Member Info for sadoldgit

I contacted HL to transfer 19.880k of shares on Monday to go into ISA account.

Looking at my account has not gone through but l see a trade today at 0942 a trade for 19,880 shown. There is also a trade at same time 19,770.

The did tell me that it would be completed in 4 days.

Regards and not long for the start of toxicology studies now.

Good morning celtic007, it will certainly do it no harm.

Clearly there is interest in 747 as Sareum round not have negotiated it's ownership.

I dare say the BoD know more people in the pharma industry as opposed the newbie CP F crew.

They get paid the same whether selling a compound or not.

Regards

As much as l can see some advantage in areas of AI it leaves a lot to be desired.

How does AI work?

It can only work with the information it is given.

With regards to intelligence all that means is that it has the capacity to learn.

So we ask AI a question on oncology.

I don't know about some on here but l would rather find out those that carry out and conduct studies.

'Michelle Garrett is Professor of Cancer Therapeutics in the School of Biosciences at the University of Kent and Visiting Professor of Cancer Therapeutics at the Institute of Cancer Research, London, UK.'

I place far more faith on the phenomenal amount of work she has carried out on CHK 1 inhibitors which include 737 and Prexasertib ( Prexasertib is a Chk1/2 inhibitor.

Resistance to CHK1 can be achieved by using an alternate pathway ie avoiding the p53 Che kpoint and typically is most cases activation of the P13k/AKT pathway.

Now from memory it deemed to be to warrant further investigation of 737 with AKT/P13k inhibitor.

Now to work in combo with an AKT inhibitor that inhibitor must be approved for clinical use to give any chance of this type of chk1 AKT combo to succeed.

This was getting close to 5 years ago.

Now we have an approved inhibitor AKT approved for clinical use by the NHS.

CCT245737 has a greater capacity than Prexasertib with regards to compatability with other inhibitors.

Michelle Garrett involved in both development of CCT245737 and AZD5363

I have an idea that Professor Garratt has a better understanding than any AI out there.

I have posted reams on this subject albeit 4 to 5 year ago.

Plus look at the timing of gaining 737 basically a month before AZD5363 approval for use by the NHS.

I could be wrong.

Was not wrong in my predictions of 1801 in Phase 1a clinical.

It takes a lot to learn and understand.

Effectively we have an inhibitor containing Jak 1 2 and 3 that with regards to safety has pi55ed all over the others.

The doubters will not doubt say 'what a out efficacy ?'

Efficacy is normally limited due to dose limiting toxicities incidents that is found out in Phase 2 clinical trial hence the approx 60% failure rate at this stage.

Perhaps some will now realise the I.portance of the longer term toxicology study prior to entering phase2

Regards

Michelle Garrat involved in the development of both CCT245737 and AZD5363

It was proposed to use or to be more precise to use a chk1 inhibitor with an AKT inhibitor.

Interesting developments on this front to follow in my opinion.

CCT245737 back in the UK!

Https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-lookig-at-the-effect-of-drug-called-azd5363-on-breast-cancer-cells-stakt

Capivasertib was discovered by AstraZeneca subsequent to a collaboration with Astex Therapeutics (and its collaboration with the Institute of Cancer Research and Cancer Research Technology Limited).12 Jun 2023

The perplexing point to me is.

Chk1 inhibitor resisistance leading to AkT pathway activation.

Much work was carried out by Michelle Garratt on this research work, much of which l have posted a couple of years back..now in combo therapy was a prime recommendation for a Chk1 inhibitor with AkT or P13k inhibitor from memory.

In effect they are the two major pathways that cancer can when restricted of one pathway develops resistance and uses the other.

This new drug capivasertib is a targeted therapy.

Now the new drug is listed below.

This new drug capivasertib is a targeted therapy. It works in a new way, blocking the activity of a protein molecule called AKT which drives cancer growth. Scientists started working on the drug's development 20 years ago and say it's the most effective cancer drug they've seen for advanced cancer.10 hours ago

Multiplex analyses revealed that drug combination treated tumors had reduced their plasma levels of sERBB1, sERBB2, sVEGFR1, sVEGFR2, sIL-6R, HGF, PDGFAB/BB and CXCL16 and enhanced the levels of CCL26, IL-8 and MIF. Surviving tumors had activated ERK1/2 and AKT. This finding argues that IL-8/ERK/AKT signaling may be an evolutionary survival response to [SRA737 + niraparib.

Now interestingly l heard on the radio coming home a new approved treatment for breast cancer.

To follow

Is Tim bang on with the optimum amount of Jak1?

Roughly looking at the description we have hit the vital Indications with the Jaki inhibition ( it also important to note the ratio or selectivity of Jak1 over 2 and 3. That my opinion anyway.

Plus we have this added advantage with Tyk2 being at least 12 fold selective over Jak1.

Dare l say all the benefits of the additional efficacy from the Jaks but without the unwanted off target effects.

If this indeed the case, l am not surprised at Tim saying wait till the world sees what we have to offer.

From a modest person too.

Before being accused of ramping there is a very slight chance l may be incorrect.

Pleased to add around 80 k at the average of around 12p. Shares that is.

ISA beckons Monday.

I would not be wanting to be short on this at the moment. Fingers will be well and truly incinerated. Installing a stomach churning sense of fear and acts of desperation.

Regards to all.

Good afternoon HbD.

Great find,

Very interesting if you look through the patent description.

Fair detail

.

dependent gene expression and functional responses of interleukin-12, interleukin-23, and type I and III interferon receptors.

These cytokine pathways are involved in the pathologic processes associated with immune-mediated disorders, including psoriasis, and are reported (Papp et al., idem) to be distinct from responses driven by Janus kinase (JAK) 1 (JAK1 ), JAK1 and JAK3 in combination, JAK2, or other signalling kinases.

Interleukin-23 (IL-23), composed of two subunits p19 and p40, is considered to be essential for the survival and expansion of Th17 cells which produce pro-inflammatory cytokines such as IL-17A, IL-17F, IL-6 and TNFa

. These cytokines are reported as being critical in mediating the pathobiology of a number of autoimmune diseases including rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease, and lupus.

IL-23 acts through a heterodimeric receptor composed of IL-12Rpi and IL-23R.

IL-12, in addition to the p40 subunit in common with IL-23, contains a p35 subunit and acts through a heterodimeric receptor composed of I L-12R1 b and I L-12R32. IL-12 is essential for Th1 cell development and secretion of IFNy, a cytokine which plays a critical role in immunity by stimulating MHC expression, class switching of B cells to IgG subclasses, and the activation of macrophages.

TYK2 associates with the IL-12Rpi subunit in the IL-12 and IL-23 receptors.

The importance of the p40-containing cytokines in autoimmunity is demonstrated by the discovery that mice deficient in either p40, p19, or IL-23R are protected from disease in models of multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease, lupus and psoriasis, among others (Kyttaris, V.C. et al, "Cutting edge: IL- 23 receptor deficiency prevents the development of lupus nephritis in C57BL/6-lpr/lpr mice", J. Immunol, 184:4605-4609 (2010); Hong, K. et al, "IL-12, independently of IFN-gamma, plays a crucial role in the pathogenesis of a murine psoriasis like skin disorder", J. Immunol, 162:7480-7491 (1999); Hue, S. et al, "Interleukin-23 drives innate and T cell-mediated intestinal inflammation.

Notably, their combination synergistically reduced the viability of all CRPC cell lines and tumor spheroids in a concentration- and time-dependent manner. Importantly, in a transgenic mouse model of NEPC, both agents alone or in combination suppressed tumor growth, improved overall survival, and reduced the incidence of distant metastases, with SRA737 exhibiting remarkable single agent anticancer activity. Mechanistically, SRA737 synergized with AZD1775 by blocking AZD1775-induced feedback activation of CHK1 in prostate cancer cells, resulting in increased mitotic entry and accumulation of DNA damage. In summary, this preclinical study shows that CHK1 inhibitor SRA737 alone and its combination with AZD1775 offer potential effective treatments for CRPC and NEPC.

Regards

Old but still very relevant.

https://www.edisongroup.com/research/progress-with-ongoing-trials-and-future-plans/20848/

From Edison in 2018

'The company also provided a rationale for a study examining SRA737 in combination with the poly ADP-ribose polymerase (PARP) inhibitor, Zejula (Janssen/Tesaro). The company concurrently announced that it had reached an agreement with Janssen to provide the drug for a Phase Ib/II study in patients with metastatic castration-resistant prostate cancer (mCRPC). The study is expected to initiate in Q418. In other news, the company provided an up-to-date timeline for the initiation of an SRA737/immuno-oncology combination study for which it expects to have clinical trial authorization in Q418. Finally, it announced that its Cdc7 inhibitor SRA141 should have a completed IND application submitted in H218.'

A large buy by anyone's standards.

Took a while to fill and a great day for the mm that the order went through l would hazard to guess.

Indicative of not many shares being readily available.

0.4% shares bought in company triggered a 50% increase before terracing to 13% increase.

Sareum have as we know have been water tight.

However when outside parties are involved not always the case.

It may well be that informal talks of somesort are concluding prior to formal discussions.

SP had indicated previously that they had been approached by interested parties ie greater than one.

The question here l bring to this board is:-

Has SP been in discussions with at least one of these parties with regards to obtaining 737 in whatever format?

Note there is now IND approval but little detail is given with regards to as and what.

In addition we have the finalisation of the 1801 phase l a SAD and MAD clinical trial results.

In effect until these are indeed signed off they are not an official agreed verified report.

Hence in reality any interest in this compound cannot have relied on results to progress discussions past informal stage.

We are scheduled to start long term toxicology studies in May.

At what point does an interested party bite the bullet?

If there is more than one even better?

But l do sense that an investment of 500k shares on Friday is by someone a tad more in the know than us.

Will he an interesting day on Monday.

Regards

From July 2024

https://www.cell.com/iscience/fulltext/S2589-0042(24)01200-8

I would hazard a guess that the IND would be for income therapy since phase 1 and 2 trials were completed at phase 2

If not the above then would be looking at phase3 trials with LDG and 737.

How long did it take for the private US pharma to achieve IND approval?

I may be wrong but l have a feeling it would likely be a phase1 in combination therapy with Parpi or PD-1 inhibitor.

The indication to treat are also unknown to us.

I doubt unknown to the BoD.

Regards

dependant on what the ndt inspector undertakes

basic dye pen mediocre.

then you can get into radiography or even better ultrasonics.

ultrasonic results are difficult to determine. it comes under the interpretation of the ndt engineer.

a basic dye pen ie die penetrant is easy to learn.

some welders highly skilled are worth way more than a basic dye pen ndt tester.

the best welders l have known have been bab**** but these are the best they select.

much work now is done by automatic welding machines. tig welding with wire feed. it is not new but results are top notch. no human error!

a good post potnak with regards to valuations as per range.

regards

in all l reckon you are spot on with the ball park figure.

Interesting post there Krone.

Yes we managed 737 with IND approval already in place.

Pharmaceuticals are corrupt.

I have noticed over the past 3 years where the appears to be a lacking of standards.

Many drugs are approved with boxed warnings.

Of course they put these boxed warnings on but they would not dare refuse them continued use as the pharmas be in uproar.

Place the burden on the health care provider that prescribed it.

Some good pharma companies over here straggling yet the UK choose to use old end of their live inhibitors from the USA.

Some new ones to ie Deucravacitinib.

They of course do not require the patients to have lab tests.

The system works where they can make it easy for some but difficult for others.

It don't help when pharmas pump money into the regulating bodies.

I sincerely hope that the IND is triple combo 737 LDG and a PD-1 inhibitor.

The mutts nuts l would think.

Regards

I won't say exactly, it involves work on Nuclear Plants both here and abroad.

2 years spent recently at Naval research test establishment.

Regards

Ps that impecunious wolfy fellow convinced l am a security guard.