Member Info for sadoldgit

Https://pmc.ncbi.nlm.nih.gov/articles/PMC11279846/

Good morning Gunner68.He did indeed state it was a nice problem to have. But also followed with it might come back to bite us later on.

Clearly you remember the interview well.

Good morning Damion.

With regards to preclinical, at the time this was carried out, it is a requirement to establish a maximum tolerated dose.

In the event of a maximum tolerated not bring achieved it is regarded sufficient if a dosage if 30x the maximum therapeutic dosage is received without serious adverse events ie risk of facility.

It is not the same as long term toxicology trial.

It is in my belief highly likely that the events have occurred in trying to reach a maximum tolerated dose. In this instance it may be realised that this has come from tge carrier and not the TYK2 Jak1 compound itself.

Tim remarked in an interview with Sndrew Scott that they had not reached a mtd. No problems at over 30 times maximum therapeutic dose.

Oh he says we may have to go as high as 100 times.

Also bare in mind here that the dosing would be done intravenously st thus time.

Confirmed by the fact that the formulation of an oral method of taking 1801 fid not exist then.

Now in a human being 1000mg is maximum stated therapeutic dose.

1000 mg equals 1 gramme

100 grammes is a phenomenal amount of a treatment to take.

Also take into consideration that animals tend to be tested or trialled at higher doses due to the faster metabolism they have.

So the worst case scenario it could be concluded is restrictive dosage which also restricts fhe amount of 1801 that could be administered.

Correct me if l am wrong but is it not normal for the concentration of compound to carrier to remain the same irrespective of compound dosage size.

Regards

John Reader did talk of making a ' dirty batch' st AGM last year.

Was 1801 administered intravenously or orally?

I would suggest intravenously as more precise than the oral route in animals.

One thing we can conclude is thst there was a significant reduction in the 1801 active group.

It may be something along the lines of a contaminated carrier.

Animals euthanased and autopsy can be carried out.

Of course we are not informed of the dosing rates here.

There was mention of reaching a Maximum tolerated dose.

Could it be that the 1801 is safe at very high levels and the carrier not so safe

I do find the adverse events odd as in oreclinical trusks in animals dosing was carried in 2 different species at 30 times maximum therapeutic dose with no adverse effects observed.

What has changed?

Insufficient data at the moment !

Interesting read albeit long.

A lot if effort has hone into the germination of the active vompound.

Has the same attention to detail hone into the preparation of tge inactive vompound?

Providing the CRO has adhered to GLP. Practices there should be no difficulty in finding out the root csuse of the problem.

https://pmc.ncbi.nlm.nih.gov/articles/PMC7960226/

One thing we can defence us there gas not been clear and regular dialogue between sareum and thus internationally recognised CDO.

As usual the minimum amount if into released by Sareum.

PCS1954.

Do uou know the date thst the trial started?

Yes or a know will suffice

If uou font know the date it started then how can you post drivel that it only has one or 2 weeks left?

You either know or you do no not.

In my opinion for ehst ut us worth the trial was initiated some time before the actual .start of dosing.

I may be wrong but am of the belief dosng not started until around mid July.

As usual very little information given by SAR but just enough to panic people.

I am certainly looking forward to going to the AGM thus year. Questions will be asked!

NO IT IS NOT A FORMULATION ISSUE.

FROM WHENCE YOU DERIVE THIS DRIVEL.

THEY DID NOT FAIL TO REACH AN MTD.

THEY ACHIEVED 30 FOLD OF MAXIMUM THERAPEUTIC DOSE WHICH IS SUFFICIENT IN THE ABSENCE OF REACHING AN MTD.

SO WHST IS THIS KNOWN FAILURE YOU CLAIM?

PURE BS!

HI DP64..

It is certainly not a problem with 1801 or Sareum.

Read the RNS for what it states.

Regards

Good morning Rebster408.

Since this study will be documented from bumble to breakfast time the route cause should be easy enough to identify.

Specification of the inactive compound, over dosing .

I have witnessed cases my self whereby readings have been calculated at a factor of over a thousand under read.

It is a delay and now wait and see what the next steps are.

Regards

Toolkit

'The reality, is the tox studios were only to test the safety of the molecule. It's taken years and failed. This studios had nothing to do with weather it works or not.'

Safety has already been tested in SAD and MAD dosing.

If it were a problem with the molecule then it would be in the active group st a far higher incidence than inactive group.

Correct Colbaltblue.

A delay of course being we are where we are 12 months ago.

Investigation required to see if tge CRO are culpable.

Good morning Colbaltblue.

My views are close to identical to those of BB.

The failure of long term toxicity trials is not an outcome. No indication in MAD and a clean safety profile as stated by John Reader in the interview.

Why some here postulate doom and gloom on our compounds beats me.

Prices are in my opinion are manipulated by traders. Similar to crypto in a sense .

All jump on a rising price then bail out without really knowing what they are invested in.

The likes of Avacta, Hemo, IMM and Novacyt have all been hit with the downward pressure before news is due.

I have watched the presentation and the only irritant being looking at developments of CNS candidates early in 26. I trust thus will be no different yo the early in the New Year by Stephen Parker.

1801 progresses nicely the toxicology as l see ut nothing mire than a formality.

As l gave asked before those that doubt the safety put their reasonings behind it.

The major concern to some us efficacy.

Let me remind you that Deucravacitinib was given a clean profile and all it has achieved is a mediocre improvement over the placebo in Psoruasis

4 billion dollars.

Nothing to do with efficacy in Psoriasis.

Sotyktu can be trialled in whatever indication BMS see fit with no serious adverse events or severe problems with long term use due to its safety profile.

We have a clean safety profile as stated by John Reader. I suggest that that disagree or doubt contact John Reader and not spread fear and doubt on here.

With regards to efficacy we should prove superior to deucravacitinib in iome indication

We are a dual inhibitor ie Tyk2 Jak1

Important for inhibition of interleuken 10 that Jak 1 inhibits IL'10 receptor 1r and Tyk2 inhibits IL-10 receptor 2r. Both sub units.

No Jak2 activity detected.

Many here do not understand why this is so important.

CLEAN SAFETY PROFILE!

An A1 generated excerpt below.

Some JAK inhibitors don't penetrate the blood-brain barrier (BBB) because they are too large, are water-soluble molecules, or are substrates of efflux pumps like P-glycoprotein (P-gp), which actively pump them out of the brain. While JAK inhibitors are generally small molecules, they still need to possess specific lipophilic properties and not be recognized by these efflux transporters to cross the BBB.

You can Google ' why dont some Jak inhibitors cross the blood brain barrier' and use this to start your research.

Sareum new over a year ago that Jak 1 they have can cross the BBB.

If we look at it in greater detail we can also conclude that Sareum were aware of the potential for their Jak compounds to ornetrate the BBB as designed/ formulated 1801 not to have or at least minimal crossing if the blood brain barrier.

Clearly they can formulated a compound or compounds to prove effective as at first you must have a molecule thst can penetrste the blood brain barrier.

A huge potential here with the added advantage that the molecules subject to selectivity have indicated a very favourable safety profile.

Regards

Gold morning JBond007.

You appear one of the most balanced and knowledgeable posters on here irrelevant of hiw long you have been here or much you have invested.

SDC1801 does look to me as first class best in class a potential world beater.

Strategies change for companies over time.

Pharma us corrupt and l have pointed thst out on numerous occasions with in depth accurate reporting.

The same can be said with regards to efficacy sns safety profile of 1801.

The more you look in depth and try to understand the data the greater faith you have in tge compounds.

Most here dont understand fir what ever reason.

Simplistic dumb arguments come to mind such as if it were that goid why has it not been bought out yet?

CNS diseases and involvement in developing in this arena is vital to maximise potential commercialisation value.

I can understand the general feelings regarding going on and on with nothing of any financial gain indicated o the horizon

However l do feel we are on are on the home run.

Regards

Hello Jbond007.

I have not watched the interview yet.

I am not overly concerned with taking on development for CNS diseases.

Many early generation inhibitors being pushed into Alzheimer's and Parkinson's disease in a vain effort to jump on the band wagon.

I have posted before on this and have pointed out the advantages with regards to increase in commercialisation value.

Our SDC compounds sre proving very safe. I forecast this over 3 years ago.

Of course in the ideal world you need proven safe compounds.

Advantage here for us in having clean profile.

How many other competitors out there have the benefit of a clean compound to begin clinical studies in diseases of the CNS.

A1 generated response on investment returning to CNS indications. It does not do justice to the topic.

'Big Pharma Resurgence: Following a long period of reduced investment post-2008, major pharmaceutical companies are renewing their focus on CNS disorders, as seen in significant acquisitions like Bristol Myers Squibb's purchase of Karuna Therapeutics and Pfizer's acquisition of Biohaven.

Biotech Leadership: Smaller biotech companies played a crucial role in sustaining CNS research, developing innovative pipelines that have now attracted major investments and partnerships.

Rising Deal Activity: Overall deal activity in the CNS space has been increasing for several years and shows no signs of slowing down. '

'

It is the biggy at the moment.

An poorly mined gold mine st the moment.

Regards

Thankyou Cobaltblue.

AI generated SMKI below.

AI Overview

+14

Demand for small molecule kinase inhibitors is high and growing significantly, driven by the increasing prevalence of chronic diseases like cancer and inflammatory disorders, advancements in targeted therapy, and the expanding therapeutic scope beyond oncology to include neurodegenerative and autoimmune diseases. Market growth is further fueled by continuous technological innovations, rising investments in pharmaceutical R&D, strategic collaborations among key industry players, and the inherent advantages of small molecules in terms of pharmacokinetics, cost, and patient compliance compared to macromolecules.

Note the neurodegenerative diseases inclusion.

Good morning Cobaltblue.

A new phone and predictive text not good.

Good morning has turned into gold mining.

You can change it but chooses to revert back.

Plus have cut on end of thumb.

Apart from that all fine

As long as yge medication gas benefitted you then yhst us all.that matters Salford Red.

Many of the older drugs drugs are now being offered at negotiated liver prices as new safer treatments become available.

Not long before news will arrive.

RINVOQ (upadacitinib), approved in August 2019, is another blockbuster drug, which is a selective JAK inhibitor used to manage multiple inflammatory and autoimmune conditions. RINVOQ achieved impressive global net revenues of USD 5.97 billion, a nearly 50% year-over-year increase, highlighting its growing clinical adoption. Of this, USD 4.26 billion was generated from the U.S. market, reflecting its strong domestic performance and therapeutic impact.

You can but sometimes without success click on link of Jak inhibitor market for further information.

Https://finance.yahoo.com/news/tyk2-inhibitors-market-drive-enormous-213100459.html

Take a look at the revenue if upadacitinib Rinvoq and see in mind it has black boxed warnings fir serious adverse events