Under the Companies Law, the board of directors of an Israeli public company must appoint an internal auditor recommended by the audit committee and nominated by the board of directors. The role of the internal auditor is to examine, among other things, our compliance with applicable law and orderly business procedures. An internal auditor should comply with the requirements of the Companies Law and the Internal Audit Law, 5752-1992, and may not be:

We were and continue to be organized in Israel. Substantially all of our executive officers and directors reside outside of the United States, and all of our assets and most of the assets of these persons are located outside of the United States. Therefore, a judgment obtained against us, or any of these persons, including a judgment based on the civil liability provisions of the U.S. federal securities laws, may not be collectible in the United States and may not necessarily be enforced by an Israeli court. It also may be difficult to effect service of process on these persons in the United States or to assert U.S. securities law claims in original actions instituted in Israel. Additionally, it may be difficult for an investor, or any other person or entity, to initiate an action with respect to United States securities laws in Israel. Israeli courts may refuse to hear a claim based on an alleged violation of United States securities laws reasoning that Israel is not the most appropriate forum in which to bring such a claim. In addition, even if an Israeli court agrees to hear a claim, it may determine that Israeli law and not United States law is applicable to the claim. If United States law is found to be applicable, the content of applicable United States law must be proven as a fact by expert witnesses, which can be a time consuming and costly process. Certain matters of procedure will also be governed by Israeli law. There is little binding case law in Israel that addresses the matters described above. As a result of the difficulty associated with enforcing a judgment against us in Israel, our shareholders may not be able to collect any damages awarded by either a United States or foreign court.

(a) ADPR levels were determined after treatment of NK cells with 30 μg PME for 40 s. Rp-8-Br-cAMPS (100 μM) or Rp-8-pCPT-cGMPS (20 μM) was preincubated for 30 min. 100 μM N6-benzoyl-cAMP (PKA activator, 40 s) was used for ADPR measurement. Data are mean ± SEM of three independent experiments. *P < 0.001 vs basal; #P < 0.05. (b) cAMP levels were determined after treatment of NK cells with 30 μg PME. Data are mean ± SEM of three independent experiments. (c) Inhibition of tumor cell-induced sustained Ca2+ increase by a PKA inhibitor, Rp-8-Br-cAMPS, and an adenylate cyclase inhibitor, SQ 22536. Rp-8-Br-cAMPS (100 μM) or SQ 22536 (250 μM) was preincubated for 30 min. (d) SOCE induced by bafilomycin A1. Bafilomycin A1 (1 μM)-induced SOCE was inhibited with 50 μM SK96365 but not by 20 μM ACA. SK96365 or ACA was pre-incubated for 30 min. Data shown in c and d are mean ± SEM of three independent experiments. n = 10.

        1.     I have reviewed this Annual Report on Form 10-K for the year ended December 31, 2018 of Ra Pharmaceuticals, Inc.;

We next investigated whether the tumor-induced [Ca2+]i increase was dependent on CD38. Similar to TRPM2−/− NK cells, Cd38−/− NK cells displayed the tumor-induced initial rise in [Ca2+]i, but failed to maintain the elevated levels (Fig. 2d and e; 36.1% of AUC of Ca2+ trace in Cd38+/+ NK cells). These results demonstrate that CD38-mediated Ca2+ signaling may be involved in the granule polarization and cytolytic degranulation process of NK cell during contact with tumor cells.

Li, J. H. et al. Smad7 inhibits fibrotic effect of TGF-Beta on renal tubular epithelial cells by blocking Smad2 activation. Journal of the American Society of Nephrology: JASN. 13, 1464–1472 (2002).

Section 102 of the Ordinance allows Israeli employees, directors and officers, who are not controlling shareholders to receive favorable tax treatment for compensation in the form of shares or options. However, under this route we are not allowed to deduct any expense with respect to the issuance of the options or shares. Israeli non-employee service providers, consultants and shareholders who hold 10% or more of our total share capital or are otherwise controlling shareholders, may be granted options pursuant to Section 3(i) of the Ordinance, which does not provide for similar tax benefits. In order to comply with the terms of the capital gains route pursuant to Section 102 of the Ordinance, the granted options as well as the ordinary shares issued upon exercise of these options and other shares received subsequently following any realization of rights with respect to such options (such as share dividends and share splits), must be granted to a trustee for the benefit of the relevant grantee and should be held by the trustee for at least two years after the date of the grant. If such options or shares are sold by the trustee or are transferred to the grantee before the end of the two-year period, then the grantee would be taxed at top marginal rates upon selling the shares.

Wang, Y. et al. Development of fluorescence imaging-based assay for screening cardioprotective compounds from medicinal plants. Anal. Chim. Acta 702, 87–94, 10.1016/j.aca.2011.06.020 (2011).

Our employees, principal investigators, consultants, commercial partners or vendors may engage in misconduct or other improper activities, including non-compliance with regulatory standards.

Our business depends heavily upon the success of zilucoplan, which is still under development. If we are unable to obtain regulatory approval for or successfully commercialize zilucoplan, our business will be materially harmed.

I agree that pharmaceutical companies in general cannot be trusted, but Michael Fossel is a guy like yourself who would ordinarily be thinking about retirement, and has no need to do this for money, but I believe genuinely wants to make a difference. I think he has a fair shot at success, and I would take you up on your bet if I had a cool million to spare! But that also doesn’t mean I don’t think your approach at prevention would not work. So far pharmaceutical companies have not managed prevention or cure! Although thinking about it, the ‘failed’ recent trial that cleared amyloid beta but did not improve symptoms probably would work as a vaccine.

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: