Member Info for sadoldgit

They should be able to email that detail over to them electronically. Should take no longer than a day or so.

Regards

No problem Spurs312,
The MHRA must give a decision within 60 days. It not look like they have done so. We understand that there are backlogs. All they have effectively done is ask for a review by the Good Laboratory Practices Authority.

We should get due to the delay by MHRA 14 days to respond and/or apply for an extension.
If I were Sareum I would question as to why this was not picked up on initial assessment? By abiding by the MHRA timelines it would give ample time for this problem to be rectified.

I would conclude in the manner in which the RNS were released that Sareum received this response today.

Nothing to do with the science or the funding. Somebody has gone through it with a fine toothed comb and can not find documentation relating to Good Laboratory Practices which will be slightly different than Good Manufacturing Process which would have been supplied.

The term GLP is most commonly associated with the pharmaceutical industry and the required non-clinical animal testing that must be performed prior to approval of new drug products
Good Laboratory Practice (GLP) embodies a set of principles that provides a framework within which studies are planned, performed, monitored, recorded, reported and archived.
Good Laboratory Practice is not less important than Good manufacturing practice. In the manufacturing of drugs, overall Control is essential to ensure that the customer receives drugs of high quality.

Along these lines I would hazard a guess which should not prove too difficult to resolve.

Regards

More than half of all clinical trial authorisation (CTA) applications for investigational medicinal products (IMPs) received by the Medicines and Healthcare products Regulatory Agency (MHRA) require additional information to be submitted before they are considered approvable. Many of the issues identified are common and avoidable if available guidance is followed or if a satisfactory justification for not following the applicable guidance is provided in the application.

How long you been invested in SAR then Nubex?

Nubex you have not been here 2 minutes.

It is not a rejection of a CTA. MHRA have requested a review that is all.

This should have been raised on initial assessment after 30 day.
We are informed of this after a 100plus days. 14 days to respond and around 3 to 4 weeks if satisfactory.

Whoever involved in submitting the application has not done due diligence i feel.

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.

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

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.

ALL THE MHRA HAVE REQUESTED IS FURTHER INFORMATION TO SUPPORT THE APPLICATION.

It should not prove to be a big problem. Sareum have 14 days in which to respond.
This should have been notified to Sareum after 30 days and not after the 60.
Need find out exactly what is required
No formal notification so do not see a reason to resubmit, it has not been rejected, so should just require the approval of the good standards laboratory monitoring authority.

A highish percentage of applications are delayed due to lack of information supplied. ( Wht the neck companies do not laise with these people is beyond me, they are human and should you ask their advice are normally keen to help.

Much of this advice is layed out in the clinical trial.gov website.

On the plus side it indicates no funding required at this stage in time for phase1b. Non clinical and exactly what it pertains to am not sure. Hazard a go at manufacture of capsules.

Somebody needs their bottom kicked

What makes an SMR viable? Most people know very little about them and Laura Kuesensberg will be no exception.

JR these are target prices ie 40 to 115p that were set before news of application for chapter 11. I believe these to be rather optimistic in short term. I may be wrong, As I posted some time ago, Cineworld are cute if they choose the chapter 11 route. They have had some extremely favourable outcomes. The only bugbears are cineplex lawsuit and maintaining a reasonable turn over in their cinemas. They are well able now to reduce debt and in a sense sit better than they were 6 months ago.

Not completely without risk I might add but disagree immensely with the MF. MF is a business that makes money from a subscription service, that they then constantly hound you to upgrade.

However, am of the opinion in the current swing that a price target over next 1 to 3 months 20 to 40p which is not far from a PH target price end of August at around the then reduced target of 30p.

Regards

Good afternoon C79

Some very pertinent points.

Some or the data take note 75 is from 2012 whereby the later refers to 2022.
i did post some info but vanished into the internet ether. will try again later

MattyBoy1965
Great post!
The subscriptions are where they make their money.

Afternoon 007.
Maybe because I have been here ages, I am more excited with 737 than 1801.

Michelle Garrett in from day one with CCT245737. The woman in her field of expertise is world class and 2nd to none. Phenomenal work on CHK1i resistance in cancers post SO cessation of development. In effect 737 derived from this woman. Michelle Garrett not allow 737 to go by the wayside. Hard to treat cancers is her objective. Ovarian, breast and pancreatic. The three that are the most difficult to treat mainly due to resistance to treatment.

https://www.pancreaticcancer.org.uk/news-and-blogs/meet-michelle-garrett/

https://www.kent.ac.uk/biosciences/people/1185/garrett-michelle

Regards

Yes it is evident they know very little Potnak.
Sareum were never partnered with Sierra Oncology. It were returned to the CPF from whom they obtained the license from in the first place.
I would expect a great deal of interest in 737 especially later post SO development. I note that research this year specifically refers to SRA737 and not CHK1 or Prexatirb.

It looks like someone is determined to get 737 into the clinic.

Regards

Great to see you here AtMKD

Would speculate much going on with CCT245737 outside of research ( overcoming resistance pathways)
Seriously believe it will blow GSK triple combo therapy out of the water.

No more from me for a bit, much to the relief of some here.

Regards

Regulation of CHK1 inhibitor resistance by a c-Rel and USP1 dependent pathway

'Previously, we discovered that deletion of c-Rel in the Eµ-Myc mouse model of lymphoma results in earlier onset of disease, a finding that contrasted with the expected function of this NF-?B subunit in B-cell malignancies. Here we report that Eµ-Myc/cRel-/- cells have an unexpected and major defect in the CHK1 pathway. Total and phospho proteomic analysis revealed that Eµ-Myc/cRel-/- lymphomas highly resemble wild-type (WT) Eµ-Myc lymphomas treated with an acute dose of the CHK1 inhibitor (CHK1i) CCT244747. Further analysis demonstrated that this is a consequence of Eµ-Myc/cRel-/- lymphomas having lost expression of CHK1 protein itself, an effect that also results in resistance to CCT244747 treatment in vivo. Similar down-regulation of CHK1 protein levels was also seen in CHK1i resistant U2OS osteosarcoma and Huh7 hepatocellular carcinoma cells. Further investigation revealed that the deubiquitinase USP1 regulates CHK1 proteolytic degradation and that its down-regulation in our model systems is responsible, at least in part, for these effects. We demonstrate that treating WT Eµ-Myc lymphoma cells with the USP1 inhibitor ML323 was highly effective at reducing tumour burden in vivo. Targeting USP1 activity may thus be an alternative therapeutic strategy in MYC-driven tumours

Dont worry about the science so much. It very much looks like continuation of Michelle Garrett and Co research, definitely same area. Am looking at whether their intent is to combo with SRA737.
Very recent as dated 14th October 2022.

In addition from October 2022
Up-regulation of the PI3K/AKT and RHO/RAC/PAK signalling pathways in CHK1 inhibitor resistant Eµ-Myc lymphoma cells.

These findings demonstrate that up-regulation of multiple bypass pathways occurs in CHK1 inhibitor resistant Eµ-Myc lymphomas. Consequently, drugs targeting these pathways could potentially be used as either second line or combinatorial therapies to aid the successful clinical application of CHK1 inhibitors.

Regards

March 2020

"Our new study establishes the basis for a potentially exciting new approach to treatment involving a two-pronged attack on cancer. We found that doubling up on drugs that target the systems for repairing DNA could be effective even against cancers that do not respond to single-drug treatment.

"Our findings also provide us with a way of picking out which patients are most likely to benefit from existing CHK1 inhibitors like SRA737 - a highly innovative drug discovered at the ICR and currently in clinical development.

"At the ICR, we believe that combinations of targeted drugs will be critical as we aim to overcome the major challenge of cancer evolution and drug resistance - just as they have been in other diseases such as HIV."

Study co-leader Professor Michelle Garrett, previously a Team Leader at The Institute of Cancer Research, London, and currently Professor of Cancer Therapeutics at the University of Kent, said:

"Our study shows the potential of targeting DNA replication for adding to the effect of an existing drug that blocks a system that helps respond to DNA damage.

"It's exciting too that detecting tumours with low levels of B-family DNA polymerases could be used to identify patients most likely to respond to a CHK1 inhibitor, presumably because of natural weaknesses in DNA repair within these cancers.

"The next step is to develop new drug candidates that could be used to target B-family DNA polymerases in combination with the CHK1 inhibitor SRA737, as we have shown that this could open up a potential new therapeutic approach."

Good morning CB

'GSK didn't want 737. get over it.'

I for one have no problem with GSK with not wanting 737. It will go back to far more capable hands. Sierra Oncology have carried out some sterling work but Michelle Garrett has carried out has achieved more on 737/CHK1i since 2020.

Not a gloat on my part by any means. But it does wee on the matches of those that argue that as GSK are big resourceful company and an implied it has been returned as a product that does not work. As it is a big company does not mean they know better.

MG involved in SRA737 since day 1. Reading her reports are factual and not open to misinterpretation unlike big pharma press releases.

https://www.pancreaticcancer.org.uk/news-and-blogs/meet-michelle-garrett/

regards

Good morning C79.

We must not forget about SRA737 either.
Easy read below regarding SRA737

https://sciencecodex.com/two-pronged-attack-dna-repair-could-kill-drug-resistant-cancers-642857

Regards

Fax. I stand corrected.
Thanks for the input.

Regards