitors are under investigation, SRX3225 is the only triple HDAC/PI3K/BRD4 inhibitor that we know of" said SignalRx’s scientific advisor and founder Donald L. Durden, MD, PhD. "This new approach of inhibiting three targets simultaneously yields a more complete block of multiple key cancer signaling providing increased lethality coupled with less toxicity than a combination of three single agents. This novel 3-in-1 anticancer drug paves the way for more sophisticated and cost-effective combinations in cancer patients that should block development of resistance resulting in longer duration of benefits in more patients."

"We achieved this milestone by leveraging the experience in multi-targeted inhibitors and discoveries we have made in our advanced BRD4/PI3K program coupled with the knowledge we have acquired on these targets as exemplified in our recent PNAS publication (View Source)" said Dr. Joseph Garlich, Chief Scientific Officer at SignalRx. "Rational combinations of targeted agents in clinical development often face a common detrimental limitation: unwanted additive off-target toxicities from the individual agents used. This leaves no option but to reduce the effective dosages of the agents resulting in less than optimal therapeutic administrations and inefficient treatments. Our approach combines 3 drug mechanisms into one resulting in 1 single agent with a single ADME/safety profile which also simplifies and expedites its development."

SignalRx is interested in partnering discussions to quickly take these novel small molecules through clinical trials together with companion diagnostics for streamlined development and approval.