Both technologies are very very new and have hope and dreams the technology potential can offer. Both, in my and others' opinion, have tremendous challenges to overcome before they can be translated into medicine. This does not mean that there won't be some successes in applications of the technologies in future. Both technologies have to deliver RNA bits into the cells without being degraded by endonucleases. Moderna's potential drugs have to cross the cell membrane to be translated into proteins inside the cells. The latter has to occur in human body, not in vitro setting. There are great deal of claims than proofs. Moderna has a large number of patents to backup their claim that their chemistry can overcome nuclease degradation. I would like to see the proof of this happening in the human body. I have yet to find a clinical trial in which the goal is to create a new protein in the human body.
I remember I found the piece somewhere in a Yahoo Finance site but I cannot remember which site. I don't subscribe to TheStreet.com.
A group which includes an author at UCI, where Regulus' CMO received education, identified HCV mutants that can evade XRN2 without miR-122. There might be another molecule that can protect these mutants from degradation. This has to be less efficient than miR-122 in protection because otherwise those mutants would be the most prevalent. These mutants may easily succumb to polymerase inhibitors. Anyway, they can now go after the best oral DAAs against these identified mutants in combining with RG-101.
[[ ... HCV infection requires miR-122, which is expressed only in liver cells, and thus is one reason that replication of this virus occurs efficiently only in cells of hepatic origin. To understand how HCV genetics impact miR-122 usage, we knocked out miR-122 using clustered regularly interspaced short palindromic repeat (CRISPR) technology and adapted virus to replicate in the presence of noncognate miR-122 RNAs. In doing so, we identified viral mutations that allow replication in the complete absence of miR-122. This work provides new insights into how HCV genetics influence miR-122 requirements and proves that replication can occur without this miRNA, which has broad implications for how HCV tropism is maintained.]]
[[... Celgene stock looks underpriced. At 17.6 times this year’s earnings forecast, the biotechnology company trades almost exactly in line with the Standard & Poor’s 500 index of big U.S. companies. But earnings for the index are tracking below levels from two years ago, while those for Celgene are up about 50%. And after this year, Celgene’s (ticker: CELG) earnings per share are likely to more than double by 2020. It’s a faster grower than Bristol-Myers Squibb (BMY), which trades at 28 times this year’s earnings forecast.
CELGENE RECKONS that its hematology portfolio, including Revlimid, Pomalyst for more advanced multiple-myeloma cases, and two other small contributors, will bring in $14.8 billion in revenue by 2020, up from an estimated $8.7 billion this year. It forecasts total company revenue of more than $21 billion by then, and earnings per share exceeding $13. ... ]]
Applying a P/E multiple of 35 to an annual earnings of $13 or more, I get a share price of 455 or more in 4 years.
Yesterday's issue of Science has a special section on RNA. Its subsection mentions ALN-TTR02 and TTRsc.
[[... Advances in siRNA formulation allow efficient delivery to the liver (26). The utility of siRNA-mediated silencing of transthyretin (TTR) mRNA in the liver of patients with familial TTR amyloidosis (31, 32) is being studied in two separate phase 3 clinical trials. The first trial uses a siRNA formulated with lipid nanoparticle technology (ALN-TTR02) and intravenous administration to attempt to improve neuropathy in patients. This is the therapeutic siRNA that is closest to potential approval. In contrast, the second trial uses a TTR-targeted siRNA (ALN-TTRSC) that is formulated with N-acetylgalactosamine (GalNAc) to facilitate uptake by and release into the cytoplasm of hepatocytes, as well as to allow for subcutaneous administration (Fig. 2 and table S1). Many other receptor-targeting agents are being evaluated preclinically to determine whether siRNA can be selectively and effectively delivered to the cytoplasm of other cell types in other tissues.
Jun 17, 2016 | 10:22 EDT
[[Piper Jaffray analyst Edward Tenthoff noted that the U.K.'s National Institute for Health and Care Excellence, or NICE, has announced its intent not to cover Orkambi, but he views the guidance as "simply the latest phase" of the negotiation for reimbursement coverage. The analyst added that if the board's final guidance, potentially in July, is still negative, it will have no impact to his 2016 estimates for Vertex, which do not include U.K. sales. The firm keeps an Overweight rating and $131 price target on Vertex shares.]]
There appears to be awful misunderstandings by Dirk H. I want to clarify.
One patient who had the liver reaction was also taking Soliris. He or she was taking steroid and cyclosporine because soliris failed to maintain a low LDH level and the breakthrough occurred (patient 0083), who was pretty sick; both drugs affect the liver and the person also had viral gastroenteritis about when there was a spike in the liver enzymes. He was taken off all of the drugs (except for soliris) and the enzymes returned to normal. Remember because of the durability of ESC-GalNAc, the effect of ALN-CC5 persisted long after he stopped taking the drug so that liver enzymes returned to normal while C5 levels continued to be suppressed by CC5.
Only two analysts on the conference call asked about the AE, and they seemed satisfied with the answer. Over all you can tell the analysts were intrigued but aren't sure about the commercial value of ALN-CC5 (i.e. will they try to undercut soliris on price).
Maraganore was talking about a quarterly dose of CC5 coupled to monthly (instead of bi-weekly) doses of soliris at 600 mg (instead of 900 mg biweekly). That would certainly save money depending on the price of CC5. You can do a quick calculation and figure that such dosing might save 2/3 of cost of soliris and then maybe CC5 could be priced at 1/3 of soliris so that there would be a 1/3 savings.