Member Info for sadoldgit

Upadacitinib

Serious infections. RINVOQ can lower your ability to fight infections. Serious infections have happened while taking RINVOQ, including tuberculosis (TB) and infections caused by bacteria, fungi, or viruses that can spread throughout the body. Some people have died from these infections. Your healthcare provider (HCP) should test you for TB before starting RINVOQ and check you closely for signs and symptoms of TB during treatment with RINVOQ. You should not start taking RINVOQ if you have any kind of infection unless your HCP tells you it is okay. If you get a serious infection, your HCP may stop your treatment until your infection is controlled. You may be at higher risk of developing shingles (herpes zoster).
Increased risk of death in people 50 years and older who have at least 1 heart disease (cardiovascular) risk factor.

Cancer and immune system problems. RINVOQ may increase your risk of certain cancers. Lymphoma and other cancers, including skin cancers, can happen. Current or past smokers are at higher risk of certain cancers, including lymphoma and lung cancer. Follow your HCP's advice about having your skin checked for skin cancer during treatment with RINVOQ. Limit the amount of time you spend in sunlight. Wear protective clothing when you are in the sun and use sunscreen.

Increased risk of major cardiovascular (CV) events, such as heart attack, stroke, or death, in people 50 years and older who have at least 1 heart disease (CV) risk factor, especially if you are a current or past smoker.

Blood clots. Blood clots in the veins of the legs or lungs and arteries can happen with RINVOQ. This may be life-threatening and cause death. Blood clots in the veins of the legs and lungs have happened more often in people who are 50 years and older and with at least 1 heart disease (CV) risk factor.

It is tragic if Thoth2 has died.
He is and will be missed.
He took a lot of stick too, I will add.

I did not always agree with everything he said but, he certainly calmed many on this board including myself during periods, of low down beat sentiment.

As for what the future hold here, nothing is a100% certainty.

737 will be open to development in one form or another. It has too much potential in combination to be ignored.

SDC1801 as we know is a dual inhibitor of Tyk2 and Jak1.
Tyk2 has at the moment a good safety profile.
Jak 1 inhibitors have proved problematic in the past due to lack of selectivity over Jak 2 and 3
It will most likely be in my opinion the amount of Jak1 in this dual inhibitor that will limit doses in dose escalation trials.
Just being very balanced here. There is a ratio in SDC compounds of Selectivity of Tyk 2 over Jak1 and also Jak1 over Jak2 and 3 of this in my opinion I believe is vital to its indications and success thereof.

We can look at other pharma's results ( jak1 2 &3) in clinical trials and see the levels where toxicity and adverse effects come in.

There really is not a great deal of difference if you take a look across the board , they all have in common a postulated maximum therapeutic dose. In the clinical trial, efficacy is dose dependent as are adverse events. That is where many problems arise. Not to be confused as maximum tolerated dose I might add.

With regards to Jak1 inhibition and safety.

Abbvie's Upadacitinib ( Rinvoq)
Approved for UC by MHRA on the 22nd November 22.
Approved for CD by MHRA 2nd Feb 2023

Note
'JAK1 selective drugs, upadacitinib and filgotinib, have broadly come with the same overarching safety recommendations as other immunosuppressive drugs for RA: caution is needed regarding infection risk; monitoring for laboratory abnormalities, including lipids and muscle enzymes, is indicated.'

Yes there are safety concerns with Jak1 inhibitors but that has not prevented the approval of AbbVie's Upadacitinib for CD and UC. Originally granted FDA approval for Rheumatoid Arthritis in June 2019. Now also available as treatment for Active Psoriatic Arthritis and currently undergoing late clinical trials for ankylosing spondylitis.

You can make your own minds up as to how and where SDC1801 can fit into this market.
Effectively combined Tyk2 and Jak1 should prove at least similar efficacy but significantly reduced adverse effects.
As for the combination of Tyk2 and Jak1 with regards to safety. I have not come across anything to suggest in the slightest that this would result in non approval
As I have stated, make your own minds up.

Regards

Regards

Thanks DeAar.

DeAar
where is the following statement in the Edison link
'Safety profile of combined TYK2/JAK1 inhibitor not certain or proved yet.'

Please accept my apologies on that one Warthog.

A great balanced post HbD.
I did mention to our resident expert here on Nitrosamines that it could be controlled by adherence to GLP. He informed l were wrong.

Good you have clarified the situation here with your post.

Warthog l will post what l like at who l like. Freedom of speech.

Not see a reply to you query BillyBunter.

MHRA were unable to approve CTA as required further supportive information or a review by thr Good laboratory practice monitoring authority.

Turned down indicates absolute refusal which is clearly not the case.

Regards

Kool kat you were not laughing you are5e off when you were hovering over the button at mid 50's.
I was when l read your post.
You and others like you post nothing of substance.

Never have and never will.

Have a good day.

2 articles, the first of a new stage 2B trial in Psoriasis in OZ.
The 2nd is the PASI score.
Effectively the baseline for PASI score is 75% and was achieved with Deucravacitinib over a 16 week period from memory. I believe our goal is to at least reach the same in a 12 week period.
Tyk2 Jak 1

https://www.uq.edu.au/news/article/2023/03/clinical-trial-success-psoriasis-drug

https://www.healthcentral.com/article/what-is-the-pasi-score

Abstract Aug 2018
Cytokine signaling is an important characteristic of autoimmune diseases. Many pro-inflammatory cytokines signal through the Janus kinase (JAK)/Signal transducer and activator of transcription (STAT) pathway. JAK1 is important for the ?-common chain cytokines, interleukin (IL)-6, and type-I interferon (IFN) family, while TYK2 in addition to type-I IFN signaling also plays a role in IL-23 and IL-12 signaling. Intervention with monoclonal antibodies (mAbs) or JAK1 inhibitors has demonstrated efficacy in Phase III psoriasis, psoriatic arthritis, inflammatory bowel disease, and rheumatoid arthritis studies, leading to multiple drug approvals. We hypothesized that a dual JAK1/TYK2 inhibitor will provide additional efficacy, while managing risk by optimizing selectivity against JAK2 driven hematopoietic changes. Our program began with a conformationally constrained piperazinyl-pyrimidine Type 1 ATP site inhibitor, subsequent work led to the discovery of PF-06700841 (compound 23), which is in Phase II clinical development (NCT02969018, NCT02958865,

As Tim said there will be areas in immuno of which TYk2 will prove greater profile over TYK2 and Jak1 and vica versa.

Pure Tyk2 has given good results in clinical trials of psoriasis
In Ulcerative colitus it did not cut the mustard ( krones and UC are IBD's)

The proof of the pudding as we say is in the eating.

Bio markers are an important tool to in predicting outcomes and as a diagnostic.

https://en.wikipedia.org/wiki/Biomarker#Medicine

Yes it is wiki, not a favourite of Thoth I might add, but ample to get an understanding.

Regards

Since you have been posting here Bluenose, just what exactly have you contributed of any substance?

I will tell you . SFA.
I don't mind constructive criticism. What do l mind is spineless little individuals of which you are a classic example, that cannot put a reasoned argument together substantiated by anything of substance.

I will reinforce the point, you and others like you that whinge and complain bring nothing of substance to this board regarding Sareum worthy of note.

There will be several on here that dislike me. I am not bothered. No one to be feared here.

There are reasons l post here and that is to shine a positive light to what we have here. People can and do become nervous and there are those that will play on that.

I must add I have rather enjoyed my time here today. Nice to unwind and give a balanced view against the recalcitrant derampers.

No problem. I think it maybe prudent to take it as market sentiment.

The element of doubt with regards to timescales for CTA final decision have now been removed.

Statutory time frame is 60 days from receipt of application.
A request for further information is likely to add considerably to this time frame.

Indeed it were around 100 days that MHRA took to respond that in fact they aim to respond within 15days
Statutory time frame of 30 days for Initial assessment.

Covid vaccinations or whatever but the time taken by the MHRA to respond is just unacceptable. Other companies have suffered too.

Sareum has taken the decision and with considerable effort, accomplished initiation in a relatively short time scale.

They have been in possession of all relevant documentation since CTA in July, yes.

Should it, in the unlikely event of a decision of non approval, by the board, equivalent of our MHRA, then we really would take a hammering, big time.

Ahfam l ask why the SP rises and it says day traders.
I ain't a day trader but added a few.

Market saw it as positive sentiment.
They are in it to make money too.

Do you know Ahfam that none of these people challenge about the science. The only one who has and trying to be clever lost that abysmally.

For a balanced view you must to a certain extent understand even very basics of science and understand what science is.

Now as someone who has just admitted they don't know anything about the science or any science come to that, then go on to state they have a balanced view.

Science is not the be all and end all l will admit, but without it we would be pretty worthless in the current climate.
What people fail to understand is the failure by the MHRA.
30 days initial assessment.
Sareum not informed until 8th November. Over 100 days later.
Request for further information in this sense a GLP monitoring authority review.
We have heard no more and if we take 16th Dec when Tim we requested further clarification ( at the same time the review had not even been started).

Sareum are not alone in these unjustified delays.

There are the new libellous negative posters now that make out they give a balanced outlook.

24 carat dyed in the wool cobblers as you never hear from them when significant price increase.

Is it any wonder that the world is in such a state when we have such dregs in the human race, from all walks of life. Those that will decieve and lie to get what they want.

You lost all the discussions so far.
Nothing of substance to back your opinions up.
Says a lot about somebody.

Kool.Kat you could have saved yourself a lot of time but just shortening your post to ' l don't have a clue ' would have been spot on.

LMAO

Balanced views?
You were asked on what factual basis do make such an absurd statement.

I have not replied as l go to work for a living too.

Unusual but I your case you are both ignorant and arrogant. On top of that you have nothing of substance to back your statements up with you imbecile.
Have a nice day and try not to lose it to much.

Lots of hugs

Warthog. Perhaps it could be those dreaded Nitrosamines that is all the rage at the moment.

MHRA a shambles like most other government departments. You only have to look at the top department to realise this

They are not interested what is best just interested in what boosts their own ego's. Career politicians.

You could take David Cameron out for lunch. Cost you 200k but a decent government contract is what you will get in return.
Programme about that around 5 to 6 year ago.
That why you not see poor politician especially senior ministers.

Enough.
Onwards and upwards

Kool kat give it a rest as you making yourself look a bigger fool than you already are.

You don't know and do not have the knowledge or experience to prove any different.

As the Aussies would say you are a real Leo.

regards

Kool kat . Sareum not put a strong enough case'

What do you know to make such a ridiculous statement?

The MHRA has serious failings in understaffed and inexperienced. Already been identified by the government.

Too many MP's in pharmas back pockets.
Covid completely different cookie. The government had to be seem to be doing something. Absolute shambles with RPE and PPE for covid with millions spent and nothing recieved in return.

What exactly is do you intend to achieve by posting here. For certain it is not a well thought out balanced opinion.

Regards

Happy

Absolutely HbD.
Nitrosamine CoL here.
He not got back.to.us sdc.compounds and Nitrosamine risk.

He has learned a lot in the past week. With a bit of luck keeping his gob shut is one of them.

Nitrosamines are not new
Have been around many years. Epoxy resin hardeners and Hydrazine that we used as a deoxygiser in steam systems.

I dare say we will.here from.here again but will not answer my questions l.put to him directly. Never has and never will.do.

Just read through what he posts. No substance and behaves like he is some all.powereful.judge

Onwards and upwards now.
Regards