Member Info for sadoldgit

Further evidence in no way means further testing. Testing is completed.
It is not the results of the test that are in question it is the question of abiding by regulatory adherence and the proof thereof.

Regards

Edison cannot legally hold any information outside of an RNS only their opinion based on their interpretation that lies within.

Sareum outcomes/options

1. Understand and submit supporting documentation within 14 days in Sar reply to MHRA (constructive)
2. Request extension to 14 days to enable sufficient time to understand and gather all required supporting documentation. (constructive)
3 Request extension to 14 days to enable review by GLP ( may prove a little lengthy). if cannot supply documentation) Constructive
4 Do nothing and accept Clinical Trial Application has been unsuccessful. ( non constructive)

Investors options.
1 constructive discussion accepting predicament we are in looking at all possible information we have to explore probable outcomes/ scenarios
2 Constructive discussion which result from recently selling and or wanting to buy in lower
3 Non constructive discussion by the utilisation of non topic, non factual related arguments leading to insults and a slow but sure degradation of the quality of posts.
4, Do nothing apart from become resentful and pessimistic.

There is factual information and there are opinions. But opinions should be based on fact. We are all in the same boat here albeit with differing agenda's

Regards

4

Edison opinion?

The company had planned to initiate the Phase Ia trial (safety and dose-finding study in healthy volunteers) in Q422 which, in our opinion, is now likely to be delayed until 2023 at the earliest.

Unfortunate use of wording here which again is open to interpretation.
Delayed until 2023. This implies beginning or end? can be interpreted as from Jan 1st 2023.
By the addition of 'at the earliest' implies later than 2023 which can be interpreted as 2024 or later.

Edison will have no more information than Sareum have.

From Sareum RNS
Due to uncertainties around the timeline for resubmission, we therefore no longer expect the trial to commence before the end of 2022.

This is all we can go on. Further clarification can only be obtained via RNS.

Good morning Bobbler. I doubt 100% that the cause for concern is with regards to non establishment of a MTD.
In these instances in the absence of a MTD, a MTD is taken as 30 x maximum therapeutic dose.
12.5 mg per day up to a maximum of 1000mg per day therapeutic dose. At 30 grammes a day it would be similar to eating a packet of smarties.

Whatever the results of the clinical trials are, is irrelevant. The objective here by the MHRA is to establish that GLP has been adhered to. Nothing more and nothing less.

However, if such problems come to light as use of uncalibrated/ calibration out of date or operating procedures not being adhered to then it places Sareum in deep 5hit.

CRO would have undertaken all work under GLP. if they have failed in this ( which I doubt 100%) then there are negligent.

Too much scaremongering going on here, although I do acknowledge this is a cause for concern to some investors.

Regards.

I have had several dealings with NII on an audit, not found them to be difficult but they are thorough, very.

Anyhow back to situation in hand. I will refer to the following from the RNS
'
Whilst the Company has yet to receive a formal letter of non-acceptance, the MHRA has indicated that it seeks a review by the UK Good Laboratory Practice (GLP) Monitoring Authority, or further support, of the non-clinical data submitted as part of the application to approve the clinical study. Sareum and its advisors are seeking additional clarification from the MHRA and will provide an update on next steps for resubmission as soon as possible.'

All they have asked for is additional information or a review by the UK GLP.

It does not state that as we have not received further support or a review by the GLP that your CTA has not been granted.

To the contrary, they cannot continue the process of approval until this information has been received. Over half of CTA's require additional information. 95% of these are successful in approval.

If the CTA were declined there would be no need to seek a GLP or further supporting material.

Some posters here are interpreting this RNS based on their negative attitude or their agenda.

Regards

As you say Cobradan Sareum do leave gaps in their communications.
Contact the MRHA and request exactly what information is required. Sareum will not have this ie they will have no records of testing equipment calibration certification or the procedures for the selection qualification and training of staff. QA procedures. This information will be held by the CRO.
It is not the data that is at question it is the practices used in gaining this data.

It will take a few days to gather the required information, I would think having been involved in audits before (NII). Not difficult, not nasty just time consuming.
Should Sareum be granted further time in excess of the 14 days in which to reply then no reason for it to be a problem.

It is not even a week yet since the RNS so give the poor buggers some time to gather required information.

Sareum have a responsibility, as does the CRO and especially the MHRA the approval body for regulatory compliance. Nothing more than removing all element of doubt that procedures and the control of have been effectively adhered to.

Regards

Good morning Utahsaints,
Why would the CTA not go through. AT the moment all the MHRA have done is request supporting information to prove GLP conformity or failing this a review by the GLPA?
Time consuming yes.

'Good Laboratory Practices (GLP) Requirements for operations
good laboratory practices regulations, good laboratory practices, good laboratory practices guidelines, good laboratory practices fda, glp practices, glp guidelines, glp regulations,
Good Laboratory Practices guidelines
To assign responsibility for sponsor management, study management and quality assurance
Standard Operating Procedures must be followed.
Calibration and maintenance of instruments.
Right construction of laboratories to maintain integrity of the study
Raw data should be processed and achieved.
Employees should be well qualified and trained as per the job assigned'

full link below
https://regulatoryinfo.org/good-laboratory-practices-glp-guidelines-regulations-fda/#:~:text=Good%20Laboratory%20Practices%20%28GLP%29%20Requirements%20for%20operations%201,qualified%20and%20trained%20as%20per%20the%20job%20assigned

Regards

Good afternoon C79

As we know Baricitinib is a Jak1 Jak2 inhibitor and there are ever increasing concerns about the adverse reactions from Jak2

Tyk 2 effectively signals through the pseudo kinase domain (JH2) to the kinase domain (JH1), However, it is becoming apparent that addition of Jak1 which acts directly on the active kinase domain (JH1) has distinct advantages iover Tyk2 alone.

However with JAK1,2 & 3 we cannot isolate these Jaks individually only succeed in selectivity over the other 2. Early Jak inhibitors have/had insufficient selectivity and therefore as a result adverse effects are encountered due to off target effects

The days of baricitinib and similar compounds I feel are numbered.

Good posts from you as always.

Regards

Abstract
Inhibition of signal transduction downstream of the IL-23 receptor represents an intriguing approach to the treatment of autoimmunity. Using a chemogenomics approach marrying kinome-wide inhibitory profiles of a compound library with the cellular activity against an IL-23-stimulated transcriptional response in T lymphocytes, a class of inhibitors was identified that bind to and stabilize the pseudokinase domain of the Janus kinase tyrosine kinase 2 (Tyk2), resulting in blockade of receptor-mediated activation of the adjacent catalytic domain. These Tyk2 pseudokinase domain stabilizers were also shown to inhibit Tyk2-dependent signaling through the Type I interferon receptor but not Tyk2-independent signaling and transcriptional cellular assays, including stimulation through the receptors for IL-2 (JAK1- and JAK3-dependent) and thrombopoietin (JAK2-dependent), demonstrating the high functional selectivity of this approach. A crystal structure of the pseudokinase domain liganded with a representative example showed the compound bound to a site analogous to the ATP-binding site in catalytic kinases with features consistent with high ligand selectivity. The results support a model where the pseudokinase domain regulates activation of the catalytic domain by forming receptor-regulated inhibitory interactions. Tyk2 pseudokinase stabilizers, therefore, represent a novel approach to the design of potent and selective agents for the treatment of autoimmunity.

Keywords: Allosteric Regulation; Janus Kinase (JAK); Molecular Pharmacology; Pseudokinase; Signal Transduction; Structural Biology.

Protein kinases regulate a plethora of diverse cellular functions. Their highly controlled activation is subject to an equally diverse repertoire of regulatory mechanisms. Pseudokinases, a class of proteins that possess a structurally related protein kinase domain that lacks phospho-transfer function, are emerging as critical yet mysterious regulators of other protein kinases. A new structural and functional analysis of the pseudokinase STRAD provides insight into the mechanism by which it allosterically regulates the catalytic function of the protein kinase LKB1 and hints at an evolution from a classical kinase-substrate relationship.

Regards

CoL Not anywhere I believe have I stated my hopes as factual information.
Perhaps you could point out where I have participated in this.

Regards

I would like to think that Sareum are at least in close dialogue with MHRA and the CRO in an effort to resolve the current issue.

Regards to all.

COL

No one stated that Sareum are entirely patent-centric. My viewpoint that a couple of people dedicated to finding cures for diseases as opposed to outright profit. About 3 persons in Sareum. I mentioned nothing about small companies, I mentioned Sareum as that is who we I am invested with. My view is that a Sareum with very few employees will not commit criminal offences and place patients at risk in return for profit . That is all. I have given just a couple of examples out of many of GSK proving my point.

'"Across the U.S., pharmaceutical companies have been pleading guilty to criminal charges or paying penalties in civil cases when the U.S. Department of Justice finds that they deceptively marketed drugs for unapproved uses, putting millions of people at risk of chest infections, heart attacks, suicidal impulses or death. Since May 2004,

Pfizer, Eli Lilly & Co., Bristol-Myers Squibb Co. and four other drug companies have paid a total of $7 billion in fines and penalties. Six of the companies admitted in court that they marketed medicines for unapproved uses."

Can I take it that your opinion that this is all due to the midranks and that the directors at the top that are ignorant of what is going on in their company. Whatever happened to accountability.

Hope is about all you do have CoL as i do not think there is much we are ever likely to agree on.

Your doubts are doubts and by definition are not facts. I have concluded that whether right or wrong that your posts in themselves are indeed BS.

Regards

What I posted is not BS.

Sareum can apply for an extension by the MHRA, in this case the 14 days is not absolute.
Sareum not known for good comms.

Good pertinent post Snoop18.
Sareum are aware of GLP. All that remains is for Sareum to supply supporting evidence to substantiate that GLP has been used throughout.
Sareum I doubt have copies of management control procedures from the CRO, detailing

selection qualification and training of staff
operating instructions
procedural use and adherence
handling of data
Storage of data

These to name just a few.

Sareum should have received documentation confirming that all work carried out will be to GLP. That is all they will have.

All they (MHRA) require is evidence that supports that this has been the case.

A mountain is being made out of a molehill

Regards and beer time

Are you denying that the information below is false?
GlaxoSmithKline Scandal
A Chinese court ordered GlaxoSmithKline to pay $492 million in 2014. The fine resolved charges of bribing doctors in China to use GSK products. It was the biggest penalty ever imposed by a Chinese court.

The court sentenced Briton Mark Reilly to four years in prison. He was the company’s British executive for China. Four other Chinese employees received the same punishment.

But the employees may never serve prison time. The court postponed the sentences. Reilly was deported.

In February 2018, GSK was still answering to fraud investigators in its home country.

Step forward to 2020
In March 2020, the Department of Justice (DOJ) sent GSK a notice of a civil investigation it had opened into allegations of False Claims Act violations by the company because of Zantac. DOJ requested documents on June 18, 2020. On the same day, the New Mexico Attorney General filed a lawsuit against GSK for violations of false advertising statutes and state consumer protection, among other claims.

2011
GSK set aside $6.4 billion for future lawsuits and settlements.

Much earlier 1993 to 2003.

Wellbutrin: The United States also alleges that, from January 1999 to December 2003, GSK promoted Wellbutrin, approved at that time only for Major Depressive Disorder, for weight loss, the treatment of sexual dysfunction, substance addictions and Attention Deficit Hyperactivity Disorder, among other off-label uses. The United States contends that GSK paid millions of dollars to doctors to speak at and attend meetings, sometimes at lavish resorts, at which the off-label uses of Wellbutrin were routinely promoted and also used sales representatives, sham advisory boards, and supposedly independent Continuing Medical Education (CME) programs to promote Wllbutrin for these unapproved uses. GSK has agreed to plead guilty to misbranding Wellbutrin in that its labeling did not bear adequate directions for these off-label uses. For the Paxil and Wellbutrin misbranding offenses, GSK has agreed to pay a criminal fine and forfeiture of $757,387,200.

Putting the patient first my ar5e

It would not be a problem if the data suggested were not best in class. The data submitted is the data submitted and that is that. GLP is to ensure that good laboratory practices are adhered to in the derivation of these results.

Is all the equipment calibrated and in date.
it is normal practice in any laboratory work that equipment used in addition to the above, serial number of item of equipment. Calibration due date, Pre use checks. ( are calibration seals still in place) Post use checks,
Recording of information with dates and accurate times.

Dont look at it as duff or misleading results, look at it as compliance of which much is derived from statute law.
The CRO if reputable should be able to provide all this information. If they cannot supply then they will be negligent.

What you are looking at is legitimacy.
As an example you may be stopped by a police patrol car for speeding. He has caught you doing 38mph in a 30 mile per hour speed limit.
You may accept or go to court. It is a requirement that the calibration of the patrol car is carried out on a daily basis ie validity for a 24hr period. Your barrister may then request the calibration check required prior to use in this instance.
If the police cannot supply the calibration record or it is out of date, then they have not followed compliance. In effect they are using equipment that is not valid, even though it may be accurate. Therefore in this instance the charge becomes void.

It is all down to what procedures you have in place and a record of such that you have and are maintaining these procedures.

A company will have Management control procedures.
Recording and storing of data.
Documentation that specify practices during laboratory work.

I have been present on several audits in the Nuclear industry by the NII ( now ONR) WANO and involvement in an OSART review.

There were a person who could never be bothered writing the date and would, when he thought he could get away with use ditto marks.
Whilst not bad it was pointed out very clearly that this was not best practice.
Peer checking and independent verification, almost the same but a big difference. When a signature is required you put a signature and not write your name or your initials.

It may appear trivial but they will pick up on these points.

My thoughts are that the data is available but should Sareum not supply the required data then the MHRA will request an audit by GLP. Most importantly The MHRA asked for a GLP review or supporting evidence.

Regards

Woodyjohn40. Thankyou for the acknowledgement. Bigger companies swallow up smaller companies in the journey towards globalisation.
Sareum small company where the dedication it to finding cures as opposed to putting profit first.
The methods and means they use at times are somewhat questionable.
if we explore all avenues and possibilities and rule out the ridiculous we should be better to understand the predicament. we are in.
The last compound we were involved in for clinical trial application were our CCT245737. This would have been submitted by CRT well versed in applications.
Sareum a small company and have made use of a CRO and in this case the MHRA may well be naking sure that all the i's are dotted and all the tees crossed.

Regards

Good evening Salfordred.
Not tonight unfortunately as required in work tonight for a period of 6 nights. I hope all is well with you and back to full health.
A few beers would be nice,
A bit of a shambles since the 9th here. Poor communicating dont help plus a degree of panic. All understandable. May take a few days for Tim and co to resolve.

Would expect an RNS giving us an update mid week if only to clarify situation at the moment.
Nothing much we can do apart from wait. If I can get a few less than 1.8p old money i will buy.

Enjoy your evening and you look after yourself.

Regards

Best case scenario is to supply some evidential supporting documentation
Worst case scenario is a GLP audit of the CRO if fail on the above.

Ther does not appear to be any other outcome. Not far out from SYNOOGOLD post a few days ago.

Rehgards