Member Info for sadoldgit

Good afternoon Laz,

News is indeed imminent l believe.

Results of clinical trial and Sareums intent.

Then dependant on content of RNS time to light the blue touch paper, so as to speak.

Regards

Good last 3 posts from Lutonnews Oracle and Basil Alderman.

The only thing l will add is informal discussions cannot conclude until trial data is known.

Regards

Lsesar,

Good afternoon.

You state you would expect the BoD to state as early as possible if there will be a delay and why.

As you have used 'if there will be a delay' then clearly you acknowledge there is no delay at the moment.

What exactly is your problem?

You had an expectation timescale of early to mid June, as indicated by your post in May.

RE: Boring few days ahead 10 May 2024 09:18

Maximum 7 weeks of waiting but i would expect the report to be ready early to mid-June (hopefully no delays). Between now and then there are likely to be quite a few rises and dips - enjoy the ride!

Regards

They expected the results in Q2 as per RNS release.

I expected to get home from Scotland on Friday at 15.30 hrs, due to delays on A1 and A14 l did not get home until.18.40 hrs.

Very easy to confuse 'expectation' with 'due'.

There were some people expecting this share to go back to 10p.

Your imagination, or is that an expectation of the markets?

If you are that concerned of the expectation date then take it up with the Sareum BoD.

Regards and let us know how you get on.

Reality10 from the RNS

'The multiple ascending dose (MAD) study of SDC-1801 is ongoing and topline data from the Phase 1a clinical trial are expected to be available during Q2 2024.'

No mention of the word 'due' so why have you

manipulated the original content contained within the RNS by the word due?

Expectation is not the same meaning as due.

We are at the moment still in Q2.

All they can really put is an expectation of the timelines. What would you like them to put?

We will issue an RNS giving results Thursday 27th June at 7.00am.

There are and will always be delays.

If it runs a week or two over what is the problem?

It will arrive when it arrives!

Good safety profile is one thing but to establish a valuation it will need to be known in what indications a compound can treat.

Pharmas are there to make money, once Indications are known then you can look at the available market size and assign a percentage thereof.

Psoriasis is nigh a definite.

We don't know other Indications such as

SLE

UC

CD

Cytokine storm

Diabetes

Alzheimers

Or indeed a myriad of other auto immune ailments that exist.

Regards

I agree Leggster, I don't see any current involvement with Sierra.

The interesting point is that Franconi focus on cancer, they have also used research Pembrolizumab a PD1 inhibitor and 737 a CHK1 I inhibitor. There would be plenty of cross comms between Franconi and SO.

Perhaps undertaking development of 737 in combo. Franconi can set up funding start up companies.

It would make sense if these people somewhere along the line are involved

Licence contract is very similar.

The person to keep an eye on here would be John Diaz

Regards

Https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-of-sra737-for-advanced-cancer

Fanconi anemia is caused by mutations in one of 23 genes—including several cancer susceptibility genes such as BRCA1 and BRCA2—that impact the genes’ ability to function properly in the Fanconi anemia/BRCA DNA repair pathway. Compared to the general population, patients with Fanconi anemia are estimated to be around 868 times more likely to develop acute myelogenous leukemia (AML). Another study found that patients with Fanconi anemia are also 986 times more likely to get head and neck squamous cell carcinoma and have significantly higher chances developing tumors of the larynx, vulva, cervix, and breast.

An interesting post HbD.

Short post from me but after a little searching l came across the following

https://www.aacr.org/blog/2024/05/31/new-grant-will-fund-fanconi-anemia-related-cancer-research/

A quick well half hour read and it would make sense to at least test 737 in the difficult to treat areas.

Https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6156173/#:~:text=On%20August%2030%2C%202017%2C%20the,years%20of%20age%20and%20older.

Good morning Salfordred,

Very little apart from ending in mab it is a monoclonal antibody.

These work on cell recognition and hence destroy the cell from the outside.

Jakis work by destruction of the cell from the inside as you already know.

Hence we have entered an area of combo approach. This of course includes checkpoint inhibitors. Checkpoint kinase inhibitors also have an important role.

Will have a butchers later.

Regards

Ruxolitinib and Tofacitinib NDA approval 2011.

Ruxolitinib patent protection expires 2028.

Are companies getting desperate by using drugs in combo with the goal of achieving further patent protection?

Just a thought

Good morning HbD.

An on licence l believe is in the throws for 1801.

Non dilutive funding. Upfront payment with large milestones and high single to low double digit Royalties.

The Kinase inhibitor market is hotting up.

Sareum have been awfully quiet in Indications for 1801 and 1802.

Developments may well be progressing since the last meeting in the states.

Indeed it is also very quiet with 737.

We are getting overdue for news.

Regards

An excerpt shown below.

Take into account that Tofacitinib and Ruxolitinib are not new. 1802 still being developed during the trials of the combo therapy. All pointing good to 1802.

'Given the recent clinical evidence regarding the sensitivity of T‐cell prolymphocytic leukemia to JAK2 inhibition and the preclinical data in transformed lymphocyte cells regarding the inhibition of JAK1/JAK3 using the JAK inhibitors ruxolitinib or tofacitinib [3, 4], the decision was made to pursue therapy with ruxolitinib in combination with tofacitinib. Due to major contraindications to tofacitinib in our patient (deep vein thrombosis of the jugular and subclavian vein and heart failure NYHA III), the salvage therapy with ruxolitinib 10 mg twice daily was initiated. '

Good morning all.

I think many will miss just exactly what is implied in the tweet. It does not refer to SDC1801.

Ruxolitinib is not used here as a monotherapy but incombo therapy.

Importance of Jak selection. Ruxolitinib a Jak1 Jak2 inhibitor has adverse effects.

Now as we are Tyk2 Jak1 we should have no problem bettering Ruxolitinib at least in the area of adverse events.

'Combination of tofacitinib and ruxolitinib increased the efficacy by 53- to 161-fold versus that observed for monotherapy, respectively, and each drug applied alone to primary human lymphocytes displayed similar efficacy against HIV-1 containing various polymerase substitutions.'

The importance here is immuno therapy overlapping with immuno oncology.

As far as l can remember and correct me if l am wrong but the indication for 1802 is T ALL.

I would put a pretty educated deduction that our SDC1802 will pretty much do the same if not better as a monotherapy.

There is a difference in immuno therapy and immuno oncology. Very close but not the same.

A very subtle indication as to the potential of 1802.

From patent description 1802 may be used as a supportive therapy with other inhibitors which may lead to 1802 being the main or sole inhibitor being used.

Regards

There exists an overlap in this area. The decision to patent 1802 to protect the use of 1802 in immunotherapy was done for a reason.

Good morning Philboro,

The wonders of political correctness.

Is it AI generated?

Of importance here is that it relates to tyk2 Jak2.

Jak 2 will Pair up with Jak2

Tyk 2 will Pair up with Jak2

Hence l believe that in the absence of Tyk2 the associated problems of Jak2 become apparent leading to EPO, basically an overabundance of red blood cells with potential blood clots and thrombosis.

We have Tyk2 selectivity over Jak1

The Jak1 is selective over Jaks 2 and 3.

There have been inhibitors that inhibit all 4.

Basically discontinued.

It is therefore about getting the balance right and of course it relates to the particular indication.

No one inhibitor will treat everything as proven with deucravacitinib. Failed to meet either of its end points in UC.

Wow the allosteric inhibitor that regulates the active site. GSK hyped up report on this miracle cure.

Did not do a good job in UC as the placebo had better results.

SDC1802 is very quiet, too quiet l feel.

Both Tyk2 Jak 1 inhibitors.

Interesting to know the difference which l would suggest be down to selectivity.

Highly likely that SDC1802 may have greater efficacy in immunotherapy Indications such as UC than 1801.

The patent protections for 1802 in immunotherapy indicate that 1802 has a much broader scope outside immunoncology than maybe previously thought.

Regards

Wow,

I can put hetrodimerisation

But it does not allow ho modimerisation.

Good week coming l feel.

Regarding 1801 and covid19 work was carried out in vivo whereby impressive results were obtained.

As it stands the nearest similar approved drug to us is baracitinib albeit we should not carry the limitations of black box warning

good morning,

you are correct 007 in your belief that 1801 trialled in healthy patients only in oz.

as bobbler says most likely cause of the link being down is it has jumped the gun so as to speak as most likely done at the point of cta application.

our nearest potential competitive competitor is likely ropsacitinib a tyk2 jak 2 inhibitor.

jak 2 has associated problems:-

'the jak2 v617f point mutation makes the normal hematopoietic progenitor cells hypersensitive to thrombopoietin, erythropoietin, and myeloid progenitor cells, leading to trilinear hematopoietic myeloproliferation.'

effectively looking at blood clots!

however, if we delve deeper and knowing that jaks work in pairs.

jak2 can pair with itself ie ****dimerisation and this is problematic.

tyk2 will pair with jak 2 heterodimerisation.

advantages being interleukin 17 and 22 or 23 (can't remember which) are inhibited leading to dual inhibition.

this l would suggest may be the reason as to why ropsacitinib is in the process of developing good safety profile with regards to serious adverse events in early clinical trial now at phase 2 l believe.

sdc1801 does inhibit small amount of jak2 and hence may benefit from let's say the slight off targets of jak2 and jak3 as at these dosaging levels will not prove detrimental to the safety of the compound.

the are other indications we may prove to have the ability to reach commercialising in.

sle being one

alzheimers may prove to be another but a tough cookie to crack and current treatment is the use of monoclonal antibodies to reduce plaque in the brain.

links to problems with high cholesterol and diabetes of which the latter is an immune system problem.

new strains of covid 19 emerging with an increase in hospital admissions. not serious yet but treatment for those who suffer worst would benefit from inhibitors that reduce the effects of the cytokine storm.

regards

ps 100% certain we will better deucravacitinib in psoriasis as dual inhibition which is proving to have greater efficacy.