Janatuinen, T. et al. Plasma asymmetric dimethylarginine modifies the effect of pravastatin on myocardial blood flow in young adults. Vascular medicine 8, 185–189 (2003).

To determine if the effect of cholesterol modulation on HCN1 channels could be generalized to other human HCN channel isoforms, we further examined the effects on the other cardiac isoforms, HCN2 and HCN4 (Figs 2 and 3). Intriguingly, we observed differential effects of cholesterol modulation on these isoforms. Similar to HCN1, both HCN2 and HCN4 channels showed a decrease in current density upon cholesterol depletion by either MβCD (Fig. 2A,B; Fig. 3A,B) or mevastatin (Supp. Fig. 1B,C). Moreover, current densities in cells expressing these isoforms enriched with cholesterol remained similar to control (Fig. 2A,B; Fig. 3A,B). HCN2 channels showed no differences in steady-state activation properties with changes in cholesterol content, however, steady-state properties of HCN4 channels were shifted approximately +10 mV by either cholesterol depletion or enrichment (Fig. 3C; Table 1). Tail currents were too small in HCN4 expressing cells treated with mevastatin to reliably enable us to determine steady-state activation properties. Intriguingly, the effects of cholesterol modulation on human HCN2 and HCN4 kinetics differed from our observations in human HCN1 channels. The activation kinetics of HCN2 and HCN4 channels were unaffected by cholesterol modulation (Figs 2D and 3D,E). However, unlike HCN1 channels, the deactivation kinetics of HCN2 and HCN4 channels were slowed by cholesterol enrichment (Figs 2E and 3F). These data suggest the effect of cholesterol on HCN channels is isoform specific.

The following table summarizes the Company’s marketable debt securities as of December 31, 2018 and 2017.

Kram, L., Grambow, E., Mueller-Graf, F., Sorg, H. & Vollmar, B. The anti-thrombotic effect of hydrogen sulfide is partly mediated by an upregulation of nitric oxide synthases. Thromb Res. 132, e112–117 (2013).

During early times, laboratories had to make their own PLG polymers and monomers. These polymers, especially polymers with high glycolide content (e.g., 50:50 lactide:glycolide polymers) had solubility challenges due to their long glycolide blocks. Also, polymer solubility varied from batch to batch, making it difficult to perform robust formulation processing and achieve reproducible drug-delivery performance from microparticles and implants. Resomer polymers offer more consistent properties with better and reproducible solubility. 

        In December 2018, the Company completed a follow-on public offering of 9,645,161 shares of common stock, including the full exercise of the underwriters’ option to purchase an additional 1,258,064 shares, at $15.50 per share and received aggregate net proceeds of $140.2 million, after deducting $9.0 million of underwriting discounts and commissions and approximately $0.3 million of offering expenses.

        We are a clinical-stage biopharmaceutical company using our proprietary peptide chemistry platform to develop novel therapeutics for the treatment of serious diseases that are caused by excessive or uncontrolled activation of the complement system, a critical component of the immune system. Inappropriate activation of the complement system can quickly turn it from a beneficial defense system to an aggressor that plays a major role in immune and inflammatory diseases. The complement system, which consists of approximately 30 interacting proteins, offers a target-rich opportunity for us to leverage our proprietary peptide chemistry platform, which was pioneered by Nobel Laureate Dr. Jack Szostak and allows us to inhibit certain uncontrolled complement pathway factors involved in complement-mediated diseases. Known as our Extreme Diversity platform, this proprietary macrocyclic peptide chemistry technology allows us to produce synthetic macrocyclic peptides that combine the diversity and specificity of antibodies with the pharmacological properties of small molecules. We believe this technology will allow us to pursue challenging targets for which only monoclonal antibodies have been developed.

Schott, P. et al. Myocardial adaptation of energy metabolism to elevated preload depends on calcineurin activity : a proteomic approach. Basic Res. Cardiol. 103, 232–243, 10.1007/s00395-008-0696-1 (2008).

Thanks to Mark, I went to Telocyte’s website and read Blasco paper about telomerase gene therapy in mice. Results looks really interesting when applied at mice of 1 year or 2 years old. Having said that, I am wondering why no other studies have been published since 2012.

If commenced, the ARMOR Study may also be terminated as a result of, but not limited to, safety signals. In addition, the ARMOR Study or other clinical trials may be suspended or terminated by us, the FDA or other regulatory authorities, the principal investigator at a site, the IRBs at the sites where such boards are overseeing a trial or the data safety monitoring board, or the DSMB, that is overseeing the clinical trial at issue, or other regulatory authorities due to a number of factors, including:

As of December 31, 2018, options to purchase 1,920,046 of our ordinary shares granted to our Office Holders as a group were outstanding, of which options to purchase 1,039,994 of our ordinary shares were vested, with a weighted average exercise price of $3.28 per ordinary share.

Fan, Z. et al. BCOR regulates mesenchymal stem cell function by epigenetic mechanisms. Nat. Cell. Biol. 11, 1002–1009 (2009).