Why cite a year-old paper as if it is news?
I am unclear concerning the relation of these results to any presumed mechanism of action. Frankly, the discussion of the relation of metal binding activity to outcomes in the paper reads like making random changes to a delicate mechanism to see if its performance might be improved. (I can't help thinking about watch repair in Alice in Wonderland)
Not that there's necessarily anything wrong with a mysterious mechanism of action--the mechanism of action of Aspirin wasn't known until the early '70s. But I feel better about a long shot drug candidate when the pharmacology and the biology line up nicely. When they don't line up, I'm concerned that modest changes in conditions (say replacing as subject a small rodent with a larger mammal) might cause an outcome entirely unlike the reference outcome.
My reply seems to have been eaten because it contained a URL. The URL linked to flurizan, a drug I had high hopes for, which altered cleavage of amyloid precursor and also reduced "stickiness" of the fragments, both decreasing aggregation. Despite early promise, it didn't help in practice. The appeals to total zinc and copper availability that I saw in old papers don't really wash, but I was getting the idea that real potential targets were fixation of amyloid (converting a form that can be resorbed to one that can't) or activation of harmful proteins when bound to metalated amyloid.
I read the paper. Not exactly compelling pro or con. TMT Part B was part of a composite measure, and the other parts didn't show as good a response.
I think you didn't look up 'forlorn hope.' I think you know less than diddly about celiac disease, but that's beside the point. Closer to the point is that in remote intellectual territory, even the weakest analogy can be a help. I'll look at the pdf.
Just trying this out for comment. Apparently, the theory is that whatever the actual cause of the big CNS degenerative diseases, the mechanism of damage is metalloenzyme actions, and with a nice library of modulators of metal availability it ought to be possible to alter their courses [for the better]. Sounds like a long shot, but plausible--and the risk::reward is super. Actually, I'm pretty familiar with celiac disease, where you could, to a degree, say the same thing. There's a warning there: in CD the same metalloenzymes are involved in healing and in progression from transient to permanent damage.
Extending the tentative opinions: it seems that clinical experience to date is discouraging, but that the REAL goal of a phase 2 has been accomplished (clinical improvement is nice, but ability to get the desired drug level to site of action without major adverse events is necessary) (I've often said that it's unethical to try to achieve statistically significant benefit in a phase 2 because many patients are intentionally treated wrong).
This would leave Prana still as a long shot with a big potential upside. I can see the 'forlorn hope' (look it up) against HD as a try to generate enough money to keep going without diluting all the way to zero.
Talk to me, someone?
The short case is clearly refuted. Any sane short is trying to trade toward neutral, which doesn't increase pressure on the stock price. Nov and Dec are silly season, so any move is plausible short-term, but we can be pretty sure that there will be breakout guidance in the July CC, which gives shorts a generous but finite time frame.
This is still silly season, and moves need less explanation than usual. But for all that, the more nimble investors might buy in anticipation of positive response to Lilly's topline and the PV approval (since I don't think either of those is of fundamental importance, and I expect a bad reaction to the Feb CC, this is more milking than really increasing a position).
I'm reluctant to do transactions that put a ceiling on gains because the stock price is rising faster than I guesstimate management's idea of a fair buyout price is rising, which may make a takeover possible in the next 18 months. I DO think that strictly for ego satisfaction, top managers want to get approval for a non-partnered drug before letting go of the company, but that could happen suddenly, even without a p3, for a checkpoint-like candidate.
Let's see it it comes through today. It looked fine right after I posted it.
There's a lot of air in the stock price now. INCY presentations at ASH don't look like anything dramatic. Tefferi gets to run his mouth, and he's an appealing sort of fellow who HATES Incyte. In the immediate future we're waiting on tests from Lilly (I don't expect anything bad, but it's a theoretical possibility. But the p3 reporting out won't bear on the issues that have dogged Xeljanz) And we're waiting on approval for PV, where the commercial prospects are murky. It's certain that in the next CC Incyte goes from reported to reporting a loss, and there's a chance that Jakafi sales may disappoint (back loading of last Q)
Not a good article. Starting from the end, who wants to hear from the moron at GS? But also, there's no distinction among the JAK subtypes, which is necessary to marginalize the troubles of Tofacitinib and to motivate the whole JAK1 drug story. Nothing about RA. Nothing about potential capture of part of the MPN market by interferon (not a good drug, but helps some patients a lot, and has strictly limited side effects). The GILD (formerly YMI) candidate appears to be a "me too" of Jakafi. Without a real advantage, it will have trouble making a dent in the 3 years of clinical experience for Jakafi.
I'm starting to get concerned about HH's control of his mouth. I recall, as he doesn't seem to, when Incyte's business model was selling access to its patented collection of human genes. There wasn't much of a gap between the end of that model and very focused attention to the value of JAK 1/2 inhibitors against MPNs. If there was a stage of hoping to target "big name" cancers it certainly didn't show outside the company, and frankly, it would have been such a suicidal business model that I can't believe the bright people there considered it for longer than a week.
Traditionally, the oracles of the ancient world failed after Christ was born. So what's the source of your prophecy?
The way the deal is structured, GERN shareholders are left with all of the Im safety risk. I've said it before: I don't think it's approvable. Run trials, sure; release for general use no.
In the long run, I'm not sure that charisma is necessary to lead others. To take over immediately, probably. But at the top of a company, other things can get people's compliance until respect takes over. We've certainly seen that (Mr Imelt at GE may be an example).
Perhaps it's a mistake, but I thought the term 'charisma' was a reference to my observation that the way a presentation is made to analysts can move a stock meaningfully (and the recent CC was an example of the negative side). Not charisma, not command of the facts, not obvious intelligence, not common language with analysts. Those and other things. Maybe it's like the old definition of pornography: "I know it when I see it."
Safety remains a big concern (the standard to continue studies is far weaker than the standard for approval). In addition to the ongoing surveillance of liver toxicity, there is the risk that a single overdose of Imetelstat can be fatal (such things happen).
Geron had to find a big friend somehow. Company had no money, no credit and nothing to sell except the one patent estate. So it's done. This particular format of finding a big friend gets the drug to market (again, if it succeeds) later than some others.
At best, this leaves Geron in bad shape. At worst, J&J can back out over safety issues (100% of safety risk falls on Geron). Given high concern over liver toxicity and a case of aplastic anemia from overdose, the safety risk is substantial.
The upside for Geron owners is that something generally like this had to happen for Imetelstat to have any chance at all of reaching market. There is an upside for Incyte owners, too: a big company like J&J is not going to take risks to get a drug candidate to market sooner (as Incyte did to start with Ruxo--SPA so the whole bankroll could back one p3).
Tefferi is unlikely to be able to cooperate with J&J management, so one may wonder where he'll land next.
I, at least, don't care about charisma in the sense of dominating a group (In the company I often use for comparisons, both frequent presenters were highly charismatic, but one moved the price up and the other moved the price down). The last CC was a bad presentation but that may have been because of last minute changes. We'll see.
I DO care about over-reliance on packaged strategies from consultants (buzzwords are the most prominent symptom). We just heard too many buzzwords. I agree that the news out of EZ sounds like good things being done, but it'll take a couple of Qs to learn what's really happening. The pawn and pdl/CSO businesses are neither retail nor banking, and I doubt that purchased advice will be as good as the home-grown variety.
Cohen keeping to the strait and narrow is very much one of the unknowns. My impression is that he tends to have wild ideas, but tones them down when he has to help implement them. If anyone recalls the Florida pawn acquisition, it was almost certainly one of his big ideas, but the negotiations dragged on because the asking price was too high. In the end, the deal was made, at too high a price, but it wasn't the mess some more recent deals have been.
The problem is that the only hidden value within Incyte to unlock is the pipeline, and that is [extremely] difficult to set a value to. The only out-of-proportion spending is research, but that is the entire point of the company.
The company could be sold for $85 a share tomorrow if management wanted to, but I think all of us expect it to grow to that vicinity organically in not too long a time, and to pass that price convincingly. Let's do a thought experiment: suppose someone put a resolution on the proxy to cut research spending in half and sell rights to any pipeline candidates not yet in clinical trials. Do you think it would have a chance of passing?
I have learned to be put off by rah-rah management. Too often, their optimism is the only positive in sight. It's hard to lead cheers without promising more than you can deliver, and the market doesn't forgive under delivery. There's a line, though, and Dr Paul couldn't be left as main presenter to the analyst community. HH comes across as neutral It's possible that HH is also more suited to be the ultimate head of a business going from little drug developer to big pharmaceutical company with not much of a pause in between. But I don't see much opening for someone to say that IF Only my boy was top honcho, the stock price would be substantially higher.
Net: not much for an activist to be active about, and he probably wouldn't get much shareholder support.
We've been here before. You're using a word that usually has one meaning in a way where that meaning can't apply. An activist investor is nearly always trying to change corporate behavior so that a "sleepy" asset is contributing to visible performance. I see no cash horde. I see a research program that is churning out drug candidates at a pace a little faster than they can be developed, but not faster than they can be developed after Incyte turns GAAP profitable. I see a marketing build-up for PV that is earning its keep in the mean time by goosing Jakafi for MF.
So when you say 'activist,' what do you mean?