Could you be more specific?

You know, actually make a point.

Also, even if someone would buy the whole platform now, the value would be drastically underestimated if the drugs actually work.

For example, a gram negative equivalent of Brilacidin will be bigger than B by a lot.

Why not let things play out?

IF the other mimetics are safe and effective their value will be much much higher down the road.

A different assessment. Let the wrath of the board rain down

There is one proven HDP thus far, Brilacidin. All else is wildly speculative. Would a company buy the entire platform with that little data? I doubt it. How do you value a gram-mimetic that exists mostly on a poster presentation coming soon in Copenhagen? That has no human trials? The same is true of the Hidradentis Suppurativa drug. And the ulcerative colitis drug. No one knows if they will be safe or do the job.

If a few of them reach the stage where Brilacidin is now in terms of safety and efficacy, the company will look awfully good- BUT that is years , many years, away.


We are about to hear how things have been going with K- if the news is very good, then between B and K there is much to drive value.

Maybe by 2020 the other will prove their worth.

calling kmbjn, or whatever the letters are.

the PNAS paper is an attempt to better characterize the interaction of MDMX with p53. MDMX is an inhibitor of p53. They are saying that protein fragments that mimic parts of p53 will block this inhibition.

So, as you can see, I cannot understand it not very far, after reading it several times....

I have not prev taken the time to read every PR and then see how well Leo has followed through. As you suggest, it's a good idea.

I agree

Does the CEO have significant problems with overpromising/underdelivering? Very little reaction to what are hints of good things to come

could there be a less sexy umbrella for the "updates"than hidradenitis supparativa? I mean, I suppose the PR could be more proctitis trial action, and that would be even less exciting.

Would be very nice for some news about Brilacidin trials / partnership which does not get a mention.

On the other hand, nice to be getting some info soon about other HDPs, esp the gm- poster v soon.
Somehow i wish they called them AMPs(anti microbial peptides)- it has more zip

Re antibiotics and meat: as a decades long veg/vegan let me put in a plug for a plant based diet.

So almost all of the snow is gone now in the Boston area except where it was heaped in big piles a bit remains. I expect the thaw will correspond to a heating up of CTIX shortly. Agree that CEO hints of good things to come and Aspire funding are very positive indicators.

For those with a bit of time, I entered p53 as a search at clinical trials.gov site and there are 249 entries to scroll through. Much of it simply documents the failures of various attempts at p53 vaccines and adenovirus platforms.

#23 is the APR 246 trial, metastatic ovarian ca.

#51 is a Merck trial, similar to Aprea, using drug MK-1775, similar patient profile, metasastic ovarian CA( I will look into this drug more and report back)

#62 is using something described as a heat shock protein to impact p53 in GANNET53 study, drug name Ganetespib, in advanced cancers.

#64 is a failed trial for AML using Cytarabine and a drug called Cenersen from Eleos Inc

#67 is Astra Zeneca AZD 1775, another ovarian CA trial(1775 sounds like the Merck one)

#73 is K

Looking through the previous set of trials I read about last weekend, the MDM2 drugs, was helpful, just in terms of seeing how tough it is a move a drug forward, since some of those trials had lots of adverse events -the Roche drug with neutropenia and thrombocytopenia, for example.

Hearing that K has so far no adverse events is good of course esp in this context.

Looking forward to more data, and then maybe I won't have to keep averaging down...

I am off to a really strong start here. Every time I buy shares the price drops. So it goes.

reads like sci fi

I agree with you. I have continued to buy. I believe that worst case eventually the stock will be worth much more than today.

I agree with most of what you posted, and believe that I can influence some parts of life by my attitudes. At least I know it works in reverse- the attitudes of others can really influence how I feel about something.

Thank you for that. More reading now.

Idle speculation That is what we are left with now, right? Update on everything, around the corner?

Worst case- nothing on NASDAQ, K safe, but no details, B- working on FDA... everything else,works in progress. NO impact on share price, or more likely, decline....

Best case- NASDAQ thumbs up, K shrinks some tumors, increases p21, FDA agrees to phase 3 for B(or even better pharma deal for B) B-OM starting trials, more info on ulcerative colitis(yes I am sticking with ulcerative colitis) Share price doubles?

OK so reality puts us where?

I have the sense that it is much closer to worst rather than best case. Sigh. Glad to hear what others think of course.

George: can you pls enlighten? I assume there is an HDAC p53 connection but I do not get it

Leo and Dr Menon and we the shareholders- none of us-"know what we have."

No one knows how well K will work, alone or in combo with other agents.

Brilacidin looks to be the only sure bet and it is a long way off from hitting the market.

All of the other stuff- B-OM, other HDP mimics, are wanna be's

Really excellent points. I am not smart enough biochemically to write about the p53 stuff with confidence, but of course the info you highlight is precisely what was mentioned at the conclusion of the paper as to limitations of MDM2 drugs- effect on wild type, development of resistance.

It encourages me that there are some actual scientists on the board(if in fact you are one. If not, you have the ability to express points clearly and right to the point, about tricky scientific subjects)

Will try to get through the posts you put up, thanks.

This corner of biology is fascinating but difficult for me because i knew nothing about it before running across this stock. As one would expect, there is a high degree of complexity in cell cycles involving life and death. It is a little bit like starting to get your head around the clotting cascade for example, with its endless checks and balances.

I thought the last link was the most interesting, with one of the posters providing a brief history of the MDM2 drugs that I posted info about earlier today.

Most of the MDM2 drugs so far(understandably)seem to be focusing on liposarcomas, good for K I suppose-less competition-although as noted there are solid tumor and AML trials

The Merck drug is interesting

search for MK-8242 shows 2 trials, phase one, both completed last fall but NO results reported, and the Merck web site does not even mention MK8242 so far as I can find

the trials were of real interest to this board: one, completed(!) was for refractory AML in combo with Cytarabine. I assume this sounds familiar, right, since the Bologna trail has yet to start for K plus Cytarabine. Trial listed as terminated on trials site with no results reported.

Also true for a solid tumor trial for MK-8242

The Amgen drug

The Med chem review was high on this one too

Amgen232
3 phase 1's

1- AML, single drug and combo with trametinib. Start 4/14 finish 8/16 130 pts

2-Solid tumors 155 pts start 11/12 finish 11/15

3-Metastatic melanoma in combo with trametinib and dabrafenib start 12/14 finish 9/18 138 pts

UC ulcerative colitis

First look. Dana Farber also doing trial of single agent Sanofi drug SAR405838- only in those with liprosarcoma

Other SAR405838 with pimasertib expected completion 4/16

Back for a second to ulcerative colitis. Thanks to those who sent private messages about earlier posts. I do not have that feature.

I would only say again that I see this as really potentially important, but who knows how effective CTIX therapies will be. One of my first patients not long out of residency(internal medicine) was a young woman who had not been followed carefully for a couple of years for her UC. I referred her back to GI for reeval. She had metastatic colon CA diagnosed shortly thereafter, and she died within months, and she was in her 20's. (This was not in the backwaters of America, but at at a major Boston teaching hospital) Also, I have a niece with UC.

CTIX is so hard to value because so much is potential, which may or not be realized. It is exciting to read about treatments that MIGHT work.

Still doing own due diligence. At risk of repeating info long ago posted, the competition, in part: the MDM2 inhibitors currently in trials as noted by review article J Med Chem 2015 58 1038-1052. (I would simply put up article, but my wife got it for me and she is a strong believer in not doing so- copyrighted, subscription. Sigh)

They(the compounds/drugs) seem to have different numbers assigned to them, and I have yet to go to each drug co. site to see what they say about the drugs, or to correlate with sclimmuno link to the clinical trials. ) Although I am interested i reading about the ecstasy studies too).

That of course is next obv step- again, perhaps also posted log since.


Roche RO5045337 First developed. Oral. 20 patients took for 6 mos. 12 SAE esp neutropenia and thrombocytopenia. Used in liposarcoma, a good target since 80% liposarcomas overamplify MDM2

Roche RO5503781 also oral. Similar toxicity. In 3 phase 1's according to article

Sanofi SAR405838 Developed at UMich Authors seem to favor it- but authors of review article are from UMich. In two phase 1's, no pub results One trial is single agent, another is with an MEK drug pimasertib again an oral agent

Amgen AMG 232 phase 1 started 2012 Oral.

Merck MK-8242 Oral


Next for me is to look more at each pharma info for these- apologies if you guys have already been over this in detail.

Novartis CGM097

Daiichi Sankyo DS-3032b

NEJM 4/2: yet another article on Staph Aureus skin infections, and the role of adipocytes- fat cells- in the process. Somehow they play a key role. More after a night's rest.

Look: almost every day I see a pt where I think how great Brilacidin will be:

A cantankerous older guy, who does not really want to be in the hospital, but he's getting older and more frail The podiatrist trimmed his nail a month ago, where it was ingrown and then it got red, and then he went on Cephalexin as an outpatient, and then Bactrim, and yet still his foot has turned red, and the trimmed toes are a real mess, macerated, and he has failed routine therapy and must be admitted to the hospital with an ugly cellulitis. I give him Vancomycin and he is admitted to the hospital, with its attendant costs. He is sad and unhappy but there is no great alternative.


Wait till Brilacidin hits the market Yes it's a game changer.

Only concern: should the US govt keep Brilacidin in reserve, as a drug of last resort, as part of antibiotic stewardship? How might they compensate CTIX?

update on side issue etc

that is how I see it, side issue. I do not mean to make the proctitis/colitis thing any more than it is, which ain't much(OK, I brought it up)

I sent an email to CTIX and heard back fr Dr James Alexander, from the company

He said that his GI consultants referred to the problem as ulcerative proctitis, and he attached a chapter in a GI textbook as part of his response

NOTA BENE: the first paragraph of his article, sent to me, says that UP is part of UC, not some completely separate issue, but the same medical condition. OK? UP is UC.

For those who wanta quibble about outside inside the colon; look it up: proctitis refers to the rectum, the first six inches of the colon, starting from the bottom. My rectum is inside me, not on the outside, just as yours is. Yes, I know: the therapeutic implications are that you can use topical meds to get at the rectum. I am well aware of steroid treatments etc given from outside, into the rectum, and that may be what CTIX has in mind. But I think of my rectum as inside me, and I am sure that you do too.

So: who cares what they call it, proctitis , or colitis. I would RATHER they use ulcerative colitis- that puts CTIX firmly in the category of potentially having viable therapies for inflammatory bowel diseases such as Crohns and UC and that is a BIG deal. A major deal, if it works.

For those who care to vilify my earlier remarks, get a life. You sound like tribunal lawyers for state trials in the Soviet Union, decades ago.

For those who wish to criticize me directly (or simply converse)I am at samsockwell@gmail.com. I would be glad to hear from you. I am not going to spend the bucks to have private messages. Part of my job every day is bantering back and forth about what is wrong with any given pt, and my job is to make a case that I know what is wrong, or not. I am proven right some of the time, and I am also proven wrong, and that is how it goes. Medicine is not simple.

I bought a lot more shares today, and think the company will do well, even if it takes a while.

Next assignment: I have a long article on MDM2 inhibitors from J Medicinal Chemistry 2014 and will see what it says and report back

wow

when I have time to reply I will try

But you make it sound so serious...give me a break

They may be different

But then why is the company talking about ulcerative colitis and Crohn's disease - see reference from sclimmuno a few posts back

Look- ulcerative colitis is commonly used

Ulcerative proctitis is not

My "book" is the internet based health reference used by every internist and hospital in the US, including your doctor- just ask him or her

Whether you can find things with google is not the point

I think you are right- they are thinking broadly

So it sends the wrong message to keep referring to a very limited form of inflammatory bowel disease- limited to the very last portion of the colon

Go ahead, include more of the colon!

(Maybe this only bothers a doctor, I don't know)

then he should still say ulcerative colitis, which is what the medical community calls it, limited or not

I am not saying you cannot google it and get a result

I am saying it is not a commonly used medical term

Again with the ulcerative proctitis, in the announcement

What is up with that?

i just did a search on the trusty Up to Date(most standard physician reference for Internal Medicine / Emergency Medicine / all around info.

There is no result for ulcerative proctitis. if he means ulcerative colitis, then say so please. That has to be his intention

I will email about it to Leo

Interesting.

Some impact of K on MDM2 also.

A year behind, and counting. APR-246 PiSSARO trial began enrolling ovarian CA pts 4/14/14...

misunderstanding is one of my fortes, so entirely possible.

I suppose he means mechanism of action is inducing p53 - but then the point of that is cell death, esp tumor cell death, or am I missing something?

Then why was the info presented(surely you jest)?

Let's see: could it be because they would like to use the drug in patients with these tumors?

My post was talking about efficacy of K vs the other usual suspects, and the data from the Am Cancer Soc poster shows what is concluded by the poster itself: not so powerful against solid tumors vs paclitaxel cisplat etc (higher drug concentrations needed)

If those concentrations have already been reached at much lower doses than cohorts 10,11, then that is good news

Why the higher dose cohorts matter: Look back at the original poster presentation for K, at the solid tumor dosing required for effect. You will see that compared to other chemo agents, K needs MUCH higher concentrations to kill the same amnt of multiple solid tumor cell line types.(I am not calling K chemo) Thus the fact that the drug is well tolerated is probably very much in our favor, because patients will likely need to get a lot of K for it to work(vs other standard agents)

(This of course says nothing about how much K is needed for combo therapy with other agents to be effective)

does that mean a need to redo some of phase 1- change in dosing schedule?