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Rdunn, are you discounting Adam Feuerstein? I think that his piping in on Mako's side is still hurting the share price.
What is this fuss over Dana Farber?
Dana Farber has currently 18 trials involving ovarian cancer in some form, at least 2 of them P3. Beth Israel seems to have 3 more, one P3. Did it ever occur to either of you that recruiting subjects might get tight in Boston area? And leave it at that.
As far I know the area is not ovarian cancer hot spot, but, naturally, and inferring from the importance you put on DF involvement, you might know better. In which case I recommend that you contact NIH so that they can investigate further. We, here can't really do much about emerging cancer epidemies, expect cringe and be happy that, at least, we are not, well, Bostonian ovaries.
Also Dartmouth and Mary Crowley are not exactly candle lit backroom operations which sort of can be, again, inferred from the importance you put on DF involvement. But, naturally, you may know better. In which case I recommend that you enlighten NIH also about this matter. They might want to revoke some designations before things get really embarrassing.
I recommend that you settle this dispute the gentlemen's way reserved for this level of silliness. Stand opposite sides of unvarnished and unleveled pine table (white pine is looked down upon in better circles, which perfer to do the operation on mountain varietals) and open your zippers at the count of three.
No clear idea. Radiation with taxanes or anthracyclines seems to be associated with relative high rates otherwise I really don't know. This gives some ideas about who and when somebody might get OM.
Thanks M. That means about 100,000 new cases per year in US and EU combined. Nice market size.
ffrol, agreed, but let's put some more flesh on what happens.
After agreeing on CDA (which itself can take a month to get done) the buyer will spent time going thru all the data IPIX handed over, doing general due diligence of IPIX, maybe even making site visits to interview trial runners. Some dudes need time to crunch numbers for
1. Estimates for timelines and likelihoods for successful commercialization (P3:s and approval processes)
2. Estimates for future sales
Estimates are then combined into something called risk adjusted net present value (rNPV). After that comes a low ball offer to see if Leo takes the bait. Leo probably counters with moderately outrageous ask (if not, he should be replaced as CEO).
While the buyer has been spending time to get to the initial offer things that should be happening on the seller's side:
- Entertain all comers and make sure the suitor(s) you value the most do know that they are not the only one(s) after you goodies.
- Fake (artfully) additional interest if needed.
Offers get generated and countered until there is a deal or deal falls through. Only after there is an agreement in principle will the lawyers start filling in the details.
Meanwhile on the retail shareholder boards.
WHAAAA! it has been what, 33 and half days AND NOOOOO DEEEAAAL! Losers!!!!
I don't think Leo ever quoted upfront values for licensing deals. He used total values. That is customary.
Yes, all that. Upfront payment would probably be sized to take them comfortably through FDA's approval for trial design, in which case a loan might not even be necessary.
Rdunn88, you may be right, but it could also be Leo playing suitors against each other in order to get what he wants.
They say that the best way to grow your research is with somebody else's money. Vertex is a splendid example of that.
Maybe 20 M$ upfront does not move SP, but, say,
400 M$ in total payments + royalties just might.
Generally, if a deal happens, we will know those 2 things: upfront payment and the total value of payments. Anything in between the upfront payment and commercialization gets known when payments are made. Exact royalty percentages are seldom publicized.
Keep in mind that upfront payment is usually play money for the management - not tied to any performance clause. After upfront payment comes bigger structured payments starting, for instance, with initiation of phase 3 trial.
A partnering deal with 20 M$ upfront payment sounds reasonable. One publication had these numbers for 2013 published pharmaceutical partnering deals per drug development stage:
stage : median upfront payment in M$
preclinical : 10
Phase 1 : 17.5
Phase 2 : 20
Phase 3 : 25.0
I don't think that the pricing has changed much since.
I think so, too. The only one of the whole bunch.
Soligenix has money problems,
Monopar has money problems,
IPIX has money problems,
but probably not GALERA.
Finally - It is all clear now. They are all calculated over ITT.
Great find KMBJN. I found the peace thanks to you. Figure 1 was the key!
Well, incidence numbers do look good - about the same as with GC4419 and Dusquetide, which I think are the two serious contenders. Brilacidin's delay of onset also seems to be similar to GC4419. I truly wish that Leo had released duration numbers. He didn't, sigh. Dusquetide had reduction from placebo 18 day to treatment 9 days. GC4419 median duration is probably what they say 1.5 to 2 days, maybe 3, but likely not more. These numbers are all medians calculated over ITT.
So, if brilacidin duration reduction (my guess) is 30 % or better we should be fine because Duesquetide has the problem of very low incident rate reduction (6 %), which may trip it's commercial changes.
It seems that IV drugs, for some reason have better duration numbers that oral. Even Kepivance scores medians of 4.5 and 5 days. But, then they have much higher risk of drug interaction (doing Kepivance in one indication revision at the time) than oral drugs. It is sort of wash - nice duration, if you can have it vs near certainty of no drug interactions but longer duration of SOM.
I guess there is room for both B and G.
BTW: check KMBJN:n post. There is a nice link to some earlier results with GC4419. That cleared me how GC4419 numbers are calculated. The article you found probably suffers from misunderstanding by the reporter.
ffrol,
I have a theory that Kepivance's blood cancer trials with SOM incidence rates for placebo at 98.1 % and 80 % created this expectation that incidence rate in placebo arm should be high. If you take only head and neck cancer trials placebo arm SOM incidence rates are
Duuesquetide: 73.7 %
Validive: 58.1 %
Kepivance head and neck 1: 66.0 %
Kepivance head and neck 2: 66.0
Brilacidin: 60.0
GC4419: ~ 58.0
As you can see only Dusquetide trial had placebo over 70 %.
I Smell Fish Market. But start is with relevance.
Dear ffrol, HPV+ is not irrelevant if you compare GC4419 performance to drugs in other trials. HPV+ skews the comparison in favor of the highest HPV+ proportion.
Little backgrounder on SOM vs Radiation
SOM emerges when cumulative radiation dose in ORAL CAVITY (not on target) exceeds 40 Gy, incidence rate and intensity correlates with mean radiation dose > 50 Gy and maximum dose > 65 Gy. What little has been reported of duration seems to be this: longer durations are associated with doses exceeding 40 Gy, which sort of follows from the preceding sentence.
From Kepivance to GALERA
Head and neck cancer trials with Kepivance included subjects having cumulative radiation dose less than 50 Gy. Still, the trials had mean cumulative radiation doses 68 Gy and 60 Gy. Compared to these means GALERA's 60 Gy cap does look strange. But strangeness does not end here.
The Kepivance trial with 68 Gy mean radiation doses in both arms recorded also these facts: in the placebo arm the median duration of severe OM for intent-to-treat population was 26 days, and for subjects who had severe OM the median was 37 days.
Now, Your 'find' purports that in GALERA's trial the mean calculated for placebo subjects with severe OM is 19 days. Really?
Median to mean ratio for exponential distribution is Ln(2) or about 0.7. OM duration distributions usually have fatter tails that exponential distribution i.e. the ratio is even less. Let's use Ln(2) as upper limiting factor for median to mean ratio.
We can now calculate the upper limit for GALERA's median duration for subjects with SOM in placebo arm: 0.7 * 19 = 14 days. Whoa! At least 62 % improvement over median for subjects with SOM in placebo arm of Kepivance head and neck trial. And more than 46 % improvement when compared to median calculated over ITT.
You can interpret the upper limit value in several ways
1. Subjects in GALERA's trial were very, very, very though
2. Something else is at work in the trial, and administered at least to placebo arm. Probably also to experimental arm.
3. Mean radiation dose across GALERA's trial is really measly
4. Or the usual: Fish Market
Enjoy.
A Cheap and Dirty Trick. I like It.
Below are traditional Kaplan Meier curves for Brilacidin and placebo PP subjects. Except I multiplied populations, events and censor by 3. A downright dirty way of making the graph more comparable with GALERA's trial. In order to mask my shenanigans as educational I have included at risk curves (dashed) to demonstrate the effect (and the lack of it) of censors. I wish that Leo provided event and censor data also for ITT populations. But we take and distort what we can (old pharma marketing motto).
Individuals easily offended over presumably unfounded optimism should take a look at hazard ratio and p value. Please, do enjoy your day.
Great find KMBJN. Thanks. Most subjects HPV+ positive. Virus is driving the cancer -
That is treatment friendly!!!!! Faster recovery, shorter SOM durations. This was pointed out on critique of Kepivance trials for SOM in head and neck cancer back 2012. One reason why Amgen probably canned the idea to go to FDA for expansion of indication for Kepivance. If the same is true for P2 trial then it is getting hairier and hairier with GALERA's GC4419. Meaning, only gods know what the big time H. is going on.
Well, meaningfulness of median and averages depends on what is reported. SOM trials report (when the bother) duration median against intent to treat population, which becomes silly if you don't have events to hit 50 %. Median will be zero. Also, median does not tell you the distribution shape. People tend to assume that it is exponential. In case of SOM it is anything but. Average does not tell you shape, either. But it tells you what is the area under the distribution curve. That is always useful.
The thing is a bit different if median is reported only for subjects experiencing SOM. Then it has meaning (even to me).
Scottsmith,
Yes, I walked back a little. Eventually there is too little exact information to make any reliable conclusions. My opinion of GC4419 hinges on one word "average". If GALERA really reported duration improvement based on average duration as described in one news report then GC4419 is very likely a great drug. But if the reported improvement is based on medians then GC4419 is still a good drug, but not much different from the others.
Galera's website is currently inaccessible (at least to my Chrome) but Google cache got me this:
Galera Therapeutics Reports Statistically Significant Results in a 223-Patient Phase 2b Trial of GC4419 for Severe Oral Mucositis in Patients with Head and Neck Cancer
• Achieved primary endpoint against placebo (p=0.024) demonstrating a statistically significant and clinically meaningful reduction of 92 percent in the duration of severe oral mucositis (SOM)
Secondary Endpoints Consistent with Primary Endpoint
• GC4419 reduced the incidence of SOM through completion of radiotherapy by 34 percent (p=0.009)
• GC4419 also achieved a 36 percent reduction in the overall incidence of SOM through 60 Gy of radiation (p=0.010)
• GC4419 reduced the incidence of debilitating Grade 4 oral mucositis (OM) by 47 percent (p=0.045)
plus:
As reported in December 2017, top-line results from Galera’s 223-patient, double blind, randomized, placebo-controlled Phase 2b clinical trial demonstrate GC4419’s ability to dramatically reduce the duration of severe OM from 19 days to 1.5 days (92 percent)
Then there is ffrol's find with some additional (interview?) information:
Patients in the placebo arm endured having severe oral mucositis for an average of 19 days, whereas the group of patients who received the 90-mg dose of GC4419 only experienced the side effect for about a day and a half – a 92 percent reduction.
Severe oral mucositis occurred in 58 percent of the placebo arm, but in only 40 percent of patients who received the 30-mg dose and 37 percent of those who received 90 mg.
Where did that word insert-text-here come from (this IS the only place it shows up)? Is it reporter added color (sentence looks like it), or not?
Summary of problems that make evaluation of GC4419 hard
- are we talking about averages or medians?
- no minimum or mean radiation dose reported
- lowest reported (with Validive) incidence rate in placebo arm may indicate lower mean radiation dose as was the case with Validive. The same goes with reported duration of SOM in placebo arm (if it is median).
Another thing to consider:
GC4417 is IV drug which adds logistics and cost complications to evaluation. I am not fond of putting a person into IV in order to prevent the person ending into IV.
Why I am so keen on average vs median? Well, average has one great advantage over median - if you know the average and number of subjects you can calculate a measure often called total patient/treatment time (ie. area under the curve). You can't do that with median and number of subjects, you need to know also the shape of the distribution. Insurance companies love averages for treatment durations because those enable them to create metrics (in their case - cost metrics) and compare various treatments. The same goes for me.
BTW: I took IPIX brilacidin PP Kaplan-Meier curves for incidence rates and multiplied populations, events and censors by 3 to get headcounts close to what GALERA had. Guess what:
Relative risk reduction is (still) the same as for GC4419 thru 60 Gy, 36 % and p value = 0.0020. But GC4419 would probably eat Brilacidin's lunch in SOM duration. But then there is that IV thing with its complications and additional risks. In sum: if both get approved there should be room for them both.
Cheap and unfair comparison, I know.
Hi, F1ash,
They could have filed a drug marketing application with FDA and with the approval probably gotten some exclusive rights but they chose not and probably go with only trademark protection. One reason, of course, is that providing evidence is costly (trials etc..) but also that then they would have to prove efficacy.
Also, they are abusing FDA terminology in their marketing - there can't be phase IV after marketing approval study if there was not marketing approval based on phase III study. You know, if it smells like ...
Ffrol, Your find may change everything, or not.
Your tidbit uses term 'average' instead of median for durations. That would be the first. So far all other reported measures comparing OM durations have been using medians, which is, in my opinion, very misleading when the duration distributions are fat tailed as they tend to be with OM.
But, if GALERA is reporting real averages then...
The reduction reported would be immense if it is FROM AVERAGE of 19 days with placebo to AVERAGE of 1.5 days with GC4419.
But there might be a problem brewing...
I can't find the word average in any other report about GALERA's trial results.
Galera's site is currently inaccessible but Google cache shows no word average in the item on Galera's own site. See this:
"Phase 2b clinical trial demonstrate GC4419’s ability to dramatically reduce the duration of severe OM from 19 days to 1.5 days (92 percent)"
and the same in here.
It looks like your quote is the ONLY one using the word average as if the writer had decided to add some color into otherwise dry report.
Let's see how this will go:
If GALERA is REALLY reporting real changes in real averages then Leo has reasons to be worried, not desperate, but worried.
If the reported values turn out to be medians then it is the same old garbage, and not that much better garbage than what was reported for Kepivance
Surprise, surprise
Several of currently marketed OM treatment are approved under medical devices, which mean they really don't have any proven (to FDA), biologically significant effect. I truly doubt the claims made by Mueller Medical (all publications in 'scientific' journals (like nursing navigator) seem to be by the same guy).
Notice their nice caveat 'if prescribed in timely fashion', which is hardy a medical term. The company can argue a lot things not fulfilling the meaning 'in timely fashion'. Are they outright lying? Who knows? Stretching the truth? Very likely.
Prothelia has not gone thru any efficacy scrutiny by FDA. It was approved for marketing based on the fact that it is sufficintly similar to stuff on market since 1976. Period.
Oh, The GALERA trial is growing more hair. Thanks, cabel, should have checked clinicaltrials.gov by myself (I blame overt excitement and need to get my salt bath like now!)
Some OM trials exclude the use of IMRT method of radiation, some don't. GALERA's may the the first that specifies it exclusively. Modern boys and girls over there.
IMRT is more accurate in targeting tumors and hence radiates healthy tissue less than traditional radiation treatment. Also, in IMRT radiation doses do vary in intensity and the subjects may end up averaging less radiation over time.
GALERA says 60 Gy over 6 to 7 weeks, minimum. Traditional is about 70 Gy over 7 weeks. Notice also specific 'delivered to the tumor'. In studies accepting or sticking only to traditional radiation treatment (like in IPIX trial) you usually see 'delivered to oral cavity'.
Next, guess if your find makes the results more comparable or less comparable?
I guess you will guess right :)
As I said elsewhere it is not. It's garbage. And depending how they calculated the p value it might be utter garbage. If their p value is based anything else than Log-Rank type tests or some Cox model (i.e. assumption of near normal distributions) it might survive peer reviewed publication but FDA will not be impressed.
Yes and no. They had about 70 subjects per arm. If relative risk ratio is of order 0.75 (as they are reporting) then p-values should be impressive in that size trial. What is not so impressive is that the drug seems to work better with cumulative radiation below 60 Gy. What were the percentages for subject with radiation above 55 Gy, which is what IPIX and Soligenix reported? We don't know.
BTW: IPIX had (IN A SMALL TRIAL = TAKE IN WITH PLENTY OF MENTAL SALT, head counts per arm about 30 % of GALERA's) relative risk ratios 0.72 for all subjects receiving over 55 Gy radiation and .45 for their mysterious per protocol group.
So assuming that above numbers will hold in the future:
GC4419 seems to be, at best, as good as Brilacidin and if my hunch that it works better with low radiation doses is accurate - not as good as Brilacidin.
DO not put much value on the 96 % reduction in duration. Calculated in similar manner Brilacidin had duration reduction of 100 %. Those numbers are based on medians and are, by their lonesome, utterly, frivolously useless.
For those nitwits (there are bound to be some) who come and say that I can't say anything about Brilacidin SOM durations and particularly about median duration. Wrong, I can. Follow THIS:
These medians are based on ITT population, not on the number of subjects that had SOM. So, if less than 50 % of brilacidin subject had SOM then the median duration of SOM with Brilacidin can't be above 0 days because more than 50 % had SOM of ZERO duration. Clear?. Reduction from anything above zero to zero is 100 % reduction, always. Clear? GC4419 DID not have 100 % reduction but 96 % reduction AND that means more than 50 % of subjects treated with GC4419 had SOM. Clear?
Of course, there is slight chance that GALERA's scientist are completely off their rockers (that might explain 60 Gy fixation, for instance. A nuthouse) and are reporting reduction based on, say, 1st or 3rd quartile.
I hope that made it clear that reporting these types of reductions should be made criminal offense.
About Galera SOM trial. Difficult to say how comparable Galera's trial is. For indecipherable reason they introduce results below 60 Gy with slightly better incidence reduction than overall (36 vs 34 %). Stressing results below 60 Gy is strange, because the traditional target for cumulative radiation in treatment of head and neck cancer is 72 Gy making 60 Gy subjects about a week shy of full treatment.
IPIX and Soligenix, for instance, excluded from analysis everybody below 55 Gy. Making any comparison to Galera at this point useless.
BTW: Galera had more than 200 subjects in phase 2b trial. Not much to quibble about the size.
In the past Novartis has been associated with privately held Galera Therapeutics Inc from Pennsylvania USA. Last December Galera DID publish promising results for phase 2B trial in severe oral mucositis. Could possibly be the company in the austrian article. Slightly more detail about Galera trial here.
It's from my corporate site: PP's Excel workbook on IPIX.
Hot D., I can upload images.
If this works it will ruin me. Anyway, I noticed that people are starting to anticipate prurisol topline results. Maybe this image helps in the ensuing interpretational melee:
Old methotrexate is the king of nastiness (contested, thou. Sometimes it is not number of items in the boxed warning but Da' size!). Xeljanz is the undisputed king of cost and efficacy plus the crown prince of nastiness. Otezlas claim to fame is that is mild in every way.
As far as it is possible to say prurisol tracks Otezla favorably. I put pricing info in as a constraint on those with tendencies of seeing multiple billions.
Good luck.
In this case it total nonsense means data from similar historical clinical trials. Biased as they are.
Lesson learned: Never, ever sacrifice detail for brevity.
BTW: I mean that biased business.
Absolutely! That's the reason why I try to do some 'sensitivity' tests.
I calculate, if possible, at least
1. Some statistical test (Fisher's exact, Log-Rank etc.) to check for type 1 error (even if values are given, I try to double check). In this case, 6/18 or 6/19 vs 4/23, Fisher's two-sided exact test gives p = 0.289 or p = 0.468. Now I know that statistically speaking there is about 30 to 50 % chance that the prurisol phase 2a results are a lucky coincidence and 50 to 70 % chance that there is at least the difference of 31.6 to 33.3% vs 17.4 % in 2+ point IGA drops.
2. Check historical values for like drugs i.e. oral psoriasis drugs. The only ones that I found with near comparable results available are Otezla Esteem plus Liberate trials. I repeat results with a worst case correction I did NOT DO BEFORE (my bad).
Otezla vs placebo, sPGA/IGA response: Final IGA = 0 or 1 and 2+ point drop in IGA at week 16.
Esteem 1: 21.7 to 30.4 % vs 3.7 to 5.4 %
Esteem 2: 20.4 to 28.1 % vs 4.4 to 6.9 %
Liberate: 21.7 to 27.3 % vs 3.6 to 5.0 %
About that worst case correction and some other things. Otezla numbers include IGA 4 subjects, prurisols do not. Worst case assumption: Only IGA 3 subjects in Otezla trials satisfied sPGA/IGA response. That gives you the upper limits you see above. Note that All results are for week 16, prurisol results are for week 12. Eyeballing from available graphs Otzela scores improved slightly between weeks 12 and 16. Hence what you see are slight overestimates for Otezla when compared to prurisol.
So, I learned something, again.
A. Otezlas result are very consistent.
B. With worst case correction prurisol percentage is barely above Otezlas upper limits, but it is above.
C. The percentages for placebo in prurisol trial is well above that seen in Otezla trials. Maybe my assumption that all 2+ IGA drops in placebo happened in IGA 3 group is too harsh. That has consequences in Fisher's exact test. 6/18 to 3/23 gives p = 0.147 or p = 0.257. In this case there is about 15 to 25 % probability that the result is just a coincidence and 75 to 85 % change that the difference is at least 31.6 to 33 % vs 13 %.
The difference between Infinity and me is not that we do not agree about the above results. I think we do. The difference is that we see them differently. For Infinity the above is still too high risk, to me it is a risk worth taking. Currently we are in quantum situation: neither of us is wrong, yet. That gets resolved with P3 trial or just possibly earlier.
About a month or so ago, when I was still mulling over whether to write an article about IPIX I came across this trial. Otezla Unveil trial. It happens have ONLY moderate subjects, IGA = 3. So here is UNVEIL:
Otezla (n = 148) vs placebo (n = 78), percentage of subjects having PGA/IGA score 0 or 1 at week 16
30.4 % vs 9.6 %
The numbers for 2+ point IGA drop are also the worst case scenario for prurisol trial considering IGA 0 or 1 score. So let's repeat:
prurisol (n = 18 or 19) vs placebo (n = 23), percentage of subjects having PGA/IGA score 0 or 1 at week 12
31.6 to 33.3 % vs 13.0 to 17.4 %
So far, prurisol is, at least, tracking Otezla. And if the situation stays the same it is more than enough because prurisol has one major trump card. Otezla is immunosuppressant, prurisol is not. Prurisol is based on abacavir which is an antiviral. A slight exaggeration:
With Otezla psoriasis goes and tuberculosis comes.
With prurisol psoriasis goes and so does influenza.
Scottwny, it is a statistical conclusion based on trials being underpowered.
Think of it this way. The drug has a beneficial effect of some measurable size in the WHOLE patient population. A sample of certain minimum size is needed to ensure there is a reasonable probability the differences is present also in the sample (trial) population. The probability that the difference will show up in a given trial population is called power. A trial with 80 % power will miss the difference 20 % of times. If one wants to have 90 % probability that the existing differences is captured within the trial population the size of the sample must be increased significantly. And that is costly.
Few early p2 (p2a) trials have even 80 % power. For P3 trials 80 % is considered the bare minimum and hence 'bad form' - most P3 trials have at least 90 % power.
Correct Frrol. My artfully obfuscated point was that one should not put much weight on p values in low power trials (ooh, that should make Infinity happy!).
Infinity, patient numbers were in as ITT=
Well, silly or not, I, at least, need some comparable measures of benefit, even in small trials. Fractions, like 6/18, are probably better that percentages, like 33.3%, because the expression includes the population. And it is easy to compare 6/18 to, say, 4/23. One spots the difference instantly.
Of course it dangerous to compare results from 50 head trial to 500 head trial - only an ingrate would assume that the comparison is level and fair.
Unfortunately, one needs some kind of historical decision landscape and history is what history is.
Cabel, an anecdote about damage done with statistical significance.
Some years ago one fella (don't remember who and forgot to save the link) did a study about statistical power and statistical significance in early stage (p2) clinical trials. His conclusion:
Several probably efficacious drugs got short shrift and were abandoned because of too heavy emphasis on p value in small trials. His advice, if I remember, was either run larger trials if you can afford it or relax with p value.
So, there :)
Infinity I beg to differ little bit.
Yes, prurisol is the least favorite of mine in IPIX pipeline. But if it ever gets approved it has its own unique charms, besides being an oral drug.
1. Not immunosuppressant
2. Presumably low manufacturing cost
One month of abacavir 600 mg daily has gone below 500 USD, Otezla is around 3000 to 4000 USD montly.
As to big pharma investing based P2a data. Some even prefer to do it then - because of the risk discounted price they can get. Novartis went public not so long time ago saying they see prices for late stage developmental drugs as too high and therefore prefer to go after riskier but cheaper earlier stage drugs.
It seems that my percentages, delightfully, do annoy you. Well, in that case, I can't resist but put few more here. These are from Otezla Esteem 1 and 2 (you know, those pivotal trials) and may help explain why I am optimistic even with prurisol.
Esteem 1, percentages for 2+ point drop in sPGA/IGA
Otezla 30 mg ITT = 526; 21.7 %
placebo ITT = 282, 3.7 %
Esteem 2, percentages for 2+ point drop in sPGA/IGA
Otezla 30 mg ITT = 274; 20.4 %
placebo ITT = 137, 4.4 %
Is it only stupid me, or does it look like prurisol percentages from that little trial can go down a lot in P3 trial and prurisol still eats Otezlas lunch?
Cabel, I am like Infinity about 30 % of time, especially in the mornings.
I don't know about balanced opinions. Mine are skewed with my base optimism, which I need to keep in check. Guys like Infinity do help in that and I do appreciate it.
Infinity, thanks for comments. Some clarifications:
Slide 12, right graph is for 200 mg PP group of 20 total subject. 65 % or 13 them were IGA 3. This is the group IPIX refers to in the press release: 46.2 % experiencing at least 2 point drop. That 46.2 % gives 6 subjects. 7 out of 27 refers to all responders in ITT and includes original IGA 2 and IGA 3 subjects.
ITT numbers I used come from the table in slide 9. It says for 200 mg group that 9 were IGA 2, 18 IGA 3 and 1 subject with missing baseline value. You have a choice of two baseline values for 200 mg IGA 3, 18 without the missing subject or 19 with the missing included. Totals for 2+ point drops are from the table in slide 10.
Percentages for 2+ IGA point drop for 200 MG IGA 3 Group, PASI 75 percentage probably the same or a bit better
6/18 --> 33.3 %
6/19 --> 31.6 %
Making investment choices based on results from small is risky, very risky. I don't deny that. But small P2 trials are a fact of life with almost all small biotechs. Don't make IPIX sound like an exception.
Anyway, I rather risk my money based on good results from a small trial than on bad results from the same trial. There is a difference.
I just did a screen on common US stock (no ADRs):
Industry: Biotech and Pharma
Revenue TTM: 100M to 2000M
Revenue Growth TMM over TTM: < 200 %, to cut off cos having a insane revenue jump TTM over TTM
Surprise: Average price to sales ratio still about 9 and average revenue growth 23 %.
Apply that to future IPIX with 1 B$ revenue from one drug with growth potential in excess of 23 % year over year, which IPIX should be able to achieve easily with the rest of its pipeline. You get
potential (and conservative) market cap 9 billion. Let's assume 200 million share (now about 140 million).
That gives for potential (and conservative) share price 9000/200 = 45 bucks.
Version 2: Assume 15 % royalty income. That is 150 million. But this income goes directly to earnings (no cost of goods etc). Can't use price to sales ratio because it does not apply here. Must use P/E for 75 cent per share earnings. Screen gave average P/E 50.
That gives future IPIX (conservative) share price of 37.5 USD.
I have to agree, it is rare to see premium over 200 %. One caveat: often there has been a run up on the SP before the buyout announcement.
However, it seems to me that everybody is thinking that the choices are either partnering or buyout. Folks, there is a third option, which might be the best option for IPIX (if they can make it happen) - sell one product line for a cash payment and use the money to develop the remaining two. At right price probably the best way to increase market cap.
Some people who were in much better position to know what they were talking than I ever was mentioned to me this quick drug pricing estimate ie. how high big pharma might be willing to go:
Price cap for a drug with FDA approval or perceived high potential for approval: about 2 to 3 (I have never heard of higher multiplier than 3) times the expected peak yearly sales. Drugs not yet on the above near risk free stage will have a risk dependent discount factor on cash value payment or heavy reliance on payments based on commercialization milestones and royalties.
So, if IPIX manages to sell or partner something most of the money is likely to be tied on milestones and royalties. And my idea of selling a product line for cash is probably a pipe dream.