Ann: Prima BioMed's CVac granted Fast Track D, page-49

re: Ann: Prima BioMed's CVac granted Fast... Lol sorry Macenroc I really shouldn’t post at night.

HCREC means an Ethics Committee which in Australia more properly is known as a HREC. Why I used HCREC is because at large institutions there are often a few ethics committees (eg a social and behavioural one, an animal one etc) and locally people distinguish them by the “C” to denote Clinical. So Human Clinical Research Ethics Committee (HCREC).

I shouldn’t make the problem seem worse than it is though. PRR probably does have enough money to complete Can-004b but it may mean delaying or cancelling the Pancreatic trial. I haven’t done the accounting maths from the analyst’s report to work it out.

But Kbear1 we can good naturedly probably disagree on this one (and your generous comments are reciprocated). And yes it is my prediction that PRR will try and secure funding for Can-004b through a capital raising at the first opportunity there are positive results coming out of Can-003.

And PRR will be right behind the eight ball on this one. It has always struggled to raise money – right from the start of Can-003 into the last raising. The failure of QRX alters the landscape for Aussie biotechs. Its not going to be simple.

The sharp share price increases on PRR announcements is something quite spectacular. The announcements (Bulgaria approval, fast tracking etc) are non news but the sp rises 50%. Imo traders don’t manipulate these increases – rather they are the victims of it. Somehow or other online punters on the ASX are snared in these pumps and dumps that then fail to follow through on PBMD.

Given that the US would have 10 times the number of traders than us ... why is it that we are 10 times more likely to be snared. There is minimal analyst coverage of PBMD so the average US punter can’t be that much smarter than us and the ability of shorts to be taken to dampen spikes doesn’t seem to occur. So what explains it is a mystery. But someone understands the loose shareholder base of PRR and ASX market psychology extremely well.

So as a community service (knowledge is power sort of thing) ... what will good results coming out from Can-003 look like. My impressions would go something like this ...

Grade A results.

Two survival analyses will have be conducted on first and second patients for OS separately. From these analyses a Hazard Ratio (HR) statistic will be reported with a 95% confidence interval. The HR tests the difference between the Overall Survival for Cvac versus SOC controlling for exposure. The lower the HR and the tighter the 95% CI the better the result for Cvac. If the 95% CI crosses 1 it will not be statistically significant.

Step one look at the HR for OS compared with the HR for PFS for first remission patients. If this is lower this it tends to support PRRs idea that the good result for PFS in first remission in the SOC has not translated to better survival.

Step two. Check that the PFS advantage (HR=0.41) for second remission patients has been maintained. It shouldn’t mathematically change much. Ideally it may become statistically significant from p=0.09 (but most likely not).

Step three. Look at the two HRs for OS in first and second remission patients. Are these lower than the two PFS HRs. If so this tends to support the idea that OS is a better outcome measure of Cvac than PFS.

Step four. What is the OS HR in second remission patients. Is this lower or around the mark for what Can-004b has been powered on – which is 0.67 for P=0.10 (one sided). Note at this point that the p coming out of Can-003 is two tailed with the aim of producing p<0.05

This gives a bit a bit of insight into actually how compelling the signal was from Can-003 at the design stage of Can-004b that the bar was set so low for Can-004b. But if the Can-003 OS HR is quite a bit lower than 0.67 all is good that Can-004b might be successful.

Step five. Is the OS HR in second remission patients statistically significant? If so this is the icing on the cake – and even I will agree the signal coming out of Can-003 is moving toward the compelling territory.

To be honest I would ignore or discount the T-cell activity data. There is too much confusion about how T-cell activity translates into PFS or OS which is the main game.

The scenario I have outlined here argiably is impossible to meet because it is just too early and the sample is too small. So I would expect a bit of greyness and variability.

What would grade F results look like. The first fail would be not to show any update for OS at all. The second fail would be to present raw numbers on first and second patients combined and not to perform a survival analysis on them. Particularly if there have been a reasonable number of death events.

This would make it virtually impossible to make a judgement about the quality of the results because the exposures between patients on Cvac and SOC will be impossible to establish because no one quite knows how the randomisation - stratifying and blocking was performed.

And you would assume there is a negative reason for not performing a survival analysis. Another big fail will be if there is missing OS data or if PRR start making another argument that results will get better as the data matures.

The funny thing will be that mysteriously the market will know exactly what these complex results mean in an instant. Adding to mystery is that ML plans to make another announcement after the results announcement – so it will be mystery on mystery.

All the best Southoz