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Biotech / Medical : momo-T/FIF -- Ignore unavailable to you. Want to Upgrade?

To: Biotech Jim who wrote (11128)	6/6/2017 5:19:04 PM
From: tuck	1 Recommendation Recommended By Biotech Jim Respond to of 12215

Yes, looking at the presentation. In it they say they have completed the interaction study with statins. I see no actual results or PR, however. Should we assume it's a-ok? That is important: most patients will be on statins, yes? The Metabasis program has been dead in the water since the acquisition by Ligand. I have the worthless CVRs in one of my accounts from that munch. It had a slight issue with liver enzyme elevation and thyroxine reduction in humans, and I don't expect those CVRs to ever be worth anything. Here's a fairly recent review article that addresses some of these items, and confirms 3196 as the only thyroid hormone receptor agonist in the clinic. Thyroid Hormone Mimetics: the Past, Current Status and Future Challenges It notes hypercoagulation/hypofibrinolysis as a potential safety issue, citing an article for which I can only get the abstract (which isn't too specific): >> Thromb Haemost. 2012 Dec;108(6):1077-88. doi: 10.1160/TH12-07-0496. Epub 2012 Sep 26. The effect of hyperthyroidism on procoagulant, anticoagulant and fibrinolytic factors: a systematic review and meta-analysis. Stuijver DJ1, van Zaane B, Romualdi E, Brandjes DP, Gerdes VE, Squizzato A. Author information Abstract Several coagulation and fibrinolytic parameters appear to be affected by thyroid hormone excess; however, the net effect on the haemostatic system remains unclear. We aimed to update our previous review and systematically summarise and meta-analyse the data by assessing the effects of thyrotoxicosis on the coagulation and fibrinolytic system in vivo . Data sources included MEDLINE (2006-2012), EMBASE (2006-2012), and reference lists. The sources were combined with our previous search containing studies from 1980-2006. Eligible studies were all observational or experimental studies. Two investigators independently extracted data and rated study quality. Weighted mean proportion and 95% confidence intervals were calculated and pooled using a fixed and a random-effects model. A total of 29 articles consisting of 51 studies were included, as in several articles more than one study was described. We included four intervention (before and after treatment in hyperthyroid patients), five cross-sectional (hyperthyroid subjects and euthyroid controls), and four experimental (before and after use of thyroid hormone in euthyroid subjects) medium/high quality studies for meta-analysis. We found that thyrotoxicosis shifts the haemostatic balance towards a hypercoagulable and hypofibrinolytic state with a rise in factors VIII and IX, fibrinogen, von Willebrand factor, and plasminogen activator inhibitor-1. This was observed in endogenous and exogenous thyrotoxicosis, and in subclinical as well as overt hyperthyroidism. We conclude that both subclinical and overt hyperthyroidism induce a prothrombotic state, which is therefore likely to be a risk factor for venous thrombosis.<< This appears to be talking about humans, though it also mentions "subjects." I don't know how long it might take for such an effect to show up during a trial. Have current trials been long enough to discount this effect, assuming they've been testing for it? Cheers, Tuck

To: Biotech Jim who wrote (11128)	6/6/2017 10:06:46 PM
From: Miljenko Zuanic	Read Replies (1) \| Respond to of 12215

<I know MZ followed VKTX, perhaps he has a view on VK2809?> Yes, VK2809 and MGL-3196 target is the same thyroid hormone receptor-beta (agonist, activator), expressed on liver. As Tuck pointed, side effects can be problematic and so far hindered development of this drug-type. I do not know for MGL-3196, but VK2809 is liver-specific ????( pro-drug, activated by liver enzyme????), so maybe there is hope that 5/10 mg dose may open Therapeutic Window and have positive data in PII trial.