In the annual general meeting to be convened in 2019, our Board plans to nominate Mr. Baharaff and Mr. Heinberg for re-election to serve as Class II Directors until the close of the annual general meeting to be held in 2022 and nominate Prof. Oren for re-election to serve as a Class III Director until the close of the annual general meeting to be held in 2020.

Higgins, J. P. & Green, S. Cochrane handbook for systematic reviews of interventions . Vol. 5 Wiley Online Library 2008).

If the conditions set forth above are not met, the purchaser may not acquire additional shares of the company from shareholders who accepted the tender offer to the extent that following such acquisition, the purchaser would own more than 90% of the company’s issued and outstanding share capital.

        In March 2019, we announced pre-clinical data for our first XR formulation of zilucoplan, with a single subcutaneous dose resulting in rapid attainment of target drug concentrations for greater than one week in non-human primates, supporting once weekly or less frequent dosing. Of note, near complete inhibition of terminal complement activity for greater than one week was achieved without the need for prior intravenous loading doses, as measured by an ex vivo hemolysis assay.

        3.     Based on my knowledge, the financial statements, and other financial information included in this report, fairly present in all material respects the financial condition, results of operations and cash flows of the registrant as of, and for, the periods presented in this report;

3.        Based on my knowledge, the financial statements, and other financial information included in this report, fairly present in all material respects the financial condition, results of operations and cash flows of the Company as of, and for, the periods presented in this report;

        In October 2016, we closed our initial public offering. Prior to that offering, there had been no public market for our common stock. Although shares of our common stock are listed and trading on The Nasdaq Global Market, an active trading market for our shares may not continue to be sustained. If an active market for our common stock does not continue, it may be difficult for our stockholders to sell their shares without depressing the market price for the shares or sell their shares at or above the prices at which they acquired their shares or sell their shares at the time they would like to sell. Any inactive trading market for our common stock may also impair our ability to raise capital to continue to fund our operations by selling shares and may impair our ability to acquire other companies or technologies by using our shares as consideration.

Bohm, M. et al. Heart rate as a risk factor in chronic heart failure (SHIFT): the association between heart rate and outcomes in a randomised placebo-controlled trial. Lancet 376, 886–94 (2010).

Failure to build our finance infrastructure and improve our accounting systems and controls could impair our ability to comply with the financial reporting and internal control requirements for publicly traded companies.

In renal fibrogenesis, matrix-producing cells integrate various fibrogenic signals and regulate ECM production and assembly. These fibrogenic factors include TGF-β1, platelet-derived growth factor, fibroblast growth factor, connective tissue growth factor and angiotensin II15. Among these cytokines, TGF-β1 is the key contributor to EMT in tubular epithelial cells29. In the kidneys of patients with IgA nephropathy, P311 protein expression correlates with TGF-β expression and proteinuria30. Thus, we next examined whether TGF-β1 was involved in EMT related to P311-mediated renal fibrogenesis. As predicted, obstructed kidneys from P311−/− mice showed impaired TGF-β1 protein expression. Interestingly, there was no difference in TGF-β1 mRNA levels between the P311−/− and P311+/+ groups. These results differ from our previous observations in human fibroblasts, which showed that P311 transfection induces TGF-β1 mRNA expression and that interfering with P311 expression in fibroblasts decreases TGF-β1 mRNA expression10. The different models (in vivo versus in vitro) and different cell types (human fibroblasts versus mouse tubular epithelial cells) might be responsible for the discrepancy. P311 binds to latency-associated proteins to regulate TGF-β1 expression31. Recently, P311 was reported to bind to eukaryotic translation initiation factor 3 subunit b to promote TGF-β translation and to be the first pan-regulator of TGF-β expression under steady-state conditions8,32. These findings may explain our results.

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