This is not only a huge public health problem, but a fascinating issue from a scientific view-point. Although it needs to be solved, I foresee a slew of new regulations coming down on the industry, which may make it almost impossible to change a synthetic route. I’d like to believe that the FDA/EMA would propose some sensible focused regulation around this (something clearly needs to be done), but what we may end up with is a whole new regulatory morass. Have fun, chemists!

RSUs. We have granted RSUs to certain of our Office Holders. Such award agreements may contain acceleration provisions upon certain merger, acquisition, or change of control transactions. See also “Item 6. Directors, Senior Management and Employees—E. Share Ownership.” We describe our 2013 Plan under “Item 6. Directors, Senior Management and Employees—B. Compensation—2013 Incentive Share Option Plan.” If the relationship between us and an Office Holder is terminated, RSUs that are vested shall be settled in accordance with the settlement schedule set forth in the applicable award agreement.

We generally enter into non-competition agreements with our employees and certain key consultants, or our employment and consulting agreements contain non-competition provisions. These agreements, to the extent they are in place and in effect, prohibit our employees and certain key consultants, if they cease working for us, from competing directly with us or working for our competitors or clients for a limited period of time. We may be unable to enforce these agreements under the laws of the jurisdictions in which our employees work and it may be difficult for us to restrict our competitors from benefitting from the expertise our former employees or consultants developed while working for us. For example, Israeli courts have required employers seeking to enforce non-compete undertakings of a former employee to demonstrate that the competitive activities of the former employee will harm one of a limited number of material interests of the employer which have been recognized by the courts, such as the secrecy of a company’s confidential commercial information or the protection of its intellectual property. If we cannot demonstrate that such interests will be harmed, we may be unable to prevent our competitors from benefiting from the expertise of our former employees or consultants and our ability to remain competitive may be diminished.

Ingredients, excipients and other materials necessary to manufacture zilucoplan may not be available on commercially reasonable terms, or at all, which may adversely affect the development and commercialization of zilucoplan.

Data are represented as the mean ± SEM of at least three independent experiments. Statistical analysis was performed using Student’s t-test or one-way ANOVA as appropriate. P < 0.05 was considered significant.

        The Company files income tax returns in the U.S. federal, Massachusetts and foreign jurisdictions. The statute of limitations for assessment by the Internal Revenue Service and state tax authorities remains open for all years since the Company’s inception. There are currently no federal or state income tax audits in progress.

Di Nicola, M. et al. Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood 99, 3838–3843 (2002).

MiRNAs are single-stranded, non-coding RNA molecules of about 20–26 nucleotides in length that regulate 50–60% of mammalian gene expression by interacting with the 3′-untranslated regions (3′-UTR) of specific mRNA targets and inhibiting translation15. MiRNAs play significant roles in the regulation of various cellular processes, including proliferation, migration, differentiation, and apoptosis7,16,17. Recently, miRNAs have been implicated in the development and progression of PAH, especially in the presence of hypoxic stress. Increased expression of miR-451 and miR-30c as well as differential expression of miR-21 and let-7a has been reported in rat models of PAH induced by monocrotaline and chronic hypoxia18. A recent study reported that miR-20a and miR-17, through the STAT3 pathway, participate in the regulation of morphogenetic protein receptor type 2 (BMPR2), which is a key determinant of idiopathic familial pulmonary hypertension19. Another study revealed that miR-20a inhibition could restore functional BMPR2 signaling and reduce vascular remodeling in hypoxia-treated mice20.

        Ravulizumab-cwvz is a long-acting, monoclonal antibody C5 inhibitor that binds C5, preventing its cleavage to C5a and C5b, thereby inhibiting the activation of the complement pathway. Ravulizumab-cwvz is administered intravenously by healthcare professionals every eight weeks.

        Since inception, the Company has generated an accumulated deficit of $188.2 million and $123.2 million as of December 31, 2018 and 2017, respectively. The Company has devoted substantially all of its efforts to research and development, business planning, acquiring operating assets, seeking protection for its technology and product candidates, and raising capital. The Company has financed its operations to date through the public offering and the private placement of its securities and funding from its collaboration and license agreement with Merck (the "Merck Agreement").

To date, Genentech is the only company that launched an extended-release PLG microparticle product for the delivery of a protein. This product, Nutropin Depot, releases recombinant human growth hormone for the treatment for growth hormone deficiency in pediatric patients. This product went on the market in 1999 (11). 

Our operating history is limited to pre-clinical and clinical development of one product, and our operations to date have been limited primarily to research and development, raising capital and recruiting scientific and management personnel and third-party partners. Therefore, it may be difficult to evaluate our business and prospects. We have not yet demonstrated an ability to commercialize or obtain regulatory approval for any product candidate. Consequently, any predictions about our future performance may not be accurate, and you may not be able to fully assess our ability to complete development and/or commercialize Aramchol, and any future product candidates, obtain regulatory approvals or achieve market acceptance or favorable pricing for Aramchol and any future product candidates.