In both the United States and other countries, sales of Aramchol and any future product candidates will depend in part upon the availability of reimbursement from third-party payors, which include governmental authorities, managed care organizations and other private health insurers. Third-party payors are increasingly challenging the price and examining the cost effectiveness of medical products and services. 

The present study aimed to explore the holistic mechanism for the antihypertrophic effect of a compound in Chinese medicine, QiShenYiQi Pills (QSYQ) and the contributions of its components to the effect in rats with cardiac hypertrophy (CH). After induction of CH by ascending aortic stenosis, rats were treated with QSYQ, each identified active ingredient (astragaloside IV, 3, 4-dihydroxy-phenyl lactic acid or notoginsenoside R1) from its 3 major herb components or dalbergia odorifera, either alone or combinations, for 1 month. QSYQ markedly attenuated CH, as evidenced by echocardiography, morphology and biochemistry. Proteomic analysis and western blot showed that the majority of differentially expressed proteins in the heart of QSYQ-treated rats were associated with energy metabolism or oxidative stress. Each ingredient alone or their combinations exhibited similar effects as QSYQ but to a lesser extent and differently with astragaloside IV and notoginsenoside R1 being more effective for enhancing energy metabolism, 3, 4-dihydroxy-phenyl lactic acid more effective for counteracting oxidative stress while dalbergia odorifera having little effect on the variables evaluated. In conclusion, QSYQ exerts a more potent antihypertrophic effect than any of its ingredients or their combinations, due to the interaction of its active components through a multi-component and multi-target mode.

On February 2, 2014, we underwent a reorganization, or the Reorganization, pursuant to which all of our current business (including our intellectual property) was transferred to us. The Reorganization was effected by way of share transfers and asset transfers, as follows: First, GHI, our predecessor, transferred the entire share capital of Galmed 2000 Inc., a holdings company incorporated in the British Virgin Islands, or GTTI, to the Company; next, GTTI transferred the entire share capital of Galmed International Limited, a company incorporated in Malta, a European Union, or the EU, member state, or GIL, to the Company; then, GIL transferred and assigned all of its intellectual property to Galmed Research and Development Ltd., a newly formed Israeli company, or GRD. GIL held all of the equity rights in and to Galmed Medical Research Ltd., an Israeli company, or GMR which was subsequently liquidated in February 2019. In connection with the Reorganization, we obtained a tax pre-ruling, or Tax Pre-Ruling, from the Israeli Tax Authority. The Tax Pre-Ruling confirms that the transfer of shares and assets resulting in the Company as the parent company and 100% equity-owner of GRD, which holds all of the Group’s intellectual property, including the Company’s patent portfolio, GIL and GTTI, is not taxable pursuant to the provisions of Section 104 of the Income Tax Ordinance (New Version) — 1961, or the Israeli Tax Ordinance, as long as certain requirements are met. However, we have not obtained a tax pre-ruling from the tax authorities in the British Virgin Islands with respect to the transfer of the shares of GTTI and the transfer of the shares of GIL to the Company, or from the tax authorities in Malta with respect to the transfer of the intellectual property of GIL to GRD. We believe that such transfers of shares and assets are not taxable in the British Virgin Islands and Malta, respectively. However, there can be no assurance that we will not become subject to the payment of taxes in the British Virgin Islands, with respect to the transfers of shares as aforesaid, or in Malta, in connection with the transfer of the intellectual property as mentioned above. See also “Item 4. Information on the Company—Historical Background and Corporate Structure” below.

Ding, Y. et al. Neuroprotection by Acetyl-11-Keto-β-Boswellic Acid, in Ischemic Brain Injury Involves the Nrf2/HO-1 defense Pathway. Scientific Reports. 4, 7002 (2014).

CD38 is a multifunctional enzyme that catalyzes the synthesis of Ca2+-mobilizing second messengers, cADPR and NAADP, from β-nicotinamide adenine dinucleotide (β-NAD+) and its phosphate form (β-NADP+), respectively22,23,24. NAADP and cADPR are further converted to ADP-ribose 2′-phosphate and ADPR, respectively22,23,25. CD38 has long been known to trigger cytotoxic responses and release granzymes in activated NK cells26, but the precise mechanisms by which CD38 mediates cytolytic activity have remained obscure. Interleukin 2 (IL-2)-activated NK cells are more lytic to target cells than resting NK cells, suggesting that IL-2 induces the de novo expression of proteins that act between CD38 and the lytic machinery in NK cells27.

Sumu: High calorie diet, 5-7000/day. Low in sugar and processed foods. Intense exercise schedule leading to elevated adiponectin levels and insulin sensitivity. Low cholesterol, triglycerides, and glucose levels. Low visceral fat and ceramides ( toxic lipids)

        In addition, manufacturers of approved products and those manufacturers’ facilities are required to comply with extensive FDA requirements, including ensuring that quality control and manufacturing procedures conform to current good manufacturing practices, or cGMPs, which include requirements relating to quality control and quality assurance as well as the corresponding maintenance of records and documentation and reporting requirements. We, our contract manufacturers, any future collaborators and their contract manufacturers could be subject to periodic unannounced inspections by the FDA to monitor and ensure compliance with cGMPs.

Although we cannot predict the full effect on our business of the implementation of existing legislation or the enactment of additional legislation pursuant to healthcare and other legislative reform, we believe that legislation or regulations that would reduce reimbursement for, or restrict coverage of, Aramchol or any future product candidates, could adversely affect how much or under what circumstances healthcare providers will prescribe or administer our products. This could materially and adversely affect our business by reducing our ability to generate revenue, raise capital, obtain additional collaborators and market Aramchol or any future product candidates. In addition, we believe the increasing emphasis on managed care in the United States has and will continue to put pressure on the price and usage of pharmaceutical products, which may adversely impact any future product sales.

FDA released analytical methods for detecting the contaminant in August 2018 (2). Later, regulators in Germany found low levels of another nitrosamine, N-nitrosodiethylamine (NDEA), in one batch of losartan manufactured in India by Hetero Labs. Zhejian Huahai had also detected NDEA in some lots of its valsartan API, and alerted FDA; subsequent testing by FDA confirmed its presence in several lots of valsartan API and in three lots of valsartan sold by Torrent Pharmaceuticals (3), that used that API. 

Each U.S. Holder should consult its own tax adviser with respect to the applicability of the “net investment income tax” (discussed below) where a mark-to-market election is in effect.

So rather than kissing my wife under the mistletoe this year, I’m going to reach up and eat the stuff, thus confirming what she’s always suspected about me.

The BMSCs were seeded on the samples (5 × 103 cells/well) and cultured in the basic medium (DMEM supplemented with 10% FBS) for 3 days. Afterwards, the cells were fixed in 4% paraformaldehyde for 30 minutes, incubated with Phalloidin-TRITC (10 mg/mL, sigma) for 2 hours, and counter-stained with Hoechst 33342 (5 mg/mL, Sigma) to identify the nuclei. Image collection and superimposition were processed by LSM 700 (zeiss, German) and Axio Observer. The experiments were repeated at least three times.