On October 2016 Karus Therapeutics (‘Karus’), a leader in the development of innovative, orally-active medicines with breakthrough potential in the treatment of cancer, reported that the first patients have been dosed in a Phase I study for its lead candidate, KA2237 (Press release, Karus Therapeutics, OCT 5, 2016, View Source [SID:SID1234515610]).

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This is the Company’s first product to enter clinical trials. KA2237 is a dual-selective inhibitor of two PI3K isoforms, p110β and p110δ. Inhibiting these two isoforms combines an immunotherapeutic response and a direct effect on tumor growth, through selective, targeting of the PI3K pathway. Karus believes that KA2237 has broad therapeutic applicability in the treatment of hematological and solid tumors, as a single agent and in combination with other drugs.

This study forms part of the pre-clinical and clinical collaboration between Karus and the University of Texas MD Anderson Cancer Center, the world’s leading cancer research and care center. The first part of the trial has been designed to assess the safety of KA2237 alone in relapsed, treatment-resistant B cell lymphoma patients. An expansion cohort study will follow and is scheduled to start in 2017. Karus anticipates that up to 40 patients will be treated over the entire study.

Dr. Simon Kerry, CEO of Karus Therapeutics, commented: "Our first clinical trial is a major milestone for the company. Karus has made exceptional progress and our collaboration with MD Anderson will help us to accelerate this clinical program. We believe that as an orally-active dual p110β/δ inhibitor, KA2237 has significant potential in the treatment of hematological and solid tumors in areas of high, unmet medical need."

Professor Stephen Shuttleworth, CSO, added: "Our R&D programs are built on many years’ investment in research that have given us a deep understanding of PI3K medicinal chemistry and tumor biology. To take a scientific concept through rational de novo-design to create KA2237, a dual-selective, small molecule PI3K inhibitor that has been designed specifically to address areas of unmet medical need, is a very rewarding moment in our journey towards developing new cancer treatments for patients with few remaining therapeutic options."

The agreement with MD Anderson covers a number of preclinical studies of Karus’s two cancer programs, KA2237 and KA2507, with a focus on identifying optimal drug combinations and the appropriate patient populations for further clinical development. The second program, KA2507, a selective-HDAC6 inhibitor, also has both a targeted therapy and immunotherapeutic action and has potential in the treatment of multiple myeloma, B- and T-cell lymphomas and PD-L1 expressing hematological and solid tumors.

On October 5, 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 that a Phase II clinical study evaluating YELIVA (ABC294640) in patients with advanced hepatocellular carcinoma (HCC) has been initiated, with enrollment expected to commence shortly, pending final regulatory clearance (Press release, RedHill Biopharma, OCT 5, 2016, View Source [SID:SID1234515596]).

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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 and evaluating with YELIVA multiple clinical programs in oncology, inflammatory and gastrointestinal indications, as well as potential collaboration opportunities with larger pharmaceutical companies to evaluate YELIVA as an add-on therapy to their existing oncology treatments.

The HCC Phase II study will be conducted at the Medical University of South Carolina Hollings Cancer Center (MUSC) and additional clinical centers in the U.S. It is supported by a $1.8 million grant from the National Cancer Institute (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 for the treatment of HCC. The Phase II HCC study will be supported by additional funding from RedHill.

The Phase II study will evaluate YELIVA as a second-line monotherapy in up to 39 patients with advanced HCC who have experienced tumor progression following treatment with first-line single-agent sorafenib (Nexavar). Carolyn D. Britten, MD, Chief of the Division of Hematology/Oncology in the Department of Medicine at MUSC and Associate Director for Clinical Investigations at the MUSC Hollings Cancer Center, is the Principal Investigator for the Phase II study.

Dr. Carolyn D. Britten, MD, said: "We are looking forward to testing YELIVA in advanced hepatocellular cancer, a devastating disease with no approved systemic therapy beyond sorafenib."

HCC is the most common primary malignant cancer of the liver, accounting for approximately 85% of liver cancer cases1. It is the fifth and ninth most prevalent cancer worldwide in men and women, respectively, and the second most frequent cause of cancer-related deaths worldwide2. Annual worldwide incidence of liver cancer was estimated to have reached 782,000 cases in 2012, with a mortality rate of 95%; the corresponding U.S. numbers are 30,000 and 80%, respectively3. Most patients with HCC suffer from liver cirrhosis, which develops following long periods of chronic liver disease. The majority of HCC cases are associated with hepatitis B and hepatitis C virus infections. Few treatment options exist for patients diagnosed at an advanced stage, representing the majority of HCC patients. Sorafenib (Nexavar) is a targeted drug approved for the treatment of HCC in patients who are not candidates for surgery and do not have severe cirrhosis. The worldwide and U.S. markets for the treatment of HCC are estimated to reach approximately $895 million and $471 million in 2017, respectively4.

Results from a Phase I study with YELIVA in patients with advanced solid tumors confirmed that the study, also conducted at 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 of which had stable disease 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 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 quarter of 2017.

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 in the coming weeks 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 ongoing 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 October 5, 2016 Chugai Pharmaceutical Co., Ltd. (TOKYO: 4519) reported that the US Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation to ACTEMRA /RoACTEMRA (tocilizumab), a Chugai originated drug, which is currently under development by Roche and Genentech for the indication of Giant Cell Arteritis (GCA) (Press release, Chugai, OCT 5, 2016, View Source [SID:SID1234515594]).

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"We are very pleased that the FDA has once again granted Breakthrough Therapy Designation to ACTEMRA/RoACTEMRA, following last year’s designation for systemic sclerosis," said Chugai’s Senior Vice President, Head of Project & Lifecycle Management Unit, Dr. Yasushi Ito. "This designation indicates that ACTEMRA/RoACTEMRA is highly regarded, and has great potential to fulfill unmet medical needs in auto-immune diseases."

This designation was based on the GiACTA study, which is a global Phase III study assessing the efficacy and safety in patients with GCA. This is the fifth Breakthrough Therapy Designation for a Chugai originated drug, following these three products: alectinib (ALK-positive non-small cell lung cancer with disease progression on crizotinib, first line treatment for ALK-positive non-small cell lung cancer), tocilizumab (systemic sclerosis), and emicizumab (prophylactic treatment for patients 12 years or older with hemophilia A with factor VIII inhibitors).

Based on Chugai’s business philosophy "innovation all for the patients," Chugai will collaborate with Roche and Genentech to submit marketing applications for ACTEMRA/RoACTEMRA in a number of countries around the world, with the intent to increase access to this new treatment option for patients and healthcare professionals as soon as possible.

About Breakthrough Therapy
The Breakthrough Therapy Designation was adopted as part of the FDA Safety and Innovation Act (FDASIA) enacted in July 2012 aiming at expediting the development and review of drugs for the treatment of severe or life-threatening diseases or symptoms. In order to grant Breakthrough Therapy Designation, preliminary clinical evidence is required demonstrating that the drug may have substantial improvement on at least one clinically significant endpoint over existing therapies. Breakthrough Therapy Designation includes the features of a Fast Track designation, with the addition of intensive guidance on efficient drug development as well organizational commitment from FDA.

About Giant Cell Arteritis
Giant Cell Arteritis (GCA) belongs to an autoimmune disease called large-vessel vasculitis. GCA is a granulomatous vasculitis occurring primarily in the aorta and aortic branches, mainly the temporal arteries. Common initial symptoms include headache, systemic conditions such as fever, and loss of vision. GCA is prevalent in Western countries and affects women more than men with the typical age of onset 50 years or older1). Vasculitis can be classified into three different groups depending on the size of the inflammatory vessels, such as large vessel vasculitis, medium vessel vasculitis and small vessel vasculitis2). Besides GCA, Takayasu’s arteritis which appears more commonly in Asian young ladies is also included in large-vessel vasculitis.

About the GiACTA Study
GiACTA (NCT01791153) is a Phase III, global, randomised, double-blind, placebo-controlled trial investigating the efficacy and safety of ACTEMRA/RoACTEMRA as a novel treatment for GCA. It is the largest clinical trial ever conducted in GCA and the first to use blinded, variable-dose, variable-duration steroid regimens. The multicenter study was conducted in 251 patients across 76 sites in 14 countries. The study’s primary endpoint was the proportion of patients achieving sustained disease remission at week 52. The secondary endpoints were the time to first GCA flare after clinical remission, cumulative corticosteroid dose at week 52, and also safety outcome measures.
The GiACTA data will be submitted for presentation at an upcoming medical conference and to regulatory authorities around the world for approval consideration.