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Here here. Excellent post. Someone with Leo's ear. Make sure he sees this.
I believe in K, but as a skeptic the K results to date prove nothing. Stabilization was noted to have been followed by progression and a few people appearing to have stable disease does not an effective drug make. People who would invest on proof of K works will need much more shrinkage with much less qualification. P21 was exciting but then he even took that back as requiring additional confirmation. I have to respectfully disagree that showing a cure in 6 people for Psoraisis would have had no SP impact. K is simply not at the dosages that we need to be safe. When we hit 200 dosage then K news including just continued safety will get people excited.
Lol. Just because they made a silly choice regarding canceling the PoC does not mean I am ready to jump ship. I have less confidence than Bioman when it comes to not missing the boat. I feel there is value in the acquisition that the market hopefully just needs to get its mind around. That takes time and runups happen unexpectedly. Still I think they really need to explain the abrupt bout face when Leo was overseas for weeks on this trial. Everything was good to go. And it would have provided Wall Street with something real they could value. Reduce the risk discount and the value of the Company goes up. Good for everyone. This decision does not seem to have a logical reason based on the I do we have. That makes me want to dig. Sorry if your skin is raw and you would like to look away but frankly I don't give a damn.
POC would have done it. It turns a prospect to a proven agent. That has real value. Right now we have no idea if the drug works in people.
Interesting. I guess between Kard and the hedge funds they will figure it out. Good to know. Still do not see the merit of not spending the money to assure the world that P works. Even if you don't want to partner it off for the Phase 2 if you wanted a catalyst to push the price up for uplisting that would have been perfect and relatively cheap. Did anyone dig into why they thought it was best to cancel POC if money is not a concern?
No question the Company can raise the money. However one of the nice things had been no need to raise cash until we know P works and even then may have been able to get by on just the Aspire money. Now they clearly will need more an will need to tap aspire for more funds sooner rather than (the much preferable) later. If they were going to need to sell more shares I wish it would be for a higher price like after we had confirmation P worked. I still don't like they cut the POC short. Dual track it. The increase to the market value of the Company with confirmed P efficacy would have been worthwhile 200k. Just don't understand the rationale.
So where is the $7M for the 2B trial going to come from? Sounds like Leo may be hunting for a second Aspire type deal.
What would that next catalyst be? All I can see happening is the start of one of the trials and even that seems unlikely so quick. We probably will not be done with Cohort 6 two months from now as Karin's prediction on 2 month cohort advancement appears to continue to pan out.
Unless you take a closer look at what they got their hands on through this acquisition. Gold. They got their hands on gold. The valuation of a drug with a Company that doesn't have the funds to advance it and the value of it in our hands. Well it's night and day. That was the real news and I don't think it has been fully priced in.
I was glancing through the slide links posted this morning.
Your steady stream of over exuberance is as always less than helpful.
P21 is in a materiality gray zone I think. Does not prove it will work. Just a strong reassurance.
Everyone saw the P21 activation news right?!?!? The slides. Look at the slides! 4 of 5 patients had p21 activation at 20/30 doage!!!
From our newly acquired asset's ihub board. Seems like results were indeed impressive. Getting excited again.
Phase 2 Discussion
In the Q+As, they explained that the drop off in the mid-dose group was due to a combination of the small size of that arm (35 patients in per protocol population vrs 39 and 40 in the high and low arms) and that there were several patients in the mid-dose arm who responded to treatment but who didn't return for the later evaluation (most sites were in Russia and Ukraine). Since they didn't return, they had to be considered treatment failures and this skewed the mid dose figures lower than the high and low dose arms.
The close similarity between the high and low dose efficacy suggests that all dosing levels were likely higher than needed for good efficacy, and this jives with the PK/PD data from the Phase 1 and from preclinical animal efficacy data. The next trial will include arms using a lower dose, and also shorter dosing periods - 1 day (single dose) and 3 days (rather than the 5 days of dosing used in this Phase 2).
PMX-30063 has a very long halflife of 23 hours in humans, and the time it remains in tissue is also very long at 17 hours. The CEO explained that all their animal studies have shown that efficacy for PMX-30063 depends primarily upon C-Max rather than the length of time of dosing. With the defensin mimetic mechanism and the very long halflife of PMX-30063, all that is required for complete efficacy is getting the blood and tissue concentration of the drug to a high level once. So unlike other antibiotics which must enter the bacterial cell and disrupt biochemical pathways to be effective, a long period of dosing isn't required with defensin mimetics - the drug quickly binds to the outer cell wall, creating pores which allow water into the bacterial cell which then bursts. It's a quick process requiring only a single exposure to the drug, or a very short exposure.
Side effect-wise, there were 2 patients who discontinued treatment due to high blood pressure, one in the high dose arm and one in the mid-dose (the trial had 215 patients), and these were patients with some existing hypertension. In the conf call they said the elevation of blood pressure occured over time, so the proposed shorter dosing regimen (1 day and 3 days, rather than the 5 days in this trial) should minimize any side effects. The main side effect for PYM-30063 has been transient paresthesia (tingling, numbness) which didn't cause any treatment discontinuations, and was mild and resolved after the study.
The sustained clinical response data for the per protocol population (days 10 and 28) looked very good (mid-dose skewed a bit due to the factors noted above). For antibiotics you need to show non-inferiority, and other factors are also considered such as the lack of bacterial resistance developing, much shorter dosing required (only 3 days, or perhaps just 1 day), etc -
Day 10 -
***********
Low Dose --- 92.3 %
Mid Dose --- 93.8 %
High Dose -- 100 %
Daptomycin - 97.7 %
Day 28 -
***********
Low Dose --- 97.2 %
Mid Dose --- 87.5 %
High Dose -- 100 %
Daptomycin - 97.8 %
Honestly would love to be sure the drug actually works before sinking larger amounts into it. Canceling a two month study to save a couple hundred grand?!?! How about continue the study to see how well It works and simultaneously apply for the PH2. A few hundred grand to know for sure whether something works is a pittance.
Lack if POC is a definitely disappointing because it means no results for god knows how long. We really need to know more about this acquisition as well. Like why this antibiotics Company couldn't find 1M or a partner to avoid bankruptcy after a successful Phase 2 study.
I'm sure lots. Animals don't have to worry about a corrupt FDA controlled by big pharma.
He also said Kerx would go to zero when it was at 3 and said TTNP would see approval. Just keep those facts in mind. The only time you should listen is when his mystery hedge fund short bear friend speaks through him. That guy seems to really know his shit. I have not seen him be wrong yet.
Worried about the price running away from you eh? Beware those who seem to become unadulterated pumpers (think back to your posts around ASCO) or Debbie downers (now). Dosage was too low to expect results earlier this year so who cares that p21 tests weren't done. It was a long long long shot to have those results positive so early and that moon shot didn't come to pass. Who cares! We are now getting to the expected time for such results. Cohort 6 is the money shot and we are almost there. The patents have their own timetable and are not worth worrying about. If the stuff works we will see a 300 percent gain regardless of the patent situation. Also the timetable for the start of the P trial has been August for months and months. You can't call an August start a delay anymore.
Lets all continue to bask in Karin's news. One of the few voices on here that has always kept a level head and never exaggerated.
God I hope for something as straightforward as this they snuck the drug to some family friend with psoriasis and said hey let me know if this takes care of the problem lol. FDA be damned.
How do we know all of those things are so different? I didn't read any comparisons between the unaltered compound and P in treating psoriasis. Is this difference in efficacy, side effects etc something that has been documented anywhere? Does not seem to be explicitly documented in the patent itself. I see they changed a few things between the starting compound and P, but the starting compound is still the active moiety and the basis of FDA advance to Phase 2. I can't take Tylenol and add a non important H somewhere and patent as my own compound. I agree they must have made some improvements, but what those are seems a bit mysterious. I would have hoped the original patent never mentioned application to psoriasis. Welcome additional insight on this.
Just to clarify, given that psoriasis was contemplated in the old patent as a medical use how is that not a problem for CTIX. It would seem to make patenting the molecule for use on psoriasis would come under prior art / obviousness since somebody had already shown the molecule treats psoriasis in a patent. I'm sure I am missing something but can this just be clarified. How is CTIX getting around this issue?
That is the same study completion date they estimated since shortly after the start of the study according to the archived versions (date of that change was October 2012). I don't think it takes into account the delays and the reduced dosing that have happened. Hard to imagine the trial really wrapping up then if things are still going smoothly with escalation.
Lol don't call a yahoo board citation of a 2012 article on esters and NCE status buzz. We already know that they wouldn't be entitled to 5 year NCE in all likelihood on P because it contains an already approved moiety. Has nothing to do with the patents. Patents are a completely separate issue and have nothing to do with esters.
For sponsors developing new chemical structures based on previously approved active ingredients, two new FDA decisions offer a clear – though hardly satisfying – standard for determining whether a new structure will be awarded 5-year “new chemical entity” (NCE) exclusivity. In two letter decisions issued on the same day, the agency firmly explained that NCE exclusivity will not be awarded to a new structure that relies on an ester bond to link a new appendage to a previously approved active ingredient.
Ordinarily, this would not be newsworthy. It has long been the case – indeed, it is memorialized in the governing statute – that new esters of previously approved active ingredients are, at most, entitled to 3-year marketing exclusivity. However, FDA had also recognized that in exceptional cases, it could award NCE exclusivity to a “stable ester.” That is, where an ester-based appendage is critical to the physiological or pharmacological action of the drug substance, the entire molecule, including the ester, would be considered the active drug substance and would be eligible for NCE exclusivity.
What's the worry? That there are other potential treatments in development? We already know that. There are at least 2 big pharmas with p53 drugs in development. So what? There are also multiple chemo therapies. All are still extremely valuable if they work.
Also what is your point about p53 null cell lines? Exactly which little piece of the cell pathways that K is interacting with that is causing the cascade that activated P53 and also activation of other mechanisms that promote Cancer cell arrest and death is difficult to trace. Calling the drug p53 activating is a bit of a oversimplification. There are lots of things that can mediate cell arrest as shown by the article you posted. As your link showed there is usually something else that is being affected that in turn upregulates P53. They stumbled across something wonderful that works by throwing things at the wall and seeing what stuck. Same as the discovery of the other p53 drugs in development. Doesn't mean it doesn't work, just means our knowledge of cell regulation still has a way to go. The preclinical results remain spectacular.
Ugh not this paper again. If only things could be deleted from the Internet.
Easy answer is listen to the webcast on the Conpany's website :) They say the name for your viewing pleasure.
Indeed K will be the flagship of new non-chemo therapy cocktails. Combine that with immune therapy treatments to prevent recurrence and cancer will go the way of malaria. Completely cureable.
And lets not forget that interesting connection between p21 and HIV. Potentially broader implications than any of us dare to dream.
Indeed independent preclinical verification will be very useful to silence skeptics. Lets hope these types of tests don't take very long.
I like our odds. The effect on tissue at a cellular level by K and the success of animal models at predicting Psoraisis success tells me that the odds are on out side. Low toxicity in dogs of K which had been and continues to be our biggest risk factor (since we know on a cellular level this thing is highly disruptive to cancer) makes me extremely confident in success.
I think you are confusing CE which is a Euro registration mark and allows solid EU protection with NCE which is an FDA construct applicable only to the US which happens to be a far more lucrative market.
It by definition relies on the same active moiety of an already approved compound and so is not eligible for NCE. However that does not mean that the patents will fail to be successful in providing a defense against generics for longer than 5 years.
There was an article posted by Sox that I called out for being excellent that said that mouse models like the one Dr. Mennon used were extremely successful in predicting success in human trials of Psoriasis compounds. I think the inflammation failures you refer to are in a different class per the NYT article which was talking about inflammation reactions to burns, trauma, and infection. I don't think psoriasis falls into that category but the Sox post eased my concerns greatly. Unfortunately needed access to Medline to read actual article or to pay 20 bucks, but Sox posted the conclusion of the abstract which was quite encouraging.
Terrible and not worth responding to or reading. Certainly not worth reposting.
It certainly sounded like it really happened even if it was months ago. Search for references to "the Nurse" and you will find the guilty parties.
We found the guy who PC saw talking to Shapiro at ASCO lol
At Cohort 3 dosing of 30 it seems very likely that they didn't see anything yet. The Company always characterized P21 at such a low dose to be extremely unlikely. I don't think they were just hedging the call when they expressed surprise at the plan to test for it so early. The redirect away from P21 in the latest PR makes me think that Cohort 3 didn't show anything. But dosage is going to finally start going up quickly if there are no AEs and soon they will be cooking with fire.
Keep in mind AF was bashing Kerx long before results of Z tripled the stock and was sure TTNP would be approved. Don't know who Patrick is but haven't seen a call by him worth listening too. No dilution and management not taking a salary so balance sheet is irrelevant. The Aspire deal covers any cash burn and should not be taken so lightly. Data delays followed by positive outcomes happen all the time. It's usually the on-time results that punch you in the nuts.
Yea no tests done and even if tests were done it was likely too early to see anything. That becomes less the case every day.
Why not from 5 to 6? Worrying about hitting DLT and getting stepped back down? I don't think we have much to worry abou in that respect. 100 percent increases sound fine to me until we are at 400mg/m2.