Member Info for sadoldgit

Good morning again Rebster408

To elucidate further.

When any scientific data is produced the means and procedures to be adopted must show regulatory compliance to ensure the data provided is accurate.
The onus will be on the person supplying the data. That is all the MHRA require.
In addition to calibration and procedural use of equipment by suitably qualified and experienced staff, there must also exist a method by a company that these measures are sustained in most cases by Quality assurance documentation.

This I might add is the most likely of evidential documentation required by MHRA and that may well be all they need.
Sareum wont have it. the CRO will.

Time for me to blow the froth off a few.

Spot on Rebster408.

I note Tim and Co regularly stated GMP but little to no mention of GLP. GLP is just as important if not more so. Conclusion is that Sareum have not paid the GLP side of things the attention it deserves.

You will get in all study reports, the equipment used and the results. Of equal importance is the calibration and correct use of that validates the data that you provide.

That is the crux of the matter.

I have worked in Nuclear industry since 1986. Unheard of for requests pertaining to legitimacy of results that have been provided. Small companies have asked for additional info to satisfy their requirements of procedural use and adherence.
I have been happy to oblige with additional documentation that would not ordinarily be supplied.

What used to be considered good enough is no longer good enough. increasingly so over the past few years.

I will add that as these studies were concluded around March time it may very well take a few days by the CRO to gather all the requested supporting data. How much do the CRO want? It a pity that MHRA not dealing direct with the CRO.

Regards

Smart_inv. Good morning.

It is all about compliance. MHRA require evidence that GLP has been adhered to.

That is all that can be stated with fact.
Sareum would not have been in possession of this information. All Sareum at the very least will have is assurance and should be in a contract/pre agreement that all work will be carried out to GLP.

The procedural documentation and relative proof of compliance will be in the possession of the CRO conducting the research. Unfortunately the MHRA are not requesting the information from the CRO as they are not the sponsor. They are requesting supporting evidence from Sareum who in this instance are acting as the middle man and also a further chain of communication.

All the requierd information with regards to conformity can only be held by the CRO. Sareum can request the supporting evidence from the CRO to submit to the MHRA. If this does not prove satisfactory then The MHRA can request the GLP authority to conduct an audit on this study.

Regards

Any test facility which conducts, or intends to conduct, regulatory studies must comply with good laboratory practice (GLP) regulations when carrying out safety tests on:

pharmaceuticals
agrochemicals
veterinary medicines
industrial chemicals
cosmetics
additives for human food and animal feed
biocides

UK GLP compliance monitoring programme members
See Current Members of the UK GLP compliance programme (PDF, 228 KB, 17 pages)

All facilities within the UK GLP compliance programme should be able to provide a statement of compliance on request.

Email gxplabs@mhra.gov.uk for information about facilities not on the list.

To leave the UK GLP compliance monitoring programme email gxplabs@mhra.gov.uk.

Audits
Any regulatory authority in the UK or overseas can ask the GLPMA to audit a study that has been submitted to them.

The GLPMA checks that the study complies with the principles of GLP.

Not much else can be put down that we can work on.

Regards

Good morning Warthog,
Timescales. if we follow the initial notification timelines Sareum should have recieved initial notification within 30 days.
Clearly this has not happened and would look to be around 100 days before Sareum have received request for additional information ( just like the other 51% off CTA applicants)
It is through no fault of Sareum that this backlog has arisen.
I would suggest that the aim of the MHRA would be to complete the decision making process within 30 days of first notification to Sareum of inability to progress due to lack of supporting evidence. This is only an opinion from my point of view in light of recent events.
Time consuming it will be. If the required information is not supplied then the Good Laboratory Practice Authority will become involved which will be even more time consuming.
|Sareum could well reply with we are unable to supply the supporting evidence that you require and then the MHRA would request an audit of the CRO by the GLP authority.

Simples but bl00dy time consuming.

Sareum will need be very careful what they put in an RNS so as not to make a bad situation appear worse.

Regards

Just for fun. Since lockdowns and Covid timeframes have gone to 5hit. in the judicial system, speeding offences are taking 12 months for a court attendance date.

backlogs will not be removed overnight

I am not of the belief you will get an RNS from SAR for a while yet.
They need send the supporting evidence of GLP.
Whilst we are at it when was the BoD last in a lab? Are the aware of GLP procedural adherence. Can Sareum supply calibration and pre use checks prior to use of testing equipment? I doubt they are even aware of it.

Unfortunately as Sareum have submitted the CTA they are the people thet need progress the requirements. If reputable CRO has carried out the research work then there really should be no problem in the slightest.

I would take it that the inability to supply is the initial assessment. A real backlog here if this is the case. However, Sareum will have 14 days in which to respond and may be granted an extension to this time frame. You are effectively looking at 30 days from 8th of october for the result of the MHRA decision.

GLP is something that has to be complied with. In effect you will be subjecting health people to a compound in ascending doseages. The preclinical data from whence the initial trial dosages originate must be 100% reliable.
The data needs to be legitimate. The MHRA have a responsibility to public safety and due diligence will be vigorously carried out to the highest order.

It is certainly not a case of dropping an email to the MHRA . The application cannot progress further without this additional data irrespective of how good that data may be.

How many of you here have worked in laboratories? I have spent on and off over a period of 35 years in laboratories. Not known as GLP at the time. We did have procedures that we used and the biggest subject that government inspectors looked at were calibration and usage of instrumentation and the suitability and qualification and training staff in the correct usage of. If this is not followed then it seriously removes any legitimacy from your results.

Not a big problem but will be time consuming.

Regards and dont fret.

I will add that the patent only applies to the country it is issued in.

Easiest thing to do by SO is transfer the Patent License.
A third party can apply for a patent to be revoked ( in this case the CPF) giving their grounds for revocation.
For example, we will take 737 in combo. No further development can be undertaken of the patent protected in combo therapy without the express permission of the patent holder. (Patent infringement)

Patent and patent application is part of IP.

Outcomes are transfer ownership of patent or have the patent revoked.

It depends on how the CPF and SO ( under the influence of GSK) choose to handle it.

Early statements made by SO were that SAR737 may prove to be more commercially viable than momo.

There exists significant value in 737.

As for the outcome, it is still a waiting game for those that are here.

Regards

Patents. SO own the patent and believe this comes under intellectual property.
Intellectual property will be returned or at the request of CPF be destroyed.
Patents are to protect the inventor and have a monetary value.
All down to the small print in the original contract between CPF and Pronai therapeutics.
A can of worms here.

But a link briefly indicating patent transfer below.

https://www.upcounsel.com/blog/how-to-transfer-a-patent#:~:text=As%20objects%20of%20intellectual%20property%2C%20patents%20and%20patent,or%20as%20the%20result%20of%20some%20legal%20action.

Good morning HbD
Post a link here which was recently posted by Krone ( bless him)

Look at section 15
https://www.sec.gov/Archives/edgar/data/1290149/000119312516765907/d255357dex101.htm

The original patent licenses will be returned and SO no longer have to pay licensing fees.

Now as I understand it and I may be wrong here. That any patent granted ( non licensed) would be cancelled. I were of the belief at one time that this would become the property of CPF/ICR. I dont think this is quite the case . i remember years ago, thinking that if pronai returned the 737 it will be of benefit as would become property of CPF.

Will delve into this more later.

Regards

Weird goings on since GSK bought TESARO ( concluded Jan 2019) and the non development and non opportunity to on license 737 since.

Only realistic competition in this area is below.

Prexasertib licensed from El Lilli 29thJune 21.

Acrivon signs exclusive worldwide license agreement with Eli Lilly and Company to develop and commercialize prexasertib, a clinically advanced, selective inhibitor targeting DNA Damage Response (DDR) kinases CHK1 and CHK2, which has shown durable activity, including complete responses in a proportion of patients across multiple cancers in Phase 2 studies
Acrivon aims to accelerate development and improve clinical success rate of prexasertib and pipeline of oncology drugs through its proteomics-based, drug-specific OncoSignature® companion diagnostics for prospective identification of patients most likely to benefit from treatment
Company also discloses equity investors and announces experienced founding and executive leadership team to advance precision oncology drugs in multiple solid tumor types with high unmet need.

In addition from April 2020. This just after release of Michelle Garret and co on CHK1 inhibitor resistance had completed
studies with 737 and prexasertib in combo and recommendations as such of AKT and Pl-13 inhibitors.

Prexasertib in combo with. Now bare in mind clinical trials had been started by El Liili around 2014 but none I can find involving prexasertib outside of chemo.

LY3023414 (Part E) [An inhibitor of phosphoinositide 3-kinase alpha (PI3K alpha) and mammalian target of rapamycin (mTOR), DNA-dependent protein kinase (DNA-PK), and other class I phosphoinositide 3-kinase (PI3K) family members]

Also note that sponsor is shown as El lilly and Acrivon reported to have in licensed.

Good news for CHK1 inhibitors.

I will add her whilst not hitting the science too much

CHK1 more prevalent in lung cancers whilst CHK2 in breast cancers. slight difference here on what phase part of the cycle each can control.

Now whilst CHK2 would appear more effective in Breast cancer when used with the chemo (Doxorubicin). Doxorrubicin was discontinued due to severe adverse effects. Much of this detailed in Michelle Garret and co recent studies with CHK1 and CHK2 inhibitors ie SAR737 and Prexasertib whilst working on combination studies and CHK1 inhibitor resistance.

https://www.icr.ac.uk/our-research/research-divisions/division-of-cancer-therapeutics/head-of-biology-leader-of-cell-cycle-control/research-projects/cell-cycle-checkpoint-kinases-chk1-and-chk2

Prexasertib was and still is available for studies.
Michelle Garrett and co were using this in combo Chk1 combo studies in the absence of 737.

odd that not only under SO's control that 737 was taken off the for sale list but also ,indications are that was not readily available for use in combo therapy whereby SO had patented the combination therapy. The patent I conclude had prevented further development work by non SO organisations.

The patents will now be cancelled. Until formerly notified of withdrawal the patent protection will still be in place. Maybe then we will see some serious deserved development of 737.

Genetic profiling to indicate patients most likely to benefit has already progressed with 737.

CHK1
CHK1 is important for the activation of S, G2 checkpoints in response to DNA damage and replicative stress and is involved in DNA repair. In addition, studies have shown that in tumour cells which are deficient in the tumour suppressor p53, CHK1 inhibition will sensitise these cells to genotoxic cancer treatments. Inhibitors of this kinase are therefore expected to lead to sensitisation of tumours to both radiotherapy in the form of ionising radiation (IR) and chemotherapeutic agents which are used in the clinic for the treatment of cancer.

In collaboration with Dr Ian Collins (Medicinal chemistry Team 2), other teams in Cancer Therapeutics and Sareum Limited, Cambridge, we have used crystallographic structure-based design to optimise the biological activity of hits identified through fragment-based screening against CHK1. We developed a cascade of cellular assays, evaluated these compounds in vitro and subsequently developed robust pharmacodynamic (PD) biomarkers for compound evaluation in vivo.

This led to the identification of SAR020106 as a potent and selective inhibitor of CHK1 with in vivo activity in human tumour xenograft models and provided proof of both mechanism and concept for the project that CHK1 inhibition was therapeutically relevant. We have recently generated cell lines with resistance to both in-house and external CHK1 inhibitors and are currently investigating potential mechanisms of resistance.

Full link below and inclusive of CHK2

https://www.icr.ac.uk/our-research/research-divisions/division-of-cancer-therapeutics/head-of-biology-leader-of-cell-cycle-control/research-projects/cell-cycle-checkpoint-kinases-chk1-and-chk2'

Good post C79.
737 did prove to have good efficacy and safety profile. Far superior to AZ CHK inhibitor that got discontinued due to adverse effects

Interestingly these reports appearing along with recent study work with CHK1i and especially 737.

Two options here are on return of 737 to CPF and put up for on license or go back to CRT via CPF and continue combination and development studies.

Phase two results were good.

Regards

Speculation is speculation whether it is discussed on these boards or released via media.
I have been here a while and have added today. I regard the shares as too cheap at the moment, as i look at where I believe we stand with what we have.

Regards

Agree wholeheartedly Potnak. No news is certainly better than any news that creates uncertainty.
As scientists you would think the BoD would do all they can to eliminate uncertainty.

Regards

Traded at 14.40 would indicate a buy at 97.5p

Hence step up in price

L2 at 1523 PH have entered 115 buy price