Member Info for sadoldgit

007 I am not convinced it is about best in class. More drastic than that, as in are the results valid? If no supportive evidence with regards to GLP or GLP authority review of the situation then outcome is dire. If we cannot produce tha required supportive information with a time extension I find it very difficult for them to supply in 3 months time. In effect nothing has changed.

MHRA Sareum can you prove that your data and the formulation there of is reliable, accurate and not been doctored?
That is all I believe is the purpose of the proof of GLP compliance.

A reputable CRO will have carried out work to GLP. This needs to be entered where required on CTA application. A brief overview and then where required at each investigational and experimental operation.

It will be time consuming. Not sure that sareum will achieve much by them stating we believe we have submitted the required supportive information.
Not much to do apart from wait.

Regards

As for patent protection of SRA737 i did see somewhere could run to 2038. Will delve into that at some time in not too distant future.

Good evening HbD

It certainly has not been forgotten about. I have a feeling that CPF since 2020 had an inclination that 737 would be returning.

Most information in the link is preclinical of which clinical trials have taken place. Information now being released of 5 and 6 year old data.

Two outcomes here. Either on licence by CPF or return to CRT for further in combo work. Maybe a co partnership.

Some of the questions I would like to put to Mr Tim.
What is your intended involvement in the development of 737? Would you be in a position to develop a compound to be used in combo with 737?
What is Sareums perceived best way forward for 737 with regards to share holder value?

I posted earlier that P53 mutations are present in 98% in HGSOC. Parpi will have little use here.

A highly selective CHK1 inhibitor is required with no high toxicity affects. Not on its own but in combo.

Last on license was around 312 million with no clinical work carried out and no investigational work in combo outside of 737 and LDG. 737 has come a very long way forward.

Would suggest 737 and LDG in phase 3 trials and also further trials with other inhibitors of which recent research suggests plenty of compatible partners.

GSK committed themselves end of 2018. SO were still carrying out later stage phase 1 trials with little released clinical data. A big market for GSK as Tesaro already had NDA approved compounds. In addition no CHK1 has has regulatory approval for clinical use as majority failed due to poor PK.

Now the worm has turned with CHK1 posing a serious threat in not only NSCLC but also Ovarian given time finance and clinical trial opportunity.

An on license agreement would have far more financial value than the original agreement due to the nature and amount of progress made. Further research work carried since the non continuation of development by Sierra.

The most influential contributor would be CRT themselves.

It waits to be seen as does the CTA result.

Regards

A good idea just to give an overview of 737. Not going into the Science as annoys people and at times understandable.

SRA737 first orally available 2nd generation CHK1 inhibitor, that lacks the serious issues of PHK profile and off target indications that lead to the discontinuation of 1st generation CHK1 inhibitors.

Sierra Oncology (originally Pronai Therapeutics) licensed 737 from CPF in Sept 2016.

Valuation by Edison at Sept 2017 of $ 119.4 million, based on 15% probability of success.
SO has balance of 117 million in cash and was forecast to last until mid 2019. ( This also includes development of SRA141). Projected further requirement of 170 million for forecast of approval in 2023.

At this stage no clinical trial results for SRA737 in mono or SRA737 in combo with LDG.

P53 Checkpoint (protein 53) transformation relation protein also known as Tfp53 or TP53. Activated in response to DNA damage. Cancers that have mutated copies of P53 are able to replicate and acquire additional mutationswithout triggering apoptosis ( just a posh word for programmed cell death). This mechanism drives many cancers and very common in solid tumours.

P53 mutations are in 34% of lung, 42% in colorectal and 45.5% in Ovarian.

A company MSK which specialises in DNA mutation ( MSK-IMPACT)found in advanced cancers there exist significant higher rates of P53 mutations. 55% non small cell lung cancer, 72% colorectal and 71% Ovarian. rising to 98% in high grade serious ovarian cancer.

Synthetic lethality basically inhibition or control of more than one signalling pathway.

PARP inhibitor have been shown to exhibit positive results in BRCA mutated breast cancer. PARP inhibitors signal differently.
ChK1 identified as important for preventing progress of cell cycle ( basically allowing mutated cell replication) in response to cell damage. It both triggers arrest in cycle progression and recruits ' machinary' to address DNA.

Synthetic lethality seen with P53 makes Chk1 an exceptionally attractive target for anti cancer therapies because of the exceptionally high rate of P53 mutations across different cancer types.

Major pharma's Pfizer, Merk, Merk,Serono, Eli Lilly have developed CHK1 inhibitors. At least 7 programmes have been terminated. AZD7762 an MK-8776 terminated dut to cardiotoxicity.

737 around far more selective over CHK2 than prexasertib. Due to its lack of selectivity prexasertib will exhibit counter productive responses.

No account taken here of 737 LDG and a PD1 inhibitor which exhibited 'astounding' results in pre clinical.

Regards to all

Much development has been carried out since this report.

You can make your own minds up at to a current valuation as this were around 5 years ago.

Regards

Take a look at the 2022 Biotech Graveyard report released about a week ago.

Fierce biotech.

It has been recognised that CHK1 inhibition resistance can be overcome when used in conjunction with certain alternative pathway inhibitors. Recent work by Michelle Garrett

A wiki description of the two main alternative pathways are covered in the Wiki link below. Do not concern yourself with no mention of CHK1. These are the main alternative pathways created by the Checkpoint kinase one inhibitor resistance.

Very heavily researched and latest paper around mid 2020 by the MG crew.

PI 13K and AKT pathways

https://en.wikipedia.org/wiki/PI3K/AKT/mTOR_pathway

Regards

In the link below you can download in pdf file.

It is dated 2022 but refers to work from much earlier period. There is definately a push for Sareums/ CRT developed CHK1 inhibitor.

https://www.researchgate.net/scientific-contributions/Michelle-D-Garrett-38542729

I have several others reports when I can find them.

RMM3383.
Already proven to work well in combo with LDG.
Potential is huge in the difficult to treat cancers that develop resistance such as Ovarian and Breast. In addition as stated in the Patent description for SDC 1802 that 1802 could be used as a supportive therapy not only with overcoming resistance to LDG but also used as a supportive therapy with CHK1.

Sareum must have some idea of the effectiveness of 1802 with regards to supportive treatment if only in the 'model stage'

No idea of value as it stands but a massive market exists.

Officially nothing can be done until receipt of relevant documentation and rights to CPF.

But I will reiterate why has much research and development been done with a discontinued CHK1 inhibitor in the absence of 737? No other CHK1 oral inhibitors exist as far as I know.

Regards

There was much work done by Michelle Garrett with regards to CHK1. Earlier part of investigation was with SRA737. Then we had SO granted patents for 737 in combo. After this time development was continued with Ell Lilly Prexasertib which has inferior safety profile to 737. ( Prexasertib no longer in development as stopped by Ell Lilly)
I would say confidently that the CRT will welcome back 737 to progress in combo therapies with other suitable agents.
Good results with 737 and LDG in clinical. Preclinical results in vivo outstanding with LDG 737 and Pd1/Parpi. Low to mid toxicity results.

CHK1 inhibitor resistance heavily researched with potential to use with AKT inhibitor. Michelle Garrett University of Kent (heavily involved when worked for CRT/ICR in development).

SO took down the for sale sign around the same time the patents were applied in early 2020. Clearly somebody did not want SRA737 to progress.

Basically sat on it for 2 and a half years.

It may arise that a partnership with CRT may be formed if the CPF do not on licence.

Would not take much to put 737 into commercialisation just for 737 and LDG combo, but there exists phenomenal potential with 737 in other combinations. Ovarian and Breast cancer are in desperate need of more effective treatments than we currently have. Would take very little to demonstrate superiority over GSK in combo therapy compounds in these indications.

90 days notice period to return to CPF as Krone has stated.

I do find it strange that there has been very heavy research work in the absence of the only CHK1 inhibitor available that has not been discontinued.

The Chinese have developed there own CHK1 which is approved for clinical use for the treatment of large tumours.

Regards

Jeez Grover lad. Are you aware of the 737, LDG and PD1/PARPi in combo.
Much work undertaken recently with M Garrett that used Prexaterb in later stages. 737 protected by patent. Very convenient for GSK.

Governance. Clearly your thoughts been found to be incorrect.

No l don't have a thing for you CoL You have done nothing but attack me from your very first post here.
Undermine from.day 1. That is not balanced sonny. You still think that GSK would allow SO to develop 737 as good for a back up and case lead drug fails?

No logic in this at all and all done to discredit the value of 737.

As l have said it does not fit the GSK business plan. At the same time they would not want 737 to be in competition.

SO shareholders were up on arms on the buyout of SO for 1.9 billion. With all sorts of talk of legal action. SO stated that the commercialion of SRA 737 may prove to be more viable.
They go as far as patenting 737 in combo. There is also further preclinical.work with with PD1 inhibitor which way exceeds 737 and LDG.

We're you aware of this?

Regards

Sneckieboy I never stated that you couldn't research. All I stated was that 'you should be able to research'
You really do have a chip on your shoulder. I have acknowledged that you have a degree and merely pointed out that this should give you the ability to research.

Apart from that. if you are going to make such bold statements, please ensure the accuracy before pressing the post button.

Regards

If you are able to research Sneckieboy then do so. If you not sure where to look then all you have to do is ask.
Debate is good,
Why on earth did you become invested? Based on what ? What influenced you?
Good informative information is good even though you may not like the conclusion.
Uncertainty is never good and people will play on that.

Regards

A simple question sneckieboy.

Why would a reputed CRO not work to GLP behaviour?
As I have posted before. There willl have been an assurance that all work is undertaken to GLP.
That is all Sareum will have had. clearly not enough as the MHRA have asked for further supportive evidence.

Sareum are not going to send out an RNS leading to further speculation and SP volitality.

When news is due it will come.

Chill out man, life was never meant to be easy.

Sneckieboy. If you do a proper degree you will know how to research. End of.

Mine was an OU degree in theoretical physics in early 90's. It has served me well. it teaches you how to think and remove unsubstantiated fact. However even without knowing all the facts you can establish a base to work from ie maxima and minima which will also allow you to determine an element of uncertainty.

You come from a humble background you state? Clearly the temperament of your postings prove otherwise. Prove me wrong But I have never found anything of substance which is of benefit to this board. I have no need to filter you. Best you join the ranks of the CoL who also has nothing of substance to post.

The SP has moved south. I am not bothered. I dont blame TIm and co they are doing their best. If you do not like then sell if you have any and leave.

No one has forced anyone to buy here or sell, It is at the decision of the individual.

Greed and fear are the only enemies of an investor.

Whatever your decision Sneckieboy unlike some I bare no malice, I sincerely hope that all will work to your financial benefit. I really do mean that.

There were times in my early life when I have been down and I mean down. Dreading the next letter that comes through the door. But I learned determination and also not to be deterred. There are many people in this life that will want to bring you down ( you will not always recognise them at the time) but very few that want to bring you up. Remember that always.

Your opinion of me is your opinion. That is all it is and does not give me any form of concern.

Regards

10 out of 10 mice were never cured
there is also 10 out of 10 mice 100% remission and no sign of recurrence in the next 30 something days.
Two differing reports with a big difference,
Which one of these reports prompted your alleged joining CoL and pray tell me the difference between the two.

A good education should teach you how to think. Research to take it back to the bare bones and work up.

Am fine with the science and fine with my expectations of a positive decision. It may prove a little time consuming but am firmly 100% in the belief we will get there.

Regards to all.

I have not expressed any view on PI actions whether buy or sell. I have been clear that I would like a rising SP and some clarity and I accept that delays happen. BBs provide useful leads, however anyone who trusts BB posts without DYOR and going back to the original source and context is playing against a loaded deck

I for one personally not interested on your views. Along the lines of sell out now and buy in cheaper later on I would imagine.

Supposedly here since 10 out of 10. kept in and not sold despite increase in SP at peak at over 800%. Why on earth would you accept its views?
At the same time it states

'In all seriousness, it does further challenge sog's position on why GSK returned SAR737. Despite having spent £B's already on Tesaro, why allow such a promising compound to be available for license to a competitor. Far better to develop SAR737 as a 2nd generation product and extend the commercial advantage. Unless it was a prescribed takeover condition which doesn't appear to have been suggested to date.'

As I have pointed out to you before. A company is not going to invest twice it already has mono/ combination therapy in similar indications to 737. Why pay a 300 million milestone payment and 10% royalties.

You clearly have no idea of how big pharma work.
You working producing drugs? Are they legal and do they smoke them inhale them or inject them?

More piffle from the CoL
'What I find amusing is the resorting to insults in the face of challenge. Some I don't pretend to understand, some are bizarre (take out an easy access ISA instead- ouch!) and not forgetting the old favourites e.g. sog's Wildean dismissal today of Cobradan as a t**t because he had the temerity to not explicitly like his post yesterday. Grow up! I don't know about others but, as only a partial believer, I am scarred for life by such comments - the playground is such a harsh place and the big girls play rough. Why can you not accept that some people see through a different perspective, it doesn't mean they want the SP to collapse and a BB is not the place to instigate that anyway.

Nothing to do with not not liking it was insulting and abusive. This was indicated by the LSE removing it.
You made a comment pointing out how bad i am but had not even read the post yourself as you admitted. I have copy of post on mobile phone if you would like me to repost. So much for your balanced opinion. One thing thing your post was not CoL and that is balanced, rather like yourself.

Regards

Warthog4, We are all getting older. I understand, which is inclined to make the patience where a bit thin.
CCT245737
Auroro FLT+3
And now SDC1801 and 1802.
4 years I thought at first now approaching for me 11 years.

Regards