Probably worth a listen. PaCa p3 probably enrolling from April, with magic subgroup probably described then. '110 Will probably be the JAK1 targeted toward oncology, the other announced one likely toward inflammation. Finances sketched able to support 2, maybe 3 simultaneous registration studies.
I'm being nice because you aren't as irrational as either the earlier wave of Geron posters or our home-grown crazies. But this is the Incyte board, and out first concern is what news means for INCY. Bonkenx apparently has something special against Tefferi, which he may explain or not. The rest of us have been through Tefferi's fraudulent account of a Ruxolitinib withdrawal syndrome, his fraudulent presentation of survival data on patients who had been treated with Ruxolitinib and a couple other dishonest attacks. As a scientist, [fill in name of a known liar] is as reliable. He has never been caught falsifying raw data, so we trust him that much. ANYWAY:
We look at the Mayo results and break them down. Nominally, 33 subjects and no controls over 6 months. 3 Deaths, including one leukemic transformation and one from aplastic anemia. Both symptomatic improvement and low-grade AEs comparable to Jakafi. Some nice histology. This is not a breakthrough.
Tefferi is known to be more partial to lab results than to patient experience (this is part of why he uses a lot of hydroxyurea). There is in fact sparse data on the experience of the earlier patients, although that is corrected later on.
If you want to talk about PRs and CRs, please explain why they should matter. I've sketched why they don't. Healthy life does.
Listen to the Geron CC. If ever I heard an executive backpedaling away from an investigator's overstatements...
Price? In both cases the price is set arbitrarily. Ruxolitinib active ingredient costs essentially nothing to manufacture. Imetelstat active ingredient costs more, but still probably not comparable to selling price.
Consider too how the drugs are administered. People can feel pretty healthy even if they need to take 2 pills every day. It's hard to feel as healthy needing a 2-hour IV infusion twice a month. (Polycythemia vera patients needing to be bled twice a month tend to be unhappy about it.
I have found Mr Lacey's CCs generally encouraging. It seems like his permanent appointment is an owner-friendly development.
Of course, Mr Nothaft gave great CCs and the company got out of control during his tenure. I'd like to see the relative openness about legal matters continue, and a return of fairly regular boasting about the value of Tessera's products to the company web site. A dog-and-pony show every third year wouldn't be out of place either, and it would be appropriate soon. It would also be nice to see a rationalization of the division between 'root' Tessera and Invensas. (Actually, I'd like to see DOC spun off and Tessera renamed to Invensas, but anything that doesn't sort IP products by age would be an improvement).
If one drug (call it drug R) relieves all symptoms apparent to the patient but leaves some laboratory findings bad, and another one (drug I) relieves all symptoms apparent to the patient and also improves the lab findings, and in both instances the disease returns when treatment is discontinued, it isn't clear that the lab findings are important. Mass lesions are special, because they can impair health in ways unrelated to main disease processes (blocking stuff, crowding stuff, bleeding, probably some others). 'Complete response' is mostly appropriate in the world of mass lesions. It isn't out of place in the world of fully-liquid tumors where it implies that the illness won't return [quickly] when treatment is stopped. But a non-mass-forming solid tumor that will come right back when treatment is discontinued? Word play. And the CC harps on the fact that it's word play. 'Partial response' is hardly appropriate at all outside the mass lesion world.
I am pretty sure aplastic anemia connected with a drug candidate is the #2 hot button issue for FDA (second only to teratogenicity). A drug may be approvable if it occurs in an abandoned leg of a p2, but they will be careful to require further testing sufficient to set a very low risk before allowing marketing. Hence, 6-7 years.
Don't feed me straight lines about sticking heads places.
Given the evidence available, Imetelstat is going to have a relatively hard road to market. There will probably be a need for more than one study to establish dosing schedule and response to treatment problems. The registration studies are likely to have to be relatively long, as the claimed advantage over best available treatment takes a while to appear. Rates of leukemic conversion and catastrophic drug toxicity must be lower on protocol than in the somewhat-random series reported so far. All the talk about PRs and CRs amounts to word play for a tumor type that doesn't produce masses (unless a CR persists after treatment is discontinued, something not claimed here). FDA is extremely resistant to word play.
To some extent, Tefferi's strength works against the Imetelstat case. He is a transcendent clinician, obtaining good results even with hydroxyurea (a seriously awful drug). We haven't seen a series of patients treated by a more ordinary physician.
As an investor, possible competition 6 or 7 years from now doesn't bother me.
The volatility comes from changing beliefs about the importance of factors other than day-to-day business in projecting future earnings. Lately, the stock has dropped because of a large risk that Medicare will substantially cut reimbursement for BRACAnalysis, the company's predominant product.
Myriad's prospects depend to a remarkable degree on maintaining (or not) the perception that its trademarked tests are better than other providers' near-equivalents. That is a difficult and uncertain enterprise, and frankly, more familiar in the prepared food industry than in medical testing.
I listened somewhat casually. Interesting results to be sure. In some ways, a classic investigator-sponsored phase 2: the principal investigator does whatever he pleases, having gotten an investigational drug to try to help his patients, but paying for the privilege by reporting in detail. The company maintained a degree of discipline, but with obvious struggle. For all that, the most essential dosing information seems settled. Dose scheduling and adjustment in the face of adverse events will still need to be settled with a formal phase 2.
It appears that the benefit is fairly durable, in the sense that no patient who achieved a good response later became refractory to the drug, but the longest-treated responding patient was studied for about a year. There is no claim by the company that a "complete response" should be interpreted as a cure; drug is continued indefinitely
The deaths of subjects were plausibly related to failure of treatment--one possibly due to drug toxicity, the others likely from disease progression.
Sample size is still much too small to talk about less-common effects.
The REAL old-timers may recall that one of the business breakthroughs that permitted ruxolitinib to succeed was convincing FDA that reduction of spleen volume is a worthwhile endpoint. Geron may be headed for a similar effort: convincing FDA that 'PRs' and 'CRs' are worthwhile clinical endpoints for a drug treating a cancer that does not form mass lesions.
I made Tefferi the third problem. Everyone can look at his data; he hasn't been caught falsifying data. But we are obliged to ignore his interpretations and let others do the interpreting, because he emphatically has been caught falsifying interpretations.
I'll stick with my first point first: at best, Imetelstat can't get to market in under 3 years; with FDA suspicion, 6 years is a better guess.
Even if I grant "complete response," to get to "cure" you need "with no relapse," something that a short-term study is incapable of demonstrating.
They'll be presenting a study on Imetelstat on Monday, and if history is a guide we'll be flooded with triumphalist postings. They will be garbage, for several reasons.
First, and most important, is that the drug can't reach market by a time that means anything to INCY investors. The study being reported shows efficacy and gestures at determining dose, but it is not a proper dose-determining study. A proper phase 2 to set dosing will take most of a year. Following that, two registration studies (phase 3s) will be required to obtain licensing in the US. Call it another 2 years. After that, there is an unknown delay for FDA to act--typically most of a year. So marketing is 4 years off if everything goes right.
Less important at this stage is that Imetelstat combines several features that have been bad news for drug candidates in the past. It is a lipid-conjugated polynucleotide targeting telomerase. Lipid conjugation tends to produce immune responses, polynucleotide (I switch from 'oligo' to 'poly' at 8 nucleotides, but nemmine) drugs tend to be very toxic, and targeting of telomerase has caused a lot of problems. Not to say that it can't be a good drug, just that FDA is going to be especially cautious.
Less important yet is that the text describing the results is written by A. Tefferi, who has lied repeatedly in public about myelofibrosis treatments. The preliminary release referred to partial and full responses on the basis of histology, with no evidence given on symptomatic improvement nor acknowledgement that it is part of the definition. Deaths occurred that were judged not to be treatment-related. Tefferi is a superlative clinician, but whenever he has touched a study, other people need to interpret the results.
Least important of all right now is durability of response. Myelofibrosis is a chronic disease, so a durable response is important. Even if a 6-month study shows 'full responses', it doesn't speak at all to durability.
Non-voting shares have certain rights (most significantly equal dividends to the voting shares and fair distribution on change of control) under the governing documents of the corporation. We are protected by the fiduciary duty of the board of directors to ALL of the owners of the corporation. Let's say that this hasn't worked to the satisfaction of everyone, especially in the last year or so,
It's getting close to time for the company to decide what condition to target with this candidate. FDA is unreceptive to claims that you have developed The Panacaea. I guess lung cancer would be about the largest patient count for a manageable registration study.
The problem for shorts is that management knows how to skyrocket the share price (gestures of friendliness to owners), and might do it if a bear attack became embarrassing.
This drug is at least 3 years from market. It is a monoclonal antibody, which makes it an undesirable drug for long-term treatment (dosing of monoclonals tends to be intrusive). Some [on-target] side effects are expected from completely blocking a growth factor; larger sample size is needed to characterize them. The actual improvement reported in some patients is highly encouraging. The degree of improvement is well short of a cure, and there is no obvious reason why this drug should not be given simultaneously with Esbriet.
Overall, this report strikes me as neutral for Intermune.
But an excellent underlying for options transactions. Consider, for instance, selling Jan 2015 puts naked, or buying the stock and selling Jan 2015 calls. Strikes of 35 or 40. Or as a pure option play, buying the 35 call and selling the 45. These kinds of transactions are sweeteners you can add to a successful long position to harvest a little extra gain without adding much risk.
I HAVE outsmarted myself in the past with complicated option plays; these are simple and have little in the way of traps. But DO diagram price at settlement vs return for any strategy you don't know well, and consider your response to an assignment. Consider the possibility of rolling favorably, too.
I've seen almost every variation on timing (except very late publication of favorable results...wonder why that never happens?). I think the prejudice here is toward early announcement. For some reason, execs here are very sensitive to possible legal problems, and the best way to head off suspicion of trading on non-public information is to get it public right away. So unless there's something odd like a direct conflict between raw primary and secondary endpoint reads, I'd expect a top o' th' topline release within 2 weeks of primary completion. The really slow analyses happen when many subjects leave the study and multiple treatments of missing data have to be generated. Part of the protocol for ASCEND is aggressive action to avoid missing data, and in the last CC it was stated that subject drop-outs have not been a problem. So I'd put the most likely first announcement right about at the earliest plausible date, say second week in March. But data collection could drag on an extra month and there could be tricky calls. Basically, I think that a mid-May first read wouldn't be a happy one.
Given the old advisory panel and European clinical experience, even a 10% chance that placebo did as well as drug would probably give us a good chance of US approval, but the stock price probably wouldn't take off ahead of time. We want full significance, and we want it NOW
I answer people like you the first time.
You seem to think that something from Geron might make a business difference to Incyte. Let's engage in some fantasy: suppose a drug made MF go away every time and stay away. It STILL couldn't take a single patient away from Jakafi treatment in less than about 15 months. But all that's going to come out Dec 9 is 6 months data on a trial with no pre-announced protocol enrolling 30 patients. And we already know that there were too many deaths in the group (yeah, yeah...but it's true) At the very least there will need to be a p2 to determine dosing and a p3 to establish safety and efficacy.
And as for Incyte's prospects, Jakafi for MF is not the greatest driver behind the company.
I notice that any drug backed by Tefferi gets enthusiastic followers. I hope he doesn't ask patients to pump his hobby horses.
Mar 15 calls 25 cents asked.
Most hopeful thing I can think of short-range is that some of the present pain is tax loss selling.
Just saying. We've hit Rachel McMinn's published price objective. If you go back to her sum-of-parts valuation and try to correct the numbers she says to a decent estimate of what she means, you (well, I) get a number in the mid-60s. So let's say no longer DEEPLY undervalued. People get giddy and irrational at these heights. I'm no longer saying NO takeover bid. You'd have to be nuts (or very very confident) to make a $60-ish offer for a $30-ish company knowing that there was a good chance you'd set off a chain-reaction leading to either you or a competitor buying it around $130. It still doesn't make SENSE, but, well, giddiness.