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still not clear to me how K promotes the non transcriptional direct interaction that you mention that draws you back to the original K info.
I do understand a bit more now, the more that I read, how complex it all is, how different mutations can have varied effects on p53, and yes i hope K can impact several pathways.
we shall see.
I went into medicine a bit later in life, was doing residency 88-91, and watched many destroyed/die of AIDS. And now of course AIDS is manageable.
Who can say now where oncology is headed. The reality is that those with loved ones dying now of cancer, or say parkinson's disease, will look back the same way as we now see AIDS. In a generation, or even less, today's killers will be manageable. It is difficult, but very likely to be true.
How dare you put up such a post. I am having my coffee and listening to the news and then I have to recognize how poorly i understand the science of this science driven stock..
OK humor me. I will try to restate, based on looking at the papers recently cited and your post, and then if you wish you may correct.
There are many ways that p53, a critical gene for tumor suppression, may be disabled. It is possible that these different mechanisms of disabling the gene will lend themselves to different approaches to regulating cancer cell growth with p53 targets. More specifically, a missense mutation in one area of the gene may well do better with one small molecule than another, in terms of downgrading or restoring function.
Two drugs, APR246 and A190,appear to work by helping mutant p53 bind and function again.(Although A190 works not via p21 but through NEDD9 in this lung ca model)
K works to 1)degrade mutant mutant p53 and 2)directly induce apoptosis by reactions of this degraded p53 with cell cytoplasm/mitochondrial proteins.
It is not yet clear which approach will work best and if in fact many different approaches are needed.
Does that sound right to you?
On another note: remember when triple therapy for HIV was started, and how revolutionary it was at the time? Are we headed for triple p53 therapy?
A control group getting usual care is the standard for any proof of efficacy. You must prove it works in people and not just in the lab and, you also must show there are no serious side effects.
I agree with you that I would not want to be in the control group for this trial!
Your last point, about the trial comparison being placebo, is important. Some areas of treatment are crowded, but here is an unmet need. No need to beat a lot of other good drugs.
17 pages and 166 references. Type AML into ASCO 2015 and that is what you get.
How will K fit in? Presumably the bologna trial is for consolidation therapy for AML, with and without the standard, cytarabine. Standard treatment for AML now is cytarabine and daunarubicin for induction and then cytarabine in high doses for consolidation or maintenance. Can K improve on this consolidation cycle of treatment?
Much also written on treating older AML patients or those with other illnesses,who cannot tolerate the standard approach, and are given less toxic options. If K works in AML patients it is easy to foresee a role in this population too, since it is so well tolerated thus far
So much going on though, including CAR T cell approaches, the new bandwagon as many of you already know. This immune approach appears revolutionary. Could K be given at the same time as CAR T ?
Fingers crossed for efficacy.
I am sorry but I cannot follow your logic. I think that we should now turn our attn to AML but what you say escapes me. WBC lives more than a month so if you give K over that time frame you contain it?!?
Cannot follow
How do they decide? Look, if you were Dr Menon, how would you possibly know how to dose K for Bologna and for renal cancer(Beth Israel trial with sunitinib, my guess as to the next trial about to be announced)? There is no max dose, and they are about to experiment with new dosing as approved at Dana Farber. But as of yet of course those doses and those effects on p21 or patients are not yet known.
So seriously, how do they pick the doses and intervals? 750 once a week? Or twice a week? Or 1000 or 1250 or 1500 once a week or 3x a week? Will the choices be optimal? Will the difficulty selecting doses hurt the efficacy?
Tough questions, interesting to hear the answers.
We already know how crititcal dosing is- witness what happened when the B dosing was optimized.
Of course dosage escalation will help. It's just not news. Which is supposed to be something new.
I have more stock than I wanted. I have been a believer for a while, and as I have said I am sold on brilacidin(in all its manifestations) alone as a driver for CTIX, and hope that some of the other stuff incl K pans out
I am still waiting for real K news about efficacy...like we all are. This PR and the Leo vote of confidence as a special announcement are confident, but offer little real news.
Someone has to say the simple truth. As an overextended shareholder whose average price is way above current prices I am sad to have to read the corporate update and the current PR and state the obvious. WHEN we get efficacy data I will be as excited as anyone, moreso I would guess, since part of my job is seeing cancer patients almost every shift at work
Leftovers, warmed up? Most of PR is old news, rehashed corporate update. More tries to find best K dosing. the phase 2/3 will be sunitinib/K at beth israel, as suggested in update(that is my guess, certainly)
Interesting though is BLURRING 1/2/3- I have not heard this prior.
And what if the 2/3 is anything other than renal ca at beth Israel? i doubt it strongly, but that would be exciting, since it would mean a new target.
RK mentions ovarian, which CEO has hinted about. Anything at all- ovarian, pancreatic- and all those other ugly cancers: would be great to know that CTIX has identified other regimens, partners, trials.
Now all we need is data to show that it works: not in a lab, not on a mouse, not just p21. Of course they are treating people and not biomarkers, and wouldn't some efficacy info be nice. That is still a ways off I believe. Anything at ASCO? One can always hope.
I am afraid, though, that this amounts to old news, rewarmed. Except for 1/2/3 blur
Trend in medicine is to use ONLY generic names at all times.
Have not looked at reports /links
They may get new names but generic names will be the ones used
Oh yeah I get it- you mean they were unable to provide the headline story about the vanishing spleen lesion?
with respect to K absolutely. We keep hearing how good it is and the only data is how safe it is.
I am not George. Who I am is easily findable- search my posts.
I am not a trials guy. I work in emergency depts seeing patients
Tom- don't let your hopes be deflated prematurely. As if we need more delation talk around Boston.
Too soon to know- dosing not even decided as of yet
Much much more importantly is what we do not know about how it works with other drugs. I know I am a broken record on this but the future for K is with other combo therapies. K plus others may be excellent- but too soon to know.
it is a slow process.
thanks- If I failed to clearly distinguish the CTIX vs Polymedix trials that is indeed my fault and they are light years apart and represent the essence of brilliance of the whole Polyheist. truly a stroke of genius to fix upon the lower dosing
And that has made all the difference(to swipe a phrase from Frost)
Without writing it in CAPS I did mention the dosing differences -of which we are all aware, I think.
Quick follow up to blood pressure discussion. Look at Brilacidin antibiotic fact sheet Feb 2013 put out by Polymedix. There is a discussion of adverse events including a statement that two patients left the study due to increased blood pressure. Those dosing regimens were different than those currently used- specifically, those were multiday and the recent phase 2 was two one day 0.6 and 0.8 as I suspect you all know very well. The one time dosing esp the 0.8 did as well as the 3 day so a once daily dosing is bound to be the future for B.
But it means that Jorgensen mentioned it 1) some patients do get BP increases, and 2)BP increases represented a real problem with the Polymedix phase 2 trial
I once again say that I do not see BP changes as an issue for Brilacidin. We will have phase 3 data to look at some day too.
let's talk about blood pressure(BP) . this comes up under AE for briliacidin in the Phase 2 trial, see jorgensen talk slide 20 of 24, and his explanation, ECC MID, to set the stage.
If anyone knows where there i more data I am glad to look at it . The slide shows that about 1/2 of 3 day dosing pts have incr BP. But we don't think that will be the dosing, so let's move on
At 0.6 one time dosing 2 pts or 3.8% had increased BP
At 0.8 it was 9 patients or 17%
Nota bene Daptomycin at 10%
I will say at outset I know nothing of drug trials.. But I know a lot about blood pressure. All day long every day I see people who are surprised at how high their BP is in the emergency dept. Not at all a surprise- they've cut a chunk out of their leg with a saw, or broken their wrist or hip, or done this or that. They very frequently comment that they have never had such high pressures. Does it affect them? No not at all. What is the downside of an elevated BP? Stroke or heart failure or heart attack, to take the major concerns. Does that happen in these every day, patient after patient, increases in BP? No, not at all.
So I do not worry in the least about the issue.
But, I will say that in terms of trials and how drugs are judged, that Jorgensen is clearly concerned about it. Maybe that was part of what sunk Polymedix- I do not know.
The details are nonexistent. What were the starting blood pressures? How long did they remain elevated? We are not told this info as far as I know.
We are told that it is an AE to have BP increase to above 160(systolic, the top number). I see no more
details- more than 180, or 200? Who knows? For 10 minutes? Or 10 hours? Or 10 days? Who knows? I will write to Jorgensen/Leo and ask and share my responses.
Note that they report no serious adverse events related to BP increases: no strokes and no heart attacks and no congestive heart failure. Just as you would expect. Some percentage of people will have their BP rise and it will have no important consequences.
I believe that clinically it is of no importance. In the world of drug trials I do not know. But Brilacidin single dosing is very unlikely to be much different than Daptomycin for the BP AE, and I think it is a non-issue.
Would I like more details? Yes, esp given Jorgensen's attn to the issue. Will they go with 0.7 in a single dose, or 0.8 or 0.6? We shall see. Worst case current data is 1 in 6 at 0.8 doing with some BP increase and no SAE.
This has me losing no sleep at all. And in fact it is close to bed time, work in the morning.
Again, I bow to those who might wish to amend / correct above remarks.
It's not easy being green.
Let's go CTIX. Longterm positive outlook for the company, hoping for that NASDAQ move.
Laughter is the best medicine
Sometimes the only medicine.
Re Cellceutix/ASCO: let us suppose that we are in fact at the presentation, right now:
Speaker:K has been so well-tolerated that we cannot yet find a maximum dosing. In fact, we are now 10 times our original dosing, and it may go higher.
Audience: (Hushed tones, or even whispers.)I told you that it was well-tolerated. Now do you believe me? Just show me a better tolerated anti cancer compound than that already.
Other audience members: tones not hushed, rise to their feet: Go higher, go higher with the doses! More cohorts! Higher and more!!
Speaker: Our next agenda is to work to find ideal doses and intervals. This may take some time.
Audience, murmurs: Time- we've got some more of that don't we? Surely we do. Safety first. It's Phase 1.
Other audience members, again the rabble, shouting, in a reprise: Higher and more! Higher and more!
Speaker: Also, as expected, p21 levels have risen in the later cohorts. If you will look at slide 17 you will see...
Audience, murmurs: Wasn't that in the corporate update? At least now we can get some details- look, actual data. I think that's a graph! Look!
Speaker: we plan to initiate the Bologna trials with Cytarabine and Kevetrin
Audience, chanting: Bologna, Bologna, Bologna
Speaker: There has been stabilization of tumors in some patients.
Audience, subdued: OK OK, here we are at the appropriate venue. This is it! This is what we came for. C'mon, c'mon...
Speaker: You must remember these are very small patient samples, and we hope to make more data available later.
Audience, crestfallen, building toward sullen: Is that all there is? Is that all there is? Special K?
Speaker: We expect more trial data to become available as new dosing regimens are in place.
Audience, stumbling toward exits: what room is the xyz presentation in? Do you think Brilacidin has anti-tumor activity? Wasn't this all in the update?
I hope I am wrong.
If I were at ASCO I would go -but otherwise, a special trip? Strongly doubt you will learn any more than the poster will say, and I still predict the presentation will not say much more than we already know right now, seated at our respective keyboards.
Hopes here way too high...
My prediction was many posts ago based on the corporate update and not the poster, but I can take some hope in what you say about abstracts and what will not be in them.
I still hope for much more info out of ASCO re K
As already predicted there will be no "splash" They will say
1) K is so well tolerated we cannot reach a maximum dose after 3 years of trying, and
2)p21 levels went up in later cohorts
Which will leave all the big questions: does it actually work in patients? what are the right doses to give ?, and how well will K work with other agents?
All of the critical data is unanswered, but we have to say it is safe before we can get the other answers...
1807 replaces 1502. PR mentions 1807, which we recently heard about as a gm- current best hope in that area. Prev for Candida website mentions 1502 but now 1502 apparently on the way out as an otic drug to be replaced by 1807. Nota bene 1807 also better for gm - than 1502.
Interesting. What if 1807 has antifungal activity when given IV, and not just as a topical as suggested here. It has problems with Pseudomonas as we have discussed prev. It would be a more attractive drug if it had some other value added- antifungal would be interesting
We need something to talk about now that ASCO appears to be a .....snooze.
Wow. I really hope there is more info in the actual talk. Abstract tells you nothing new at all.(Yes back from another board- too much hassle in back and forth)
Agreed of course. Extremely soft con. You could hope that every antibiotic was available in every form but it is not always so.
This con is far less impt given the fact that one dose -count 'em- one dose, will likely be the recommended dosing
very helpful summary and nice of you to take the time. I had not seen prev explanations and was just searching around the earlier posts that I mentioned in my prev post.
It is lucky that you have some background in these matters and you are generous with your time.
Blepharitis. This also is a target of Brilacidin potentially, related to its eye use, recently discussed on the board. Another company I have followed, InSite Vision, did careful trials showing that the antibiotic component of treatment was not important compared to the inflammatory component. Specifically, adding Azithromycin to treatment was of no extra benefit to a steroid. The steroid was helpful, however. InSite Vision has done poorly, but the trials are helpful in suggesting the importance of inflammation in the problem.
Brilacidin has this antinflammatory activity, a bit hard for me to grasp, but I see the graphs for various immune modulators as just presented in Denmark, for example. And CTIX keeps stressing this aspect- with ulcerative colitis, esp, and mucositis.
There is no approved drug for blepharitis. InSite Vision estimated the market at $500 million. Blepharitis is a chronic disease of the elderly, for the most part. That number may or may not be correct, but this is another area Brilacidin might fit that is a bigger opportunity than one might suspect.
The specific picky "cons"mentioned are not answered directly by the posts you mention. Those posts 1)generally explain volume of distribution, and 2)say that the drug works well, so the picky points are not of the essence.
I agree with BioDoc that if the drug works that is what counts. But it does not address directly Smooth's question, and the specific "cons" . As I said I do not know those answers, not my line of work.
Only competent to comment on what has already been said- that the paresthesias are not a big deal and that the blood pressure issue is either unimportant or manageable.
missed the pancreatic ca pt info- where to read? Thanks
Wish I had the cash to add at these levels...so it goes
Any idea for drop? Someone trying to lower price enough to keep CTIX off NASDAQ? Gumshoe holders had that much stock? Dalvabancin(sorry, spelling) out? Leaked data about Kevetrin?
Mysterious because seems like pretty determined selling.
I thought things were lining up pretty well here, not for price jumps predicted by some, but I thought CTIX was headed up not down
I know- don't invest in biotech yadda yadda
Surprising slide to me, esp since I did not buy in at 1 or 1.5 as some here did.
hope you're right
ASCO in about 3 and 1/2 weeks
Meet me back in this space in 10 years and we can then see how often K is given alone
How am I failing to be clear? Look at the Aprea Apr246 data. They show survival curves for refractory ovarian ca treatment with cisplat plus apr246. That is what CTIX needs to show for K, not to mention all the other data for all the other very difficult to treat cancers that are out there begging for some effective intervention. The future of K is adding value to other therapies.