Member Info for sadoldgit

In essence we are looking at prolonged administration and applies particularly to immuno therapy as opposed to immuno oncology.

They are 2 different requirements that ideally need both to be established

We never achieved maximum tolerated dose

We achieved 30 times treatment dose with no adverse events.

Tim said in around 2020 it was a problem but a nice problem to have and may come back to bite us later.

Thoth2 did point out that 30x Treatment dosage is an acceptable valuation if mtd has not been established.

Somebody new to the MHRA very likely to be up on this. As they say no substitute for experience.

We have endured tge bad it of the problem but it is about time the good part of the problem shone through.

Regards

Good afternoon PC1954.

I am sure it was stated at one of the meetings they would be starting on a higher dose.

Below extract of MTD below from 2015 just beforeskifgt changes made

Introduction: Traditional dose-limiting toxicity (DLT) definition, which uses grade (G) 3-4 toxicity data from cycle 1 (C1) only, may not be appropriate for molecularly targeted agents (MTAs) of prolonged administration, for which late or lower grade toxicities also deserve attention.

Patients and methods: In collaboration with pharmaceutical companies and academia, an European Organisation for Research and Treatment of Cancer (EORTC)-led initiative, Dose-Limiting Toxicity and Toxicity Assessment Recommendation Group for Early Trials of Targeted therapies (DLT-TARGETT), collected data from completed phase 1 trials evaluating MTAs as monotherapy. All toxicities at least possibly related to the study drugs that occurred during C1-6, their type, grade (CTCAEv3.0), and duration as well as patients' relative dose-intensity (RDI), were recorded.

Good morning MegRS300.

Mid point, Tim did mention attempting MTD as we have not established. However this is a little difference to Long term toxicology study and dosing to achieve this maybe 100 times maximum therapeutic dose. 30 x was achieved with no problem at all. Tim did say we may have to go to 100 times that was over 4 years ago.

Certainly look forward to see what has been achieved on this period of testing.

Regards

Luvelyjubley, sareums values and developments have been pondered here for tge last 13 years..

In addition Sareum cannot release any news on deals with strategic partners until after a deal is finalised formerly and inclusive if a formal offer I made.

Regards

While no Janus kinase (JAK) inhibitors are specifically approved for dermatomyositis (DM), they are used off-label to treat this condition, particularly in cases of refractory or juvenile dermatomyositis. Tofacitinib and ruxolitinib are two JAK inhibitors that have shown promise in treating refractory DM.

Good norni g citizen79.

Interesting can of worms there with Riovant.

'Cantor Fitzgerald anticipates the results of the Phase 3 trial for the drug brepocitinib in dermatomyositis by late 2025, with a potential market launch in early 2027. Meanwhile, H.C. Wainwright highlighted the upcoming trial results as a key catalyst for the company.'

Breprocitinib which is proven on safety profile alone is inferior to SDC1801.

Phase 3 trial safety v efficacy in dermatomytosis with Breprocitinib l would not wish to gamble mo ey on.

It may indeed have a degree of efficacy but l feel off set by off target effects primarily increase in creatinine levels proven and jak2 inhibition albeit minor.

Possibly OK for short term but would hazard a guess not a future in long term use.

This just emphasises the importance of these long term toxicology study.

Now surely if you were a director of Riovant you would have a concern of competitors.

If you were aware if SDC1801 you would have a far greater concern.

Breprocitinib will ot be taken forward into psoriasis due to off target effects.

What value is given to Breprocitinib?

Riovant l feel are clutching at straws in attempting to find an indication that Beprocitinib can obtain a satisfactory safety and efficacy profile both of which needed to commercialise.

With regards to MACE and Jak inhibitors early results point to SDC1801 not proving to be problematic in thus area.

Note tge importance of no detected jak2 activity.

Regards and l am sure there is plenty going on in background of which the long term toxicology results are of the utmost importance.

Interesting light reading.

https://academic.oup.com/neuro-oncology/article/26/Supplement_5/v72/7825291

A new immunotherapy drug trial for glioblastoma, the deadliest form of brain cancer, is now recruiting patients in the NHS. The trial follows a previous study where patient Ben Trotman's tumour vanished, and he has shown no signs of the disease for over two years, a rare outcome for glioblastoma.7 mins ago

Top notch post there HbD.

Also of importance is our patent life and duration

Regards

Not a fan of AI,

But!

Normally completed before human trials

We now have decent results on biomarker data to indicate efficacy

Al

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Good morning PC1954.

Yes there is a vast difference.

The 'interested' party may well pushing in the direction that they desire.

With only them on board it will be that way as Sareum do not have much else as an option.

I dare say that Sareum will be looking or have other parties on board with an interest to which they would be looking at a data package.

It very dependant here on a Co.pany that will develop to sell on commercialisation similar to Sierra Oncology and GSK or aco.pamy looking to become involved with finance and perhaps a licence partnership with option of buyout further down the line.

My reckoning is that we may well be looking at the former.

In this sense a Tyk2 jak1 inhibitor that has a satisfactory safety profile for long term use and a potential in several other indictations other than Psoriasis.

After toxicology results it may be that finance could be raised to carry out trials in an indication or indications.

Regards and trust all goes well with you at Addenbrookes.

Good morning Celtic007,

My chain of thought is that we are in in informal discussions with one party at least.

Remember the John Reader comment at the AGMacouple if years back 'Wellesbourne ussome data'

They require data. They did not say' give us a peer reviewed full breakdown of the data.'

The data will give themsomething to go on.

They will know at the moment phase 1 a results and certainy had preliminary data before July1st.

We are now entering the next phase of that which a pharma requires

Sareum may well of wanted to do a phase 1b in Psoriasis to indicate efficacy inan Indication.

Theoretically the on target selectivity nigh guarantees success here.

Limits being dose limiting toxicities of which none have been detected within SAD and MAD dosing.

Co.mercialisation value

What indications are 1801 viable?

Some indictations may require lifelong treatment

Before we can treat life long Indications we need know that 1801 is safe for long term use.

Once this is established then true potential values can be realised.

Clearly a change of direction in the past 12 months.

I don't thin Sareum have sufficient funds to run both toxicology Long term and Psoriasis at same time.

The priority is safety profile which has restricted our nearest competitor

Regards

PC1954,with all due respect the data results will be known way before they enter in journal.

The lab will know before anyone else.

Data results will be known but verification will be needed before any interpretation of the results.

They will of course have preliminary results and eventual finalisation as was the case in Phase 1 a.

There was a massive change in direction from July 1st on release of preliminary data.

No phase 1

Long term toxicity/ toxicology

Long term toxicology on satisfactory results will allow 1801 to be used in any trial indication that a pharma sees fit.

Basically looking at the safety as bei g suite for life long treatment.

Such indictations as SLE and PSA.

We are the biggest threat with regards to mass commercialisation of the likes of the very much hyped up Deuctavacitinib

There will be pharmas looking at making inroads into these lucrative areas.

Turnover of Deucravacitinib forecast in excess of 4 billion a year by 2030.

Sareum sit with current market cap of 25 million.

That is Drucravacitinib 1 year predicted turnover 160 times the current market cap of Sareum

to

We have been told we are.im discussions with Interested parties for many moons.

These are the people that will have an interest.

The newspapers reporting would only generate interest from potential investors that most likely do not even know Sareum exist.

Entries in journals again willake no difference to the people we arein discussions with.

Pharmas look.to fill gaps in their pipeline and or seek drugs that have a commercialisation value

A heavy penalty with risk

Once the risk is removed the value of any drug increases dramatically.

Risks with safety profile are the most damaging.

Hence why we are running long term toxicity testing.

It cannot be hurried.

It does not matter a monkeys chuff what gets put in a journal prior to the completion and analysis of toxicology data.

Trial is 16 weeks it has started and is progressing

Be interesting MegRS300 to input same data but with current market cap of 100 million which l believe is where we should be sitting.

Regards

Not sure how are derives values.

What does it take as a yard stick?

Looking good for Deucravacitinib in SLE another feather in the hat for Tyk2.

https://pmc.ncbi.nlm.nih.gov/articles/PMC12142172/

In addition we have been treading around CNS.

750 million a tad under valued for a complete buyout.

Regards

Looks like a couple of Benghal Lancers from the Wolf of Wall Street anti AIM institute.

He claims to have a couple of comrades on the LSE chatboard.

Notice the identical sales patter.

Could it be a reincarnation? One is the left nut the other the right.

The wolf.

Toxicology testing is in progress and absalutely nothing they say or do can change the outcome.

That is a fact

Regards

Good morning C79.

A good post from you with regards to Jak inhibitors UC and CD.

It is indeed in.depth and rales a wile to digest.

A slight change of topic but the link below relevant to current kinase inhibitors.

https://pmc.ncbi.nlm.nih.gov/articles/PMC12180671/

Pretty recent report.

June 21st 2025

Interestingly scroll down to Srs and Tyrosine kinase inhibitors and look at the associated safety profile disorders severe albeit rare.

Csrdiotoxicity

Hepatotoxicity

Cardiotoxicity we look fine on but the Hepatotoxicity is yet to be determined.

Damage to liver basically and as posted by HbD a while back on selection of dogs being used for testing toxicity of the liver for which l am grateful that he posted.

The final hurdle !

Regards

AI Overview

+2

Yes, content in most science journals undergoes a peer review process before publication. This process involves experts in the relevant field evaluating the submitted manuscript for accuracy, validity, and significance. Peer review is a critical mechanism for ensuring the quality and reliability of scientific publications.

Potnak you put

'Whoever has been 'advising' Sareum re trails, obviously doesn't believe the data so far is goes far enough to answer the Tox questions around legacy TYK 2,jaks and MTD so they advised an extended tox study.'

Why would they not believe the data?

Nothing 'obvious'here so why use the word.

Long term toxi ology is what the tria is all about.

A prerequisite required before long term use either in trial or clinic and certainly by whoever chooses to finance it.

We have no observed or measured activity for jak2 at the givenSAD and MAD dosing

I take it you understand the Importance of not having h0m0 dimerisation along with its well documented off target effects.

Itegards

Good afternoon c79

Interesting post with regards to Tyk2 and IBD

So much for the regulation of the active domain by the psuedo domain attachment of the allosteric I hibitor Deucravacitinib.

So it does not regulate as what we would percieve as regulation. No surprise here. How does is regulate Jak2 or jak3?

It cannot.

I put that down well over a year ago.

It act via an upstream STAT pathway.

It cannot pair with Jak3

It can pair ie heterodimerise with jak1 and Jak2.

That is about it.

Then ofcourse we had Tofacitinib originally classed as a Jak3 inhibitor.

It is not.

It is a Jak1 selective over Jak3 inhibitor which also habits Jak2.

Efficacy good in IBD. However, it clearly notall rickety boo in the areas of safety.

May l suggest that this is caused by the h0m0dimerisafion of Jak2 leading to EPO and associated heart related problems this causes.

Interestingly we had no detectable jak2 activity in our Phase 1 safetytrial.

That means we have no problem with hom0dimerisatuon of Jak2.

Allosteric Tyk2 is single inhibition

Our SDC1801 is dual Inhibition albeit very high selectivity of tyk2 over Jak1.

In addition we now have patent protection for 1802 in auto Immune.

Due to the lesser selectivity of tyk2 over Jsk1 in 1802 l amof the firm opinion that 1802 would prove to be far more adept as a treatment for IBD due to its profile.

Of course penetrating the blood brain barrier and CNS is possibly another string to the bow.

I see very little serious competition to our SDC pipeline inhibitors.

I doubt whoever sold or bought 500k shares has any idea either.

The price is subdued at the moment as it is what it is.

Regards