Member Info for sadoldgit

Good morning MegRS300,

An interim report would be welcome although in a long tem toxicology study I don't believe there can be much to report at this period income

Tox study is 16 weeks/4 months.

This will be treatment period.

Doses can be gradually increased and of course what is the initial starting dose as a baseline.

In addition there will be a period after cessation of dosing to establish and confirm safety data.

Would guesstimate 4 to 6 weeks.

Remember long term toxicity means exactly that and as such long term results cannot be achieved in a short period of time.

It may well be there are or will be additional studies going on supportive of SDC pipeline.

Sareum also stated that they intend to dose to

achieve a level where toxicity is observed but does this include DLT or MTD?

Now if we goback to around 2020 sareum had not observed any toxicity at 30 times therapeutic dose in toxicology tests, primarily to establish a maximum tolerated dose which Tim did say was a 'nice priblemto have but may comeback to bite us'

The MHRA debacle certainly did that.

Now bare in mind that at 30% of maximum therapeutic dose, excellent ADMET properties were observed in MAD yrial,and that includes no increase in creatinine levels.I.t does look extremely promising to say the least.

With regards to peer review it is after all just that.

One person could paint very positive and another less so as after all opinion ions based on how we interpret fact.

It all boils down to toxicology results and we may well have more than one interested party however with differing objectives.

Hence all very quiet

Good morning Lazarus.

As you say it certainly was not for professional fees.

It is a conversion.

The markets would of course had wind of this yesterday and hence slight drop.

The after hours late trade to me looks certain as a forward sale of 500k.

Individual or investor may keep half and forward sold the other half of the 1 million share conversion.

Regards from one of PC1954 imbeciles.

If dummy sells are submitted, there is very little chance of the SP raising.

Those that try the system by seeing how many shares they can sell or test liquidity contribute negatively to the SP.

Take a look yourselves at Dummy selling and effect on share price

An extract below.

' Overview

+5

In stock markets, "dummy sells" often refers to a form of market manipulation where individuals artificially inflate the price of a stock through misleading or false statements, then sell their shares at the inflated price, causing the price to crash and other investors to lose money. This manipulative practice is commonly known as a "pump and dump" scheme. '

Regards

Bluenose, your posts are relatively short as you have nothing that us of any use to anyone.

We all know the SP is low as most other AIM companies are.

It is my choice to work as have option not to.

It must be an easy transition to you to go from benefits to retirement.

I will submit posts for as long as l like when l like ,

People can chose to read them or not. It is not for you to judge whether my posts are too long or not.

You have a problem with me still working?

Let's have a little debate on the Bbb and CNS Indications especially with regards to most recent investigational work with 6 of their compounds.

Or maybe a chat about Deucravacitinib failing in UC to the extent that the placebo gave better results.

Now BMS is going to increase the dosing?

There really is no point in this as will end up water of money and failure.

Perhaps you could give us tge benefit of your all inspiring knowledge on this one.

Tell us your opinion with regards to down stream signalling or to be precise lack of. As it cannot change the down signalling to its allosteric selectivity how the hell can increasing the the dose achieve benefit that is non existent in the first place.

Do you not think that a dual inhibitor would at the very least prove efficacy in UC here beyond the abilities of allosteric Tyk2?

BMS claimed their allosteric Tyk2 regulates the active site.

Is this true ?

Would it be correct to suggest that increasing dose of a dual inhibitor would have far reaching benefit due to the addition of non Tyk2 Jak?

Who are our major competitors and

what do they have?

Perhaps you could give us the benefit of your wisdom here.

4. Overcoming Challenges in CNS Drug Development:

The development of drugs for CNS diseases is known to be challenging, with high failure rates. Inhibitors offer a potential strategy to address these challenges by targeting specific pathways and mechanisms.

For instance, the inhibition of efflux transporters can enhance drug penetration into the CNS, overcoming the blood-brain barrier.

5. Examples of Inhibitors and Their Applications:

Kinase Inhibitors:

These are being explored for a variety of CNS diseases, including neurodegenerative disorders and stroke.

HDAC Inhibitors:

These are being investigated for their potential in treating traumatic brain injury (TBI) and spinal cord injury (SCI).

PDE5 Inhibitors:

These have shown potential for treating neuroinflammatory and neurodegenerative diseases, as well as memory loss.

BTK Inhibitors:

These are being studied for their ability to modulate inflammation in the CNS and improve outcomes of various neurological diseases.

6. Ongoing Research and Development:

Research continues to identify new targets for inhibitors and develop novel compounds with improved efficacy and safety.

Scientists at the University of Birmingham have identified a potential target for treating long-term neurological conditions like Alzheimer's Disease and fostering nerve regeneration For CNS.

Factoring in the value of indication?

How do you place a value if you do not identify the potential Indications that a compound can treat?

Joey you have done nothing but spout negative drivel since you been posting here.

Absolutely nothing of substance do you contribute even with your vain attempt at inserting the word fact now and again.

We all know the the SP is low sonny as are companies like Avacta, Novacyt and several others.

Is this the Sareum Bods fault too.

No new safety signals observed at Year 5 in the POETYK PSO long-term extension trial, consistent with the established Sotyktu safety profile

Following five years of continuous Sotyktu treatment, clinical response was maintained in nearly half of patients for Psoriasis Area and Severity Index (PASI) 90 in the POETYK PSO long-term extension trial

Sotyktu cost around 7k dollars for 30 day supply of 6mg.

After 5 years clinical response maintained in nearly half of PASI90.

Less than half in other words.

In addition should have less efficacy than dual inhibition that has already been proven.

Now give a reason on here why a pharma would not have mire than a passing interest in 1801.

Pharmas in competition with BMS are going to allow Deucravacitinib to dominate to the point of exceeding 4 bullion dollar annual turnover by 2029.

I don't think so.

Panacea, good afternoon.

May l inquire as to how long long you have been invested here and a listener?

Since you class yourself as a long term holder what did you make of the last AGM and the Invstor meet at end of last year with regards to progress of 1801, phase 1a results and potential Indications.

As for your comment of the science being as good over the past 12 weeks as over the post 12 years you could elaborate on this.

In effect it is a country mile apart.

This 1 in 10 chance of success is very much milsleadond znd wY out of date.

Deucravacitinib feed in Ulcerarive colitus.

Is this one of the 9 out of 10 failures?

It was satisfactory in Psotiadis since o I this one of tge one in10 successes.

A new statistical model needs developing as currently very archaic.

I take it you understands the potential value of the BBB penetration and CNS Indications for which there is an urgent unmet need.

SDC1801 has given excellent results in Phase 1a .

Perhaps you could give your opinion or view on this.

Go on surprise us all as it may even be the keast bit positive.

We have a compound ie SDC1801 that has delivered class leading results in Phase 1a SAD and MAD clinical trial.

Deucravacitinib was bought for 4 billion at end of phase 2 trial results in Psoriasis.

In this instance ot will be that BMS would have decided due to its profile that Deucravacitinib has potential in many other Indications.

Now as Tim Mitchell stated there will be Indications that Deucravacitinib will perform better than SDC1801 and vica.

Should our SDC1801 prove to have similar safety profile to Deucravacitinib then it game on.

This can basically be established by the long term toxicology study results.

At the same time any interested pharma will want to know the Indications that the 1801 compound isIkely to show most potential in

Now for those that follow and read the RNS's then you will know that the original intention was for 1801 to be trialled in Psoriasis.

Psoriasis is an extremely competitive market.

Treating abnormalities with regards to the CNS is now becoming the subject of focus.

No mention at all of the blood brain barrier and central nervous system.

The earliest l recall is post AGM in Dec 2024

To me this is avery clear sign of change of direction.

The question here ultimately what has caused this change of direction?

Tim is now occupied with transformational studies in 1802 and investigational work with regards to BBB and CNS.

So for those who claim to be long term holder or this that subtly try to undermine by stating previous short comings with the performance off the BoD then please feel free to express your views and reasonings behind your opinion.

There are many companies that have gone under in the AIM market

Main cause lack of investment. Sareum have had their fair share of experience in this.

Regards

Psoriasis treatment alone is not worth 4 billion and you would have to be very naive to think it is.

So a question here is when did BMS approach the company for its pipeline?

Was there any mention of these informal discussions taking place?

Stephen Parker is temporarily CEO.

It is now coming up to a year.

What do you define as a long term holder?

How does one derive a probabity of success?

What was Deucravacitinibs probability of success?

Probability here Potnak rather like using a fruit machine or winning the lottery.

All down to chance or luck.

I am not saying this is a 100% certainty however.

Deucravacitinib went from completed Phase 2 in Psoriasis and.bought for around 4 billion?

Why was it worth 4 billion?

It was worth 4 billion with a further 2 billion in milestones due to its at the time superior safety profile.

But Tyk2 is not the be all and end all. It will be good at some Indications and not so good in others as verified by its failure in UC.

Tyk2 Jak1 ie dual inhibition hypothetically will give greater efficacy than Tyk2 alone.

This has been proven.

All that is required is to establish long term safety.

Are you saying this safety is subject to chance?

Results from phase 1a would certainly suggest far greater odds of success than 1 in 8.

In addition to this 1 in 8 that you give, is this just in one indication or one of a possible half dozen Indications.

Whilst success cab be represented statistically it is very rarely down to luck.

Regarding Sierra Oncology and 737?

In my opinion it was the intention of SO to develop 737.

Sierra oncology had a change of CEO

There then came a change of direction.

Subtle in that we are exploring further options to finance 737.

Nothing happened here apart from the final design stage that never materialised.

GSK did not want as GSK had Tesaro pipeline and certainly would not want to be taken by a competitor.

Why did Sierra Oncology take the for sale sign out of the shop window in early 2020.

It would coincide in my belief as when GSk expressed mure that a passing interested in SO for Momoletonib.

Regards

Worthwhile having a Google on kinase inhibitors and CNS.

I am not a fan of AI, however:-

TLL-018:

Another selective TYK2/JAK1 inhibitor, also showed promising efficacy in a Phase 2 trial, with high rates of clear or almost clear skin (IGA 0/1) and PASI 90 response.

Brepocitinib:

A TYK2/JAK1 inhibitor that is being investigated for psoriatic arthritis and other inflammatory conditions.

SDC-1801:

A selective TYK2/JAK1 inhibitor, completed Phase I clinical development and is being explored for autoimmune diseases.

Most important part l missed.

In effect we would have the benefit of dual inhibition. Subject to long term tox report if course.

Put a price on 1801 with satisfactory long term safety results as a Tyl2 Jdk1 inhibitor.

Deucra was 4 billion at later end f phase 2 trials.

I dare say BMS we're instrumental in bringing into force the labelling and consequently restriction of prescribing Jak inhibitors due to boxed (safety warnings).

What made Deucravacitinib successful?

Anyone care to give a reason as to why 1801 should not our perform Deucravacitinib on more than 1 indication?

A good post Krone.

There is a big mad rush to push this Tyk 2 in all sorts of Indications.

Now we have it being pusher forward fir diabetes types. Yes brilliant.

However, we do have deucravacitinib approved for Psoriasis due to its safety and most certaiblynot on its Psoriadis Area Severity Index score.

It failed abysmally in Ulcerative Colitus.

Now we have the type 1 diabetes.

Now Jak1 plays a role here In diabetes too, albeit not crucial.

We should have no problem here bettering deucra in Psoriasis with respect to efficacy

The type 1 diabetes market as yet has not been set upon by the kinase inhibitor pharms.

The treatment here will tend to be lifelong.

More and more kinase inhibitors are being pushed into Indications related to problems with immune system.

Has the penny dropped yet with regards to Sareum progressing long term toxicology studies with 1801.

The question here is also, are we looking at or more importantly developing a BBB CNS compound?

If l were BMS of which l am not l certainly would not want that Sareum 1801 close behind me, hot on my tail as competition.

Remember our selectivity of Tyk2 over Jak1 is as Tim put it as what 'we believe to be the optimal amount'.

'Wait until.the world sees what we have to offer'

A few have mocked many times on this.

I am looking forward to the outcome.

Regards

Buy,showing as a sell

11 Sep 2024 18:19

Bought at 4:29 ok it was only 8774 shares but being relatively new ,don’t understand.

Looks like you bought around 28p

Welcome to the world of AIM.

Quite a few companies shafted through lack of or poor investment. That includes crooked investment companies.

We sit at an absurdly low SP and corresponding market cap.

Always the darkest before sunrise.

Pipeline is v good due to SDC1801.

A very safe latest generation Tyk2 Jsk1 inhibitor with demonstrated high safety and great LAdMET properties.

Long term toxicology studies initiated.

Will take it that the start has been initiated but not sure when.

It could be interpreted that the initiation started at the AGM last December.

Big change in development and direction Iin past 12 months..

We have funding for around next 12 months and to complete 1801 tox studies yet we sit approx 70% lower than we did last year on preliminary phase 1 a clinical trial.

SP does not reflect current worth of assets.

Regards

Shepherddollar.

Good morning.

Definitely on the last stretch or the home straight.

We are not sure of how long the home stretch is or how many hurdles to jump.

I would say all is going the way things should but a no great pace.

Thoughts on the phrasing of 'initiated' as to opposed use of the word stated or commenced when discussing trials progression.

I would say that dosing has not started yet.

I can see no reason as to why there would be a delay of any significance.

The only thing l could percieve is if there is a new compound from us.

There was never a mention of investigation of starring bbb cns.

Be nice to k ow intentions here

Regards

Thankyou for the post HbD.

I dare say we are being steered HbD

July first preliminary results which are very favourable.

July 10th change of management.

Since then a change of direction with a distinct focus on SDC compound potential.

Sareum do notnotcurrently have access to funding to fully realise the potential of the SDC pipeline.

Why not go the whole hog and put 1802 through at the same time?

Regards

goid afternoon hbd.

yes interesting comment you make regarding potential to interact with other drugs.

i understand your reasonings on this but would this not better been identified with pharmacokinetics.

would not have thought this will take 4 months.

then again as you say looking at long term affects and possible interactions coming into play with regards to patients that areon current treatments

all.very interesting and would think that tim has been very busy over the last 11 months on investigational research.

very convenient that he is now coo and not ceo.

as several have pointed out myself included that there are a plethora of compounds coming to the end of their commercial lives.

several that are in development will never make the grade.

since deucravacitinib the epitome of kinase inhibitors with its excellent safety profile has decimated the potential of your average jak inhibitor, later stage , more selective jak inhibitors with greater efficacy with satisfactory safety profiles will become the desired choice for commercialisation.

tell me who our nearest competitors are.

tim.says our closest rival is breprocitinib. it may well be the most developed but has now been discontinued in several indications of which psoriasis is one.

now being put into trials for the likes of sle ad and one or two other obscure indications.

so in a sense here they are working **** about face.

rather than develop a compound to treat a specific indication that can be attained by precise jak selectivity and the binding affinity, they develop a fairly broad spectrum jak inhibitor that is like a jack of all trades and master of none.

it fails not neccassarily by much but sufficient to cease development on a particular situation and search desperately for another with the idea of being the first one in.

now surely the best approach is to look for indications and specialise in developing the inhibitor to precisely target that indication

you can adjust or create at an early stage.

molecules so far have give good safe ladmet results albeit not long term toxicology.

my belief here is someone pushing the buttons to see just what potential sdc compounds may have,not just for now but in the future.

it is such that the advantage lies with the interested party at this moment in time. they can choose whoever they want.

ultimately they will get what they want and will pay the price to get it. but first it has to meet their requirements.

many small companies will fail.

a few will benefit handsomely.

i believe we are the latter

it's pnly been just over 5 months since clinical trial phase 1a data results have been finalised and signed off.

it would be great if we have more than one interested party.

potnak you stated previously you don't bother reading my posts and just scroll through.

you little fibber.

regards to all

Good morning PC1954.

A good RNS much underestimated.

'The studies, designed to support longer-term dosing of SDC-1801, will investigate the general toxicology and potential of SDC-1801 to interact with other drugs. These are key regulatory requirements ahead of the planned Phase 2 clinical development programme'

Note' the potential to interact'

This is not referring to toxicity,

It is a very clever way of letting slide possible combination therapy.

This is not something that Sareum have dreamt up.

If it were they would be adding to an RNS the possible indication for this 'potential to interact'

The feeling of growing control, guidance, advising by a very interested 3rd party is nigh all but confirmed, that is my opinion.

Opinion of 3rd party buyout / control since change of plans in July 24 very strong.

Great results albeit preliminary released 1st of July.

That was a timeline that was indeed adhered to by Sareum.

Perhaps that Riceyboy would acknowledge this.

But l doubt as is so twisted.

Potnak up and down with is negativity and positivity as usual.

He was half expecting an RNS stating a delay.

Sareum.blew him out the water on that one.

Read very carefully what is put in an RNS, it is carefully worded for a reason.

I did state that I believed Sareum would be bought out before toxicology test completion or prior to commencement of phase 2 clinical trials.

I may be wrong but still stand by that.