Member Info for sadoldgit

I don't believe we will find a maximum tolerated dose in the maximum dose of 300mg per day given in the escalation range of 5 to 300 mg per day.

Should all go well in the continuing dose escalation studies then l am certain this will provide the required safety data needs that our interested parties will be looking at prior to serious negotiations taking place.

However, do not rule out the possibility of a deal of any sort being struck before we reach the end of dose escalation studies if the price is right.

As Thoth2 said many times expect a bumpy ride

Regards especially to those that have taken advantage of the recent drop.

Looks like the large sells that look to be an individua or Thoth2 estate for whatever reason have been exhausted. I would expect a gradual rise on this Sp and low spread. Good buying opportunity for sure .

I don't think we are due news imminently but Sareum.have been known to surprise. Dose escalation at the given levels should pose absolutely no threat as doses derived from Jak1, 2 and 3 from current compounds in clinical.use.

Worth a quick read H5N1 flu.

https://www.cytokinestorm.com/

How long are Sareum funded up to Sfif?

I think you will find it will.all boil.down to dose escalation studies. Good results . Good results are what the interested parties want.

Better than all the rest Chk1 inhibitor toxicity and safety results. No mycocardia problems encountered as has been with others. That is where other inhibitors have fallen down.

Our compounds have had a phenomenal amount of research put in to not just obtaining efficacy but also safety

Once a safe limit is established we can then concentrate on efficacy. Efficacy will be dose related. We will be using bio markers to predict the efficacy in other Indications.

These dose escalation trisls are the pivotal point.

They are not going to last forever.

As Tim stated in the AGM the interested parties ' well give us some data' once data is received and analysed then serious discussions will proceed and not before. We now need to demonstrate that all the work gone into development of SDC compounds prove their potential value.

Thir objective is or will be to market 1801 and l am of the firm belief we will not need raise funds via dilution. It will be there as an option yes.

On licence deal of comparable compounds up to 4 billion and we are looking at a market cap at present of one seventieth of that amount for one compound..

But l will stress again a large pharma will not be investing hundreds of millions of pounds unless they have suitably adequate data. I got in anway think that Sareum will let it go gor peanuts either

They will k ow better than anyone here the value of the compounds or at least ball park figures.

Regards

Regards

I agree a single seller most likely the culprit here. We had Thoth2 that died late last year so would hazard a guess that those that have benefitted from his estate have sold their share .

On a train back to Thurso the signal us poor so not able to look at much posted. I am surprised that there has not been a plethora of late buying this afternoon.

Nothing to suggest any bad news on the horizon as some may suggest. There rill be those that will paint a bleak picture. What we have is good, very good it is just taking a damn long time to reap the rewards.

Regards

Good morning belhus. Definitely not deserted

Been busy travelling Thurso to Suffolk and back again.

Confident all will be fine here it is no news syndrome and a few who know who they are will so seeds of doubt. I looked a couple if times recently and even see deliberate misinformation stating someone had reported a death. Desperate and disgusting what some individuals will sink to, to be able to get in.

Ought be no safety concerns. 1801 will fly through these lower dose escalation studies.

Until positive dose escalation results become news or any developments on 737 then people that have an agenda will.post as much negativity as possible. Integrity is very rare these days.

So much negativity and seeds of doubt laid on a potential best in class multi million dollar dual compound. DOSE ESCALATION RESULTS ARE ABSOLUTELY PIVOTAL.

Regard to all GLTH'S

Yes tis a very good article there C79.

Sareum were seriously intent on getting 1801 into clinical trial. Data needs to be fed back to interested parties. This indeed will be the pivotal point.

i would suggest that the discussions with interested parties are warming up. But of course to reduce risk safety data is maust for any interested party. Once past this point we can expect offers to be put forward with the added bonus that this will pave the way for SDC1802. That as we know is well protected by patent.

Just a waiting game at the moment ( not a surprise to many here)a and if we look at what we have in its current stage an 80 million pound market cap is peanuts.

The Aussies had no problem working it out ,why did our authorising bodies not have the ability to do the same? One thing we can be certain of is that on the receipt of good safety profile it will put our MHRA to shame.

Regards

From the AGM. Come back to us when you have the data.

An astute post there Lazarus.

GSK bought out the Tesaro pipeline for 5.1 billion. None of these compounds have anything in common with 737 .

These compounds have been heavily pushed into commercialisation in areas of high unmet needs ie lung and Ovarian. they were approved for use by the EU albeit with concerns on safety. But as first in the door it will require someone else to knock them off the pedestal. GSK are not going to fork out 5.1 billion then spend money on developing a product in an area where they are already entered into that market. Neither would they want it to go to a competitor. The surest way to pull in the big bucks is shelve 737 or delay development for as long as possible.

Much development has been undertaken with regards to CHK1i's. It will take many weeks for a company to fully understand these developments. WE must understand that the value of 737 is not in monotherapy but in combination either with LDG, PARPi, WEE1 or a PD-1 inhibitor as main examples. there are others. Preclinical outcomes vary from good to verging on outstanding.

Monotherapy has established the PK and toxicity of 737. 737 allows LDG to be used as opposed to high doses of Gemcitabine. Gemcitabine has toxicity and adverse effects at high doses.

ideally we would be heading down the road of CHK1i, LDG plus a PD-1 inhibitor, that is my current thoughts and it has also been mooted in medical journals.

The question here is what type of company will take this type of ask on?

With our own SDC compounds ,a major pharma may very well be interested in 1801 or 1802. As Tim stated a while ago Pharmas tend to go for either oncology or immunotherapy. However he did not rule out the possibility of both. to the contrary he said if they want them both then they will have to pay the price,

A major pharma will want data to satisfy at first the safety and then the efficacy in an indication or indications.

Although no indication of raising further funding this in itself does not appear to be a dire urgent need for Sareum.

Options therefore can be that there are 3 likely outcomes.

1. Ongoing discussions with reagrds to 737 regarding a deal in whatever form likely to conclude in the not too distant future.

2. A pharma either to on licence to, or a partnership for SDC1801 ( subject to satisfactory clinical dose escalation studies)

3. The raising of funds via investors.

oO the upmost importance is good results in the dose escalation studies that is the main precursor that will provide data that will attract the attention of interested parties.

Pesronally I see no problems with dose escalation but would be interested if there are any affects if taken with certain foods that may influence uptake.

I also make no bones of the fact that in the areas of immunotherapy the competition is becoming increasingly competitive.

Regards to all

A fairly expensive drug from the US circa 40k plus per year if taken for the full 52 weeks. Provided of course by our NHS.

Very few drugs of UK origin around l may add. MHRA do not appear to have any problems approving drugs for use from the US of A.

The plethora of drugs from the US heavily marketed directly at our NHS was forecast nigh 30 years ago.

On the plus side it does reinforce the importance of Jaki's as a treatment especially where cancer is concerned.

Regards

Pronai Therapeutics would have known how CCT245737 was progressing in trial prior to taking on the licence.

Whilst we are not at present treating an indication ie Psoriasis we are still going through a vital phase with dose escalation studies.

Should we take it that 1801 has commendable safety profile in dose escalation studies and the theoretical attributes of efficacy of dual inhibition over allosteric Tyk then on confirmed good safety profile expect a deal of some sort to arise fairly rapidly. I dare say any interested parties who we are in communication with will be kept well up to date on dose escalation data.

If allosteric Tyk2 was the mutts nuts or the dogs danglies, whatever you want to call them, it would have reached the objectives laid out by BMS for Deucravacitinib.

Ask yourself a question here. Why did it not work in UC? Are we at the level of thinking of years ago? Broad spectrum inhibitors 1,2 and 3 intended to treat everything or so they thought. Not selective enough and hence toxicity problems and safety concerns, black box warnings too.

Now apply the same methodology to allosteric tyk2. In an effort to provide something which is ultra safe it may well be too selective. Allosteric tyk2 does not directly treat the active site. However it does regulate the active site.

What happens if this level of regulation poses insufficient benefit to the active site? Would providing a higher dose prove beneficial?

As Tim stated several.years ago they have what they believe is the addition of an optimal amount of Jak1.

In addition to this we have two similar but non identical Tyk2 Jak1 compounds.

A lot to go for and pharmas are going to want to see results before they start dipping there hands into their pockets.

Most likely outcome here is an RNS involving a deal of some sort. A little early yet but give it a couple of months.

Regards to all

Great Post Num4 there is really nothing that can be added to that.

I remember around early 2020 Tim saying we are 'not experts in biology but what we are very good at, is chemistry.

Attention to detail will pay off and separates the wheat from the chaff.

Dose escalation study results are not only what we are waiting for, but also the interested parties that require that safety data. I am of the firm opinion that on satisfactory results in dose escalation that it will not remain in the hands of Sareum for long.

I will also add that the dual approach ie Tyk2 Jak1 will prove to be superior to Deurcravacitinib or any other allostetic Tyk2 inhibitor in efficacy. I cannot stress the importance of good dose escalation results enough.

Regards

Interesting point there C79.

It does indicate the importance of CHK1 in treatments in certain difficult to meet cancers.

A possibility here of Aurora kinase and Chk1i in combo. We do have an Aurora FLT +3 that has been shelved due to solubility issues with the oral formulation.

Early stages it is.

Surely must raise some sort of interest here amongst the pharma's

Regards

Definitely worth a read. Long read but you can skip much of it.

https://patents.google.com/patent/EP3528806B1/en

Not sure if relavent at this time but had occurred to me some time ago as the compounds are similar but not identical that maybe 1802 may be eyeballed for IBD which is auto immune disease. In many cases IBD can lead to bowel cancer and hence in possibility 1802 a back up to 1801 in this indication.

I may be barking up the wrong tree or just plain barking.

Regards

BH459

There are several patents which protect our SDC compounds . we have 2 compounds 1801 and 1802.

These patents protect the molecules which make up our compounds ( of the upmost importance) and also the manufacture of ie crystallisation of a compound.

Whilst both 1801 and 1802 are covered by these patents and afford some protection, 1801 has not in itself received a patent that specifically covers 1801. The patent for SDC1801 here relates as to what the compound will be used for ie immuno therapy.

Interesting point here is 1802 is in the process of patent application for SDC 1802 outside of immuno oncology if I have understood the RNS correctly. I know that there has been mentioned that SDC 1802 can or maybe used as a back up to SDC1801. The exact detail or reasonings behind this is not known to us at the moment. Tim and Co clearly in the know, but looks like they keeping that one under their belt. Translational studies still on going with 1802.

As far as I know we are the only Tyk2 Jak1 in immuno oncology.

Regards

One further snippet of info in the link below.

This was from DEC 2019 and indeed points to an effectual treatment of certain cancers. Triparna Senn.

I am of the firm opinion that had SO not ceased development of 737 we would be heading

towards clinical approval. Effectively we have been shelved for 3 years enabling perhaps lesser effective treatments to be approved for clinical use in areas of high unmet need.

Possibility here ( but in no way guaranteed) of development with a pharma. Considerable dialogue will need to take place before a deal of some sort is struck.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7141083/

The only up to date relevant info with regards to 737 in link below.

737 in combo has been trialled in combo with LDG. High doses of gemcitabine circa 1000mg and associated with myelotoxicity.

There is much to be done on this front and whilst we have received info on phase 1 and 2 clinical studies there will be far more potential with regards to combo involving immunotherapies.

PD-1 and PD-L1 whether alone with CHK1i and or in combo with LDG warrants further investigation, as 737 in combo with LDG was well tolerated and the use of PD-1 inhibitors have already been approved for clinical use. ( this has been specifically mentioned in journals). We have not had any detailed data for SRA737 in combo with LDG and immunotherapy specifically relating to the rationale behind their at one time ' finalising of trial design.'

Would put an educated guess that the RP2D of 500mg per day plus LDG at 250mg per day could be used as a baseline for the inclusion of in combo with PD-1 inhibitor.

https://aacrjournals.org/clincancerres/article/29/2/331/713982/A-Phase-I-II-Trial-of-Oral-SRA737-a-Chk1-Inhibitor.

Regards

https://aacrjournals.org/clincancerres/article/29/2/331/713982/A-Phase-I-II-Trial-of-Oral-SRA737-a-Chk1-Inhibitor

As far as i know from memory ,reports available showed very good results with 737 in combo with Gemcitabine but unacceptable toxicity issues with cisplatin ( platinum based therapy)