gMG.    gMG is currently treated with cholinesterase inhibitors and nonspecific immunosuppressive agents most of which are not approved for gMG, including azathioprine, cyclophosphamide, cyclosporine, IVIG, mycophenolate, prednisone, and tacrolimus. Eculizumab, marketed by Alexion Pharmaceuticals, is approved for the treatment of refractory MG in Europe and Japan and gMG in the U.S. Ravulizumab-cwvz, a monoclonal antibody C5 inhibitor, is in clinical development by Alexion. Anti CD40 product candidates, in development as CFZ533 by Novartis Pharma and bortezomib by Takeda, are in clinical development for gMG. FcRn antagonist product candidates in clinical development include efgartigimod by argenx, rozanolixizumab by UCB, M281 by Momenta, and ALXN1830 by Alexion. A therapeutic vaccine targeting B and T cell receptors (CV MG 01) is in early clinical testing for gMG.

“Pharmaceuticals found in US drinking water. Trace quantities could endanger wildlife, humans. By Jeff Donn, Associated Press / March 10, 2008 NEW YORK – An array of pharmaceuticals – including antibiotics, anticonvulsants, mood stabilizers, and sex hormones – have been found in the drinking water supplies of at least 41 million Americans, an Associated Press investigation found. … The investigation also indicates that watersheds, the natural sources of most of the nation’s water supply, also are contaminated. Tests were conducted in the watersheds of 35 of the 62 major providers surveyed by the Associated Press and pharmaceuticals were detected in 28.”

Pierce, G. N. & Dhalla, N. S. Sarcolemmal Na+-K+-ATPase activity in diabetic rat heart. Am J Physiol 245, C241–7 (1983).

Under the provisions of the Sarbanes-Oxley Act, the audit committee is directly responsible for the appointment, compensation and oversight of the work of the company’s independent auditors. However, under Israeli law, the appointment of independent auditors and their compensation require the approval of the shareholders of a public company. Pursuant to Israeli law, the shareholders may delegate the authority to determine the compensation of the independent auditors to the board of directors. In addition, pursuant to the Companies Law, the audit committee is required to examine the independent auditors’ fees and to provide its recommendations with respect thereto to the appropriate corporate body. Accordingly, the appointment of our independent auditors is required to be approved and recommended to the shareholders by our audit committee and Board and approved by the shareholders. The compensation of the independent auditors for audit services is required to be approved and recommended to the Board by our audit committee and approved by the Board. The Board has delegated its authority to approve the compensation of independent auditors for non-auditing services to the audit committee.

        We protect our intellectual property rights related to the Extreme Diversity program through a combination of licensed patents, trade secrets, and know-how. For more information, see the section titled "Intellectual Property."

Kielstein, A., Tsikas, D., Galloway, G. P. & Mendelson, J. E. Asymmetric dimethylarginine (ADMA)—A modulator of nociception in opiate tolerance and addiction?Nitric oxide: biology and chemistry/official journal of the Nitric Oxide Society 17, 55–59 (2007).

Independent directors. Although Israeli law does not require that a majority of the directors serving on our Board be “independent,” as defined under Nasdaq Capital Market Listing Rule 5605(a)(2), but rather requires we have at least two external directors who meet the requirements of the Companies Law, as described above under “Item 6. Directors, Senior Management and Employees—C. Board Practices—External Directors.”, a majority of our Board is independent based on the Nasdaq Capital Market rules. We are required, however, to ensure that all members of our audit committee are “independent” under the applicable Nasdaq Capital Market and SEC criteria for independence (as we cannot exempt ourselves from compliance with that SEC independence requirement, despite our status as a foreign private issuer) and we must also ensure that a majority of the members of our audit committee are “independent directors” as defined in the Companies Law. Our independent director’s conduct regularly scheduled meetings at which only such independent directors are present, as required by the Nasdaq Listing Rules. Our Board has affirmatively determined that each of Mr. Nir, Mrs. Yaron-Eldar, Mr. Marth, Dr. Sidransky and Dr. Brosgart qualifies as “independent” under the Nasdaq Capital Market independence standards.

Lipoprotein-deficient serum (LPDS) was prepared following the protocol of Renaud et al.31 with slight variation. Briefly, FBS was adjusted to a density of 1.215 g/mL by adding KBr. After overlaying the FBS with a KBr solution at the same density, the mixture was centrifuged for 65 h at 235,500 g at 4 °C. The floating lipoproteins were removed and the remaining serum was dialysed against 6 changes of 4L Phosphate-buffer saline (PBS) pH 7.4 at 4 °C.

suffered significant setbacks in late-stage clinical trials after achieving positive results in earlier development, and we could face similar setbacks. The design of a clinical trial can determine whether its results will support approval of a product and flaws in the design of a clinical trial may not become apparent until the clinical trial is well advanced. We have limited experience in designing clinical trials and may be unable to design and execute a clinical trial to support marketing approval. In addition, pre-clinical and clinical data are often susceptible to varying interpretations and analyses. Many companies that believed their product candidates performed satisfactorily in pre-clinical studies and clinical trials have nonetheless failed to obtain marketing approval for the product candidates. Even if we, or any future collaborators, believe that the results of clinical trials for our product candidates warrant marketing approval, the FDA or comparable foreign regulatory authorities may disagree and may not grant marketing approval of our product candidates.

As of December 31, 2018, we had cash and cash equivalents of approximately $24.2 million, short-term deposits of approximately $6.0 million and marketable debt securities of approximately $60.0 million invested in accordance with our investment policy, totaling approximately $90.2 in highly-liquid assets, as compared to cash and cash equivalents of approximately $13.0 million and marketable debt securities of approximately $6.0 million invested in accordance with our investment policy, totaling approximately $19.0 in highly-liquid assets as of December 31, 2017. The increase is mainly attributable to the approximately $70.3 million in net proceeds raised in an underwritten public offering that was completed in June 2018, together with $5.9 million in net proceeds raised in a registered direct offering during April 2018.

Chelsea Therapeutics International Ltd. (NasdaqCM: CHTP ) Chelsea Therapeutics is a biopharmaceutical development company that acquires and develops innovative products for the treatment of a variety of human diseases. The Company is currently developing a library of metabolically inert antifolate compounds engineered to have potent anti-inflammatory and anti-tumor activity to treat a range of immunological disorders.

Cardiac hypertrophy (CH) is initially an adaptive response to pressure or volume stress, which is characterized by increased cardiomyocyte size, re-expression of fetal genes, and activation of signaling pathways governing protein synthesis1. However, persistent and severe CH becomes a maladaptive response and ultimately contributes to subsequent heart failure2 that is a major and growing public health concern, as well as a leading cause of morbidity and mortality worldwide3. Thus, it is critical to suppress CH timely to prevent the progression of CH to heart failure.