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Expanding Role of Kinase Inhibitors:

The increasing number of clinical trials involving kinase inhibitors for AD reflects a broader trend of utilizing these targeted therapies in various diseases, including cancer and neurological disorders.

FDA-Approved Kinase Inhibitors:

Many FDA-approved kinase inhibitors are being repurposed for neurological treatments, with a focus on identifying safe and effective combinations to optimize efficacy while minimizing side effects.

Importance of Kinase Inhibitors:

Kinases play a crucial role in many cellular processes, and their deregulation can contribute to various diseases. By targeting specific kinases, inhibitors offer a promising approach for treating diseases with complex etiologies.

As it stands we are far more advanced than these vaccines.

It will take a goid while longer before they are anywhere near ready for clinical evaluation

Degree fully that Sareum need to sttp on the gas so as to speak wit regards progressing of compounds especially 1801.

Interesting excerpt below on AD which affects over 50 million people worldwide

'All the findings of studies exhibited the promising role of kinase inhibitors in the management of Alzheimer's disease. However, it still poses the need of addressing current challenges and opportunities involved with this disorder for the future perspective of kinase inhibitors in the management of Alzheimer's disease. Further study includes the development of biomarkers, combination therapy, and next-generation kinase inhibitors with increased potency and selectivity for its future prospects.'

Now there are several inhibitors that have or are carrying out trials for AD from memory Baricitinib being one.

In my honest iopinion Baricitinib will not be successful here nothing more than an early stage Jak inhibitor with associated high risks of serious adverse events including major adverse cardio events, pushed into areas of unmet need in a vain attempt to maintain a dwindling income.

New competition is emerging of which we are a major competitor with 1801 and auto immune.

Crossing the blod brain barrier we can achieve, and will not hesitate to add that l reckon Tim putting in a lot of work with regards to what we can achieve with the molecules we have.

Indicative of a for sale sign as opposed to an on licence.

The need is to develop inhibitors aimed at treating an indication as opposed to making a broad spectrum inhibitor and then seeing how it responds.

Regards

Good afternoon JBond007.

1801 was not referred to as in crossing the blood brain barrier. It is more to do with the individual molecules that make up the compounds.

We have if memory serves me correctly 31 molecules.

All these molecules are not used in 1801 or indeed 1802.

Crossing the blood brain barrier is well known to Sareum. They have I effect mini.ised crossing of the blood brain barrier with 1801 as is autoimmune.

There would and this is my opinion here, a need to develop another inhibitor to address blood brain barrier penetration even though we have 1802 which has higher jak content.

In agreement with you regarding possible or for the use of a better word probable buyout.

As has been stated before. For a sale to take place all of our items in the shop window need displaying.

The main benefits here as am sure you will realise is indeed the heavily patent protected 31 molecules. They can't be copied!

To create the same desired results more complex molecules with likely compromise .

How these molecules bind and with selected binding affinity determines degree of success.

With regards to 1801 tox study.

With regard to value of 1801 long term toxicology study results cannot be over emphasised.

Long term use?

Now looking at diseases of central nervous system and associated potential.

These are long term treatments potentially.

I would express my beliefs that it is not the jak selectivity that is important per se but rather more involved with the binding affinities that can be controlled with around 31 to choose from.

Slight bias can be obtained.

In all at the moment a rather in depth value and that can lead to a monetary value with regards to potential of our SDC compounds.

Tox study l don't believe a red herring buy as a requirement for long term use and commercialisation value. These are the questions that large pharma will be asking and have concerns about.

No hurry to progress completion of 1801 tox study. Crossing the bbb for CNS and formulating acompound will take time, certainly longer than a few weeks and optimisation some months.

We are looking at a range of possible indictations and suitability for long term possibly life long use.

On good results the company will be worth many times the 30 odd million value it has at the moment.

Regards

Interesting link there Krone

Looks like the inhibitor here is Deucravacitinib..

It should perform well and has the best safety profile do far.

Type 1 diabetes I also an indication in the patent description for 1801.

A huge market for the tapping.

Be interesting if dual inhibition could work here.

I dare say Tim would know.

Am of the opinion that Tim and Co looking into every viable indication for 1801.

This can take several months.

Should tie in nicely with completion of toxicology study

A very interesting topic you raise regards to Tim.

At the time of the CEO being taken up be SP there became a change in direction and plans for 1801.

No longer was it to go into phase1b but a change to toxicology studies long term.

Is there a difference with regards to intent?

Should we take a look at the October eebcast with regards to 1801.

The focus is on safety and conformation they had hit all intended targets with no detectable Jak2 activity. Side effects basically as per placebo.

Since the intended targets were hit and we are not talking of Tyk2 Jak1 jak2 or Jak3 but IL-10, Il-17, Il-6 ( Interleukin examples) also interferons related to that the required targets for phosphorylation are met.

These targets as we know are disease or indication specific but some diseases share similar targets. The targets are known to have efficacy in Indications.

Ac company manufactures an inhibitor.

Tyk2 Jak1. Sounds good. Sounds familiar?

Hits all the required Interleukins, GMC-SF and interferon. Unfortunately it hits a few off target by hitting a few off target or unintended we now have problems as that when we increase dose these off target effects and consequently risk of major adverse limit the dose that is considered safe to be taken.

In practise this reduces the efficacy of the drug to the point of being non Competitive to abject failure..

What can be done with Breprocitinib?

It has dose limiting toxicities.

Pfizer/Priovant still trialling in other Indications I a desperate attempt at worthwhile commercialisation. It is not Competitive. Not Competitive as will never be in demand.

It will always carry dose limiting toxicity.

1801 with way way superior safety profile.

A list of potential Indications.

Psoriasis

Systemic Lupus Erythematosis

Crohns Disease

Ulcerative Colitus

Arthritis.

The days of the early generation jak inhibitors and rapidly produced later stage inhibitors with failings have a very poor outlook for anyone wishing to capitalise on commercialisation.

Long term safety study crucial which ought to be obtained as a matter of procedure given the excerpt results obtained in Phase 1a.

Regards to all

Riceyboy,

Good afternoon, are you not concerned of your 66% losses on QBT?

Why you post here?

A chip on your shoulder from buying at a peak?

Wolfie claimed to sell at a peak in 2021 made a fortune then claims the BoD have achieved nothing.

You two are out of the same mould and apart from that a couple of losers.

Let's ask you a simple little question what is your big problem since you are not invested here?

You post libellous information about Sareum on the WBT chat board.

What is your intent here if not sick in the head?

Regards and have a super day old chap

It worthwhile remembering that Sierra Oncology changed the CEO, they announced that all funding was diverted to Momoletonib including some of the funding allocated to 737.

This around 18 months before they were bought out by GSK.

Who called the shots here?

With the GSK pipeline bought for 5.1 billion they certainly would not want a competitor to threaten GSK getting their foot in the door first.

We are now 3 years down the line, GSK have foot in the door and established commercialisation.

Resistance to Parpi identified as is efficacy with PD-1 inhibitor LDG and 737.

If l were a pharma exec and l am not. l would obtain 737 for use in combo to extend patent life and commercialisation value.

Patent life for 737 is not restricted to monotherapy. In combo therapy can generate fresh patents.

Just my thoughts on this.

With regards to timescales on 1801 the trial length is 16 weeks fact

That is the period of treatment time.

When the treatment is finished there will still be a requirement for monitoring of the animals for a period of time afterwards. Normally around a period of a month.

Full data analysis results could wait onto Feb 26.

However, preliminary data will give a very strong indication. And any interested party is not going to wait until finalised data before putting a bid in.

Again this is my opinion.

If we were were looking to on licence 1801 and focused on we would not be spending money on 1802 development, the return of 737 or even may l add the toxicology study of 1801.

To on licence there.was only really a need for a phase 1b study.

Toxicology study fir long term suitability is not to be underestimated.

We are 99% of the way there. Take it that toxicology studies are a confirmation of what we already know and thst is the safety profile of SDC-1801.

There is very little else to debate that has not been debated over the past few weeks.

Again we have another all we can do is wait period.

Sareum have always excelled in supplying these wait periods unfortunately. But if it means getting things bang on right then who are we to complain.

Regards

Good morning Shepster,

Tis ok for the rant as we all have our opinions.

737 was never returned back to us as we never owned it on the first place.

The CPF o don't believe have the understanding to treat as a priority. Wages get drawn whether they sell something or not.

With regard tox studies being delayed agree that there appears no sense of urgency.

As for the BoD and what do the do all day, that can only be based on what we know.

What is going on in the background? We don't know.

A change of CEO nigh 12 months ago.

My opinion for what it is worth is we're under the influence of an interested pharma or we have an interested party that is prepping us for a buyout.

The other way of looking at it is l don't see Tim and Co wanting to spend all their time at sareum when they are in their 80's. They will be of they don't sell.

Licence 1801 for example. End of year?

What they do with the money?

Spend the next 5 years progressing 1802 ?

To me it all points to prepping the company for a sell.

To do that a buyer needs to know all the assets we have.

This is my opinion only. Reasons for are given.

Regards

Stephen Parker give him is due is pushing Sareum

He is in effect an interim CEO.

Typically an interim CEO remains one year to 18 months.

We have an expanding pipeline.

Aurora FLT3 shelved due to solubility issues

CCT245737 63.5% ownership. High potential of incombo therapy with PARPI and also LdG and PD-1 inhibitor.

SDC1801 immuno therapy with excellent phase 1a results awaiting commencement of toxicology studies

SDC1802 immuno oncology tyk2 Jak1 inhibitor nearing completion of translational studies.

Probability here of another inhibitor for blood brain barrier penetrant for central nervous system Indications. At this stage it will primarily modelling to look atclikelyhood of success and indeed optimisation is important but it adds another string to the bow. Many new drugs at early preclinical bought out.

1 in Phase 2

1 approaching phase 2

2 in preclinical.

I at very early preclinical ie investigational stage.

Tim.relieved of the CEO position l believe has reduced stress levels and now able to firmly focus on pipeline of 1802 and possible new compound likely to be called SDC1803?

John Reader focused on 1801.

The question is who is steering us?

I agree with you Steve .

We were around a pound before the RF debacle.

Very little money in bank.

737 had been returned to the CPF

Phase 1 a trial in its infancy for 1801

Phase 1a excellent results and better than expected by the BoD.

Phase 2 commencement for long term toxicology study imminent.

63.5% financial ownership of 737. Sareum BoD sit in the driving seat on this one.

1802 has commenced development in translational studies a step closer to ending of preclinical development.

A recent hinting of news on the possible development of BBB CNS inhibitor that may be of acceptable suitability from our patented molecules to put forward with careful optimisation being noted.

Sufficient funds until at least this time next year estimate of around 3.5 million left.

Of course toxicology studies will make a whole in.

Yet here we sit at approx 17% ( sp) of where we were pre RF deal.

Yes the amount of shares have nigh doubled.

In effect then 66% down from Pre RF deal

At a pound a share some 70% down from its peak price in 2021.

Larry Fink visited Kier Starmer his opinion that many sectors in the UK on the point of nigh capitulation and looking now to invest considerably as Mr Fink thinks time of invest.tnt to make considerable growth.

His budget not overly large at 500 billion.

Major eye on banks of which one is NAT West.

A pound a share about right as to where we sit at the moment. That the opinion of someone who holds shares. Of course those that don't will l believe, have a much more negative view.

That Wolf very quiet over on ADVFN.

Imprisoned me thinks.

He has a few comrades he claims on this chat board . Identical traits.

Regards and look forward to the price ticking up in anticipation.

Myc overexpression in cancer cells can lead to replication stress and DNA damage, making these cells more vulnerable to CHK1 inhibition. CHK1 inhibitors are being explored as a therapeutic strategy for Myc-driven tumors, especially in aggressive subtypes like triple-negative breast cancer (TNBC). Dual targeting of CHK1 and mTOR, another pathway often dysregulated in Myc-overexpressing tumors, shows promising synergistic effects in preclinical models.

They also mention an expected completion of toxicology in Q4. Originally Q2.

Expected to start inMay. If it started very end of May they would take it until.end of Q3.

At times Sareum.give the impression they have all the time in the world.

Now from.the last meet to end of toxicology approaching a year..

Give him his due Potters not far out on this one.

Pipeline looks fine.

Regards

Am definitely wrong C79 tis Vitamin D that is sunshine vitamin .

Regards

Goodmorning C79.

Rinvoc/Upadacitinib

Owned by Abbvie.

Patent expiry 2033 to 2038.

Early generation Jak 1 inhibitor.

Suffers from the boxed Jaki warnings

I am not sur who controls who here.

Do we have Abbvie that far up the FDA's backside via funding activities to grant approval for these fading black boxed ridden aged compounds in so called recent Indications with a claimed unmet need. Or do we have the FDA looking after the commercial.interests of big pharma especially US pharma to strangle any new compound that shows promise on this particular indication.

Safety being of paramount importance of course.

Regards and a good day to too up on the sunshine vitamin.

Sure that was mentioned as Vitamin K a long while back. I may be wrong as 45 plus years ago.

Morning Potnak.

100k of shares good buy in my opinion.

Do you not bother to read your own posts?

If you did l doubt you would buy.

As for the 'desperate to get in to SoGs truly invested gang.' Comment Potnak, don't be a clown all your life,take a day off.

I take it you are aware of certain developments down under in Myc investigations?

There is Nick Glover but not the Nick Glover from Sierra oncology.

Mei

There is a connection between Myc, Jak1 tyk2 crossing the blood brain barrier and CNS.

Nothing definate or anywhere near of course.

Since you stated failure as a probability of 1801 could you elaborate on exactly what is your definition of failure and how can this be

achieved?

Yes Warty l did read the comment again. Apologies for directing towards you.

Regards to all ,including the newly enrolled Sogs truly invested gang individual.

' A lot here want an imminent buyout, we all do, but IMO, yesterday's RNS signals that Sareum will be around long enough to prove some value from the SKIL platform. How long is that. I dunno but at least in mice. With translational studies done. Like I said, I welcome the move. Those that disagree, do so because they want out now.'

Above paragraph just about sums you up Potnak.

' A lot here want an imminent buyout, we all do'

Clearly from this Potnak you are in this 'we'.?

In effect Potnak you are saying a lot her want an imminent buyout like you do.

Then you say those that don't agree with what you are saying you state want out now.

You don't make sense.

With regards to RNS and SKIL platform what Re you on about?

It is a library of information that can create templates for kinase inhibition nothing else.

It is the information containedwithin this library and will be updated on a regular basis or becomes ineffective in drug design.

The feedback l recitved from the AGM being mostly pist AGM not recorded is that theSareum BoD are getting on in age.

More time they want to spend with family, basically time out.

They not want tieing down for god knows how many years.

They are looking Togo into phase 2 trials with 1801. For this they need to raise funds.

It was pointed out to me by Tim that should an offer that they consider reasonable to or gor a buyout then we would accept.

Clearly this has been discussed.

Since a buyout at a reasonable price would be accepted, then what does the main focus become?

Some here settled for a pound, I would sell around 25% at a pound but the remainder closer to the 5 pound mark.

That around 750 million market cap.

For what we have at this moment in time and developments expected within next 6 months l do not see this figure as far fetched.

You will get those that state Sareum have achieved nothing In 21 years.

Well with what Sareum have at the moment l would call that an zcbeivement.

Not sure what these muppets have achieved over the last 21 years especially when they cannot to he invested.

Why be here. ?

I do find it oddas one canine character is removed from AdVfN another comrade turns up here with an ìndentical spectrum

.

The traits are identical.

All the best to the truly invested.

People try to disrupt. It not just this board but also many others.

My focus is on licence or buyout whenever that may happen. Nothing is 100% definate for sure I this respect.

But l listen to those more knowledgeable.

Regards

Warty, enlighten us with your wisdom on how 1801 can fail.

How do you define a failure here.

Do you not see it as a measure of how good the compound is, opposed to pass or fail?

CHK1 Inhibition and MYC-Overexpressing Cells:

When Chk1 is inhibited in MYC-overexpressing cells, the cell cycle checkpoints are bypassed, and the accumulated DNA damage cannot be repaired. This leads to apoptosis (programmed cell death).

Synergistic Effects:

Combining Chk1 inhibitors with other therapies that target DNA damage repair pathways (e.g., PARP inhibitors) can further enhance cell death in MYC-driven tumors.

Clinical Relevance:

Clinical trials are exploring CHK1 inhibitors as potential treatments for various MYC-driven cancers, including lymphomas, neuroblastomas, and some breast and lung cancers.

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Ina sense Leggster l believe that you nearly right.

We have demonstrated via the development of 1801 that we can produce a compound that does not or severely impedes the compound crossing the brain barrier.

As can be seen we can identify the molecules that can cross the brain barrier.

I will liken it to having a jigsaw.

Most pharmas have one or two pieces missing but only have a random 2 pieces as a spare. Might work, chances are it will not fit.

Sareums jigsaw has one or two pieces missing they can identify and replace the pieces as have an entire spare identical jigsaw with all the pieces as backup. They can also replicate to replace those pieces that are missing

We can think of molecules and especially couples molecules at jig saw pieces.

Simple indication a jig saw made up entirely black squares. Every piece fits everywhere else so no problem. Does not matter which way you rotate the piece it will fit.

We then have a 4 sides square but one side has an added teet like a jigsaw. It will only fit one way but of course may fit upside down.

We can understand how complex these pieces can become, some pieces almost fit, fit but wrong colour. They can indeed become very complex and with complex molecules we are looking at simplistically complex 3 dimensional jigsaw.

A very early analogy l remember from Open University many moons ago.