On September 12, 2016 RedHill Biopharma Ltd. (NASDAQ:RDHL) (TASE:RDHL) ("RedHill" or the "Company"), a biopharmaceutical company primarily focused on development and commercialization of late clinical-stage, proprietary, orally-administered, small molecule drugs for gastrointestinal and inflammatory diseases and cancer, reported a research collaboration with Stanford University School of Medicine ("Stanford") for the evaluation of RedHill’s proprietary Phase II-stage drug, YELIVA (ABC294640) (Press release, RedHill Biopharma, SEP 12, 2016, View Source [SID:SID1234515076]).

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The research collaboration is intended to complement RedHill’s planned Phase Ib clinical study to evaluate YELIVA as a radioprotectant for prevention of mucositis in head and neck cancer patients undergoing therapeutic radiotherapy.

As part of the collaboration, Stanford will evaluate the effect of YELIVA on mucositis reduction and tumor control in a murine model of head and neck cancer. YELIVA will be administered in combination with a chemotherapy agent and radiotherapy, similar to the design of RedHill’s planned radioprotectant Phase Ib clinical study with YELIVA, expected to run in parallel with the Stanford research collaboration. Results from the research collaboration are expected in mid-2017.

The Stanford research collaboration is led by Dr. Quynh-Thu Le, MD, a radiation oncologist, Chair of the Stanford Radiation Oncology Department, Co-Director of the Radiation Biology Program of the Stanford Cancer Institute and the Chair of the Head and Neck Cancer Committee of the NRG Oncology Group, part of the National Cancer Institute (NCI) supported National Clinical Trial Network (NCTN).

YELIVA is a proprietary, first-in-class, orally-administered, sphingosine kinase-2 (SK2) selective inhibitor with anti-cancer and anti-inflammatory activities. By inhibiting the SK2 enzyme, YELIVA blocks the synthesis of sphingosine 1-phosphate (S1P), a lipid signaling molecule that promotes cancer growth and pathological inflammation.

RedHill is pursuing with YELIVA multiple clinical programs in oncology, inflammatory and gastrointestinal indications. RedHill is evaluating potential clinical studies for additional oncology and inflammatory indications, as well as potential collaboration opportunities to evaluate YELIVA as an add-on therapy.

Results from the Phase I study with YELIVA in patients with advanced solid tumors confirmed that the study, conducted at the Medical University of South Carolina (MUSC), successfully met its primary and secondary endpoints, demonstrating that the drug is well- tolerated and can be safely administered to cancer patients at doses that provide circulating drug levels that are predicted to have therapeutic activity.

Among the 16 subjects that were assessable for response by RECIST 1.1 criteria (Response Evaluation Criteria in Solid Tumors), one subject had a partial response with a progression-free survival of 16.9 months, and six subjects had stable disease with a progression-free survival of between 3.5 and 17.6 months. Of the three patients with cholangiocarcinoma, one had a partial response and the other two had stable disease, one for over a year. YELIVA was well-tolerated over a prolonged period at doses inducing the expected pharmacodynamic effects.

A Phase Ib/II study with YELIVA for the treatment of refractory or relapsed multiple myeloma has recently been initiated at Duke University Medical Center. The study is supported by a $2 million grant from the National Cancer Institute (NCI) Small Business Innovation Research Program (SBIR) awarded to Apogee Biotechnology Corp. (Apogee), in conjunction with Duke University, with additional support from RedHill.

A Phase II study with YELIVA for the treatment of advanced hepatocellular carcinoma is planned to be initiated in the coming weeks. The study will be conducted at MUSC Hollings Cancer Center and additional clinical centers in the U.S. It is supported by a $1.8 million grant from the NCI awarded to MUSC, intended to fund a broad range of studies on the feasibility of targeting sphingolipid metabolism for the treatment of a variety of solid tumor cancers, including the Phase II study with YELIVA and will be further supported by additional funding from RedHill.

A Phase I/II clinical study evaluating YELIVA in patients with refractory/relapsed diffuse large B-cell lymphoma (DLBCL) was initiated at the Louisiana State University Health Sciences Center (LSUHSC) in New Orleans in June 2015 and is expected to resume later this year following administrative hold and pending a protocol amendment aimed at improving overall recruitment. The study is supported by a grant awarded to Apogee from the NCI as well as additional support from RedHill.

The studies with YELIVA (ABC294640) are registered on www.ClinicalTrials.gov, a web-based service by the U.S. National Institute of Health, which provides public access to information on publicly and privately supported clinical studies.

About YELIVA (ABC294640):
YELIVA (ABC294640) is a Phase II-stage, proprietary, first-in-class, orally-administered, sphingosine kinase-2 (SK2) selective inhibitor with anti-cancer and anti-inflammatory activities. RedHill is pursuing with YELIVA multiple clinical programs in oncology, inflammatory and gastrointestinal indications. By inhibiting the SK2 enzyme, YELIVA blocks the synthesis of sphingosine 1-phosphate (S1P), a lipid signaling molecule that promotes cancer growth and pathological inflammation. SK2 is an innovative molecular target for anticancer therapy because of its critical role in catalyzing the formation of S1P, which is known to regulate cell proliferation and activation of inflammatory pathways. YELIVA was originally developed by U.S.-based Apogee Biotechnology Corp. and completed multiple successful pre-clinical studies in oncology, inflammation, GI and radioprotection models, as well as the ABC-101 Phase I clinical study in cancer patients with advanced solid tumors. The development of YELIVA was funded to date primarily by grants and contracts from U.S. federal and state government agencies awarded to Apogee Biotechnology Corp., including the U.S. National Cancer Institute, the U.S. Department of Health and Human Services’ Biomedical Advanced Research and Development Authority (BARDA), the U.S. Department of Defense and the FDA Office of Orphan Products Development.

On September 12, 2016 Celsion Corporation (NASDAQ:CLSN) reported that the National Institutes of Health (NIH) has conducted an independent retrospective analysis of data from the intent-to-treat population of the Company’s HEAT Study, a 701-patient study investigating ThermoDox, Celsion’s proprietary heat-activated liposomal encapsulation of doxorubicin in combination with radiofrequency ablation (RFA) in primary liver cancer, also known as hepatocellular carcinoma (HCC) (Press release, Celsion, SEP 12, 2016, View Source [SID:SID1234515065]). The findings of the NIH study will be presented during an oral session on Monday, November 28, 2016 at 1:50 pm CT during the 102nd Scientific Assembly and Annual Meeting of the Radiological Society of North America (RSNA) to be held on November 26 – December 2, 2016 in Chicago, IL. Celsion is currently studying the use of RFA as a heat source both for tumor ablation and to activate ThermoDox as a means of treating the area surrounding the tumor, where untreated tumor may be present.

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The NIH analysis, which sought to evaluate the correlation between RFA burn time per tumor volume (min/ml) and clinical outcome in patients treated with ThermoDox, concluded that increased burn time per tumor volume substantially improved survival in patients with solitary lesions treated with RFA + ThermoDox compared to patients treated with RFA alone. These findings are consistent with Celsion’s analysis of the HEAT Study data showing that in patients treated with RFA for more than 45 minutes, standardized RFA plus ThermoDox resulted in a statistically significant improvement in overall survival (OS) compared to standardized RFA alone.

"The NIH’s independent analysis provides new confirmatory support indicating that the use of RFA for more than 45 minutes in patients treated with ThermoDox can have a correlative impact on reductions in tumor size and overall survival in patients with primary liver cancer," said Michael H. Tardugno, Celsion’s chairman, president and chief executive officer. "We are encouraged that the NIH findings are consistent with Celsion’s analysis of the HEAT Study data showing that in patients treated with RFA for more than 45 minutes, standardized RFA plus ThermoDox demonstrated a statistically significant improvement in overall survival compared to standardized RFA alone."

Mr. Tardugno added, "We also think it is noteworthy that Celsion’s latest 285 patient subgroup OS readout from the HEAT Study reported that over a 3.5 year period, there was a consistent two-year survival benefit for patients with primary liver cancer – one of the most prevalent and most deadly types of cancer in the world – who were treated with ThermoDox plus optimized RFA over the optimized RFA-only group."

"We are pleased that the NIH findings will be presented to the scientific community at the 2016 RSNA Annual Meeting. We firmly believe that this event will advance the understanding of new and potentially curative approaches to the treatment of primary liver cancer, and that it will also provide strengthened validation for our ongoing global Phase III OPTIMA study, which is evaluating ThermoDox in combination with optimized RFA standardized to a minimum of 45 minutes versus standardized RFA alone in the treatment of primary liver cancer," Mr. Tardugno said.

Presentation Details
Abstract Number: 16013790
Title: RFA Plus Lyso Thermosensitive Liposomal Doxorubicin Improves Survival Using Metric of RFA Duration per Tumor Volume: Retrospective Analysis of Prospective Randomized Controlled Trial
Session: Interventional Oncology Series: Hepatocellular Carcinoma and Cholangiocarcinoma (VSI021)
Date and Time: Monday, November 28, 2016, 1:00 pm to 6:00 pm

About the OPTIMA Study
The Phase III OPTIMA Study is expected to enroll up to 550 patients in up to 75 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 standardized 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 (iDMC).

On September 12, 2016 CirclePharma, Inc., reported that it will apply its computational design and synthetic chemistry platform to design and create a physical screening library of novel macrocyclicpeptides (Press release, Pfizer, SEP 12, 2016, View Source [SID1234525198]). Once completed, the library is initially expected to comprise several hundred macrocycles that will be designed to potentially disrupt bioactive conformations commonly found in protein-protein interactions known to drive disease processes, and will deploy backbone scaffolds screened in silica for intrinsic cell permeability characteristics. In addition, the design of the library will permit the simple creation of derivative libraries tailored to specific features of a therapeutic target class.

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PfizerInc.(NYSE:PFE) has entered into an agreement with Circle under which Pfizer will provide support for the library build, and Circle has granted Pfizer non-exclusive rights to screen the library against certaintargets. The rights granted to Pfizer exclude specified targets for which Circle has reserved exclusive rights to screen the library.

"This physical library will complement Circle’s target-specific computational design toolkit," said David J. Earp, J.D., Ph.D., Circle’s President and CEO. "We expect to use the library for our internal pipeline discovery work, and we will make it available to all of our collaboration partners in drug discovery."

About Macrocyclic Peptides

Macrocyclic peptides have the potential to provide access to the large proportion of therapeutic targets (estimated at up to 80%) that are considered undruggable with conventional small molecule or biologic modalities. Inparticular, there is great interest in developing macrocycles to modulate protein-protein interactions, which play a role in almost all disease conditions, including cancer, fibrosis, inflammation and infection. However, the development of macrocyclic therapeutics has been limited to this point by the need for a greater understanding of how to design macrocycles with appropriate pharm acokinetics, cell permeability and oral bioavailability. As a result, most clinical-stage macro cyclic peptide drugs address extracellular protein targets because of the challenge of identifying cell permeable macrocycles. The ability to design potent macrocycles with intrinsic permeability is expected to give access to a large number of important therapeutic targets that have been out of reach to this point.