Verona Pharma Share Discussion Threads

[aimshares] 29/6/2014 08:36

Thanks TimboWould you think they would now consider speeding up rpl554 in anyway ? By the way forgot to mention, I met you with Muzzy after AGM for lunch.

[jeddicat] 27/6/2014 09:08

Thanks timbo, it was just an elementary thought that may have escaped some. I would not agree that the Italian (Mediterranean) diet is anything like ours,to be honest. They also get a lot of sun. Oh! They are also very quick and handing over their rifles and asking where the POW camp is situated,they never need an escort. Lol!

Anyway, many thanks, and as I say it was only a thought.

Regards

[timbo003] 27/6/2014 06:19

I should add that diet (in relation to ethnicity) can also be very important in the case of orally delivered drugs (GI transit times can differ immensely with diet). Indians/Asians seem to have faster GI transit times than Europeans in that respect (lots of noodles and vegetables), which can have profound effects on drug absorption.

[timbo003] 26/6/2014 21:34

JC

I doubt if that will be much to do with it. Italians and Brits are too similar in ethnicity (and diet). Having said that there certainly are examples of where different ethnicity (and diet) can effect drug response due to different genotype.

I think the best known example is Alcohol dehydrogenase (ADH) and Aldehyde dehydrogenase (ALDH). Generally Europeans have a lot more ADHL than Asians and hence a much higher capacity for alcohol, as explained here:

[jeddicat] 26/6/2014 14:29

Timbo -
s
Italian -v- UK people tested?

[timbo003] 26/6/2014 08:53

>>>>>share price

See slide 7 of the analyst presentation.



From fundraising £14M, which is around £12M net

I guess they have £4.8M more to spend now than they thought they would have.

Cash burn (standing still with little no R&D) seems to be around £1.2M/p.a.

They stated they will spend £5.3M on RPL 554 (over approximately 2 years)


>>>Shakin

Without seeing the actual data from the two studies, it is difficult to say, but one explanation could be that VRP700 is effective in a minority of individuals (responders) but in ineffective in others (non-responders).

In the Manchester study, they missed the primary end point, but they do not state whether they just missed it, or whether they missed it my a mile. As I think Nigel inferred earlier, the prolonged wait for the results, could have been because the results showed that the VRP had some activity, but not enough to be considered good enough to progress.

The only real details we have of the first (Florence study) are in one of the VRP700 patent applications, which I reviewed in a few posts starting here:



Details are very scant and clinical study results cited in patent applications are not subject to a peer review process, but there appears to have been a pre-selection process, so maybe only responders were included in the data analysis for Florence, whereas both responders and non-responders were included in the Manchester study.

[shakin not stirred] 26/6/2014 01:16

Two 1st in class drugs? Maybe one!!!! How can two trials be so differing and how accurate is the measurement for the 1st and 2nd trials.

[share price] 25/6/2014 11:00

Timbo Or Anyone else

How much would now be left from the amount set a side for VR700 now it's development has been dropped.

My understanding was they were going to spend 2.6 million to finance the VRP700 clinical trial & 2.2 million to finance pre-clinical work on VRP700.

[thebossman] 24/6/2014 20:10

Looks down and out....

[jollynews] 24/6/2014 06:07

Verona Pharma to drop VRP700 development after Phase IIa trial fails to meet endpoint
Today, 4:45 AM

[kfp] 23/6/2014 18:33

Still a one trick pony.

[127tolmers] 23/6/2014 18:10

I suspect the price drop is overdone. We now have single focus on the main chance with no other cash drain.

[fludde] 23/6/2014 13:07

I doubt this news will shut Weekly up so there isn't even a silver lining!

[duplicate book] 23/6/2014 13:06

I reckon they knew about these results prior to the AGM, but have released it now so that they didnt get all the flack and awkward questions put to them personally!!

[timbo003] 23/6/2014 12:58

That is a good point nigel, the shares are probably better value now, although I won't be buying any more either, bottom draw now for the next few months at least, as there is no significant news flow on the horizon regarding RPL554 clinicals until 2015.

The AGM format makes a bit of sense now. No Chris Evans present (presumably he knew about this) and considerably more time spent on RPL554 than VRP700.

Some might think that the lowly share price in the run up to these results may have been telling us something, but I very much doubt it, although some people involved with the study may have had an inkling about the outcome.

Even though it was a blinded study, it may have been apparent to the investigators that neither treatment was having much effect, in which case they do not need to know which treatment is placebo and which is active to have a guess at the outcome.

[buywell2] 23/6/2014 12:06

Too many cash strapped small would be BioTechs

Scrimp and don't spend wisely on getting meaningful data by carrying out pre-clinical 'quality innovative 'human cell based' ADME Tox testing of their new drug compound.

Summit (SUMM) for example just had a bad Phase 1 result showing poor 'uptake'

Getting bad CLINICAL TRIAL results when humans get used later hits shareholders hard .... which is why living human cell based assays are at long last being adopted but fast.

Many decent CRO companies actually provide help and guidance on putting right issues found in pre-clinical tests .....

[gnnmartin] 23/6/2014 12:03

Does the failure of VRP700 affect the value of RPL554? If not, then the shares are better value now than they were. They have half their IP assets and are valued at cash.

The failure of VRP700 certainly reduces one's confidence in the company, but I don't know how rational that is. VRP being late with the news but being certain they would none the less get the news to us by the end of June suggested to me that they had the data but were unsure how to interpret it: in other words, were looking for a more optimistic interpretation than was immediately apparent. I tried to probe that at the AGM, but (I suppose quite correctly) I did not get any clarification. It was very tough for the board having to duck questions to which they knew the answer. All the same, since they left me in no doubt their confidence was undimmed I do feel just a little bit deceived: I'll not bother to attend another VRP AGM.

I'll hold, but I think I'll resist the temptation to buy more.
Nigel Martin

[timbo003] 23/6/2014 11:47

This is a salutary lesson in trying to extrapolate from preclinical studies and data from small clinical trials with woefully small numbers of patients, especially those that do not tick all the right boxes.

The preclinical data was fairly impressive, but it was just that, it was preclinical and just because it is effective in guinea-pig, does not mean it will be effective in man, as I know only too well from working at the coal face for a number of years.

There have been two previous studies in humans (both referred to in the recent VRP700 patent applications), the first one using a highly objective induced cough model did not show an antitussive effect. We have never seen details of this study, but the fact it was induced cough, rather than in patients suffering cough, leads me (and I'm sure others) to assign only little weight to its significance.

The second study (Florence) with a very low number of patients (8) did show an effect, it was a randomised, placebo controlled study which used objective measures (but with some subjective pre-selection). Headline results were impressive. I reviewed the protocols and designs for the Florence study and this recently failed Manchester study a while back


Looking back, I think I would have still concluded that the manchester study was likely to be successful, but perhaps should have paid more attention to the low numbers and unusual contingency design which involved a subjective assessment.

I'm beginning to wonder, whether VRP 700 (carcainium) is just another me-too local anesthetic but with a low potency. Perhaps the reason that it has previously been shown to exert a selective antitussive effect, has been due is local anesthetic properties.

[buywell2] 23/6/2014 11:02

Thanks , here is another

The most frequently used statistics are "90% drugs tested on animals fail" – British Union for the Abolition of Vivisection

"92% of drugs fail in clinical trials, having successfully passed through animal studies" – Safer Medicines Trust
 "In fact according to the FDA's research, nine out of ten drugs deemed successful in animal tests fail in human clinical trials" – Humane Society International

The main sources of this information come from the US Food and Drug Administration (FDA). In 2006, Mike Leavitt said:
"Currently, nine out of ten experimental drugs fail in clinical studies because we cannot accurately predict how they will behave in people based on laboratory and animal studies,"
said Health and Human Services Secretary Mike Leavitt.

The 92% statistic comes from an earlier report which showed only 8% of those drugs passing animal testing stages would go on successfully to be FDA approved.

"For example, a new medicinal compound entering Phase 1 testing, often representing the culmination of upwards of a decade of preclinical screening and evaluation, is estimated to have only an 8 percent chance of reaching the market." – Challenges and Opportunities
Report, FDA, 2004






So doing the 'RIGHT' set of pre-clinical assays on a new drug compound using the RIGHT CRO or company to carry out latest 'Human Cell Based Assays ' can save LOTS of time an $1 BILLION and more

[patelk] 23/6/2014 10:47

You both make good points. Drug discovery is not dis similar to a lot in life. Only a few footballers or musicians make it big but it certainly makes the rest aspire. I personally have faith in people... Good people. There are a lot of learned people in the lancet article who seem to think this final drug has some promise. Yes very few drugs make it to FDA approval. But investment is about timing and sentiment on this could change and that could be a better time to exit!

[buywell2] 23/6/2014 10:35

so you like to gamble eh

well here are the odds




For every 5,000 to 10,000 experimental compounds considered, typically only one will gain Food and Drug Administration (FDA) approval, after 10 to 15 years of research and development costing an average of $1.2 billion, based on a 2007 study. -

[kfp] 23/6/2014 10:30

I think he was talking about established companies with visible earnings and dividends.
He only invest's "in companies he understands" I doubt many of us understand drug discovery and regulatory approval !

[patelk] 23/6/2014 10:19

Final post. Just bought 50k more. Shows up as a sell. I am not a ramper. Just a gambler! But as Warren Buffet says. Be greedy when others are fearful!

[patelk] 23/6/2014 10:06

InterpretationIn four exploratory studies, inhaled RPL554 is an effective and well tolerated bronchodilator, bronchoprotector, and anti-inflammatory drug and further studies will establish the full potential of this new drug for the treatment of patients with COPD or asthma.Efficacy and safety of RPL554, a dual PDE3 and PDE4 inhibitor, in healthy volunteers and in patients with asthma or chronic obstructive pulmonary disease: findings from four clinical trialsLui G Franciosi PhD,Prof Zuzana Diamant MD,Katharine H Banner PhD,Rob Zuiker MD,Nicoletta Morelli MD,Ingrid M C Kamerling PhD,Marieke L de Kam MSc,Prof Jacobus Burggraaf MD,Prof Adam F Cohen MD,Prof Mario Cazzola MD,Luigino Calzetta PhD,Prof Dave Singh MD,Domenico Spina PhD,Prof Michael J A Walker PhD,Prof Clive P Page PhDThe Lancet Respiratory Medicine - 1 November 2013 ( Vol. 1, Issue 9, Pages 714-727 ) DOI: 10.1016/S2213-2600(13)70187-5

[patelk] 23/6/2014 09:53

Do what do we do with this ,VRP paper! Sometimes it is best to open the bottom drawer and put it away. One day you will open in and there is just a chance that this paper has turned to gold! Life has a habit of throwing these surprises at you. Sometimes we fail to see the value of what we have. Time is an amazing educator. Or you can cash in some and put some away! Just the ramblings of an old man. Thank you for listerning.