4SC AG, of Planegg, Germany, and Singapore-based Menarini Asia-Pacific Holdings Pte. Ltd. entered a licensing and development partnership for 4SC's oral histone deacetylase inhibitor, resminostat, for the Asia-Pacific (APAC) region. Menarini, part of Italy's Menarini Group, will pay 4SC up-front and milestone payments of up to €95 million (US$101.2 million) in exchange for exclusive licensing rights for the development and marketing of resminostat in all APAC countries, excluding Japan. Menarini will be responsible for the clinical development, regulatory approval and commercialization of resminostat in all oncological indications, including liver cancer. 4SC will be eligible to double-digit royalties linked to product sales. Resminostat is partnered with Tokyo-based Yakult Honsha Co. Ltd. in Japan. (See BioWorld Today, Oct. 1, 2014.)

Astellas Pharma Inc., of Tokyo, and Ventana Medical Systems Inc., of Tucson, Ariz., a member of the Roche Group, entered a master collaboration agreement to develop automated tissue diagnostics in support of therapeutic compounds in development. Initial projects will support early stage clinical trials for Astellas' ASP5878, a small-molecule fibroblast growth factor receptor inhibitor that has been shown to block the kinase activities of FGFR1, FGFR2, FGFR3 and FGFR4. Ventana will develop, in parallel, an immunohistochemistry test identifying FGF19 in certain solid tumors. Financial terms of the agreement were not disclosed.

Athersys Inc., of Cleveland, and partner Chugai Pharmaceutical Co. Ltd. of Tokyo, announced interim results from its exploratory phase II study of the intravenous administration of Multistem cell therapy to treat patients who have suffered an ischemic stroke. Athersys disclosed that the study missed the primary endpoint of global stroke recovery and the secondary endpoints of performance on individual components. But when the analysis was limited to patients who got Multistem within 36 hours (n = 27), the response rate improved markedly on the primary endpoint (odds ratio 2.21, p = 0.07) and on the proportion of subjects described as doing especially well (p = 0.03), gaining an "excellent outcome." The company also pointed out that Multistem treatment was associated with lower rates of mortality and life-threatening adverse events, infections and pulmonary signals. Early last month, Tokyo-based Chugai and Athersys disclosed their partnership and licensing pact to exclusively develop and sell Multistem for stroke in Japan, where the aging population means an increasing health care burden, with the indication on the rise. Athersys has begun preparations for clinical development in Japan, including engagement with the Japanese Health Authority. Chugai will be responsible for the development and commercialization of Multistem for ischemic stroke in Japan, and Athersys will have responsibility for product supply, collecting an up-front cash payment of $10 million from Chugai, with more payments as the program advances. Athersys could get development and regulatory milestone payments from Chugai of up to $45 million, and up to about $150 million more if sales goals are reached.

Benitec Biopharma Ltd., of Sydney, and Asklepios Biopharmaceutical Inc., of Chapel Hill, N.C., said they entered a broad license deal granting Benitec rights to Asklepios' adeno-associated virus (AAV) gene therapy technologies. The technologies currently are being used in Benitec's phase I/II trial evaluating TT-034 in hepatitis C virus. Under the terms, Benitec will maintain access to the use of Asklepios' advanced recombinant AAV gene therapy technologies. Specific terms were not disclosed, but Asklepios will receive an up-front payment and is eligible for milestone payments as well as a related product royalty.

Bionomics Ltd., of Adelaide, Australia, said it presented data at the American Association for Cancer Research annual meeting in Philadelphia describing biomarker data obtained from trials in three indications, including renal cancer, ovarian cancer and mesothelioma. The composite analysis identified biomarkers that consistently change following administration of its lead candidate, the vascular-disrupting agent BNC105, as a monotherapy or in combination with standard of care. The company also said the studies uncovered a correlation of those biomarkers to progression-free survival at six months. In addition, the company presented two posters it said showcase data supporting further biomarker-driven clinical development of BNC101, a monoclonal antibody that targets cancer stem cells, in pancreatic cancer and solid tumors. In other news, Bionomics said it started a phase II study of BNC210, in development for the treatment of anxiety and depression. The study will use functional magnetic resonance imaging (fMRI) to assess the effects of BNC210 on brain activity in patients suffering from anxiety. The double-blind, placebo and lorazepam-controlled, four-way crossover single-center study will be conducted in 24 patients with untreated generalized anxiety disorder. Patients will be randomized to receive one of two doses of BNC210 (300 mg or 2,000 mg) or one of two controls, placebo or 1.5 mg lorazepam. The study will evaluate the capacity of BNC210 to engage brain systems relevant to anxiety. The endpoints include both significant changes in cerebral perfusion and in task-related brain activity using the emotional faces task during fMRI. The clinical phase of the study is expected to be completed by Q2 2016 with results due in Q3 2016.

Curadev Pharma Private Ltd., of New Delhi, India, said it entered a research collaboration and licensing agreement with Roche Holding AG, of Basel, Switzerland, to develop and commercialize IDO1 (indoleamine-2, 3-dioxygenase-1) and TDO (tryptophan-2, 3-dioxygenase) inhibitors. Under terms of the agreement, Curadev will receive an up-front payment of $25 million and will also be eligible to receive up to $530 million in milestone payments based on achieving certain events and sales levels. Curadev would also be eligible for milestones and royalties on additional products, which result from the collaboration. Roche will fund future R&D, manufacturing and commercialization costs.

Daiichi Sankyo Co. Ltd., of Tokyo, said Swissmedic, the regulatory authority of Switzerland, approved Lixiana (edoxaban), an oral, once-daily selective factor Xa inhibitor, to prevent stroke and systemic embolism in adults with nonvalvular atrial fibrillation. In addition, the company said the drug has obtained marketing authorization in Switzerland for adults with venous thromboembolism including deep vein thrombosis and pulmonary embolism, following prior treatment with fractionated or unfractionated heparin for five days, as well as to prevent the recurrence of VTE.

D-Pharm Ltd., of Rehovot, Israel, said co-development partner Jiangsu Nhwa Pharmaceutical Co. Ltd., of Jiangsu, China, received an approval letter from the CFDA to allow clinical development of DP-VPA, through phase III, in epilepsy. The specific clinical protocols will be communicated to the CFDA before the start of each new study. Nhwa will begin with a bridging safety study and then proceed with a large dose-ranging phase IIb study in epilepsy patients. DP-VPA, a derivative of the valproic acid, previously was granted fast track status.

Enanta Pharmaceuticals Inc., of Watertown, Mass., said the Japanese Ministry of Health, Labor and Welfare has granted priority review for collaborator North Chicago-based Abbvie Inc.'s investigational, two direct-acting antiviral combination of ombitasvir/paritaprevir/ritonavir for the treatment of genotype 1 chronic hepatitis C infection. That all-oral treatment is ribavirin-free and interferon-free and will be dosed once daily.

Eyenovia Inc., of Tampa, Fla., disclosed the signing of an exclusive license and development agreement with Senju Pharmaceutical Co. Ltd., of Osaka, Japan, whereby Senju acquires the exclusive rights to develop and commercialize microdosed ophthalmic therapeutics in Japan and the rest of Asia. Senju is also joining the series A investment syndicate alongside Private Medical Equity, Eshelman Ventures and Mario Family Partners. Senju will also assume responsibility for all Asia research and development activities. Terms were not disclosed.

Garvan Institute of Medical Research, of Sydney, said that despite failing to recruit eligible patients to date, the ongoing pancreatic cancer trial, IMPACT, or Individualized Molecular Pancreatic Cancer Therapy, has so far identified many ways in which the trial can help bring about "a new paradigm of personalized cancer care for pancreatic cancer and other aggressive cancer types." Andrew Biankin and Lorraine Chantrill, clinical researchers from the institute and authors of an article published online Monday in the American Association for Cancer Research's journal Clinical Cancer Research, said that they encountered many hurdles, including the newness of the technology involved, skepticism about genomic medicine and "many complex administrative processes and protocols demanded by current clinical trial frameworks." Biankin, who is now based at the Wolfson Wohl Cancer Research Centre at the University of Glasgow in Scotland, will be undertaking parallel trials in the UK, implementing the lessons learned through the IMPACT trial. The data were released at the American Association for Cancer Research meeting in Philadelphia.

Imugene Ltd., of Melbourne, Australia, said its lead candidate, HER-Vaxx, showed an increase in the production of cancer-fighting antibodies in animal models. The new formulation showed responses up to 10 times those produced in previous formulations, and showed a shortening in the time taken for the immune system to respond to HER-Vaxx. The research was conducted by a team at the Medical University of Vienna under the direction of Ursula Wiedermann, principal investigator for the preclinical development of HER-Vaxx, and member of Imugene's scientific advisory board. The enhanced formulation of HER-Vaxx combined an existing vaccine carrier protein called CRM197 together with an adjuvant. CRM197 replaces the virosomes used in previous formulations of HER-Vaxx. Last Friday, Imugene filed a new patent application based on the new formulation for major jurisdictions.

Nektar Therapeutics, of San Francisco, reported that its partner, Baxter International Inc., of Deerfield, Ill., said it submitted a new drug application to Japan's Ministry of Health, Labour and Welfare for the approval of BAX 855, an investigational, extended half-life recombinant factor VIII treatment based on Advate (recombinant antihemophilic factor) for patients older than 12 with hemophilia A.

Novogen Ltd., of Sydney, said it will work with the New York-based Feinstein Institute for Medical Research to develop TRXE-009 (trilexium), the lead candidate from its super-benzopyran platform (SBP), as a treatment of both primary and secondary brain cancer in adults and children, including glioblastoma and medulloblastoma. The partners will also explore the potential ability of the SBP technology to convert cancer stem cells into stem cells displaying normal stem cell behavior and the develop drug candidates as radio-sensitizers designed to augment the effectiveness of radiotherapy in treating brain cancers. The financial terms of a memorandum of understanding established between the parties were not disclosed. In other news, Novogen, its subsidiary Cantx Inc., and Yale University disclosed key preclinical data on experimental anticancer drug, Cantrixil, justifying its ability to significantly improve the survival outlook for patients with ovarian cancer. Researchers at the Yale Medical School have established clinically relevant in vitro and in vivo models of chemo-resistant ovarian cancer, providing a tool that drug developers increasingly are accessing to screen prospective drugs against. This is a highly stringent screen that Yale contended provides a rapid go/no-go decision point for lead drug-candidates. To date, no drug candidate has provided a meaningful or durable anti-cancer effect in this model. In this highly aggressive model, intra-peritoneal Cantrixil treatment effectively prevented tumor recurrence by 95 percent. The data were released at the American Association for Cancer Research meeting in Philadelphia.

Otsuka Pharmaceutical Co. Ltd., of Tokyo, and H. Lundbeck A/S, of Valby, Denmark, said results from a multicenter study evaluating the effects of the investigational compound brexpiprazole, as monotherapy in adult patients with schizophrenia, were published online by the American Journal of Psychiatry. The study evaluated the efficacy and tolerability of brexpiprazole in adult patients with an acute exacerbation of schizophrenia, and results will be featured in the September 2015 print issue of the publication.

Regenerx Biopharmaceuticals Inc., of Rockville, Md., said its U.S. joint venture with South Korea-based G-treebnt (Regentree LLC) retained Ora Inc. to conduct a phase III trial for the orphan disorder neurotrophic keratopathy, and a phase IIb/III dose-response, confirmatory trial for dry eye syndrome in the U.S. Both trials will test Regentree's preservative-free eye drops, RGN-259/GBT201, this year.

Takeda Pharmaceutical Co. Ltd., of Osaka, Japan, and the Center for iPS Cell Research Application (CiRA) of Kyota University are working together to develop clinical applications of induced pluripotent stem (iPS) cells in areas such as heart failure, diabetes mellitus, neurological disorders and cancer immunotherapy. The "Takeda-CiRA Joint Program for iPS Cell Applications" is designed to expedite multiple research projects for drug discovery and cell therapy using iPS cells, with Takeda providing long-term funding – more than ¥12 billion (US$101 million) over a 10-year period – as well as recommendations on research management and facilities at its Shonan Research Center, Fujisawa, Japan. Once set up, roughly 10 projects will be pursued concurrently.