Our audits included performing procedures to assess the risks of material misstatement of the financial statements, whether due to error or fraud, and performing procedures that respond to those risks. Such procedures included examining, on a test basis, evidence regarding the amounts and disclosures in the financial statements. Our audits also included evaluating the accounting principles used and significant estimates made by management, as well as evaluating the overall presentation of the financial statements. We believe that our audits provide a reasonable basis for our opinion.

Once the submission is accepted for filing, the FDA begins an in-depth review. The FDA may refuse to approve an NDA if the applicable statutory and regulatory criteria are not satisfied or may require additional clinical or other data. Even if such data are submitted, the FDA may ultimately decide that the NDA does not satisfy the criteria for approval. The FDA reviews an NDA to determine, among other things, whether a product is safe and effective for its intended use and whether its manufacturing is cGMP-compliant. The FDA may refer the NDA to an advisory committee for review and recommendation as to whether the application should be approved and under what conditions. The FDA is not bound by the recommendation of an advisory committee, but it generally follows such recommendations. Before approving an NDA, the FDA will typically inspect the facility or facilities where the product is manufactured and tested. The FDA will also inspect selected clinical sites that participated in the clinical studies and may inspect the testing facilities that performed the GLP toxicology studies cited in the NDA.

The requirements associated with being a public company require significant company resources and management attention.

Pierce, G. N. & Dhalla, N. S. Sarcolemmal Na+-K+-ATPase activity in diabetic rat heart. Am J Physiol 245, C241–7 (1983).

Based on the above findings, we extended our study to the B16F10 experimental metastasis model in C57BL/6 mouse to test whether the adoptive transfer of NK cells to mice with B16F10 cell metastasis could reduce the number of tumor nodules and increase survival rates. Indeed, Cd38+/+ NK cells significantly reduced the number of metastasized B16F10 cells in the lung, which did not hold true for Cd38−/− NK cells, indicating that CD38 was essential for the antitumor activity of NK cells (Fig. 7a). In vitro cytotoxic assays demonstrated that the cytolytic activity of Cd38+/+ NK cells was superior to that of Cd38−/− NK cells against not only B16F10 but also YAC-1 and EL4 murine lymphoma cell lines (Fig. 7b), indicating that Cd38+/+ NK cells exhibited a broad spectrum of natural cytotoxicity. Both Cd38+/+ and Cd38−/− NK cells expressed equivalent amounts of perforin and granzyme B mRNA and protein levels (Fig. 7c and d). However, B16F10-induced secretion of granzyme B was lower in CD38−/− NK cells than CD38++ NK cells (Fig. 7e). These results suggest that the enhancing effect of CD38 on the cytolytic activity of NK cells results from the stimulated release of granzyme B to target cells.

Anadys Pharmaceuticals Inc. (NasdaqGM:ANDS ) Anadys Pharmaceuticals, Inc. is a clinical-stage biopharmaceutical company dedicated to improving patient care by developing novel medicines in the areas of hepatitis C and oncology. For the treatment of chronic hepatitis C, the Company is developing two potentially complementary agents, ANA598, a non-nucleoside polymerase inhibitor and ANA773, an oral TLR7 agonist prodrug. The Company is also developing ANA773 for the treatment of cancer

        Provisions in our corporate charter and our bylaws may discourage, delay or prevent a merger, acquisition or other change in control of us that stockholders may consider favorable, including transactions in which you might otherwise receive a premium for your shares. These provisions could also limit the price that investors might be willing to pay in the future for shares of our common stock, thereby depressing the market price of our common stock. In addition, because our board of directors is responsible for appointing the members of our management team, these provisions may frustrate or prevent any attempts by our stockholders to replace or remove our current management by making it more difficult for stockholders to replace members of our board of directors. Among other things, these provisions:

If we acquire or in-license additional technologies or product candidates, we may incur significant, incremental expenses, may have integration difficulties and may experience other risks that could harm our business and results of operations.

We manage our business through a small number of senior executive officers. We depend on them even more than similarly- situated companies.

        As of December 31, 2018, we had an accumulated deficit of $188.2 million. Our net losses were $64.9 million and $54.4 million for the years ended December 31, 2018 and 2017, respectively. We have incurred significant net operating losses in every year since our inception and expect to continue to incur increasing net operating losses and significant expenses for the foreseeable future. Our net losses may fluctuate significantly from quarter to quarter and year to year. We anticipate that our expenses will increase significantly as we:

Rashkin, M. J., Hughes, R. M., Calloway, N. T. & Waters, M. L. Orientation and alkylation effects on cation-π interactions in aqueous solution. J. Am. Chem. Soc. 126, 13320–13325 (2004).

The 2011 Amendment canceled the availability of the benefits granted to Industrial Companies under the Investment Law prior to 2011 and, instead, introduced new benefits for income generated by a “Preferred Company” through its “Preferred Enterprise” (as such terms are defined in the Investment Law) as of January 1, 2011.