In addition to our focus on developing novel therapeutics to treat complement-mediated diseases, we have validated our Extreme Diversity platform by successfully identifying and delivering orally-available cyclic peptides for a non-complement cardiovascular target with a large market opportunity in a collaboration with Merck & Co., Inc., or Merck. In December 2018, Merck paid us a development milestone as part of this collaboration.

We determined that the transaction price at contract inception was $2.1 million consisting of the upfront, non-refundable payment. None of the clinical or regulatory milestones were included in the transaction price upon inception, as all milestone amounts were fully constrained. Management assessed that the likelihood of occurrence of the other performance obligations in the Samil Agreement was remote upon contract inception. As such, the standalone value of such performance obligations was deemed de minimis and none of the transaction price was allocated to those obligations. Any consideration related to sales-based milestones and royalties will be recognized when the related sales occur, and therefore have also been excluded from the transaction price.

The Company holds a wholly-owned subsidiary, Galmed International Ltd., which was incorporated in Malta. Galmed International Ltd. previously held a wholly-owned subsidiary, Galmed Medical Research Ltd., which was incorporated in Israel, and had been an inactive company since 2015 and was liquidated on February 2019.

Mark you asked earlier about the implications of using rapamycin before old age, again if we look at it from an Aesthetic point of view what we see in old age is the enlargement of nose, ears and hands, i believe this to be mainly driven by mTOR (and to some extent: HGH, IGF, Insulin), these changes is not something that happens overnight but is changes that occur over many years of increased mTOR, i believe that this increase/negative effect of mTOR begins already when you are fully grown, late 20’s early 30’s and at somepoint later in life really goes haywire.

So virtually all of their protection is secondary to their exercise regimen and adiponectins. Once they retire, it’s rapidly down hill.

        The patent application process is subject to numerous risks and uncertainties, and there can be no assurance that we or any of our future development partners will be successful in protecting our product candidates by obtaining and defending patents. These risks and uncertainties include the following:

I was thinking about cellular senescence the other day, and it occurred to me that cells are arrested all the time, say due to replication errors, or damage from ROS. When this happens there is effectively a battle between catabolism and anabolism – AMPK and FOXO (triggering autophagy)vs. MTOR and P21 (trying to continue growth and degrading mitos further). Unless the former can hold out long enough for DNA repair to be completed the cell will permanently become senescent, and there’s no way back from that (without telomerase or epigenetic reprogramming). So we can immediately see the importance of keeping low MTOR and ROS, and high AMPK, and possibly better DNA repair too. I think this process is happening all the time, with MTOR mainly winning, and it is just the robustness of the youthful immune system that removes this constant loss of functional to senescent cells. With time this changes in favour of senescent cell accumulation, and by the time this causes inflammation to rise too high, we get stem cell and telomere dysfunction too.

My thoughts on excessive high intensive exercise is that it may be the depletion of essential minerals (such as magnesium), may lead to worse health outcomes. This may be because it would then lead to poor blood sugar control. I say this because as a heavy gym user (combined with excessive alcohol use), I suffered muscle twitching and some high blood sugar episodes (resolved by giving up alcohol for a week and going low carb).

We prepare our financial statements in accordance with U.S. GAAP. In doing so, we must make estimates and assumptions that affect our reported amounts of assets, liabilities and expenses, as well as related disclosure of contingent assets and liabilities. In some cases, we could reasonably have used different accounting policies and estimates. Changes in the accounting estimates are reasonably likely to occur from period to period. Accordingly, actual results could differ materially from our estimates. To the extent that there are material differences between these estimates and actual results, our financial condition or results of operations will be affected. Significant estimates include, but are not limited to, those related to deferred revenue, revenue recognition and stock-based compensation. For further significant accounting policies please see Note 2 to our audited consolidated financial statements of this annual report. We believe that our accounting policies contained therein are critical in fully understanding and evaluating our financial condition and operating results.

The composition of matter patents directed to Aramchol will expire on March 25, 2019 worldwide. We will not be able to submit an NDA seeking approval of Aramchol prior to the composition of matter patents’ expiration date. However, because Aramchol is regarded as a new chemical entity, or NCE, following approval of an NDA, if we are the first applicant to obtain NDA approval, we may be entitled to up to five years of patent term extension in the United States with respect to such NCE, and provided that the use patent with respect to Aramchol in the treatment of fatty liver will still be in force when the approval of the NDA is received from the FDA. The non-extended patent term for such use patent, is due to expire on April 15, 2022 worldwide and on April 17, 2021 in Israel. The U.S. patent was extended by a patent term adjustment of 567 days, resulting in an effective expiration date in the U.S. of November 3, 2023. Analogous mechanisms for protecting the interests of innovator drug companies to compensate for regulatory review and other hurdles they must overcome, of varying duration, may be available in Europe and other foreign jurisdictions. In addition, a term of data exclusivity of up to 5 years will be available for the first approved clinical use of this NCE in the U.S. and for longer periods in other jurisdictions, if Aramchol receives regulatory approval. Although we believe that we may be able to protect our exclusivity in our field of activity through such use patent portfolio and such period of exclusivity, the lack of composition of matter patent protection may diminish our ability to maintain a proprietary position for its intended uses of Aramchol. Moreover, we cannot be certain that we will be the first applicant to obtain an FDA approval for any indication of Aramchol and we cannot be certain that we will be entitled to NCE exclusivity.

        Of the large number of drugs in development in the pharmaceutical industry, only a small percentage result in the submission of a new drug application, or NDA, to the FDA and even fewer are approved for commercialization. Furthermore, even if we do receive regulatory approval to market zilucoplan, any such approval may be subject to limitations on the indicated uses or patient populations

If our ordinary shares become a “penny stock,” it may be more difficult for investors to sell their ordinary shares, and the market price of our ordinary shares may be adversely affected.