Member Info for Fadec92

Mathsprof ask him kindly if you know him what the hell is glover doing! Please! Thumbs up!

Wip JAK2 has toxicity issues! Thumbs up!

So what if so

So what if Sierra cannot find an interested party to fund further development with Stoney pointing out a clause that they must proceed with every endeavor to maintain progress what happens if they can’t, but have for-filled the every endeavor in finding partners and can’t, is that still a contract breach, and with a declaration to ICR that interested party’s are unable to proceed in the current environment, with all the good work they have achieved with the work and costs Nick will not want to give back the molecule and loose that, it’s not in their interest too, they will want too renegotiated contract milestones as per mentioned to continue, maybe dropping all interest in the RNS for DDR assets in the company model is a conscious move it has definitely got us thinking what’s happening and they could drag this out within the legal framework unless we they get the contracts repositioned because of X and Y it’s going to cost more going forward than originally thought there’s all kind of things happening imo, but we don’t know Jack it’s a chess game!

Perhaps the current valuation of the agreement made between Sierra Oncology and ICR that was agreed is too high in Sierra’s opinion as I think they were hoping for a better outcome as they based the strategy of CHK1 being of tumour agnostic development but as we know it is a particular in Gene Type!

“Substances to treat cancer based on the cancer’s genetic and molecular features without regard to the cancer type or where the cancer started in the body. Tumor-agnostic therapy uses the same drug to treat all cancer types“

So the valuation is reduced with not very good in monotherapy and for all gene types so now would cost more with research and expansion trials, it’s a bit silly as DDR was always a combo molecule as it needs a molecule to kill cancers first pushing the cancer cycle into “Replication stress” RS and what Chk1 does is stop certain cancer genes repairing itself, so how could Sierra expect Chk1 to be something it’s not, in my eyes monotherepy is to ascertain which gene network SRA737 has efficacy in no matter how much!

Hi Krone I don’t think Stephen Parker pressure is going to do much, it hasn’t done anything already not that he could and is just lip service to us investors to be satisfied that Sareum are doing something, but we are passengers unfortunately, as thoth said after results there may be a few months grace to decide if the data is worthy we can see it is in respect to no toxicity issues, high degree of synergies with other molecules, but he can use that as an excuse to drag out, then he could say understandable covid has effected plans they had or other companies plans into, so I’m negative as Nick has shown little respect to SRA737!

Tim has said that their preferred route would be on license, any company taking it on would have to have a lot of capital, (You wouldn’t just push forward in anogenital and not combos PARP/PD-L1 plus Milestones) think Sierra would have liked to partner it and have more of an involvement, ie have their cake and eat it by delaying as much as they can until they were in a better position to get going again, as they have enough money to get Mome throught to registration and have been looking for a non dilutive partner for coming up too a year, (after ASCO) has this now changed possibly with covid19 and company’s lost interest I think companies priority’s are Covid!

There is now no mention of DDR assets in the about Sierra the company section, always has one eye of the other asset the Cdc7 they have had for for god knows how long in pre-clinical and ever wondered that SRA737 could become like that, just held, the answer is we can speculate all we want that Gilead want SRRA because of SRA737 none of us know what is going on, I want to see a more of a link between Gilead/SRRA and SRA737 as haven’t seen anything yet, sure there could be some rationale for doing but SRRA was testing SRA with Mercks PD-L1 at the MD Anderson and I thought they were the interested party as was on the slides at ASCO, and Nick stated that they were speaking to a big immunetherepy company last year, but noting since that, I think Gilead give MOME back to SRRA as they couldnt do much with it and if SRRA could make it commercial then for Gilead to get something out of it rather than shelved would be much better financially!

Basically SRRA have had enough time to arrange the progression of SRA737 but nothing not even an update on anything to do with SRA737 it has been the same since last year “seeking non-dilutive partner” the only change is now they have dropped completely as it dosnt even exists, I don’t get it and don’t have enough information too second guess, the ICR will need the money as they have a new Cancer Research Center to fund the end of it £10m I think the article said, and them pushing the DNA polymerase test which there is an article about this and Paul Workman, Michelle Garret going back to 2017/2018 so why now issue the research recently, is it a public push to SRRA?

I would think that in business you have to get blood on your hands and start rattling the saber, but unfortunately I don’t think ICR are like this which are a clinical payed for by grants/charity and are not a business entity so I don’t think they are savvy in such, I really don’t know what’s going on but SRRA could always play the Covid19 card why they are not progressing now and can’t see anything short term unfortunately!

What’s the question! Lol..

The tyrosine-kinase inhibitor in the list even though it sounds the same as TYK2, it is not similar to SDC as they target different than Jakinib family and are vascular endothelial growth factor receptor, fibroblast growth factor receptor in cancer and has been chosen as a solution!

The other molecules Tofacitinib (Pfizer), Ruxolitinib (Incyte) and Baracitinib (Eli Lilly) as are JAK inhibitors there is no TYK2 variants put forward by the article as a solution, one reason could be that they are new molecules not commercial yet and a lot less understood and in clinical trials Pfizer and BMS, personally if TYK2 was a solution I don’t understand why Pfizer would not put their JAK1/TYk2 forward or be identified by this article!

It’s on ADVFN as well!

https://imgur.com/a/ztqi1zA

https://twitter.com/fadec92/status/1258366084450746369?s=21

12.06 : 19 @48.34

Not even mentioned about the business section, have they totally dropped SAR737?

https://twitter.com/fadec92/status/1258369007062855681?s=21

https://imgur.com/a/Mur7VKe

That was the SDC-1801 Patent 16/351620 which was rejected in February as a Final Action, so we are waiting for a response from John to examiner for that one too!

More work required for US TYK2 Cancer Patent SDC-1802!

US - Patent 16/343639

US20190350905 patent

https://imgur.com/a/C7WkbSF

‘Claims are subject to restricted and/ or election requirement’

“This application contains the following inventions or group of inventions which are not so linked to as to form a single general inventive concept”

“Applicant is required, in reply to this action to elect a single invention to which the claims must be restricted”

Thanks Krone!

“highly selective JAK1 kinase inhibitor, is reported. Compound 21 has good preclinical pharmacokinetics. Compound 21 displayed an enhanced antitumor activity in combination with an approved EGFR inhibitor, osimertinib, in a preclinical non-small-cell lung cancer (NSCLC) xenograft NCI-H1975 model.”

Not much of a concern if you hold medium term, it would be sensible to raise funds for SDC-1801/1802 when in the excitement phase of Covid19 and interest in any company covid related so would be good to cement the likelihood of Sareum future and maybe take one into trials and license another and with the licensing money provide cash flow to progress one, I don’t know which one I would pick and has been discussed before, the company model is for a license deal late preclinical early clinical so could be taking rubbish, I think license SDC-1801 as has more clinical validation with BMS/Pfizer in phase 2/3 with good data and put SDC 1802 into clinical trials, I think RMM/Thoth/CFP the guys that went to the AGM said that one was easier or less work/money involved with a clinical trial, something about Cancer indications being easier I guess, can’t remember full details, but then we could have milestone cash if Sierra Oncology sort their end of finding a partner with SRA737, it’s a tough call!

It’s a concept only and brought forward by Tim/John and that’s why, needs validation by research funding and from other areas ie Academics, Peer Reviews other Pharmaceutical Companies ie Pfizer to involve their JAK1/TYK2 and not just trials of their Tofacitinib which is underway!

RMM classic...Herd Immunity lol... Could a JAK inhibitor be used for this! Lol..

Here is the selectivity range of the molecules of both SDC-1801 a More selective TYK2 than JAK1 and Pfizer’s more JAK1 than TYK2 only slightly could call it a dual inhibitor!

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

Pfizer JAK1 is more selective than TYK2 Pharmacological profile is a potent dual inhibitor of JAK1 and TYK2

Pfizer PF-06700841

IC50(JAK1) = 17 nM
IC50(TYK2) = 23 nM
IC50(JAK2)= 77 nM
JAK3 (IC50 = 6494 nM) or (6.49 µM)

https://www.medchemexpress.com/PF-06700841.html

With most BMS/nimbus Tyk2’s being pure but Sareum or Pizfer, which are the most similar TYK2/JAK1 inhibitors over the BMS/Nimbus, but different as the selectivity for Sareum is more TYK2 than JAK1 where Pfizer is more JAK1 than TYK2 what counts is the right selectivity of them from the literature, as Tyk2 is the IL12/IL23 which is inflammation and immune response but whats just as important is what is going on the JAK1, with their Interleukin and interferon signaling!

Yes that’s right Andy IL-6 is JAK1 related and JAK2!

Hence Incyte and Eli Lilly’s JAK 1/2 inhibitors—Jakafi (ruxolitinib) and Olumiant (baricitinib), Pfizer’s JAK 1/3 inhibitor Xeljanz (tofacitinib) in Covid-19!