Motif Bio Share Discussion Threads

[timbo003] 03/11/2016 09:41

Thanks Vulgaris

I was informed by the PR agency yesterday that GL will be in London week commencing 14 November so there should be a chance to quiz him then on short term financing and the outstanding questions raised by the two recent poster presentations

(OT: On BSC2, I believe there's a punitive management performance fee that has just kicked in which may curtail generous dividends going forward, I am hoping that the BOD earn their crust and renegotiate the terms on that one to bring it into line with best industry practice)

[waterloo01] 01/11/2016 17:41

Also a BSC2 holder. Been enjoying the divi's for about 7 years +.

[vulgaris] 01/11/2016 17:23

So far as I understand (and this is not my area of expertise), Immbio's approach is to grow pathogens in stressed conditions in tissue culture, purportedly mimicking those in infection, rather than in normal lab culture. This leads the pathogen to express so called 'heat-shock proteins', which are then used as the basis for the vaccine - see

The approach certainly looks interesting and plausible. They are targeting Meningococcus B, Strep pneumoniae and TB in the first instance. There already are vaccines for these pathogens and issue will be whether Immbio's approach is better..... The existing TB vaccine is not considered to be very good, but it is a tricky bug, lying dormant and hiding inside cells. The current 'conjugate' pneumococcal vaccines, manufactured by Pfizer and Glaxo, are good but only cover some 'serotypes' (=surface types), with the result that they tend to knock these out of circulation, creating a niche for other serotypes to fill. Immbio assert that their product will achieve wider coverage against different S. pneumoniae serotypes. If so, that'll be an advantage and they won't have to play Pfizer's game of catch up (original vaccine covered 7 serotypes, 2010 one covers 13 but with some folks asserting non-vaccine types are a growing issue). In the case of meningitis B there is a recently-licensed vaccine (Novartis) that is cutting incidence I'd have thought that'd be quite a tough one to beat.

I also hold BSC2 VCT and (though this hadn't sunk in previously!) am evidently exposed to this investment via them. It won't cost me sleep.

[timbo003] 01/11/2016 13:19

>>>>Vulgaris

Whilst on the subject of Vaccines for pathogens, have you come across this company/technology



I have an indirect interest through a couple of my VCTs (British smaller companies 2 VCT and Oxford Tech 3 VCT).

Their claims seems impressive, but I suspect it is too early to make a judgement call.

"ImmBioVax™ vaccines contain multi-protein complexes designed to elicit broad immune system priming to protect against multiple pathogen strains and thus address the problems of genetic variation and mutation."

[vulgaris] 01/11/2016 12:43

Your questions about whom to vaccinate a good ones. The answers depend on cost and duration of protection. If you say each C diff case costs £10000 (


and a UK rate of 14000 cases p.a. (it had dropped lower than I thought, sorry ---

then the cost to NHS is £140m pa. From memory, about 1 million people turn 65 each year So, if your vaccine case £100 a shot and gives long lasting protection then you should come into balance if you vaccinate everyone as they reach 65 ---- it's an illness that affects the elderly. Or you could just vaccinate over-75s and care home residents, many of whom are revolving door patients for their local hospital.

If the vaccine only gives brief protection then the gain is more dubious--- you'd have to vaccinate 2-4 weeks before elective admissions and many admissions are emergencies, who wouldn't get vaccinated.

Note ----- I do not claim any insight into the particular vaccine under trial and have not looked out duration of protection data, which may be available. This is just to lay out principles. And, in any event, my main point is that Summit's drug, good as it may be, faces a range of competitors and potential competitors.

[waterloo01] 01/11/2016 11:28

O/T.

Vulgaris, you certainly know your stuff. Not sure what traction a vaccine will have, as they would need to vaccinate all at risk patients, regardless of having the disease or not, and suspect the cost of doing might be prohibitive (Vancomycin usually used as 1st line mainly due to it's low cost) and 'poop' treatment has been around for a while, and seems effective(less so in the synthetic versions) not sure the yuk factor will be overcome, nor some of the unknowns about infusing 3rd party poop on the individuals microbiome, which one suspects is quite 'individual'.

From what I know Summit are hoping, post phase 3, to go for 1st and 2nd line treatment and will price it competitively (if it makes it). Yet to see data against super strains, but so far it looks good.

Anyhow, many thanks. Most informed.

Edit: for those that don't know Summit, the antibiotic plays 2nd fiddle to their work with Utrophin in DMD and doesn't much figure in broker valuations compared to rare disease work.

[waterloo01] 01/11/2016 07:47

OT. Not in Motif but have followed at a distance as value Timbo's posts elsewhere. Vulgaris, you seem to have a fairly clear view on the science. Have you any view on Summits,ridinilazole. Do PM me if you don't want to clutter this BB.

[timbo003] 01/11/2016 07:38

>>>>Vulgaris

I contacted Motif’s PR agency yesterday to alert them to the problem with the links from the PK modelling abstract to the corresponding poster, they told me that they will get it fixed, although it may take a while as the documents are located on the conference web site (i.e. they are hosted on a third party server). In the meantime, they have sent me a copy of the PK/PD modelling poster, which I have now loaded onto a google drive for easy access:


I have now had a chance to read both of the posters and to re-read the EMA assessment report on Iclaprim (see link below)



The work described in the posters seems to address most (but not all) of the concerns raised by EMA, especially given that the target indication for Iclaprim is now ABSSSI in patients who cannot take vancomycin due to renal impairment. The modelling work certainly seems to confirm that the new dosing regimen will result in much improved drug serum concentration/time profiles. It would have been helpful if Table 4 in the Global Survey poster had included Vancomycin as comparator to show that there is a similar prevalence of resistance to Vancomycin, also it does look odd that the Asian and S American data is not presented, especially given that they refer to it in the methods. Perhaps they just ran out of room on the poster?

Given all of yesterday’s news, I am now rather more concerned with the immediate funding requirements than the detail that will go into the new EMA submission, especially given that we haven’t seen what other data Motif have generated (but not yet published) to support the next submission.

[dice1950] 31/10/2016 21:31

Is Motif Bio at death’s door?
31 October 2016, 13:52

[dice1950] 31/10/2016 21:31

Is Motif Bio at death’s door?
31 October 2016, 13:52

[vulgaris] 31/10/2016 16:21

Adorling------

'Good announcements' are the poster critiqued above

[adorling] 31/10/2016 07:10

Um... 2 good announcements on Iclaprim disguising a need to raise cash as there is an urgent funding requirement of 4.0million - disappointed that US listing still "in discussion on pricing" so ADR's with warrants attached will be issued.

[timbo003] 27/10/2016 09:18

Thanks Vulgaris

I'm a bit tied up today, but I think I will follow up on your suggestion tomorrow and write a note to the investigator with a few questions.

[vulgaris] 26/10/2016 16:23

You might also enquire why the methods says 1636 Gram-positive bugs, 69% of them from the US & Europe, but Table 4 only includes 737 of these. Also why does Table 4 omit the Asia-Pacific and Latin America bugs? Did their MIC distribution differ from that of the Europe / US collections?

[vulgaris] 26/10/2016 14:06

Thanks for the link to the second poster, Timbo.

I don't find it encouraging, I'm afraid.

We do not know where the breakpoint would be. It'll certainly be much lower than the 2 mg/L trimethoprim, which has a similar regimen but a much longer serum half-life. The EMA report suggested, if I recall, 0.12-0.25 mg/L. So, given the slightly improved regimen, above, let's tentatively take the upper value---- 0.25 mg/L. Based on this, using Table 4, I count 63/737 bacteria resistant, vs (Table 2, used in combination with none resistant to daptomycin, linezolid or vancomycin, all of which are now generic.

High level resistance (by any reasonable definition), with MICs >8 mg/L, was seen in a few isolates of all target species (S. aureus, beta-strep, Strep pneumoniae) (Table 2 & 4). What mechanism(s) cause this resistance? Are they transferable among bacteria? Or can resistance arise readily by mutation. Circulating high level resistance before launch isn't a good sign for any antibiotic

Given the high MICs for some isolates (above), I can make no sense of the conclusion bullet that reads 'ICL was potently active against all S. aureus, beta-hemolytic streptococcus, and S. pneumoniae clinical SSSI and HABP isolates globally from 2012-2014.' They can't mean the ones with MICS >8 mg/L can they??????? How have they excluded them from this point??? Were the highly resistant ones from some earlier/later year?

I am also surprised that the 'authors' ONLY comprise academics from Motif's advisory board & from Motif itself. The work was done, as the Methods says, at JMI Labs. JMI's own folks appear as an acknowledgement only. I have never seen this before with any poster based on JMI work------ JMI's folks, whom I know well, always appear as the authors of their own work.

You may wish to put these points to Dr Shukla, who appears as corresponding author.

[timbo003] 26/10/2016 11:10

Thanks Vulgaris

It's a shame that the link on the abstract to the full poster pdf (as presented) sends us off to another poster concerning Dalbavancin, but there's enough info in the abstract to see what they are up to.

It had not occurred to me that they would be dosing over 2 hours rather than 30 minutes, which should obviously help along with the change to a fixed dose of 80mg rather than 0.8mg/kg.

I assume they will be conducting some PK measurements during the new REVIVE studies to confirm.

Whilst on the subject of the ID conference, it's worth a look at the second poster too "Global Antimicrobial Surveillance of Iclaprim Against Clinical Strains Causing Hospital-­‐;Associated Bacterial Pneumonia (HABP) and Skin and Skin
Structure InfecBons (SSSI)"

Abstract:
Poster:

[vulgaris] 25/10/2016 23:32

Timbo---- here is the abstract for the ID Week Lodise pk/pD poster



Essentially they are giving as a slow infusion (80 mg over 2h twice daily, rather than 0.8 mg/kg over 30 min twice daily as in the failed Arpida trial) and assert: (i) this gives a c. 30% increase in the key pharmacodynamic ratio ('Area under curve: MIC') believed to drive efficacy and (ii) reduces the peak serum peak level (Cmax), which they say was the main driver of toxicity.

This may give some improvement, but I struggle to see it as overwhelming.... They will still be left with a lower breakpoint (MIC defining the boder between sensitive & resistant) than for trimethoprim, (ii) long antibiotic infusions, tying down a venous access, are not widely favoured outside the ICU and (iii) the toxicity-driving Cmax is less than 10% lower than with the Arpida regimen---- (655 ng/ml vs 702).

[pjj71] 13/10/2016 11:20

Motif Bio files amended F-1; to offer 42.5M new shares through H.C. Wainwright
Thursday, October 13, 2016 10:17:01 AM (GMT)

Offering includes shares in the form of ADSs together with warrants to purchase ADSs in USA and shares together with warrants to purchase shares in a European placement
Ordinary shares are currently listed on the AIM Market of the London Stock Exchange under the symbol MTFB.LN and the ADSs have been approved for listing on The NASDAQ Global Market under the symbol "MTFB".
An existing shareholder, Invesco Asset Management Limited, which beneficially owns approximately 25% of Motif Bio's ordinary shares, has indicated an interest in purchasing up to an aggregate of $8.582M of ADSs and ADS Warrants in the U.S. offering at the public offering price per ADS.

[timbo003] 15/9/2016 07:25

>>>>>Vulgaris

One of the poster's referred to in today's RNS sounds like it might address the PK questions posed by the European Regulators:




'The Use of PK/PD Systems Analyses to Determine the Optimal Fixed Dosing Regimen of Iclaprim (ICL) for a Phase III ABSSSI Clinical Trial'.

Unfortunately we don't get to see it until after October 29th

[hays1] 09/9/2016 21:38

The share is gaining traction and is acting more like a non AIM share with tight buy/sell margin, which is good news.Also there were 2 positive RNS' so it's just a matter of time when it'll be listed on the Nasdaq and I believe they are planning to do something in Europe too.

[vulgaris] 25/8/2016 09:57

Can't provide a broker note, timbo, but can tell you about the AZ drugs.....

Meropenem is out of patent. Generics available and increasing their share of the market. Long been a standard against multi-resistant gram-negatives, but now being itself undermined by resistance, esp. e.g. in Italy, Greece, India and part of Latin America. Most of this resistance caused by enzymes called 'carbapenemases' which inactivate it.

Ceftaroline is one of two cephalosporins (the other is ceftobiprole, which is only available in the EU)active vs. MRSA. Despite good clinical results uptake has been slow and sales not very good. And, as I've said apropos Motif-- the anti-MRSA market has become crowded. Pfizer may make a better job of marketing it. AZ's heart hasn't been in antibiotics for a while now.


Ceftazidime-avibactam. Overcomes some carbapenemases, not all ----- good answer to meropenem resistance in e.g. US, Italy, Greece, not e.g India, where different sort of carbapenemase are prevalent. In the US has been priced @ $10000/course, vs. $750 for high end generic meropenem and c. $2000-3000 for other newish antibiotics.

Aztreonam-avibactam. Overcomes all the carbapenemases (at least in the lab) but still only just going into Phase II, so a lot of work left to do, and aztreonam not everyone's favourite antibiotic.

The price tag is a lot lower than Merck paid for Cubist - where they also got 3 antibiotics (daptomycin [about to go generic, though hard to make], ceftolozane-tazobactam [has potential, but licensed for wrong indications, so will need investment in trials for the right ones] and tedizolid [linezolid me-too; unlikely to do well given linezolid gone generic]). Big difference is that AZ retain US rights to their agents - even so, the disparity looks large.

[timbo003] 25/8/2016 07:58

A bit of relevant industry news from yesterday, I'm not familiar with these Astra Zeneca antibiotics so will need a broker note (or GL) to put it into context.....

[vulgaris] 19/8/2016 13:49

dice1950

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.

Cempra is lower risk. Inter alia they are trying to bring fusidic acid onto the US market, getting some mkt exclusivity under the GAIN Act. Fusidic acid has long been licensed in the UK and Europe and it's likely it'll get a US license. They also have solithromycin, which has completed one Phase III, as i.v. in pneumonia, albeit with some issues of pain at infusion site. As an oral, it is well advanced in a gonorrhoea trial. It's hard to see them not ending up with some sort of product(s) to sell.

Paratek has omadacycline, an oral & i.v. tetracycline previously outlicensed to and returned by Bayer, Merck and Novartis over a 5-6 year period. Big pharma looked three times and didn't like what it saw, which would worry me. Nevertheless Paratek raised funds when the going was good and the panic on 'no new antibiotics' was strong and appear to have had a successful Phase III in ABSSSI So, it too is rather ahead of Motif/iclaprim.

In short, both these companies are a lot closer to licensed product than Motif, which supports higher ratings. I'd take Norland's 'billions of $' with a pinch of salt. At peak, just before patent expiry Pfizer's linezolid reached $1.36 bn and daptomycin around $1 bn. And, iclaprim (if successful) and omadacycline will be competing against these as generics, not to mention other still-under-patent anti-gram-positive agents such as ceftaroline, oritavancin, dalbavancin etc.