Member Info for sadoldgit

BD, good morning,

Can find nothing in the SAR Directors Deals above.
Only thing I see is options of circa 6 million at 0.26 and a sell of circa 3 million of these options at a price of 1.14p on the same day 19th Oct 2020 by Tim Mitchell

Previous shown sell was around March 2011.

Regards

Cereus, good morning,
Am of the opinion that these companies look into the latest new line of treatments, bring out their own version and bang it into the clinic ASAP. GSK are now hitting the objective of 'overall survival' as their agenda. First into market and get the samolians rolling in.

A lot of the early kinase inhibitors have their problems. Much has been learned and rather than ttempt to overcome these problems big companies jump on to treatments where their performance is certainly not proven. Most of these should be ironed out now.

Cobolimab is a GSK product involved in its combination therapy to treat SCLC. The one the 'cleared the hurdle' primarily this is to increase the sales of Jamperli by creating a new market for unmet needs. Cobolimab a monoclonal antibody administered intravenously.

look at the c0bblers that GSK marketing put down

'The mid-stage study compared GSK’s Jemperli with Merck’s Keytruda in patients also receiving chemotherapy for metastatic non-squamous non-small cell lung cancer (NSCLC). The trial was positive, GSK said Wednesday, without giving detailed results. The study wasn’t designed to show superiority, but rather that patients had similar outcomes on either regimen.'

The study wasn’t designed to show superiority, but rather that patients had similar outcomes on either regimen.'

Very little point in running the trial! GSK have spent loads of money on something that has proven to be no better than what is currently available.

These monoclonal antibodies i feel are not all they are cracked up to be.

From RNS at 07.00hrs
Brings a tune to my head . Another One Bites the Dust

GSK plc (LSE/NYSE: GSK) today announced that DREAMM-3, the phase III open-label, randomised head-to-head superiority trial of Blenrep (belantamab mafodotin) monotherapy versus pomalidomide in combination with low dose dexamethasone (PomDex) in patients with relapsed or refractory multiple myeloma (RRMM), did not meet its primary endpoint of progression-free survival (PFS)

Only one director sell and that were by TM since 2011.

Definately not a Sinclair C5. Maximum power output on par with early generation and prototype AGR reactors. Dont be fooled by the physical size of the reactor.

Small modular Reactors. very similar to those used on Nuclear subs.
These are in some ways far superior to present commercial reactors in that they have a far wider power operating range. Much better easier, faster control and can run at 10 to 15% power up to 100% power.

From 28th July

'Preclinical development activities required to apply for the CTA have been successfully concluded and, consistent with the Company's clinical development plan, an application for a CTA has now been filed.'

Further down the RNS it then goes on to state :-

Provided satisfactory safety data is obtained from this initial study, and subject to additional funding, a Phase 1b clinical study will commence in psoriasis patients in 2023. The CRO conducting and managing the studies has extensive experience in conducting trials in inflammatory diseases and will recruit up to 120 subjects at a site in Manchester, UK.


Further down it then goes on to state. ( Clearly this is taken from an extraction of a prior CTA )

"We have completed most of the preparatory work for the clinical trial and have built a robust data package to support our ongoing partnering activities for this asset. Subject to regulatory approval by MHRA, we look forward to advancing SDC-1801 into clinical development."'

This release is made prior to any feedback from MHRA.

No other option apart from wait at the moment.

No it will not be the case to release in an RNS. Once obtained and authorised then it will be a yes.

The only thing I would add is that the CRO would have notified Sareum of the projected cost of the 1a and 1b trials.

although the link below relates to the US procedure it will be very close to what we have here.

https://www.sofpromed.com/what-is-the-cost-of-a-clinical-trial/

Regards

Gunner68 should there be an on licence in progress or co development since the application was made then it will change the status of sponsor. It is a prerequisite of the CTA that the sponsor or sponsors are identified.

Remember that Sareums intention is to on license or co partner at late stage preclinical or early stage clinical.

We have no idea how far and/or with who this may have progressed.

Application was made over 3 months ago with good results with regards to safety profile from a competitor with Tyk2.

The Nuclear energy in this country has become somewhat bu99ered since early 1990's by the break up of the old C.E.G.B.
No further on line build since. That is a period exceeding 30 years.

There were to be built 2 further Westinghouse reactors at sizewell ( effectively twin Sizewell B at 1188Mwe) and two further reactors of similar design at Hinkley. A proposal at this time was to build further Nuclear plant at Orford Island. These pans were of course scuppered by the break up of the CEGB. At that time 6 billion pounds from the sale was taken up by the treasury which at the time would have nigh funded the 4 reactors in total.

The country does need new reactors but would suggest here that better reactors can become available of which Rolls Royce have the technology and expertise to manufacture, requiring less down time for maintenance.

As for the picture the old Magnox gas cooled (twin reactors) are shown in the foreground and the Westinghouse PWR shown at the back.

Not a case of if new reactors need to be built the question is when will they be built.

Regards

An interesting point that Lazarus bought up with regards to backlog. Severe backlogs in all walks of life have suffered from effects of Covid. Court systems ( a local lad attended court 13 months after the alleged speeding offence along with 2 others that were caught on the same day). Hospital waiting lists. Council applications. Most of the administrative sectors paid people to stay at home to work. Unfortunately very difficult to gain access to them.

So with a vast backlog, the timescales which they have given that apply to normal day to day running are pretty dire.
My annual medical which normally takes 14 days to process took 8 weeks.
To an extent you join the back of the queue.

Whist the Communication informing the applicant of the MHRA and ethics committee decision following receipt of the responses will usually be sent within 60 days of us receiving the original valid application. If an extension to the response date has been agreed this will impact the final decision timeline.

Notification of the decision relating to a gene therapy, somatic cell therapy (including xenogenic cell therapy) product, tissue engineered product, or products containing genetically modified organisms (Regulation 19 of SI1031) will be sent within 90 days of us receiving the original application unless otherwise advised.

So whilst they state ' will usually be sent within 60 days of us receiving the original valid application' the application and use of the word 'usually' in effect allows scope for longer time frames.
There are some lovely responses when you try to make contact to certain bodies either by phone or email

All our agents are busy at the moment. We are experiencing high call volumes.
Such and such is out of the office at the moment or until such and such a date.
Due to the increased work load we are unable to deal with your problem at the moment.

Unfortunately these inevitable delays will cause problems and beyond the control of Sareum.

I am still firmly of the belief that provision and proof of ability to fund shall be a requirement of approval. Whist Sareum seek or may have obtained in principle the funding requirements, delays beyond their control are bound to happen, albeit not of their making.

Regards

Regards

Good description below. Brief and simple.
https://study.com/learn/lesson/allosteric-site-of-enzymes.html

Tyk2 by the process of how it works is in itself an allosteric inhibitor. That my belief. There is no data available on non allosteric TYK2 it just does does not exist.
But we are not allosteric with our compounds as both contain Jak1 2 and 3 the latter being in somewhat reduced amounts.

Tyk 2 will signal via JH2 domain ( pseudo kinase domain) the JH 1 ( kinase or active domain).

We have the advantages of the Tyk2 allosteric inhibitor but also additional inhibition of Jak 1.
Tyk 2 is specific whilst the other tyrosine kinases are selective.
JH2 domain will also negatively regulate Jak 2 and Jak3.

It is not a case of one treatment fits all. It never has worked and will never work.
Psoriasis, or to be more precise the treatment of is predicted to be more effective with Tyk2 and Jak1 than tyk 2 alone.
2 different signalling pathways.

Quality control and consistency of compound are crucial.

Tyk2 and inhibition of AKT ans Pl-13 pathway. It was recently identified by Michelle Garrett et al that resistance to our Chk1 inhibitor ( by passing the P53 checkpoint using an alternative route) could be overcome by inhibiting the ATK and Pl-13 pathway.

In our patent description SDC1802 is compatible as a combination therapy with chk1 inhibitors. Around 90 seconds into link below is an interesting indication pathway inhibition.

it was also an option in combo ( 737 and autoimmune inhibitor) put forward by Sierra oncology but due to financing (so they claim) never materialised.
Potential is phenomenal in this combination, especially in the difficult hard to treat cancers ie Ovarian and breast to name just two.

https://www.bing.com/videos/search?q=Tyrosine+Kinase+Inhibitors&&view=detail&mid=A90F79E3BE91B4724230A90F79E3BE91B4724230&&FORM=VRDGAR&ru=%2Fvideos%2Fsearch%3Fq%3DTyrosine%2BKinase%2BInhibitors%26FORM%3DVDMHRS

Regards and well into my beer at the mo.

Good evening Citizen79.

A couple of links below which you may find of interest. It is indeed a complex issue. There is so much cross talk between signalling pathways. the pseudokinase domain JH2 can control tyrosine kinase active site JH1 domain. Basically there are 2 main domains but in all there are 7 domains of which Jak3 is combined of all 7 domains.

JH2 domain will negatively control Jak2 and Jak3 at the same time however it does not affect the interaction between Jak1 and Jak2.

It really gets to the stage of the significance of SKIL ie Sareums kinase inhibitor library. Information here with regards to kinases and signalling pathways as well as adverse effects and most likely the causes. The formulations which they have chemically developed and patented are made to address diseases in auto immune and immuno oncology.

1802 alone is made up from a selection of 31 patented molecules to form a compound. Each of these molecules are covered by the corresponding patent protection. No one else can use them, they have to look elsewhere and there is a limit as to what molecules can be used. We have entered at around the best stage, where the disadvantages of first generation inhibitors have been realised. Our Tyk2 development programmes goes back as far as 2013. Nigh 10 years. Preclinical ( SDC1801) ended around early 2022.

I could write page upon page of views and corresponding data to indicate.
However, time permitting i will in the next day or so post here an analogy of kinases and domains. In a sense easier to explain via an analogy but at least be easier to understand.

https://www.bing.com/videos/search?q=what+is+a+tyrosine+kinase&&view=detail&mid=18934C1C05F2573667EA18934C1C05F2573667EA&rvsmid=98B50E2BABF48104F75498B50E2BABF48104F754&FORM=VDQVAP

https://www.bing.com/videos/search?q=what+is+a+tyrosine+kinase&&view=detail&mid=161FADC8CC17FE7826EE161FADC8CC17FE7826EE&rvsmid=98B50E2BABF48104F75498B50E2BABF48104F754&FORM=VDQVAP

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC545791/

https://pubmed.ncbi.nlm.nih.gov/12351625/#:~:text=The%20Jak-JH2%20deletion%20mutants%20are%20catalytically%20active%2C%20activate,to%20connect%20these%20signaling%20events%20to%20receptor%20activation.

regards

A link here with regards to Covid and SLE.
Very basic but sheds a little light.

https://pubmed.ncbi.nlm.nih.gov/33494816/

Nice to hear from you notalot and pleased you are in remission. Long may it continue.

Ps Strange that the US were researching 1802 for SLE prior to the Covid 19 pandemic.

Thanks for that Star786 there is now beer all down the front of me, I could not help but laugh my cobs off.

good evening Star786.
Sar good at times and at other times will have you pulling your hair out from your head. Just over 2.5p now in old money which is pretty abysmal to how far we have reached.

Regards and keep the faith.

Seawolf yes you have hit the nail on the head!

sareum not in a position to juggle too much with funds. I dont think a takeover in progress but more likely now than ever before now that 737 returned. 1.5 to 2 billion for the whole lot is not out of the question. Not suggesting this will happen soon. However, cannot be ruled out.

JFF
GSK spent 5.1 bi;;ion on an acquisition of Tesaro in 2019.

GSK have had a very easy ride into Europe by the approval of their combination therapy. Effectively no treatment available in this area. Cleared the hurdle? As they stated in their news release the trial was not done to prove superiority,

Big business deals. To such an extent they will do what ever they can to scupper any competition.

Our current CTA is a matter of around a year old. The previous CTA was submitted by CRT/ICR for CCT245737. in reality nothing to do with us apart from a 700k up front fee which Sareum paid 2 months before the CTA was made. The authorisation was granted within 60 days. We have a vested financial interest of 27.5%

Sareum have told us that further funding is required. it is in their hands the means which to raise this funding.
They have 2 options. Raise funds via investors or through a partnership or on license.
They will certainly not disclose which route they are intending to take, news will be released when and only when agreements are finalised. Whether it a day a week or a month or so.

If the CTA was not granted we would know by now. There are conditions which are required before authorisation can be granted.

If Sareum are in the process of finalising negotiations, there will be no news until finalisation of an agreement is made.

There are some here that think you pick up a phone a make a quick deal. that is as far away from reality you can get.

if Sareum released info next week on a 100 million upfront milestone payment you would be singing the bods praises.

i know developments take time. i remember being here when the SP was 0.3p a share and there were those posting the company is going nowhere. it has gone up and has gone down over the previous nigh 11 years now since I have been invested here.

yes i am aware it can prove very frustrating, you put money in. It is a company that painstakingly carries out research to treat auto immune and oncology not a big fruit machine. Understand what you have or intend putting your money into.

A few more months or a year does not bother me in the slightest. If you are a trader and not happy pick a more volatile share where the prices go up and down 50% a week. But dont moan about the bod here. they are doing their best and if you not happy with that then just vote with your feet and leave.

Regarding the science being good, What were the difference in science 3 months before GSK offered 1.9 billion dollars and when the deal was concluded?