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CLDN and BTD:
According to you, FDA panel might make a mistake to grant CLDN the Breakthrough Designation Therapy without looking at the info you presented?
I doubt that the company mislead the FDA on the CUPID1 data or the FDA shortsighted on the info you mentioned.
Qure:
Hard to have much of an opinion. S100 has shown results in murine models but then again, what hasn't?
Qure do not seem to show which AAV serotype they're using, and no indication of mode of delivery of the virus. A cursory check says they're looking to enter the clinic in 2016. Safe to say that there are still some steps left to take.
So at this time, your guess is as good mine.
Re: CLDN
BNP is correlative to disease, but I think there is significant concern as to whether or not it has a causal role. I wouldn't base my investing decisions on it.
I think notwithstanding all these endpoints and markers, there are some easy questions to ask of any possible drug intervention:
1) Does it do what they say it does? In the case of CLDN's AAV, it does not increase SERCA protein expression in the pig model.
2) Is it dosed reasonably? From the brief calculations I posted*, it isn't dosed reasonably.
So you have an intervention that doesn't seem to do what they say it does, and it's not dosed reasonably. At that point, does BNP matter?
* Corrections welcome. They were done quickly.
Re: Celladon
Not sure how important the persistence of the vector is (a metric mentioned in the PR linked below), if it won't transduce, but how do you explain the apparent success in meeting actual clinical endpoints of the CUPID 1 trial? Your thesis suggests to me this should already have flamed out in the clinic.
Re: Myokardia.
Ah yes. I misunderstood your post.
FWIW, the people working at Myokardia have overlap and/or have transitioned from CYTK. The mindset seems similar to CYTK, so I'm dubious that the results will prove better.
Re: CLDN
I've harped on about this one on twitter, likely to the point of boring readers.
I've worked hands-on with AAV (serotype 9), and I know from first hand experience that the doses CLDN is using in humans are high doses for a rat. These doses are insufficient for a dog heart, let alone a human heart. Dosing does matter, since these AAV are replication defective, so dosing needs to scale with heart size.
Second point is that intracoronary bloodstream administration is not effective in large animals. In the dog, intracoronary does not work whereas in the rat it is highly effective and cardiotropic. Some of it has to do with the tissue tropism of the virus. However, we found that if the virus isn't directly injected into the myocardium, you see no expression. At the near placebo doses that CLDN uses, their wishful delivery method will assure very little transduction.
Their papers also do a very poor job of convincing that large animal models show actual expression. In fact, one of the papers using pigs shows that SERCA protein expression does not increase following AAV administration.
That's just a weak structure upon which to build a clinical program.
Re: Cardio3
Their concept does not seem totally outrageous though!
Re: BMY etc...
Did you mean SNY and Myokardia (rather than BMY)?
Re: Cardio3
Honestly, it's junk. I know it well... almost too well.
I wish their patients the best.
Re: heart failure / gene therapy success
2. Heart failure explodes on the biopharma scene with gene therapy success
Who is working on it? What projects are in the works? What are they targeting?
Re: INCY
Whooo!
Obviously there is much more to consider here, but INCY has been on a run lately and this may have been a significant driver.
I think they can take market share from Xeljanz in the short term. Biologics, unlikely any time soon.
SRPT:
ive met with the FDA many times. they are conservative, but generally consistent (unless there is a division change). they have always been open to push back for me.
SRPT:
At this instant, yes. But in an AdCom I'll bet 10:1 other items pop up as big as this. E.g. :
Re: SRPT:
I don't think we should be too surprised that the FDA's major sticking point looks like the dystrophin quantitation data.
Honestly I'm still floored by the shoddy data SRPT released to the public in this regard. Was it willful disregard, laziness or just outright ineptitude?
SRPT:
Well, the duplication didn't help but I was disenchanted before that.
I really did not like the quality of their Western blots. I would not accept that from a summer undergrad, let alone a biotech company. That made me very skeptical about the general quality of their work, and whether it was trustworthy as you usually save your "best" image for presentation.
Also, the "% of fibers that are dystrophin positive" was very hokey and could easily be manipulated when doing immunofluorescence.
In effect, I found none of their dystrophin data remotely comforting. That was a dealbreaker for me, because I actually believe in dystrophin as a valid surrogate.
SRPT:
For me, D started my skepticism. But from what I could observe on the outside (never any position), the company definitely used F to their advantage because young children are impacted. We can argue whether or not the company was explicit in pushing this angle, but it was interesting to see many skeptical biotech traders and investors in my Twitter feed re-tweeting the daily progression of a few of the kids in the trial. I think many people became rapidly invested emotionally in the story.
One thing is pretty clear. We cannot trust the government, health authorities, military, politicians or press to tell us the truth.
Lying is pandemic. Given that, the scaremongers are left with fertile ground to sow seeds of fear.
Shkreli's comments...
There are some gems in there:
- "I make drugs for dying kids."
Obvi. Who can disagree with that? Now that I know it, I think he should double the price above and over the first 30x.
- "We asked patients and physicians before we raised the price of Thiola and they blessed our move."
Blessed the move! Not simply approved, but divine providence.
- "In the United States of America, patients do not pay cash for drugs. Insurance pays for drugs."
Yes. Insurance. That nebulous entity that is completely dissociated from patients and people, that simply prints money out thin air without any impact on society.
- "we make drugs for dying kids."
Recurring theme. At least he added a few more contributors this time and changed the 'I' to 'we.'
I don't understand why you would prefer a huge short-term dump to a 10b5-1 trading plan. This is highly unusual activity for a CEO and I would be pissed if I was a shareholder.
I don't think you meant that RTRX is "rent seeking," which refers to a company devoting resources to influencing politicians to bend the law to favor its products over those of its competitors.
RTRX:
I would argue two directions on this. First, there is value-add beyond approval (in many ways beyond what I will suggest). Second, Profits and Capital Allocation - our system allows pricing freedom and relies on market functions to operate on pricing (generics and competing products) and capital allocation producing profits that are a key driver of capital allocation promoting drug development in next-stage growth.
The amusing thing to me is that many of the people (scientists) who benefit the most from this state of affairs, are oblivious to their benefactor.
Of course, then the 2,000 would not get treatments. There is no free lunch and when government makes approvals cost hundreds of millions, those costs will get paid or the work will not be done.
The beauty of being a biotech investor is you can be an altruist and potentially make a buck along the way.
I have my doubts about that - this stuff is viewed as cutting-edge, and hospitals are likely reluctant to give it up even if it can be done more cost-effectively elsewhere.
Re: FMI
One intangible into the model is that over the next 2-3 years there will be some attrition on the part of medical centers who currently do their own genotyping for specific / limited targets. I think that cost cutting / outsourcing efforts at these centers will begin, sending more work to FMI.
TRVN:
I've followed and interacted with the scientists that spawned this company. Impressive group (including a nobel laureate), but I have reservations about their cardiovascular program. The science behind it is intricate, but I think it tries to make too fine a point of extrapolating from their cell culture experiments.
I'd be pleasantly surprised if their CV agent TRV027 makes an efficacy impact. I know nothing about their pain programs.
While the outbreak hysteria might have similarities between the two, but impact on the companies will be quite different IMO.
TKMR: Ebola commercial prospects?
Not clear to me that the newer antibodies have a "fusion" like the lead drug. In any event, I realize this is very early stage work and plenty could go wrong but at just over $100M fully-diluted market cap and one of the only public ways possible to play what sounds like an emerging target in CD47, I'll continue to take my chances, for better or worse.
What does the term, de-immunized signify in this context? T.i.a.
Not sure what you mean here as producing immune response is exactly what IO is....is it not?
$ENTA
$TGTX
$SCTPF (After r/s and nasdaq listing)
But thats just me.
G$
FWIW I bought some ENTA and GILD today at close, will buy more if they go to $30 and $60 respectively.
INCY CC Notes:
- Early comments were focused on Jakafi sales. Salient facts for me were that the use of 5 and 10 mg doses are increasing, suggesting that their education efforts in starting patients off at low doses are being adhered to.
- They note that 1/3 of prescriptions now are from docs who are new to prescribing, a number that is falling. That suggests that the MF market for jakafi is maturing and most that are prescribing have had a history of using the drug with their patients.
- They have updated the authorities on the survival data from Comfort I and II and are expecting to hear back in regarding to having survival information added to the jakafi label in 3Q14.
- Sales projection of around 320 million next year. The guidance is available in the PR.
Upcoming Trials and Data:
- They're working to develop the Jak1 inhibitor 39110 in 2 double blind trials in nonsmall cell lung cancer using two different regimen backbones
- From the P2 pancreatic cancer RECAP study, the subgroup information will be released at ASCO. It is being termed as a marker that is reflective of "tumour induced inflammation"
- For this indication, two phase 3 trials will be running (Janus 1 and 2). The first trial is under an SPA with the FDA and will enroll only the pancreatic cancer subgroup that was identified for benefit in the RECAP study. The SPA does not require validation of a companion diagnostic for the subgroup marker.
- Although the first pancreatic P3 trial has an SPA, they are running a second trial to both increase their change of regulatory approval, and because the second trial has more symptomatic benefit endpoints that they had not had time to incorporate into the first trial.
- Both trials will enroll ~300 patients and have overall survival as the primary endpoint
My take regarding this program is that they are not confident in relying on the SPA for approval based on one trial and are therefore running a second nearly identical trial to improve the package. Still lots of speculation on the marker that defines the subgroup, but these trials will address its validity.
- based on the RECAP subgroup, they are running trials of jakafi in breast, nonsmall cell and colon cancer. All three are enrolling based on the RECAP subgroup, but the colon cancer trial is enrolling in 2 groups, one that meets the subgroup requirements from RECAP and one that does not. They noted that the breast and nonsmall cell trials will not be sufficient for approval, but noted that the trial in advanced colon cancer may have an outside shot if the data are unequivocal.
Jakafi in polycythemia vera:
- I thought this was the most important part of the CC. They expect the phase 3 trial to provide top-line results in March / April and, if positive, an sNDA in June
- they note that the addressable population in PV breaks down as such: 100K patients are diagnosed and treated, mostly with hydroxyurea and 25% of those are resistant / intolerant or progress from hydroxyurea and are the targeted population for the PV trial
- they noted that sales in PV are not part of 2014’s sales guidance
My note from this is that the previous PV phase 2 data for jakafi was very encouraging, and I think the soon-to-be-released P3 data have a high chance of being positive. If the data are available promptly and they’re able to execute on the sNDA filing expeditiously, there is a possibility of sales contributing to the bottom line this year. More importantly, sales for 2015 could rise significantly from 2014 if PV is approved. I think this indication provides a good chance for improving INCY’s performance over the next 18 months.
Amusing note: the new CEO, Herve Hoppenot, sounded very much like the stereotypical Frenchman speaking English in Monty Python’s Quest for the Holy Grail. Unless I missed it, no one on the CC was taunted ey se-cond tay-mah.
MDVN / Xtandi
I am not sure I understand. By looking at (the smoothness of) the time to chemo graph, I can see that a large number of patients used chemo in the Xtandi arm.
My guess is that less than 5% of pona's lifetime sales will be from indications outside of CML.
GIST is competitive so that's a tough road. Pona hits various kinases upregulated in other cancers, but I'm not sure that investigators have the stomach to explore with pona given the publicized safety issues.
The caveat to my opinion is that from conversations around my circle, the issues that derailed pona were non issues. In other words, there were no complaints of unexpected CV events above and beyond that seen with other 2nd gen inhibitors. That may be due to a myriad of reasons as different places have different treatment strategies. But I should also note that from these conversations I was more bearish on pona than most insofar as the timetable for sales. No one around me was willing to use it in first line absent strong survival data.
pphm's trial wasn't preclinical... screwed up, yes...but preclinical, no
whether fast track is worth anything or not, has the fda ever granted it to a drug which they don't believe has shown efficacy in earlier trials?
can anyone answer that question rather than one i didn't ask?
GERN / INCY
Yes, unless INCY closes above $40 next friday.
And before you say it, yes I'm talking down GERN on the internet because that will protect my INCY position!
Seriously though, there is nothing controversial in what jq and I are saying. The data are written in the abstract and the response criteria are clear. You'll note that in the Sanofi JAK inhibitor abstract from that group, they note the spleen responses.
And seriously your hematologist should know about Jakafi's survival data. That ain't no joke.
GERN:
I suggest you (and iwai) read it and then tell us what you think.