Member Info for sadoldgit

Good afternoon PC1954.

Not wishing to pull your post apart, but

'There is a misconception on here, if people think that week 16 is the “tick box” for SDC-1801, it’s only the dosing period - data analysis, evaluation and reporting of GLP on all matters relating to that dosing to be scrutinised before regulatory submission to MHRA for efficacy to continue into Phase2 trials.

'regulatory submission to MHRA for efficacy to continue into Phase2 trials.'

Toxicology pertains to the safety with respect for suitability for long term use, it has absolutely nothing to do with efficacy apart from establish if any dose limiting toxocities.

Indeed there are many indications.

With regards to a 16 week trial there will be preliminary results just as there were in phase 1a trial.

This is the teaser of course. As the maximum dosing reached will be known and also adverse effects if any. ( 1802 will be a tad different of course)

However, it also needs to be taken into consideration that dosing of animals in mg per kilo weight differs significantly in dosing human mg per kilo as metabolism is vastly different unless of course using primates.

As l am sure you understand around two thirds of compounds fail in a phase 2 study. This is in the main due to Dose Limiting Toxicities.

A drug can pass in a phase 3 clinical study but at a later date fail at a later phase 2 in a different indication. As an example Deucravacitinib authorised for use in Plaque Psiriasis but failed dismally in Ulcerative Colitus.

With regards to efficacy in a psrticular indication this is determined by phase 2 trial.

Let me remind you of the interview involving John Reader with the identified target of Il-6 Il-17 Il-22 Il-23 interleukins as well as interferon gamma crucial in many indications.

In effect it is the inhibition of these targets that will lead to satisfactory efficacy. Unwanted inhibition of targets outside these areas or unbalanced inhibition highly likely to give rise to unwanted off target events that will compromise efficacy v safety.

As both JR and TM have stated we will be better in some indications and not so good in others ie Sotyktu, as we are a dual inhibitor of Tyk2 with what TM described as their belief of the optimum.amount of Jak 1 hence best of both world in a compound.

Full confurmational results are still undeniably crucial.

My opinion FWIIW is outright buyout or as back up an onlicence or partnership on more than ome front.

All of our compounds are available and no complications as such if total buyout is the objective. Known as optioneering.

These are what l believe are Sareums objectives but outcome is anyones guess.

Regards

Good afternoon PC1954.

Not wishing to pull your post apart, but

'There is a misconception on here, if people think that week 16 is the “tick box” for SDC-1801, it’s only the dosing period - data analysis, evaluation and reporting of GLP on all matters relating to that dosing to be scrutinised before regulatory submission to MHRA for efficacy to continue into Phase2 trials.

'regulatory submission to MHRA for efficacy to continue into Phase2 trials.'

Toxicology pertains to the safety with respect for suitability for long term use, it has absolutely nothing to do with efficacy apart from establish if any dose limiting toxocities.

Indeed there are many indications.

With regards to a 16 week trial there will be preliminary results just as there were in phase 1a trial.

This is the teaser of course. As the maximum dosing reached will be known and also adverse effects if any. ( 1802 will be a tad different of course)

However, it also needs to be taken into consideration that dosing of animals in mg per kilo weight differs significantly in dosing human mg per kilo as metabolism is vastly different unless of course using primates.

As l am sure you understand around two thirds of compounds fail in a phase 2 study. This is in the main due to Dose Limiting Toxicities.

A drug can pass in a phase 3 clinical study but at a later date fail at a later phase 2 in a different indication. As an example Deucravacitinib authorised for use in Plaque Psiriasis but failed dismally in Ulcerative Colitus.

With regards to efficacy in a psrticular indication this is determined by phase 2 trial.

Let me remind you of the interview involving John Reader with the identified target of Il-6 Il-17 Il-22 Il-23 interleukins as well as interferon gamma crucial in many indications.

In effect it is the inhibition of these targets that will lead to satisfactory efficacy. Unwanted inhibition of targets outside these areas or unbalanced inhibition highly likely to give rise to unwanted off target events that will compromise efficacy v safety.

As both JR and TM have stated we will be better in some indications and not so good in others ie Sotyktu, as we are a dual inhibitor of Tyk2 with what TM described as their belief of the optimum.amount of Jak 1 hence best of both world in a compound.

Full confurmational results are still undeniably crucial.

My opinion FWIIW is outright buyout or as back up an onlicence or partnership on more than ome front.

All of our compounds are available and no complications as such if total buyout is the objective. Known as optioneering.

These are what l believe are Sareums objectives but outcome is anyones guess.

Regards

An easy by longish read below. From 2025.

https://www.explorationpub.com/Journals/eds/Article/1008116

Good morning PC1954.

Two posts were made. Presenting a post is not an attempt.

You were asked from whence and where did l give you cr.p as you claimed.

Clearly l did not. But you lack the integrity to at least acknowledge.

Provacative?

I suggest you have a look through some of your posts.

If in doubt l can copy and paste.

Regarding reality?

Are you implying that potential is not part of reality?

If the potential is reached it becomes a long awaited achievement that will ultmately be reflected in the market cap. However, without potentual we would indeed be subject to further decline.

I note no comnent with regards to importance of IL-22. Clearly you cannot comprehend that which l post so may l suggest you use AI?

AI is not infallible and does frewuently get things wrong or make false assumptions leading to incorrect information.

Good that you are having bowel screening presumably on a regular basis. Early diagnosis leads to early treatment and potentially proper control or cure.

As l am sure you are aware processed foods are one of the major causes associated with bowel cancer. To a certain degree also red meat.

Of importance is a balanced diet of course. Has a marked effect on our immune system.

However, in an age where convenience foods have become the norm it is no suprise that we are a nation suffering with obesity and bowel complications.

Regards to me being a Hammer and your 'dissapointment on my provacative stance' i tend to focus on what we can achieve as opposed to where we stagnate at the moment.

Early part of life l worked in mechanical engineering with time spent in research and development. The dreaded 725 Die Platten Cutter.

Revolutionary but sinple in design with the intention of achieving far greater output by utilising 4 crankshafts instead of two camshafts.

It was a US company thst went bust fue to debts in Harlem and Dundalk, Leiston was profitable .

Enjoy your day

I must apologise for my apalling spelling mistakes PCS1954.

I should correct my spelling mistakes prior to submitting the post.

I am restricted to this little mobile phone with tiny little keys and oh so easy to hit wrong key.

Do you think that it may be a possibility that Laboratory testing periodically of patients may be reduced or required less frequently dependent on toxicology results?

FWIIW my opinion is that the level of Laboratory testing will become apparent in the first clinical trial in Plaque Psoriasis. Requiring in the end perhaps a 12 month or routine blood test and count.

Of course the same conditions would not apply to 1802 due to the higher Jak content, unless used in autoimmune as originally intended for immuno oncology.

As for values, is it not nigh impossible to assign a value to Sareums entire compound range both individually and collectively? Imperative that indications suitable for commercialisation are identified via high efficacy and satisfactory safety profile?

It is my belief that there are ball park figures subject to results, all in discussions and of course informal, the critical component being 1801 closely followed in advances in blood brain barrier penetration for diseases pertaining to the central nervous system.

Potential here of course, as Interleuken 22 identified as major contributory factor in both MS and AZ.

Sareum 1801 already proven preclinically to inhibit IL-22, However, crossing BBB and the behaviour of kinase inhibitor compounds in cerebral fluid is vastly different to plasma.

I still remain optimistic on more than one front.

Nighty night

Ps l am pretty certain there is only one spelling mistake.

PCS1954,

You really are a one aren't you

You were asked exactly as to how exacyly have l given you Cr.p?

I have not. That is the answer.

An over reactuin by you at a quarter ti 12 at night.

A few too many or aee you Chalfonts playing yiu up old son.

You post regarding respected posters.

You have shiwn very little respect.

You clearly are unable to hold dialogue regarding the science. Tell me is this down to ignorance or the inability to comprehend basic chemistry and biology?

I put questions too you regarding our and competitors conpounds. Clearly the above paragraph applies to you here as relavent here as confirmed by your dissapearance to Italy and remark about not looking at the 'bb'

You post AI data. No difference to that l was saying 18 months ago.

Long term toxicology study to enable phase 2 studies with high degree of success as will prove suitability for long term use periodic or otherwise as will not suffer from the restraints of dose limiting toxicity.

The question is as follows.

On favourable toxicology results, does SDC1801 a Tyk2 Jak1 inhibitor come under the classification of a Jak inhibitor requiring constant periodic laboratory testing in clinical trials that allosteric Tyk2 appears to be exempt from?

These labaratory tests as l am sure even you are aware are very costly.

Nighty night

Good evening PC1954.

Thankyou for your reply but you did not address the points l made.

1. Is Breprocitinb more advanced than Sareum?

It is more advanced but certainly does not make it worth more.

It is all down to safety and efficacy.

2.Dual inhibitors preclinically proven to have greater efficacy than Tyk2 alone.

3. However, Jak inhibitors as such relates to the early generation, were poorly selective intentionally to give broader scope or not.

This lack of selectivity gave rise to serious adverse events including Major adverse cardiac events.

4. It is not beyond the realms of belief that just maybe we have the best of both worlds here.'

5 We are also encouraged by the continuing TYk2 with no safety concerns. Sareum themselves stated this as l am sure you are aware.

With a good toxicity profile we will not be hampered by dose limiting toxicities with the resultant more than satisfactory efficacy result in numerous indications. The more approved indications the greater value.'

I bought Thoths figure in of 14 pounds a share as derived from 1 billion market cap with 70 million shares in issue.

A poster here put a value on Sareum of 2 billion recently.

The point l were making is that with 140 million shares in issue would make each share 14 pounds each.

So in essence, not predicting £ 14 a share merely that it is a possibility.

Huge advances would need to be made on all fronts.

In my opinion for what it is worth is that dear old Sareum will be taken over providing ;-

1.SDC1801 completion toxicology study allowing authorisation for long term use.

2 The possibility of treating CNS indications i given in preclinical testing.

Funding at some stage will be required if we are not bought out.

I am not taking this personal as indeed it were a short while ago deliberately set out to undermine.

You want to play little games PC1954 then do so. I thought you were beyond that. I have never given you any crap. I am more than capable of doing so.

Night night

Good morning PC1954,

Is Breprocitinb more advanced than Sareum?

It is more advanced but certainly does not make it worth more.

It is all down to safety and efficacy.

Dual inhibitors preclinically proven to have greater efficacy than Tyk2 alone.

However, Jak inhibitors and thus relates to the early generation were poorly selective intentionally to give broader scope ir not.

This lack of selectivity gave rise to serious adverse events including Major adverse cardiac events.

It is not beyond the realms of belief that just maybe we have the best of both worlds here.

Long term toxicolgy results will give suitability for long term use.

We are also encouraged by the continuing TYk2 with no safety concerns. Sareum themselves stated this as l am sure you are aware.

With a good toxicity profile we will not be hampered by dose limiting toxicities with the resultant more than satisfactory efficacy result in numerous indications. The more approved indications the greater value.

Nothing 100% guaranteed of course.

I am not sure why you think my posts are hyoerbole as what is written above is basically fact.

Are you of the opinion that Thoth2 posts were 'hyperbole' regarding £14 a share, ie around 1 billion. Interesting l note that you are looking at a figure of 0.9 billion in one of you recent posts.

From where do you derive this figure? Is this not hyperbole too?

There are twice the amount of shares now and we are further forward with 1801 1802 and now looking in to diseases of the central nervous system with a compound we have has being identified as showing potential but requiring optimisation.

Yes we do still have hurdles. We have increasing competiveness and more biotechs entering this arena and vast strides being made in China

In my opinion the current SP in no way reflects the value of what we have.

What is does reflect is the value of Sareum market sentiment.

Investors moved out out of biotech after the covid peak and rapidly invested into the military manufacturing companies.. to invest in guaranteed returns in this indusry eg Rolls Royce up 1200 percent in 5 years investors will not be looking into high risk albeit potential high gains, hence phenomenal market Cap decreases in small bio with many going under.

The question here of course is as follows.

Is a world class inhibitor worth more or less to a buyer than say 6 years ago?

If the market Cap of a company drops 90% does the value of its pipeline drop by 90%?

Mayket sentiment is a strange beast.

Regards to all

Where exactly us the insubstantiated hyperbole.

The price of a biotech company is valued on its pipeline not tge size of the company.

Momoletonib was owned by Sierra. 1.9 billion was paid by GSK.

Momoletonib has nowhere near the potential market as the likes of Sotyktu or indeed TAK-279.

Once a compound has approval in an inducation it will be snapped up by big pharma. Then it is commercialised by trialling it in every indication they can.

GSK Momoletonib is one example but of course limited in indicstions.

Chk1 and Wee 1 inhibitor returned to sender.

2 billion l would personally put on a value with great results on tox trial and approval for Plaque Psoriasis.

BBB achieing any sign of potential should significantly increase the SP

Agree with Potnak looking at sround 2 years perhaps a tad less. Certainly l would not value Sar at 2 billion at the moment. Possibly worth as much as 400 million on decent tox results.

Efficacy should not be a problem in Sareums stated indications as highly unlikely 1801 would suffer dose limiying toxicities experience wuth othe Dual inhibitors including our most advanced competitor Breprocitinib.

Where is the insubstantiated hyperbole in this?

Biopharma market suffered as all investment now mainlt to do with military sector. Many with a thousand per cent increase over past 5 years.

Regards

Good afternoon Steve i am of the same opinion myself eith regards to selling the company.

TMdis mention 2024 AGM that they were all getting on and if an offer was placed which they deemed reflected the value they would accept

1801 has not really progressed since July 24 with exception of now recomnence ment of trial.

It does bug me that a CRO that is regulated and has a duty of care to animals allowed a compound with a non safe excipient to be used. It is normal procedure for a CRO to go down that route.

A new batch of 1801 had been made up and deluvered to CRO. Question here is had the excipient ie the carrier already been included in the compound?

Blood brain barrier penetration and CNS indications?

It would not be unreasonable to expect progress development in next few weeks.

This in effect is an untapped market with huge potential for any inhibitor that has a positive result with respect to a treatment that even just limits progression. MS similar to SLE except MS is CNS and SLE is PNS ( peripheral nervous system).

Should 1801 and BBB CNS compound materialise then Thoths 14 pound a share becomes a possibility. A 2 billion buyout with 140 million shares balances nicely.

That of course not inclusive of 737 and 1802.

One thing however is that, how much value a compound has is not always reflected when offers are made. Pharmaceuticals are a business and a very cut throat one at that.

When positive news does come through expect a significant rerate!

Ideally the efficacy of Jak inhibitors with a safety profile of an allosteric Tyk2 inhubitor is the objective. This would be a first.

Regards to all LTH

Good morning.

Not new but reasonable overview on injibitors.

https://pmc.ncbi.nlm.nih.gov/articles/PMC9959504/

Thankyou 007,

A long read but worth reading on IL-22!

https://pmc.ncbi.nlm.nih.gov/articles/PMC9514046/

I remember hearing Tim and his ' We believe what we have to be the optimum.amount of Jak1'

A while ago during an interview with the smooth talking Aussie Andrew Scott

Now they claim that Tyk2 is selective.

Yes it is very.

So how do these allosteric Tyk2 inhibitors inhibit IL-22 effectively as IL-22 part of the IL-10 family which requires Jak1?

That aside my belief is we will be bought out some time after toxicology study completion.

Preliminary results will come out first then months later the final audited study results.

I cant see it being licensed.

My reasoning?

A large pharma will not buy a licence for a potential blockbuster inhibitor that 1801 is.

At the same time we are developing a pipeline

737 cannot be taken as a certainty but will come in very useful to comkanies that want to prolong the lifespan by increasing patent timescale via incombo therapy.

1802 has potential in T-ALL leukemia possible also as treatment in some immuno therapy but needs safety testing.

BBB and CNS, ppotentially very promising and we are getting a tad overdue on news for this.

My opinion fwiiw is we are in talks ( well have been since July 2023).

Producing an effective CNS inhibitor is by no means an easy task

All goes well amd with a tail wind 14 pounds a share ( even with the current amount of shares we have) is achievable.

How much GSK pay Sierra Oncology for Momelotinib? 1.9 billion plus shareholders up in arms as undersold.

Whre do we sit at?

A measly 30 million.

2021 we were at a msrket cap if 300 million!

Enough from me

regards

Good evening

279 v 1801

TAK-279 has given impressive class leading results in Plaque Psoriasis, an allosteric Tyk2 inhibitor as is Deucravacitinib, albeit with far greater selectivity over other Jaks of 1 million fold.

PASI scores of 90 and 100% being reported

within 16 weeks or less.

It should be suitable for long term use in Psoratic Arthritus as has an excellent safety profile. Breprocitinib was withdrawn from PP due to safety concerns.

Zasocitinib’s extended half-life (16.5 to 30.7 hours) compared to deucravacitinib (10 hours) contributes to its capacity for sustained inhibition and once-daily dosing convenience. The absence of JAK1/2/3 inhibition suggests a safety profile potentially superior to that of both TYK2 orthosteric inhibitors and JAK inhibitors.

As you can see greater efficacy in TAK-279 most likely due to its vastly superior half life. Interesting to note that JR at 2024 (AGM) was looking at tweaking the compound to increase half life of 1801.

1801 so far has given excellent better than expected results in phase 1a SAD and MAD trials.

No increase in dose limiting creatinine levels that put the Kybosh on Breprocitinib!

We are both TYk2 Jak1 inhibitors.

Advantages of Tyk2 Jak1 dual inhibiton

Inhibition of IL-10, Il-6, IL-17 IL-23 and of course the all important IL-22 ( consists of 2 sub units IL-22 R alpha and IL-10 R beta)

Heterodimerisation of Tyk2 with Jak1 is required for Inhibition of IL -22. End of!

As a side note IL-22 is generally being acknowledged as being crucial with regards to inflammation of the brain but as yet not seen specific indications.

Back to 279 v 1801.

In theory 1801 should trump 279 with regards to efficacy.

But also in theory 279 should have a superior safety profile being an allosteric Tyk2 inhibitor.

Our safety profile is on par on light dosing with allosteric inhibitors.

No such thing here as absolute failure in the tox study. We need to prove is how good we are. If we prove we have similar safety profile to the allosterics then it is game on.

We sit better than Breprocitinib with regards to safety at this moment in time

IL-22 plays an important role in IBD. Deucra failed but l gather 279 is going to be trialled in this area. Best of luck on that one!

Sareum been tight aroind 1801

They dont want the world to know what they have just yet. Once we become known we become a target to beat. JR expressed these concerns 2024 AGM! Almost reluctant to have put forward to go into a journal at that time.

We are looking at long term toxicity as opposed to serious adverse events.

It would make sense to establish an MTD here.

Both seriously affect the value of the compound.

Knock on effect to 1802 not much as is intended for immunoncology. The downside being it would restrict being used as back up for 1801 in autoimmune.

We have dosed at 30 x therapeutic dose in precinical.

ALL EYES ON LONG TERM TOXICOLOGY RESULT.

Not just ours!

Regards

A very good positive post from you Colbaltblue.

Nothing has changed one little bit from what we had yesterday and what we have today. Only our perception.

Agree wholeheartedly with you.

A potential buyout would be shelved on the commencement of any litigation.

If it went tits up the new owner would pick up the costs and possible compo and months upon months of litigation. Yes not worth it.

That ho9ld tell you something if you read positively in it.

Strange is it not that l have remained very positive here for over 90% of the time. Early dsy past and have learned a lot about Sareum its products and people.

Some on here sicken me.

Riduculed and undermined by some. Indeed also to the point of insult.

Out to prove me wrong, to gain what?

No longer will l waste of my time posting here. Much to the delight of some l may add.I have added fairly considerably since beginning of year which indicates my faith in the company along with the science.

Those long term invested here l genuinely wish all the best.

Yes when things look grim we can all feel a tad peeved.

I am certain CB the SP will be at least at a price to put a smile on your face

Regards

Checking out

It is always good to read several times ans even then eait a while read and digest.

Good morning Potnak, the RNS is encouraging to say the least and no imimnent requirement for fund raising.

Progress being made with CNS preparation for preclinical work encouraging ie manufacture of several compounds and clearly here has saved time.

Regards

I have copied and pasted excerpt from chaimans corner.

Late last year l posted that fault likely due to bad comms.

Making assumptions and complacency can lead to serious injury ir even death.

In this instance this does appear to be addressed by Sparker

'Ahead of restarting the programme, we completed preliminary pharmacokinetic work to evaluate tolerability and exposure across a range of formulations. This work allowed us to select a vehicle with appropriate precedent for long-term studies and provided confidence to move forward. We have now appointed a leading global contract research organisation (“CRO”) with extensive experience in long-term toxicology studies to conduct the programme; we worked closely with the CRO to determine the optimum formulation for these studies.'

In addittion we have the best bullet butnot having a rifle anology.

Personally l dont see this as valid as the bulket and indeed tge rifle eorked bettrr than expected in phase 1a

With regards to long term toxicology they used the wrong rifle. That mistake with nigh 100% certainty should be resolved with Sareum and the newly appointed CRO in constant confirmational correspondence.

People overlook the most simplest of requirements. Many many failures are a

direct result of bad or no communications.

Regards

Underhanded tactics by big pharma C79.

Allosteric Tyk2 not all it is made up to be.

They claim it regulates.

Regulates implies control it also implies a correct amount of inhibition to differing inteferons and interleukins.

As allosteric Tyk 2 works on the JH2 ie allosteric or pseudo kinase domain it cannot by definition regulate all aspects of JH1 the active domain. Ot has partial control over.

It is a means of creating selectivity over and mothing more. Better selectivity certainly but overly selective not good either.

Is a light switch a regulator or controller?

It is a controller as turns light on and off.

It cannot control brightness as for that you need a dimmer or rheostat that controls the voltage. This is regulating. It is also control.

You can liken this to allosteric Tyk2 Jak inhibitors.

The word 'regulates ' is used inappropriately.

If it regulates and by this to mean, controlling optimim sgnalling within cells to correct any imbalance and maintain them, why has it not regulated the imbalance in a cell to give first class efficacy in Psoriasis and failed to meet endpoints in UC resulting in cessation of trial. Oh BMS stated looking at increasing dose! That not going to work. Been very quiet for past 3 years on that front.

Just a tad harder to resolve than a minor problem as per Sareum with a recipient not suitable for use in animals.

TYK2 does not directly inhibit interferon gamma.

Jak1 and Jak2 heterodimerisation at cell membrane is crucial for production of interferon gamma to cell DNA and is downstream of Tyk 2 signalling pathway.

On current results and information we have been supplied we do appear to hit the sweet spot.

Mostly Tyk2 small optimum amount of Jak1 which has high beneficial selectivity over Jaks 2 and 3.

And yes C79 we now live in an age where corruption and lies are rife. Little to no integrity left. As long as it ticks the box, how you grt thete dont matter

Regards

President Sparker.

These ongoing discussions with interested persons can you clarify the following.

Are we talking the same people with different duscussions or different peoplw with the same discussions?

What do you currently have planned with regards to continuation of funding pipeline?

In all fairness little can happen to inrease share holder value until 1801 toxicology results unless licence for 737 or significant progress on 1803.

Good afternoon Potnak.

Whilst toxicology good result for 1801 would work wonders basically okaying it for long term use. 1802 is adifferent kettle of fish as is for T ALL cancer and hence less likely of adverse event restrictions as in auto immune.

On the plus side, increase in capsule dosage capacity looks extremely promising.

2.5 to 12.5 mg per kilo therapeutic ( yes before anyone chimes in there is max of 1000mg per patient daily intake)

Better than expected ADMET in phase 1a albeit comparatively low dose. Good pharmakinetics and pharmacodynamics.

With regards to SLE being an indication there is a good possibility tgat we will better Deucravacitinib. Whilst allosteric Tyk2 controls downs stream signaling of interferon gamma, jak 1 is predominent in its production. That is as l understand it.

All on all 1801 should prove to be safe for use long term use and have more than satisfactory efficacy than current approved treatments in several indications.

Putting a Market Cap of 150 to 200 million within a week or so of release of satisfactory

toxicology data woild not seem put of the question, 100 million certsinly should be achievable

We must not forget that we have suffered 2 years of delays with the CTA and 1st attempt at toxicology study. It is not exactly vonfidence inspiring

Regards

Very difficult to evaluate a current value with any precision. Too many uncertainties. Will change considerably on toxicology successful outcome.

A link below. Ling but decent read

https://www.drugpatentwatch.com/blog/valuation-of-pharma-companies-5-key-considerations-2/