Member Info for sadoldgit

Goverment and MHRA

https://www.gov.uk/drug-safety-update/janus-kinase-jak-inhibitors-new-measures-to-reduce-risks-of-major-cardiovascular-events-malignancy-venous-thromboembolism-serious-infections-and-increased-mortality

Firstly thankyou DP64 for appreciation.

Secondly l believe there is so much behind these further toxicology studies.

There is a link that l will post that was compiled 2023.

Mainly looking at myocarditis and the inhibitors effects thereof.

So let's take a look at the options the board have regarding on licence and buyout.

An on licence will come with upfront payment and milestones.

Milestones are not paid until they are met and this runs right up to commercialisation

How far is this away?

In an indication such as Psoriasis you may be looking at 3 years plus.

Within this and as phases are reached information and data is compiled with regards to adverse events whether through of target effects as well as on target effects.

Since the long term toxicology in effect has not been established this will be reflected in the monies offered by an interested pharma.

Now if we look at gaining the prerequisite long term safety data results this can be used as a bargaining chip.

This applies to on licence as well.as buyout.

Whilst it is possible for Sareum to continue to raise funds taking us into phase 2 in an indication we do not have anywhere the considerable amount of funding to open clinical trials in multiple Indications.

We require the financial input of large pharms as well as the influential clout that they carry.

As a financial contributor to the MHRA by Bill Gates l don't believe any pharma has interests in suffering the same problems with the MHRA.

Long term toxicology studies will enable negotiations after determining how safe the compound is irrespective of what indications are proposed to exhibit satisfactory efficacy.

Tom and Co are not getting any younger.

I am of the firm view that they strongly prefer a buyout as opposed to running a company with on licence and milestone conditions that run for many years.

Although not quite the same CCT245737 was on licenced to Sierra Oncology in 2017 and after a promising period of development nothing.

Delay tactics with the politics of dealing with a buyout cannot be ignored.

My reasoning is completion of toxicology studies, complete SDC1802 to end of preclinical.

I intended to ask how far are we from completion of preclinical study completion are we for 1802.

I will conclude in as far as l can see a buyout for the company being vastly preferential by the BoD.

I did not ask Tim about a buyout.

It was given to me that of course a buyout maybe an option they would take. Followed by comments of an ageing board and Tim looking at time to spend on other activities outside the time consuming commitment to Sareum.

They have awarded themselves with considerable share options. Most likely to offset some of the catastophic damage carried out by RF.

Why issue this amount of options if you have no idea what will be the in the near future of the company.

I suggest that in discussions with interested parties that saleability value range ha

From 2023

https://investor.roivant.com/news-releases/news-release-details/roivant-and-priovant-announce-results-phase-2-study-oral

Oops silly me forgot about Ropsacitinib the Tyk2 Jak 2 inhibitor for Psoriasis!

Not sure how the Rusdian vaccine got there but best ignored me thinks

Riovant, the pharma that is developing Beproitinib has a markey cap of 8.37 billion dollars.

I can find nothing else in its pipeline.

Pfizer has 25% ownership.

The safety profile as far as l can read into as the same as other Jak inhibitors.

I will delve into this more deeply over the weekend.

I believe as far as l can see 7 Indications that priovant are expressed as suitable for Beprocitinib.

We have Priovant with this first in class dual inhibition Tyk2 Jak1 inhibitor and as l say can find no other development drug in the pipeline albeit approval has recently been given approval in one indication on November 2024.

We sit with a market of just over 30 million.

Priovant has market cap approx 250 times higer ie 25,000%.

Agreed we are at a far earlier stage of development in 1801 and of course we do have 1802.

Indications so far that we are superior to Breprocitinib at least .with regards to safety profile

It makes predictions of 500 million takeover look incredibly cheap.

It makes an on licence of a billion plus including milestones look even cheaper.

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Regards to all

Good question HbD

More of a positive sense of direction. I would not use the term optimistic but they did appear focused. More of a sense of this is what we are doing as opposed to ' well we will see' if we can do this or ' hoping for this' and that.

Meeting was a little short, l felt and could have done with more members to ask questions.

No need for RF orientated questions as l think they have especially Tim suffered in this respect.

A sense of direction and being focused on getting a deal done in 2025.

I did ask Tim about the 1801 performance to date and that it had performed better than expected.

Clearly he was very pleased with the results.

A new you will start soon and the ' meat on the bones' data is now out for all to see.

I did ask about feedback from the so called interested parties who said 'well show us some data'

That data and interpretation of is now available.

I don't believe an interested party will hang about waiting for toxicology studies to complete.

1801 not suffering from or likely to suffer from boxed warnings. Too much attention to detail with regards safety.

Indeed it us important to have safety as otherwise the efficacy is compromised by DLT.

I don't think we will experience dose limiting toxicities anywhere up to Sareum stated maximum therapeutic dose of 1000mg per day.

We,will not be best at every indication with regards efficacy but we will be best in some.

The likes of Tofacitinib, Baricitinib and one or two other early Jak inhibitors that have boxed warning ( yet they are still approved for use) are way past their use by date.

Far more effective compounds developed and being developed now which in my opinion should bring an end to the early inhibitors with a multitude of off target effects.

Big pharmas have enough clout to extend life by repurposing, but just delaying inevitable and just to add many are coming to the end of patent life.

I wonder how far we would have progressed had we not had problems with MHRA, would we on that nigh 12 month delay been able to secure a better form of funding than the RF disaster.

SP would have been a lot higher too.

Very little was mentioned around 737 except for shares and conditions that may be put in place with regards to selling. So although should we receive we may not be able to sell.

The important point here is where the focus is on and whilst a almost insignificant payout may be made it pales into insignificance with regards to our 1801 and 1802.

Regards

You are more than welcome PCS1954 along with wishing you a speedy recovery wishing you a happy Christmas and an extremely prosperous 2025!

Regards

I did ask Tim if the current long term toxicology studies were a result of the MHRA.inability to grant.

Not a clear cut yes or no.

I asked about GLP and were the early preclinical studies in compliance and conform to this code of practice.

Tim was adamant that all the work undertaken was GLP compliant.

We have contacted them he said with a degree of irritation but we have not received a response.

He said following Brexit many people were lost ie returning back to European country and those that were left were scattered over the country with most being posted up North.

As as he could tell there was only one person in the MHRA that dealt with clinical trial applications.

He did not use the word incompetence but described in similar manner.

As much as we have written to them they will not reply as they will not admit they are wrong were his exact words.

That about it.

Good evening funnyguy.

There was no mention of 2026 or 2027.

I personally believe we will be bought out in 2025.

No piddling about with milestone payments that will take a couple of years at least to come to fruition.

Compounds have a potential worth which Tim put a value on of circa 800 million each albeit no given indication at to what stage and one can rightly or wrongly say that is the value placed at that moment in time.

A takeover of around 750 million is my gut feeling.

That would equate to around 6 pounds a share.

It is not far off the view of BB who posted a figure of around 5 pounds a year plus a few months back.

What is important is the development of 1802 to complete preclinical and l believe this may be a reason for not putting 1801 for clinical trial 1b due to costs so funding a tad more focused on completion of 1802.

We then have not one but 2 marketable compounds of which 1 will be in cancer.

I will state and as Tim has pointed out before thus field of medicine is becoming increasingly competitive.

We are now with validated data report in a position to state we are better than our closest rival Beprocitinib.

This was a point that Tim made to me.

The discussions that took place post meeting are clearly off the record.

Genuine down to earth reasonings , that l perceived to be very open and honest.

Whilst Tim did not say there will not not be an AGM next and indeed stated he would like to see me at the next one, he did mention being open to takeover should the opportunity arise.

Tim is 64 and Tim l believe stated John R being a quite a bit younger was 52.

That is it.

Very little l can add to reflect what l garnered from the meeting..

Oh yes just a tad.

Regards

'Harmful effects

JAK inhibitors can have harmful effects on the CNS, including:

CNS demyelination: A patient with rheumatoid arthritis who took the oral JAK inhibitor tofacitinib developed reversible multifocal CNS demyelination.

CNS sequelae: A patient with Aicardi-Goutières Syndrome who took baricitinib for over four years experienced CNS sequelae, including global cerebral atrophy, diminished white matter, and calcifications. '

Regards

Good evening Krone.

When speaking to Tim regarding the difference between 1801 and 1802 the molecules used in each are the same to make up the compounds.

When asked as to the reasons it were as follows.

Entry via crossing the blood brain barrier was OK for cancer but believed to be not good as far as Tim was concerned in auto immune.and Tim did not believe to have a possible problem Jak1 entering the brain.

Now if we look at 005 by Alumis it is a Tyk2 allosteric inhibitor with no Jak1, 2 or3.

I believe in patent description we are looking at 1801 for MS and Systemic Lupus Erythematosus

It does indicate that Tim had concerns here regarding Jak1 crossing the brain barrier.

It was after all based on what Tim stated a ouple of years back saying that they believe they have utilised the optimum amount.

Ot really is a balance. In effect here you are creating highly selective compounds that target different Indications.

Some will work better than others and clearly it is becoming apparent that their exists subtle but distinct differences.

He was clear on the not wanting the Jak1 crossing the blood brain barrier.

Ok for cancer but not auto immune were his words.

However, Jak can be used on the brain as such to reduce inflammation.

We cannot have a compound that is best at everything each indication requires a precise amount of selectivity.

I note that Alimis has different Tyk2 inhibitors to treat a variety of different Indications including psoriasis.

That the best l can do.

Unless Tim happy for me to keep him company for a few days whilst continuing development on 1802.

Regards

In all honesty funnyguy l am of the firm opinion that the meat on the bones clinical report is finalised and signed off that sareum will onlicenced or taken over in 2025.

The board were calm and had a sense of direction and purpose.

They are now pushing 1801.

I am not saying sp shattering news in next few weeks.

What l am saying is as from now it is likely that on licence or partnership in any form is very likely with increased prospect of takeover.

The after meeting discussions were worth the visit alone.

I believe myself that 2025 is the big year for Sareum,

Before the meeting started there were 2 persons discussing Scancell ? And Sareum to which they were saying that nothing companies were drastically undervalued.

That is as much as l know and gut feeling is we will be taken over as opposed to on licence or pursue 1801 into phase2 trials ourselves.

Regards and have a good day

HbD good evening.

I asked Tim the difference between 1801 and 1802.

No difference in the molecules used.

However, 1802 has a higher Jak1 content.

The Jak1 selectivity over Jak2 and Jak3 remain the same.

There can evolve safety concerns with Jaks penetrating the blood brain barrier as found in earlier generation jackis.

With 1802 whilst ok for treating cancers where the benefits outweigh the disadvantages ( cancers are life threatening).

We are now looking at 1802 and treatment for cancer as well as auto immune.

Indeed 1802 has patent protection for use in auto immune

However, it was deemed inappropriate to have an auto immune treatment ( that is not deemed acceptable to pose such a potential safety concern in auto immune) that could have such an off target effect compromising the performance of the inhibitor.

That is it in a nutshell.

Regards

Good evening Salfordred.

Talking with Tim and certainly he is not against a takeover.

He is liking his part time role and gives him time off.

He is relieved of the pressures of running the business. In the hands of Stephen Parker now of course.

Good afternoon Salfordred.

Just home from AGM

I had a chat with Tim circa 15 mins

I believe l know the reasonings behind 1801 and indeed 1802.

Well it came straight from the horses mouth.

1802 has a higher jak1 content than 1801.

It is to do with blood brain barrier and crossing.

I will not go into detail here.

But needless to say l am very impressed with the level.and attention to detail that has gone into 1801.

A very calm BoD l will add.

The important aspect to be taken away is that this clinical trial data review is now signed off by Dr John Reader.

It will be at this stage that the data review will satisfy the requirements of ' well show us some data' to any of the interested party or parties as is now authenticated.

The opinion l took away is that yes, partnership and that includes on licensing is their objective and to continue into phase 2 themselves if need requires, ultimately if their is a decent deal involving takeover that will indeed happen.

Glad l attended and l will say that l am in 100 % agreement with Dr.Zed 6th paragraph.

Regards to all.

My first attendance at the AGM.

Met some nice folk John and Steve in particular and a decent 15 min chat with Tim

Relaxed atmosphere, no questions about RF debacle, what happened has happened.

The clinical trial data is now of significant importance and now being signed off by Dr John Reader is the ' well give us some data' relevant pfficial report as opposed to mere company dialogue.

The meat on the bones so as to speak.

Regards

Pleased l attended.

Funny guy, someone has now over 1.2 million invested after recently adding.

I would not call that wishful thinking.

Maybe they have a better understanding of the company and its pipeline than you do.

Whoever this individual may be there is nothing to say he will not continue to add.

As a holder now exceeding 5% he will have a degree of clout.

Look up the advantages of holding 5% shares in a company.ay well be a previous high net worth individuals investor.

Around 6.5 million shares

Ironic that Sareum board award themselves options a day before increase in share holding

Just coincidence?

Good day to all and regards

This is not what l posted originally, but gives an indication of Chk1 inhibitors being plausible.

Liposomes can be used to deliver checkpoint kinase 1 (Chk1) inhibitors to enhance anti-tumor activity and reduce toxicity. Chk1 inhibitors are a potential treatment for cancer because they target the DNA damage response in cancer cells:

How Chk1 inhibitors work

Chk1 inhibitors prevent DNA repair and cell cycle arrest in cancer cells, which can lead to apoptosis.

How liposomes can help

Liposomal encapsulation can modify the pharmacokinetics of Chk1 inhibitors, which can improve therapeutic index and reduce side effects.

Regards