Zilucoplan is a novel therapeutic compound and its potential therapeutic benefit is unproven. Our product candidates may not demonstrate in patients any or all of the pharmacological benefits we believe they may possess or compare favorably to the approved C5 inhibitor therapy. We have not yet succeeded and may never succeed in demonstrating efficacy and safety for these or any other product candidates in clinical trials or in obtaining marketing approval thereafter. For example, although we have evaluated zilucoplan in pre-clinical studies and have evaluated zilucoplan in early-stage clinical trials and in two Phase 2 clinical trials, we have not yet advanced zilucoplan into Phase 3 clinical development, nor have we obtained regulatory approval to sell any product based on our therapeutic approaches.

Indicate by check mark whether the registrant has submitted electronically and posted on its corporate Web site, if any, every Interactive Data File required to be submitted and posted pursuant to Rule 405 of Regulation S-T (§232.405 of this chapter) during the preceding 12 months (or for such shorter period that the registrant was required to submit and post such files). Yes x No ¨

The Companies Law permits merger transactions if approved by each party’s board of directors, and, unless certain requirements described under the Companies Law are met, a majority of each party’s shareholders, by a majority of each party’s shares that are voted on the proposed merger at a shareholders’ meeting.

Kang, K. et al. A novel real-time PCR assay of microRNAs using S-Poly(T), a specific oligo(dT) reverse transcription primer with excellent sensitivity and specificity. PLoS One 7, e48536 (2012).

Licensing revenue amounted to $1.1 million during the year ended December 31, 2017, compared to $0.5 million of revenue for the year ended December 31, 2016. The above-mentioned revenue resulted from the amortization of the upfront payments under the Samil Agreement.

Aspirin: It seems that a low dose of Aspirin in the range of 50 – 81 mg or even as low as 30 mg has the same anti-blodd-clotting effects as a normal to high dose of 300 – 1200 mg. 1) https://books.google.de/books?id=GnIQGmiSylkC&pg=PA1108&lpg=PA1108&dq=aspirin+75mg&source=bl&ots=iXpVbhuZQ7&sig=m1sJvOT_tDJzHXcony2F9MATen0&hl=de&sa=X&ved=0ahUKEwi01cuq_bDQAhVKDsAKHRMOAYY4ChDoAQhzMAM#v=onepage&q=aspirin%2075mg&f=false 2) https://www.ncbi.nlm.nih.gov/pubmed/4082090 3) https://www.ncbi.nlm.nih.gov/pubmed/10870801

        Our commercial success may depend in part on our ability to obtain and maintain patent and other proprietary protection for our product candidates, technology, and know-how, defend and enforce our patents, prevent others from practicing our technology by enforcing our proprietary rights, preserve the confidentiality of our trade secrets, and operate without infringing the proprietary rights of others.

Similar to the findings observed with CD38 and TRPM2 in NK cells, perforin was scattered inside the NK cells mostly inside cytolytic granules and co-localizing with TRPM2 even before stimulation with tumor cells (Fig. 6c, upper panel). Like CD38, perforin co-migrated with TRPM2 to the immunological synapse upon stimulation with B16F10 cells (Fig. 6c, middle panel). Such tumor cell-induced perforin migration was not detected in TRPM2−/− NK cells (Fig. 6c, lower panel), suggesting that TRPM2 was essential for perforin migration towards the immunological synapse. The finding that perforin migration towards the synapse requires CD38 as well (Fig. 2b) suggests that both CD38 and TRPM2 are absolutely essential for the migration of perforin (or possibly cytolytic granules as well) toward the immunological synapse when NK cells encounter tumor cells.

Under the Companies Law an “independent director” is either an external director or a director appointed or classified as such who meets the same non-affiliation criteria as an external director, as determined by the audit committee, and who has not served as a director of the company for more than nine consecutive years. For these purposes, ceasing to serve as a director for a period of two years or less would not be deemed to sever the consecutive nature of such director’s service.

We further examined the type I TGF-β receptor (TβR I), type II TGF-β receptor (TβR II) and downstream targets of Smad signaling. We found that TβR I and TβR II mRNA levels were dramatically increased in both the P311+/+ and P311−/− UUO groups compared to the Sham groups but were higher in obstructed kidneys from P311+/+ mice compared to P311−/− mice (Fig. 6A, TβR I, P311+/+ compared to P311−/−, 2.25-fold difference, P = 0.001; Fig. 6B, TβR II, P311+/+ compared to P311−/−, 1.71-fold difference, P < 0.001). Total Smad2 and Smad3 protein levels were markedly increased in obstructed kidneys from both P311+/+ and P311−/− mice, but were significantly higher in the former than in the latter (Fig. 6C,D, Smad2, P311+/+ compared to P311−/−, 1.65-fold difference, P = 0.007; Fig. 6C,E, Smad3, P311+/+ compared to P311−/−, 4.03-fold difference, P < 0.001). Moreover, phosphorylated Smad2 (p-Smad2) and phosphorylated Smad3 (p-Smad3) levels were significantly higher in obstructed kidneys from P311+/+ mice compared to P311−/− mice (Fig. 6C,F, p-Smad2, P311+/+ compared to P311−/−, 1.80-fold difference, P = 0.002; Fig. 6C,G, p-Smad3, P311+/+ compared to P311−/−, 2.01-fold difference, P = 0.001). Smad4 expression was also increased in obstructed kidneys from P311+/+ mice compared to P311−/− mice (Fig. 6C,H, 2.16-fold difference, P < 0.001). After UUO, Smad7 protein levels in both P311+/+ and P311−/− kidneys decreased compared to the sham operation. Unexpectedly, Smad7 levels were higher in P311+/+ kidneys than in P311−/− kidneys after UUO (Fig. 6C,I, 2.50-fold difference, P = 0.008). Taken together, these data showed that P311 deficiency down-regulated TGF-β1 expression, TGF-β1 receptors expression and TGF-β1/Smad signaling activation.

The polyethylene (PE) pellets as a model of the polymeric implant were purchased from Lucoil Chemical (Grade 277–73), press molded into 10 cm × 10 cm pieces with a thickness of 0.5 mm, and ion implanted using a Kauffman ion source. The base vacuum was less than 1.0 × 10−5 Pa. High-purity argon (99.99%) was introduced into the ion source and argon plasma immersion ion implantation (PIII) with an ion implant fluence of 6.14 × 1015 ions/cm2 was conducted at 5 kV for 10 min. Calibration of the ion implant fluence was accomplished by a Faraday cup and the working pressure in the vacuum chamber was 2.0 × 10−2 Pa during ion implantation. Afterwards, high-purity nitrogen (99.99%) was introduced in place of argon, and nitrogen PIII was conducted with the same ion implant fluence. Afterwards, the samples remained in vacuum for 10 min. The argon ion-implanted PE was denoted as PAr whereas the PE implanted with both argon and nitrogen was labeled as PArN.

Hara, Y. et al. LTRPC2 Ca2+-permeable channel activated by changes in redox status confers susceptibility to cell death. Mol. Cell 9, 163–173 (2002).