Motif Bio Share Discussion Threads

[dice1950] 19/8/2016 11:13

Motif Bio (MTFB) sales of the treatments could easily reach billions of dollars a year

Aug 18, 2016 1:04:20 PM
Motif Bio continued to push ahead in its clinical trials for two antibiotics against drug-resistant bacteria.

During the first half of the year the company initiated phase three clinical trials for its Iclaprim treatment against Acute Bacterial Skin and Skin Structure Infections (ABSSSI).

The company also continued to make preparations for beginning phase three trials for Iclaprim against pneumonia acquired by patients at hospitals by the end of 2016.

AIM-listed Motif was also carrying out a preclinical development programme to develop a formulation of Iclaprim suitable for adolescent and pediatric patients, alongside work on its MTF-101 treatment for osteomyelitis and for patients with prosthetic joint infections.

Analysts at Northlands Capital said there was a “chronic under-investmentR21; in the area by the pharmaceutical industry, but that means big potential for Motif.

The broker said that there is a significant valuation gap between Motif and its US peers.

Other companies operating in the same field in the US include Cempra (NASDAQ:CEMP) and Paratek (NASDAQ:PRTK), both listed on NASDAQ, are valued significantly more than Motif.

“We believe that the discrepancy in pricing between the group and its US-peers would be thrown into sharp relief,” said the analysts.

Motif already has all-important FDA consent to conduct Phase 3 clinical trials for iclaprim in two requested indications, Acute Bacterial Skin and Skin Structure Infections and Hospital Acquired Bacterial Pneumonia.

Northland estimates sales of the treatments could easily reach billions of dollars a year once it reaches the commercial market.

With the potential of the drug in the US and the up-coming listing, Northlands Capital has raised its target price from 114p to 140p, indicating a significant potential upside of 312% on the current price of 45p per share.

[dice1950] 19/8/2016 11:13

Motif Bio (MTFB) sales of the treatments could easily reach billions of dollars a year

Aug 18, 2016 1:04:20 PM
Motif Bio continued to push ahead in its clinical trials for two antibiotics against drug-resistant bacteria.

During the first half of the year the company initiated phase three clinical trials for its Iclaprim treatment against Acute Bacterial Skin and Skin Structure Infections (ABSSSI).

The company also continued to make preparations for beginning phase three trials for Iclaprim against pneumonia acquired by patients at hospitals by the end of 2016.

AIM-listed Motif was also carrying out a preclinical development programme to develop a formulation of Iclaprim suitable for adolescent and pediatric patients, alongside work on its MTF-101 treatment for osteomyelitis and for patients with prosthetic joint infections.

Analysts at Northlands Capital said there was a “chronic under-investmentR21; in the area by the pharmaceutical industry, but that means big potential for Motif.

The broker said that there is a significant valuation gap between Motif and its US peers.

Other companies operating in the same field in the US include Cempra (NASDAQ:CEMP) and Paratek (NASDAQ:PRTK), both listed on NASDAQ, are valued significantly more than Motif.

“We believe that the discrepancy in pricing between the group and its US-peers would be thrown into sharp relief,” said the analysts.

Motif already has all-important FDA consent to conduct Phase 3 clinical trials for iclaprim in two requested indications, Acute Bacterial Skin and Skin Structure Infections and Hospital Acquired Bacterial Pneumonia.

Northland estimates sales of the treatments could easily reach billions of dollars a year once it reaches the commercial market.

With the potential of the drug in the US and the up-coming listing, Northlands Capital has raised its target price from 114p to 140p, indicating a significant potential upside of 312% on the current price of 45p per share.

[aimsharesone] 19/8/2016 07:55

Motif Bio (MTFB) sales of the treatments could easily reach billions of dollars a year August 18, 2016 1:04 PM PDT

[aimsharesone] 19/8/2016 07:55

Motif Bio (MTFB) sales of the treatments could easily reach billions of dollars a year August 18, 2016 1:04 PM PDT

[timbo003] 17/8/2016 08:06

That is a fairly blunt (but fair) assessment from Beaufort following last week's announcement on the Nasdaq listing:

Motif Bio (MTFB.L, 46.88p)– Hold
Motif Bio, the clinical stage biopharmaceutical company specialising in developing novel antibiotics, yesterday announced financial results for the half-year ended 30 June 2016. Back in March, the Group announced first patient dosing in its two REVIVE (Randomized Evaluation IntraVenous Iclaprim Vancomycin treatment) Phase 3 clinical trials in Acute Bacterial Skin and Skin Structure Infections (‘ABSSSI’;). It is now enrolling and dosing patients in two global Phase 3 clinical trials with an intravenous (‘IV’) formulation of iclaprim, for the treatment of ABSSSI. Data from the two trials are expected in the second half of 2017. Net cash used for these operations was US$8.9 million (H1 2015: US$1.2 million) during the period, which reflects the continuation of the clinical development of iclaprim. Research and development expenses increased by US$11.4 million to US$12.0 million, primarily attributable to the commencement of this process, of which US$10.1 million was spent in relation to contract research, US$1.0 million for clinical operations and US$0.9 million in relation to chemistry and manufacturing development. At half year stage, the Group had remaining cash/cash equivalents of some US$19.5 million (31 December 2015: US$28.6 million).

Our view: The reality is that Motif Bio’s half year statement did not actually answer the question that shareholders are now most concerned about. On 9th August, management shocked with an announcement that its much vaunted public offering of American Depositary Shares and listing on the NASDAQ Global Market had seen its pricing deferred. Given what has quite evidently been exceptional progress with iclaprim’s development, for a giant international market that is now becoming desperate for delivery of novel and innovative new antibiotics, investors appeared to believe that the only genuine barrier to it securing a US$1bn+ opportunity from just its first two indications was availability of funding. And that problem seemingly had been resolved. Understanding US investors’ greater willingness to place a premium rating on such early-stage development opportunities, particularly when there are obvious peer comparisons, management extensively toured sector specialist US investors in order to gain sufficient confidence to appoint book runners in anticipation of the issue of, perhaps US$35m in new equity to be quoted on the NASDAQ. Shareholders has expected to be told during August of just such a successful raising, which they hoped would be priced at or close to that being achieved in London. But this was not the outcome and, in truth, yesterday’s interim statement provided little additional transparency. To say that the Group ‘remains in registration with the Securities and Exchange Commission and is continuing to engage with investors’, unfortunately is as clear as mud. Whether the shock result was down to bad ‘summer’ timing, simple inadequacy of the appointed book-runners or some other complication remains unclear. Whatever, Motif’s management states in its own assessment of risks that a ‘…lack of funding would limit any strategic initiatives to in-license or acquire additional product candidates or programs’. Its remaining pool of cash is simply not enough to keep its programmes in track and right now a new London fund raise would likely be extremely complicated, so management appears to have no choice but to ‘try again’ in the US. Perhaps a rabbit, in the form of a major new US core investor matching the subscription pledge already committed by 25% UK shareholder, Invesco Perpetual, could be pulled out of the hat to save the day? Or perhaps a pharma major could look to get involved? Beaufort genuinely feels that such an opportunities are not unrealistic but, given the recent disappointment and continuing lack of clarity, downgrades its recommendation to ‘Hold’ from ‘Speculative Buy’ while awaiting further information. That said, Motif’s eventual successful securing of the necessary development funding should, in due course, ensure significant upside for shareholders who have had the courage to remain aboard.

[123prezzie] 15/8/2016 15:28

Thanks lanb. I remain cautious till nasdaq in the bag.

[timbo003] 13/8/2016 19:15

Thanks for those thoughts Vulgaris

The next time GL does his investor roadshow in London. I will ask about b.i.d. vs t.i.d for iclaprim and whether Motif have any residual concerns regarding the EMEA objections from Arpida's previous studies and if not why not.

Your experiences with Regulatory agencies sound similar to my own, they are usually more then willing to offer broad brush strategic advice and to discuss what data you should be generating for the file, but that's about it.

[ianb5004] 13/8/2016 12:40

123pressie

Main holder reffered to who is invesco perp they hold 25% now and will be the biggest holder following nasdaq ipo. (Amp own 26%)
Last 2015 mtfb accounts show they have cash of $28million. However they do need to raise further funds for completion of all phase 3 trials inc HABP.
Nasdaq is one option which i am very confident will happen in sept. Stratagic partners for ROW milestone payments expected in 2016 will also be well in excess of the initial analysis of £30m.

[vulgaris] 13/8/2016 11:24

Timbo,

I agree that T1/2 of 2.3h (as EMA cite) is more suited to thrice daily, but can think of three reasons why Motif might prefer twice daily over thrice daily:

Toxicity issues----- if tox is associated with a high trough level

Convenience----- competitors (vancomycin, linezolid, teicoplanin and daptomycin) are once or twice daily. A thrice daily agent would be less convenient for the nurse who has to put the infusion bag up and for pharmacy. I have seen companies fixate on these aspects. They are lots of widely used, thrice daily iv antibiotics, but these are directed against other pathogens, not MRSA/S. aureus.

Existing Phase I and II data are for twice daily and there may be (leastways I can't find) no Phase I data for thrice daily, meaning that they'd have to go a further step back to explore this.

I have no insight as to which of these is correct.

I agree that 80 mg twice daily is simpler and will be somewhat improved over the weight-based regimen. But as above, the increase for the average (80 or 85 kg) patient, the difference will be small and, in my view, trivial. On the other hand a 50 kg (8 stone) patient, receiving 80 mg twice daily will receive double the previous dosage (i.e .1.6 mg/kg). What does this do to the tox risk? Note the EMA's comments on the narrow therapeutic margin between efficacy and toxicity. A 1.6 mg/kg regimen was tried in Phase II but had a higher side effect rate than 0.8 mg/kg --

Apropos your last point, what is meant is that the EMA has reviewed the trial design, but -- from experience -- they and the FDA are very wary of ever saying anything that gives any early commitment. Pharma says to them 'We're thinking of a trial like this......' and pose a series of questions about its acceptability. And they say 'You should think about this, and consider that, and we'd expect such and such statistical power.' They don't say 'If you achieve x, y, and z you'll get a license'. They also are very careful never to get into the position of being a development collaborator/partner. It can be pretty cryptic.

[timbo003] 13/8/2016 08:26

>>>Vulgaris

Dosing every 12 hours with a drug which has a 2-4 hour half life does not seem like an ideal dosing regime to me, especially one which may not have a particularly large therapeutic window, so I am not sure why they didn't opt for a t.i.d dosing regime, any ideas why they wouldn't want to do this?

Having said that, switching to a fixed dose of 80mg b.i.d. is likely to give a much improved pharmacokinetic outcome compared to the variable dose used in the Arpida studies and this is something that EMEA have already proposed (top of page 18).

Lastly, it's worth remembering whatever we postulate over here (without access to the source data), Motif already have agreement with the European agency on the proposed phase III clinical trial program for Iclaprim, I assume that in the meetings with EMEA they will have discussed how they intend to address the shortcomings of the previous Arpida submission, before agreeing on the proposed program:

[vulgaris] 12/8/2016 18:17

timbo

Average body mass for a man is about 80kg so, under Arpida's 0.8 mg/kg regimen the average patient would get two doses of 64 mg per day--- the maximum (for a pretty obese patient was 100 mg twice a day). In fact the patients in Arpida's phase II ( I can't find their phase III) averaged 85 kg and so would get 68 mg twice daily.

As you say, Motif's regimen is 80 mg twice per day..... 25% more than 64 mg or 18% more than 68 mg. This difference isn't going offset the shorter half life or the other issues identified by the EMA.

What is more

1) The EMA noted a narrow margin for toxicity and an 18-25% increase in dosage may increase the hazard here (note MAY -- I claim no expertise on toxicity aspects)

2) Cmin (the drug level remaining in the serum before the next dose) is not the driver for a drug of this class: AUC:MIC most likely is (Arpida certainly believed this and EMA's report seems to accept the view). An 18-25% increase in dosage cannot give more than a proportionate increase in AUC. So, at most they might end up with a breakpoint 10-fold below trimethoprim rather than 20-fold.... most of the 16-fold potency advantage therefore remains negated.

[123prezzie] 12/8/2016 15:58

lanb5004. In your post 706 you say that the 'main holder' is supporting the NASDAQ fund raising. You don't say who you consider to be the main holder. If it is Amphion (AMP), who held 26% at 31/12/15, then I suggest you need to define what you mean by 'support'. AMP appears to be pretty short of cash and has already pledged well over half its MTFB shares as collateral against loans charging 10% (!) interest. The latest tranche is covered by the MTFB RNS above dated 18/7/16 where AMP has borrowed $750,000 with 1.4m MTFB shares as security ie an implied value of about 42p/share. Followers of Quindell and similar will know that the way these deals usually work is that the lender, probably with the benefit of a Put arrangement, sells if the share price falls near 42p, thus recouping the loan.

MTFB is unlikely to survive for many months unless it can convince investors that its products will be successful. I strongly recommend that any investor, actual or potential, should read the AMP and MTFB accounts and then tell me if/where I am wrong.

[timbo003] 12/8/2016 15:55

>>>Vulgaris

In the document you cite above, EMEA were commenting on PK data generated when the dose was based on 0.8mg/kg body weight iv every 12 hours (Arpida’s ASSIST studies)

In the new ongoing REVIVE studies the dose is 80 mg intravenous every 12 hours (irrespective of body weight)

This means that the dose given in Motif's studies is going to be quite a bit higher than the average dose given in the ASSIST studies, so Cmin should be correspondingly higher (circa 30%) for REVIVE vs ASSIST

See my notes from the Rocket Bar meeting for further details (link in the header)

Problem solved

[vulgaris] 12/8/2016 13:02

Here is the relevant part of the EMA's report from iclaprim's previous outing:

In the SPC the applicant proposes one susceptibility breakpoint of 2 mg/L (equal to trimethoprim).This proposed breakpoint has not been assessed by EUCAST yet. However, the plasma concentration of iclaprim at the end of the infusion (30 min) is only 0.8 mg/L, the mean plasma half-life is short, 2.3 h, and the dosing interval is long, 12 h. So the lower in-vitro MICs of iclaprim and its higher in-vitro activity as compared to trimethoprim are neutralised by the lower plasma concentrations of the compound as compared to trimethoprim, which can be dosed orally at a much higher dose (160 mg)and has a much longer half-life (11 h). Based on these pharmacokinetic parameters and considering the very short post-antibiotic effect, currently a breakpoint concentration of 0.1 mg/L iclaprim at the most is acceptable at this stage.

top if p11/61 in

To translate for you. A breakpoint is the concentration of antibiotic that defines the border between susceptible and resistant. For trimethoprim (the old chemically related drug) the breakpoint is 2 mg/L. If the MIC (the drug level you need to stop the bug growing in the lab) is <=2 mg/L the bug is susceptible; if it's >2 mg/L the bug is resistant. Because iclamprim is given at a lower dose and doesn't persist so long in the body ('shorter t1/2')its breakpoint should be lower than trimethoprim, EMA thinks around 0.1 mg/L

Sixteen-fold greater 'potency' in terms of lab MICs amounts to almost exactly zilch if your breakpoint is 20-fold lower.... (2 divided by 0.1).

[vulgaris] 12/8/2016 00:39

'A study has shown the drug to be 16 times more potent than the only antibiotic of its class currently out on the market.'

In terms of what?

MICs (i.e. concentration needed to inhibit bacterial growth in the lab)?
AUC:MIC ratio (the pharmacodynamic driver for a dihydrofolate reductase inhibitor -AUC is the area under the concentration curve, and integral of dose and persistence in the body)?
Dosage needed to cure infection?

The EMA, on it's previous outing, took the view that a shorter t1/2, leading to a lower AUC, largely negated iclaprim's MIC advantage.

A word of advice..... pin them down EXACTLY on what they mean by 'potency'.

[ianb5004] 12/8/2016 00:07

Looks like links not allowed on here.

Graham Lumsden, chief executive of Motif Bio (LON:MTFB), says results from a recent lab study ought to give investors’ confidence that its phase III programme for Iclaprim will be successful.

The firm told investors today that a study has shown the drug to be 16 times more potent than the only antibiotic of its class currently out on the market.

Iclaprim is known as a dihydrofolate reductase inhibitor, which means it should be effective against certain resistant strains of bacteria.
.................................
Worth watching the interview in august last year on th e potency of iclaprim..
Ill let others find it as cant post the link.

[ianb5004] 12/8/2016 00:05

Looks like links not allowed on here.

Graham Lumsden, chief executive of Motif Bio (LON:MTFB), says results from a recent lab study ought to give investors’ confidence that its phase III programme for Iclaprim will be successful.

The firm told investors today that a study has shown the drug to be 16 times more potent than the only antibiotic of its class currently out on the market.

Iclaprim is known as a dihydrofolate reductase inhibitor, which means it should be effective against certain resistant strains of bacteria.
.................................
Worth watching the interview in august last year on th e potency of iclaprim..
Ill let others find it as cant post the link.

[ianb5004] 12/8/2016 00:03

Thans for your thoughts -

The companies view

[...]

[vulgaris] 09/8/2016 23:04

lanb5004......

Completely agree there is a need for new antibiotics to overcome resistance. But that doesn't make every new antibiotic a good prospect.

Iclaprim does very little to overcome any of the major resistance problems, in particular those among gram-negative bacteria, where the issues are most acute. Against them it behaves almost identically to its 1960s analogue, trimethoprim. Any gains are against gram-positives, principally Staph aureus/MRSA and streptococci, where multiple treatment options almost always remain -- vancomycin, teicoplanin, linezolid, tedizolid, ceftaroline, daptomycin (Staph), tigecycline, dalbavancin, oritavancin, telavancin and, prospectively, omadacycline, lefamulin, delafloxacin etc. And, as the EMA report cited above states, iclaprim had significant efficacy and toxicity issues in its earlier trials.

This remains a high risk punt on an drug with an iffy track record to date.

[ianb5004] 09/8/2016 22:20

The aim placing of £22mil was completely bought by institutions at 50p. I know the main holder is also subscribing to a big chunk in the usa ipo. There is no problem getting investors in, the problem is more like where to price it.

The world needs this antibiotic without it and others ab resistance in 5 years will wipe out millions of people.

Nasdaq is deffered whilst they get the best deal imo ... i think sept now which was always my expected date. Was surprised it was rushed through in early august.

[1savvyinvestor] 09/8/2016 18:01

I was chucked off the Twitter group for daring to mention I sold yesterday . I felt yesterday's rise was a spike and sold as a result . Really didn't expect this mornings rns but my feeling now is avoid until all becomes clearer

[bowles22] 09/8/2016 17:38

Good post courtesy of someone on III


useful article here
hxxp://www.fiercebiotech.com/biotech/motif-bio-hits-pause-nasdaq-ipo-sinking-stock-price-london

seems they could not get enough interest to get this IPO away. Be careful, as this may mean other types of funding are explored.