Sadly you are right, of course.

Cannot mix up my mimetics with my anti cancers....

I am optimistic I am a shareholder

But CMC thanks thanks a lot for the opening, I mean why not talk about safety profile, when that is about all we know about Kevetrin thus far. The cohorts keep coming.

Not that there's anything wrong with that!

It is well-tolerated-always a good thing.

Maybe one day we will find out if it works!

Um, please reread your own post, to discover that it is about the safety profile of kevetrin,and not its stand alone efficacy.

Gosh, sorry if you or your grandson mistook actual potential Kevetrin applications as humor. (See prev PR by CTIX) Or was the company only joking, hoping to amuse the 4 year olds who follow their press releases? I never really thought of inflammatory bowel disease and cancer as that funny, but you could be right

This is a well-reasoned response. K as the drug for those who want to do something with little in the way of side effects. Let's see how it shakes out: can K offer much help in such a scenario?

With the understanding that for the vast majority of pts you will want to hit your tumor hard, not gently.

You could be onto something though, if it works. But consider: My own family situation, metastatic pancreatic CA, many cycles of FOLFIRINOX, significant toxicity from platinum agents(peripheral neuropathy), and the lovely individual with the disease says treat me aggressively, I would rather be alive in a wheelchair rather than dead. But there are many types of cancer and many types of patients, and I hope K could have such a role.

the number of cancers where p53 is the sole mutation ? Zero, so far as I know. That will the # of times it'll be used as a single agent. Zero.

(Correct me if wrong, oncologists)

Hey but what about single agent use in proctitis? As an antiinflammatory? Who knows then.

You guys do realize that Kevetrin is not a one and only drug?

It will be given in combo with other agents, which have yet to be tested together.

Some of the posts seem to suggest otherwise.....

For fans of today's PR:
maybe future PR's can give you updates when the first patient of cohort 11 has made it out of the parking garage, and into the registration area at Dana Farber.

sigh

What about anything substantive- as prev noted: plans for combo trials, or combo data with other agents(Like APR-246.....you know, our competition)

Is that what I said?

I have kept buying through downturn

I think it is not much of a PR

Oh I get it

Maybe he can reissue old press releases...
It's an interesting strategy, I give you that

PR? OK It is good to know the drug is well tolerated

But main impact of PR is to say hold on for another 3 weeks for any K data.

How about some indication of K's efficacy with other agents? Next set of targets for K?


There is always a chance for some very preliminary skin product updates before mid-April- watch your email.....

again thnks for interesting article

Nice figures in the article, and kudos to immuno for posting prev link

Yes , I know the trial is ongoing, and no, I cannot imagine for a second that they have just been sitting on their hands waiting until every cohort is done, before planning next moves. At least, as a shareholder, i hope not. i would have expected them to have next steps thought out, whether we have the data regarding those plans, or not.

I like the specifics of the book chapter

Basic science review, if it interests you. You all may know it already. I was trying to read more about HDP etc resistance. (I cannot cut and paste- sorry)

If you search hdp molecular pathogenesis resistance you will see at top of list what is a chapter in a 2012 book about Molecular Pathogenesis (Locht/Simonet) that I thought helpful. This is stuff I know nothing about, at baseline.

It has a chapter that comes up in the search a few short pages, starting on p305 by John Hale called "Bacterial Resistance to Antimicrobial Peptides" It describes some of the ongoing battle between HDP and bacteria in some detail. He calls it a cat and mouse game and cites numerous examples of bacterial defenses.

it helps me begin to understand why it is that HDPs kill some bugs well and not others. of course it makes sense that this would be so, but why, and what might it portend for the CTIX(formerly PMX) strategy.

It lists,and then describes specific examples, the following ways that bacteria fend off HDPs

1-Charge modification at the outer surface
2- Charge modification in the cytoplasmic membrane
3-Sequestration by secreted poteins
4-Sequestration by surface attched molecules
5-cell expulsion
6-Biofilm
7Suppression of host HDP genes.

It is a quick read, and this may be very old news for this board. Hale notes that this is not resistance to HDPs in the sense of usual resistance mechanisms, which are transferred between bacteria(NDP-1, for example)

This is a thought( a very obvious one) Again I am not an oncologist, and do not follow clinical trials much. For those of you who know more, or see other logical next steps, please correct me

Next for K? A question posed for the board a coupla days ago. One thing I would like to see is a series of slides similar to one shown for apr-246 , under the R&D section on their website. They show activity of Cisplatinum and of apr-246 in an ovarian resistant tumor cell line. It looks bad. They are equivalent and each drug works halfway. BUT put them together and tumor growth stops. The same is shown from a pt sample

One thing for K would be a series of such tests for different tumors, such as pancreatic. Such data would be the basis for choosing candidates for next round of 1-2 trials. If any such data exists I have never seen it, and I have tried to read through what I can.

This is the logical next step for K and it'd be nice to know what the team has already done in this regard.

Really?(Subtle word play on the german word for really which is....)

Thanks

To partner or not to partner

B phase 3. Has Erlich ever made intentions clear?

b is pmx30063.

Lower numbers are better, the lower the better, to determine drug concentration needed to stop bacterial growth

Helpful. As has been said before brilacidin alone, as the table suggest, does have gm - activity. It is helpful to kill E Coli and Klebsiella. It certainly suggests that the HDP model PMX develpoed and CTIX now owns may work against gm -: Brillacidin can do it, in part

The question is, what does it not work against. I found a study by PMX dated 4/3/13 about NDM-1 , and Brilacidin works in bugs with NDM-1.

What is the lead gm - compound referred to by company? On website it mentions ctix1278

Searching pmx 1278 google yields a poster 2012 about foodborne pathogens- EColi and Campylobacter esp, but I cannot find much else

Also: Brilacidin and teixobactin and cell wall destruction all pertinent for gm+ efficacy. How well can the HDPs work on a different kind of target, the gm negatives? What will be their toxicity? Looking forward to poster from Copenhagen. Again: if they have a new type of gm - drug that works as well as brilacidin and has little toxicity, then the stock is gold. How long till we know? Before 2020?

Mentioning Rio 2016 seems way out of the realm of possibility, but I thought Erlich was talking about gm negative drugs and not Brilacidin. Heck, Brilacidin would not be available then except as a sort of exception. I wonder if that was what he meant about summer games superbugs- Brilacidin, but again I thought he meant gm -.

OK. Have had a chance to read a bit more of the NEJM stuff- pretty short article really.

Agreed that it highlights a drug- also a gm + agent- years away from where Brilacidin is. So why the attention?

Much of the hoopla was centered on the iCHIP, a new method for growing bacteria that normallly could not survive in the lab. Some of the team that developed iCHIP also then found the new substance in soil (taken from a Maine field in 2009). It was named after the greek word for wall Teixobactin. No evidence of resistance noted thus far in testing.

I mean, you have got to be kidding, right? A novel drug that destroys bacterial cell walls with no evidence of resistance? And it is not Brilacidin? Sheesh.

I think the article got major play in the NEJM because of the ability to grow bacteria in labs that could never have been grown before. This was what led to the big paper in Nature in January.

The profs behind it are at Northeastern here in Boston, and their company NovoBiotics is in Cambridge and the NEJM, as noted in published in Waltham, another Boston suburb. In addition to the truly novel nature of the iCHIP, and the promise of the drug. I would guess there is some personal connection somewhere, but who knows.

I agree with the rest of you- the story of Brilacidin is also pretty damn compelling.

I do not know if they would immed reject - since I am a shareholder. Will find out.

Not a bad idea, esp given disparity between where Teivobactin is in the process

Thanks

What's next for K? Phase 1 wrapping up. Next clear step appears to be the Bologna trial, as a combo with cytarabine. What else?

Aprea chose ovarian CA with Cisplatinum and Doxorubicin as an add on for salvage chemo for PiSSARO and their p53 drug.

What else on the slate for Kevetrin? Unsure if there has ever been an indication.

I do not know enough about cancer trials to know if each time you use a drug, say, K, with a new combo, that you must calculate dosing over again. So it appears to be again in Pissaro where first part of trial for APR-246 is to establish dosing, so it is a Phase 1-2 together.

NEJM 3/19- part of the fun of getting the New England Journal of Medicine is that you get the online version the day before it comes out A glimpse of the future.

This is prob the most widely read journal for MD's worldwide, published right here in Waltham MA.

Tomorrow's edition includes 3-count 'em 3-articles about skin infections. One is even about Gm + drugs, and antimicrobial resistance, and is focused on Teixobactin. ( Brilacidin not mentioned ) .Teixobactin gets a lot of press and "no resistance "(known so far) also played up. Part of its appeal is its activity against tuberculosis(M. Tb) Will try to summarize when not beat.

If you build it they will come

If CTIX has a gram negative drug as good as Brilacidin- and that is a big IF- the story of the company will be everywhere.

And if they have that PLUS a viable p53 anticancer agent- yowza.

But you 573 already know this...

I get what you mean and the prress release means- it is a surprise. Look forward to hearing more

Much more interested in hearing about gm - news/developments, as we all are

Of course you are right and the whole point is that K is not cytotoxic, like the usual chemo drugs of the past(and present).

I know i know- lots of stuff in labs

The reason it is odd is that Brilacidin is such a gm positive beast, and HS is a skin(gm Positive problem)

Maybe it has to do with half life- since those pts- HS-often end up on chronic suppressive therapy, taking one drug for a month, and then another, on and on.

Oral Brilacidin?not mucositis prep, but a regular old pill?

It is interesting that they think they have something better than B for HS etc. I will read more about HS and see what I am missing

hey ffrol- thanks for pointing it out.

Unclear if people read too quickly through a post- a mistake I make often, or what exactly.

Which HDP for HS? And other "skin products"?

Hard to believe it is not Brilacidin, which as we know is a great skin/gm + drug. Makes perfect sense that it would be the HDP in question. But if it were B then shoulda been said already, right?!?

But as it is not yet named it means they have an alternative?

Odd. Because safety and dosing already established for B

The patient that the company just wrote about(the disappearing spleen met) had metastatic ovarian CA- she would have fit just fine in the Aprea 246 protocol,for example.

But I would not suggest that only one p53 drug will end up in use, not by any means.

I just hope CTIX has the most effective one.

I am just as hopeful as you are about phase 1 and would not dismiss an essential part of the process

Thanks for such a close reading of the situation, as if being questioned has anything to do with people misreading or misunderstanding my posts.

I do like your tough love approach though.

one more thing: I am a shareholder and a believer in the potential of CTIX despite my questions. I realize some of you doubt this- big deal. Get over it.

Any cytotoxic drug- I am not saying that ugly five letter word chemo- which may play a role in treating half of all cancers today is a potential life saver for the patients, which is what counts, and a potential windfall for investors, such as us