I think the weakness stems from a number of unanswered questions, which may remain unanswered until the Phase III results are available.. In my research I had the Qs below.. I only have access to public domain data though..
1. Data supporting the primary at a week 52 endpoint?
I assume the long-term endpoint was to support a long term label claim with the FDA. SLE is a relapsing/remitting condition which means patients experience periods of flare and periods of remission (relatively quiescent disease periods). Trials in other immuno-inflammatory conditions e.g. Crohns disease (CD), generally separate studies into induction and/or maintenance studies. In an induction study patients with an active flare (moderately to severely active disease at baseline) are recruited with the aim to induce remission/or response in a relatively short time frame (6-12 weeks). In a "maintenance" study its about maintaining a patient in a quiescent disease state, typically over a one year period. In Crohns some drugs work well for induction (e.g. corticosteroids) but not so good for maintenance, and other drugs work well for maintenance (e.g. immunosuppressants such as azathioprine) but dont work so well for induction. The Phase IIb study with Lupuzor was an induction study (week 12), however as the Phase III study is evaluating subjects at week 52 it becomes an assessment of how well Lupuzor can maintain response. As far as I could see this is still an unknown for Lupuzor? The effect size seen in a 12 week induction study doesnt necessary reflect a week 52 time-point, which relies on inducing a response and then maintaining it for a further c40 weeks.
Its been stated by S Muller, that the precise mode of action of P140 peptide is not fully understood, but suggests it doesnt suppress the immune system. Most maintenance drugs I know do work by dampening the immune system to some extent, to prevent a flare (flare caused by increased immune-inflammatory activity). Although by not supressing the immune system this improves the safety profile, it raised questions for me about how well it will work as a maintenance therapy. I'm a little unusual in that actually I'd have been reassured by seeing side effects in the Phase III - as it would reassure me of the drugs activity.
There are also other questions such as tachyphylaxis (reduced response with time if a patient develops tolerance, so may need a higher dose).
2. In the Phase IIb study why should less frequent dosing perform better? Normally a higher dose is ruled out as a) its less well tolerated or b) it adds no additional benefit. In the initial Phase IIa 200ug given every 2 weeks performed well, and was taken forward to the Phase IIb but performed worse than 200ug every 4 weeks. I couldnt find an answer as to why, and S Muller quoted in another paper that in a dose-dependent manner, P140 peptide in saline provoked a downexpression of HLA molecules at the surface of B cells (as also found in MRL/lpr B cells) i.e. in mice the higher the P140 dose the better the effect (work by Page et al, annals rheum BMJ 2011). Without a scientific explanation for why a lower dose in man worked better in the IIb study a reader is left wondering whether the difference between the 2 doses is simply a chance effect, and the true response could equally be the response seen with the more frequent dosing?
3. Can trehalose have a systemic effect to inhibit P140 activity, when given in small doses, every 4 weeks,? Study C33457/2047 was undertaken by Cephalon on the back of the above Phase IIb study. Subject were treated for 24 weeks and results showed a placebo response rate at week 24 of 40% and an active (P140) response rate of 34%. The failure to show a positive difference in this trial was attributed to the excipient trehalose dihydrate, a disaccharide of glucose. A question arose to me as to whether trehalose dihydrate given in relatively small doses in man (circa 50mg) every
Interesting. I derisked some time back but keep a decent sized holding. I also expect a 2nd phase 3, and I've no idea how the market will react to that, although it's the most likely option. Key for me though is proof of concept as IF it does actually work, even at such low levels, then it opens up P140 with platform potential, so while the market might like it or not, anything other than a failure (ie no better than placebo) would be a win IMO.
Hi DD Id imagine IMM have the timeline for DBL pre-agreed with their Vendor (typically c4-6 weeks after last subject out). Normally DBL is a milestone that the clinical team work to (with the PIs and sign off as well), but maybe I can understand TCs reluctance to share the date . Agree with you about the speed to which the primary can be pulled following DBL.
However, I decided yesterday to sell my long held stock, (get the impression the market wont be so accepting of another Phase III as me) so my interest now is curiosity in results. Might buy back in after?
Hi, and yes but not often. Was alerted to it on twitter group. Good post by the way and agree once locked it could take seconds to the top line results, but as I suspect you have experience of, it's only once all the data is in that they can check any potential conflicts/issues with trial centres. Depending on the nature and number of these, it would delay the lock. Having said that, can't be long now.
I'm not on any of the other forums but had a look at LSE and ADVFN and some very good updates on last nights event.... Have to ignore the clinical interpretation by a lot of the rampers on ADVFN (they don't look like they've had any pharma experience) but some good snippets in-between the ramping posts..
Is anyone going to the investor meeting tonight? One question, if possible, would be the timeline for database lock (DBL) - this is the point at which you can unblind the data? If anyone can ask, that would be great, as were now over 5 weeks since last patient out, and 9 weeks since the last week 52 visit. The study would have used electronic data capture (eCRFs) and the data cleaned as the trial progressed, so database lock should have probably happened, especially as Simbec-Orion have an invested interest, and would have put their A team on the data management.
Although there will be literally 000s of pages for the full tables and listings, as this is Phase III there is one table that counts more than any other and thats the responder analysis for the primary endpoint at week 52 in the Full Analysis Set (ITT pop). To generate this table, following DBL, is very quick (could do same or next day if you really wanted to). It will take several weeks to generate the full tables and listing, analyse the subgroups, and write a report, but IMM should know now whether the trial has been successful.. Phase IIIs a bit more black and white than Phase II in as far as a definition of success goes at least.
I was hoping an RNS would be released ahead of todays meeting? I couldnt work out the purpose otherwise we know what Venture Life aims to talk about, but not IMM? The other indications are interesting, as is the size of the market, but in a nutshell we really need the Phase III topline result first I think
Presenting on the night will be;
Mr Tim McCarthy Chairman of Immupharma plc IMM.L (www.immupharma.co.uk). TPI acted as Placing agent in the recent £10m fundraise.
Mr Jerry Randall CEO of Venture Life Group plc VLG.L (www.venture-life.co.uk) TPI is joint broker to Venture Life and Jerry will be providing an update on recent developments and future plans for the company.
Raise was at 144p too - and, as Rick points out, that was indeed not them out looking with cap in hand but an approach from ii(s) wanting to get involved - and so s/p weakness from 180p ish can be categorised as significant now...and for bulls here a potentially good buying opportunity has arisen, perhaps.
As a bull here I have started to buy back small amounts recently - had sold down 90% of my original holding from 80p ish up to 170p ish - and will likely continue to do so, especially if goes sub 100p..
Not long to wait either as there will be and announcement on phase 3 trail results sometime in next 6 weeks and that will have a huge impact one way or other here.
Granted, a nagging doubt on leak about some lack of 'success' does creep when the s/p has come off like it has recently but my guess remains that it will have been a successful trial and will get some sort of FDA ok - maybe not fast track - to progress towards market off the back.
Also I note also they said in the raise update RNS that discussions are ongoing with partners towards getting Lupuzor to market:
''The proceeds of the Placing allow the Company to make investment into potential indications emanating from the Company's P140 platform, in addition to lupus. The Placing further strengthens the balance sheet and enhances ImmuPharma's position in ongoing and future negotiations with potential partners for Lupuzor.
We look forward to providing our shareholders with further updates regarding the Lupuzor Phase III trial with key data still on track to be announced before the end of Q1 2018." ''
I think that a top partner coming on board in some shape or form here could be transforamtion to s/p
Unfortunately drop outs are part and parcel of any long term trial Im afraid. Even open-label studies, with licensed products, and good safety/efficacy profiles, we still see 20% dropouts in a year. There are many reasons for discontinuation, worsening of condition (even with the best drugs), AEs, lost to follow up, or even patients withdrawing consent because they wish to receive a new licensed product that wasnt available when they initially consented to a placebo controlled blinded study. To power a study you normally account for dropouts, but of course this could be slightly higher or lower than your assumptions. As a note I see that the estimated enrolment for the new extension study is 100 patients (as per clinicaltrials.gov). I would assume however more than 50% of patients made it through week 52 though.
Im not the same PJ, sorry. My background is very much in clinical/drug development so there are better people when it comes to the financials, and charting. It's why I sometimes look at BBs as well..
What other SLE trials had so little in the way of side effects as Lupuzor? Lupuzor has been described as benign in terms of side effects. Why would anything like as many as 20% of the active arm Lupuzor patients drop out? Their lupus symptoms will be decreasing as the trial progresses and they will not have been put off continuing in the trial as a result of side effects.
Hello PJ (assume that you are the same as pharmajiles on the FUM bb but if not ,apologies). I hold a few IMM as well as (rather a lot more) FUM and given your proven ability on charting the FUM share price I wondered whether you have charted IMM to such a degree?? I just also wondered where the share price might end up if you are correct and they need another study?
All is dependent now on whether the trial is successful. As this is a Phase III study, success means reaching statistical significance (p value <0.05) on the primary endpoint (at week 52). Although the FDA may look at the secondarys, unless the trial hits on the primary, the secondarys will really only be of academic interest (and another study will almost certainly be required). So the key question is whats the probability of the study hitting its primary?
To evaluate this if we first look at the likely placebo response rate. (Note: this isnt a true placebo group as its an add-on to standard of care, thus increases the placebo groups response rate). If we look at the Benlysta study with a similar primary endpoint, study design, at the same primary time-point, we saw placebo rates of around 48% (as per GSK website). If we look the Lupuzor phase II we saw at week 24 the placebo rates were 53% (placebo patients off treatment). This gives a starting point for assumed placebo rates at the longer term (primary) time-point of week 52. Its harder to gauge the likely Lupuzor response rates at week 52 as I could only find one other trial at the longer term time-point (Study C33457/2047), which failed to demonstrate a difference between placebo and active.
So working backwards, if we assume a best case scenario of 40% placebo response rate and we have 200 patients in the trial, we would need a >60% response rate in the Lupuzor group to achieve statistical significance (based on an 80% power). Power determines the ability to detect a treatment difference when one exists. Phase IIIs are often powered to 90%, but you would need at least 258 patients to achieve a 90% power, based on a 20% difference in treatment arms (hence the Benlysta Phase III studies recruited over 800 patients to each study, and achieved statistical significance with a smaller difference). Now, we have to consider drop-outs. In a trial of this nature the normal drop-out rate, over 1 year, would be around 20% (and this appears to be the case with other SLE trials). The trail will most likely consider drop outs (missing data) as non-responders (i.e. assuming no LOCF will be used). What this means is although 100 patients will start on Lupuzor, around 80 will complete to week 52. The denominator however will be based on the starting number of 100 (ITT population those who received at least one dose of study drug ). This means to get a >60% response rate on active you would need >60 out of the c80 patient completers (i.e. >75% response rate in those evaluated at week 52). Although not impossible, based on probability it will require another study to satisfy the FDA.. IMHO
A long winded answer as to why raise £10 million now but hope it helps..
The recent interview was very positive, the impression that was given was the results would be excellent and that it's basically a "done deal"...
I hope the results are as good as everyone is expecting them to be, but just an honest question.. please don't shoot me down for asking this...
If the management are so confident, why dilute existing share holders now to raise funds? It's not like there was a massive waiting time till the results of the clinical trials are released so why raise funds now? If I were management and confident of good results, I would have waited till end of 1Q and if funds were needed, I would have raised them then, in a much more powerful position....
"Last week, I wrote about companies that have disappointed in recent times, but have potential to bounce back this year. This week covers health and pharma companies that may have been taking years to develop a product or technology and they could ..."
I am very happy to have bought and held a substantial number of these shares since early 2016 at an average price of less than 100p. The latest news from the company about Lukozor is good. You can make money here as a dealer, but for me this was and still is a
gamble on Lukozor.
is please can I have the 12,000 shares I've sold between 80 p and 160p back.. I've only 3000 left to sell now.. yikes..
The market cap you're talk about off the back of the future s/p target numbers you quote is incredible to me .. especially, are you sutre about 877p ? (It's now the guts of a quarter of a billion mc.. that factorial is a big big big number indeed...)
<b>ImmuPharma PLC 40.2% Potential Upside Indicated by finnCap
Posted by: Amilia Stone 12th December 2017</b>
ImmuPharma PLC using EPIC/TICKER code (LON:IMM) a pharmaceutical company focusing on developing novel medicines with high sales potential has had its stock rating noted as Initiates/Starts with the recommendation being set at BUY this morning by analysts at finnCap. ImmuPharma PLC are listed in the Health Care sector within AIM. finnCap have set a target price of 237 GBX on its stock. This indicates the analyst now believes there is a potential upside of 40.2% from the opening price of 169 GBX. Over the last 30 and 90 trading days the company share price has increased 71 points and increased 121.75 points respectively. The 52 week high for the stock is 171.75 GBX while the 52 week low for the stock is 36 GBX.
ImmuPharma PLC has a 50 day moving average of 105.55 GBX and a 200 Day Moving Average share price is recorded at . There are currently 129,665,818 shares in issue with the average daily volume traded being 360,049. Market capitalisation for LON:IMM is £222,340,888 GBP.
And i'm still selling down by increment but am alas down to a third of my original holding now .. and having started selling way before 100p - less than 80 p from memory - it is now occurring to me that I may well end up having under sold my holding considerably - aka massively - here.. still eveyone is wiser with the benefit of hindight and pharma is an area that I'm relatively new to betting on and so I live and learn for when such situations come again ( hopefully with Futura or Midatech for eg )
PS; As we're still at phase 3 here - although it looks like that will now be successful and they maybe get a fast track licence path - this may well go much higher again from here .. I guess.. unless issue(s) come out in final testing results .... probably unlikely that now, I'd guess..
Still, very - very - thankful for this... and still a fair few thousand left to sell..and will keep doing that by increment on further strength , hopefully
I've stopped selling now Chrissp.. but that's perhaps 'for now' instead of 'now' though.. I'd think about selling a little more at 115p if it were to go there.. obviously if in a years time this is approved and on the market then it would be a lot higher s/p than this.. how high I don't have a clue..also there has got to be a decent chance of some sort of a deal / buy out with a bigger player... although they may go it on their own too..
It's approaching 150m market cap already I see....so perhaps multi baggering from here is a big ask...
Nice to Michu - interesting that you have sold some of your holding. I am keeping all mine that I have accumulated over many years at an average of 62P. This is the first time that I am showing a gain.
I am amazed that they have jumped by nearly 20% this morning with no comment from the company.
maybe it's buy and hold institutional money coming in here..
I sold another 10% at 100p just now.. maybe I shouldnt be selling at all .. only time will tell .. still have a decent chunk left though and my average is 50 ish p..
surprising and nice...
please keep going up ...
Seems some serious money is doing some stake building here today.. question is how big a stake are they building and are the traders or buy and holders etc.... and thats a guesssing game...
I'm thankful to have done very nicely here so far but I still have high hopes fro here .. however I sold 15% of my holding near end of today as I've seen two quick big rise occurrances like this since i've been involved and both were followed by good subsequent falls, in due course.. However, we're getting close to phase 3 results and hopefully allotment of slot on super fast approval process - 6 months ish I think from RNS memory - and so it could be very diffeerent this time (hopefully)
Effectively a one trick pony though which is always tricky :-).. but that one trick might be a hell of a trick.
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