My friend quantman may have lost it a bit at the end.
You could make the same objection to most powerful RA drugs (corticoids, immunosuppressors, anti-TNFs). It turns out that you can knock down a lot of granulocyte activity and its side effects with a mixed JAK1/JAK2 inhibitor before things like anemia and infections stop you. In fact, the p2 on Baricitinib (mixed JAK1/JAK2 with low affinity for the marrow compartment) dragged on because no dose-limiting toxicity was seen. So it may work out. Regulators are now looking for protection of joint structure, and that requires somewhat longer trials to demonstrate. There's also a chance that Bari may be useful against diabetic nephropathy, which would be a jackpot.
I'm a little uncomfortable about valuation right now. The PV market for Jakafi might be twice as large as the MF market, but that is more a marketing issue (VERY soft science) than a medical one. Some use of Jakafi against pancreatic cancer seems assured, but it's delayed pending identification of the magic subset of patients who benefit most (and how much use will depend on results of trials not yet announced). Recent inclusion on brokerage lists appears to depend on a belief that at least one among the JAK1-only inhibitor family, the IDO inhibitor and the cMET inhibitor will become a hot drug candidate within the year. I'd rather see more evidence before paying up. The long argument going forward is that an only mildly rosy view gives ultimate sales for Jakafi vs MPNs of $1.5bln, and the same for Incyte's share of Bari, while there's a lot of pipeline behind them. I'm concerned about just how far forward you have to look for those dollars.
It's not a terribly bad way to look at things thinking of today's Incyte as a completely different company from the one that owned so many human genes and was going to make money licensing them.
The thing about paying consulting fees to Madison Park is that the advice gotten in return has been sub-par in recent years. Bridge loans in the Crediamigo acquisition took like 6 months to refinance. The merger with Cash Converters was a hybrid creature that fortunately didn't survive currency fluctuations. I'm still leery about Go Cash terms, but there are ways that could work out ok (and ways it couldn't)
The attraction of a dividend to owners who feel marginalized is that once a company starts paying a dividend, the market punishes discontinuation of the dividend. That doesn't usually apply to stock buy-backs.
Old kid joke. What held it up? Answer: bandits.
What's holding Incyte up? I don't know. Partly buzz: if it would be such a big deal for Geron to take away Incyte's business, that business must be worth taking (I think this might be $3-5 of the stock price). Partly belief in management (they have made several financial moves that look very nice in the rear view mirror) Jakafi for MF looks good, but that business puts the value of the company in the $30-s. Hope for Jakafi in PV? Perhaps, but I'd expect skepticism to persist. The solid tumor programs? Depending on buy-side intelligence gathering that's a possibility. Bari? Again, possible with some espionage, but for the most part too far in the future to matter much now.
With a normal January Effect INCY should be fairly safe for the next month, but I'll want some new news by March to feel comfortable.
You're somewhat ahead of yourself. General acceptance of Prolaris would be huge. This is a step toward that. And yeah, the timing is good. But look at how much work it took to get general acceptance of BRACAnalysis. The topline leaves open the possibility that Prolaris may not be quite good enough to be an easy sell. Another issue that may make adoption slower than adoption of BRACAnalysis is that because the mutations are somatic rather than germline, one positive doesn't sell tests to lots of relatives of the patient.
One toll gate on the highway.
We really need a better class of basher. ASCEND is the name of a trial, not of a drug. It doesn't get approved.
Why do you cite that paper? The abstract suggests that no snapshot of tumor genetic complement is going to be definitive by itself (that is, that Prolaris has a fundamental limitation).
Once you have basic marketability of a test, it becomes a selling exercise. Myriad is good at selling novel tests, but with prediction of metastasis merely better than the other (very poor) tries, and not very good itself, selling is going to be a challenge. Longer follow-up may help.
Near as I can tell, the board has been very careful about staying just the right side of the law on this. An extra $2MM to Cohen for doing what he is already being paid to do through the management agreement might have been a stumble, though. Needless to say, I consider this a healthy development.
The Geron flap has been good for our stock price. There may be blips connected with the present situation, but since Geron was never an actual business concern, the net price shouldn't be affected in the longer run.
Geron's president impresses me. He may be able to salvage the company yet again.
Historically, the bear case on Intermune has had these legs: pirfenidone doesn't work at all; if it does work, the benefit is not worth the "trouble" (expense, intrusiveness, side effects, etc) of taking it, the side effects are intolerable and anyway, there isn't enough REAL IPF to make a market. Oh!-and better drugs will be there early on.
Pirfenidone works. Add the ASCEND data set to existing data and that is clear. The benefit and trouble are hard to quantify, but over the last 4 years benefit estimates have been steadily increasing while trouble levels have lowered a bit (better management of side effects, more convenient dosage form expected). Absolute tolerability of side effects has a cultural component: Shionogi encountered the misfortune that The Japanese are less tolerant of indigestion than Europeans. Ascend results clearly show that the side effects are tolerable to a transatlantic subject population. The lowest defensible estimate of IPF prevalence in Intermune's territory is 170,000 (the patient association estimates over 300,000). At a treatment price over %50K/yr that is a big enough market. The only competitive drug that might be near approval is the BI one, and the best public information is that it is moderately inferior to pirfenidone. The new p3 enrolling suggests that marketing is several years off, at best.
So the classic bear case is demolished. There are some new elements: many otherwise-reasonable people are certain that the European introduction was disappointing. This is mostly because they believed the LIE that management had predicted $60MM of European sales in the first full quarter (I first saw it on Motley Fool, but it popped up EVERYWHERE). Management actually said that they hoped the introduction would track ahead of the acknowledged blockbuster Tracleer, which it did. The newest item is the single Hy's law (elevation of certain liver enzymes warns that a treatment is able to cause liver failure) case in ASCEND[more]
I was there when it did those jumps and dives. I got crushed in a small way by most of them trying plausible option strategies. I've learned to keep it simple.
I'm surprised it has taken so long. It will be triggered by pricing of Jakavi in either The UK or Italy
(what has been said is 3 of the 5 major European markets; DE and FR have priced. UK had its usual rejection on initial consideration, but there has been enough time for reconsideration. Spain is effectively without a government). If we have to wait for Italy, it could be another 6 months. Because the back-royalty is contingent on total number of countries rather than which ones, it is just barely imaginable that it could kick in first.
The problem in The UK is that the statutory pricing guideline is so much per year of life extension, adjusted for quality of life, and with an idiotically low price for a year (about $100K if I recall). So no imaginable modern drug is approvable on its face. There Are Ways, but they work on reconsideration, not initial consideration.
You might want to check the meanings of 'effect' and 'affect' when they are nouns. But I digress. Well, frankly, all I'm going to do now is digress. I've made my point, you've made your point, and neither one of us seems to think that the other one has a point. There may be a reason to re-open this discussion when the design for the IM registration study shows up on clinicaltrials.gov.
May come as soon as early Feb, but most likely late Mar. Probability of a big stock move about 90% (about 5 times as likely to be up as down). Situation complicated by ITMN being a good candidate for "January effect." How are you playing it?
I am entirely long. A failure will hurt, but I've been there before. All planned positions already in place, about 2/3 stock and 1/3 short sale of puts (both 2015 and 2016 strikes) (I anticipate holding the 2015s to expiration but trading the 2016s).
BA Harvard PhD Northwestern Former U of Chicago faculty "Scientific brother" of Robert Grubbs. Somewhat-respected gadfly in celiac disease research. I'm in Who's Who.
I feel so dirty.
Now go the @#$%^ away.
My prediction that IM will not affect Incyte's business in a way we ought to care about has only the tiniest bit to do with science. Only if the ASH results were such a slam dunk that FDA was likely to shove procedure aside was there any chance of such a thing happening, and even the abstract from way back when showed that things weren't so spectacular. Take away Tefferi's editorializing and the full presentation was somewhat weaker than the abstract.
The prediction has a lot more to do with looking at investor behavior and analyst opinions for rather a while. A merely good ASH presentation might affect GERN, but wouldn't be expected to affect INCY.
I'm pretty sure he shorted Geron based on the company's long history of disappointing investors. That may have been misguided, as there as been a management shake-up since the last catastrophe, but many of us have seen both kinds of management changes.
I didn't used to know anything about Geron, but I've picked up at least a little. It seems unlikely that the company can survive as an independent. As a takeover target, you can't assign much value to the prospects of IM against essential thrombocythemia (the cure looks worse than the disease, and it'll take a lot of data to disprove that). I'll look at the rest of the company the way I have looked at Incyte in the past: management and long-term holders clearly think IM is very valuable. Right now, a potential acquirer is going to see it as having a large risk of failing in p2 (there may be no dosing schedule that can be given explicitly that offers attractive risk::reward). That doesn't have to be true, but it's what a potential acquirer has to 'fade.' Nothing other than the IM program looks valuable. So I don't think a price can be agreed upon until a p2 is completed. There appears to be just about enough cash to get there.
I'd REALLY like a link to that review. Fatigue, thrombocytopenia and anemia are well-known AEs with Jakafi, and are manageable (note that despite the thrombocytopenia, Incyte representatives have stated that there have been no life-threatening bleeds). I'm pretty sure that if brain lesions were "commonly reported" we'd have heard of it before--one possibly-associated case of PML sure made a splash. Breathing difficulty is a little vague; I'd like to consider it secondary to other AEs, like anemia and pneumonia. Pneumonia is the interesting item on the list. JAK2 inhibition reduces the number of granulocytes produced (most importantly neutrophils, but other classes too) and JAK1 inhibition blunts immune response. All through testing and early adoption there was a lot of surveillance for opportunistic and/or rapidly-progressing infections. Nothing spectacular showed up. At the last analyst presentation, a hint was dropped that some sort of infection signal is being seen; that will certainly be followed up.
The problem with treating ET is that for most patients, the experience is fatigue and itching. The disease does not reduce average life expectancy. A small fraction of patients are much sicker, but not many. A 2-hour intravenous drug administration every other week is arguably as disruptive as the illness itself. Any risk at all of causing aplastic anemia is unacceptable. Any candidate treatment will have to go through a biggish trial to set an upper limit on rate of leukemic transformation.
A. Tefferi is a superb clinician. The personality traits that destroy him as a scientist don't harm that, and may even help. Patients, from what I have gathered, adore him. The only downside I get from gossip is that he sometimes tells patients that they're better based on lab work when they definitely don't feel better.
As for prognosis with Jakafi, it improves every time there's a clinical update.
I see nothing about FDA having granted IM any sort of fast-tracking. Clinicaltrials.gov shows a number of arguable p2 trials of IM, mostly suspended. None of the designs look especially compatible with expansion of the recent ASH results. I will accept your number of 375 patients--one case of aplastic anemia among 375 exposed patients would make a drug very unlikely to gain registration, so it will be necessary to set protocols that show the event was an anomaly, or at least completely avoidable.
Hey, someone told me that I had been mentioned here. I'm flattered. Maybe I should start a market advisory letter to capitalize on the fame.