Brioschi, C. et al. Distribution of the pacemaker HCN4 channel mRNA and protein in the rabbit sinoatrial node. J Mol Cell Cardiol 47, 221–7 (2009).

        On October 31, 2016, the Company completed an initial public offering ("IPO"), in which the Company issued and sold 7,049,230 shares of common stock at a public offering price of $13.00 per share, resulting in net proceeds of $82.8 million after deducting $6.4 million of underwriting discounts and commissions and offering costs of $2.4 million. On November 29, 2016, the Company completed the sale of an additional 1,057,385 shares of common stock to the underwriters under the underwriters’

        The majority of our service providers invoice us monthly in arrears for services performed or when contractual milestones are met. We make estimates of our accrued expenses as of each balance sheet date in our financial statements based on facts and circumstances known to us at that time. We periodically confirm the accuracy of our estimates with the service providers to gauge the reasonableness of our estimates. Differences between actual and estimated expenses recorded have not been material and are adjusted for in the period in which they become known. However, if we incorrectly estimate activity levels associated with such research and development activities at a given point in time, we could be required to record material adjustments in future periods. Examples of estimated research and development expenses include fees paid to:

激素治疗市场是成熟市场，随着新适应症的增加还在不断成长。作为传统的癌症治疗手段面临来自化疗等传统方法和生物制剂的双重竞争。leuprolide, goserelin, bicalutamide, letrozole, tamoxifen, exemestane, fulvestrant和anastrazole等产品仍未与市场前沿。总的激素治疗市场2004-2013年的年复合增长率预计为5.8%。

        The Affordable Care Act, or the ACA, imposed, among other things, new annual reporting requirements for covered manufacturers for certain payments and other transfers of value provided to physicians and teaching hospitals, as well as certain ownership and investment interests held by physicians and their immediate family members. Failure to submit timely, accurately and completely the required information for all payments, transfers of value and ownership or investment interests may result in civil monetary penalties of up to an aggregate of $169,170 per year and up to an aggregate of $1.128 million per year for "knowing failures." Certain states also mandate implementation of compliance programs, impose restrictions on drug manufacturer marketing practices or require the tracking and reporting of gifts, compensation or other remuneration to physicians.

Harzheim, D. et al. Cardiac pacemaker function of HCN4 channels in mice is confined to embryonic development and requires cyclic AMP. EMBO J 27, 692–703 (2008).

Sag, C. M., Santos, C. X. & Shah, A. M. Redox regulation of cardiac hypertrophy. J. Mol. Cell. Cardiol. 73, 103–111, 10.1016/j.yjmcc.2014.02.002 (2014).

I like Elizabeth Blackburn. After winning a Nobel prize she remained a scientist. She could have made millions becoming a pitchman. So I like scientists. I have nothing against entreupeneurs. However, I Have great suspicion of scientist turned businessman. I also believe ZERO of what businessman says about their product. So unless somebody with no financial ties to company verifies data; to me have nothing. I still remember how all CEOs in cigarette industry said… And business people haven’t gotten any more honest in fifty years. So I believe Elizabeth Blackburn.

Xiao, Y. F. et al. Hysteresis in human HCN4 channels: a crucial feature potentially affecting sinoatrial node pacemaking. Sheng Li Xue Bao 62, 1–13 (2010).

        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.

Irrespective of whether the medicinal product is assessed centrally, de-centrally or through a process of mutual recognition, the medicinal product must be manufactured in accordance with the principles of GMP as set out in Directive2001/83/EC and Directive 2003/94/EC, or, Directive 2017/1572/EU that will replace Directive 2003/94/EC expectedly by 2019.

The flow reaction was performed in a microreactor at the gram scale using continuous workup conditions involving acidic extraction of the product and on-stream recycling of the catalyst in the organic phase (10). The custom-designed rector for running heterogeneous reactions in flow combines the flexibility of CSTRs with the smooth operation, low residence time distribution and excellent heat transfer capability of a conventional flow reactor, according to the researchers.