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K and apr-246: news just out today about the competition. Aprea announces $50 million funding raised for further trials for its p53 drug, to fund many other types of cancer trials beyond ovarian, and to establish a strategic US team- no details provided.
BUT Nota bene: good news in the business wire article. The randomized phase 2 trial is about to begin- they have been working on the 1b portion of PISARRO apparently, presumably establishing dosing. Even though this trial started 2 years ago, Aprea is only now at the stage where CTIX also is now- about to begin randomized P2.
Not bad news for CTIX I think, despite the competition.
The large question of course is: is K dosing optimized at this point? Is 3x week really just right? Will there be other dosing studied in the K ovarian P2 trial?
I still find it hard to believe that the dosing is dialed in yet. They have written about long infusion times versus shorter(given short half life) Will 5x week be better? Or a pump multiple days a week dosing over 8 or12 hrs? The company says it has gathered adequate pk data to decide dosing and we shall see- such critical choices to determine efficacy.
It would be great if we could see phase 2 results before Aprea ( yes I realize the drugs work differently, and K has multiple modes of action, and yes that is partly why I am a shareholder)- bragging rights first in class p53 drug- something Aprea claims for itself currently.
As we have mentioned/discussed main issues are severity of the skin disease plus presence or absence of psoriatic arthritis- a very painful crippling joint destroying arthritis
So far as we know P is for milder skin disease as has no impact on arthritis- so far as we know now
As you note Sonis was part of the original animal research for B-OM presented at ASCO 2012. How could this not be viewed as favorable for B-OM?
Side note for P- company after company keeps rolling out new and better -umabs like ike...and of course they will have a large share of the market . But P could really nab some patients and some dollars if it works.
They have not mentioned any benfit for the arthritis part of psoriasis, and of course that is not part of the trial. Would be awfully nice if it had benefit for psoriatic arthritis also- it is a serious problem and certainly drives many patients to all the -imabs, -umabs
1/27/16- Leo talks of "expanded phase 1" being a real honor and of talks with DF about other scientific experiments, in the Streetwise interview.
Will there be such an expansion?? Clearly, he is not talking of a phase 2 there. His words- expanded phase 1.
As for it coming up prev, so far as I can tell, the IRB at DF approval mentioned 5/25/15 was for extra pts at higher doses than 750. I should not equate those 2 ideas , but I had mistakenly done so- extra pts to finish p1 vs expansion of p1. It did require a specific approved expansion but was not at all what Leo was referring to.
That however does not change in the least the question of what a p1 expansion might include, or if in fact it will occur as CEO said it might just 6 weeks ago. Dosing of extra patients at more frequent intervals are my idea about what an expansion might entail, and I think it would be a real boon. Exactly what DF has proposed we do not know.
I have no skill in importing links. Does the board have no collective memory of CTIX announcing changes in dosing protocol for phase 1 extension? If not I suppose I can look it up and post the date
I am not confusing p2 and post P1
That is exactly what I wonder.
CTIX made a big point of announcing the extension , post phase 1, as an agreement with Dana Farber to look at other doses.
As I have just written I see a benefit to patients and to CTIX and to the shareholders should such dosing move forward with many different cancers- while we wait for the phase 2's to start. It is going to be a long time till we get data back from phase 2 with K plus irinotecan for pancreatic ca, for example, and yet we could have info by the end of this year about many targets- ovarian, pancreatic, renal- if they chose to do so.
The same would be true of course for 3 or 4, or 5 or 6 ovarian cancer patients, or for renal CA . While we are waiting for the phase 2 trials, why not gain more info about the new 3x weekly dosing and treat more patients at the same time, and get all of that info back sooner rather than much much later? What if CTIX could announce drops in CA 125 for 5 of 6 ovarian CA patients by the end of 2016?
If the decision was in fact made to drop the post phase 1 expansion, I wonder why? Why not simply have both?
One reason would be if the company strongly feels that the only way forward is as a combo drug- they have chosen docetaxel for ovarian, and perhaps irinotecan for pancreatic CA.
Unsure what other advantage there might be - you could argue that having even one patient enroll in a non standard comparison trial is losing that patient to prove statistical significance a better trial, a P2 instead of a p1 add on.
The problem with that is the time lapse. They could have already been treating pts at DF/BI with new protocol and instead we are just waiting. They could have valuable data back on tolerance/effect of 3x weekly dosing too. Presumably they do not see the time lag as important. The time lag may very well be very important though- no current funds for a phase 2 with Mayo for pancreatic to go ahead, so we sit on our hands for...how long? Nothing announced about BI and renal cell CA, or AML. These might move forward with news from a phase 1 expansion that hinted at efficacy but now we are waiting for a long time for phase 2 trials to start and then to yield results(or are we waiting on those 2 cancers/trials for other reasons)
Expansion post phase 1? what expansion?
One pancreatic CA patient, treated with K mentioned 1/22/16 PR. 4 full cycles ,one month each, 3 wks treatment , one week off. In other words, very little treatment because K has such a short half life. Tumor size was stable "for more than 3 months"- I guess we should think then that tumor size then went up in that 4th month. No mention of CA 19-9 levels.
Question for the board: Which would you rather see- 1)we all sit around and wait for Mayo and Leo to get a grant(bound to be v competitive lots of applicants) OR 2) Dana Farber and BI find 3 or 4, or 5 or 6, or 10-12 pancreatic CA pts to get the new dosing decision 3x week, and get info on tumor size and CA19-9 in the very near term under whatever expanded phase protocol Leo has been talking about for a long time.
It is easy, of course, because CTIX could do both 1 and 2. That would be better for patients and better for shareholders- assuming that K actually has some measurable benefits
I say bring on the expansion, bring it on-
there will be lots of people trying to get the grant, who knows how good our chances are- we are one of many experimental approaches to this ugly cancer
as I said - we all knew that phase 1 was ending, that was never in doubt
what was and is in doubt is whether the CEO announced extension(beyond phase 1, not phase 1)which led to extra protocol discussion with DFC, as we recall, will come to pass
who knows if we have a shot at the grant money- too bad we do not have enough cash to move this forward on our own
phase 1 was going to end no matter what. My only question was, will there be an expanded phase 1?
The CEO said there would be in his recent "interview" I am now guessing it is not likely, and that we move straight to phase 2- and we agree on this
I am questioning whether the previously announced expansion is now cancelled even though we were not so informed.
sorry- missed your second post
I am surprised a poster on this board(me) announces the expansion was cancelled instead of Leo. I hope it still goes forward.
then why does leo talk of expanded phase 1 in streetwise interview?
K phase 1 expansion? Recent PR about the end of K phase 1 does not mention anything other than potential phase 2's. In the "interview" with Streetwise Leo does mention expanded phase 1 but does not say much.
I wonder if this expansion is gone, and we just move to phase 2.
It would be both good and bad. Good because earliest demonstration of efficacy would be most helpful, and a phase 2 would be more rigorous.
Bad because an expanded phase 1 would test a lot of tumors and potentially give real hints at efficacy.
Many drugs show efficacy in phase 1- I just read a bit about venetoclax, and its phase 1, with clear efficacy.
No efficacy shown by K and we say it is because of dosing- and I agree with that. But why not give 3x weekly dosing for a very wide variety of tumors and see if there is any efficacy? Why aren't they doing that yesterday!?! What would the share price be if there were 10 patients with a variety of tumors who had biomarker decreases and decrease in tumor size? Even if real efficacy versus standard treatment not known?
Presumably( duh) related to improvement in psoriasis in HIV + pts treated with retroviral therapy and yet when you google it there is not that much to read- at least with my attempts. Like many on the board I tried to find the easy connection and there is some anecdotal stuff and maybe one trial of another retrorviral for psoriasis- forget which- and then I just gave up reading.
Thanks for bringing up HERV info, another fascinating biochemical story
Agree-There is bound to be a good market for P if it works, since it is oral and has a better side effect profile. Lots of psoriasis patients with variable disease severity, some can use P. For those with bad disease-incl psoriatic arthritis, a big deal-the IV or IM drugs will still have an advantage.
Potential surprise catalysts? No big news likely till P results- a couple / several months away
What might move the stock that we do not expect?
How about news about one of the gram negative drugs- no info, no update at all about 1807. Is there too much going on for the company to focus any effort on such a drug? As we know they are working to optimize 1807 to work against Pseudomonas. Would they move forward anyway? If anything develops this will be a nice surprise, and unexpected.
Will CTIX say any more about BOM as they announce moving forward with BUC(rectal)or if you prefer BUP? Any info about its safety/benefits would be big.
Any info about ear/eye prep helpful but would not move share price at this stage.
Ovarian CA trial info available at some point- won't help share price already announced. But maybe if they announce moving forward with other phase 2's- renal CA trial at Beth Israel and with pancreatic trial at Mayo- that would help
Other thoughts about unexpected catalysts?
My sense of the data is that he had already told us 1) that p21 went up with kevetrin and 2) that no on knows what an increase in p21 will mean for survival of cancer patients.
We wait - and many unfortunate cancer patients wait- for him to announce that patients given Kevetrin 3 x week show meaningful increases in survival
The market's response is as it should be- p21 elevations mean nothing compared to real efficacy which means everything
Sophistication- a brief note.
I read a lot of scientific literature, as you prob do as well if you own this stock. If the PR does not bother you, that is fine by me.
What I see happening with CTIX suggests their PR releases ought to be be as sophisticated and nuanced as their science. the science is potentially amazing and is right at the cutting edge on so many fronts.
They have a brand new never seen before antibiotic that might not even have resistance(who knows we shall see).
They have a novel cancer drug that could prove useful in many many tumors, and a decade from now be used as a standard for many treatment plans.
They have potentially useful solutions to the problems of mucositis and distal ulcerative colitis.
we are all owners of shares in this company for these very good and truly exciting reasons.
But a company that has this much scientific potential ought to reflect its sophistication in its press releases and not sound like teenager summarizing a wikipedia article.
my take- obv not yours.
The paragraph about cancer and its complexity sounds like it was written by a junior or senior high school student. It does not read like a press release from a company deeply involved in developing revolutionary anti cancer drugs.
K paper preview: ah, let's see. For those who are actually waiting for such a paper-
We gave slowly escalating doses of a very short half life novel anti cancer drug to 4 dozen patients with endstage solid tumors. At these doses Kevetrin was safe.
We hope to report on efficacy in phase 2/3 studies, and we are in the process of starting these trials for ovarian cancer and pancreatic cancer.
That covers it folks
The military and Brilacidin: if Bp3 goes well, and there is no reason it should not, I still think there will be some major national discussion of its use/nonuse, reserve for the future, etc since it is SOMETHING COMPLETELY DIFFERENT.
I do not know which office it is, but there has to be one, the office in charge of medical care for US troops, where someone has his or her eye or antibiotic drug development.
They are looking at B and thinking- hey, one dose of one drug for the person who just got shot, a patient I am worried about, and then I have a very high likelihood of success against staph incl MRSA and strep(and a few other bugs). It is one and done.
No it is not a pill. But it is better than their alternatives at this point. get ready for an interesting discussion at the highest levels abut antibiotic use in America/the world when B is ready for prime time.(Yes I realize I wrote something similar recently. But I work near an Air Force base and started thinking about the military specifically)
Will that be 2018? Or later 2017?
Sad to admit but you are right of course. As a shareholder who bought at much higher prices it pains me to say that sure, you can wait for March and then April and then when we get P results you can hold off if they are bad, and then start to buy if they are good. Why would anyone buy now?
There could be a partnership announcement at any moment and that is the main reason to be sure to have shares.
As we all do, I wonder when the share price might actually move from these pathetic levels(barring partnership announcement of course)Can the share price really drop if P fails? I really hope not, though any negative news will hurt a bit prob.
The other items you mention: we already know that Kp2 starting this year and Bp3 also- cannot believe that actual start will change anything.
Start of a BUP might help just a smidge but doubt it- where did start of BOM get us- nowhere
OK- so near term next news in 2-3 months is P results, will help if good. If very good double of share price? All the way up to 2? Could there be a triple.....to 3?
Have not heard any dates for us to get any BOM data but that is next up for results after P. Will we hear anything about BOM this year?
Starting trials will not move the share price- at least what we have heard about so far. We await results, and that means waiting a long time. I do not when BOM news expected - but these(P,BOM) are the only results I see for the next year
I would bet anything that law suit ending would not result in a double of current price. Unsure how much of a rise- say 20%?
paper on K? ASCO? These are false deadlines with nothing new to come out.
The next real K news will be the ovarian trial interim results in 2018? Maybe exciting tidbits along the way like working with Mayo on pancreatic cancer but nothing that will move the stock anywhere at all- for a long time.
B-OM maybe will be a catalyst sooner....one can only hope
hey everybody read up on your glomerular basement membranes and their varied disease states- Kevetrin is coming to help your kidneys!
OK I am just trying to make nephrology interesting! Always a difficult subject in medicine, for me anyway, hence the exclamation marks!
As prev noted on this board: just read about the lifespans of your red and white blood cells. Neutropenia esp has proven to be a sticking point for many many drugs chemo and otherwise, incl the MDM2 drugs.
Giving K more frequently MAY have toxicity we do not know about yet- it has never been given 3x week, right? Your bone marrow has plenty of time to recover if it takes a hit with a short half life drug given once a week. Maybe 3x week no impact.
But maybe a real impact on cells whose life spans are VERY short/produced in massive numbers every hour/day. Even if DFCI has shown NO decrease in neutrophils with highest doses so far, it still does not mean K will have no adverse effects as dosing changes
! Other possible applications for kevetrin !
J Am Soc Nephrology Jan issue : Podocyte p53 and experimental Alport Syndrome(podocytes - cells impt function as kidney filters blood-urine)
p53 intact mice had decreased rates of worsening of renal disease. Alport Syndrome genetic disorder of Type IV collagen that causes problems in kidney ear eye, incl high rates of renal failure(as you know ESRD End Stage Renal Disease a big deal for health care- dialysis/transplants)
of course impact in humans not known- just a first mouse study.
But it is interesting and hints at a way forward for K in other diseases
you must be right that data out of Bp3 before Kp2. Still doubt B partner until trial results in, so 2017 data back? Kp2 data back 2018?
Recall however that the drug has not been given 3x/weekly as proposed. Not suggesting that patients will experience such dire outcomes- but side effects at increased dosing are not known.
Also surprised that such a short half life will work in 3x week dosing(K). What is there we do not know?
Very long infusion time? Will there be alternate dosing in the trial early on?
Unsure about that. How long will B trial take? Will B phase 3 results be back before some efficacy info comes out about phase 2 K ovarian ca trial? Honestly I think a drug that might prove beneficial in many cancers will be a dramatically bigger deal than a good new antibiotic(used for the most part for gm + infections)- that is obvious I suppose, and that is why I view phase 2 K trial as much more important- for patients and for investors
2 of course, yes.
Just pleased enough to write without re read-
Such good news- NO delay for starting a phase 3 to wait for further dose optimization. Things are starting to get exciting! Would be nice if they had multiple trial sites, wonder if only DFCI
Just imagine if Kevetrin produces truly meaningful results- patients will get better and we will become rich
I agree with you of course. If some national VIP committee decided to hold Brilacidin in reserve, I would expect it to benefit CTIX and to benefit us shareholders, since they would commit to purchasing some significant stock of the drug.
I think that Leo's tone and arguments in the interview suggest that this is a very real possibility. In some ways it may help the stock in the long run- we shall see.
Antibiotic stewardship and Brilacidin:
It is a good question. Look, Vancomycin presents so many hassles that all of those who prescribe it would rather write an order for another drug. I think Brilacidin should be able to replace it for many reasons already talked about on the board
What will happen if there is a cheap generic alternative Daptomycin, when it goes off patent? How much more attractive will Brilacidin be than such a drug? It depends on what exactly the competition is when Brilacidin becomes available.
One of the most interesting parts of the recent interview with Leo was the discussion about the government holding B in reserve, and not using it. You could really almost hear the conversation leo may or may not have had with the FDA and government officials.
What about a completely new class of drugs? Shouldn't we use the other drugs until we can no longer use them? What is the role of antibiotic stewardship? So far no resistance, but does anyone really belive that no resistance will ever develop? Who knows?
Leo is rehearsing future conversations with the FDA or repeating discussions he has already had, or Jorgensen has had, or whoever their best antibiotic spokesman is.
Brilacidin when it is approved-obv I hope it is a when and not an if- will be a VERY BIG deal, because it is as we all know, a whole new type of antibiotic. I think there will be a lot of discussion as to its proper role, and whether to reserve its use, and I anticipate a real serious conversation about all of these issues
He is still trying to figure out if it works- is this hard to grasp?
You know, why they have to continue with all those phases for all those trials- to PROVE it.
why might Shapiro and colleagues be working so hard on a potential flop? Promising drugs fail all the time
We just hope this one won't.
Perhaps we should have celebrated the 1 year anniversary of the Jan 20 2015 disappearing spleen press release- a true classic!
Maybe if Leo had included-in the headline- CA 125 still increasing, for the same patient, it might have less controversial. As it was we had to read down through the article to find that the key biomarker was still going up...
We are nit-picking the math of muelch when there are claims that the clinical staff at Dana Farber know that Kevetrin works? And that Leo and Shapiro know too- but you and I do not know? That Leo could refrain from notifying the world if there were real proof?
And why should he refrain? If he really really knows it works? He should shout it from the Dana Farber rooftop, he and Shapiro together, and then wow them at ASCO.
Stay tuned . We ain't there yet.
I am also hopeful