Member Info for sadoldgit

Potnak you are not sowing doubt just talking out of your backside.

'Anything from SKIL now, will have little value for at least 5 years. I'm not sowing any doubt. Just there is more to this than we have been told. It's either a change in direction or contingency.'

Potnak, the first part of your paragraph is contradicted by the second part.

'Why do you state that anything coming out of SKIL will have little value for at least 5 years?'

Based on what?

A preclinical model could be or even maybe progressed over an 18 month timescale and bought at the idea of proof of concept.

What is your opinion of that Potters?

Merck is preparing for potential pricing pressure and patent expiry for Keytruda by developing a subcutaneous version and exploring new bispecific antibody therapies. They are also actively pursuing new approvals for Keytruda in various cancer types, including lung, head and neck, and mesothelioma.

If we take the above into account and also the fact that 737 was very effective in lung cancer, head and neck cancer, then surely to maintain generation of income then is not better to patent in combo Pd-1, chk1 and LDG.

Results given by Triparna Sen were phenomenal in SCLC.

The only downside l see to this is who gets the kargest share of the pie?

Yes it can be negotiated.

Timing will.also be important as the latest hey can leave it before generics come in the better.

Question here also is who will hold the patent or to be more precise who puts its forward to be patented dnd this would happen in a relatively early stage.

We have Acrivons Chk1( ACR-368) the old Prexasertib fast tracked into certain areas of high unmet need.

The major consideration here apart from the benefit to the patient is, in combo therapy a tool to increase patent life.

Regards

The further we look the more possibilities we see.

Importance of Tyk 2 and Jak1 in IL-6 and IL-10 signalling STAT 3 pathway.

Below is an AI brief overview. It can explain better than l can in fewer words.

Then realise the potential with what we have and results achieved so far.

IL-6 signaling:

IL-6, a cytokine with both inflammatory and anti-inflammatory properties, utilizes the IL-6 receptor, which includes gp130 as a common subunit. This receptor associates with Jak1, Jak2, and Tyk2, leading to the activation of STAT1 and STAT3. Jak1 is considered the most important Jak family member for gp130-induced signaling.

IL-10 signaling:

IL-10, primarily known as an anti-inflammatory cytokine, interacts with its receptor, which consists of IL-10R1 and IL-10R2. This interaction activates Jak1 and Tyk2, ultimately leading to the activation of STAT3, which is then involved in regulating immune responses.

There is vast importance here of ratio of IL-6 to IL-10.

Regards

GlenFidrich,

Good afternoon.

With regards to AGILE Thoth made a very astute xcomment as to the reasons of non progression.

In a nutshell an agreed price of compound would need to be established in this respect treating Covid 19.

Once tge price is established the how would Sareum realise the full potential worth in 1801 when applied to other Indications of as yet urgent unmet need?

In effect the NHS round want its use for bugger all. Low price.

If any other Indications were realised this low price would remain.

The other side of the coin would be for example great value in an indication such as ulcerative colitus or even SLE where the price of treatment is vastly more expensive then when being approached for approval for Covid 19 cytokine storm a negotiated discount can be made with regards to that indication.

How many doses would be required by the NHS to cover the requirements of the pandemic?

A million plus as a ball park figure?

With regards to progress we can all feel a tad peeved that it has taken approaching a year from the completion of phase 1a to the commencement of toxicology studies ( still no commencement date but scheduled to start in May)

In a sense big changes over past year

Change of CEO.

Tim now part time concentrating on 1802.

He can do very little more with 1801.

737 looking to progress with probable CHK 1, LDG and PD-1 combo and or 737 and Parpi.

We now have control and 63.5% interest in 737.

1801 awaiting start of long term toxicology studies.

Some will state a failure risk here, but all we are looking at in reality is the suitability for long perhaps life long use.

Effectively we are looking at commercialisation value and the value is phenomenally more lucrative for a drug that can be used for 5, 10 15 years or longer than a compound that can only be used for maybe a maximum of a couple of years.

A top notch safety profile dill place us head and shoulders above what else is out there at the moment

For a pharmas interest they looking at revenue.

So they need know how long the compound can be used as a continuous treatment.

What are the Indications it can be used in.

The patent protection life.

This early preclinical studies with BBBand CNS was decided overnight.

Somebody is pressing the buttons.

To me it all adds up to a buyout.

We need as do the pharma the data satisfying the safety criteria for long term use.

No formal offer as l see it is likely until data starts to feed through or tox study completed.

Regards

Biohaven and Tyk2 Jak1

https://www.biohaven.com/pipeline/tyk2-jak1/

HbD with regards to being bought out with the major compound being SDC1801

We have 1802 coming to an end of preclinical for Cancer.

How much is the total 31 molecules involved I SDC compounds worth.

Blood brain barrier treatment for CNS is not easy.

Any early preclinical studies should give an indication as to likelihood of success.

I am of the opinion that should sareum indicate that they choose to trial in animals then a billion dollar takeover will be a bargain.

So much for those that say the BoD have achieved nothing in 20 years.

They can do very little apart from post negativity whether of ignorance, sheer malice or an agenda.

Regards

Good morning HbD.

'While further optimisation is still required, the results support the potential for Sareum's TYK2/JAK1 chemistry '

How much will the informal discussions with interested parties develop taking into account the above?

I am still of the firm opinion that we will be bought out.

I cannot understand some here that indicate negativity towards development of another compound.

The development so far will cost bugger all apart from Tim's time.

Drugs now are bought àt preclinical stage and at times very early preclinical if the concept is unique.

It may well be that an interested party has influenced this new development.

A very positive RNS.

It adds another string to the bow.

Proof of concept important and this can be achieved with modelling and the use ofcomputatuondl chemistry prior to any animal studies that costs large sums of money.

At the very least xn opportunity for a pharma to buy in or partner at an early stage with an upfront payment likely to be more than upfront payments we have recitved previously ftom 737.

After all we own the SDC molecules lock stock and barrel with the all important heavy patent protection.

Regards

Good picture C79.

Very little to do waiting for toxicology studies to progress.

Tim clearly working not only on 1802 but also looking at tge brsin penetrant barrier.

Deucra and others looking to progress in this area.

But the above two examples are not principally developed for certain Indications.

I am certain Tim can produce a decent compound.

He knows the molecules back to front and with many years experience and a PhD in computational chemistry it will likely lead to a preclinical candidate.

Regards

It can go no harm at all development of early stages in CNS diseases which are indeed an area of unmet need.

There are many not do good inhibitors being trialled in thus area.

The good side for us is that whilst other inhibitors thst have Jak associated problems are looking to enter this area we can probably create a vastly superior inhibitor.

Yes it goes involve time and money but Tim is clearly making use of the time in his new role..

Furthermore it does increase our pipeline and whilst in early stage and unlikely to attract an on licence gor a new inhibitor, longer term has potential and will be of interest to any pharma looking to purchase a company with a promising pipeline.

It can only add value,

Are we being driven by an interestedpharma

JBond007,

We are considerably further forward than in 2021 when at a peak market cap of 300 million. The CPF not focused on 737 development is a bit of an understatement.

We now have control of 737 which may prove very lucrative but if course nothing guaranteed.

Parpi resistance is causing a problem both for the patient and the pharma company selling the product. How does a pharma maintain revenue?

There is also the dwindling of patent protection and patented in combo therapy would extend protection.

Tim and Co know far more than any of us here with regards potential future of 737.

Ideally an announcement of development with an interested party would significantly lift the SP.

We are funded l would estimate for the next 12 months or so.

Several possible outcomes

Licence 1801 post toxicology results

Licence 1802 post preclinical completion

Licence 737 anytime from now onwards but take into consideration drafting up of contracts that in itself can take 3 months.

Option may well be compete buyout but in this case it is far better to have the all important long term tox data and the interpretation thereof.

We may just sit in the doldrums at these current levels with a slight increase on news of toxicology commencement.

A pharma is not going to spend many millions unless he is fairly certain what he is getting and the risk factor involved.

A few shares bought by the bod a short while ago

Share options being taken

Are we now heading into a period of NDA due to developments on any front?

Just a tad peeved at the moment the time it has taken from end of phase 1a to commencement of a long term toxicology study getting close to year.

Regards

Https://pubmed.ncbi.nlm.nih.gov/39021796/

Good evening JBond007

800 million valuation of which we would receive 27.5%

We nowsit ot only in the driving sit but also now a 63.5% financial interest.

Ot may be worth having another look at the Investor meet.

Looking very much 737 plus Low dose Gemcitabine and a Pd-1 inhibitor in SCLC

.

80% of mice treated showed no signs of tumours l think that either 30 or 60 days post treatment.

The 2 other mice had almost complete recovery.

737 and Parpi the other and or option. Looking to be of great benefit into HGSOC that has developed resistance to Parpi.

An area of increasing unmet need.

Parpi the new inhibitor that was, now finds itself troubled by resistance.

One thought here is that surely once resistance develops it must surely end the course of treatment, but may it just be that a compatible Chk1 inhibitor can prolong in combo?

Also showed great results in CRPC and ano genital cancers of course in combo.

I am not saying this will happen but l believe the most likely outcome.

Regards

Regards

Difficult to ascertain a value then again it has a profile that is very tolerant of working in combination of other inhibitors.

A very long read but, pertinent to development and safety of Jak inhibitors, competitors failures and the importance of a satisfactory safety profile.

Not bang up to date, however does give a broad picture of problems involved in Jaki inhibitor development and of course these risks which any pharma I tending to commercialise will take into consideration.

https://pmc.ncbi.nlm.nih.gov/articles/PMC10615860/

Regards.

Good evening MegRS300,

I agree 100% with your post.

I will add which is of great importance that the toxicology results will add significant value dependant on outcome.

No such thing as failure!

Why is that you may ask.

At the very worst outcome we are still better than Beprocitinib

Now Beprocitinib was discontinued for further development in Psoriasis. Basically down to off target adverse events and this of course includes dose limitation due to factual evidence that indeed Breprocitinib carries the attributes of typical Jak problems.

Psoriasis as Tim stated a couple of years back is indeed a very competitive market.

.

Deucravacitinib whilst not overly efficient compared to other inhibitors does have a vastly superior safety profile. Hence the demand will be for this type of inhibitor.

Breprocitinib to be competitive would have to drastically reduce the cost of tge drug as cost is one factor to be taken into account.

The scenario would be that if the price of Breprocitinib were dropped and found to be first class at another indication for example ulcerative colitus or SLE then the price of the compound inhibitor would have to remain the same.

Once the inhibitor price has dropped there it will remain hence Priovant/ Pfizer looking at other Indications for which there is urgent unmet need.

1802 is also unique as a first Tyk2 Jak1 in immuno oncology.

The safety of 1802 does not have to be of similar safety profile of 1801.

We are effectively majority Tyk2 with the benefit of Jak1.

We carry suitable selectivity and binding affinity that have given us vastly superior safety results to Breprocitinib.

Suitability for long long term use will be decided by toxicology data results.

That adds billions to the potential lifetime revenue of an inhibitor.

With regards to efficacy we hit the major targets to treat effectively many auto immune diseases.

The proof of the pudding is in the eating and an interested pharma can select whatever Indications they can apply to an unrestricted inhibitor with acceptable long term safety profile in which ever money making indication they want subject to efficacy of course. These will be known in advance, not all, but most.

Regards

Pleased to have put some info down that may help posters here understand the little better.

I did not always agree with Thoth but he did place a great deal of importance on our molecules and the patented protection thereof. I did agree with him on that one.

Regards and Happy Easter.

Indeed our molecules are unique and heavily patented. Unique in that no Jak2 activity detected phase1 clinical trial.

I have for some time contemplated as to why there is no Jak2 observed activity.

Our compound is made up of molecules

In thus case it is not a single large molecule( pretty pointless if we think about it as impossible to work)

However, there is great importance of how molecules bind ie strong or weak binds and this can lead to a bias.

That my opinion for what it is worth.

Binding affinity l believe is what gives us tge edge over all other Tyk2 Jak 1 inhibitors.

A general description given below.

How Binding Affinity Matters:

Drug Design:

Binding affinity is crucial in drug design, as it determines how effectively a drug will bind to its target protein and exert its therapeutic effect.

Biochemical Reactions:

Binding affinity dictates the strength of interactions between molecules in biochemical processes, influencing the rates of reactions and the overall outcome.

Specificity:

High binding affinity can lead to more specific interactions, as the ligand will be more likely to bind to its intended target rather than non-target molecules.

Food for thought especially the amount of patent protection obtained and sought.

Regards

Tolebrutinib.

It's is a Btk inhibitors (Bruton Tyrosine Kinase)

There are side effects both moderate and serious

I find it strange that approval has been granted albeit in an area of urgent unmet need as there is no current effective medication

Efficacy gave a reduction in progression to around 10% of patients.

AI and l am not a lover of AI

Following adverse effects.

Fatigue: A frequent complaint, impacting daily activities.

Diarrhea: Can range from mild to severe, often requiring adjustments to treatment or medication.

Bleeding and Bruising: BTK inhibitors can interfere with blood clotting, leading to increased bruising and bleeding.

Infections: Neutropenia (low white blood cell count) increases the risk of infections.

Muscle and joint pain: Some individuals experience myalgias (muscle pain) or arthralgias (joint pain).

Headaches: A common side effect, particularly with acalabrutinib.

Dermatological issues: Rashes, skin ecchymoses (bruising), and other skin reactions have been reported.

Serious Side Effects:

Cardiac Arrhythmias: Irregular heartbeats, such as atrial fibrillation, can occur.

Hypertension: Elevated blood pressure is another serious side effect.

Rhabdomyolysis: While rare, this condition involves muscle breakdown and can lead to kidney failure.

Severe Bleeding: In some cases, bleeding can be severe and require medical attention.

It can be interpreted that when a drug is presented in an area of urgent unmet need that safety is not taken perhaps as it should be when approving authorisation or maybe almost to the point of being disregarded.

1801 first class phase 1 clinical trial results that now require a long term toxicology study.

Without wishing to appear cynical we could have 10 people treated with BTK inhibitor whereby the only one with sympton suppression drops down of heart attack or kidney failure.

Strange world.

Regards news due soon.

Approval!

https://www.sanofi.com/en/media-room/press-releases/2024/2024-12-13-06-00-00-2996609

Tolebrutinib is currently under clinical investigation, and its safety and efficacy have not been evaluated by any regulatory authority. The PERSEUS phase 3 study of tolebrutinib in patients with primary progressive MS is currently ongoing with study results anticipated in H2 2025.

Https://www.fiercepharma.com/pharma/fda-blocks-biopharma-employees-serving-advisory-committees

Whoops that should be 0842 and not 0942.