you miss the point

sure it succeeded - for what was studied. But are they planning those doses and frequency for anyone ever again? Ahem, clearing of throat, ah..... no

Thus : Safety at actual needed frequency NOT proven

the IV dose has proved nothing, other than safety, when given at dosing frequency that no patient will ever be given again

so far frequent IV dosing for K has not ever even been done, and cannot assumed to be safe

cart before horse-Oral K under way??!?

hey everybody- such great news

I mean why waste time proving that your drug works when you develop an oral form of the drug instead. Time and money goes to...what?

Seriously, folks, efficacy can wait right? What's the hurry? Maybe they can work on a K powder etc?

On the other hand, I suppose it would be helpful.

To show that it works
In cancer patients
to prolong survival

cart before the horse?

K oral dosing incredibly important for the company and for our investment here

Oh yeah, just one condition- the drug needs to work. There is just that one hurdle.

That is, proof of survival benefit. For actual cancer patients

And we are no closer to that as phase 2 B for ovarian CA is where....limbo?

Maybe near future will be fine , and maybe it will not. It is not at a clear that P phase 2 will be a big winner.

If it is not, then we are in for truly dire times.

no post about Prurisol and how it works because I did not get permission from Leo to post his answers. I asked but did not get a yes.

Those of you who care will recall the somewhat shocking revelation that abacavir was not that active agent in prurisol when Bertolino recently spoke.

What could this mean? He misspoke? A misunderstanding? What the...?

Other than taking him at his word, and his other comments about PRINS and IL-20(if I recollect correctly), I do not know more now.

Remember renal cell CA ? Remember sunitinib? see NEJM 12/8/16

Yes, it's another edition of the tomorrow's NEJM today!

very large trial of 615 pts around the world with renal cell CA, deemed high risk post op given sunitinib vs placebo, longer survival with sunitinib>

Wonder how they might do with Kevetrin too?

Oh yeah- that was supposedly the plan we were told about- Beth israel and their focus on renal cell CA and a trial with sunitinib and Kevetrin?

Or was it all just a dream......

why no trial inclusion of pts with psoriatic arthritis yet? That woulda been a very nice addition to a 2b

hmmm. Interesting Trying to answer the question I came across the TP53 website, which I had never seen before which asserts that small cell lung CA- FAMOUSLY CHEMOSENSITIVE-has 70%p53 mutation. That is to say directly contradicting the testicular CA hypothesis.

lance armstrong and fellow testicular cancer survivors might benefit from chemo sensitizing native p53, and maybe the hypothesis is hogwash, and it is something else entirely.

Of course the obv next question is: take other highly chemo sensitive cancers. The next well-known example, perhaps within the realm of the board's experience, is small cell lung CA(by this I mean well-known to me, a non-oncologist to be sure- NOT pretending otherwise) Just as with testicular CA, even very widespread disease, shocking metastatic presentations, can have very dramatic responses to chemo.

Does small cell lung CA share intact p53 with testicular CA? Does anyone even know the answer?

I shoulda looked it up first, before writing, but I will look tomorrow, or later tonight

agree- yes, let's say that the hypothesis that p53 is a sensitizer for chemo effectiveness, then maybe p53 drug like our own will have widespread application.

That would be wonderful for all of us and for pts and I wish they would GET the ball rolling on the next K trial.

Still upset about the dosing problem- the failure to ever try K at stepped up intervals....shoulda been done a long time ago

TP53 and testicular CA: New article in Nature, from the folks at the Broad Institute, right here in Cambridge MA, and from a collaborator at DFCI. As you may know the Broad is trying to use "big data" to analyze genetics of lots of diseases and here they looked at testicular ca. One finding of note- tumor samples showed intact p53, not mutated.

Obv p53 mutated in many tumors. So here they hypothesize that maybe intact p53/apoptosis means sensitization for chemo, since many of you will be aware that even very very advanced and widespread testicular CA is usu chemo responsive(witness the striking tale one board member shared)

Frizzled-5 Had never heard of it. New article identifies it as a target for pancreatic growth identifying it as a key factor in the development of pancreatic cancer. Involved in cell growth etc- sound familiar?

since we are all interested in pancreatic cancer, among others.

Research used- yes, wait for it-CRISPR Cas-9 technology for the research

interim results may result in the bidding war you suggest.

With one small caveat- the trial results need to be strongly positive.

No one knows if that will be true

It is really very many more than that, as they say abacavir plus a pharmaceutically accepted salt- and there are lots of possible combos

Look at original patent application for prurisol by Menon re: carbocyclic nucleosides, where there are a zillion mentioned pharmaceutically accepted salts that might be linked to abacavir.

NB also as KMBJN aleady said, that prurisol originally acetate bond to abacavir- and guess what, now we have glycolate, and ziagen is sulfate

Bertolino must be mistaken in what he said at the conf, and(1) abacavir must be the active agent, and that also means(2) that ziagen should have action also. There is no getting around this that I can see

Leo wrote that he will respond today about this stuff, so we shall see

The only problem with this of course is that there are NOT 2 abacavirs

There are many different abacavir compounds, incl ziagen(sulfate) and prurisol(glycolate) and a prior post by you was very helpful in putting some of them up for a glance. But there is just one abacavir - with many potential links of course

I continue to write to CTIX daily for clarification, though perhaps all he meant was Ziagen does not work for psoriasis. But is that even really true if abacavir is the active agent?

So he meant to say then that Ziagen has no benefit for psoriasis? But he misspoke and said abacavir? That may be right, but does it make any sense really.

Abacavir we have- I have thought- must be active agent, and changing the salt should not alter that fact- unless the agent is much more key to the whole drug, and maybe glycolic acid is the key. So maybe he misspoke or maybe not. Why bother calibrating doses of prurisol abacavir (glycolate) based on Ziagen abacavir if abacavir is not the active agent? It must be some sort of a misunderstanding

oh please

this same set of facts and timetable was available as ctix just slid down to nearly one dollar

so those facts explain both rise and fall

oh yeah... maybe so it's biotech it's risky it's...volatile

I know he did not say that. The whole point of this discussion, as you of course know, is to try to understand what he meant.

I have written to the company and to Leo to try to get an answer.

If you have any better way to gain clarity it would benefit us all.

Has Dr Bertolino just said that glycolic acid is the active agent in prurisol? After all of us have presumed otherwise, that it is abacavir

cannot grasp your response- it has nothing to do with stealing lotto tickets or risk or biotech or patience

it is a simple question of how glycolic acid plus abacavir work to treat psoriasis
which is the active agent? Or is it both?

very helpful info

what can we learn from Bertolino?

at least we are on the same page

Thanks for writing about this

Still wondering what basic piece of info we are missing as Bertolino asserts abacavir has nothing to do with psoriasis treatment

why not find another delivery agent for glycolic acid?

weird

Glad to see you are paying attn, and we are all so surprised to hear Bertolino say that. I prev wrote about the most fascinating moment of the conference at 19:40, when what we thought we knew about Prurisol is overturned(!?)

I wrote Leo and have not heard back. ? can try Bertolino directly

of course how to rely on 505 with Ziagen as a drug in use if abacavir not the active part of the drug?

Pretty odd. I have a biochemist organic chemistry prof (wife) I can ask about it all when I can formulate the question well.

no one would characterize the results as robust

trial numbers and those who benefitted too small for absolute comfort

trending in the right direction to provide hope for you and me? Of course

we do not know that yet

recall the very small trial numbers

very small

would this be the price if the results were robust? No way-

I did write - we shall see.

I think in the long run this company will be worth a lot, and the short run is just that.

One always wants to buy low, but it is hard to make it so.

LOOK: it is very encouraging that Sonis hamster model predicted human results well in some cases.

It is very encouraging that B-UP shows good initial data. Not just for B-UP but for B-OM too. If these results are positive and Prurisol trial is positive then 2017 should be a strong year for us long suffering shareholders

I have not suffered as long as many - just a coupla years

too obvious for a reply? Ok. When you think you know something, and you find out you are wrong, and it is an interesting topic,then it is at least interesting, and maybe fascinating. Because I own too much of this stock, it rises to fascinating

I certainly presumed the active agent for psoriasis abacavir. Who here thought/thinks otherwise?

So now what?

I get that abacavir glycolate is a different salt from Ziagen, and that different salts might effect absorption etc, but I still thought aabacavir was the difference maker.

Bertolino really saying no?

will write to company.

The most fascinating moment in the call. The time 19:40. Bertolino says that esterases cleave Prurisol into glycolic acid and abacavir, but that abacavir has nothing to do with the treatment of psoriasis. What does that even mean? Does anyone here get that? Glycolic acid is the active moiety? Abacavir needs glycolic acid to benefit psoriasis so Ziagen cannot compete for off label use? What exactly is it all about?

Can anyone clarify?

I am sure that you realize this is easier said than done. Exactly how clear the MOA will be after the next K phase has yet to be explained in any detail.

What by the way is the MOA for prurisol? Not really known, either. Yes I know PRINS etc they say, but not really clear .

next, one searches kevetrin meets with fda trial modification to discover a 12/9/13 PR about CTIX requesting a change in dosing protocol for K infusion.Which was granted

Strange- I thought it was impossible

Impossible things are happening every day.

Yes they could have done something about the dosing frequency- a long time ago

One enters into google search kevetrin half life to discover , with one click, directly from the CTIX website that K has a half life in mice and rats of .7 to 2.2 hrs and 1 hour in dogs

gee I suppose I could look back at those first posters from ASCO years back. And I will when I get a minute

Of mice and men.

you are saying they had no clue it had a very short half life for humans?

that half life varies so widely mice to men?

I am sure they knew the half life was short- that info is bound to be on the original posters for K at conferences 2012 2013(or whatever the dates were pre trial start)

Safety is obv dependent on frequency of drug dose and not just dose

you are asserting that no cancer drug trial has ever been modified to change dosing in phase 1?

I know nothing about it, but I will be surprised if it is true.

And safety is STILL NOT proven, as I have said all along, since safety depends on frequency of dosing not just dose

biodoc- you still out there? Please comment on the recent surge of management talk about more frequent dosing info, oral dosing.

Of course anyone can wish for an oral version of his or her anticancer agent(or antibiotic. No update or mention of oral Brilacidin for cellulitis). So much simpler for a patient in every way.

But making one does not mean they could not have found out about more frequent dosing a long long time ago

1- the trial coulda been done differently from the start. The very short half life was a known entity.
2-no trial in history has ever been modified? I doubt this.

When I complained to Leo about this when I first bought into the stock the reply was, we are gathering a lot of meaningful pk data, yadda yadda. Sure they gathered data, just not enough of the much more frequent dosing data they shoulda gathered a long time ago-

K half life- enough already with this.

Look, all of the recent discussion about oral K is about opportunity for easier more frequent dosing, which is obv true, but what the heck. We have been railing on the board about the half life and the complete failure of the company to address this in a trial modification for more frequent dosing for a very long time already.

so suddenly NOW it is is a big topic for concern- why not address this concern 3 years ago!!??!?

They could hook patients up to a pump and give it all day long for a week if they wanted to- there are plenty of solutions to the short half life other than 3x day, or whatever, oral dosing

Already sick of half life talk that should have been addressed many moons ago. Ugh