We were founded by Dr. Douglas A. Treco, an experienced rare disease drug developer and our President and Chief Executive Officer, and by Dr. Jack Szostak, a pioneer in the field of mRNA display from the Massachusetts General Hospital, an affiliate of Harvard University, and Howard Hughes Medical Institute. Dr. Szostak currently serves as the chairman of our scientific advisory board and a consultant to us. Our management team consists of drug discovery, development, and commercialization experts with experience in translating scientific discoveries into innovative, approved products for rare diseases, including Replagal for Fabry disease, ELAPRASE® for Hunter syndrome, and VPRIV® for Gaucher’s disease, as well as Dynepo for chronic kidney disease, and immunology products, including RITUXAN® and ACTEMRA®.

        Under the Hatch-Waxman Amendments, the FDA may not approve an ANDA until any applicable period of non-patent exclusivity for the RLD has expired. The FDCA provides a period of five years of non-patent data exclusivity for a new drug containing a new chemical entity. For the purposes of this provision, a new chemical entity, or NCE is a drug that contains no active moiety that has previously been approved by the FDA in any other NDA. An active moiety is the molecule or ion responsible for the physiological or pharmacological action of the drug substance. In cases where such NCE exclusivity has been granted, an ANDA may not be filed with the FDA until the expiration of five years unless the submission is accompanied by a Paragraph IV certification, which states the proposed generic drug will not infringe the already approved product’s listed patents or that such patents are invalid or unenforceable, in which case the applicant may submit its application four years following the original product approval.

The activity of HCN channels have been recently shown to be regulated by membrane lipids. Voltage-dependent gating of HCN channels is allosterically regulated by phosphoinositides (particularly PIP2 but not PI), phosphatidic acid (PA), and the fatty acid arachidonic acid (AA)21,22,23,24. This regulation appears independent of the action of cAMP, since their effects are still observed in channels lacking the CNBD23,24. Cholesterol, the major sterol in all mammalian plasma membranes, has been implicated in the modulation of the function of various ion channels25. Cholesterol content in the sarcolemma of cardiac myocytes has been shown to increase when serum cholesterol levels are elevated26, increasing nearly 20% in diabetes27. A recent study has indicated that cholesterol depletion by MβCD in HEK cells and ventricular myocytes impaired rabbit HCN4 channel localization into lipid rafts and shifted V1/2 of activation to more positive potentials and increased diastolic depolarization in rabbit SAN cells28. In this study, we systematically explore the regulation of the three human cardiac HCN isoforms (HCN1, HCN2, and HCN4) by membrane cholesterol.

We may experience rapid and substantial growth in order to achieve our operating plans, which will place a strain on our human and capital resources. Successful implementation of our business plan will require management of growth, which will result in an increase in the level of responsibility for management personnel. Although we have a relatively small number of employees, as we prepare for the ARMOR Study we have been increasing our operations, including expanding our employee base of managerial, operational, clinical and financial personnel. Any future growth will impose significant added responsibilities on members of management, including the need to identify, recruit, maintain and integrate additional employees. To that end, we must be able to, among other things:

In addition, under regulations promulgated pursuant to the Companies Law, companies with no controlling shareholder whose shares are listed for trading on specified exchanges outside of Israel, including the Nasdaq Capital Market, may adopt exemptions from various corporate governance requirements of the Companies Law so long as the company satisfies the applicable foreign country laws and regulations, including applicable stock exchange rules, that apply to companies organized in that country relating to the appointment of independent directors and the composition of audit and compensation committees. Such exemptions include an exemption from the requirement to appoint external directors and the requirement that an external director be a member of certain committees. We may use these exemptions in the future if we do not have a controlling shareholder.

The tubular epithelium, which undergoes EMT, is an important source of matrix-producing cells and contributes to renal fibrogenesis. During EMT, tubular epithelial cells express vimentin, a fibroblast marker, and α-SMA, a myofibroblast marker17. To determine whether P311 regulates renal fibrogenesis via EMT, we examined vimentin and α-SMA expression. We found that vimentin protein levels as well as α-SMA mRNA and protein expression were significantly down-regulated in obstructed kidneys from P311−/− mice. Furthermore, α-SMA-positive regions and acidophilic degeneration seem to be co-localized with P311-positive areas in some tubular epithelial cells. Our previous study also showed that transfecting P311 into human fibroblasts stimulated α-SMA expression10. Moreover, P311 transfection into two murine fibroblast cells induced α-SMA expression. P311 and α-SMA co-localize in myofibroblasts during wound healing, and P311 expression occurs upstream of α-SMA expression9. These findings support our hypothesis that P311 is involved in renal fibrogenesis EMT.

The planned Phase 3/4 study is a multi-national, multi-center, randomized, double blind, placebo-controlled study designed to evaluate the efficacy and safety of Aramchol 600 mg or twice daily Aramchol 300mg as compared to placebo in subjects with NASH confirmed by liver biopsy who are overweight or obese and who have pre-diabetes or type II diabetes. Subjects will have a baseline fibrosis score of 2-3.

DARA Biosciences, Inc. (NasdaqCM: DARA ) is a Raleigh, North Carolina based biopharmaceutical development company that acquires promising therapeutic candidates and develops them through proof of concept in humans for subsequent sale or out-licensing to larger pharmaceutical companies. Presently DARA has two drug candidates with cleared IND (Investigational New Drug) Applications from the United States FDA. The Company has a pipeline of diverse drug candidates at various stages of development, with 82 granted patents and 56 pending applications (U.S. and foreign). The first drug candidate KRN5500 has successfully completed a Phase 2 clinical trial treating cancer patients for neuropathic pain. KRN5500 met its primary endpoint and was statistically significantly (p=0.03) better than placebo. A second Phase 2 clinical trial is planned to start during the second half of 2010. The second drug candidate DB959 is a highly selective, non-thiazolidinedione (TZD), first-in-class dual PPAR (peroxisome proliferator activated receptor) delta/gamma agonist in development for type 2 diabetes. A Phase 1 clinical study for DB959 is underway and the Company plans to announce results in the second half of 2010. In addition, DARA owns CPT-1 inhibitors intended for topical application for patients with psoriasis, a library of DDPIV inhibitors and a diverse library of approximately 1800 PPAR agonists of various molecular modalities. PPAR receptors are found throughout the human body and recent publications report that PPAR agonists may be useful in the treatment of Alzheimer’s disease, cystic fibrosis, liver disease, and a variety of autoimmune diseases. Because its diverse PPAR library has the potential to address the unmet medical needs of these diseases, the Company plans to explore several of these indications.

On October 7, 2000, in connection with a certain share subscription agreement, we sent a letter to Unipharm Ltd., or Unipharm, pursuant to which we agreed to negotiate the grant of an exclusive license to Unipharm with respect to the use of patents within our first patent family covering the composition of matter of Aramchol within Israel on to-be-agreed upon terms and conditions. The letter stated that, if granted, such license would at all times be subject to our best interests, as determined in our sole discretion, and all approvals and proceedings required by agreement or by law. As of the date hereof, no such definitive agreement has been executed with regard to this matter and at this stage, we have no intention to pursue such an agreement. The letter is silent as to term, termination and whether or not it is binding.

a Representative images of the PhastGel Blue R stained two-dimensional gels of Sham, AAS2M and treatments group. Colorful circles in treatments indicate the differentially expressed spots from all drug treatments groups. b The proportion of various functional category in differentially expressed proteins in each group. n = 3.

We selected to test Steamchol, in proof of concept studies through a cosmeceutical route of development. Accordingly, on October 13, 2015, Steamchol received a CAS (Chemical Abstracts Service Registry) name and number to allow its cosmeceutical development.

CytoDyn Inc. (OTCPK:CYDY) engages in the development of therapeutic agents for use against disease associated with human immunodeficiency virus and plasmid-DNA products. The company uses monoclonal antibodies to protect the immune system of the body. Its lead drug candidate, Cytolin is used to treat HIV/AIDS by preventing killer T cells from destroying the CD4 T cells in humans infected with HIV, which results in an impaired immune system. The company also owns a portfolio of patents for the development of a family of plasmid-DNA products that protect human subjects against various strains of influenza. Its other products include Formaxycin, a topical dermatological product to improve the appearance of human skin by eliminating dysplastic and pre-cancerous conditions.