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Thanks LR. I am bit surprised of Penn not being overtly greedy. Otherwise, section 5.3.2 and 'Trigger Events' seems to be part of Penn standard patent license agreement. At least Aegerion Pharmaceuticals has similar language in their agreement with Penn:
https://www.sec.gov/Archives/edgar/data/1338042/000119312510184678/dex106.htm
As does Sparks Therapeutics:
https://www.lawinsider.com/contracts/4QSLK2FqxkFEt8Jjpc73cs/spark-therapeutics-inc/1609351/2014-12-11
About $15M to $25M if Da BP is a skinflint willing to fund only first p3 trial and second trial funding is tied on how the first went. $30M to $50M if upfront will cover 2 phase 3 trials.
Useful source for ballpark numbers:
https://www.centerpointclinicalservices.com/blog-posts/driving-drive-drug-innovation-and-market-access-part-1-clinical-trial-cost-breakdown/
I it is more of your choice No 1 than 2. You may see differences between trials in which systemic drugs and dosing schedules are allowed or not and also in radiation schedules plus thresholds for 'evaluable' subjects, but that tends to be it. BTW: Some (protocol) elements were added due to the criticism of Kepivance HNC trials - stratification for HPV, for instance.
Water for injection: sterile, filtered or distilled water.
Why only 3 mg/mL concentration? It is possible that 3 mg/mL concentration comes as 'inheritance' from Polymedix - they tested Brilacidin against SOM in mice and found concentrations 1 mg/mL, 3 mg/mL and 10 mg/mL effective with not much efficacy difference in between them. I have not seen reports about safety or side effects. That's as far as my knowledge goes.
It seems that I am wasting my time. One final point. I think it was more out of fear of possible failure of Brilacidin when compared to Galera's drug that IPIX may have waited for more details from GC4419 trial. No strategic plans, just plain old fear of failure; why would FDA grant a BTD for an inferior drug to one they just awarded the designation.
Approved only to be used with ... doxorubicin. AS it says on the webpage you linked to:
The recommended dose and schedule of olaratumab is 15 mg/kg administered as an IV infusion over 60 minutes on days 1 and 8 of each 21-day cycle until disease progression or unacceptable toxicity. For the first eight cycles, olaratumab is administered with doxorubicin.
More likely the potential suitor is checking if the dining set included in the dowry is real silver or just plated. (patent rights).
Think for a while. Galera already had BTD before B data got finalised. If B had turned out to be clearly inferior to GC4419 then what that might have done to IPIX's changes of getting BTD out of FDA. Improved hugely, or gotten worse?
I am not saying that IPIX did wait for Galera divulging more details. I am saying that to me that makes sense. I feel that is more than can be said about most other scenarios bouncing around here. Usually posters and abstracts are available on-line a week or two before a conferences begin. IPIX would had had time to peruse Galera's presentation, be less than impressed and decide that it is worth trying for BTD.
Hi TIAB, maybe delay was because IPIX waited to get more details about Galera's GC4419. It is much better to go to FDA meeting with solid comparative data (same applies, BTW, for BTD application). Galera presentation in June 28-30 2018 at Vienna provided enough (swimlanes - thank you very much for them) for reasonable comparison - something that any semi-capable competitive intelligence analyst at big pharma is able to perform in few days. I managed the same in slightly longer time and then forgot the whole thing.
But because you keep insisting I dug the stuff from my hard drive. Here are the highlights without much explanation. Sure the international pharma negotiating with IPIX has done something very similar and better; some of big pharma Co:s probably do have access to GALERA's patient level data. Novartis and Novo Nordisk for sure, due their generous funding of Galera.
First image is comparison between Galera's 'evaluables' for GC4419 vs IPIX's 'mITT' for Brilacidin. Probably the fairest active treatment comparison one can create based on available data. Kaplan curve for GC4419 is created from data that matches Galera's reported SOM median for GC4419, which Galera DID calculated using 'evaluables'.
Second image is for placebos in both trials. It should give one an idea how level this particular playing field is. A bit harder comparison to create due Galera's exclusion of about 10 SOM subjects with swimlanes from their median calculation. After some experimenting I came to conclusion that the curves have practically identical medians regardless how I selected Galera's placebo data or where I put those 3 additional SOM subjects not included in IPIX kaplan meier curves for PP population. Enjoy.
Agreed. A nasty and unfortunately common difference between big pharma and out of money micro pharma. On the other hand: how much did BMS SP move up the day after the announcement of these positive news? Less than one per cent. I expect a bit better performance out of IPIX if/when they announce positive prurisol results. I guess that might be the reason why we both (?) are still sitting on our IPIX shares. Bigger risk begets bigger reward. Most of the time.
Nice drug, but not earthshaking. So far BMS-986165 seems to have about equal or slightly better efficacy than oral Xeljanz and, from the numbers, worse nasopharyngitis and other upper respiratory tract infection rates --> Atta boy, BMS-986165, you seem to be a costly immunosuppressant, after all.
Thanks. Very clear clarification. I was thinking in terms of 'scientific DD'. My experience is from that side. I guess I shows.
Thanks, rmzport. In case you have not read Justfactmam answer to my post, please, read it. It is very good. I got schooled on these things ??.
There is a hidden assumption in your presentation. You assume that the subjects available for analysis were uniformly distributed according to the original allocations. If there were data collection gaps (available data not in order of enrollment) within the subjects uneven distribution of subjects and its possible consequences was a possibility that CRO was obliged to consider and report to IPIX.
We know that something happened with the trial, and early. What, I don't know, just pointing out a possibility.
Ah, but therein lies a mystery:
Quote from 10K:
"The Company signed a non-binding term sheet in August 2018 with a global pharmaceutical company for the licensing/rights to Brilacidin for treating oral mucositis and inflammatory bowel diseases. Initial payments, milestone payments and royalties are being negotiated in accordance with the non-binding term sheet. The pharmaceutical company is now engaged in further due diligence. Management can offer no assurances that the parties will enter into a binding definitive agreement."
How these things usually go is that the potential buyer goes thru all existing info forward, backward and sideways including politely and repeatedly interrogating any expert involved. Then if BP is satisfied comes term sheet proposal and negotiations over it. When both sides reach an agreement over 'the big stuff' comes the signing of the term sheet.
I don't get the order of activities in 10K. What due diligence BP is still conducting?
MackG, What you say would work if the p2b trial would have been your usual orderly clinical trial. We have ample evidence that it was not.
I hazard a guess that last summer IPIX/CRO had sizable gaps in data from early enrollment making inference impossible - a situation where you can't absolutely rule out that you are looking at unblinded data comprised mostly of subjects on prurisol (or placebo). Plus not having a complete info from early enrollment would have made any interim report an exercise in futility:
"We are reporting interim results based on a non-random sample covering about 45 % of the subjects (70 % of enrollment) that have completed the treatment so far. Arms are not yet as balanced as we hope they will be in the final report ..." ---> Red hot roar from certain corners of STAT/TheStreet: "LEO IS CHERRY PICKING DATA !!!!!!!!!" And they would have been justified (well, sorta).
As I said, just a guess. But, the fact that they DID NOT CAN the trial then and there gives me some hope. As far as I know clinical trial contracts with CROs usually include some kind of early termination clause(s).
Thanks, LR. I was waiting for this.
Rain squalls on the home ridge - there went my biking. But maybe a blessing in disguise ... we have a discussion here.
To me it looks like this CRO is using actual cost of work-unit completed for billing, not per-cent completed of fixed price project. Also, if IPIX has a fixed price contract for phase IIb clinical trial I would expect the total price had shown up somewhere in IPIX SEC filings, not just "we pay as they bill us" kind of statements with ever changing financial commitment.
Most importantly, with fixed price project I have in my mind it would be CRO eating the cost of overruns plus paying IPIX penalties for being late. My bet is Leo would have felt obligated to let us know about that kind of bad luck.
But maybe I am wrong.
I am leaning towards Ffroldo (had to get that out of my system) on this one - around $2M left to pay. It is likely that the $4M commitment does not reflect the latest payment made to CRO (~ $2M from Aspire deal). For one thing I have hard time accepting cost of statistical analysis alone being in multiple millions. Of course, if IPIX has been underpaying for some time now, the sum might be for trial analysis plus what was otherwise owed. A complicated mess. And...
We are witnessing why CROs so desperately wanted to get rid of fixed price clinical trial contracts. They were the bagholders then.
BTW: If IPIX and CRO were in arbitration would we know about that? Maybe Loanranger can enlighten me on all this. Meanwhile ... I really need some fresh air and inspiring sceneries - I go go biking now.
ffrol,
What do you make of this sentence on page 69 of 10K:
"The Company has total non-cancelable contractual minimum commitments of approximately $4 million to contract research organizations as of June 30, 2018."
You are reading it somewhat incorrectly. Term sheet negotiations is not signed term sheet a.k.a. agreement. IT IS negotiations over what should be in term sheet. Correct reading of Pullan’s pyramid from CDA on follows.
CDA ---> Request for diligence, dropout rate 60 %
Request for Diligence ---> Term sheet negotiations, dropout rate 50 %
Term sheet negotiations ---> Signed term sheet, dropout rate 50%
Signed term sheet ---> Signed full deal, dropout rate 40%
According to Linda Pullan IPIX is facing historical 40 % dropout risk. And, according to her has so far survived historical 90 % dropout risk since CDA stage.
He would with per completed task billing, especially when it looks like even the REAL specialist (CRO) did get it wrong. You seem to regard CPA:s as demigods when it comes to estimating clinical trial costs. Do they have some secret special training for that?
But, there is one thing I think you might be able to fault Leo for. IPIX failed to build even a small general financial buffer during Q1 2018. IPIX went to Q2 practically with zero headroom. I am unable to explain why. But then I am not a CPA or CFP, so I guess I am not required to ;)
I seems the bill for P results keeps ballooning, thanks to task basis for billing. CRO gives an cost estimate for a task --> IPIX attempts to scrap monies together and may even succeed, barely --> CRO bill arrives with sizable overrun. Put any over bantamweight pharma in place of IPIX and this CROw would be dead bird in water, but this CROw does know IPIX is flyweight. So, round we go, and go ...
In defence of the said CROw.The birthplace of this mess is at IPIX offices. ffrol's notion that cancelled interim was the first indication of a mess agrees well with my thinking.
How to create a clinical trial money pit in 10 steps or less:
1. Start a clinical trial and try to manage it with your own resources, which are far too small for the task.
2. Wait until mid enrollment before you admit that you are way too deep in manure
3. Call help - contract a CRO.
[narrative interlude starts]
timewise about here is the first indication in IPIX filings about any involvement of a contract research organization
[narrative interlude ends]
4. Because of the difficulties in estimating the cost for fixing the mess CRO will sensibly take the job only with per completed task billing.
5. Also sensibly CRO first concentrates fixing the clinical trial process and the data mess from early enrollment is left mostly as it is.
6. No interim report because there is no reliable early data available for interim report.
7. Clinical trial run ends.
8. CRO attacks the data mess from early trial stages.
9. Time and cost overruns ensue or "Look, it's a money pit".
Or partial payment, only. That might make CRO to plop its fat bottom on data.
Yeah. Being a slow poke, It took me some time before I spotted the stuff in 10K. Dr. Bertolino did discuss screening for HLA-B*5701 allele at least in one interview/press release. But you may be right: it is probably the first time it shows up in this level filing.
Thanks for education - never though upfront payment being encumbered. I would have made a really bad banker.
Thanks. For a while I thought that I am the only delusional one with a Biig problem: thinking IPIX is real company :) I wonder if SS sounds like DT. and I don't mean Delirium Tremens.
ffrol, I don't think a 'reset' is forthcoming. (big if part coming): As I see it the only thing IPIX should or can do is use 2017 purchase agreement with Aspire to fund few more months of operations (if they can) and to try to get the binding OM plus whatever contract done the soonest. Then use guaranteed upfront payment to secure a short term bank loan.
"The pharmaceutical company is now engaged in further due diligence". I think this may refer to two possible items:
a. a closer scrutiny of IPIX patents to see if there are any issues. This is usually less than one month's gig by a patent lawyer/agent with proper medicinal chemistry background, so it should be finished by now.
b. lab-tests to verify some IPIX data.
To Non-Bound Panic-Boys: In pharma business licensing term sheet is almost always non-binding. It is a high level tentative agreement on main items (license scope, payments...) to be included in the final, far more detailed contract. Having it signed usually means that it is the lawyers turn to work out the details.
"I do believe that this black box warning issue ..." would you please clarify?[1] Otherwise I think I got the gist.
[1] prurisol/abacavir has a well known serious allergy issue affecting about 5 to 10 % of population, which would probably end up in black box warning. That is all I know. Are you speaking about something else?
Same main devotion here. Which denomination are you? I am bumpkin. As in bumpkin ignoramus.
MXAMDUD. Did you just call jewish religion frivolous? To them High Holidays (Rosh Hashanah and Yom Kippur) are a serious, not frivolous matter. Also, I don't think Leo's butt working extra hard would make much difference. His brain, maybe.
As I have said before: this the most educational board I have been on. Thanks, top123.
It is my understanding that one should attend at least High Holiday Services on Monday. That is, if one is devout. Sinners are another story, like my downstairs neighbor, or Billy the pianist from Texas who was married to a pretty filipino girl. Ah, Inwood - sometimes I miss you so.
All my grad school advisors were jewish, one of my lab mates there was an orthodox jew, other reform jewish, the rest chinese. After college my first job was in a small company owned by a jewish guy. On the side I did some consulting work for a law firm where both senior partners were jewish. At pharma I did report to a jewish lady and after promotion I had, among others, two jewish underlings, one orthodox, the other reform. But I guess you got me, I have never had a jewish next door neighbor. Does a downstairs non-practising, jewish drinking buddy count? And that's the short list. I used to live in New York, New York.
BTW. I am fairly certain that your next door neighbor is not an orthodox jew.
How about doing some DD :) Today is Jewish New Year's eve. No biggie. Rosh Hashanah is on Monday and Tuesday. If Leo is of traditional vein he may celebrate both days, if he is reform Jew then maybe only Monday.
Take your pick when to start complaining.
SS, totally agree. Sums involved makes one wonder why Frost even bothered.
I did dig into the article you are quoting some time ago. I believe the author uses Polymedix paresthesias study results without proper attribution to comment on IPIX (CTIX then) phase 2b trial. So you are not confused, Da author is confusing.
A tidbit that is likely to be outdated and possibly mostly wrong if not this year then next: 'ION channels' listed by the author and in Polymedix study are (well, were when I last time checked) associated with pain sensing. If that's still the case then maybe dulling pain is not so bad for antibiotic side effect.
Happy that we agree on Rosen's quality as reference.
A Disclosure of potentially misleading omission: I was not quite right about the awareness some people might have had about the level of systemic exposure from topical application of Brilacidin at the time of IPIX p2b trial. There was a study about Brilacidin as ocular anti-infective started while Polymedix had Brilacidin and finished when B was already Cellceutix property. In the study author notes that B is effective when epithelium is abraded but not when it is intact. The first published indication I know of that talks about Brilacidin having very low absorption rate thru intact epithelium (Am I getting fancy here?). May well explain Leo & Co's decidedly changing direction towards cheaper studies with abraded stuff: OM and UP/C.
Link:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4742993/
A few comments:
"I'm not sure why this footnote appears at the end of the paragraph shown"
1. Polymedix did ran a p2 ABSSSI trial with Brilacidin plus a study for causes of paraesthesia. The ION channel inhibition business is the result of the latter.
Links to Polymedix presentations:
Polymedix P2 Brilacidin trial at ClinicalTrials.gov:
https://clinicaltrials.gov/ct2/show/NCT01211470?term=PMX30063&rank=2
Polymedix Summary for P2 Brilacidin trial:
http://files.shareholder.com/downloads/ABEA-4ITCYZ/1997024712x0x611205/FEA66C67-D02F-4FF2-B230-AA711F46ED7F/PMX-30063_Antibiotic_Fact_Sheet_Nov_2012_.pdf
Paraesthesia:
http://files.shareholder.com/downloads/ABEA-4ITCYZ/0x0x502110/5074f905-da25-4a90-95e0-1b443a14b944/Investigation_of_Potential_Mechanisms_Paraesthesia_5-7-10.pdf
2. We may have been a bit off by using $30M as a cost for FDA requested Brilacidin phase 3 ABSSSI trials. Rosen law firm gives an estimate of $100M in their class action suit. We can, of course, discuss how reliable Rosen's estimate is, especially in light of some rather innovative (but profoundly silly. No wonder they P.O.ed the judge) mixing of biomarker and substitute endpoint definitions by Rosen.
Link to Rosen class action suit (now dismissed). The estimate is on page 15:
http://securities.stanford.edu/filings-documents/1056/CC00_07/2016111_r01c_15CV07194.pdf
But, if Rosen estimate is even half right Cellceutix was far from having financial resources to run ABSSSI p3 trials.
Sorry that I am late in answering (been trying to electrocute myself). If I get you correctly below is simplified summary of your current thinking:
Reporting obligation in case of final denial of BTD, non-success in prurisol p2b trial or signed partnership agreement. Otherwise no reporting obligation.
I have no problems with that. Thanks.
KarinCA, I agree and would like to add this mindbender:
The fun does not end with BTD application being re-submittable under certain conditions. It looks like IPIX is under NO legal obligation to disclose what is happening with BTD, prurisol P2b trial results and possibly even with the partnership deal as long as the company (obviously includes management individually) adheres to what is essentially stated in the latest purchase agreement with Aspire, under Restriction on Sales of Capital Stock.
In addition, in order to avoid future complications (legal problems) it is advisable to abstain making any public comments relating to status of BTD, prurisol p2b trial results and possibly even partnership negotiations until definitive disclosures.
In short: as long as IPIX stays silent it can legally stay silent. But one public peep on wrong topic or even a hint of certain financial maneuvers might force a disclosure. Meanwhile, all we can do is to speculate about what is likely or not with all whys available to our imaginations.
Quote from unnamed pharma executive:
“The only thing that you can guarantee about any valuation is that it is wrong.”