Member Info for sadoldgit

One more thing which is of importance is that teplizumab is a monoclonal antibody. They either work or do not in a patient with the added benefit that after a period of time they become ineffective.

Yes, and to answer your initial asking is that type 1 diabetes is an indication that SDC1801 could potentially treat.

Regards

A copy of a nigh year old post from patent description.

A lack of activity against kinases typically considered to be anti-cancer targets is beneficial in compounds that may be used in chronic treatment of inflammatory and autoimmune diseases for example.
It is envisaged on the basis of their TYK2 inhibiting activity that the compounds of the invention will be useful in treating at least some of the diseases and disorders discussed below, including inflammatory diseases or conditions, immunological diseases or conditions, autoimmune diseases, allergic diseases or disorders, transplant rejections (allograft transplant rejections); Graft-versus host disease; treating sepsis and septic shock.

In the context of the present invention, an autoimmune disease is a disease which is at least partially provoked by an immune reaction of the body against its own components, for example proteins, lipids or DNA. Examples of organ-specific autoimmune disorders are insulin- dependent diabetes (Type I) which affects the pancreas, Hashimoto's thyroiditis and Graves' disease which affect the thyroid gland, pernicious anemia which affects the stomach, Cushing's disease and Addison's disease which affect the adrenal glands, chronic active hepatitis which affects the liver; polycystic ovary syndrome (PCOS), coeliac disease, psoriasis, inflammatory bowel disease (IBD), lupus nephritis (an inflammation of the kidney) and ankylosing spondylitis. Examples of non-organ-specific autoimmune disorders are rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosus, and myasthenia gravis. Type I diabetes ensues from the selective aggression of autoreactive T-cells against insulin secreting beta-cells of the islets of Langerhans. Other inflammatory or immune diseases and disorders, sufferers from which may benefit from treatment with the compounds of the invention include skin inflammation due to radiation exposure; asthma; allergic inflammation; chronic inflammation; an inflammatory ophthalmic disease; dry eye syndrome (DES, also known as

Despite a regulatory setback for Provention Bio’s diabetes prevention candidate teplizumab, hopes remain high for T cell-regulating therapies in autoimmune indications including multiple sclerosis, systemic lupus erythematosus and coeliac disease.

According to a published report, teplizumab will have a wholesale cost of roughly $194,000 for a full course of treatment.

'TYK2 and Jak1 are critical for signal transduction of many key cytokines driving psoriasis. TYK2 is mainly associated with IL-23 and IL-12 signalling (Tokumasa et al., 2007) in T cells (Ishizaki et al., 2011), whereas many other cytokines signal through Jak1 in keratinocytes (Sohn et al., 2013).''

IL signalling and keratinocyte

http://www.sareum.com/news/press-releases-and-news/2018/selection-tyk2jak1-autoimmune-diseases/

https://www.medicalnewstoday.com/articles/list-of-autoimmune-diseases

https://www.kent.ac.uk/news/science/24627/research-discovery-shows-potential-new-approach-to-cancer-treatment

https://s28.q4cdn.com/726829854/files/doc_downloads/events/ASCO-SRA737-Analyst-Call-Presentation_final.pdf

A few oddments here and a bit hickledy pickledy

Best post this year 08.16 HbD no need to say anything else!

Regards

I dont think you are far out on your estimates there Silverfoil13. CCT245737 looks very promising with stage 2 trial with LDG. Take into account here that this was a bit of a toughie as all patients had advanced cancer, had reached a stage of basically no response from previous treatments. Triple combo should yield better results but have not been trialled in humans yet.

Our SDC1801 Tyk2 jak1 precursor:-

Looking through earlier data of SAR20347 it stands head and shoulders above TYk2 only in Psoriasis especially with inhibition of IL-22.

Couple of extracts belo from long pdf file. (It is from 2014)

In contrast, SAR-20347 markedly reduced scaling and redness compared with TYK2 mutant mice or vehicle treated, WT mice (Fig. 4A, Supplemental Fig. 2A), and mice
treated with SAR-20347 showed no gross toxicity (data not shown). In addition, histopathological assessment of the back skin indicated that SAR-20347–treated mice showed significantly reduced histological score, keratinocyte cell numbers, and Ki67
staining, demonstrating that the compound can substantially reduce disease severity (Fig. 4B–F). Although TYK2 mutant mice also showed a significant reduction in Ki67 staining, there was no change in overall histopathology score (Fig. 4D, 4F). Neither WT
nor TYK2 mutant mice showed signs of inflammation or keratinocyte hyperproliferation in response to treatment with control cream (data not shown). These results suggest that inhibition of both TYK2 and JAK1 reduces disease severity more than TYK2
inhibition alone.

The in vitro profile of SAR20347 suggests that it has the potential to be beneficial in diseases
in which cytokines utilizing TYK2 and JAK1 play a critical role. The marked preference for TYK2/JAK1 offers distinct advantages over other JAK inhibitors that can interfere with JAK2, because inhibition of JAK2 can cause some degree of unwanted myelosuppression, particularly anaemia and thrombocytopenia.

Looking through pdf data it would appear that no JAK2 or Jak3 problems were encountered with SAR20347 at high doses ( in mice)

I have a feeling that news on CTA and development of decisions of 737 will not be far apart.

Regards

Potnak l can see no indication that Ahfam is talking about a licence. I can not see the word licence in any of the thread posts. All l can glean is he was posting with referral of not needing a stage 1 ( dose escalation) trial to allow sdc1802 in patients.

You have been very negative potnak over the passed few weeks. Especially since you only mention that you take a look in here a couple of times a week. Looking to buy some more at a knock down price are we?

Why on earth would you need a P1 b 1801 trial result as a requirement to take 1802 into clinical phase study similar to 1b?
Phase 1 a will suffice. If it did not then there would be no planned running of SDC 1801 phase 1b.

Good evening HbD. I would not say it is nothing you have found,
Studies showed improved results of Tyk2 Jak1 over Tyk 2. Similar efficacy to other inhibitors if not better. From memory here we have around 80% Tyk 2 and 20% Jak 1 2 and 3. Jak 1 I believe was 5x more selective over Jak2 and Jak3 which ought to give us a better safety than the already preclinical studies of SAR20347.

Both compounds should yield excellent efficacy of pure Tyk2 and the selectivity of Jak1 over Jak2 and 3 should prove very favourable in relation to toxicity and safety profile.

Both SDC1801/1802 is superior to SAR20347., Attention to detail should pay off. Many companies would have been happy to push for commercialisation of SAR20347 as it stood.

Preclinical indicates we should be better than Pure Tyk2. Before we can establish the Value of SDC1801 we need establish efficacy and safety clinical trial

Regards.

Good morning Ahfam and HbD. Althought hey can use SAR20347 for research they will not have access to SDC1801 and of course as we know the molecules they use and compounds are also patented.

Regards

My opinion for what it is worth is that sareum could have pursued SRA20347 but instead chose to improve as indeed they have done.
Some very good results I might add with SRA20347 in Psoriasis.
The compound SRA20347 although discontinued for development ( unlike SDC1801) would and is available for preclinical studies as is CCT244747.

Should be an interesting month coming up.

Good evening HbD. I am sure you will find that although SDC1801 and SAR20347 are mentioned in same heading they are similar and not identical compounds.
SDC1801 was is a later stage development of this compound and initial looking/memory tells me that the SDC1801 is more selective compound of Jak1 over Jak2 and Jak3.

It bares similarity of CCT244747 prior to our CCT245737 ie our CHK1 inhibitor that was put into clinical trials.

I would hazard a guess that SDC 1801 is a tweaked molecule superseding SRA20347 with improved efficacy and safety with a higher degree of purity.

Good find all the same and originates from 2014 a little too early I feel for SDC1801.

from Sareum website
Sareum's TYK2/JAK1 preclinical devlopment candidate molecule, SDC-1801, demonstrates 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, also show good activity in models of inflammatory bowel disease and systemic lupus erythematosus (lupus). These attributes have supported the progression of SDC-1801 through preclinical development and, pending regulatory approval, advancement into human clinical trials.

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.

Who remembers the problems with patenting SDC1802 and then problems with a patent SDC1801 as similar compounds. Took several months and appeals but in the end was progressed as SDC1801 for autoimmune and SDC1802 for immunocology.

Regards

There is a wide spread due to uncertainty. Mid price is 87.5p Above is shown as a buy and below is shown as a sell. Until the MM decide whether bearish or bullish then these large margins will remain until news arrives. Simple as that.
There will not be many shares in free float.

It has happened before on expectation of news and news can be positive or negative.
It is called market sentiment and the MM's know how to play this.

Regards

It really does depend on how you define best in class. Not all Tyk2 Jak 1 will be equal with regards to Tyk2 Jak1 2 and 3 inhibition. They are not all using the same molecules as these get patented. A further deciding factor will be purity of the compound and we must not forget the oral bioavailabilty of the compound.

A lot of the time it is 'we believe' or sometimes used 'potential best in class'.

The real biggie of course is Ty2 Jak1 in cancer.

Large company BA may want complete purchase of. However, some form of results would be s sought in clinical studies on triple combo therapy.

Tim and Co would know the score on this as would the CPF hence the option of rapid on licence or develop further then on licence or sell outright.

Negotiation will take time of course.

One thing for sure is 737 must be worth considerably more than when originally on licenced 6 years ago 319 million dollars.

Regards

I think we will end up with a US on licensee for 737. Triple therapy in combo which has given unparalleled results in some indications ie SCLC. Very good results in ano genital human trials with LDG.
Not so good with cisplatin due to toxicity issues, Michelle Garrett investigations:- need careful consideration as combination therapy involving 737. Not suggesting in anyway bad, just not compatible with everything out there. Cisplatin been around many years.

Regards

As a monotherapy and understandable as to why CHK 1 inhibitors are not overly effective as a monotherapy. Acrivon are focusing on phase 2 trials with LDG.
They have advantages with their Onco signature as securing by selectivity of patient a higher ORR.
Rather a pity that Acrivon did not pick up 737 in 2021! Although saying that the 'for sale' board had been taken down March/ April 2020.

Conclusion: Prexasertib did not demonstrate activity to warrant future development as monotherapy in ED-SCLC.

SCLC whereby in preclinical studies triple combination 737 8 out of 10 mice 100% tumour reduction with no re occurrence over 60 days ( Partial response in the other 2 mice). In MG's reporting on CHK1 inhibitors 737 had a better overall safety profile.

Regards all.

We can also take into consideration that 737 is over 100 times more selective of CHK1 over CHK2 than Prexasertib.

CHK1 is proving effective
https://pubmed.ncbi.nlm.nih.gov/36192237/

Colorectal cancer on the increase.

www.cnn.com/2023/03/01/health/colorectal-cancer-statistics-2023-report/inde

G'day Paul Hogan.
People on here are not angry, inquisitve yes and maybe some irritated by the condescending judgemental slime balls that frequent here.

I am sure you are not one of these and will endeavour to post constructive views and opinions giving a somewhat balanced overview with your wealth of newly acquired knowledge.

Regards

Paul Hogan you are welcome.
Posters on here become very wary of recently registered new posters who claim to have become recently invested. Especially when they start becoming overly negative by focusing on the risk. There have been many.
It has happened without fail since my early days here and that is 2012.

I take it you are now fully versed from seeing the AGM and looking through Sareum history. I take it you have looked through the associated RNS's. They are a reliable source of company progress.

From a previous post of yours you state you invested before Christmas. Then you state you invested at the beginning of January. Which of these if you don;t mind my asking is correct?
One of them, both of them or neither of them?

Having a good circle of friends in life is good. I take it you pay good attention and are supportive of their posts.

Regards