Member Info for sadoldgit

Offler. From the time l posted a lengthy reply in a link to you rrplying is 6 minutes.

Clearly you are unable to comprehend. Have you left school or uni yet?

Not sure of you age but l think you need grow up a tad and not leave yourself to being open to so easily being shot down.

The more knowledgeable we think we become in life so does the realisation is we know less than we think.

Life is life as we see as a perception as two people will see a the same event fro two different angles

Of course there will not be 1 Russian news report involved. That down to propoganda.

The BBC was workd class 45 years ago. They reported facts to humans.

Now they make up and put a slant to amd sekect news and minipulate the truth. That been going on for over 40 years plus.

Those that control the media and the minds of those foolish enough to believe control the world.

For once in your life open your eyes and realise what is going on. I amsure if the news media told you it wasgoidfor you to put your head in a gas oven you are simple enough yo believe.

In any argument there are two sides of a story.

You go to court

You have prosecution and defence.

Ptopoganda only prisecution and any defence is ruled out.

Tell me who is most trustworthy the police or a newspaper report from a journalist?

There is no integtity nowadays . That is ftom politicians above all the way diwn to those easily gooled or who have an agenda.

I am invested here and will continue to adc as and when l feel fit bases on the changing geopolitical outlook. That is as l see it. Not MSM

I grew out of MSM sround 7years ago.

Regards and have a super weekend all

Of course there will not be 1 Russian news report involved. That down to propoganda.

The BBC was workd class 45 years ago. They reported facts to humans.

Now they make up and put a slant to amd sekect news and minipulate the truth. That been going on for over 40 years plus.

Those that control the media and the minds of those foolish enough to believe control the world.

For once in your life open your eyes and realise what is going on. I amsure if the news media told you it wasgoidfor you to put your head in a gas oven you are simple enough yo believe.

In any argument there are two sides of a story.

You go to court

You have prosecution and defence.

Ptopoganda only prisecution and any defence is ruled out.

Tell me who is most trustworthy the police or a newspaper report from a journalist?

There is no integtity nowadays . That is ftom politicians above all the way diwn to those easily gooled or who have an agenda.

I am invested here and will continue to adc as and when l feel fit bases on the changing geopolitical outlook. That is as l see it. Not MSM

I grew out of MSM sround 7years ago.

Regards and have a super weekend all

You soppy little fool. It is the intent of the discussions What was the intent of the discussions whwther formal or informal.

You can make an informal statement that creates distress. You can make an identical formal stayement that also creates distress. Both can carry a custodial sentence.

The severity of sentence will very much rely on what the oroginal intent was.

Looks like you getting s tad of bullying there Chessgambiteer. What you state is indeed correct.

Now what the West use is that this was never agreed to. Easily brainwashed are some by Western media. Propoganda and its associated propoganda are more important than military weapons. Not my idea. The Chinese. Thry have 4000 years of history. How many years of history the yanks have in the USA? Vagabonds thieves convicts and criminaks that other countries did not want gormed the backbone of those tgat would end up controlling America.

Remember the cowboy and lndian films. The Infisns were akways bad invadind white Americans land. The effing immigrants shole the land from the Indians who were peaceful people who lived there for generations.

Now controlling the US you have warmo ger ifa president that has a hip on its shoulder. Typical of jock ancestry.

I digress here.

A link to info regarding NATO not pising a threat.

There are those on here that believe that as its nots laid downand digned for makes the NATO invalidates the non expansion NATO argument.

What these people fail tto understand that you to take into account was what was the intent of these promises.

Way beyond their level of comprehension.

Rather like the tax man and you are in communicstion with.

A mistake they will be quite understanding. No contract as such. Niw tgen go to individusl and Small business Compliance.

Basically they bully. Intimidate. Manipulate information. If you think tax manhas power think again

Tax man given me tax code of k932x as been trying to claim back previous 4 years pf allowable expenses for work.

It equates to just under 8k a year.

Submitted contract of employment stating

Paslips supporting. But no! Looking anything up to 40 months to resolve. Tax code is crippling as my allowable expenses are taxed. HMRC cannit reverse.

Anyhow enough of that.

What you require initially to dupport your claim is

https://nsarchive.gwu.edu/briefing-book/russia-programs/2017-12-12/nato-expansion-what-gorbachev-heard-western-leaders-early

Regards to all

No false claim there sonny.

How old are you?

Are you out of uni or the off the dole yet?

Meanwhile Russians test Oreshnik being fired from a mobile unit.

Uou are not going to defeat Rusdia tgat have been lied to and deceived by the West for 30 years.

The world is becoming very 1984.

Even history is rewritten to cover modern day agenda.

How many if you here right rubbish remember Cuban missile crisis?

How many here remember tge bews reports if Vietnam war. Civillians icluding yoing mothers with children being burned alive with Napalm?

The setting of houses on fire and subsequent shooting of occupants that tried to leave. Raping and then mudering of young eomen and girls by US soldiers. Thousands upon thousands of such cases. Only a few out of 1000's of reports were investigated. Those tgat recieved relatively liw sentences of a few years were released very very early. Pit down to stress on young sokdiers that were only following orders.

These are the sick people that controlled them trying to control the world now.

More should be done and dpent in trying to lppk after the human race and its planet yhan yhe destruction thereof. But yhen again we have evolution which now is not the survival of the fittest but tge survival of the most powerful.

Who is the most powerful?

The US with the largest mlitary, to including NATO or Israel that controls US politics, for its own gain of globalist world control?

Who are the real threat

China

Russia

USA

Israel

Looking after a countries security?

No try using ' domination over ' instead of security

Several brain-penetrant kinase inhibitors have been recently approved or are in late-stage development for central nervous system (CNS) indications, primarily for brain metastases in non-small cell lung cancer (NSCLC) and for multiple sclerosis (MS).

The latest approvals and emerging drugs include:

FDA-Approved Kinase Inhibitors with CNS Activity

Taletrectinib (Ibtrozi): Approved by the FDA in June 2025 for adults with ROS1-positive advanced NSCLC. It is noted for being a potent, CNS-active TKI with robust intracranial objective response rates in patients with brain metastases.

Alectinib (Alecensa): Approved in April 2024 for adjuvant treatment of ALK-positive early-stage NSCLC. Alectinib is known to have superior intracranial efficacy and can effectively control brain metastases.

Ensartinib: Received FDA approval in December 2024 for the first-line treatment of ALK-positive locally advanced or metastatic NSCLC. It demonstrates high brain penetration.

Osimertinib (Tagrisso): A third-generation EGFR inhibitor, it received expanded FDA approval in September 2024 for unresectable Stage III NSCLC. It has excellent CNS penetration and is a standard of care for EGFR-mutated NSCLC patients with brain metastases.

Lorlatinib: An ALK/ROS1 inhibitor, it is effective in treating brain metastases in NSCLC and was approved for broader use in this indication.

Zongertinib (Hernexeos) and Sevabertinib (Hyrnuo): These HER2-targeting kinase inhibitors received accelerated FDA approvals in August and November 2025, respectively, for NSCLC with HER2 mutations. Their CNS penetration is a key feature in treating brain metastases.

Good evening PC1954.

Tim is no longer CEO he is COO and l dare say it is Stephen Parker who decides who says what.

Reminds me of AGM 2024 Tim Mitchell asking Stephen Parker if he wanted him TM to read out the questions.

Tim was removed from position of CEO. Calling stepping down. They give reasons.

But no guarantee that is the truth.

Tim really has little powers and may well have settled for ok you get on with it and l will keep to 1802 and 1803 development.

Compounds need manufacturing.

Whoever stated the requirements for manufacturing of the compound for the tox trial clearly made and extreme balls up.

Potnak, why do you post incorrect non factual information?

The toxicology study was stopped that does not mean it is a failure.

If it were a failure they would not be tweaking the compound and arranging new trial.

I still believe conpany may be on an intended takeover and halting toxicology study will delay.

If this proves to be the case then they will also have 1803 in their arsenal. This is in an area of very high urgent umet need.

I think there are around 10 million new cases a year in the US alone. Alzheimers not the same as Parkinsons disease

It is a distinct possibility on selecting a suitable candidate and that phuccer has already been decided from the 6 compounds albeit requires optimisation which on its own is no mean feat.

The brain is very good at removing alien invaders.

Just because you have a compound that is able ti penetrate the blood brain barrier what happens to the compound. Is this compound reduced efficacy when suspended in cerebral fluid.

How is the residue removed from cerebral spinal fluid? How much of this is down to the excipient?

It all comes to he who waits so it is said.

But many of us are getting just a tad bit tired of waiting. We have no idea hiw far we are away from the finish line .

Regards

In a nutshell PC1954 , l would suggest TM has been working on new conpound fir BBB CNS since mid 2924 if not earlier.

Computational chemistry and compound desugn

Not just a case of getting an inhibitor into the brain. What will it di when it gets there?

Binding affinity.

There us a difference in inhibitors in the same chass a d some work better than others.

As an example 1891 v Breprocitinib.

One superior to the other. That is not down to luck

More likely if course to get a buyout with such a comound being developed in the pipeline.

We are sat at a very sweet spot.

Any news of positive development on this front will propel the SP considerably.

There really is nothing out thete st the moment to lead towards a cure.

Good morning now PC1954.

Merely pointing out that 1801 would not be put put forward for CNS indications.

That became ckear post AGM chat with TM. Difference between 1891 and 1802 resulted in 1801 being used for autoimmune and not wanting jaks crossing blood brain barrier.

1802 in oncology is not handicapped in same way.

We aee in effect sub dividing further.

Mot only are we looking at immunotherapy for auto immune but also pursuing compounds that can counteract nerve damage and it consequential repair.

We are aware of 1801 to treat SLE, not yet trialled.l know. But 1801 should enable the removal of debris allowing nerve endings to reoair. Requirement and preferred outcome to reoair nerve ending damage and reverse the symptons.

If successful which highly likely, all well and good.

1801 in its design restricts the amount of Jak especially Jak1 that can enter the brain.

The broader spectrum you treat and advantages thereof are offset by increase in off target effects.

1801 not to cross the BBB for CNS deliberate in its design.

But that vwry nature we should be able to provide a compound that can penetrate BBB.

There are indications in Central Nervous System which can be treated but can only do so by crossing the blood brain barrier.

Yhe peripheral nervous system which is outside brain and spinal chord has indications that can be treated without the need to penetrate the BBB.

This can alo raise questions as to why we have not yet had a repirt of 1801 appear in a journal.

1801 may have to give info on its mechanisms of working in SLE ( PNS)

This may also identify the boundaries or limits of 1801 and for all dusease indications of the central nervous system its inadequacies to breach BBB.

Molecule makeup may come into it and as yet no patent protection protection for possible new compound.

Sareum need be extremely careful as to what they submit in a journal , to give John Reader credit he addressed that at AGM 2024.

So all very hush hush around a compound at design stage.

To treat diseaese of the CNS will not happen with early repurposed drugs. They try but all have failed so far.

What is required is in effect a hand tailored compound specifically for CNS disease indications

An untapped market in areas of very high unmet need. Alzheimers is just one. Dementia?

Regards

1801 would not be put forward for CNS.

But 1801 has promising potential in Systemic Lupus Erothemotosis. Anyone know why?

All.down to BBB.

1t was not postulated that 1801 would be safe enough with Jak penetration of BBB.

An RNS indicatung further developments in Central Nervous System.indications should work wonders for SP.

Regards

I just had a listen to the AGM presentation.

How we stand against the competition.

Are we all aware of the PASI score and what it means.

Psoriasis Area Severity Index..

Good results have been attained ie the aim to reach a Pasi score of 75 in 12 weeks. That means a reduction in the area affected by Psoriasis by 75%

Only a few % have reached 75% in 12 weeks and yes a greater percentage at 16 weeks.

Breprocitinib was astonishing in that 90% acheived PASI score of 90 in 4 weeks. Yes you have read correctly!

This was at 100mg per day. But due to off target effects 100mg cannot be used as a daily doseage.

Now it is envisaged that 1801 can be made to achieve the same result or similar due to its significantly superior safety profile.

Note the mention of our 30mg is equivalent to Brepro at 100mg. A little bit of fine tuning of the formulatuon to incease the dose that can be taken as a single dose and we are without doubt head and shoulders above the rest.

In addidition an indication SLE Systmic Lupus Erothematosis also shown.

As we know this is a treatment akin to diseases of PNS as opposed to CNS.

Tim already new over a year ago they can penetrate BBB and a main reason as to why the Selectivity of Tyk2 over Jak1 is where it is.

31 molecules

We have looked at 6 compounds

3 were found to penetrate bbb

1 compound showed significant penetration and very promising result.

Optimisation to maximise potential.

It is not a dead cert but l would say we are almost there with it.

In effect 1801 phase 2 ready

1802 completion of preclinical

Early preclinical opportunity will exist to take into AD and/or other diseases of the central nervous system.

Dont get me wrong it is not a bad thing to have a moan at times. But dont concentrate on what we have not achieved concentrate on what we have.

We have 1 very probable best in class inhibitor way above all else out there at the moment and highly likely of CNS inhibitor compound of similar class.

Those interested look in from around 32 minute mark on AGM Presentation.

As such l continue to add!

Regards

Still very new are kinase inhibitors to CNS indications.

Most advanced is Biohavens BHV8000 that comnenced phase 2/3 trials in May this year in Parkinsons Disease.

Biohaven bought out by Pfizer in 2022 for circa 148 dollars a share ie 11.6 billion

Current Market cap 1.44 billion.

Pfizer therefore have Breprocitinib and BHV 8000.

JAK1 Tyk2 and Tyk2 Jak1

Now there are indications in the central nervous system ie the brain and the spine.

There are also indications in the PNS peropheral nervous system, effictively it is a messenger system from our extremeties to our CNS. Touch, movement are things hot /cold

Whether through disease or injury nerve cells become damaged and the debris created prevents regrowth of damaged nerve fibre (Myelin Phagotosis) This MG needs inhibiting as prevents the cleaning system to remove tge debris allowing regrowth ( that is as l understand it).

Pfizer discontinued Breprocitinib in SLE. Systemic Lupus Erythemotosis.

This is basically damaged nerve endings of the peripheral neuropathy system. (PNS)

It is generally easier to treat than diseases of the central nervous system. (Not crossing the bbb)

Other indications here of nerve damage

Diabetic neuropathy damage to nerve endings caused by high blood sugar levels

HyperthyroidIsm / Kidney liver disease again damaged nerve endings

Vitamin deficiency or excess

Sciatica when the nerves become damaged

Sjogrens syndrome which is a serious autoimmune disease where the bodies immune system attacks moisture producing parts of the body. Sometimes known as dry eye syndrome.

There exists no cure as such for these indications we can treat the symptoms but do nothing to halt or reverse the disease.

Diseases of the CNS

Parkinsons Disease

Alzheimers Disease

Multiple Sclerosis.

These are as such pretty much untreated as in halting progression or indeed reversing of the disease.

Early data and hypothesis suggests that what may be suitable to treat CNS may not be suitable for PNS. There exists urgent unmet need.

Attempting to repurpose old early generation inhibitors is not the answer.

Baricitinib for one. A jak1 Tyk2 inhibitor with Black Boxed warnings.

But you have to give it to big pharma, they really are interested in treating a dusease and not just how much money they can eek out of an ancient black boxed warning drug. He who gets his foot in the door first normally wins as will be minimum term contracts post apporoval.

The world market for these indications as such are basically untapped.

In effect regarding a compound we are not just looking at CNS here.

On a final note it does appear that large pharma more likely will buyout a company with a pipeline although they may only be looking at one or two compounds.

Enough from me

Regards

The jist being

Happy New Year c79.

In will be available in February's edition.

It is progressing well and Acrivon pressing on for a phase 3 clinical trial with ACR 368 formerly Prexasertib. Results pf this should prove

interesting.

Regards

Hi DP64.

No.problem.

1801 should fly when toxicology study gets ok from results post test.

Communications here required. Ie toxicology study with revised excipient commenced blah blah blah. No it started end of April or May, or we are expecting to start by end of month.

CNS should progress during this time and indicare yay or nay. At this point looking at possibility of being taken over.

The sudden advancement into CNS is not just chance. There is a dire urgent inmet need in MS and PD and more importantly a commercialusation potential.

If we look at what has been achieved with 1801 forgetting the kok up in toxicology trial it looks very promisingfor Sareum with respect to centrsl nervous system indications.

Taking 737 and 1801 into account both these have significant advantages over competitors similar pipeline compounds.

Regards

Excerpt from what seems an eternity .

'Promising Step in Psoriasis Drug Development

Scientists at Sareum, in collaboration with colleagues at the US research institute SRI International, have developed a novel molecule that significantly decreases psoriasis pathology in a disease model. This research has been reported in the latest edition of the Journal of Immunology*.

The potential psoriasis therapy targets members of the JAK family of kinase enzymes, which control the production of cytokines. Cytokines are signalling molecules produced by the immune system, usually in response to a danger such as invading pathogens. Cytokines responsible for psoriasis are thought to be controlled by JAK family kinases TYK2 and JAK1. Autoimmune diseases, such as psoriasis, can occur when the production of cytokines is not properly regulated and immune cells are overly activated.

In the psoriasis model system, the TYK2/JAK1 inhibitor molecule, known as SAR-20347, interrupted the psoriatic cascade of events and led to reduced activation of keratinocytes (skin cells that multiply excessively in psoriasis) and a reduction of pro-inflammatory cytokine levels.

Sareum and SRI International entered into a co-development agreement to develop TYK2 inhibitors for autoimmune and inflammatory diseases in April 2013.'

12 years and way overdue to come into fruition me thinks.

Regards

Good morning DP64.

The only deal then would likely be chk1 CCT245737. IF this is what you relate to then indeed there was a Licence Agreement but we have no ssy or input as 73% owned by CRT.

What l believe you are relating to is the 'transformational deal ' that was mentioned by Tim by end of year. SP rose. No deal and zTim was well.and truly lambasted by shareholders.

He has not and l doubt ever will maje such a statement again.

If it is this, then it is not 2015 at least 2 years earlier and would relate to Aurora + FLT3.

Nothing wrong with compound efgicacy and safety in preclinical. Problems arose through the oral route. There existed and still exists a solubility issue.

I hope this helps clarify your thoughts a tad.

Regards.

Head of the presidential office has been selected by Zelensky. The CIA are apparently happy with him. That latest out of Kiev today.

The question now is, is this a successor to Zelensky? If it is then we are on the road to ending the war.

Zelensky wont move but clearly the CIA can assist in this matter. Zelenskyno longerof any use to the US

Regards

Good evening gentlemen.

I were just looking at latest developments of Jak1 and Tyk2 in CNS indications.

AI response, however:-

"JAK1 and TYK2 inhibitors are emerging as promising treatments for CNS indications, particularly neuroinflammatory diseases like Parkinson's (PD) and Multiple Sclerosis (MS), by targeting key immune pathways in the brain, with companies like Sareum developing dual JAK1/TYK2 inhibitors that cross the blood-brain barrier (BBB) to modulate cytokine signaling, showing potential to control neuroinflammation and neuronal excitability. "

That not far behind a review of 1801 in sciemce journals. No mention of anyone else.

Tale into account here that in 1801 Patent description Alzeimers Disease and Multiple Sclerosis are put as a potential indications.

To me that would indicate we are better than any early generation Jaki inhibitor and most later generation Tyk2 Jak1 inhibitor.

Now talking to Tim post 2024 AGM he is very switched on with Jak1 and crossing the blood brain barrier, primarily with regards to safety.

1801 is much more selective of Tyk2 over Jak1 than 1802.

So this they can control. They will be aware of the effects. Now in essence this should indicate a high degree of effect certainly in the ability to penetrate the blood brain barrier.

Optimisation l dare say will be the selectivity inwanted off target effects perfectinh binding affinity of the chosen molecules

If we do not dawdle we are in the right place with the right molecules at the right time. Tis a out time the good Lord smiled upon us.

Regards