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Certainly is .. I had managed to avoid it for nearly 2 1/2 years .. went to a fund raising do last Friday at the Castle in Arundel and tested positive on Wednesday as did several others there. Symptoms no worse than a summer cold .. slept all day yesterday and feel a lot better(almost normal) today! Will self isolate for another 4 days although I’m not sure this is obligatory any more.
Don’t understand why they make such a big deal now of a condition which for most people is only mildly uncomfortable and for only a short period of time.
Great to hear that you’re quickly on the mend.
The reason that it’s a “big deal” is that not everyone has your “mild” experience, though. One thing that’s becoming clearer now is that covid can cause T-cell damage, and re-infection can cause severe T-cell damage.
It’s not straightforward and an unscientific sample of one is exactly that - unscientific.
Just reading of a case where one person had a similar experience as you’ve described the first time he was infected, the second time he was infected was much more unpleasant and serious. The third infection killed him.
An interesting point you make there SCHeckler. I know of several people who have had covid more than once. Many have been vaccinated. Damage being done when infected is from very mild to very serious.
Am in the highlands at the moment and people appear to be suffering more once they get covid the later strain. 10 days and later they are still testing positive. This indicates that our immune system is not working as effective as once was, at least not to the latest strain, Although not required there are many people now taking up the wearing of facemasks.
BA 5 strain a virus of concern.
Our immune systems are very complex and in most cases are effective, However, viruses do mutate as we all know. With current events going on in the world Covid has been somewhat out of the news. Covid up to a point has led to you into believing it is all part of a normal life. Covid is mutating and becoming stronger as a result of passing through human beings immune system.
Is it a case of our immune systems weakening or is it because the virus has evolved to overcome our immune systems?
I dont know the answer. But, I believe vaccination is the be all an end all. Other treatments are required especially for those that develop severe covid.
Several people that have had no vaccinations whatsoever do not appear to suffer as much as those that have received all vaccinations.
We have potential to treat with our SDC1801 but know idea as to if and by how much this has progressed.
if the covid does take a turn for the worst then we will have not only the capsulated formation, but also early preclinical data to indicate its effectiveness in down regulating the cytokine storm without increasing viral load.
We are in a much more advanced stage than we were 12 months ago.
It is important that we get CTA submitted ASAP but not holding my breath for an RNS as timeline was put at mid year. Sareum have always ran a tad late.
But on issuing an RNS confirming submission of CTA, I would also expect a fair bit of detail as to the immuno therapy indications and in addition an update of intentions, well more that that ie plans to put forward or not SDC1801 as a form of treatment in perhaps clinical trial at least.
Likewise with SRA737 I do not believe we will hear anything until designing of combination trials have been completed.
Much work has been done in vitro and normally to progress a compound whether singular or multiple will take time in preclinical prior to human trials. That being said I am fairly certain that GSK will be looking at 737 and LDG in combo with their own PARP inhibitor. It all takes time.
I am very confident in Sareums compounds but also aware that development takes time and there are situations that have arisen beyond the control of the Sareum BOD. Negotiations take a very long time and formal stage negotiations follow informal stage negotiations. Am pretty well convinced we have entered the formal stages.
Hi SOG - I'm not sure we'll know what the intended indications are for 1801 when the CTA is submitted. From the March RNS covering the toxicology report, "Sareum is working with specialist clinical trial consultants to design the first clinical trial with SDC-1801. This Phase 1a trial will investigate the safety of ascending doses of SDC-1801 in healthy subjects prior to the selection of an initial indication for further clinical study in patients in any subsequent trials."
My interpretation is they're keeping all options open until the next phase. This is probably beneficial as it'll allow potential partners to pick and choose future direction for 1801.
More patience required, I'm afraid.
Patience is required HbD, yes. From memory Tim hinting at the less competitive areas. There are many indications and I think will be IBD and maybe SLE.
Inflammatory bowel disease problems have been encountered. Especially where Jak 2 concerned.
A brief overview of IBD below.
'Inflammatory bowel diseases (IBDs), mainly represented by Crohn's disease (CD) and Ulcerative Colitis (UC), are chronic disorders with an unclear pathogenesis. This incurable and iterative intestinal mucosal inflammation requires the life-long use of anti-inflammatory drugs to prevent flares or relapses, which are the major providers of complications, such as small bowel strictures and intestinal perforations. The introduction of tumor necrosis factor (TNF)-alpha inhibitors and other compounds, such as anti-IL12/23 and anti-alpha4/beta7 integrin monoclonal antibodies, has considerably improved the clinical management of IBDs. They are now the standard of care, being the first-line therapy in patients with aggressive disease and in patients with moderate to severe disease with an inadequate response to conventional therapy. However, for approximately one third of all patients, their efficacy remains insufficient by a lack or loss of response due to the formation of anti-drug antibodies or compliance difficulties with parenteral formulations. To address these issues, orally administered Small Molecules Drugs (SMDs) that use a broad range of novel pharmacological pathways, such as JAK inhibitors, sphingosine-1-phosphate receptor modulators, and phosphodiesterase 4 inhibitors, have been developed for CD and UC. This article provides an updated and complete review of the most recently authorized SMDs and SMDs in phase II/III development.'
Cannot access article. Abstract above from July 21.
Looking good if we go into that area of treatment.
Regards
SOG: I think there may be a typo or mistake in your 4th para?
“ I dont know the answer. But, I believe vaccination is the be all an end all. Other treatments are required especially for those that develop severe covid.”
You mean *isn’t* ?
There’s several problems with vaccines (and probably more):
- No therapeutic response to severe symptoms
- vaccines by their nature are reactive and always “behind the curve” with a mutating virus
- there’s some evidence that vaccines aren’t helping the immune system to resist infections, in fact possibly the opposite
Of course SAR has a potential role to play in the first problem area.
SOG - I certainly don't envy the task our BoD have in choosing the initial target for a compound. I'm picturing a sliding scale where at one end we try to muscle-in on an established high-value market and at the other end you have the chance of being the only drug of choice albeit in a smaller market.
No doubt this is where the various consultants we employ will earn their keep but at least it would appear 1801/2 could be highly effective in multiple indications.
I think we would definitely have the edge in IBD. Jak1 Jak2 okish, tyk 2 Jak2 bloody pointless. Jak1 Tyk 2 very good Indications. No adverse side effects from infections. We will have excellent LADMET especially in capsule formulations. Only downside l can see and the most likely is a dose related affect being mycocardia. It apparently has been identified in small kinase inhibitors but kept rather quiet. However, thus may be because other side effects established themselves long before continued doses reached an alarming degree of mycocardia.
Toxicity will be reached at some point. I feel.we are in an extremely strong position
Much attention to detail has gone into the development. As someone stated earlier we have outsourced when required to the best people in the world. Funnily enough GSK aint one of them .
The real biggy will be stage 1 clinical trial results. Our compounds are at least good if not the best. They are also extremely well protected by patents. Compatible with nigh every other type of compound going..
Sareum should have a pretty good idea what Indications to go for. After all it is they who designed the inhibitor to treat the targeted areas in the first place.
Immunotherapy therapy is vast and more than 1 type of inhibitor will be required for many years to come. The more you look into.it the more complex it becomes. There is a bloody big market out there for treatments. I am not for one moment suggesting we will capture the entire market, more along the lines of a very comfortable share of. Enough to make many financially very comfortable.
I look in here most days read some of the interesting posts and that is about it. It is good to leave the share chat for a while. I think it enables us to evaluate things looking from outside the bowl.
Regards
I may be slaughtered for this but considering most here feel Sar have the cure within their various products for every disease known to the human race who at Sar is selling or negotiating or doing anything to push this because all I can see is long term and incredibly patient shareholders blowing the trumpet and all PRket does is tweet on twitter to keep interest going but there are still no sales and no contracts and no money!!!
Should have read Parker
Excellent posts SOG, I trust you are well.
You are right to highlight Myocardial issues.
I was reading this earlier:
https://www.frontiersin.org/articles/10.3389/fimmu.2022.922782/full
ATVB
Siennaj, pharma is a very slow moving business. We’re now closer than ever with achieving our goals.
Interesting post SOG. I was under the impression that the phase 1/2 data for Pfizer’s Tyk2/Jak1 proceeded without any significant adverse effects. Is the myocardial issue something that has been found recently? As for 1801/1802 being best in class that remains an aspiration rather than a certainty atm, time will tell ultimately after phase 3 complete for whatever indication. That’s sometime away and I imagine most PI s will have bailed before then.
Good evening ndr50.
Cannot locate original links I had. This one will indicate that kinase inhibitors carry a risk of heart problems. Not all bad I might add. it has been know about for some time. Not really been a topic of that has raised its ugly head. Mainly but not wholly caused by off target inhibition. Very early link to ICR for CHK 1 inhibitor indicates the pedigree we have in our drug design and formulations also added here.
https://oxfordmedicine.com/view/10.1093/med/9780198784906.001.0001/med-9780198784906-chapter-292#:~:text=The%20most%20important%20cardiovascular%20complications%20of%20these%20kinase,arterial%20thromboembolic%20disease%2C%20QT%20prolongation%2C%20and%20pulmonary%20hypertension.
https://www.icr.ac.uk/news-features/latest-features/kinase-inhibitors-the-science-behind-a-revolution
https://pubmed.ncbi.nlm.nih.gov/20728698/
https://www.sciencedirect.com/science/article/abs/pii/S0033062010001167
https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30306-6/fulltext
https://www.nature.com/articles/s41392-021-00826-7
It does point to a need to have extreme purity in compound formulation.
Tim and Co I am certain will be aware of this and taken into consideration. Am making a guess as to why so much precision, attention to detail put into its inhibitors.. We must also bare in mind that these effects would have happened to early designs and compound creations, whereby a pharma will focus on what a compound can do without the same amount of attention to the side effects.
I will reiterate that I do not see this as a major concern. We have no idea how much and how far Tim and co have addressed this problem as any information regarding this will be commercially very sensitive. Clearly they are very confident.
Regards
PS Sometimes it may appear I am ramping like hell. But if I think there are areas not looking so positive I will post so as to raise debate. It is not fear of the known which troubles us it is fear of the unknown.
Regards
Well, the vaccines are killing people as well, I know over 20 that have been to hospital, heart attacks or chest pains, blood clots and other problems, everyone double or triple vaccinated. Herd immunity was achieved several mths ago and those test kits are useless, might as well stick them up your anus, that might be positive though. Let’s not forget, these are 2 year experimental jabs.
i will add that phase 1/2 data may not bring to a head the development of heart problems.
https://www.evaluate.com/vantage/articles/news/snippets/pfizer-bows-out-tyk2-race
https://www.evaluate.com/vantage/articles/news/snippets/lattice-miss-grating-bristol-myers
Deucracitinib is pure Tyk 2 and failed in IBD ie UC. maybe looking at trialing woth kigher doses. Higher dose of course leads to higher risk'
As far as I can tell 1L-10 inhibition is of paramount importance in treatment of IBD. IL-10 consists of 4 sub units 2 of which are Jak 1 and 2 of which Tyk2. Without this I reckon they are pretty will phu..ed in this indication.
Pfizer have gone the Tyk2 Jak1 route. They have not made public any severe side affects at the moment. They may be minor or major ones.
An inhibitor is a tool, nothing else. if we do not use this tool correctly it will fail. In this instance dosing regime with how much and to what frequency will give optimum results cannot be over estimated. Drug companies are outsourcing to specialist companies in this field. You cam include if you wish the acquisition of a company. Why? They do not have the knowhow themselves. ) Lucrative markets cost of initial investment and nippy bum time come to mind)
Discovery of Tyrosine Kinase 2 (TYK2) Inhibitor (PF-06826647) for the Treatment of Autoimmune Diseases. This was discontinued at end of 2021. I would summise as pure Tyk2 only
Enough from me.
Regards to all and enjoy what left of weekend.
Good post Citizen79. Apologies but have only just scrolled down to your post.
Important to look at all sides of the battle, Where and why others fail , why some succeed and others do not. Attention to detail. All have plusses and minuses.
I am fine thankyou and trust likewise you are the same sir.
Regards and keep those post coming, knowledge is power.
Reminds me of a very old joke Carter 19.
An elderly couple went to the doctors. Chronic constipation was diagnosed. The doctor prescribed them some suppositories.
The elderly couple returned home and duly read the instructions. One to be inserted up the anus once per day. The old boy says. ' ere Ethel what the f..k is an anus? I don't know Ethel replies but we have a dictionary and we can look it up. Ethel meanders over to the sideboard picks up the dictionary and opens it. I have found it she says. What is it then Bert asks?
It's a back passage Ethel replies.
We have a back passage that leads away from the back door he says. We are very fortunate to have found it.
Every morning they open the back door and throw out 2 of these suppositories.
2 weeks later they return to the doctors.
Good morning Bert and Ethel the doctor says, how are you getting on with your medications?
Not good at all says Bert we both took them as directed but condition has got worse. I am not happy at all with them. For what good they have done, we might just as well stuck them up our ar5e.
Sog. That's a great joke. Loved it
SOG thanks for posting those links. Until 1801 unleashed on humans and data released we just have to hope that we’re mostly clean.
Reminded me of mylast prostate exam. Doctor mutttered "dont worry its perfectly normal to get an erection in this situation." I responded i was fine. He said "i was talking to myself".
Thoth - Could be worse, he could insist on spooning afterwards.
Thoth you only have to worry when he has two hands on your shoulders
I always dread the sound of rubber gloves in these situations!!