Member Info for sadoldgit

Utahsaints

10th largest pharma bought Tesaro in 2019 for 5.1 billion, their pipeline of drugs treats same indications as 737. Why would they buy something they already have? Would you if you were the 10th biggest pharma in the world continue development of a drug that treats the same indications as your own? Tell me the benefit of doing this.

SO were looking to develop 737 further but had insufficient funding. SO has no further funding as GSK bought the company and not Momo. Access to funding via their parent company yes. But it is in the interests of the parent company that 737 does not progress.

What are your insights Utahsaints?

Warthog I added 7k @ 1.35 4th Nov

Added 8.5k @ 0.96 average 17th Nov

Just saying

How many who post here are aware that the very favourable research development report submitted by the author is also on the GSK advisory board? Not just GSK I might add but also other big Pharma.

Research report re 737 and 100% reduction in NSCLC and sustained circa35 days after treatment.

Regards

Good afternoon Glenfidrich.
GSK stated the primary objective in the takeover of SO for 1.9 billion were for momo. There was never any mention of further objectives. As GSK will control SO they can use this control to prevent further development of 737, No on licence and run the clock down prior to returning to CPF.
This is what in effect has happened.

CTA ongoing.

If there is an inability to supply evidence of GLP by Sareum or an unfavourable review by the GLP then the delays could potentially prove disastrous.
If the information cannot be supplied now or the outcome of a successful review by the GLP then should a later application be made this is also most likely to result in non approval.

All the development work done so far will become void as not carried out to GLP.

As such I see this outcome extremely unlikely. The CRO if reputable will have all the required information. In addition, due to recent reports of lack of inspections (US) the MHRA may still request a review by the GLPA .

Regards

My beliefs that Sierra Oncology turned it down are that under the influence of GSK they did not want competition posing a threat to their recently acquired pipeline of drugs they purchased from Tesaro in 2019.

A company that has just sent 5.1 billion are not going to invest money in 737 which can potentially treat the same cancer indications as their pipeline.

The on license was held by SO. GSK bought Momo and at the same time ignored any development of 737. It is not in the interests of GSK to continue development of 737. SO went as far as patenting 737 in combo. GSK own their own pipeline they will not be interested in paying royalties. GSK by developing 737 would be financially shooting themselves in the foot.

Tell me why Spurs312 that further development of CHK1 inhibitors post SO development ( by experts in this field is ongoing? CHK1 inhibitor resistance pathways have been identified. Inhibitors that control these pathways have also been identified.

As I have said before the forecast for treatments in lung, ovarian and breast cancer alone are forecast to reach 100 billion per annum.
GSK want all of it. Now tell me if you were GSK that you would happily spend 100 million on development of 737 then sell it for 2 billion to a competitor.

The GSK combination is not all that good. They are pushing their compounds into areas of high unmet need. They have no need to demonstrate superior efficacy ( and have not done so) only to demonstrate the slightest increase in SO ( survival outcome)

Spurs now you tell me why you think 737 is being returned. The only way you will find out why SO returned 737 is to ask them themselves.
The likely answer would be is it no longer fits our business plan.

As for the CTA
From the RNS it were stated that the MHRA were 'unable to approve' CTA.
Could you therefore provide here the information that supports your claim that CTA for 1801 were rejected?

They are asking for supporting evidence ( GLP) or a review by the GLP.

I will put it to you that a request for additional information is not a rejection.

A rejection would be followed by the reasons. A failure to recieve a review by the GLPA in the absence of supplying supporting evidence to indicate GLP has resulted in the decision of non approval.

As for the credibility of Sareum. Why would the return of 737 affect the credibility of Sareum? 737 has proven to be very effective in NSCLC with around 100 tumour regression in preclinical studies.

CCT245737 were developed between ICR, CRT, University of Kent and Sareum. The pedigree here is fast class. Ongoing research still being undertaken.

Back to basics as you call it. Why is this info completely irrelevant?

Regards

our nearest competitor is Prexasertib
It had higher selectivity for CHK1 over CHK2 than CCT245737
It were administered intravenously.
Higher toxicity levels.
EL Lilly discontinued Prexasertib as did not demonstrate activity to warrant future development as monotherapy in ED-SCLC.
The compound is available for clinical studies
CC245737 is available at 325 pounds per 25mg
Prexasertib 1095 pounds per 25 mg

yes there have been problems with CHK1 inhibitors ie resistance to, There have been remarkable results, as with SRA737 in combo in SCLC.

There is growing interest around CHK1 inhibitors in combo and now especially that the resistance pathways have been identified with potential treatments ie Pl-13 and AKT inhibitors.Professor Michelle Garrett and crew we have to thank for that.

I will close with
'With c-Rel-/- Eµ-Myc lymphomas we observed high levels of Phosphatidyl-inositol 3-kinase (PI3K) and AKT pathway activation. Moreover, treatment with the PI3K inhibitor Pictilisib (GDC-0941) selectively inhibited the growth of reimplanted c-Rel-/- and RelAT505A, but not wild type (WT) Eµ-Myc lymphomas. We also observed up-regulation of a RHO/RAC pathway gene expression signature in both Eµ-Myc NF-?B subunit mutation models. Further investigation demonstrated activation of the RHO/RAC effector p21-activated kinase (PAK) 2. Here, the PAK inhibitor, PF-3758309 successfully overcame resistance of RelAT505A but not WT lymphomas. 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.'

Clinical translation of CHK1 inhibitors
UCN-01, a nonselective CHK1 inhibitor, has been tested in phase I trials in patients with cancer either as a single agent or in combination with a variety of chemotherapy agents including irinotecan 36, 37, topotecan 38, 39, cisplatin 40, 41, carboplatin [42], 5-fluorouracil [43] or cytarabine [44]. Results indicate UCN-01 has disappointing pharmacokinetic profiles and has produced limited antitumor outcomes. In contrast to predictions from the preclinical pharmacokinetic data, UCN-01 had a

Note early stage inhibitor that is non selective.

Early inhibitors had poor selectivity and corresponding Pk profiles.

CCT245737 is highly selective. low toxicity

Most of the infomation below is taken from Michelle Garrrett and co from circa studies around 2019/2020.
As I have pointed out before 737 was used briefly up until around patent time when work continued with another CHK1 inhibitor prexasertib.

From Oct 22 journal
Description
The ATR-CHK1 signalling pathway responds to single strand DNA breaks and is required for cancer cells to survive the high levels of DNA replication stress and genomic instability resulting from the activity of oncogenes such as MYC. For this reason, inhibitors of CHK1 have great potential as anti-cancer drugs and are currently in clinical trials. However, overcoming de novo or acquired resistance to CHK1 inhibition is required if these are to be used as effective therapies. We discovered that lymphomas from the E?-Myc mouse model of MYC driven B-cell lymphoma, with a deletion of the c-Rel NF-?B subunit, have defective CHK1 activity and are resistant to treatment with the highly specific CHK1i CCT244747. Here we use quantitative (phospho)proteomics approaches to investigate how de novo resistance to CHK1i is acquired and can be overcome, offering potential therapeutic opportunity in patients developing resistance to Chk1i in the clinic.

Further reading of CHK1 inhibitor resistance.
Much of this work has been carried out post SO cessation with 737.

Studies have been carried out with other CHK1 inhibitors and would suggest the prime reason was the patents put in place by SO on SAR737. Effectively this would also include preclinical.

https://pubmed.ncbi.nlm.nih.gov/36240067/

You have involved the finest experts in the world on Cancer research involved in the development of 737.
Anyone, the likes of Bluenose take us up on this discussion?
Since as you state I can not put an argument together.
Instead of moan and complain lets go for it.

Regards to all

One rule for one.
It could very easily be argued that one has vast potential oneruleforone. Setbacks notwithstanding.

At what stage does someone buy back in after they have sold out? They will have same agenda as a daytrader and hence similar outlook.

All comes down to science and that is not just the results but also the legitimate derivation of.

Regards
Ps The CHK1 area is progressing nicely. A hot compound of which 737 has the current best safety profile.

Good evening Mafuta.

No not finding plute. Particles are frequently found of doserates milli sievert perhour plus, mostly Caesium. Nuvia carry out much of the survey work.

Working next door at Vulcan at the moment. Comparatively very clean but unfortunately of Dounreay mindset.

Plenty of plute about. Can say no more. I f I put anything more screen comes up strange and cannot access the LSE sight for a few moments. I were putting previous experiences down, clearly fact checkers did not like it.

Regards

I do remember looking out on a balcony when the victorious England football team were passing down East Ham High Street in an open top double decker bus. Geoff Hurst, Martin Peters, and Booby Moore.

Regards

Worst. The only problem I have is I am close to 700 miles away in Thurso at the moment with work. It is a case of I am unable to go as opposed to wont go.
Interesting media reports that state with regargs to sareum CTA , The MHRA wont approve, SRA CTA has been declined, to mention just two. Edison did Sareum no favours and more interested in their ill derived opinions. In what capacity are these people in to make such statements?

One off fee of 60k to Edisson and for what?

Have GSK or other large influential pharma got a couple of fingers inserted up their tradesmans entrance?

We are looking at potential multi billions of pounds commercialisation values here.

Big business and the money markets are there to make money.

Back to my beer, a case of Hobgobin

Regards

Many aspects come into play here.
All data should be recorded electronically. There will be times when a data base may be down and relevant information will be recorded in a log. It does happen. Much depends on how deep the MHRA will wish to delve into things hence the alternative of the GLP review.
if i take the role of MHRA I would be asking under the guise of adherence to GLP.

Basic GLP
Has the instrumentation you used proven to be calibrated and in date.
Are there any pre use checks in place.
Where is this information stored?
What procedures do you maintain to ensure that your employees are compliant with regards to these procedures.
Do you carry out periodic review.
How is the data recorded and by whome?
Where are your records kept that the animals you are testing on are approved and suitable for laboratory testing?
Where do you source your animals for experimentation from?
Are these animal certified suitable for laboratory studies?
Are your employees suitably qualified to accurately record results and in what forms is the information held.
How do you make conclusions based on the results that you receive?
Are any other parties involved in these conclusions that may influence a conclusion.
How do you maintain laboratory standards to ensure there is no cross contamination between samples?

these are just a few questions I would look for satisfactory results. However, with a reputable company it will become evident very soon if the indications are there that they have adopted GLP.

No problem to a reputable company but ideally direct communication with the CRO is best bet here.

I am sure once Sareum become of aware of the required areas of supportive evidence, they can achieve this with moderate ease. Relay and communicate in depth with the CRO.

Regards and think we have done this topic to death.

Interesting as would come from Barbera Klenke Chief medical officer of SO. Dated 15th November 2022.

Sareum were informed by SO that it intends to return 737 as per Oct 12th RNS.

Apart from their stated intent to return.
They are in breach of contract as no further development committed in past 12 month. SO been given every opportunity by the CPF including but not limited to a 5 million dollar milestone fee reduction..

They have done nothing more than stifle development of 737 over the previous 12 months. They have done nothing over the past 2 years apart from playing delay tactics. GSK do not want such a potential threat as 737 raining on their parade with their newly gained triple combo they obtained from Tesaro for 5.1 billion dolllars in Jan2019.

737 will not be staying on the shelf and my opinion is that an on licence and the respective upfront milestone payment will be the way forward. Far more development has been made in addressing CHK1 inhibitor resistance even when used in combo studies by Michelle Garrett and Co. The potential here is huge, effectively over 100 billion dollars per annum is predicted turnover that HGSOC, SCLC. NSCLC in treatments alone.

We can now develop 737 in a CHK1 inhibitor in combo with a better safety profile than prexsertib.

With regards to the use of the word 'intent'. This becomes very applicable in law. Most trials are carried out to determine determine the intent of an individual or company whenever litigation is involved.

100% confident SO will return 737 rights. Within 90 days? May not be the case. If they do not return within 90 days what happens then. Normally a period of notice to return within a defined period eg 30 days of which failure to comply will result in costs and legal enforcement.

It will come back, but do not be surprised of the antics they may come to play to delay development of 737.

Regards
Up the Hammers!

Conclusions: SRA737 in combination with low-dose gemcitabine was well tolerated with lower myelotoxicity than has been seen at standard doses of gemcitabine or with other combinations of Chk1 inhibitors with gemcitabine. Tumor responses were observed in anogenital and other solid tumors

Exactly to the point fearg. The CRO will not be negligent. By definition they will be well able to prove GLP compliance.
That is all that the MHRA are needing to approve CTA.

'provide supporting evidence' would indicate Sar have stated that all studies are GLP compliant in the CTA. All MHRA need is this supporting evidence that the CRO have.
Not Tims fault as such as inexperienced in this respect. The poorly worded RNS is indicative of this.

However,I am firmly of the opinion these issues will be resolved well this side of Christmas. A big mountain made from a mole hill.

It will have to be returned. The 90 day notice period has been given and the clock ticks away.

I dare say they will keep hold of it for the full 90 days or so.

The corruption of big business.

https://jeccr.biomedcentral.com/articles/10.1186/s13046-021-01903-z

CHK1 has never not looked good. Especially now that recently Identification of CHK1i resistance by some cancers has been well researched, identified and proposed combination therapies to address.

Good post from you as usuall citizen79.

Most of these regulating bodies will be aware of these shortfalls that have been identified in the US with big pharma. Big pharma plenty of money and influence. Most of these issues relating to insufficient inspections will have been known by the MHRA months ago. They ( the MHRA will now leave no stone un turned so as to speak)

What we are witnessing here is a lack of enforcement of regulatory control and auditing of studies by the regulatory bodies. Since the discovery of the lack of involvement which thus allows poor practices to develop. This fault lies with the regulatory bodies. Regulatory control here is far higher than in the US. I know that from experience.

More than likely this has or is leading to an over reaction here in the UK with subsequent consequences.

Regards

T