Member Info for Ivyspivey

https://www.africaintelligence.com/aem/oil/2018/10/16/savannah-petroleum-boss--azerbaijani-networks,108328283-art

Hi Zib,
That is one of issues here FRR do have past form in terms of “ fabricating facts” to mislead people.
It may be justified in terms of needs must given the situation but hardly adds credence to some of their claims

Still think this is the determinant subset of data as this is the dose rate is seeking Approval.
I would like to see the elevated AST and ALT levels at EOT/TOC and LFU for comparison but we know from David Huang comments all elevated levels returned to normal after treatment and the last opportunity to assess this would be LFU

https://1v6gj215h9gy3y4dgh3it40h-wpengine.netdna-ssl.com/wp-content/uploads/2018/06/ASM-2018-Iclaprim-REVIVE-Safety-Poster.pdf

Investing Wizard
Have now had a chance to look at the two SEC Filings and have a better idea of the exact point you have made regarding the inclusion of the Liver Toxicity details of the Assist Trials in April 2019 and no mention in 2018.
Link provided

http://ir.motifbio.com/phoenix.zhtml?c=254416&p=irol-SECText&TEXT=aHR0cDovL2FwaS50ZW5rd2l6YXJkLmNvbS9maWxpbmcueG1sP2lwYWdlPTEyODM2NzI0JkRTRVE9MSZTRVE9NTYmU1FERVNDPVNFQ1RJT05fUEFHRSZleHA9JnN1YnNpZD01Nw%3d%3d

Your analysis does seem reasonable and if you look at the Assist data I can understand why they may want more detail on why the raised ALT/AST levels which seem to continue to increase over time from TOC to FUV.

As I stated earlier the changes made to trial protocol seems to have satisfied other efficacy and Cardiac safety concerns.What I have not seen is a comparable table based on Revive 1 and 2 comparing the raised ALT/AST over the 3 stages of trial protocol.That would be interesting and a question fircAGM.
Thank you very much for raising point and apologies if it did not click with me sooner

Contained following but which was bit of blast from past-Varang or Varange.

Unaware that its plans had been revealed to FRC, MND, with OMLs support, continued its misrepresentations regarding its intentions and attempted to garner additional confidential and trade secret information from FRC. (Id., ¶ 28). For its part, FRC initiated an effort to obtain financing for a true farm-in investment from another entity and, in April 2014, FRC announced a deal with Varange Exploration, Ltd., at which time MND and OML abandoned their efforts. (Id., ¶ 29). OML and MND’s actions nevertheless caused FRC extensive actual damages, by interfering with a then-ongoing process to identify farm-in partners to
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PLAINTIFFS’ MOTION FOR PRELIMINARY INJUNCTION
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Case 3:19-cv-01996-RS Document 36 Filed 05/16/19 Page 13 of 26
help finance its development of its mineral interests in the Republic of Georgia, and by causing the failure of advanced, confidential negotiations towards such an investment with a third party. (Id.).

Back from pub.
Yes it would be part of NDA package as is any published data.
My point as to its relevance is mainly due to the fact that MTFB changed a lot of the Arpida protocols when it acquired Iclaprim from Nuprim .
So in original p3 trials the major reasons for rejection were the efficacy ( both Non Inferiority Margin and Comparator ) then safety primarily Cardiac ie QTc levels and to a lesser extent elevated Liver enzyme levels.
So FDA recommended several changes ie fixed level of 80mg I/v Iclaprim plus half dose 40mg in moderate hepatic impairment etc.

The Revive p3 trials which are the fundamental basis of the NDA display no particular liver toxicity issues and don’t mention any issues regarding efficacy or QTc at all.

We simply do not know the exact FDA concerns and any attempt to pretend that we do know is pure speculation.
It is my opinion and that is all it is that the FDA concerns are more likely to be about DILI and the age related metabolisation of Iclaprim than anything to do with a trial which is totally different from the recent MTFB p3 trucks.
I will hopefully gain a better insight next week.

Purely posted for info as a few earlier posters had raised points re Arpida ASSIST phase 3 truaksvabdvthe liver results.
Although it was submitted in the NDA it has very limited relevance as the dose rate of Iclaprim was variable.

So info is totally indifferent to answering FDAs concerns imo.

With respect to hepatic effects, the table below provides a summary of liver function tests: number of patients with extreme values. At the end of treatment (EOT) visit, 14 patients treated with iclaprim (2.92%) presented with ALT aminotransferase >3xULN compared to 17 (3.62%) in the linezolid arm. At the test of cure (TOC) visit (7 to 14 days after the EOT), 18 patients treated with iclaprim (3.87%) presented with increased ALT aminotransferase >3xULN compared to 13 (2.86%) in the linezolid arm. At the late follow-up (LFU visit), 24 patients treated with iclaprim (5.25%) presented with increased ALT aminotransferase >3xULN compared to 8 (1.83%) in the linezolid-arm. Neither patient group demonstrated a pattern of elevation in bilirubin or alkaline phosphatase or an excess in elevation in comparison to the other. No study drug discontinuations were observed due to elevation in aminotransferases, bilirubin or alkaline phosphatase in the iclaprim group. No cases met criteria for Hy’s Law [aminotransferase elevation greater than 3x upper limit of normal (ULN) with findings of cholestasis or elevation of total bilirubin 2xULN]. None of the deaths in the iclaprim group were associated with abnormal liver function tests or indications of hepatotoxicity.

51
Table of Contents

Summary of Liver Function Tests of Pooled ASSIST-1 and -2: Number of Patients with Extreme Values



Iclaprim

%

Linezolid

%

ALT >3xULN









EOT

14

2.92

17

3.62

TOC

18

3.87

13

2.86

LFU

24

5.25

8

1.83

AST >3xULN









EOT

6

1.25

9

1.92

TOC

14

3.01

13

2.86

LFU

15

3.28

10

2.28

Bilirbuin >2xULN

6

1.25

9

1.92

EOT

—

—

—

—

TOC

1

0.22

—

—

LFU

—

—

—

—

ALP >3xULN









EOT

3

0.60

3

0.61

TOC

2

0.40

2

0.40

LFU

2

0.40

1

0.20


Overall, subjects with increases in ALT and AST levels were asymptomatic, and the increases in ALT/AST were reversible. The mechanism behind increases in ALT values developing after stopping iclaprim is not known. Drugs that cause severe liver injury in humans generally have not shown dose-related toxicity, and generally have caused low rates of severe injury in humans (1 in 5,000 to 10,000 or less). Such idiosyncratic reactions due to iclaprim may not be revealed in a safety population of approximately 500.

Bermuda is right these are from the Arpida phase 3 Assist trials which highlighted liver and cardiac issues(QTc) in the European submission.
They used a weight based dose rate but the move to a fixed 80mg was designed to overcome these issues.This was at suggestion of FDA.So no QTCc questions raised by FDA and no efficacy issues so just liver toxicity wuestionscto be dealt with

Nice post and puts a nice perspective on to how this process works.
The main effect seen in the phase 3 trials were elevated ALT and AST levels which did return to normal fairly quickly ,were comparable to Vancomycin and no abnormal liver damage caused.
Your point about looking at the specific group of patients is entirely consistent with the FDA over arching concern for avoiding DILI and the fact that Iclaprim is metabolised slower depending on age of patient( But no liver concerns published) and the supplemental data presented to the FDA by MTFB posted by Investing wizard last night.
Hopefully the AGM May have a fuller understanding of these matters

Jam absolutely right imo and yes you won’t get answers but to me clues are better than nothing.

Spike I don’t think that type of Meeting which seems much more like a mini Ad Comm where members of a Committee vote is like the one MTFB have attended.
I don’t think it is a FDA Committee that will make a decision at the Meeting by voting but will consider how MTFB have presented and answered the query’s and respond accordingly

We simply don’t know and as I said this will affect outcome.
I am sure MTFB will have a good idea of path forward and will have been working on options to cover different scenarios.This does not mean they expect bad news it is simply good contingency planning and one of main criticisms mine included was lack of this planning in view of the CRL.
The AGM is just an opportunity to get a better feel for how they see things rather than simply guessing.
We know they will release any news in an RNS rather than at a meeting but any insight imo is better than nine and we know in the valley if the blind the one eyed man is king lol

Unless you are experienced in these type of meetings it is hard to precisely to know whether the official minutes are simply a confirmation of what as said/agreed or more likely imo a reflection and confirmation by the FDA of their response to MTFB position.
So yes the BOD will have a good idea of how the meeting went but depending on “ how predictable” these minutes will read is crucial.
That is the type of question along with others I want to ask at AGM and gauge response. Normally I would just e mail GL for clarification but they are very tight lipped so will simply wait for AGM.
ATB

Evening,
It is really very simple.
They won’t say anything until official minutes are released even though they will have a fair idea of how the Meeting went and likely outcome.
Anyone who is pretending they know the outcome of the Meeting is imo flying a kite.Like the PDUFA decision there will be no leaks and folk can only guess.

In any vacuum people get consumed with rumours and counter claims and make decisions based on little genuine info.
Really suggest people wait for news.
As for me yes I will go to AGM and form an opinion based on what is said and conversations and interaction with folk I have known a very long time. Not 100% as nothing is but a bit more useful than not going and simply trying to interpret folks thoughts whom I have never met and often with an unknown agenda.
Simple choices

Hi Finn,
I am much more positive about the AGM being held before likely minutes released.Not that it will make any difference to the decision but it gives us all a chance to question the BOD who will be aware of what the position is BEFORE the RNS likely hits rather than waiting for the actual RNS.
They may not tell us anything but personally I would rather have the opportunity to make a judgement call on their level of confidence rather than not have such an opportunity.

When the official minutes are released we will all be aware of the pathway forward and having an AGM afterwards will. not imo add anything to the level of knowledge so I am much in favour of one beforehand.

Of course there are some who will never attend and have already made their mind up about the outcome here.Thst is their choice but I prefer to make decisions based on the fullest info rather than purely speculating based on conjecture but each to their own.

Hi Tsbs
Wish I could I could do a better trade there than here ATM.
I won’t be likely needing one for a few years

You have to find humour in these situations.Plus am about to spend the day in Liverpool which for a Manc is not always fun.But sun is shining and I have had my coffee

They say Up North
Where there is Muck there is Brass. But there is a sayingbinnGeirgua where there is Muck you find More Muck(especially Kick Muck).
If you want to find Brass go to the local Brass House as Billy says

Taffy all,explained now