Member Info for Ivyspivey

The cost of getting Iclaprim to where we are now has been in order of £250m as compared to Omadacycline cost of $1bn by PRTK.They obviously have Approval and MTFB needs that to get full value.
This value is enhanced considerably by having patent protection until 2037

Looks like a mistake to me

Morning Vascular
All drugs are subject to post marketing surveillance whether as part of a Phase 4 or just having to face scrutiny for post Approval adverse events.
Don’t think the market will view this any differently.Any drug which is Apprived is considered safe and effective and of course may have a black box warning in advance.This is what the market wil judge and how it may restrict market development rather than any worries about what may it may not happen in the future based on possible expansion of usage numbers and any specific concerns that may materialise

Yep the benefits clearly outweigh the risks imo given the current level of evidence.
These ABSSSI patients desperately need effective treatment and overall can be quite compromised so the choice is use standard of care Vancomycin which is known to induce kidney damage or use Iclaprim which may have a very slight risk say of inducing liver damage in a very small number of patients.
As I say I think the CRL is about quantifying this slight risk and this is difficult given the temporary raised levels,the difficulties of establishing clear causal and prognostic indicator links with these to more severe liver damage,the checking of the history of these patients and the difficulties associated with short course AB treatments.
As the issue appears to have been raised late in the process more likely to be a labelling issue and could be about the exact words either in the indication panel or contra indications.
The silence from MTFB makes all this conjecture but do believe there will be clues in the near future as to how this will play out

Morning N4aP
Imo your post is a reasonable summation of where we are with Iclaprim except when it says cost-significantly cheaper
as it won’t compete on cost with other standard of care treatments like Vancomycin as they are all generic but the cost saving is on avoiding the extra monitoring etc associated with using Vancomycin in renally impaired patients( kidney issues).
The link Vascular posted re FDA concerns on overall drug safety re liver issues I think is the catalyst for requiring the additional data as reported in the CRL.
It seems liver toxicity on any drug is a particular focus for the FDA and likes to be absolutely clear on any link with raised ALT levels in particular but also AST in being prognostic indicators for causing more severe liver damage.
As the numbers involved in proving any specific linkage are very high like 1 in 10000 etc for them to place specific frequency’s of possible issues then these numbers are simply not covered by any phase 3 trials which are likely to be in the 1000 mark.
So they have to make assumptions about the linkage of raised levels and the likelihood of ore severe liver damage.This is where it gets complicated and you have to look at underlying conditions and commonality amongst those with elevated levels and how high these levels were raised etc.
This info is more difficult to assess in relatively short courses of treatment like ABs like Iclaprim which is only 10 days.
So is still not conclusive as to how much work will be required.
You don’t have to do trials involving many more patients as you simply get the additional data via post marketing surveillance and there are many other drugs there associated with causing liver damage which are already approved.
You have to look at benefits of Approving Iclaprim and these appear clear in terms of outweighing known risks.
We don’t know if it is about specific labelling claims and of course it is about interpretation of the linkage between elevated ALT levels and drug induced long term damage.
The fact that the levels returned to normal after discontinuation and the lack of biliburin displayed are positive and of course you can identify those at risk patients early in the process so for eg can say anyone who has elevated ALT levels you can simply monitor more regularly and stop treatment if considered necessary.
Food for thought and fact that big institutions appear to have maintained their holdings apart from the risk mitigation considerations on day CRL dropped is again a positive as is MTFB requesting the FDA meeting as they seem I think they can provide the necessary reassurance but just need to clarify exactly what is required to move this firearm.

TP
As I answered before I dont think we know if any patients received the 40mg dose or not.

Yep Iclaprim USP has always been kidney safety.
In the original Arpida trials they used a weight based dosage as well as fixed 80mg.
At the preliminary meeting in 2015 the FDA recommended the fixed dise 80mg to get over some of the safety concerns
Of the original phase 3 especially the Cardiac Qtc issues without compromising efficacy which proved the case

The finding of a higher rate of such elevations in drug-treated subjects than in a control group is a sensitive signal of a potential to cause severe DILI, but it is not a specific signal.

Again the differences between Iclaprim and tbe control Group were greater in AST and not ALT which is more prognostic of liver damage

Vascular
Thanks for posting link.
One interesting part

The ability to cause some hepatocellular injury, however, is not a reliable predictor of a drug’s potential for severe DILI. Many drugs that cause transient rises in serum AT activity do not cause progressive or severe DILI, even if drug administration is continued. It is only those drugs that can cause hepatocellular injury extensive enough to reduce the liver’s functional ability to clear bilirubin from the plasma or to synthesize prothrombin and other coagulation factors that cause severe DILI. It is important to identify those drugs as early as possible.

With Iclaprim no patients had bilirubin more than 2x Normal Liver Levels

Hi TP
Could be we simply don’t know.I don’t know think you can presume all patients received the 80mg dose.
Think the 40mg dose rate was for moderate liver impairment so MTFB could have gone for a clean licence and it may be labelling say re mild liver impairment that is the issue.
Overall I doubt it and think it is about the elevated AST and ALT levels but simply guessing.

Helps if you post link

https://academic.oup.com/cid/article-lookup/doi/10.1093/cid/cix987

Vascular.Please see Table 5 for elevated AST and ALT levels and imo these are the additional subset data the FDA require.
As you can see from the text all elevated levels returned to normal baseline levels once the treatment was discontinued

Jay- understand about wish of some to average down but also a question about how overexposed to a particular stock you want to be and also the CRL has changed the outlook here both in terms of risk,dilution and timeline.
My way to ease some of the pain here is to try and recover a little by trading MTFB.Dont get me wrong it will only make small inroads into my potential loss here but just doing nothing and waiting for recovery while the SP moves up and down within a narrow trading range is something I need to try and capture.
This was more so in the days immediately following the huge drop on 14th Feb and think it is important to have the odd small victory even if the overall picture is not good.
Helped me move on.
Just staying invested in these long term bios for 4 years and you take all the risk and the ATs made it difficult to exit at a decent level and you either lose money on drift or have one very bad day.
Yes I am posting less on here but purely down to the day job and also just don’t want to spend time arguing with folk over nothing.
Of course we want to list to all views opposing ones as well but to get accused of being a Pump and Dump merchant or Ramper when you have been here all 4 years MTFB have been on AIM is just beyond me.
Of course I have been confident and if you have a large investment it would be stupid not to be.
Take Petch even he thought Approval would happen and of course disappears as soon as he appeared .
So posting less as you just get distracted from what is happening in the market elsewhere and you miss out.
So more detached,bit more trading,stepping back a bit more and is helping ease a bit of pain here
When I said slap in the face yes kick in the balls was probably a better analogy lol

My point re Invesco was that so called professional investment outfits were prepared to continuously support repeated placing s at 5-8 x higher than current SP to maintain a 25% stake so about £25-30m at one stage then it as unlikely to be a “ turd”.

Morning Jay,
Not surprising that lots of new posters with different agendas and many with the luxury of a much lower average.
As everyone was hugely disappointed with the CRL and the SP response and we are not out of the woods yet and until we know the detail of the FDA concern and the necessary finance is sorted no one can be certain of how this will play out.
Most LTH will settle for a delay even if it takes a while in order to secure Approval and yes there are still things I am not entirely happy with like lack of a Plan B but I really want to look forward rather than backwards.
Must admit my experience here has changed my strategy about holding onto these bio stocks long term as just don’t think it is worth the risk until they are revenue generating which was one of the main attractions here given the timeline to commmercialisatiin.
Obviously the CRL changed everything and we have to live with that and it’s consequences certainly the last month.
Let us all hope the longer term consequences are much more positive and like you I am still positive about the outcome but a real slap in the face with the CRL

In Cayman for FRR next week

As you say people can choose who is posting informed comment.
Great insight from you and I quote “I said it was a turd”.
Well if that was the case why did Invesco take part in every raise at 50p/32p and 30p to maintain their 25%.Why did Stabdard Life and Avila buy in at 50p.Why did Sandgrove and M&G buy another 20% of MTFB at over 30p if they shared your opinion.
Why did Dr Gary Waanders give it 75% COS before the p3 trials started.
Why did the FDA give Iclaprim QIDP and Fastrack status if it was such a hopeless case.
Why the CRL only cover the liver toxicity issues and not any other part of the NDA such as efficacy or QTC considerations both of which were an issue during the Arpida claim.
Yes they did it themselves which means the risk is higher but then they get all the reward rather than sharing it big style to third parties like your favourite share where again the risk of getting to market is far higher than here.
Don’t se you posting about the risks on the SAR board.
You are right we don’t know the precise nature of the FDA concerns and we all have opinions.Your suggestion of it taking another 8 years is pure fantasy.
If the issue is a relative small one then this will be likely fixed with a short time frame if it is a major issue which I very much doubt given the available evidence then it will be solid off or a deal of some sorts done it certainly won’t mean MTFB toiling for another 8 years as Iclaprim will be sorted one way or the other within months not years imo

Seriously Thoth I really wonder why you post here.
The stuff you have posted is well known to everyone that many of the big players have pulled out of AB research so simple supply and demand curves should tell your you something.
The MTFB strategy has nothing that do with AMR which I have pointed out on many occasions but you choose to ignore to suit your own purposes.
You are constantly negative,are not invested so what are you trying to protect us from.
The SP is at an all time low but purely down to CRL so what can you gain apart from a lower entry.
Anyway ATB but peope who post on shares they have absolutely no involvement with have imo have to have questionablemotives

EBRD and energy projects

http://cbw.ge/economy/sir-suma-chakrabarti-georgia-remains-to-be-one-of-the-role-models-for-ebrd/

https://ift.tt/2HiLfWm

Presumevthis same stuff Chris posted earlier