Member Info for sadoldgit

There wee 3 posts. A pessimistic post by funny guy effectively slating our compound one by myself and one by Ahfam.

I believe thread containing the 3 posts were removed as Ahf identified someone as a p...t.

Need be aware that there exist posters who will disrupt the general well being of boards. I merely gave my views as to why we cannot receive any update on dose escalation.

I gave the reasons for my belief as to why safety concerns ought not to be a problem based on our 737 compound of being acceptably safe at 800mg per day whereby Sareum in preclinical stated treatment if up to 1000mg per day. 737 has been used in some patients at up to 1400 mg per day in monotherapy whereby safety concerns at this level developed.

I then requested for a reply detailing on what basis that we might not hear anything on 1801 until.next year or a long time?

I would hazard a guess that a particular poster has requested the post to be removed on the grounds of being insulting albeit factually correct.

All quiet and a thread removed.

Part1 of trial should be fine. Sareum cannot release any material until decided by the safety review committee.

No concerns myself just a matter of waiting outcome of review committee.

I dare say when decision to continue dose escalation then a slight tick up in SP.

A fairly old but pertinent read to SDC compounds.

https://www.biospace.com/article/potent-selective-small-molecule-inhibitor-of-tyk2-jak1-selected-for-further-development-as-potential-treatment-for-certain-types-of-leukaemia-lymphoma-and-solid-tumour/

A good result for Momo Krone but more important indicates the tolerability of Jak1 and to a certain extent Jak2.

Jak 2 as we know and as TM stated that there are safety concerns which they believe are associated with Jak2

However both our compounds have significantly more selectivity over over Jak 2 and 3.

Our 1801Tyk2 jak1 also being more selective over Jak1 2 and 3.

Treatment dose for momo indicates 300mg . And being primarily of Jak 1 and Jak2 does indicate that all should bode well for us in the latter part of dose escalation study as we are primarily far more selective of Tyk2 over the other Jakis.

Regards

We should be able to trump Deucravacitinib in psoriasis and indeed other Indications. As Tim stated there will be some Indications where we will perform more favourable and other Indications where Deucravacitinib will prove superior. No such thing as being best in class at everything.

Tim and Co will have a very good idea of what indications we should prove to be better in.

We are after all Tyk2 Jak1.

The Jak 1 is around 5 x selective over Jaks 2 and 3 from memory.

Jak1 will Pair with Jak2 Tyk2 and Jak3

Jak 2 will Pair with Jak 1 and Tyk2

Tyk2 will Pair with jak1 and Jak2

Tyk 2 will not Pair with Jak 3

Jak 1 and 3 has proven effective in UC.

pure Allosteric Tyk 2 ( Deucravacitinib) failed to meet its end points in UC.

Question here is why should this all singing all dancing Allosteric Tyk2 have such a poor result in UC?

It is supposed to generate a healthy balanced immune system. If this were the case then why failure in UC

Am of the very firm opinion that for Tyk2 inhibition to work at its most effective that a suitable proportion of Jak 1 2 & 3 are required.

Whilst Tyk2 is clearly of benefit on its own it cannot be the be all and end all otherwise end points of Deucravacitinib would have been met.

To sum up it does appear that Tyk2 alone cannot overcome all problems with immune system in U C.

Don't get me wrong Tyk2 is a major leap forward.

But in an effort to minimise adverse side effects . the use of pure Tyk 2 has indisputable limitations

SDC 1802 out of the same stable. Sareum have developed 2 Tyk2 Jak1 inhibitors. Clearly there is a slight but distinctive difference. Clearly they have also discovered that a slight variation can potentially prove efficacy in certain cancers. Indeed inflammatory Bowel disease and cancer of the bowel are closely related as such IBD in the majority of subjects if left untreated leads to cancer of.

Regards and apologies if appear a little long winded as usual

Regards to all

In addition the contract will have also to take into consideration not only 737 with LDG which is fairly simple but we also have 737 with PD-1 inhibitor which has had a degree of preclinical studies. There also exists a vast degree of research work carried out by Michelle Garrett et Al. Primarily this work carried out will be the property of CPF.

Any on licence has to take in the whole caboodle of who has done what and who owns what and in which further in combination studies with other forms of inhibitor plus LDG and maybe other chemo with exception of platinum based.

For example CHK1 plus P13k with and without LDG were also evaluated by Michelle Garrett and similar qualified like minded personnel.

Now bare in mind that Micjelle Garrett originally used 737 with LDG. After early 2020 and maybe a short while before m Garrett were using prexasertib instead of 737.

Prexasertib was on licenced to Acrivon not many moons after this

Prexasertib has little, to no patent protection life remaining plus can only be administered intravenously.

So although this will take time l do strongly believe the wheels are motion to reach an agreement of some sorts.

You can take it that CHK1 inhibition is vital to many in combo therapies. It is that 737 must be aligned with right ducks ( of which there are an ever increasing number of suitable proposed candidates to choose from) to maximise potency and efficacy.

Definitely a project any legal team would love to get their teeth into.

Around 6 months from receipt of full data l would place a guess before any on licensing / partnership news. May come quicker but l doubt will happen due to complexity of preclinical studies (especially) and clinical work already carried out.

Regards

Good morning Seawolf. Pre clinical tox were first class for 1801.

No reason to have any concerns whatsover over the current escalation dosages.

If we take CHk1 that we're proposed at 1000mg (from memory it may have been 1200) max therapeutic dose set at 800mg in monotherapy.

The important thing here to remember is dose escalation will be increase in benefit v the down side side effects. Ie efficacy v tocxcity.

Tim.and Co are have always been and still remain very confident.

Take also into consideration that they are certainly not new to immuno oncology having been involved in the momecular composition in its entirety for 737, Aurora +FLT3 ( solubility of the compound issues pertaining to the oral route) and now both SDC compounds.

Dosages had been carried out up to 1400 mg per day for 737, but adverse effects had been observed and recorded at these dosages

They therefore have considerable expertise in formulating molecular compounds that both efficacy and toxicity acceptable areas are suitably met.

It may be quiet for a while here. However, any news with regards of partnership or Co development will propel the SP considerably higher and most likely new highs.

A waiting game at the moment. Experienced this here when we were 0.2p in old money.

Regards.

I have a very strong feeling that good toxicity results both compounds will be taken on by a pharma. There was a sense of intense urgency to enter 1801 into dose escalation trials.

The results being the precursor of any deal.

Regards

Apologies for link not working.

Just goes on to say that that basically UK are at the forefront of technological expertise and how crucial small minnow companies are plus large pharma don't realise the amount of work that goes into development of new drugs.

These small minnow companies basically allow the large pharma to survive. It works both ways of course.

Regards

Https://www-thisismoney-co-uk.cdn.ampproject.org/v/s/www.thisismoney.co.uk/money/markets/article-12326661/amp/Biotech-startups-scoop-1-3bn-foreign-capital.html?amp_gsa=1&_js_v=a9&usqp=mq331AQGsAEggAID#amp_tf=From%20%251%24s&aoh=16902745723451&csi=1&referrer=https%3A%2F%2Fwww.google.com&share=https%3A%2F%2Fwww.thisismoney.co.uk%2Fmoney%2Fmarkets%2Farticle-12326661%2FBiotech-startups-scoop-1-3bn-foreign-capital.html

Good afternoon C79.

CHK1 n it's own in monotherapy achieves very little. We have established a MTD with CHK1.

However in combination therapy CHK1 is becoming an increasingly important. There are preclinical studies which have been completed and indeed ongoing studies of CHK1 in combo.

The only case as far as l know is 737 in combo with platinum based chemo. Whilst platinum.based chemo is not new it is effective.

There is without doubt a determination here to produce excellent CHK1 in combo therapy in one form or another.

Michelle Garrett was looking at 744 in head and neck cancers many moons ago in combination with radio therapy. I am sure all these recently joined long term holders are aware of these past developments.

It will however complicate the process of on licensing 737. It has potential and this was achieved in combo with Low Dose Gemcitabine.

This is just the tip of the ice berg so as to speak.

SO had carried out some excellent preclinical studies. Sadly they halted all development of 737 in favour of concentrating all available resources on Momo. We in effect did the same with our very own Aurora + FLT 3 to focus on our SDC compounds.

I dare say ther are interested parties but there really is an ever increasing trend at the moment where certain forms of in clinical use treatments as well as preclinical studies for one reason or the other are focusing on CHK1 in triple therapy combination.

A while yet before any news of on licence/collaboration or whatever on this front matures.

The link you have just posted indicates effectiveness of CHK1 with Triapine and radiotherapy.

We are the only CHK1 inhibitor that l know of available to on licence or act in collaboration with.

It is not surprising therefore at the Interested parties contacting Sareum and forming an orderly queue were highlighted in the Sareum AGM in December.

Not owned by us as most of us LTH's know but we do have a 27.5% commercial interest.

Correct me if l am wrong but are the majority of compound protection patents not under the name of John Reader?

Regards

Https://pubmed.ncbi.nlm.nih.gov/37109350/

Fairly up to date info with regards to DDR pathway and chk1. Not mind blowing but does indicate the continued development in this area.

Good advice there Blastoid7.

That will be 3 groups interested in news. Sareum, the interested parties and us the investor,

There will be absolutely no problems with this first cohort escalation dose, of that l am 100% certain.

Sareum may state that their intention is put 1801 into phase 1b as in treatment for Psoriasis but on receipt of good dose escalation results ( not necessarily waiting until.the end) the window of opportunity is Indeed open.

It is a massive decision to make and for any company to invest hundreds of millions of pounds they need to be certain that there are no major toxicity concerns. The higher the established maximum treatment dose then the higher the value of our compounds.

Good news will land. Just a matter of when.

Regards

Jeez it is always the same here when things look pretty good yet with an element if doubt we have these claimed long term holders been here for years. By the the very nature of their comments they have either neither read any of the RNS's or important research reported on this BB.

What is their objective that make vain attempts to discredit posters ?

They are not invested yet make out they are. Traders they maybe looking to make a killing

Oh yes peeps I have been a long term holder for years look at my comments. Then proceed to sow elements of doubt. For those that are fairly new to this board they can appear to be an investor with concerns. Those of us that have been here years have seen cartfulls of them come and go.

Joined 6th of June 2023. Yes put a few little snippets of info out to give the impression you have been here years. The very nature of the questions you put forward along with the date you joined here suggest otherwise.

Do yourself and us genuine long term holders here a favour stiff and go out get yourself a life.

I am fairly certain you will not be missed but rather glad to be seen the back of.

Have a good day x x x

Busy with job change at the moment. Not have much time to add anything of significance here ATM.

What l will reiterate and l cannot stress the importance enough on is the results of dose escalation studies.

Sareum intention to on licence at late preclinical or early clinical stage.

We now sit with 1801 in clinical and 1802 at late stage preclinical.

The pivotal point will be safety of our compounds which can be evaluated on dose escalation studies. It will then up significant interest in not only 1801 but also 1802. By the very nature that should 1801 prove satisfactory then the safety profile of 1802 is virtually guaranteed and and opens up the very prospect of 1802 to be on licensed at late preclinical stage.

It is a possibility that a large pharma on the release of a good safety profile may indeed look to take on both compounds. Whether these taking over of compounds are obtained by on licence or by purchase of the company remains to be seen

Speculation here, and this is far from guaranteed.

If we take as a ball park figure a value of circa 1 to 2 billion per compound with a risk factor of 1 to 10. This equates at a very rough ball park figure of between 200 to 400 million

As progress is made then risk factor goes down and the price goes up.

Large pharma not like risk and the risk is primarily to do with safety and toxicity. As Tim and Co stated they are effectively requesting data.

We will be monitored very closely by the the interested parties as such of the nature and commercial value of our compounds. As many of us are aware the big pharmas pipelines are coming ever nearer to end of patent protection to be replaced by compounds of better efficacy and safety.

Look at it from the point of view of large pharma

With the current interest in Tyk2 and the belief by a company that tyk2 Jak1 inhibitor can out perform allosteric Tyk2 in some Indications then we sit in a very healthy position.

Tim and Co not getting any younger.

There will be much going on behind the scenes that we are not privilege to know.

Regards all and l will not be posting much on here for next few weeks. We are again at a waiting stage.

As the compounds are very similar with the Jak1 2 and 3 dictating the dose escalating dosages then thete is very little to require a dose ascalation study for 1802.

With regards now to 737 sareum have released RNS's which mention sareum in collaboration with ICR in some but not all RNS's

Clearly a person that posts that sareum do not mention collaboration in any news releases then states this is a fair clearly does not know what a fact is.

Regarding this fear factor of raising funds, someone explain to me why this is such a problem at the moment and the reasonings behind it.

Sateum have a cash runway. How long does this cash runway last?

My own opinion is that Sareum will be in the position to on licence at the the end of phase 1 a dose escalation.

Interested parties require safety data.

Once safety data received then formal discussions will commence.

Yes there will be other Indications other than Psoriasis but as development continues Indications where 1801 can have great efficacy and safety can be identified.

Up font payment of 50 million with milestone payments exceeding a billion is well within reach.

They way forward for 1802 is then paved.

Sooner or later 737 will come into play

It is not guaranteed and that is a fact but looking how the market is keen on the safety aspect of the Tyk2 compound which is believed to have greater efficacy when combined with Tyk2 then the figures l have previously surmised will pale into significance.

Regards

.

Sareum were involved in the co development of 737. From the point of view of chemistry it is Sareum that produced and wreaked the compound up to the final CCT245737. For the work and financial input they own a 27.5 per cent of the value if 737.

Technically Sareum were involved in the development of 737. End of.

Good morning citizen79. It will take a time to read through in depth and digest.

As l see it Tyk2 on its own has high specificity.

If we take it that Tyk2 is a regulator of the active domain ie JH1 via JH2 then in this instance in theory àll Indications should be manageable by Tyk2.

However, it is worthy to note that Deucravacitinib did not meet its end goal in UC. Jak1 and 3 have proven successful in UC. Clearly whilst Allosteric Tyk2 does have very high specificity it clearly cannot manage all Indications.

The question must be is to why this is the case?

SDC1801 Sareum belive that their compound will have greater efficacy than Deucravacitinib. As Tim stated at AGM there will be Indications where our 1801 will have greater efficacy than Deucra and vice versa.

In the essence of Allosteric Tyk in an aim to achieve a very favourable compound with regards to safety they have in doing so compromised efficacy ( clearly evident in UC)

In Indications such as Psoriasis l believe we will be head and shoulders over Deucra and some other Indications too.

We can't be best in class at everything l would propose but in more than 1 indication a definite yes. Interested pharmas will at present will be keeping a keen eye on dose escalation.

More than 1 party involved here

737 indeed complex. This will take months to conclude as we not only have the development work carried out by SO which has proven good clinical results with LDG,but also the further research carried out by the likes of M Garrett etc al.

Regards and always a pleasure to see you post.

MS is one of the many Indications of our SDC1801. Predictions were favourable for MS but have not heard or seen nothing concrete to support this.

Apart from Psoriasis it is all very quiet on the favoured Indications of 1801. Bioassay will indeed help.but this stage really can only arise around stage 1b as far as l know. We are not alone in this approach h hence why Psorasis is an extremely competitive market.

Despite that l dare say Sareum will have a good idea as to what Indications whether an unmet need or class leading results in some Indications.

By the very nature of them developing a Tyk2 Jak1 inhibitor they rill have a good understanding of the likelihood if success in certain areas.

Why tweak the molecules.

Similar with SDC1802 they have and continued to carry out translation studies. Developing a compound that has both safety and significant efficacy , n certain yet to be determined Indications. Sareum will not be releasing info on this as we look to be first and the less our competitors know the better.

So here we sit at the moment with a piddly circa 60 million market cap. We have not even anywhere recovered the losses over the MHRA delay or to be more precise unable to approve even though now we have been approved and undergoing phase 1 clinical dose escalation trials.

Regards