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RedHill Biopharma Announces Positive Final Results with Primary and Secondary Endpoints Met in Phase 1 Study with YELIVA™ in Advanced Solid Tumors

On June 21, 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 inflammatory and gastrointestinal diseases and cancer, reported positive final results from the Phase I study with YELIVA (ABC294640) in advanced solid tumors (Press release, RedHill Biopharma, JUN 21, 2016, View Source [SID:1234513470]).

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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.

"We are very pleased with the results of the Phase I study with YELIVA in advanced solid tumors. The study demonstrated the safety and tolerability of this novel drug candidate, as well as its potential efficacy, with several patients in the study who experienced stable disease with progression-free survival for significant terms, despite the advanced nature of their cancers," said Terry Plasse, MD, RedHill’s Medical Director. "We are excited about the therapeutic potential of YELIVA for multiple oncology, inflammatory and gastrointestinal indications, and look forward to initiation of additional Phase II studies by the end of this year. Given YELIVA’s unique mechanism of action, we also strongly believe that it could provide an added benefit to cancer patients in combination with several of the leading oncology drugs currently available, and we are currently exploring potential collaboration opportunities to evaluate YELIVA as an add-on therapy."

The Phase I Clinical Study Report (CSR) confirms the positive top-line results previously announced by the Company. The final results demonstrated that YELIVA can be safely administered to cancer patients at doses that provide circulating drug levels that are predicted to have therapeutic activity, based on levels required in preclinical models. The study included the first-ever longitudinal analyses of plasma S1P levels as a potential pharmacodynamic biomarker for activity of a sphingolipid-targeted drug. Administration of YELIVA resulted in a rapid and pronounced decrease in S1P levels over the first 12 hours, with return to baseline at 24 hours, which is consistent with clearance of the drug. In addition, one patient had a prolonged partial remission and several patients had prolonged stabilization of disease.

The primary objectives of the study were to identify the maximum tolerated dose (MTD), the dose limiting toxicities (DLTs) and to evaluate the safety of YELIVA. The primary objectives were all met and the drug was found to be safe and well tolerated, with grade 1-2 fatigue and nausea being the most common side effects. Several patients experienced mild neuropsychiatric symptoms, such as anxiety and mood changes. These were resolved quickly upon discontinuation of study medication. All treatment-related adverse events were rapidly reversible upon dose reduction or study drug removal.

The secondary objectives of the study, to determine the pharmacokinetic (PK) and pharmacodynamic (PD) properties of YELIVA and to assess its antitumor activity, were also met.

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.

An important differentiating point between YELIVA and the other two compounds which act on the S1P receptor (GILENYA (fingolimod hydrochloride), approved for the treatment of multiple sclerosis, and ozanimod hydrochloride, currently under development for ulcerative colitis, Crohn’s disease and multiple sclerosis), is that YELIVA causes only modest decreases in lymphocyte count. A decrease in lymphocytes may make patients susceptible to certain infections.

Preliminary positive data from the Phase I study was presented by Apogee Biotechnology Corp. (Apogee) at the November 2013 Molecular Targets and Cancer Therapeutics meeting.

The Phase I study was conducted at the Medical University of South Carolina (MUSC) Hollings Cancer Center, an NCI-Designated Cancer Center, and was supported by grants from the U.S. National Cancer Institute (NCI) awarded to MUSC, and from the U.S. FDA Office of Orphan Products Development (OOPD) awarded to Apogee. The study was led by Principal Investigators Melanie Thomas, MD and Carolyn Britten, MD. The open-label, dose-escalation, PK and PD first-in-human Phase I study with YELIVA treated 21 patients with advanced solid tumors, the majority of whom were gastrointestinal cancer patients, including pancreatic, colorectal, cholangiocarcinoma cancers. The patients were continuously treated in cycles of 28 days with the study drug, in the absence of disease progression, and tumors were reimaged every two cycles. Patients were evaluated for an additional period of up to one year after discontinuing treatment with YELIVA.

A Phase I/II clinical study was initiated at the Louisiana State University Health Sciences Center (LSUHSC) in New Orleans in June 2015 evaluating YELIVA in patients with refractory/relapsed diffuse large B-cell lymphoma (DLBCL), including in patients with HIV-related DLBCL. Pending consideration of protocol amendment aimed at improving recruitment prospects, the study is currently on administrative hold. The study is supported by a grant awarded to Apogee from the NCI Small Business Technology Transfer (STTR) program, as well as additional support from RedHill.

A Phase I/II study with YELIVA for the treatment of refractory or relapsed multiple myeloma is to be initiated in the coming weeks. The study will be conducted 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 II clinical study to evaluate YELIVA as a radioprotectant to prevent mucositis in cancer patients undergoing therapeutic radiotherapy is planned to be initiated in the U.S. during the second half of 2016, subject to regulatory and other conditions.

A Phase II study with YELIVA for the treatment of advanced hepatocellular carcinoma is planned to be initiated in the third quarter of 2016. The study will be conducted at the MUSC Hollings Cancer Center and additional clinical centers in the U.S. The study is supported by a $1.8 million grant from the NCI awarded to MUSC, intended to support 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.

The Phase I/II clinical studies, as well as the completed Phase I clinical study in cancer patients with advanced solid tumors, 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 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. 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.

Mateon Therapeutics to Present New Improved Survival Outcomes for CA4P in Recurrent Ovarian Cancer at June 27 Investor Event

On June 20, 2016 Mateon Therapeutics, Inc. (Nasdaq:MATN), a biopharmaceutical company developing vascular disrupting agents (VDAs) for the treatment of orphan oncology indications, reported that it plans to hold an event for investors on Monday, June 27, 2016 at 12:00 pm at the Lotte New York Palace Hotel with Bradley J. Monk, M.D., a recognized leader in ovarian cancer and Director of the Division of Gynecologic Oncology at St. Joseph’s Hospital and Medical Center (Press release, Mateon Therapeutics, JUN 20, 2016, View Source [SID:1234513464]). To listen to a live version of the audio webcast, with presentations expected to begin at approximately 12:15 pm, please visit the company’s website, www.mateon.com. Under the "Investors & News" tab, select the link to "Events & Presentations." A replay of the webcast will be available at this same location after the conclusion of the live event.

New Analyses of Data Received from Study GOG-0186I

At the investor event on June 27, new analyses will be presented from a more recent (November 2015) and more mature dataset from the GOG-0186I Study in patients with recurrent ovarian cancer, including analyses to further define the patient population most likely to benefit from treatment with CA4P. Given the preclinical data and the mechanism of action of CA4P, Mateon believes that CA4P is likely to have the greatest effect in larger tumors, and therefore performed additional analyses on data from patients with "measurable disease" and on those with larger tumor volumes.

Results of these analyses are listed below.

Intent-to-Treat Population
The GOG-0186I Study compared the combination of CA4P and bevacizumab (CA4P-treated) to bevacizumab alone (control) in women with recurrent ovarian cancer, enrolling a total of 107 patients. The median overall survival (OS) in the intent-to-treat (ITT) group was 3.2 months longer for the CA4P-treated patients compared to the control patients (25.2 vs. 22.0 months, respectively; HR=0.83, not statistically significant). Data published in the Journal of Clinical Oncology (dataset as of April 2015) showed an improvement in median OS of 2.6 months for CA4P-treated patients.

Patients with Measurable Disease
The GOG-0186I Study included 81 patients (75.7% of study patients) with recurrent ovarian cancer that was deemed "measurable", a pre-specified covariate defined by RECIST criteria, and 26 patients (24.3%) deemed "non-measurable." Measurable disease is generally defined as primary tumor sizes greater than 1 cm in diameter, while non-measurable tumors are generally identified and monitored by increased serum CA-125 antigen levels, ascites, or other clinical signs of disease.

Patients with measurable disease treated with CA4P had a 5.6 month improvement in median OS (26.8 vs. 21.2 months; 22% reduction in the risk of death; HR=0.78, not statistically significant), and a 3.7 month improvement in progression free survival (PFS) (9.8 vs. 6.1 months; HR=0.60, p=0.027) compared to control patients with measurable disease.

Additional analyses were conducted on patients with measurable disease whose tumors were larger than the median baseline tumor size (tumor size ≥5.7 cm; n=41). CA4P-treated patients with these tumor sizes experienced a 48% reduction in the risk of death (HR=0.52; p=0.095) and a 6.2 month improvement in median PFS (10.5 vs. 4.3 months; HR=0.55, p=0.071) compared to control patients.

"Overall survival is the gold standard for determining clinical benefit in oncology indications. The most recent analyses from this more mature dataset show an improvement in overall survival for all patients treated with CA4P, greater overall survival for patients whose tumors can be measured, and initial evidence of an even greater survival for patients with tumors which are large and the most difficult to treat," said William D. Schwieterman, M.D., President and Chief Executive Officer of Mateon. "These remarkable outcomes align entirely with our preclinical data and the mechanism-of-action of CA4P, provide us with a deep understanding of where and how best to use CA4P as we move forward, and strongly support the efficacy of combination vascular targeted therapy for the treatment of ovarian and other cancers."

Mateon is planning to study CA4P for the treatment of patients with platinum-resistant ovarian cancer in a double-blind randomized placebo controlled study of CA4P in combination with bevacizumab and physician’s choice chemotherapy (PCC) compared to bevacizumab and PCC (the "FOCUS" study). FOCUS will only enroll patients with measurable disease, and includes pre-specified analyses in its first phase that are designed to confirm the outcomes reported today. If these are confirmed, Mateon will consider expansion of its development program for CA4P from platinum-resistant ovarian cancer to the much larger group of patients with recurrent ovarian cancer.

PharmaCyte Biotech CEO Interviewed Live During Marcum MicroCap Conference

On June 20, 2016 PharmaCyte Biotech, Inc. (OTCQB:PMCB), a clinical stage biotechnology company focused on developing targeted treatments for cancer and diabetes using its signature live-cell encapsulation technology, Cell-in-a-Box, reported that Kenneth L. Waggoner, the Chief Executive Officer of PharmaCyte, was interviewed by Stock News Now (SNN) at the 5th Annual Marcum MicroCap Conference in New York City (Press release, PharmaCyte Biotech, JUN 20, 2016, View Source [SID:1234513462]). The SNNLive video interview can be viewed by clicking on the following link: www.PharmaCyte.com/Media.

During his interview, Mr. Waggoner describes how PharmaCyte plans to use its live cell encapsulation technology, known as Cell-in-a-Box, for the development of treatments for locally advanced, inoperable pancreatic cancer and for Type 1 and insulin-dependent Type 2 diabetes. Mr. Waggoner also discusses the mechanism of action PharmaCyte uses to treat cancerous tumors and talks about PharmaCyte’s plans to begin a Phase 2b clinical trial in patients with locally advanced, inoperable pancreatic cancer. That trial is planned to start in Q4 2016.

In discussing PharmaCyte’s efforts to develop a treatment for diabetes, Mr. Waggoner talks about the preclinical studies that are being conducted concurrently by several renowned experts in the field of diabetes in various countries around the globe. All of these experts are members of PharmaCyte’s International Diabetes Consortium. Mr. Waggoner also explains that by conducting their studies as part of a consortium, rather than sequentially, the overall treatment development timeline has been shortened considerably. This will allow PharmaCyte to potentially begin a clinical trial in diabetes as early as late 2017.

Varian Medical Systems Launches Proton Therapy Blog

On June 20, 2016 Varian Medical Systems (NYSE: VAR), reported the launch of Spot ON, a company blog about proton therapy for the treatment of cancer (Press release, Varian Medical Systems, JUN 20, 2016, View Source [SID:1234513459]). Targeted at clinicians, physicists and administrators of radiotherapy centers around the world, Spot ON will deliver information about new technology developments, system deployments, research and insights from clinicians.

The first Spot ON blog entry is from Dr. Carl Rossi, medical director of the Scripps Proton Therapy Center in San Diego, California. Dr. Rossi’s blog is an introduction to adaptive radiotherapy using intensity-modulated proton therapy.

Read the first blog entry here: www.varian.com/proton-therapy/spot-news/introduction-adaptive-radiotherapy-using-impt

"Varian is creating the Spot ON blog to increase the awareness and understanding of proton therapy and the important role it plays in cancer treatment," said Bill Hansen, director of marketing, Particle Therapy Division at Varian.

8-K – Current report

On June 20, 2016 Mateon Therapeutics, Inc. (Nasdaq:MATN), a biopharmaceutical company developing vascular disrupting agents (VDAs) for the treatment of orphan oncology indications, reported that it plans to hold an event for investors on Monday, June 27, 2016 at 12:00 pm at the Lotte New York Palace Hotel with Bradley J. Monk, M.D., a recognized leader in ovarian cancer and Director of the Division of Gynecologic Oncology at St. Joseph’s Hospital and Medical Center (Filing, 8-K, OXiGENE, JUN 20, 2016, View Source [SID:1234513458]). To listen to a live version of the audio webcast, with presentations expected to begin at approximately 12:15 pm, please visit the company’s website, www.mateon.com. Under the "Investors & News" tab, select the link to "Events & Presentations." A replay of the webcast will be available at this same location after the conclusion of the live event.

New Analyses of Data Received from Study GOG-0186I
At the investor event on June 27, new analyses will be presented from a more recent (November 2015) and more mature dataset from the GOG-0186I Study in patients with recurrent ovarian cancer, including analyses to further define the patient population most likely to benefit from treatment with CA4P. Given the preclinical data and the mechanism of action of CA4P, Mateon believes that CA4P is likely to have the greatest effect in larger tumors, and therefore performed additional analyses on data from patients with "measurable disease" and on those with larger tumor volumes.
Results of these analyses are listed below.

Additional analyses were conducted on patients with measurable disease whose tumors were larger than the median baseline tumor size (tumor size ³5.7 cm; n=41). CA4P-treated patients with these tumor sizes experienced a 48% reduction in the risk of death (HR=0.52; p=0.095) and a 6.2 month improvement in median PFS (10.5 vs. 4.3 months; HR=0.55, p=0.071) compared to control patients.