On June 21, 2016 TapImmune,Inc. (TPIV), a clinical-stage immuno-oncology company specializing in the development of innovative peptide and gene-based immunotherapeutics and vaccines for the treatment of cancer & metastatic disease, reported reaching a major milestone of dosing its first patient in a Phase 2 trial for triple negative breast cancer with its cancer vaccine TPIV 200 (Press release, TapImmune, JUN 21, 2016, View Source [SID:1234513485]).

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The first patient enrolled is being treated at the University of Maryland – one of 8 sites being used in this study, conducted and funded by TapImmune.

The randomized, open label Phase 2 study is expected to enroll a total of 80 subjects. The primary endpoints are dosing regimens and safety. Secondary endpoints are T-cell specific responses and evaluation of objective responses.

Dr. Glynn Wilson, Chairman and CEO of Tapimmune stated, "Enrolling and treating this first patient represents the start of a robust and intensive Phase 2 clinical program for our lead product TPIV 200, a Folate Receptor Alpha T-cell vaccine."

TPIV 200 is currently being investigated in two other Phase 2 trials at the Mayo Clinic and at Memorial Sloan Kettering.

"Enrollment has started in the Phase 2 40 patient study at Memorial Sloan Kettering in collaboration with Astra Zeneca in late-stage ovarian cancer. In addition, the large 280 patient Phase 2 trial being run at the Mayo Clinic with a grant from the Department of Defense is expected to start enrollment later this year," Dr. Wilson added.

TapImmune has received Fast Track Status and Orphan Drug Designation for TPIV 200. The Company plans to initiate a fourth Phase 2 clinical study, in late 2016, designed to treat platinum-sensitive ovarian cancer patients.

"The clinical strategy for TPIV 200 is designed to examine the potential for this exciting T-cell vaccine in as many clinical settings as possible using the most cost-effective pathways. We are excited by the potential for this drug candidate and believe positive data from the Phase 1 study will be reflected in the results of our ongoing Phase 2 clinical investigations," Dr. Wilson concluded.

Interested investors in TapImmune’s clinical studies can learn more by going to: View Source

About Triple Negative Breast Cancer
Triple-negative breast cancer refers to any breast cancer that does not express the genes for estrogen receptor (ER), progesterone receptor (PR) or Her2/neu. Currently the most successful breast cancer treatments target these three receptors, which are lacking in triple negative breast cancer, thus making this sub-type of breast cancer more difficult to treat. This kind of breast cancer can also be more aggressive and more likely to recur than other types of breast cancer. Triple-negative breast cancer accounts for approximately 15%-25% of all breast cancer cases.

On June 21, 2016 Curis, Inc. (Nasdaq:CRIS), a biotechnology company focused on the development and commercialization of innovative and effective therapeutics for the treatment of cancer, reported that the first patient was dosed in a Phase 1 trial of CA-170 (Press release, Curis, JUN 21, 2016, View Source [SID:1234513472]).

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CA-170 is a first-in-class, orally available, small molecule that is designed to specifically target and inhibit the immune checkpoints, Programmed Death Ligand-1 (PD-L1) and V-domain Immunoglobulin Suppressor of T-cell Activation (VISTA). CA-170 is being developed under a collaboration and licensing agreement with Aurigene Discovery Technologies, Ltd.

"Today, we are pleased to announce dosing of the first patient in our Phase 1 trial of CA-170," said Ali Fattaey, Ph.D., Curis’s president and CEO. "During the dose escalation stage of the trial, we look to characterize CA-170’s safety and activity in patients with solid tumors and lymphoma. In the expansion stage of the trial, we expect to identify specific indications and regulatory paths for this highly differentiated drug candidate."

Preclinical ex vivo experiments demonstrated that CA-170 induced effective proliferation and cytokine production by T cells that are specifically suppressed by PD-L1 or VISTA. In subsequent preclinical in vivo studies, CA-170 showed significant anti-tumor activity, similar to anti-PD-1 antibodies, in multiple tumor models.

In preclinical toxicology studies, CA-170 was considered to be safe when administered at multiple dose levels using a once daily oral dosing schedule.

The Phase 1 study is designed to: (1) evaluate the safety, tolerability, and pharmacokinetic profile of CA-170; (2) identify any dose-limiting toxicities; and (3) establish the recommended Phase 2 dose (RP2D) of CA-170 in patients with advanced solid tumors or lymphoma. During the expansion stage, the study is expected to assess the anti-cancer activity of CA-170 at the RP2D in patients with specified cancer types.

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.