Wang, C. J. et al. The effects of shockwave on bone healing and systemic concentrations of nitric oxide (NO), TGF-beta1, VEGF and BMP-2 in long bone non-unions. Nitric Oxide 20, 298–303 (2009).

Togawa, H. et al. Epithelial-to-mesenchymal transition in cyst lining epithelial cells in an orthologous PCK rat model of autosomal-recessive polycystic kidney disease. American journal of physiology Renal physiology. 300, F511–520 (2011).

A further challenge to Aramchol’s market penetration is that currently a liver biopsy is the standard approach for measuring improvement in NASH patients. Because it would be impractical to subject all patients that take Aramchol, when and if it approved, to regular and repeated liver biopsies, it will be difficult to demonstrate Aramchol’s effectiveness to practitioners and patients unless and until a reliable non-invasive method for the diagnosis and monitoring of NASH becomes available, as to which there can be no assurance.

example, many foreign countries have compulsory licensing laws under which a patent owner must grant licenses to third parties. Consequently, we may not be able to prevent third parties from practicing our inventions in certain countries outside the U.S. and Europe. Competitors may use our technologies in jurisdictions where we have not obtained patent protection to develop and market their own products and, further, may export otherwise infringing products to territories where we have patent protection, if our ability to enforce our patents to stop infringing activities is inadequate. These products may compete with our products, and our patents or other intellectual property rights may not be effective or sufficient to prevent them from competing.

The FDA’s standard is to be below an amount that would be expected (by their dose/response modeling) to cause 1 extra cancer case in 100,000 people who were taking the tablets at a standard dose for 70 straight years. That’s pretty stringent, considering the background rates of cancer in people who actually stay alive for 70 years in a row, especially when you factor in that no one goes on valsartan when they’re ten years old. Unfortunately, the ZHP material (according to the FDA) would be expected to cause one extra case of cancer with only 8,000 patients taking the highest dose of the drug for only four years, and that’s definitely unacceptable. It appears that the other manufacturers’ batches had contaminants at lower levels, from what I can see, although the amounts do not appear to have been specified.

        As of December 31, 2018, we had 72 full-time or part-time employees, including 28 employees with M.D. or Ph.D. degrees. Of these employees, 58 employees are engaged in research and development activities and 14 employees are engaged in general and administrative activities. None of our employees are represented by labor unions or covered by collective bargaining agreements. We consider the relationship with our employees to be good.

We may not be able to complete or commence the clinical trials that would support our submission of an NDA to the FDA, a Marketing Authorization Application or MAA, to the EMA or any similar submission to regulatory authorities in other countries. Drug development is a long, expensive and uncertain process, and delay or failure can occur at any stage of any of our clinical trials. The fact that the FDA, EMA or other regulatory authorities permit a company to conduct human clinical trials is no assurance or guarantee that the trials will be successful. On the contrary, most candidate drugs that begin clinical trials do not prove to be successful and do not result in the filing of an NDA, MAA or similar filing. Drug candidates that successfully complete one phase of clinical trials may prove unsuccessful at a subsequent phase. Human clinical trials are very expensive and difficult to design and implement, in part because they are subject to rigorous regulatory requirements and in part because the results of clinical trials are inherently uncertain and unpredictable. Regulatory authorities, such as the FDA, may decline to permit a clinical trial to proceed or may suspend a clinical trial that it has previously permitted to proceed. Additionally, the clinical trial process is time-consuming, and failure can occur at any stage of the trials. We may encounter problems that cause us to abandon or repeat clinical trials. The commencement and completion of clinical trials may be delayed by several factors, including:

Debiopharm, a Swiss-based biopharmaceutical company, recognized that controlled-release LHRH for the suppression of testosterone had greater potential for the treatment of prostate cancer than contraception. Having licensed triptorelin, another LHRH analog, Debiopharm contracted Southern Research Institute in 1981 to develop triptorelin microparticles with PLG. This effort led to the market launch of Decapeptyl SR (sustained-release triptorelin) in Europe in 1986, which was the first PLG injectable microparticle product on the market as well as the first injectable peptide-releasing product to be commercialized (7). It is still on the market today distributed by Ferring and Ipsen-Beaufour. 

Hi Mark When have no distinction between science and science fiction; it undermines science. Science is not whatever somebody pulls out of their butt.

Hi Alan My thinking is in line with yours but it seems like he’s saying that by slowing growth one would also be impairing the growth of stem cells. I think that that is similar to the thinking that rapamycin would impair the development of the immune system until it was found, in intermittent doses, to have the opposite effect.

We enter into contracts in the ordinary course of business with CROs for clinical trials and clinical supply manufacturing and with vendors for pre-clinical research studies and other services and products for operating purposes, which generally provide for termination within 30 days of notice, and therefore are cancelable contracts and not included in the Contractual Obligations table above. We have included as purchase obligations our commitments under agreements to the extent they are quantifiable and are not cancelable.

Moreover, adenosine triphosphate (ATP), adenosine diphosphate (ADP) and adenosine monophosphate (AMP) contents in cardiac tissue from different groups were assessed by enzyme-linked immuno sorbent assay (ELISA). As shown in Fig. 6e,f, both ATP/ADP and ATP/AMP were significantly down-regulated in AAS groups compared to Sham. Except DLA and DO alone, all the treatments protected this down-regulation significantly with QSYQ being most effective. Noticeably, QSYQ exhibited more effective than any other combination treatments except ASIV+DLA+R1, which showed more significant effect than its any composition.