Member Info for Fadec92

Ahfam here is my reasons why I’m negative about 1801, for Autoimmune Indications!
1.Haven’t selected an indication where research shows different selection of JAKS/TYK2 will favor a particular indication, so after years of research then they should have an idea of a particular indication the molecule favors, it has been talked about in RNS but nothing.

2.The extended timelines for years with no solid timeline of progress and achieved goals, these have just slipped time after time, and no negative signals that they couldn’t get to MTD and then mentioned they couldn’t and were trying for a second time, I’m still not convinced this has been resolved and was thinking that the last RNS with covid19 half years results could be too buy more time too resolve this issue they still have.

3.No updated Patents for nearly 10 years, there have been talked about by posters but I’m not sure if this is even possible with SDC-1801 as what’s too update it’s got worldwide patents that’s running out as US Patents last 20 years, so after in clinic say 4-5 years, is this going too be attractive too a licensee deal.

Pharmacology Profiles

1.Same amount of JAK2 as JAK1 in profile, so why is it called as TYK2/JAK1 inhibitor when there’s nearly the same amount of JAK2.

Sareum Autoimmune SDC-1801 (SAR-20347)
Pharmacological profile

IC50(TYK2) = 0.6nM
IC50(JAK1) = 23nM
IC50(JAK2) = 26nM
IC50(JAK3) = 41nM

https://www.medchemexpress.com/SAR-20347.html

Its known in the industry about JAK2 being in the profile is not a good thing and well known that filgotinib, upadacitinib, tofacitinib and baricitinib are first generation JAK inhibitors and have black box warnings but in SDC-1801 there is a good amount of JAK2 present.

The competition have very low or nothing on JAK2

1.TTL Pharma TYK2/JAK1 has a catalytic inhibitor like Sareum but 1000nm = JAK2

2.BMS TYK2 inhibitor has over 10,000nm = JAK2

3.Nimbus Therapeutics Inhibitors have 148x + 210x TYK2 over JAK2

Plus another 2 new TYK2 inhibitors are involved that have just had large funding rounds too develop their inhibitors!

Ventyx Biosciences ($114m fundraiser)

https://ventyxbio.com/programs/#jet-tabs-control-2362

https://endpts.com/exclusive-ready-to-exit-quiet-mode-joint-entity-ventyx-debuts-its-immune-modulator-pipeline-with-114m-round/

Neuron23 ($113.5m fundraiser)

https://www.fiercebiotech.com/biotech/neuron23-uncloaks-113-5m-to-tackle-cns-disorders-through-genetic-mutations

https://neuron23.com/our-science/

TLL Pharma

https://ard.bmj.com/content/79/Suppl_1/252.1

Thanks Celtic I’ve said on a few occasions over the years that I think they are a well run company for the resources they have and only raise money when they need too, which is refreshing on AIM also was against the share holders revolt in August 2019 but have gradually found more info and have gradually become negative over the years since, I am positive on 1802 and 737 but not too fond of 1801 over the selectivity profile plus the competition and the research in lupus studies where they continued with 1802 for that study as had more efficacy than 1801!

I’ve

I’ve been invested since 2016 and I post on and off, I want to talk about Sareum as a company and the assets they have, whether if some points are good or bad...I’m going too speak what I think about things as I see them and I’m not interested in making friends or if I upset anyone, but would rather get on with posters, I can be wrong or right, I was wrong the other day on the ATM plus 737 combo and was put right in that respect and learnt that is what my motive is, and not being swayed by group culture and control, I respect Thoth and thank his respect in saying there’s nothing wrong with what I post, and many here and hope this will be good for us all as I want companys too succeed and not fail as I’m pro life and pro prosperity, I’m always polite too posters, and wouldn’t mind the same but not essential too still continue look in and communicate/comment, but this about the company and not about me just what’s right and good/bad about things here and some proved of info to be transparent!

No all good mate and is a great area in Cancer precision based gene related, I would definitely put into the top bracket of a true worthy contenter and it’s doing a good here keeping me on my feet because I have too try and find the link and learn in the process, it’s like Thoth over the years has link a lot of companies that’s going too buy 737 with no real evidence based approach, just wondering why now or is that a future based opinion on an option when 737 may get back into the clinic!

Hi Krone I’m having trouble finding a link to Sierra!

Lauren Byers is a payed to do research like in the past Sierra pay her for work she was involved in April 2019 at the MD Anderson 747 combo in SCLC and has advised Sierra in the past and has earlier involvement with PARP combos in 2017 no doubt she is the leading hand when presenting in the clinic research into DDR pathways and different types!

Lauren Byers is an Advisory board member for AstraZeneca so it’s stands too reason her involvement!

AstraZeneca have a number of molecules in DDR pathways PARP inhibitors, Wee1 and ATR Inhibitor which is very similar in mechanism to Chk1 and only stands to reason that they would be showcasing their latest reasearch at the AACR, as the same as the ICR are presenting as you found on the 11th April with the Wee1 and 737 in TP53, as Sierra was paying them to traveling fees too and from the event!

Would have hoped for more than just paying the traveling fees, but it is progressing the research and validation that 737 could work together with Astras Wee1 which is good but it would be better again for them too show some real human investment!

Thinking about the RNS yesterday how come Tim says in interviews that Covid hasn’t effected the company but put out a delayed delivery of half year results due to covid19 and will give them more time, a month!

11th of March Krone posted this, so 2 weeks ago, is there anyone at Sareum watching or did someone here email them to put this out in an RNS, unbelievable!

https://i.imgur.com/HxOh3rK.png

More than likely the product trade name for Momelotinib!

Clinical Candidates Targeting the ATR–CHK1–WEE1 Axis in Cancer

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7918546/pdf/cancers-13-00795.pdf

Esparas Pharma due to end their Chk1 phase 1/2 trial in the summer do you think it’s a possibility that Sierra could wait too see the data from this before proceeding to develop SRA737!

Estimated Study Completion Date :- June 2021

https://clinicaltrials.gov/ct2/show/NCT02632448

https://www.centerwatch.com/clinical-trials/listings/183808/a-study-of-ly2880070-in-participants-with-advanced-or-metastatic-cancer/

Potnak Sar’s is the Catalytic Site, I don’t think it’s a tweek too change, the molecule would have too change!

“The breakthrough with TYK2 came in targeting the allosteric site, also known as “pseudokinase,” “JH2,” or “regulatory domain,” which has allowed BMS (and Nimbus, to an even further extent) to push selectivity beyond anything achievable in targeting the catalytic site. This allosteric site has long been known to exist, however binding a drug to it that results in signal inhibition was only discovered in the last few years and gave rise to the allosteric TYK2 programs at BMS and Nimbus. The result of these allosteric programs has been to drive up selectivity for TYK2 by orders of magnitude over all other previous approaches.”

Don’t know the answer too that Ahfam, but from this they had too separate and choose a set of compounds group 1 and 2, if I can remember I asked in the investormeet the first one as and think it’s T-all tyk2

https://imgur.com/a/8tvFlbS

The Patent 16/343639

https://imgur.com/a/rSPkTun

It might be the T-All one as I think they had too separate the T-All from solid tumors, but that’s a guess, I remember they had too select a group of compounds over another group!

Ahfam there was 2 that was pending in the US, the one was granted in October and this one had a final rejection in December, so more work on this, that’s if they want too pursue it as they were still having dialogue with the examiner after the RNS that stated that the protection was complete for 1802!

It’s not as simple as that Patents take years of going back and forth, and it’s early days for that one, but you do wonder why they didn’t pay the money on time especially being so important and in phase trials, but they can still pay and do the international searches anyhow!

The 1802 patent had a final rejection on the 16th December 2020 and there’s no entry’s since then so it’s been a couple of months, so we would want to know if they are going too have a reassessment, in previous RNS it has said that the last one they received would complete the US protection for 1802 but they were still trying too attain it after that RNS!

It’s not as simple as that Patents take years of going back and forth, and it’s early days for that one, but you do wonder why they didn’t pay the money on time especially being so important and in phase trials, but they can still pay and do the international searches anyhow!

The 1802 patent had a final rejection on the 16th December 2020 and there’s no entry’s since then so it’s been a couple of months, so we would want to know if they are going too have a reassessment, in previous RNS it has said that the last one they received would complete the US protection for 1802 but they were still trying too attain it after that RNS so let’s see!

Allosteric mechanisms so that’s the same as Tyk2 inhibitors like Deucravacitinib (BMS - 986165) which had good results in phase 3 they have no or hardly any JAKS!

Basser you are correct, and further it combines both the molecules as a combo AZD6738 and SRA737, black and white and there is a reason too license as too combo!

“Given that ATR activates CHK1, we hypothesized that the CHK1 inhibitor in clinical trials, SRA737, could also overcome chemoresistance in SLFN11-KO cells. Accordingly, SRA737 reversed the resistance of SLFN11-KO cells (SI Appendix, Fig. S2 H–O). Together, our findings show that combining clinical ATR/CHK1 inhibitors with widely using clinical DNA-damaging agents is highly effective for overcoming the chemoresistance of cancer cells that do not express SLFN11.”