Member Info for sadoldgit

Abbvie.

Not jak related.

https://www.biopharmadive.com/news/abbvie-emraclidine-failure-schizophrenia-bristol-myers-cobenfy/732534/#:~:text=AbbVie%20lost%20about%20%2440%20billion,acquired%20for%20almost%20%249%20billion.

An overview on Jaki nibs, not as long or in depth the other report l found but a good indication of events.

The later parts are worth reading but do require a tad of knowledge to comprehend fully.

https://ard.bmj.com/content/83/2/139

I will add much of this is very recent, it will give very valid reasons why further toxicology studies are required.

Although there is supposed greater selectivity with 2nd generation inhibitors most exhibit unwanted adverse events yet can considered acceptable.

Also of importance is how molecules bind and the mode of which in this report does not go into great detail as the other report l cannot now find.

The recent Nov report by Edisin gives a decent report highlighting our safety profile.

We do have competitors.

Posts below indicate that both Breprocitinib and Ropsacitinib have their limitations.

The good news for them is that indicates efficacy.

Many of the Indications trials have ceased.

Breprocitinib is Tyk2 Jak1

Ropsacitinib has higher selectivity for Tyk2 albeit higher Jak2

Sometimes is put as Tyk2 Jak1.

Selectivity 15nano mol Tyk2

Jak1 356nmol

Jak2 74 nmol

Jak3 >1000

As can be seen Tyk2 approx 25x Selectivity over Jak1

Only 5 fold Selectivity over Jak2

Selectivity over Jak3 many fold.

Basically we have Ty2 Jak2 inhibitor.

Goods results claimed in Psoriasis.

So the question is Why discontinue?

Ropsacitinib exhibits side effects one of which is increased creatinine levels.

What is the impicstion here?

Renal damage ie can develop to such an extent to lead to kidney failure.

Now in the report it states a glancing remark that adverse events in line with previous studies.

Is that good or bad?

It is bad enough in that when looking to commercialise what is the cost of the treatment with regards to its performance.

Whilst reported an acceptable safety profile it merely places it in the same category as other poorly selective Jak inhibitors.

Effectively if commercialised would not generate enough revenue to make progress worthwhile in such Indications.

Indeed they then look I to other Indications such as areas in urgent unmet need.

When people refer and moan about here it is all about deal making, l trust that they take I to consideration of the SDC candidates performance and how it compares with other competitors attempts at developing compounds for commercialisation.

The science is completed.

Objective or Aim of experiment

How it is set up

How the experiment is performed

Results

Conclusion and this effectively the evaluation of the data.

May be reviewed by a other individual.

I learned that over 45 years ago in school.

The degree of complexity and detail are far greater here with our compounds ut ultimately the process is very much the same.

We need understand where we fit.

As Tim has commented and stated we can now supply data to prove that with regards to safety we are better than Breprocitinib.

Better than Ropsacitinib too.

Two later stage candidates that have been withdrawn in most of their originally planned Indications.

No big deal made about it.

Look at the plus points here!

Regards

Https://pmc.ncbi.nlm.nih.gov/articles/PMC9959504/

Brepocitinib failed to achieve an SRI-4 change of 4 at week 52 in adults with lupus

The manufacturer plans to continue with the drug’s program outside of lupus, citing promising results in other trials.

Discontinued conditions

Brepocitinib has been discontinued for alopecia, alopecia areata, atopic dermatitis, lupus vulgaris, plaque psoriasis, psoriatic arthritis, systemic lupus erythematosus, ulcerative colitis, and vitiligo.

Conditions still being developed

Brepocitinib is still being developed for non-infectious uveitis (NIU) and dermatomyositis:

Non-infectious uveitis: The FDA granted fast track designation to brepocitinib for the treatment of NIU. Roivant plans to initiate a Phase 3 program in NIU in the second half of 2024.

Dermatomyositis: The ongoing Phase 3 study evaluating brepocitinib in dermatomyositis is expected to be fully enrolled in the third calendar quarter of 2024, with data expected in calendar year 2025.

Goid post fearg.

Don't forget ano genital.

Good to see positive normality returning.

A question here is that should the market cap of over 300 million remained and with current developments what would be the value of them now, since with current progression we are more forward with better than expected results?

Julie1, trust you are enjoying Christmas and truly believe the holders here will have a rewarding 2025.

End of the periods of delays and inability to approve.

Validated data and interpretation of from December 18th as signed off.

A massively undervalued pharma at the moment that in 2025 should provide multitudes of current value.

Regards to all

I don't think Tim Mitchell wants to wait to 68 either!

Yes l wish you all a merry Christamas and an extremely prosperous 2025.

As most know l attended the AGM.

Meeting was fine, no squeaky chairs, Michael Owen was quiet, sorely tempted to get up and check if he had a pulse, but have a feeling that may of ruined the atmos.

The after chat reassuring with indeed a degree of focus on pushing 1801.

Data is validated now and that is what a pharma whether on licence or buyout require.

737 we or rather the boards expectation that milestone will be paid plus a few shares.

1802 development now back in progress.

Share price of a paltry 27p a share is indeed a paltry sum for what we have currently have with our pipeline.

On a different note Steady Danny gives this board a read now and again and indeed was a good contributor. I will wish him a great Christmas and prosperous 2025.

It was great to meet John and Steve at AGM and indeed the effort they put into attending.

Time to blow the froth off a couple.

Regard to all and a great Christmas

Good morning Funnyguy.

Regards to on licence and 50% rise l you referring to SRA737 or SDC1801?

Commercialisation is based on what we have and what stage we are at in development.

How we compare with similar inhibitors and the requirements of interested pharma.

Safety is paramount with 1801 and whilst other similar inhibitors exhibit unwanted off target events we must prove via long term toxicology studies that our compound exhibits little to no toxicity concerns.

Regards

An excerpt from the patent

,'SRA737 activity was significantly enhanced by a Weel inhibitor in SW620, HT-29, Calu-6, KURAMOCHI, OVCAR-3, 5673, TCCSUP, J82, MIA PaCa-2, Pane 03.27, FaDu and CAL-27 cancer cell lines. In contrast, SRA737 activity was not affected by the presence of additional Weel inhibitors in the wild-type cell lines. Finally, Weel inhibitors such as MK-1775, in combination with SRA737 demonstrated significantly increased anti-cancer efficacy across a broad range of cell line panels representative of tumor types that include, but certainly are not limited to: bladder, colorectal, lung, ovary, pancreas and head and neck cancer cell lines.'

I was not aware of this patent

Sierra Oncology.

Can find very little on Sareum RNS's spotlighting this.

https://patents.google.com/patent/WO2018191299A1/en

From memory it was in the status of final trial design around end 2020 early 2021.

Agree HbD, it would be good to know just who the private pharma is in the US as well.as current state of affairs with 737.

A small private bio.pharma owned and controlled by who is indeed something we need answers to.

Rather weird that their has been complete anonymity since Jan 3rd.

Has sufficient funding been raised and if not what has progressed.

Are they looking at large funding requirement to enter into clinical trial?

We should get an update but not as much as we would like a out payments , shares and progression.

Regards

Https://pmc.ncbi.nlm.nih.gov/articles/PMC10539020/

Https://www.sciencedirect.com/science/article/pii/S1556086419306926

Gsk bought the Tesaro pipeline early 2019

https://www.gsk.com/en-gb/media/press-releases/gsk-completes-acquisition-of-tesaro-an-oncology-focused-biopharmaceutical-company/#:~:text=GlaxoSmithKline%20plc%20(LSE%2FNYSE%3A,billion%20(%C2%A34.0%20billion).

We have Jemperli a monoclonal anti body and Zejula which is a Parpi.

Cannot see any benefit of incombo therapy here

Yes chemotherapy can be used.

I am of the firm opinion that as there is no DDR pathway inhibitor along the lines of a checkpoint kinase inhibitor then the maximum potential tial of in combo therapy can ot be reached.

Triparna Sen 2019 at Asco singing the praises of 737 with PD-1 inhibitor and LDG.

Sheer bloody greed by a company prepared to compromise the efficacy of a treatment as they want the total caboodle themselves.

No surprise of failure here for the GSK

I think it one of the areas fast tracked for ACR-368 by Acrivon with their intravenously administered prexasertib in Ovarian cancer.

HGSOC has a mutation rate in the p53 check point of close to 98%.

Without the use of a DDR pathway inhibitor of some sorts I think GSK pretty well f...Ed.

Perhaps they have a pharma over in the US developing some sort of ChK1 inhibitor they can use in combo so they can reach their endpoints.

Regards

Interesting find HbD but not surprised.

Look in the link below at the date.

737 development stopped in late 2019.

Yes GSK obtained their major objective of buyout of Sierra Oncology fo Momoletonib.

What was their non major objective?

737 especially in combo would have posed a threat.

To reduce the threat and as you can't make you own product better you undermine through any means possible your competitor.

Discussions for buyouts take months, many many months.

Ceased development of 737 robbed some of its funds and 18 month later GSK buyout SO.

https://www.ema.europa.eu/en/medicines/human/EPAR/jemperli.

Regards

With regards to first in class you have hit the nail on the head. First to buy will get. Get in first and commercialise.

Then a competitor has to knock that approved compound off its perch.

What l will say is that our compound performed very well and indeed exceededed the expectations of the COO.

Time and attention to detail in getting a compound as best as they can achieve without compromising safety.

We are at current put into the class of Jak inhibitor with its associated recognised adverse event bracket with other Jak inhibitors.

All about selectivity that is crucial.

I do believe that we have the best inhibitor under development that will prove to be vastly superior to any Jak inhibitor currently in development whether pre clinical or in clinical trial and certainly those which are approved for clinical use.

Long term toxicology results should provide no doubt to this.

Deucravacitinib not adverse event free and of course all jumping on the allosteric or non allosteric Tyk2 wagon as deemed so safe.

Deucravacitinib not work in UC.

No interferon gamma l believe to be the reason

Regards

Do you know what HbD?

The further you go into it the more contradicting reporting is found.

Look at gov report below

https://www.gov.uk/drug-safety-update/janus-kinase-jak-inhibitors-new-measures-to-reduce-risks-of-major-cardiovascular-events-malignancy-venous-thromboembolism-serious-infections-and-increased-mortality

Regards

Ps bare in mind this relates mainly in my opinion to early generation inhibitors

Goid afternoon Celtic007.

The payment and shares will be due.

As for an update with 737 l have very little idea.

Devopment in these areas is very slow, Acrivon is progressing albeit slowly no indication that we will be any different.

Providing 737 has been taken on with goid intentions l see no problems.

Clinical trial in in combo therapy or progression to would be great news.