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Many thanks SOG. Fingers crossed for next week.
Pretty engrossed in watching live YouTube of La Palma. Not good.
Great analysis you sadoldgit.......yes indeed..
This new respiratory patent..
.lovely.....money men bending over backwards to give money......
Good evening SD, apologies for late getting back, Looking through loads of old posts. Regarding blood clotting a post from June
First time I have seen the Sareum presentation.
Some interesting points. Control of interferon alpha and gamma controlled by Jak1 ( covid affected)
Secondly is Jak2 effects (EPO) Erythropoiesis Tyk2 and Jak 1 does not.
Why do I think this is important?
Erythropoiesis controls production of red blood cells. Our bodies can over produce red blood cells which is not good. What does it lead to? Thickening of blood and hence blood clots. Our bodies in most cases can regulate this. The cytokine storm which can cause lung problems reducing our amount of oxygen will produce more red blood cells. Jak2 may seem to counteract this. However, if we treat the cytokine storm which will reduce the inflammation of our lungs then blocking of ERO is not necessary. In this case reducing ERO will prove to be counterproductive to effects of treating covid as will limit production of red blood cells and at best would be dose dependant ie serious side effects.
jak 3 is too broad a spectrum ( ie it will again hit some of the keys we do not want to hit)
Tyk 2 along with Jak1 will control inteferon alpha and Interferon gamma. In addition Tyk 2 will hit one Interleukin 6 Jak stat pathway whilst Tyk2 will further control Interleukin 6 from another STAT pathway.
Interesting in the slides it does neither give the full spectrum for Covid 19 with regards to inhibiting all the Interleukins required for control of Covid ie no mention of IL-10. IL-7 and IL-23 for example and neither the full spectrum of what our Tyk2 and jak 1 will control.
I will research further as beginning to understand and enjoy. What I will add is that our TYk 2 Jak ! as far as I can see hits all the right targets for control and treatment of cytokine storm, whilst certainly having no serious side effects and looks also looks effective as a recovery treatment. There are a couple of Interleukins it also hits but I cant see if likely to be detrimental in any way.
With regard to Covid 19 Jak 2 and Jak 3 are about as much use as Jak 5hit.
I have been very certain of our Tyk2 Jak1 with regards as an effective autoimmune treatment in other indications but as I see it at the moment I am aware of nothing that comes even close with regard a treatment for Covid 19. Is it any wonder Tim and Co are so excited.
I repeat it again, nothing else come close. Jak2 and Jak 3 over selective. Pure Tyk2 misses vital Interferon control but the addition (optimum amount as Tim put it) adds to what pure Tyk 2 misses. No need I feel for another compound. It is to all intensive purposes all there all ready.
Regards and thanks to whoever posted the presentation.
Evening all, hope you've had good weekends.
Not ramping, pumping, cross promoting or trying to put on a furry womble jacket ... just idle Sunday evening conversation ...... but has anyone looked at Spectral MD and Trellus Health? I'm giving them both the once over for an hour tonight. Purely interested if others have looked at them.
Good luck for all portfolios this week ..... Sierra have to budge soon one way or another surely
Hey Danny ... the pressure is on Sierra so expect something soon ... Next week could be interesting ... Mafuta
Hi Mafuta. Appreciate your response. I was just thinking the dry powder nebuliser could be distributed deeper into the respiratory system due to being put on a ventilator.
Anyways, interesting times .
Best regards Steadydanny
Sierra has another conference this week (and the fireside chat after just prior to end of September)and Q4 updates from us surely re forthcoming trials re money at bank and how it will be spent incoming ......
Danny ... There was a dry powder inhaler for asthmatics in the 70s called the spinhailer made by fisons ... a small capsule was placed in a propeller socket and pieced by sliding the inhaler jacket down ... sodium cromoglicate was the compound ... Not very effective and rotted the teeth and gave a bad taste in the mouth ... The thing needed washing constantly ... Give me an aerosol any day ... Mafuta
Following on from your post SOG. I appreciate treatments have been discussed. Pill or via a nebuliser. I note GSK who produce asthma inhalers are noting its impact on the environment. I further note they actually produce a 'dry powder' inhaler which is common in Scandinavia but not UK or US.
I then bring into discussion il 6 which I find rather intriguing. This is an extract from The Lancet 26th June 2021. Just putting it out there but is it possible nebuliser administration of a treatment might be something we add value to re covid treatment?
Currently, the guideline strongly recommends the use of anticoagulation in all patients admitted to hospital with COVID-19, and strongly recommends the use of systemic corticosteroids in all patients admitted to hospital who require supplementary oxygen or ventilatory support. Conditional recommendations were made for IL-6 receptor antagonist monoclonal antibody therapies only for patients in hospital with COVID-19 requiring oxygen or ventilatory support who have received corticosteroids, and for use of high flow nasal oxygen or continuous positive airway pressure in patients with hypoxaemic respiratory failure. Currently the guidelines strongly recommend against the use of hydroxychloroquine and lopinavir–ritonavir, and makes conditional recommendations against the use of azithromycin, colchicine, interferon beta, and remdesivir (eg, the guideline recommends not to offer remdesivir to patients in hospital with COVID-19 who require invasive mechanical ventilation, but make no recommendations regarding when remdesivir could be used).
Just a further point for perusal re Sareums treasure chest.
What chance SAR are the next passengers in Musk's space programme.
Interesting Thoth BMS Celine v Nimbus TYK2 spat.
Would it be that Celine want to aquire Nimbus TYK2 and then sell one of the. TYK2's to a third party. Totally agree that If this continues indefinately in the courts its really good for SAR's on licensing prospects. Well spotted again. Exciting times coming down the tracks
Following on from last night and my point re REGN COV2 and monoclonal antibodies.
I note from Cancer research UK news release 28 July 2011 that Blink therapeutics was formed 13 June 2011.
...Blink will develop the novel platform to generate therapeutic and diagnostic monoclonal antibodies towards clinically relevant targets.
It goes on re end of 2005 Astra Zeneca acquired KUDOS for £121m....to progress innovative therapies relating to DNA repair. ( those used to my rambles know I go on about dna damage re rna dna crossover and tyrosine being replaced by uracil leaving toxic cytosine to build up causing cytokine storms)
Also Plramed acquired by Roche in April 2000 ( they are REGN COV2!)
Back to Blink Therapeutics. Sareum RNS re appointment of Michael Owen update on forgetting to initially add his time at Blink Therapeutics
Mon, 29th Jul 2019 16:29
RNS Number : 0933H
Sareum Holdings PLC
29 July 2019
29 July 2019
Sareum Holdings plc
("Sareum" or "the Company")
Additional disclosure concerning Michael Owen
Sareum Holdings PLC, the specialist small molecule drug development business, announced on 13 November 2018 the appointment of Michael Owen as a Non-Executive Director of the Company.
It has come to Sareum's attention that whilst his former directorship of BliNK Biomedical SAS ("BliNK") was detailed in that announcement, his former directorship of BliNK's subsidiary Blink Therapeutics Limited during the five years prior to that announcement should also have been included.
Maybe we are not so removed from the rollout next week as thought.
Best regards Steadydanny
Also SOG Many thanks for the chronology of 1802. Great reading.
SOG = SmartOldGit
From now on, I name you VVSOG
We are unique in our compound with much of the research being done with SRI. Clearly they had found that pure TYk2 could be improved upon. Although Tyk2 can inhibit the IL-6 group it would appear that a precursor is required for this, in this instance the Jak 1 interacting with glycoprotein 130 to enable IL-6 to be inhibited by signal transduction. Furthermore Jak 1 is the only Jak that gp130 interacts with.
So from this information which I cannot substantiate conclusively it does appear that unless Jak1 is used alongside TYk2 then its kinase inhibition of certain interleukins are somewhat restricted.
As much as we can speculate about who is looking for what, and how much we think we can pay at the end of the day it is the science that does the talking. From the valency of atomic elements, the formation of molecules to the inhibition of the activity of enzymes. Enzymes are mostly protein, as they do contain other constituent parts ie metal ions and cofactors (in the form of vitamins) required for catalytic activity. Proteins are made up of amino acids. Enzymes speed up chemical processes in our body. We have a complex immune system that relies on these for correct metabolism,
Enzymes can change the constituent parts of a molecule and reform a molecule made up of the constituent elements. ( think of a 3 dimensional jigsaw.)
Without science we would not be able to deduce why our TYk2 is effective in inhibition of IL-6 and others are not. I will admit I am far from being an expert, ( The likes of Tim and Co along with researchers like SRI, the ICR are the experts) the complexity of bio chemistry whilst intriguing is extremely complex to say the least and I have not even scratched the surface.
All we can do is speculate on what is happening or about to happen. That said, the facts of what we know are about to happen in the coming Q4 are enough to keep me sat firmly on my hands. We have:
SDC-1802 ‘associated’ patent
The submarine patent
CTA for SDC-1801
Announcing of the indication for SDC-1801 CTA
SAR Financial Year end approaching with updates
AGM with more release of updates
Going to be a great end to the year and this is without consideration of the wide speculation we have regards large pharma interest in our TYK2s, the covid/bacterial pneumonia angle, UK/WHO covid trials, take overs & buyouts, license deals and finally SRA737 news!
Hold for gold folks
Stoney, I'm with you on that one. Seems like the planets are lining up esp. now with Thoth's discovery of a big pharma on the hunt for a Tyk2.
My guess is that the patent secret or otherwise is the key to the licencing deal- I would think that give the celgene court issue this pharma probably doesn't want to touch it with a bargpole seen as it could drag on for 10yrs+.
It's allosteric as well. So my guess is the big pharma saw what Sar had Dr Reader gave Dr Owen a heads up he got his contact book out.
We spoke to said big pharma and showed them the data, they requested the secret patent filing- hence the BOD's push back to any info. on it with the reply 'it's confidential and we need to protect the IP'.
Only an opinion- what do you chaps think.
Whilst science is great and ive done my share.
The celgene court documents yesterday. A big pharma interested in licencing tyk2. And its only us now. I will say it again. **** my luck.
Great synopsis SOG
You are correct with the original SDC-1802 sub patent, it was considered too similar by the examiner to our existing patents for TYK2s. John appealed and eventually won. That was the Jan 2020 award. Now the new SDC-1802 patent ‘notice of allowance’ for an ‘association’ is very intriguing - this could be as mentioned another molecule or indication which maybe the bacterial pneumonia angle (covid).
We then of course have the submarine patent which was described as crystalline formulation......everything lining up nicely
Good morning SD, may be of use and give you a general idea of which what and how came first.
Been surfing through all old news. Regarding Tyk 2
Initially as auto immune Feb 12 Tyk 2
Agreement with SRI Apr 2013 auto immune and inflammatory.
First mention of Tyk2 Jak1 immune Feb 2014
Proof of concept Tyk2 Jak1 auto immune June 2014
First patent ( European) grant Tyk2 programme Nov 2014
Evaluation of Tyk2 in IBD, MS and Lupus Feb2016
Successful outcome of Cancer feasibility study of Tyk2 ( T-ALL) October 2016
Patent Grants in Japan and China for Sareum’s TYK2 Inhibitors Dec 2017.
Sareum reaches preclinical milestone in TYK2/JAK1 inhibitor programme - Potent, selective small molecule inhibitor of TYK2/JAK1 selected for further development as a potential treatment for autoimmune diseases ( note this is first mention of SDC 1801), closely related molecules Sar 20347 also evaluated ( Tyk 2, Jak1,2 &3) 10 Sept 18.
Potent, selective small molecule inhibitor of TYK2/JAK1 selected for further development as potential treatment for certain types of leukaemia, lymphoma and solid tumour ( first mention of SDC 1802) 26 sept 2018.
Sareum TYK2/JAK1 Inhibitor SDC-1802 Demonstrates Anti-tumour Activity in Multiple Cancer Disease Models Sept 2019.
Encouraging Preclinical Results Generated with Sareum’s TYK2/JAK1 Inhibitors in a Disease Model of Lupus. This was with Sar-20351 now known as SDC-1802 July 2020.
US Patent Allowance for Sareum’s SDC-1802 TYK2/JAK1 Inhibitor Oct 2020. I do recall some difficulties in obtaining a patent for SDC 1802 as was considered to close to the original compounds. This from memory ran on for some time.
TYK2 Identified as a Key Genetic Mechanism of Critical Illness in Covid-19 and as an Important Potential Target for Therapy Dec 2020.
US Patent Formally Granted for Sareum’s SDC-1802 TYK2/JAK1 Inhibitor Jan 2021. patent number no. 16/351,620
US Patent Notice of Allowance for Sareum’s SDC-1802 30 July 2021 patent number (US Patent Application no. 16/343,639)
That brief background of our Tyk2 Jak1 kinase inhibitors.
Will piece together your ideas on who how and what may be going on from your previous posts.
SOG. Very interesting. I thought I had a fair understanding of sareum. I'm definitely swotting up further this weekend. It is interesting how world politics and protocols seem to have a part dovetail into our research.
Very best regards and very many thanks Steady.
From 2018 RNS note the following
The preclinical development candidate SDC-1801 was nominated from a novel series of compounds designed and identified by Sareum following a rigorous selection process. The company is also completing its assessment of further dual TYK2/JAK1 inhibitors for the potential treatment of certain cancers and/or as a back-up to SDC-1801 and expects to nominate this candidate in the near future.
note the last sentence of 'completing its assessment of further dual Tyk2 Jak1 inhibitors for potential treatment of certain cancers or as a back up to SDC1801'
AFAIK candidate selection has already been established for 1801 and 1802. However, the above sentence would intimate that there would be a very high probability of at least one more candidate. I am fairly certain that the rule of thumb would be patent protection before selected candidate at end of pre clinical.
Those that have postulated another molecule or candidate may be proved correct after all.
Indeed Sareum have got us on a guessing game. There is so much going on that we are not privvy to.
This gets really interesting SD. looking through old RNS.
It will take a while to dig into. There have been many patent applications which of course different application numbers.
I will digress a bit. Do we have or have we ever had a TYK2 jak 1, Jak2 and Jak3 inhibitor?
The candidate molecule, SDC-1801, demonstrated high selectivity for TYK2 and JAK1 kinases (particularly over related JAK2 and JAK3), compelling activity in disease models of psoriasis and rheumatoid arthritis, the potential for once-daily oral dosing and a good early safety profile. Closely related molecules, including SAR-20347, have also shown good activity in models of inflammatory bowel disease and systemic lupus erythematosus (lupus). These attributes strongly support the progression of SDC-1801 into preclinical development and, pending satisfactory progress, advancement into human clinical trials, which could begin in 2020.
The preclinical development candidate SDC-1801 was nominated from a novel series of compounds designed and identified by Sareum following a rigorous selection process. The company is also completing its assessment of further dual TYK2/JAK1 inhibitors for the potential treatment of certain cancers and/or as a back-up to SDC-1801 and expects to nominate this candidate in the near future
A JAK family kinase inhibitor (IC50s = 0.6, 23, 26, and 41 nM, for TYK2 and JAK1-3, respectively, in cell-free assays); inhibits IL-12-induced TYK2-dependent phosphorylation of STAT4 in NK-92 cells (IC50 = 126 nM) and IL-6-induced JAK1-dependent phosphorylated STAT3 signaling in TF-1 cells (IC50 = 345 nM); inhibits IL-12-induced INF-? production and reporter gene activity in PBMCs at 5 µM; inhibits the production of serum IFN-? in mice at 60 mg/kg; reduces keratinocyte activation and skin levels of IL-12, IL-23, IL-6, IL-22 and IFN-? in a mouse model of imiquimod-induced psoriasis
Greatly appreciate your response and your posts. I Have been a bit quiet here for a couple reasons. But hey ho.
Excuse my naivety but if you could (I appreciate you have better things to do) advise my further thoughts given your response.
1802 is a tweak of 1801 I believe. We upped our patent application in US. When I read large companies feeds I often look at what they are withholding.
Roche advised partnering in US. Regeneron or something. And others. But they would need to finance their own further trials. So maybe could it be not a drip? And re US and tommiblium ( I can never spell it) and Sierra and they advised they were able to access $33m if required within a time frame for further trials. Then we have our own subscription raise in blighty. Then our ceo mentioning the Patent update to cover us in US to further protect our ipr.
And the 19th August could just be a coincidence re Rothe and Sareum.
I'm not great at being succinct but am I looking at clouds in the sky and seeing patterns that are only in ones mind?
I am a bit of a nimbus.
Once again many thanks SOG and i will scuttle off and do more research. I keep reading this bb and enjoy the genuine posters.
Best regards Steadydanny
Good evening SD.
Monoclonal antibodies are not new. Similar to an anti viral.
These may well prove 'satisfactory' short term until virus develops resistance. It provides breathing space for a period of time.
I am surprised they give to HIV infected persons as they are a breeding ground for new strains of Covid 19. In addition this new treatment has been agreed/ appraised/ evaluated before we had variants of concern, weeks ago.
It certainly does not rule out SDC1801.
The virus shows no signs of retracting. The virus is now classed as endemic and not pandemic. That means treatments will be needed for the foreseeable future.
We still are at risk from a more contagious and damaging strain.
Government can only work with and put into clinical use treatments that have a known positive effect. Has our SDC1801 been fully evaluated?
Of concern is this winter when the virus will be at its most dangerous in cold damp conditions and people mostly restricted to indoors.
Next year new strains and new treatments required.
One important difference here is this mono clonal antibody is a treatment for acute and mild Covid 19. SDC1801 when described as 'indeed does down regulate the cytokine storm' is clearly for a different kettle of fish. One may be classed as a preventative and the other a cure with regards to cytokine storm.
I have a feeling here that although this mono clonal antibody will be used from next week further treatments will become necessary. We need be one step ahead and not one step behind.
Extract 30th July RNS
The patent (US Patent Application no. 16/343,639) will protect the SDC-1802 molecule and pharmaceutical preparations thereof as a therapeutic to treat cancer selected from pancreatic, colorectal and kidney cancers, melanoma, and B-cell lymphoma by inhibiting TYK2 kinase. This programme is in preclinical development.
The Company expects that the patent will be granted within three months, subject to certain formalities being completed.
Sareum's CSO, Dr John Reader, commented:
"The granting of this patent in the US will provide a further layer of protection around SDC-1802 following the granting of patents protecting the molecule in the US and other major markets in recent years. These patents are important to enhancing the value of the programme as part of our discussions with potential partners."