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RedHill Biopharma Announces YELIVA® (ABC294640) Abstract Presentation at the 2017 Cholangiocarcinoma Foundation Annual Conference

On January 6, 2017 RedHill Biopharma Ltd. (NASDAQ:RDHL) (TASE:RDHL) ("RedHill" or the "Company"), a specialty biopharmaceutical company primarily focused on the development and commercialization of late clinical-stage, proprietary, orally-administered, small molecule drugs for gastrointestinal and inflammatory diseases and cancer, reported the presentation of an abstract relating to YELIVA, the Company’s proprietary, first-in-class, orally-administered sphingosine kinase-2 (SK2) selective inhibitor, at the 2017 Cholangiocarcinoma Foundation Annual Conference, on February 2, 2017, in Salt Lake City, UT (Press release, RedHill Biopharma, JAN 6, 2017, View Source [SID1234517295]).

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The abstract, entitled ‘Targeting Sphingosine Kinase-2 for the Treatment of Cholangiocarcinoma (CCA)’1, was authored by scientists from the Mayo Clinic, Apogee Biotechnology Corp. (Apogee), the Medical University of South Carolina (MUSC) and RedHill. It will be presented by one of its authors, Dr. Lewis R. Roberts, M.B., Ch.B., Ph.D, a gastroenterologist and hepatologist at Mayo Clinic and the External Co-Chair of The Cancer Genome Atlas (TCGA) Cholangiocarcinoma Project of the National Cancer Institute (NCI).

The authors of the abstract assessed the effects of YELIVA on cholangiocarcinoma cells in culture and in patients in the Phase I clinical study with YELIVA, concluding that the findings from these studies suggest that YELIVA may be an effective drug for the treatment of cholangiocarcinoma. Cholangiocarcinoma (bile duct cancer) is a highly lethal malignancy for which there is a need for more effective systemic treatments. Surgery with complete resection remains the only curative therapy for cholangiocarcinoma, however only a minority of patients are classified as having a resectable tumor at the time of diagnosis2.

RedHill announced in June 2016 that the final results from the Phase I study with YELIVA in patients with advanced solid tumors confirmed that the study, conducted at MUSC Hollings Cancer Center, 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.

Of the three patients with cholangiocarcinoma in the Phase I study, one subject achieved a sustained partial response (Overall Survival (OS) = 20.3 months) and the other two subjects had stable disease (OS = 17.6 and 16.3 months).

YELIVA is a Phase II-stage, proprietary, first-in-class, orally-administered sphingosine kinase-2 (SK2) selective inhibitor with anticancer and anti-inflammatory activities, targeting multiple 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.

A Phase II study with YELIVA for the treatment of advanced hepatocellular carcinoma (HCC) was initiated at MUSC Hollings Cancer Center. The study is supported by a $1.8 million grant from the NCI, awarded to MUSC, which is 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, with additional support from RedHill.

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

A Phase I/II clinical study evaluating YELIVA in patients with refractory/relapsed diffuse large B-cell lymphoma was initiated in June 2015 at the Louisiana State University Health Sciences Center in New Orleans and was recently amended to address overall recruitment prospects. The study will now also include Kaposi sarcoma patients. The study is supported by a grant from the NCI awarded to Apogee, with additional support from RedHill.

A Phase Ib study to evaluate YELIVA as a radioprotectant for prevention of mucositis in head and neck cancer patients undergoing therapeutic radiotherapy is planned to be initiated in the first half of 2017.

Additional Phase I/II studies with YELIVA for other indications are in various stages of preparation.

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 Phase I study included the first-ever longitudinal analysis of plasma S1P levels as a potential pharmacodynamic (PD) biomarker for activity of a sphingolipid-targeted drug. The administration of YELIVA resulted in a rapid and pronounced decrease in S1P levels, with several patients having prolonged stabilization of disease. 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.

Puma Biotechnology Expands Cohort in Phase II SUMMIT Trial of PB272 in HER2 Mutation-Positive Cancer Patients

On January 6, 2017 Puma Biotechnology, Inc. (Nasdaq: PBYI), a biopharmaceutical company, reported it has expanded the fourth cohort from its Phase II SUMMIT clinical trial of its lead drug candidate PB272 (neratinib) as a single agent in patients with solid tumors who have an activating HER2 mutation (basket trial) (Press release, Puma Biotechnology, JAN 6, 2017, View Source [SID1234517291]). The cohort that has been expanded is the cohort that includes patients with metastatic cervical cancer and whose tumors have a HER2 mutation.

The Phase II SUMMIT basket trial is an open-label, multicenter, multi-histology, international study to evaluate the safety and efficacy of PB272 administered daily to patients who have solid tumors with activating ERBB mutations including EGFR, HER2 and HER3. The cohorts included in the basket study receiving neratinib monotherapy are hormone receptor-negative breast cancer; biliary tract cancers; endometrial cancer; gastric/esophageal cancer; ovarian cancer; and all other solid tumors with a HER2 mutation. The cohorts receiving combination treatment are hormone receptor-positive breast cancer (neratinib plus fulvestrant) and bladder cancer (neratinib plus paclitaxel). The cervical cancer patients initially entered the study in the "other solid tumors with a HER2 mutation" cohort, and due to the preliminary activity seen in the trial, the Company has expanded a separate cervical cancer cohort pursuant to the protocol for the trial. The expanded HER2-mutant cervical cancer cohort will now enroll a total of 18 patients.

Dr. David Hyman, Director, Developmental Therapeutics at Memorial Sloan Kettering Cancer Center and principal investigator of the trial, stated, "We are pleased to expand our evaluation of neratinib in metastatic cervical cancer, an orphan and deadly disease with few treatment options. We believe this once again demonstrates the value of the basket study approach, in particular for developing targeted therapy for rare diseases with clinically-actionable mutations. We look forward to presenting the full results of the SUMMIT trial at a medical meeting in 2017."

"We are pleased to expand the fourth cohort in the basket trial," said Alan H. Auerbach, Chief Executive Officer and President of Puma. "Although it is early, we are pleased with the initial activity that we are seeing in the patients with HER2 mutated cervical cancer in the trial. We look forward to continuing enrollment into this expanded cohort and look forward to presenting the full results from the SUMMIT study in 2017."

Atreca, Inc. to Participate in Immuno-Oncology Panel at 9th Annual Biotech Showcase

On January 6, 2017 Atreca, Inc., a biotechnology company focused on developing novel therapeutics based on a deep understanding of the human immune response, reported that Tito A. Serafini, Ph.D., Atreca’s President, Chief Executive Officer, and CoFounder, will participate in a panel discussion on immuno-oncology (IO) during the 9th Annual Biotech Showcase Conference on Wednesday, January 11, 2017, at 11:00a.m. Pacific Time (Press release, Atreca, JAN 6, 2017, View Source [SID1234522958]).

The panel, titled "The Overflowing IO Buffet: Next Gen IO Antibodies, Oncolytic Viruses, Bispecifics, Adoptive Cell Therapies and Oral Immunometabolism / Immuno-Epigenetic Agents," will be held at the Hilton San Francisco Union Square in Continental Room 2.

Rgenix Announces Treatment of First Patient in Phase 1 Trial of RGX-104, its Lead Immuno-Oncology Therapeutic

On January 6, 2017 Rgenix, Inc., a clinical stage biopharmaceutical company developing first-in-class small molecule and antibody cancer therapeutics using its unique target discovery platform, reported treatment of the first patient with its lead candidate RGX-104 in a Phase 1a/b study (Press release, Rgenix, JAN 6, 2017, View Source [SID1234517299]). The 80-patient study consists of an initial dose-escalation stage involving patients with advanced solid malignancies and lymphoma, in which an optimal biological dose is being defined using pharmacokinetic, pharmacodynamic, biomarker and safety studies. This will be followed by an expansion stage in at least four cancer types, in which detection of preliminary efficacy signals will be determined.

RGX-104 is an orally administered small molecule that selectively targets the nuclear receptor LXR to activate the expression of the ApoE protein that becomes silenced in human cancers as they grow, become invasive, and metastasize. ApoE silencing is related to reduced survival in cancer patients. The LXR-ApoE pathway was originally identified as a cancer target using a novel microRNA-based discovery platform developed by Rgenix’s scientific co-founders at The Rockefeller University who demonstrated that the pathway regulates the ability of cancers to evade the immune system and recruit blood vessels.

Rgenix’s scientists showed that RGX-104 reverses the immune suppressive and pro-angiogenic effects of cancers by potently activating ApoE expression in cancer and highly specific circulating immune cells, leading to the elimination of these immunosuppressive cells and blood vessels in the tumor microenvironment. RGX-104 treatment confers robust anti-cancer activity and suppression of metastases in a wide range of well-established animal models of multiple human cancer types, including drug-resistant malignancies. In addition to its profound and diverse actions as a single agent, RGX-104 blocks resistance to immune checkpoint inhibitors, providing a rationale to combine RGX-104 with these therapies in patients who either do not initially respond to immune checkpoint inhibitor therapy alone, or those who at first benefited, but soon after developed resistance. RGX-104 was granted Orphan Drug Designation by the FDA for the treatment of several cancer types of high unmet need.

"RGX-104 represents the first LXR-ApoE targeting drug in clinical development for cancer," said Masoud Tavazoie, MD, PhD, Chief Executive Officer and co-founder of Rgenix. He added, "Because of its ability to inhibit tumor growth and metastasis as a single agent in drug-resistant cancer types via a novel mechanism, RGX-104 has the potential to transform the treatment landscape for several common cancers types, addressing urgent unmet needs in oncology."

Dr. Michael Postow, a member of the Melanoma and Immunotherapeutics Service at Memorial Sloan Kettering Cancer Center, one of the RGX-104 study sites, commented, "We are excited about RGX-104’s potential to treat a broad array of cancers given its unique effect on the immune system and strong pre-clinical activity both as a single agent and in combination with a checkpoint inhibitor."

The same discovery platform used to identify the ApoE pathway in cancer has been used to discover several other key regulators of cancer progression that Rgenix is targeting with first-in-class small-molecule and antibody drug candidates as part of its novel therapeutics pipeline.

For more information about the clinical trial visit: View Source

VBL Therapeutics Announces Completion of Enrollment in the Pivotal GLOBE Study

On January 6, 2017 VBL Therapeutics (NASDAQ:VBLT),reported that it has completed enrollment in the GLOBE Phase 3 study evaluating the efficacy of its lead candidate ofranergene obadenovec (VB-111) in patients with recurrent glioblastoma (rGBM) (Press release, VBL Therapeutics, JAN 6, 2017, View Source [SID1234517297]). Enrollment in the study, 256 patients in total, has been completed five months ahead of schedule.

"We are very encouraged by the high level of interest shown by both patients and physicians in GLOBE, resulting in completion of enrollment five months ahead of plan," said Professor Dror Harats, M.D., Chief Executive Officer of VBL. "VB-111 has generated positive data in several tumor types, including a statistically significant overall survival benefit in rGBM. We are hopeful that the GLOBE trial will confirm these positive findings and generate the data required to support registration."

VBL has also received FDA approval for adjustments in the GLOBE protocol. These major modifications relate to the triggers for the interim and final analyses. The SPA covering GLOBE remains in place. Originally, the interim analysis in GLOBE was to be conducted after 91 deaths. The modified protocol specifies that it will be conducted after 105 deaths, and after 50% of the patients have more than 12 months potential follow up, whichever occurs later. The final analysis will be conducted at 189 deaths (75% of events), versus the original planned for 151 deaths (60% of events).

These adjustments to the GLOBE protocol are intended to provide better powering and increase the probability for a clearer efficacy signal. Given the fast recruitment pace and completion of recruitment ahead of schedule, the company continues to expect that the interim analysis will occur in mid-2017 and that the top-line results from the full dataset will be available in early 2018.