Member Info for Grace83

A1 sorry, not AB!

Hey OB!
I like Grace O’Malley. It has a great ring to it :) It is addictive, especially after the drop in price these past couple of weeks. I trust you are well? Did you take the opportunity to top up on the silver stuff?

AB...don’t worry, I have plenty of both :)

I will finish the other thread tomorrow, as the day seems to have gotten away from me. Adam has described half of it more succinctly than I could though :)

Hi Borgie. Interesting, as I definitely remember reading something about the higher dose and an adverse event and knowing it didn’t end up being used, but didn’t know about the jaundice. Then it turned out that the adverse event was at 8mg/kg, which Adam has just addressed, so a full explanation never seemed to be given?! I believe that Mer400 and Noise were having a conversation about it before...?
It’s certainly an interesting topic for discussion, so maybe Tommy would like to put it to Suzy to clarify :)

Great question Tommy. Initially, I also expected the results to include a 16 mg dose and presumed the adverse event to be at this dosage, which prevented results being obtained at this level. As it turns out, this isn’t the case. As Adam has suggested, I also believe it’s down to money and time running out in the extended trial. We started off too low with the dose (problems with biochemistry being different between other animals and humans), which is why myself and Adam pretty much exclude the lower dosages when viewing the results.
Now for the interesting bit. Strap in as I suspect this might be a long answer...
If you look at the pharmacokinetic product for patients 13 and 14 in the bottom right hand corner of the full results, the 8mg/kg dose is pretty much as well tolerated as the 4mg/kg dose. It absorbs nicely into the body in almost the same timeframe. Also, the levels in the blood after administration aren’t double the amount, which is encouraging . This means the body is quickly absorbing the drug and dealing with it well. After a few hours, the levels in blood are low. The error bars are tiny at this stage, after a couple of hours, which means there isn’t much fluctuation in these values, so they are reliable.
Hang on, I’ll carry on with this later, as I’m on my way into the vault to deposit some gold...

I know I shouldn’t, but I just laughed out loud at this...

Great post SamBar. I agree and am always happy to ponder all aspects of companies and not just focus on positives. As long as views don’t directly contradict the science, then they are welcome. Bias will always play a part in people’s posts though, as it has already affected judgement. Whether that’s in a positive or negative way. Makes for an interesting forum though.

Also Iceman hit the nail on the head. As if anybody has any questions, Suzy is very receptive to hearing and subsequently responding to them.

Sorry Adam, I have only just read your post about patient 8 and his infinite doubling time not being included in the mean :)
May I ask if your question is anything to do with the heterogeneity of the results? I’m debating sending a question in along those lines, but you may have already covered it.

Oh and hey OB! Apologies I didn’t respond the other night. I fell asleep. We are all good thanks and hope you have managed to replace your wife’s car and are all well :)
Pup is coming along nicely now and it seems to be a good time to be buying more of the shiny stuff.

Patient 13 is particularly intriguing me. That cancer appears to have been particularly aggressive, as indicated by the ridiculously short PSA doubling time of 7.9 days and a 49mm mesorectal local tumour. To have effectively curbed the spread of that is particularly impressive...also it happens to be our 8 mg/kg patient.
Adam, I think I remember patient 11 from the initial dataset...wasn’t he castrate sensitive? I can’t get the initial results anymore, for some reason, but I remember patient 8 was our castrate resistant who had the initial big PSA drop and maybe patient 11 was castrate sensitive. There was one other high dosage patient that was castrate sensitive that I can’t remember...any ideas? Or does anyone have the data?

Thanks mathsprof. I should have thought of you earlier, as there didn’t appear to be another obvious reason for that patient not meeting the criteria. So basically, his metastatic tumours decreased in size, and the doubling time increased a lot...but this just went over the 25% for the overall timeframe of six cycles. I’d say that’s pretty positive, as he was so close to meeting the criteria. Also silenced the people that said we couldn’t achieve statistical Significance with our sample size. Happy with p<0.05 and maybe we could have achieved p<0.01 when removing the lower doses? Also patient 8 was removed from the dataset, due to his levels dropping, making the doubling time infinite , but he is actually our best performing patient and can’t be used to calculate the mean. Ah well, that’s life, but a happy problem to have :)
I’m pleasantly surprised that we have been given as much information as this, so thanks to Suzy.

Tommy85
It’s a good indicator, yes. This isn’t always the case, but there’s generally a correlation between PSA levels and cancer progression. That’s why other factors are also taken into account, such as tumour size and bone lesions, as PSA is more of an indicator and doesn’t necessarily paint the whole picture. It’s a good piece of the puzzle though :)

I plan to sit down with the data this evening, to have a more detailed look, rather than just the cursory glance of this morning. Would have liked to see which patients were castrate resistant or sensitive in this, but we can’t have everything at this point. That is where I feel the importance may lie in the patterns of data.
At least we have been given tumour sizes and PSA doubling times, so that’s something to go on. Thanks for replying everyone.

After having a quick scan of the data (and I mean quickly, as I’m on my phone on the way to work, so I may be incorrect), it seems that patient 14 had a decrease in the size of his Lung tumours and the PSA doubling time increased by over 100%. But as I can’t see any other information, I’m trying to work out why he didn’t make the pgcwg2 criteria. Could it be that even though the doubling time increased, the overall PSA levels increased by too much? As he didn’t appear to have any additional lesions...unless this hasn’t been printed yet. Shows how difficult it is to achieve PCWG2, as I would be pretty happy if I were him!

I’d be surprised if it was immediately, as the results would need to be peer reviewed, by other experts in the field, first Teamhanz

Thanks, but I wouldn’t be too complimentary towards me, as when the results were released, I was for some reason expecting them to go with RECIST criteria. Instead they went all out with PCWG2, so it was a bit of a scramble to double check the meaning of the results last time! I plan to be more prepared for this release. Who knows, we may be blessed with more detail and a bit of a breakdown...all depends what Suzy can feasibly get away with squeezing into the RNS...
Just hoping for a good outcome really :)

Hi Balanced66

You are scarily efficient and of course, completely correct. I was also drawn in and just tried to address that point, such is the power of suggestion, without even stopping to think that this isn’t the actual issue! Excellent work and great posts :)

I would just like to say that I echo Albinio’s sentiments in that we should take time to re-evaluate each of our stocks every now and again. I believe also that it’s a healthy thing to do

Hi HunSen
I have always valued your contributions to this board. I’d like to discuss one of the points raised, if I may? Regarding phase three trials, the figure of them failing 50% is the time is a crude estimate, as this varies between areas of study. It happens that this figure is very close to the phase three trials for endocrinology, as this has the lowest success Rate outside of oncology. This is mainly due to lots of drugs for endocrinology being off orphan status, so are therefore less well researched and poorly served. I cannot find the figures for reformulated drugs passing phases, so while I suspect this to be higher, I won’t guess, as this would be purely an estimate.

I know that you’re aware of the details of the trial and the subsequent reapplication, so I’m wondering about your thoughts on the 50% value attributed in general? As we both know, the details of this particular trial were that the primary endpoints for phase 3 were not very well thought through, initially. Which subsequently led to its failure. This has since been amended, by changing the endpoints, with Chronocort showing detailed benefits over the current standard treatment. Especially since the longer term benefits were then studied, of a marked reduction in steroid use, better management of androgen 17-ohp, fewer sick days, along with other unexpected benefits.
For me, these points satisfy my curiosity, increasing my confidence of approval (especially considering DNL were given the nod to reapply with amended endpoints). Obviously nothing is set in stone in pharma, which is why it is so risky, so gut feel over whether this is going to be enough to gain approval is all that anybody has to go on at the moment. I completely understand your point about being too heavily invested in this particular stock and wanting to re-evaluate, especially considering the decreasing share price here, coupled with the current rise in FTSE (rebalancing sounds sensible from that point of view, as plenty of FTSE companies still have a way to go yet for seemingly short term better gains). Which is why I’d like to discuss this point in particular about the chances of success of chronocort, without the current share price playing a part in this aspect. As for me, a general 50% chance of success is meaningless, when looking at the chances for a particular drug in a participle scenario, which is why we research and subsequently invest. Counter points welcome :)

I have never spoken anything other than fondly to my gin. It understands both Welsh and English.

Hi Jenny!
I am here. Just having a busy time at the moment. I was going to reply to Adam’s excellent post last night...then promptly fell asleep! Still keeping the faith and waiting for the full analysis. There are a couple of points that I want to discuss regarding the things Adam said yesterday, so will be posting this evening. Have a good day all :)