jantham: i searched the 10Q and there clearly is no reference to death spiral financing. It does give warnings about Aspire selling and causing share price to drop. The quote from the 10Q reads: "...The sale of our common stock to Aspire may cause substantial dilution to our existing stockholders and the sale, actual or anticipated, of the shares of common stock acquired by Aspire could cause the price of our common stock to decline...."
But nowhere, and I mean NOWHERE, did they state anything about a death spiral.
If there was to be a death spiral, clearly we would need a warning for that. I didn't sign up for any death spirals.
I believe you do not see the CEO's actions objectively.
That you see not convincing the market to the value of sapa. that he had to sell over half the company at just over $3 per share as not failing in his duties to preserve shareholder value.
I believe you present valuable information to this board.
But one area where I see lack of objectivity is in your undying reverence for the CEO.
anyone who knows stats/probability and how dsmb likely works... the trial enrollment trajectory probably had a very important factor in dooming the futility.
almost half the study enrolled in final 8 or so months (60 percent per May cc were enrolled).
the sickest of those bubble of patients triggered the futility.
If a smooth patient enrollment would have lead to a 'close call' at futility. Surging their enrollment and being fully enrolled right at futility then killed their chance to squeak by... as that surge reduced the 'yet to be added' patients (narrowing the lens of futility probabilty calcs) and pushed results away from the hoped k-m tail by having the full study on board and almost half being 6 months or earlier.
Sprio's great trebling may have cooked the futility's goose.
l2l: i look at facts and align an opinion to meet those facts. I look at a company like AGIO, which I mentioned here in April/May timeframe. I see huge potential and you don't.
I see Wall St ignoring this company and its had 5 years to get a better appreciation for sapa and its promise. Its now days away from the biggest milestone in its history and Wall St just shrugs.
I have looked at k-m curves objectively. I don't see .725HR ; i just don't. I see low .80s and its a reasonable thesis for the low pps but gives hope to a chance at a path to appreciating pps and eventual nda filing. no slam dunk, but a possible chance.
I just disagree with sapa being a super drug. I don't see it.
I don't see a snss like run... hoping for a fraction of such a run.
positives are I see futility passing, which should be pps supportive.
'less' than positives...
i believe the criteria of the futility is not a high bar to pass that it is a derisking event, but not one that drives a partner.
and that I see dilution coming next year with top line results coming as late as 2016
Hope is Spiro times the secondary better than previous ones.
I believe we'll see pps rise, I'm not confident in a strong surge... somewhat due to the overhang of secondary, somewhat due to the 'close call' I think the market sees for final results.
So a prediction is a decent run up after secondary closer to top line readout. Key of course, is where that run up 'starts'...
Why would company agree to a stringent futility? Does anyone think SNSS had a stringent futility?
I believe cycc has a modest criteria on SEAMLESS? Why? It allows for company options should trial not meet SPA. daco approved in EU with top line study read out of .85 HR. SNSS still believes they have shot at approval with top line .85 HR.
I believe any curve separation trending favorably will yield positive futility.
market pricing in the expected SEAMLESS failure and subtracting off the 5M remaining on the study.
Assuming poor top line data + not moving forward with rmds and assume 12M in cash in 2H 2015.
only thing left is preclinical compounds unless they launch a phase 1 in 2015.
I don't suspect there will be any data from 'solid tumors'. Its coming up on 2 years without an update?
The only abstract of recent note is CYC065 which is primarily being funded by a grant right now. They've talked about an IND, but have never targeted 2015 for filing the IND for CYC065.
What do Paul, Judy, Spiro do for the next 6-9 months? Without any upcoming data and waiting for top line SEAMLESS with a poor outlook.
What does Spiro say or present at the next conference? What will his slide deck look like?
I recall Spiro touting the fact that the DSMB had to give clearance on the pilot's early mortality rate. To make sure no worse than intense chemo.
The numbers were an astonishing 4 percent mortality at 30 days and 13 percent at 60 days. Were healthier patients selected to ensure DSMB clearance? Or just poorly selected
That should have been a huge red flag.
The numbers themselves were probably too good. But that coupled with the fact that the experimental arm doesn't start providing sapa until day 30 should have been a hint of the data likely being skewed to healthy patients. Or at the very least, sapa not playing a significant role at all in the low mortality rate. In fact it had zero to do with the 30 day mortality rate.
The trial itself is interesting and is hugely harmed by a higher than expected 30 day mortality rate. The trial begins on day 30, not day 0. And separation in the curve at that point is truly noise... And potentially damaging to sapa if its in the wrong direction.
If the 30 day mortality rate is 10 percent, that means 10 percent of the patients don't even take any sapa, reducing the power of the study by 10 percent. Which is very significant. Reducing the study size to below 450. It also harms the hazard ratio...
If a relatively high number pass away by day 90, the trial is truly barely testing sapa at all. And based on the early deaths, this number is high. The study's power and ability to achieve statistical signficance would be highly affected.
The trial design begged for a patient increase check... if early mortality rate is much higher due to patients with exceptional poor prognosis a study size boost was warranted because the trial is not really getting a chance to do what its supposed to do... and that is study sapa... Truthfully, the study shouldn't start calc'ing the hazard ratio until day 30 and should have been powered accordingly.
Where did those shares come from? If not put to Aspire between October 1st and the November conference call.
That is a good question.
Only the new director had form 4s during or after Q3. That would not account for the 300k shares.
300k shares during the October run up, would be about 1million.
ice: i think protocol is such that dsmb is instructed to give cycc basic info and a thumbs up or down and recommend halt or continue study based on best interest of patients.
company is blinded to detail results, so we are basically in dark until top line results.
If results are poor, i don't expect to get any detail breakdown.
If results warrant hope or hype, cycc will quite surely get them published/presented at a medical conference (like snss did)
i like your reasoning... the weaker you make daco though, puzzles me as to why they pulled the sapa only arm. and puzzles me as to why sapa isn't given first due to superiority of efficacy because of such a weak control arm.
With a trial where days of mOS could make the difference, why allow the weak control to get the first cycle in the experimental arm and 2 of the first 3? Wouldn't one have greater curve separation at day 30, 60 and 90 if sapa were given earlier?
I would guess the HR would have to be .sub .80. We don't know what exact criteria the DSMB was using.
But with the trial fully enrolled, the range of statistically possible HRs was narrowed versus if the study was not as far along. Combine that with high early mortality rate and your sunk. That's why I believe the surge also hurt futility (narrowing range of probable outcome given current data)
An increase in patient enrollment could have allowed a higher HR value to be statistically significant (SNSS futility). Perhaps that was part of SPA and perhaps boxed the study in a bit. A larger patient pop also makes post analysis subsets more statistically significant.
ice: solid tumors is not happening. phase 1 study with zero updates in 2 years means they are just waiting to remove it from the slide deck. its harder now since its only other active study. I question how active it is.
look at other promising phase 1 programs. They give updates at least every 6 months if not more often
it won't happen.... just saying a humane policy for drugs which improve approaches to therapy administration would be nice.
I'm not suggesting this is possible. Just something that would be humane given the possible statistical conclusion that the therapy is equal or slightly better than dacogen alone.
I'm also not suggesting that CYCC could benefit.
I think if there is no separation from curve, its efficacy for approval. has to be questioned in MDS. My opinion.
Sprio himself implied SEAMLESS would be considered re: MDS.
I don't think they are 100 percent decoupled.
I think you need some curve separation. Without any curve separation, one has to consider that the bulk of the work is being done by daco in this study and that sapa has some but limited effect. Again, IF no separation.
That's the risk of doing either indication first. Results must show 'something' to warrant further development. IMO. If AML is too tough, than high risk MDS isn't going to be significantly easier.
the stat is percentage of deaths occurring before 6 months is 70%. For example... at 18 months, 26% of patients were still alive in above data... so 35/74=47% of deaths occurred within first 6 months in above data.
current 70 percent rate is really high. I'm guessing much higher than anticipated across both arms. I would expect the number to trend down because soo many patients have enrolled in past 6 months. The bubble of enrollment would likely skew the rate higher because a large # of patients still living haven't been able to get to 6 months so if/when they do pass, they would add to the events occurring past 6 months...
That's the super super super long shot Spiro referred to. I don't think its worth spending the $5M for a company that has less than $25M left.
i'm not here to debate future of AGIO. I'll only say i've done better investing in AGIO than CYCC so far.
My original intent of this thread is to discuss the near term milestone of futility. That I believe the bar is set as low as it can go for good reason. I think setting it at SPA height is not likely nor wise.
I believe the company will get a thumbs up or down from DSMB and remain blinded.
I expect positive outcome ; positive but earth shattering pps response ; no partner; eventual secondary and inching closer to top line results...
it is an interesting question. futility is usually much earlier in the study, where a negative outcome can save the sponsor company significant funds as a percentage of the full cost of the trial.
In this case, enrollment is complete about same time as futility. Not normally the case. They've probably spent 85-90 percent of the funds based on management overhead allocation and funding the trial through full enrollment
Would not performing the futility save significant funds? I would think company would still do futility analysis to get a better view of what's going on in the study.