Member Info for sadoldgit

Good morning Silverfoil13
I would suggest we will not here anything further until late this week or the following week. Will be dependant on the receipt of the reply from Tim & co.

If you go into the link below and scroll down to Phase 1 application process.
MHRA and REC, consolidated initial outcome. Then 14 days to respond to request for further information.
Then they aim for final outcome within 10 days of the submission date.

Regards

https://www.hra.nhs.uk/planning-and-improving-research/policies-standards-legislation/phase-1-clinical-trials/#:~:text=Following%20feedback%20from%20our%20research%20community%2C%20applicants%20undertaking

Over half of companies that submit CTA's are requested for further information and of these 95% are approved

regards

You are missing that GSK had bought Tesaro along with its pipeline for the treatment of Ovarian, Breast and now lung cancer, That is what they are committed to developing, nothing else.

'The obvious driver is if they believe existing drug/candidates are far better prospects'

The word 'obvious' and 'if' in the same sentence!
It would be obvious if my aunt had balls she would be my uncle.

It is down to control and greed. GSK wholly own all 3 compounds why would they invest in something and have to pay royalties and over 300 million in milestone payments.
I suggest you do a bit more research especially on our CCT245737 and the tactics played by big companies before you post such nonsense. Clearly very little thought has gone into it.

They have just spent 5,1 billion on acquisition of Tesaro pipeline.

https://www.gsk.com/en-gb/media/press-releases/gsk-reaches-agreement-to-acquire-tesaro-an-oncology-focused-biopharmaceutical-company/

Regards

If we look at the little box near the bottom in the Research Ethics Committee

We are one box away from final decision. We are in the box requesting further information.

Once submitted aim for final decision in 10 days.

Yes NUM4 spot on there.

Over half of companies that submit CTA's are requested for further information and of these 95% are approved..

Regards

This may shed a little light on timeframes

https://www.hra.nhs.uk/planning-and-improving-research/policies-standards-legislation/phase-1-clinical-trials/#:~:text=Following%20feedback%20from%20our%20research%20community%2C%20applicants%20undertaking,submit%20an%20application%20closer%20to%20the%20REC%20meeting.

I think this is the best indication we can get.

Regards

Good evening HbD
I dont think you are far out at all HbD. It would make sense to have completed ethics committee meeting as this requires booking in advance and if completed now does not cause issue further down the line.

As for grounds for non acceptance ,there has been, as far as we know no formal letter. Which indicates only informal and thus just a request for additional supportive evidence.

We are somewhere in the below

The initial combined review assessment will be completed within 30 days of being submitted. Applications for healthy volunteer trials and sponsor-determined phase I trials in non-oncology patients may qualify for a shortened assessment time and MHRA will work with the research ethics committee to endeavour to expedite these applications. You should state on your covering letter if you think your trial is eligible. Note that trial designs that stretch to investigating the benefit of the treatment to participants may not be eligible for the expedited assessment timeframe.

We will tell you the outcome of your submission along with the outcome of the research ethics committee review, via the combined review process, which could be:

acceptance of the request for a clinical trial authorisation
acceptance of the request for a clinical trial authorisation subject to conditions
grounds for non-acceptance of the request for a clinical trial authorisation
If we raise grounds for non-acceptance you will have the opportunity to respond, usually within 14 days; however this may be extended on request.

Communication informing the applicant of the MHRA and ethics committee decision following receipt of the responses will usually be sent within 60 days of us receiving the original valid application. If an extension to the response date has been agreed this will impact the final decision timeline.

We have explored all avenues. Tim and Co should know by now that which is required, they may opt for a review by GLP authority. They dont give much information away.

It is not by any means a rejection of the CTA, it as an opportunity that has been given subject to a timeframe, which can be extended to produce the prerequisite supportive evidence.

Regards

All we can do is wait.

I would like to think that Tim and Co have made some progress.

I dont think a resubmission as such.
MHRA have requested GLP review or supporting evidence. Sareum can request an extension to the 14 days in which to submit their reply, The 9th Nov being day one.
As I see it Sareum have been provided a reason for not approving. Effectively this is the initial assessment.
As an update sareum could state we have requested further time to gather the required information whether this is due to either submitting supportive evidence or a review by the GLP authority is immaterial.

They may well have supplied supporting evidence and await the outcome. This can run two ways. GLP review required or non acceptance.

As the MHRA have used the word 'or' it gives Sareum a choice.
With good communications the issue should be resolved either way. Sareum can apply for an extension and I see no reason why this cannot be accepted by the MHRA, The first communication from MHRA received by Sareum is over 100 days since submittance of the CTA, for whatever reason they have not stuck to timelines themselves,

I doubt they have gone through an ethics committee meeting yet. 30 days from the 9th of November with no applied for extension I feel would be the earliest. That is my best guess.

I have been waiting nigh 6 weeks for registration at doctors up here that i was told will take a few days. Still not heard anything. I go visit the doctors here on the 15th October and doctors is closed, It is an Argyle and Bute public holiday.

Expect delays in this processing of CTA.

Regards

PCS1954. Good evening.
You are welcome.
Investors of which I am one, have genuine concerns. It is understandable.

Very little update from Sareum which is only to be expected. They lack detail in RNS, a knee jerk reaction. 51% of CTA applicants are requested for additional information.
In the swing of things no big deal. SP will go up when CTA approved but have little idea when.

There are shorters that is a certainty.

Regards

Not massively by any means as dwindled somewhat just into the red. Most i hold are in the blue but my later recent buys are in the red.

Yes I have banked a decent amount,

My remaining average now is 91.8 p per share. 1.84p old money.

regards

A couple of thoughts here.

Just to add. The CRO conducting preclinical studies would give assurance to Sareum that all work undertaken is to GLP.
That may well be all Sareum have.
The final signed preclinical results will not contain detailed information of GLP compliance.
The MHRA will require proof ie regular audits and QA. as evidence of this compliance. If not supplied by Sareum then GLP review to be undertaken of the CRO concerned.

Apologies for rambling on.

I think we may have more than one CRO involved. If this is the case then most likely where the issues arise.

Sareum, working alongside a specialist contract research organisation (CRO), has designed a Phase 1a/b clinical trial with SDC-1801 in healthy subjects and psoriasis patients.

The Company has now received the final signed report from the Contract Research Organisation that conducted these studies and, as previously reported, these data fully support the Company's plan to submit a CTA application in mid-2022 and to commence a Phase 1a clinical trial with SDC-1801 in H2 2022.

Why are CROs important in clinical trials?

CROs are important in clinical trials because they assume several specialized tasks that cannot be handled by the clinical trial sponsor. Clinical trials require many overwhelming activities beyond the scope of the sponsor’s know how and resources, so that subcontracting this work becomes the best option.

CROs guarantee the technical proficiency required in clinical studies, ensuring the quality of the research and its results.

Clinical CRO not a problem. They would have vast input and met the criteria for Clinical studies.

Pre clinical studies of which Sareum have received a final signed report. Ultimately it is the responsibility of the sponsor that the data is correct and carried out to regulatory procedures. Pre clinical has submitted final signed report to Sareum. This may satisfy the requirements of Sareum ( ie in receiving the results) but not meet the criteria of the MHRA that require evidence to adherence to GLP.

https://www.egnyte.com/guides/life-sciences/contract-research-organization

Regards

However good your opinion may be of the 10yth largest pharma in the world, SRA 737 would be in direct competition.

GSK set Jemperli's list price at about $10,400 per 500 mg vial, which is initially given once every three weeks for four doses and then at a larger dose for longer intervals thereafter.

Their study ran for 24 weeks . you are looking at 80k plus.
what ratio were there in the study of 108 women and the 43.5% statistic were tumour reduction to non detected tumour was there?
All due to lack of treatments.
GSK have their foot in the door with Jemperli the last thing they will want is a competitor.

Jemperli
In the European Union (EU), medicines that are being monitored particularly closely by regulatory authorities are labelled with a black inverted triangle (?) in the product information. These medicines are described as being under 'additional monitoring'. The European Medicines Agency (EMA) maintains a list of all medicines that are under additional monitoring in the EU.

Medicines under additional monitoring have a black inverted triangle displayed in their package leaflet and in the information for healthcare professionals called the summary of product characteristics, together with a short sentence explaining what the triangle means:

Additional monitoring icon This medicinal product is subject to additional monitoring.

The symbol does not appear on the outer packaging or labelling of medicines.

Additional monitoring aims to enhance reporting of suspected adverse drug reactions for medicines for which the clinical evidence base is less well developed. The main goals are to collect information as early as possible to further inform the safe and effective use of these medicines and their benefit-risk profile when used in everyday medical practice.

The concept of additional monitoring was introduced by the 2010 pharmacovigilance legislation, which came into effect in July 2012. The black triangle started appearing in the package leaflets of the medicines concerned from the autumn of 2013.
Taken from the Europeans Medical Agency

'Jemperli was found effective in a study involving 108 women with endometrial cancer that was
advanced or had come back and had got worse despite treatment that included a platinum-containing
medicine. The cancers involved mismatch repair deficiency or high microsatellite instability. At follow
up after at least 24 weeks, the cancer had shrunk or could no longer be detected in 43.5% of women
receiving Jemperli.

Now we have as a fact that based on a study of 108 women 43.5% had either a reduction or could not be detected.
GSK have used this study to market Jemperli. Rather a small study group but due to lack of available treatments allowed to be marketed. Have they followed GLP?

Full link below
https://www.ema.europa.eu/en/documents/overview/jemperli-epar-medicine-overview_en.pdf#:~:text=The%20Agency%20therefore%20decided%20that%20Jemperli%E2%80%99s%20benefits%20are,can%20be%20authorised%20for%20use%20in%20the%20EU.

This 10th largest pharma is not having a great time with its new pipeline.
Take into account the recent reports

'GSK acquired Zejula as part of its $5.1 billion takeover of Tesaro in 2018, along with other oncology drug candidates, including latecomer PD-1 inhibitor Jemperli (dostarlimab) and others targeting TIM-3 and LAG-3 checkpoints.

Sales of the drug have failed to gather much momentum, adding around $140 million in the third quarter, and GSK said in its update on that period that Jemperli is now the primary focus in its oncology business.

Other PARP inhibitors have also run into problems. Market leader Lynparza (olaparib) from AstraZeneca and Merck & Co also lost its late-line ovarian cancer indication, while Clovis Oncology warned last week that it faces bankruptcy as a result of shrinking sales of its PARP drug Rubraca (rucaparib), after losing indications for the drug in ovarian and prostate cancer.

GSK’s setbacks in oncology, meanwhile, come amid a challenging period for the company’s R&D pipeline, which in recent weeks has seen the abandonment of late-stage trials for rheumatoid arthritis hope otilimab, an advisory committee meeting for renal anaemia drug daprodustat that recommended narrower use than hoped for, and the end of a partnership with Adaptimmune on NY-ESO-1 antigen-targeting drugs.

That has placed much more pressure on GSK’s recently filed respiratory syncytial virus vaccine to deliver, along with other late-stage candidates like new HIV therapy Apretude (cabotegravir).

It does question the credibility of the data submitted by not only the 10th largest pharma in the world but also others.

Maybe a reason why the FDA have suffered damning reports of lack of investigations into GLP. I can see no other unless someone here can make a case for this defence.

Regards

No problem Rebster408.
It is very easy to post such comments along the lines of ' why would GSK return 737 if it were any good' Lack of knowledge and posted as a last resort.
GSK have their own totally owned pipeline to treat similar indications as 737 in combo. Why waste money on devoping something that will we in direct competition to their own pipeline.

They have already committed to the purchased TESARO pipeline

'Apart from ovarian cancer, Zejula is being evaluated in patients with lung, breast and prostate cancers.

Tesaro oncology pipeline includes multiple other products such as anti-PD-1 antibody dostarlimab and antibodies against TIM-3 and LAG-3 targets.'

14th Nov 2022
GSK has had another setback in its oncology business, after the FDA asked it to restrict use of its PARP inhibitor Zejula in ovarian, fallopian tube, or primary peritoneal cancer to patients with a specific mutation.

The narrower label for Zejula (niraparib) means it can only be used as second-line maintenance therapy after platinum-based chemotherapy in patients with these cancers whose tumours carry a germline BRCA mutation – around 15% of the population.

It’s the second blow to GSK’s cancer drugs portfolio in the space of a week, after the company revealed that its BCMA-targeting drug Blenrep (belantamab mafodotin) failed to meet its objectives in a multiple myeloma study, threatening its current accelerated approval in the US.

The label change also comes after GSK voluntarily withdrew another indication for Zejula as a late-line treatment for women with recurrent ovarian cancer, after it emerged that PARP inhibitors may have a detrimental effect on survival in this patient group, based on a “totality of information” from the class.

Zejula was approved in 2017 for the second-line maintenance indication in ovarian, fallopian tube, or primary peritoneal cancer, becoming the first drug in the PARP class that could be used in all patients in this category, regardless of their BRCA status.

That early approval came on the back of the NOVA trial, which showed improved progression-free survival (PFS) with GSK’s drug, and was granted on the premise that GSK would run an extension to the trial to confirm Zejula’s benefit on overall survival (OS).

The company revealed recently however that the OS data showed a small excess in death rate for non-BRCA patients, with a trend in the other direction for the BRCA group, which prompted the FDA to convene an advisory committee meeting to discuss the data. That was due last Friday, but cancelled when GSK opted to withdraw the approval.

CB to the contrary 182k shares

I am not sure as to how Sareum can be involved in future developments as such.

Possibilities are
On license or return to CRT for further development.
What input would Sareum have apart from financial?

Devlopment of new combination compounds eg Pi-13 and AKT inhibitors will take years. There are however, studies underway in phase 1 and 2 trials of these later generation inhibitors

Spank.Themonkey,
dont know what happened to WIP. Not heard anymore rumours of password protected 737 developments from him.

Regards

Warthog. I sold over 1.7 miliion at average of 8p mid last year. Average purchase price was just under a penny

Just saying