W.Z. and N.L. made equal contributions in this study. W.Z. conceived the experimental plan, performed material preparation and all data analysis, and co-wrote the manuscript. N.L. performed the animal experiments, identification of cell characterizations and biomedical analysis, and wrote the draft manuscript. H.G.S. and B.Z. performed molecular experiments and the analysis. J.L., L.X.S. and H.Y.W. performed materials characterization. J.H.J. and P.K.C. conceived the experimental plan and finalized the manuscript. All authors reviewed and approved the final manuscript.

There are currently no drugs approved by regulatory authorities for the treatment of NASH. Even though certain drugs, such as insulin sensitizers and antihyperlipidemic agents, are prescribed for some NASH patients, they are not approved for the treatment of NASH and their efficacy has not been proven in adequate and well-controlled clinical studies.

Biosante Pharmaceuticals Inc. (NASDAQGM: BPAX ) BioSante is a specialty pharmaceutical company focused on developing products for female sexual health, menopause, contraception and male hypogonadism. BioSante’s lead products include LibiGel® (transdermal testosterone gel) in Phase III clinical development by BioSante under a U.S. Food and Drug Administration (FDA) SPA (Special Protocol Assessment) for the treatment of female sexual dysfunction (FSD), and Elestrin™ (estradiol gel) developed through FDA approval by BioSante, indicated for the treatment of moderate-to-severe vasomotor symptoms associated with menopause, currently marketed in the U.S. by Azur Pharmaceuticals. Also in development are Bio-T-Gel™, a testosterone gel for male hypogonadism, and an oral contraceptive in Phase II/III clinical development using BioSante patented technology. The current market in the U.S. for estrogen and testosterone products is approximately $2.5 billion and for oral contraceptives approximately $3 billion. The company also is developing its calcium phosphate technology (CaP) for novel vaccines, drug delivery and aesthetic medicine (BioLook™).

Patients in the ARREST study were planned to undergo MRS, and a liver biopsy at baseline and week 52, which were centrally read, blinded to treatment allocation. The statistical analysis plan included pre-defined analysis sets: (i) a full analysis set for MRI (FAS – MRI): all intent to treat, or ITT, patients with baseline and at least one second MRS. 214 patients were included in this analysis set (41 in placebo; 90 in Aramchol 400mg; and 83 in Aramchol 600mg); and (ii) a full analysis set for liver biopsy (FAS – biopsy): all ITT patients with baseline and a second biopsy. 198 patients were included in this analysis set (40 in placebo; 80 in Aramchol 400mg; and 78 in Aramchol 600mg).

We are subject to extensive government regulation and the failure to comply with these regulations may have a material adverse effect on our operations and business.

If an entity or arrangement treated as a partnership for U.S. federal income tax purposes holds our ordinary shares, the tax treatment of such entity or arrangement treated as a partnership and each person treated as a partner thereof generally will depend upon the status and activities of the entity and such person. A holder that is treated as a partnership for U.S. federal income tax purposes should consult its own tax advisor regarding the U.S. federal income tax considerations applicable to it and its partners of the purchase, ownership and disposition of our ordinary shares.

Our Articles permit us to exculpate, indemnify and insure our Office Holders to the fullest extent permitted by the Companies Law. Each of our Office Holders have entered into an indemnification agreement with us, exculpating them, to the fullest extent permitted by Israeli law, from liability to us for damages caused to us as a result of a breach of the duty of care and undertaking to indemnify them to the fullest extent permitted by Israeli law, including with respect to liabilities resulting from certain acts performed by such Office Holders in their capacity as an Office Holder of the Company, our subsidiaries or our affiliates.

Either party may terminate the OWL License Agreement (i) upon the other party’s breach if such party fails to cure such breach within 60 days after receiving written notice thereof; or (ii) upon customary events such as the granting of a winding up order or upon the appointment of a temporary or permanent liquidator or receiver if such order or act is not cancelled within 60 days. We may terminate the OWL License Agreement for any reason upon 30 days’ prior written notice. Further, OWL may terminate the OWL License Agreement upon 30 days’ prior written notice, in the event that within 18 months of receipt of the required regulatory approval to market and sell the first Licensed Technology Product in the U.S, there has not been a first commercial sale, unless such failure or delay is caused by (i) force majeure; or (ii) the requirements of a regulatory or other governmental authority, any contract manufacturer, or due to any market shortage; or (iii) a significant technological and/or scientific barrier. 

Our market is subject to intense competition. If we are unable to compete effectively, Aramchol or any other potential product candidate that we develop may be rendered suboptimal, noncompetitive or obsolete.

        All financial statement schedules have been omitted because they are not applicable, not required or the information required is shown in the financial statements or the notes thereto.

Huggins, C. E. et al. Functional and metabolic remodelling in GLUT4-deficient hearts confers hyper-responsiveness to substrate intervention. J. Mol. Cell. Cardiol. 44, 270–280, 10.1016/j.yjmcc.2007.11.020 (2008).

Maybe acute mitochondrial failure as in mitochondria paper you posted about 3 months ago. Remember big holes mitochondrial membrane.