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The NHS may soon recommend baricitinib based on these new results. A 10-day course of the pills costs around £250, although the NHS may be able to negotiate a discount.
Excerpt from:-
The Genomicc study has been trying to understand why some people with Covid have no symptoms while others become extremely ill.

It has been looking for answers in people's genes, comparing intensive-care patients' genomes with healthy people's DNA.

And it has pinpointed some key genetic differences - including one in the TYK2 gene.

If this gene is faulty, the immune response can go into overdrive.

And this genetic discovery led to baricitinib being added to the Recovery trial's list of treatments.

Genetics is crucial for understanding how Covid-19 affects the body - and combining this DNA knowhow with a major clinical trial has provided another weapon in the fight against coronavirus.

https://www.bbc.co.uk/news/health-60601750

Baricitinib is a Jak1 Jak2 inhibitor. Tyk2 is regarded as more selective. No reason as to why 1801 should not outperform Baricitinib in Covid. Far too many American drugs in the UK NHS pipeline as it is.

I know Thoth2 mentioned in very early Covid days alopecia. Not sure where the topic originated, but around the time of the Recovery programme start.
BJ the ex PM was stating before long we will be able to treat covid by taking a pill a day. Early Baricitinib being pushed by Eli Lilley via our NICE system I would guess.

We should to be superior to Baricitinib on side effects alone.

Rebecca Morelle needs a good look at Jak inhibitors then SDC1801. Dosen;t know the difference between a Jaki and a Tyki I would guess.

Regards

Good morning Cereus. Always good to keep aspirin close at hand. Good that you are taking it easy and feeling better. As batonrouge indicates, advantages to be had in reduction of caffeine. Energy drinks have much to answer for this also.

Regards

Cost of treatments
The ICERs for niraparib and olaparib compared with common baseline placebo were $235K and $287K per PFS life-year, respectively, with olaparib extended-dominated by niraparib. Both drugs were associated with lower ICERs in patients with a gBRCA mutation than in patients without a gBRCA mutation.

Now both these PARP inhibitors have been involved in preclinical studies with CHK1 inhibitors. Niraparib has the edge at the moment.

https://www.cancer.gov/about-cancer/causes-prevention/genetics/brca-fact-sheet
PARP is approved for use as a cancer treatment. It is more effective when used with CHK1

From 2011 .
Clinical development of UCN-01 has overcome many initial obstacles, but the drug has nevertheless failed to show a high level of clinical activity when combined with chemotherapeutic agents. One very likely reason for the lack of clinical efficacy of Chk1 inhibitors may be that the inhibition of Chk1 causes the compensatory activation of ATM and ERK1/2 pathways. Indeed, inhibition of many enzyme activities, not necessarily components of cell cycle regulation, may block Chk1 inhibitor-induced ERK1/2 activation and enhance the toxicity of Chk1 inhibitors.

Difficulties here due to CHK1 inhibition resistance identified.

however by 2021 sept
Checkpoint kinase 1 (CHK1) plays a central role in the response to replication stress through modulation of cell-cycle checkpoints and homologous recombination (HR) repair. In BRCA-deficient cancers with de novo or acquired PARP inhibitor resistance, the addition of the CHK1 inhibitor prexasertib to the PARP inhibitor olaparib compromises replication fork stability, as well as HR proficiency, allowing for sensitization to PARP inhibition.
full info in link below.
https://aacrjournals.org/clincancerres/article/27/17/4710/671668/Phase-1-Combination-Study-of-the-CHK1-Inhibitor

Taken from the research paper by Michelle Garrett from May 2021.

'The data reveals an NF-kB regulated pathway controlling CHk1 activity in cancer cells and identifies a potential mechanism for both acquiring and overcoming CHK1 inhibitor resistance in cancer patients'
Note carefully the excerpt. :-
' The dramatic loss of CHK1 signalling we observed in the C- Rel Eu-Myc lymphoma cells raised the question of how these cells were surviving and coping with ongoing DNA replication stress. Especially given our previous observation that lymphomas in these mice arise earlier than in wild type controls.
The activation of compensatory signalling pathways is a major contributing factor in the development of resistance to kinase inhibitors and often goes hand in hand with the tumour cell having bypassed the need for the drug target, which we observed in our models of both de novo and acquired resistance.'

'Our data implies that a treatment with P13K or AKT pathway inhibitor could be an invaluable strategy either in the treatment of patients whose tumours develop resistance to CHK1 inhibition or potential as a combination therapy to enhance the effectiveness of the initial treatment'

P13K or an AKT inhibitor ( both which exist)!
I
Chk 1 inhibition it is envisaged, can be overcome when used in combo. Vital for HGSOC, Breast cancer and pancreatic cancer. This is a huge market. Sierra had patents for SRA737put in place.

The science has evolved.

Regards

Hi HbD i would hazard a guesstimate that Clinical Trial recruitment will be announced fairly soon.
As opposed to we envisage or we expect much better to have it will commence on such and such a date.
We may get that next week we may not.
Tim an co never have given much away and I dont think will change now.

We have a market cap at the moment of circa 125 million. For what we have and that is included in a 27.5% interest in 737 it is peanuts. The success of 737 in milestones of 70 million plus and around 2.5% royalties on gross turnover is worth more than that alone. At a meagre half billion a year that would be around 12.5 million in Sareum coffers.

Regards

Hi HbD i would hazard a guesstimate that Clinical Trial recruitment will be announced fairly soon.
As opposed to we envisage or we expect much better to have it will commence on such and such a date.
We may get that next week we may not.
Tim an co never have given much away and I dont think will change now.

We have a market cap at the moment of circa 125 million. For what we have and that is included in a 27.5% interest in 737 it is peanuts. The success of 737 in milestones of 70 million plus and around 2.5% royalties on gross turnover is worth more than that alone. At a meagre half billion a year that would be around 12.5 million in Sareum coffers.

Regards

Following on from there Loopylo, I would suggest our means to additional funding has been submitted in CTA.
It will be a requirement by the clinical trial sponsor. We have applied for 1a and 1b.

Also need take into account regulatory procedures with medicinal products, which may cause a delay especially for first in human trials.

https://www.gov.uk/guidance/clinical-trials-for-medicines-apply-for-authorisation-in-the-uk

https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-strategies-identify-mitigate-risks-first-human-clinical-trials-investigational-medicinal_en.pdf

Regards

Interesting posts/opinions this morning HbD and Loopylo.

A rough overview but should give an even rougher indication of costs regarding trials. Bear in mind the figures are for the US and a little dated. Their trials not exactly the same as ours.

https://www.sofpromed.com/how-much-does-a-clinical-trial-cost#:~:text=How%20much%20does%20a%20clinical%20trial%20cost%3F%20The,States%20cost%20a%20median%20of%20%2441%2C117%20per%20patient.

Median costs per trial patient 41k is mentioned it will be higher for immuno and more for lesser numbers of patients.

I agree with the ball park figure put out by Potnak I believe, of circa 2 to 3 million. 2 low and 3 high.

15 to 20 patients ( if we take a ball park figure of 50k) 750k to 1000k cost. Plus administrive fees cost of tablets etc.
Phase 1 b approximate 100 patients at a ball park figure of 45k equates to around 4500k. This is a guestimate and if we combine the two figures it is not far out from the 6.6 million dollars median price for phase 1 immuno. The US have a slightly different trial phase to UK. Our 1a and 1b nudges us into phase 2 almost.
Now coming to the end of Phase 1 a Sareum will have I would estimate around 1 to 2 million left in the pot.. 4;6 million as at end of June 22. We will be experiencing high burn up rate soon.
We will have 1 a to have paid for by end of 1a trial, then will need funds for 1b ie trial in psoriasis patients and also of equal importance although not such a high priority with continued development of SDC1802.

Correct me here anyone if they find me wrong but I have always found Sareum have gained finance in one form or another way before ie 6 months at least before funds are needed for ongoing activities.

As far as I can see , when the CTA is submitted, a requirement is how a company is going to raise funds to support this.
1a Sareum have funding, so no problem here
1b would guestimate either demonstrate how can raise funds from investment ie dilution
or evidence to provide means of obtaining finance via an interested party either partnership or on license. ( of course amount of funding from this has yet to be determined)

Can anyone else reason an argument for any other form of fund raising. HNWI 's are a very slight perhaps as they sit at present slightly to quite heavily underwater and would not think that this could be relied upon.

Of course it would also be good if we were paid at least 1 milestone payment by GSK for 737 pretty soon, but of course this has no weight in indicating how you will fund trials.

Just my tuppence worth for the weekend.

Regards

It all coming together Num4. I reckon we are pretty much lined up and will be dependant on phase 1 a results. Tim has these ongoing discussions with interested persons, so surely they must discuss ball park figures on achievement of results. Absolute minimum would be Psoriasis. So they will have a ball park figure for this. If dose escalation is exceedingly good the may be looking at IBD Crones, Lupus and a myriad of other autoimmune diseases. Surely they would have a ball park figure for this too.

All very exciting. Pleased for those that are slightly under at the moment the recent SP rises

Regards

good evening citizen79
P13k is not new as we know. But interesting to note the link to autoimmune and oncology. We also know of the proposed advantages of using P13k with other checkpoint inhibitors and that includes especially CHK1.

Regards

good evening citizen79
P13k is not new as we know. But interesting to note the link to autoimmune and oncology. We also know of the proposed advantages of using P13k with other checkpoint inhibitors and that includes especially CHK1.

Regards

The only think I can think of is CTA result will be published with other info. Acceptance is good milestone. Not really going to set the SP on fire on its own.
We can finance Phase 1a trial but would need additional finance I believe for phase 1 b. Sareum would have to demonstrate that they can raise the funds. If it through PH investors then may explain the reasons as to why SP would appear to be suppressed. Phase 1a will make a big hole in what funds sareum have at the moment.

From RNS 28th July 2022
'Provided satisfactory safety data is obtained from this initial study, and subject to additional funding, a Phase 1b clinical study will commence in psoriasis patients in 2023. The CRO conducting and managing the studies has extensive experience in conducting trials in inflammatory diseases and will recruit up to 120 subjects at a site in Manchester, UK.'

Would be interesting to know as from who and when this funding will evolve. Good results on competitors toxicity and adverse side effects with TYk2. How are the on going discussions going with interested parties?

The better the result in dose escalation trials the greater the value of 1801. Will have knock on effect on 1802 also.
60 days have elapsed. Sareum will know the result and it would not be a refusal.

Decent size buys recently and the SP hardly moves up.

Failed on the 29th Sept RNS prediction but hey ho.

Regards

Thanks krone will have a look.

some of the odds and ends I read
https://experts.illinois.edu/en/publications/effects-of-il-10-and-age-on-il-6-il-1%CE%B2-and-tnf-%CE%B1-responses-in-mou#:~:text=IL-10%20can%20reduce%20IL-6%2C%20IL-1%CE%B2%2C%20and%20TNF-%CE%B1%20expression,on%20cytokine%20responses%20in%20skeletal%20and%20cardiac%20muscle.

https://pubmed.ncbi.nlm.nih.gov/29967259/

Good post Krone and were looking up importance of Jak1 with interleukin 6

It is indeed complex and having difficulties in getting head around. There are advantages of IL-6 there are also disadvantages, so many conflicting conclusions. I will end with:-
Conclusions: These preclinical results indicate that targeted inhibition of IL-6 may enhance the efficacy of anti-PD-L1 in PDAC.
If this is the case we are pretty well spot on. Even though we are Primarily TYk 2 and Jak1 ( bare in mind nigh impossible to have specificity on Jaks 1,2 and 3 what we have should be beneficial)
If we take our patent for 1802 this most likely reason that 1802 postulated to be used as supportive in a major or minor way to overcome resistance,. Compatibility with nigh every current inhibitor now in existance!
Not sure what the exact differences are with 1801 and 1802 are, but would hazard a guess at higher Jak 1 content in 1802.

https://pubmed.ncbi.nlm.nih.gov/32581055/

Tim and co way above me on any of this, I am not in the same city let alone the same street. They will know in themselves just how good potentially.

Regards

The only thing I would add and has been intimated by previous posts is maybe slight delay on CTA result success to be aligned with a more detailed start and programme schedule.

After 16,30 hrs SCHecks. Buy or sell is good. It just shows the trade price.

I think you will find that it was date of submittance 28th July 2022. 60 days start of date of receipt ( normally by acknowlegement) I did plump for RNS on 29th Sept.
Sareum may take a day or so to release news on this. I do not foresee any problems.

I did post a little 22nd Sept @ 2136 re patents for Sierra.
Interestingly around the time the patents were applied for the for sale sign so as to speak was taken out the window

Hello Stoney40. Patents were for combination therapy SRA 737 with LDG and SRA, LDG and a PD1 inhibitor. SRA and LD G is definite.