Motif Bio Share Discussion Threads

[hoggar] 27/2/2017 19:48

Yet again we are warned of the threat of a looming pandemic. This time the WHO have issued a dire warning of super bugs killing tens of millions in the coming years if we do not develop effective antibiotics.

[timbo003] 27/2/2017 14:33

Thanks Vulgaris

Alas, there wasn't really time to go into that sort of detail, I intend to have a more thorough look at this on my return to the UK next week.

[vulgaris] 26/2/2017 18:48

Timbo,

Thanks---- interesting.

Cidality / killing rate matters in a few infections (e.g. of the heart valve) or in some groups of immunosuppressed patients (e.g. those undergoing bone marrow transplant), but not in e.g. ABSSSI ---- very fast killers, e.g. daptomycin aren't more effective in this setting that slow killers e.g. vancomycin or bacteriostatic agents such as linezolid.

The mutant selection data - and the difference to trimethoprim - are interesting. Did they offer an explanation? Were the trim-selected mutants cross-resistant to iclaprim? There is some evidence that iclaprim binds differently to staphylococcal DHFR a little differently than trimethoprim ( and this might alter vulnerability to mutational resistance. Nonetheless the bigger issue remains the actual iclaprim resistance reported in the IDWeek poster and what causes that?

Ditto the phase II HAP/VAP data are interesting, but:
1) It's prudent to convert these 3-significant-figure percentages back to real numbers--- by my count clinical cure is 17/23 with the low dose iclaprim, 15/24 with the higher dose of icplaprim and 12/23 for vanco. If I pool all the iclaprim patients and compare with the vanco patients, the difference isn't significant at p <0.05 on a (quick and dirty) Chi square test.
2) I'm mildly confused that these are back to mg/kg dosage, not fixed. Are they new Motif Phase II or old Arpida?
3) Patients o the lower dose iclaprim seem to have fared better than those on higher dose (0.8 mg/kg q12h better than 2.3 mg/kg q8h), again supporting the view that differences among groups are random noise.

Lastly, it'll have to be bloody good to justify USD350 p.d., with generic linezolid and potentially daptomycin on the market. Even still-under patent ceftaroline would be much cheaper
see e.g. The only anti-gram-positivs that are commanding $3000 tags are 1 or 2 dose agents that allow the physician to get the patient out of hospital very swiftly --

[typhoon] 26/2/2017 10:45

Excellent overview Timbo Thank you!

[colebrooke] 26/2/2017 09:56

Very much appreciated Timbo.

[t-trader] 26/2/2017 09:29

Cheers Timbo,

Great write up, appreciate your time and effort.

[small crow] 26/2/2017 07:53

Timbo, many thanks.

[timbo003] 26/2/2017 00:43

Apologies for the late write up from last Tuesday’s Rocket Bar meeting, but I had to travel to Las Vegas to begin a 10 day vacation on Thursday morning, so have only just found time to put a few notes together (see below). Unfortunately I did not get an opportunity to ask any questions in the open Q&A session, but I managed to get one in afterwards (see last question on Q&As) :


Motif Bio held an Investor evening on Tuesday night (Feb 21st 2017) at the Rocket Bar (near Bank tube station) where there were around 35 attendees. Graham Lumsden gave the presentation using a slide deck was more or less the same as the latest corporate presentation which can be found on the Motif Bio web site (see link below):


The presentation lasted for around 25 minutes and there was around 20 minutes for Q&As. Graham and Robert (the newly appointed CFO) stayed around for around 45 minutes afterwards, before heading off to meet their Auditor for diner.

There was quite a bit of new material which I hadn’t heard before at previous presentations, details of some of the new material are outlined below:
GL emphasized that obtaining wide spread acceptance by healthcare payers is becoming increasingly important for drug developers and just gaining regulatory approval was only half the battle.

In addition to Iclaprim providing an alternatives for patients where the current SOC was potentially problematic (for example patients with renal problems), Motif are now considering further possible points of difference for Iclaprim vs the current Standards of Care (SOC) for the target indications. These additional points of difference could include a faster speed of onset and reduced propensity to resistance which alone or together could result in a clinically significant improvement in outcomes. For example, shorter hospital stays, or even reduced mortality, both of which would be compelling reasons for healthcare providers to adopt Iclaprim for more widespread use, or even to replace the current Standards of Care.

GL presented a number of slides comparing Iclaprim with the current standards of care which showed lab data showing a faster onset and less susceptibility to bacterial resistance (see slides below). GL stressed that showing differences such as faster onset, reduced hospital stay or reduced mortality were not necessary for Iclaprim to be successful and they were effectively stretch objectives, but if they could be achieved they should increase Iclaprim’s commercial value considerably.













Q and As

Q: How much do you envisage charging for Iclaprim?

A: The analysts estimates are based on $350/day, or $3.5K for a ten day course


Q: Why was the uptake by US investors low?

A: It was lower than we had hoped,. We raised $25m we were looking for $35m. It was a poor time to raise cash, we did better than many others at around that time, for example Synthetic biologics could only get their funding away with 200% warrant cover and another company (I didn’t catch the name) had to do 100% warrant cover. Motif managed to get away with 50% warrant cover. Other factors specific to Motif were that we had to inform the market that we were getting low on cash in October and SEC were accusing Motif of conditioning the market with one of the Proactiveinvestor videos, so we had to curtail marketing activities for the fund raise.


Q: Why didn’t you go for a big pharma partner?

A: We wished to go it alone in the US, although we were looking for partners for other territories. There certainly was interest, although we couldn’t find anyone who wanted to pay an upfront payment at the stage we had reached, instead they stated that they preferred to wait until the read out from the two Revive studies. We are continuing to have lots of discussions for the other territories and to explore grants.


Q: Why didn’t you raise in London Again after the successful July 2015 raise at 50p?

A: We were looking at that in June 2016 and we thought we had investors lined up, but then we had the Brexit vote and all UK based fund raising was off the agenda


Q: Once Iclaprim is approved for one indication, do you think there may be off label use?

A: Maybe, but iclaprim will only be approved for Hospital use, Hospital Docs tend to be reluctant to go off label.


Q: How confident are you that with the new dosing regime and improved pharmacokinetics you will be able to allay the EMA’s previous concerns about adverse events associated with high Cmax in some patients?

A: The adverse events that EMA were concerned about in the previous Aripida studies have not been seen in the current Revive studies and adverse events are reported on an ongoing basis. The agencies both seemed satisfied with the outcomes of the pharmacokinetic modelling we conducted to support the change in dosage to a fixed dose per patient and for a 2 hour infusion time.

[waterloo01] 20/2/2017 09:58

I guess that's one the the reasons they had such difficulty getting the ADR's away and couldn't raise enough to funds all trials that are ongoing (I'd certainly be asking about funding). I'm out for now on Motif but wish all well. Some well informed posters which is always welcome.

[timbo003] 19/2/2017 18:20

Thanks Vulgaris, assuming I get the opportunity, I will quiz GL on those points, I do know they are well aware of the EMA comments on the narrow therapeutic window, as it has come up before in conversations with GL

[timbo003] 19/2/2017 08:22

I shall go along to the Motif Bio presentation at the Rocket Bar on Tuesday. Is anyone else planning to go along?

>>>>Vulgaris, could you give me a few (three ?) of what you consider the most important questions (criticisms) regarding Iclaprim to put to GL on Tuesday. TIA


Did anyone see this episode of "Trust me I'm a doctor" the other week, in particular the item starting at 36:20


Some researchers in the Netherlands are studing patients with Eczema associated with Staph Aureus and then attempting to reduce the Staph without hitting the other benign (beneficial bacteria). They hope to acheive this by using using endolysins (which do not cause resistance). They get the read out in around 12 months (according to the program), so I look forward to that.

A quick google search comes up with quite a few hits, for example this one, which I'm guessing was written by one of the sponsors:

[pdt] 01/2/2017 13:05

I have bought my first holding here today. This seems a useful informative board. The next 12 months look like they will be interesting. I am mainly in Immupharma (IMM) and there seems to be some familiar faces here too!

[timberwolf3] 31/1/2017 15:59

Second RNS out 20 mins ago.

[waterloo01] 31/1/2017 09:22

luminoso, agree. Excellent to get trial recruited and dosed, just they have always said they will need more cash (as they failed to raise the original amount needed on Nasdaq).

Positive news today but needs to be seen in context.

[luminoso] 31/1/2017 08:47

It seems clear to me that they are saying they need to raise funds to complete Revive 2 and hope that headline results from Revive 1 will allow them to do so more easily. That could be another placing or a partnership or something else. I don't read the announcement as hinting any more than that.

[small crow] 31/1/2017 08:23

I suspect that last sentence hints at likely partnerships/T.O. and the possibility that a simple fundraiser may not, therefore, be required. If trials go well, this is unlikely to remain independent IMO.

[waterloo01] 31/1/2017 07:59

Really? This was from last week.

Financials – the company raised $25m before expenses in its NASDAQ IPO in November 2016. We expect that in 2016 Motif will have generated an operating loss for the year of $41m with SG&A costs of $4.3m and R&D expenses of $36.8m representing the vast majority of expenses and demonstrating the sharp focus on product development within the business. We estimate that Motif will have ended 2016 with cash of $23.6m but highlight that it is likely to have ended the year with accrued trial-related costs of around $10m. In 2017 we anticipate R&D spending will decrease as the company’s REVIVE-1 and REVIVE-2 ABSSSI phase III trials complete and assuming that the third phase III trial, INSPIRE (in bacterial pneumonia), will not commence in the absence of new funding. However, we believe that the likely positive REVIVE-1 results will enable access to new funding and this will allow both the completion of REVIVE-2 and the initiation of INSPIRE (estimated to cost around $40m over 3 years).

[bookbroker] 31/1/2017 07:56

Above answers your question Waterloo, trial in Revive 2 ongoing, but the cash they raised last year ample funding!

[ohisay] 31/1/2017 07:52

Comment: If this last patient was treated for only 5 days there will be a further maximum of 27 days until the final follow-up phone call is completed, taking us to the end of February for the trial to be concluded. Several weeks are ordinarily required for further data processing including unblinding and statistical analysis but the company is confident of being able to report headline results in Q2. As REVIVE-2 is still ongoing, we expect only headline safety and efficacy results from REVIVE-1 will be reported (too much detail could potentially compromise the blinding of REVIVE-2). We remain confident of a positive outcome for the study based on prior efficacy and safety data obtained using iclaprim in earlier phase III trials.

[waterloo01] 31/1/2017 07:34

A little confused as I thought they stated they needed to raise funds to complete the Revive 2 trial? Is that not now the case?

They said this in November placing:

While the Board believes that, along with the Company's existing cash and cash equivalents, the net proceeds of the Fundraising will provide sufficient capital to enable the Company to complete the REVIVE-1 trial, the Company will require additional funds to complete the REVIVE-2 trial and plans to raise the additional capital through public or private financings and/or other partnering opportunities.

[1savvyinvestor] 31/1/2017 07:24

So . Trials completed. Will There be an anticipatory rise into results?

[bookbroker] 31/1/2017 04:45

Appears they have completed P111 trials, and data read out will be avaliable starting 2Q 17, as per stated late 2016!

[bookbroker] 29/1/2017 17:04

I'd suggest a good deal higher, irrespective of the placing they have fallen considerably, a retrace of a little it would justifiable, after all they considerably strengthened the balance sheet!

[t-trader] 29/1/2017 09:11

Shares in Motif Bio could rally to 35p says Zak Mir

hxxp://www.proactiveinvestors.co.uk/companies/stocktube/6804/shares-in-motif-bio-could-rally-to-35p-says-zak-mir-6804.html

[nilsvs] 26/1/2017 12:09

Interview with Zeus Capital - Dr Gary Waanders

hxxp://directorstalk.com/interview-motif-bio-plc-get-updated-coverage-zeus-capital/