Motif Bio Share Discussion Threads

[small crow] 28/5/2015 15:48

65

Sorry, I must be blind - what's the connection?

[65jack] 28/5/2015 15:40

transformational news out at NSCI a few hours ago. can see this going pretty crazy tomm as news is digested.

NetScientific PLC PDS Biotechnology reports positive Phase I results

[protean] 28/5/2015 15:26

Proactive Investors - Motif Bio to cash in on super-bug drug market, says broker

“We believe Motif is grossly undervalued,” the broker said."

[protean] 28/5/2015 15:14

Proactive Investors - Northland Capital Partners View on the City Arian Silver, Mariana Resources, MotifBio, DiamondCorp and others

"NORTHLAND CAPITAL PARTNERS VIEW: iclaprim is set to fill a major market void in the battle against antibiotic resistance. If approved, the drug could achieve over $1bn/year in sales. Today’s FDA minutes confirm the regulator’s support for Motif’s programme. We maintain our BUY rating and 89p price target."

[vulgaris] 28/5/2015 12:57

Hi Trotters.

Place in Rx depends on trial outcome and, in a crowded marketplace, on demonstrating some advantage. These seem profoundly uncertain, given the history, but we shall see.

Yes, I do note that Motif are seeking new dihydrofolate reductase inhibitors. This has been a tricky area in the past -- Roche (where iclaprim actually originated before it was spun out to Arpida) had a big effort there in the 90s, but little to show for it. One issue is that acquired trimethoprim resistance in gram-negatives depends on rather diverse enzymes, so it's tricky to devise something that overcomes all of them. Nevertheless I have no insight into whether Motif have new chemistry/analogue series so can't comment further on that aspect.

[trotterstrading] 28/5/2015 12:46

No offense caused here, all healthy debate

To your points:

'it overcomes trimethoprim resistant bacteria' when it’s does so only for several gram-positive genera'

so you do accept that Iclaprim could have a place treating 'several' gram-positive trimethoprim resistant bacteria?

'There is an increasingly publicised need for new antibiotics, but we mustn't let that need get in the way of our critical faculties. Some will respond to medical need with true innovation, others by opportunism.'

Motif are doing both, Iclaprim is an opportunity, its P3 ready – with proven P2 efficacy. Motif are also working on a pipeline of 'novel' antibiotics - that will be their innovative contribution.

[vulgaris] 28/5/2015 12:26

Trotters. Why do you accuse me of 'peddling myths?'

It is not me who tries to say that it has a 'novel action' when, as you acknowledge, trimethoprim acts in the same way; nor is it me who says 'it overcomes trimethoprim resistant bacteria' when its does so only for several gram-positive genera, not for gram-negative ones.

There is an increasingly publicised need for new antibiotics, but we mustn't let that need get in the way of our critical faculties. Some will respond to medical need with true innovation, others by opportunism.

Other anti-MRSA agents have had a cleaner ride though regulatory and have failed to get traction in the anti-MRSA market, which is getting crowded. AZ's ceftaroline is a prime example and we wait to see how dalbavancin and oritavancin will fare....

Have I uncovered anything unknown to Motif, or its advisers? I doubt that very much, for I have never accused them of ignorance. Have I highlighted concerns about this drug that might otherwise have been unflagged on this board and to possible investors. Well, possibly..... I am surprised how much offence that seems to cause.

[trotterstrading] 28/5/2015 11:56

Vulgaris,

Iclaprim will get interest, it uses a novel action to other antibiotics (with the exception of trimethoprim), with the added bonus of being active against Trimethoprim resistant bacteria, I'm not sure why you continue to peddle the myth that Iclaprim has no place in the doctors antibiotic tool-kit? It clearly does, Motif's doctors and an external consulting agency clearly thought so, Many of these guys are leaders in their field, so, I ask you this,

Do you think there is anything you have uncovered they don’t already know?

[vulgaris] 28/5/2015 10:17

Blueblood-- thanks. Accepted. I will happily change my view once I see a serious development plan that overcomes the problems encountered last time round...

Rodders---- I am not engaged in deramping; just predicting where (whatever its earlier peak) this will end up unless the molecule's issues are resolved.

[onedayrodders] 28/5/2015 09:17

Agreed blueblood ... and of course despite all the techie words one of the posts included...."it may well see 40p before it sees 1p"

It was all reading so well until a classic deramping one liner.

[granada7] 28/5/2015 09:11

blueblood

that post does you a lot of credit

[blueblood] 28/5/2015 08:55

Impartial implies balanced views. Only see negative slant in the posts but happy to be proved wrong and see some positive posts in future. Always good to have industry knowledge on board so I withdraw my comment and will watch future posts with interest.

[granada7] 28/5/2015 08:52

blueblood

i havent noticed the chip on vulgaris shoulder, hes been and seemed very impartial and posts researched material.

maybe it doesnt fit in having an impartial view here.

[vulgaris] 28/5/2015 08:51

Trotters.

In the past 15 years there are been multiple SSSI/ABSSSI trials of new antibiotics with non-inferiority shown in all (except the iclaprim vs linezolid). Linezolid and vancomycin have been shown equivalent in such trials, so it should not matter which is used as a comparator for iclaprim.

If, however, Motif or its backers believe that the earlier SSSI trial disappointed because linezolid is a better drug than 'standard of care' vancomycin then the issue becomes the fact that linezolid goes generic in 2016 or 2017 and the price will collapse. If so, why should anyone prefer iclaprim?

Motif and its backers may have answers to these questions and, if so, I'll be interested to hear them.

Blueblood

---- I am sorry if you think that, for it is untrue. I watch this thread because I do know a little on antibiotics and I find it fascinating and salutary----- It is a great warning of how little to trust assertions made apropos new companies whose line of business I know far less about.....

[small crow] 28/5/2015 08:50

blueblood

Well, maybe, but it's as well to bear in mind that this does not have a history of plain-sailing and the future may not be easy. That said, I am invested because I think the odds are good that Motif will find a market for this and that, even if not revolutionary, the market cap for another antibiotic to add to the armoury (when multi-AB treatments are clearly one of the ways to overcome resistance)is much higher than at present. I wouldn't pretend it's not a medium-risk gamble!

[mirabeau] 28/5/2015 08:34

I hope it comes good. Any company whose aim is the alleviation or cure of illness deserves a degree of success

[trotterstrading] 28/5/2015 08:31

The reality is Motif will do P3 trials with Vancomycin as the comparator for both, which it successfully passed in P2 trials. It failed the previous P3 trials due to a poorly designed regimen, which included changing the comparator drug to Linezolid.

[blueblood] 28/5/2015 08:23

Cottoner keep posting Vulgaris has clearly got chip in his shoulder about MTFB....

[cottoner] 28/5/2015 08:14

vulgaris - only posted piece for general info.

[mirabeau] 28/5/2015 08:13

2 FDA trials are used to fully assess and collect evidence to confirm efficacy and safety. A method of ensuring a double guarantee,



It's still worth noting that this drug caused issues so it's approval is not a fait accompli by any means

[vulgaris] 28/5/2015 08:10

Cottoner-----

I'd be wary of what the Daily Mail has to say....

The statement 'Having already tested on over 1,000 patients, iclaprim’s safety and efficacy is well supported' is doubtless recycled from some company or promoter's press release and is at variance with the European Medicines Agency view, when they rejected it in 2009:

EMA's full report is here



The key concerns are below and precisely centre on iclaprim's toxicity and efficacy It may be that Motif have found some new way of dosing or formulation that addresses these issues. If so these need to be spelled out.

To quote from EMA's executive summary:

"The applicant’s answers to the major efficacy objections and other concerns in relation to the efficacy results from the two pivotal ASSIST studies do not provide convincing clinical evidence in support of the non-inferiority of iclaprim to linezolid in the sought indication at large. Consequently, there is insufficient evidence to support a favourable efficacy conclusion for the use of iclaprim in the treatment of adult patients with cSSTI at the recommended dosage of 0.8 mg/kg twice daily (with a maximum of 100 mg per dose) up to 14 days.
The dosage regimen is not adequately supported by the rather limited clinical data especially in severe cSSTI nor the pharmacokinetic profile and experimental findings concerning T/>MIC; the major objection in relation to pharmacodynamics is not resolved whereas the assessment of the susceptibility table in section 5.1 of the SPC cannot be finalised.
• Iclaprim at the recommended dose level has a narrow cardiac safety margin. Iclaprim has demonstrated propensity to induce a dose dependent QTc interval prolongation in healthy subjects. The applicant’s clarifications and available limited database on iclaprim do not provide assurance for the safe use of Mersarex at the recommended dose level in the targeted population of patients at large.
• Similarly, there is insufficient assurance based on the limited available data that iclaprim is not hepatotoxic at the recommended dose level. It remains unclear why increase in ALT values develops long after stopping iclaprim despite the observation that in vitro mitochondrial toxicity data on human hepatocytes did not reveal adverse effects. Present limited patient database and analyses do not allow identification of patients (with normal or slightly increased LFT values at baseline) with increased risk for liver function test elevations in order to include targeted precautions in the SmPC for such patients. Although, in the light of present limited patient database a risk factor analysis (e.g. patients with underlying conditions, concomitant medications) is not expected to generate conclusive findings the applicant should conduct risk factor analysis with the available data collected in clinical programme in order to identify patients with increased risk for liver function test elevations."

[small crow] 28/5/2015 08:06

Seems they have to do two Phase III's, but not sure if that is normal under current regs?

[mirabeau] 28/5/2015 08:03

I don't think it matters. Ride this as far as it will go and jump off before the results. Assess how long the phase testing should last which should give you an idea of when the phase results are due

[small crow] 28/5/2015 07:50

Question is - blank or real?

[mirabeau] 28/5/2015 07:49

Starting gun fired