Member Info for Fadec92

Morning Sadoldgit, that one it’s a human monoclonal Antibody with the IL-6 so I don’t know how that works out for any treatment inhibiting the IL-6 pathway but it’s a different method of inhibition with the JAK1 IL-6 inhibition so the next 6 months research into this will be useful to understand if this is a good target as hypothesized by academics!

Interesting Article!

A vaccine that mimics the coronavirus prompts potent antibodies

https://www.nature.com/articles/d41586-020-00502-w

It’s the date and time the trades were made, so you can see the sell price at that time!

They are not all buys the 2 x £66k + £28k are sells!

https://imgur.com/a/W2wXCWo

A lot, >10,000

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

https://s21.q4cdn.com/104148044/files/doc_presentations/2020/BMY-Investor-Series-Day3.pdf

I think it has to be better than competitors in the indications and BMS/Nimbus have a lot of disparity between TYK2 and JAK2, a lot greater than 10,000 and a lower Tyk2 IC50 of 0.2nm and clinical data too prove how good it is, I think if Sareum are a little creative in selecting indications that BMS/Nimbus are not in, ie Covid-19 research is one I guess!

I think their highlighting the different approach Tyk2 Allosteric inhibition instead of inhibiting the active site (catalytic domain) Pfizer/Sareum that’s why Jeb Keiper said only 2 in the clinic is BMS/Nimbus with this type of inhibiting, here’s the slide from BMS presentation it highlights it there!

https://imgur.com/a/uWcyrY5

See how wide the difference is between TYK2 and JAK2 they are claiming this is the best way forward for Tyk2!

Don Nicholson tweet BMS/Nimbus Allosteric Tyk2 approach I think he’s emphasizing , I’ve asked him if he means all Tyk2’s or ones inhibiting the Catalytic domain (Active site)

https://twitter.com/donwnicholson/status/1323620535234924544?s=21

This is for T-cell acute lymphoblastic leukaemia I as asked Tim/John in investor meet as I thought one of the new patents applyed for was in relation too SDC-1801 as that’s the molecule that was closest to finishing Pre-clincal and was looking to license but this is for SDC-1802!

RMM is that info in the investormeet recording?

Probably would have been a good question too ask in the Investormeet as the first mention of it was 18 months ago in the June 13th RNS?

13th Jun 2019 07:00
RNS Number : 0336C
Sareum Holdings PLC
13 June 2019

“Sareum's recent activities have focused on toxicology studies designed to gain insight to the maximum-tolerated doses (MTD) of SDC-1801 and SDC-1802 in rodents. SDC-1801 is further advanced and currently demonstrating excellent tolerability with doses up to 30 times the level that gave good responses in efficacy studies; an MTD has yet to be reached.“

So this has been going on for a while, does anyone know why from the investormeet the trouble with the formulation is, as you would think the the formulation of the compound wouldn’t change, unless they have to make the compound more pure in the chemical make up?

“A formulation that will successfully deliver a therapeutic dose level has been identified, however the Company is required to deliver very high doses to SDC-1801 in order to identify a toxic dose level (maximum tolerated dose), and formulation studies for this are still ongoing.”

TYK2 fold selectivity

JAK2 is 38.33x
JAK3 is 68.33x

So SDC-1801 (SAR-20347) Pharmacological profile

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

So difference in TYK2 fold selectivity over JAK2/3 is 38.33x

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

That is good profiles with vitro kinase assays, the differentiation between is big, JAK2 and JAK3 is greater than 1 µM (So 1 µM is equal too 1000nm) so fold selectivity over JAK2/3 is 200x

JAK1 (IC50 = 4?nM)
TYK2 (IC50 = 5?nM)
JAK2 or JAK3 (IC50 = 1000nm)

“JAK1 (IC50 = 4?nM) and TYK2 (IC50 = 5?nM) as measured in in vitro kinase assays with ATP concentrations at individual Km. Its potency against JAK2 or JAK3 is greater than 1 µM“

The line here is haven’t seen the profiles!

“another more selective TYK2 inhibitor that I have seen the profiles for so cant tell with that one!

Potnak there are 4 companies with Tyk2 molecules saying they are best in class, how do we gauge as an investor what is best in class, how do we know it is, being the most respectful as possible how does Tim know, I do think he’s honest I agree he does, and potentially it could be best in class but in all honesty we don’t know, we have to gauge that for ourselves and find what we think is the best indicator that it is the case, but for me I’m not sure it is!

Nimbus/BMY and Pfizer all saying theirs are and have clinical data that theirs are, Sareum is wanting too license a Tyk2 that in the SRI experiment was a lessor active molecule than the other asset SDC-1802 there are 4 companies with Tyk2 molecules saying they are best in class, Nimbus/BMY and Pfizer all saying theirs are and have clinical data that are, Sareum is wanting too license (SDC-1801) a Tyk2 that in the SRI experiment that they RNS’s and in the documents it is less superior too the other further behind asset (SDC-1802), plus the selectivity profiles are not as selective in Tyk2 than Nimbus/BMY, but Sareum profiles are better for TYK2 against Pfizer’s dual JAK1/TYK2 inhibitor but they also have another more selective TYK2 inhibitor that I have seen the profiles for so cant tell with that one!

“We found that the new compound SAR20351 has similar inhibitory profile against Tyk2/Jak1 as SAR20347, but SAR20351 showed a marked improvement in terms of bio- availability and had a superior pharmacokinetic profile compared to SAR20347. Moreover, SAR20351 was tested in CIA (collagen induced arthritis) mouse model and showed very good in vivo efficacy even at doses as low as 10mg/kg and 4mg/kg. Based on this evidence we decided to use SAR20351 as our inhibitor/drug of choice for the remainder of this study. Since SAR20351 shows efficacy at lower doses in the CIA model, we decided to dose the animals with 25mg/kg of SAR20351 for further animal studies”

SAR 20347 is SDC-1801
SAR 20351 is SDC-1802

https://imgur.com/a/XE0iDiY

Yes I said that the patents for SDC-1801 were key for a license deal, as this was the molecule Tim said they were going to license first, the Patent notice of allowance was given and the award is after 3 months after this so in the new year, I thought the 16/351620 Patent was in respect off 1801 but was wrong and the other 16/343639 Patent that I was checking Is for 1802 in T-cell acute lymphoblastic leukaemia so can’t find any new patents to get new coverage as the 1802 now has, I asked the question in the Q and A investermeet and the answer was that they were filed for 1801, I can’t find anything in the Uspto office with this only these two for 1802 so does that answer mean we are relying on the older patent protection it could be that we are!

There’s also a another Tyk2 in pre-clinical that has similar profiles to SDC-1801 that was made aware of in the investermeet, it’s TLL Pharma’s TLL018 a TYK2/JAK1 inhibitor and avoid JAK2 & JAK3, don’t know anything else about them as not research yet, but makes me think there is many Tyk2’s and why is Sareum’s more desirable than this one, answer is I don’t know yet, and is pre-clinical going to provide the data enough for a pharma to buy on the basis of comparing with this one, Tim said he doesn’t know if this one is better because it’s pre-clinical? Most data is made available already and as Tim said they are always speaking to potential licensing partners so have looked at data already, I think it has to go into clinical trials with the CTA filing taken 3 months and local ethics committee approvals needed to be gained before a clinical trial too start, the statement is that they will review ongoing!

“In line with our strategy and as we state in our FY results, we will continue to review the potential higher value of a later-stage licensing deal versus the requirement for any additional funding“

So completion of pre-clinical then 3 month process between filing a CTA and gaining approval for clinical trials so then commencement of studies is dependent upon further factors, such as local ethics committee approvals is what was said!

I’m not going too do any valuation as I don’t think it’s right for me too make one as I’ll leave that too professionals ie QuotedData and the current research by QuotedData suggest with their analysis that the an up to date range is £25-£45m with a share price bracket of (0.76-1.38p) they said that is the upside too the investment case for SRA737 with a deal involving Sierra Oncology but also said that Covid19 was not included in the valuation!

To me it’s worth what the market says it is longterm, and assess that with Technical Charts based on upside and downside, and with the above valuation in mind!

Interested companies want too see continuous production of plant stated barrels per day running, also the sec regulatory NI-501 report has to document that, then that opens up all kinds of opportunities/interest, the difference now is Steven Byle is in control and he has a reputation for seeking opportunities and making them work look at Valkor Energy and how involved they are and own a subsidiary Crosstrail engineering that have now the blueprint for the 10,000 bbls per day plant from working with PetroTeq, it’s down too this really they were running before hand over 300bbls a day and have Valkor/PetroTeq have identified the bottle necks in production and have included a third mix tank and the improvements too the heater system but also now (from the PetroTeq twitter pictures) includes

1. New cooler for cooling down heavy oil that returns to the tank farm.
2. 3xNew tank heaters
3. Installed a new Vapor Recovery Cooler & and Knock Out Pot to maximize solvent recovery from any vapors.

This level of detail have not been provided before this is now a proven professional company with the focus and vision too complete the task with the errors of the past!

Steven Byle has not only an interest in the project with Tomco but has a direct share interest in PetroTeq can’t remember exact figures, circa 20% maybe but that’s enough and PetroTeq will only be going up shortly, so hang and if you can top up average down, nearly all shareholders I know have a much higher average and is committed too seeing a much improved share price and also if the Quadrise stage goes well and the excitement that could bring with a licensing deal then it should increase price here, not long waiting if you been this long whats another week or 2!

I don’t believe what companies say anymore, they say best in class, but so does Nimbus/BMY with their different approach of inhibiting Tyk2, but then Pfizer (best in class said by director) with the Catalytic site inhibition like Sareum’s, all in the clinic and the companies are producing excellent data, Sareum has to be better than these otherwise what company would spend a good amount of money competing with already excellent potential products, unless they go for an indication that other companies are not covering so well, I don’t like guessing it would be better or take they their word that it’s best in class, plus I see a lot of valuation work on here of moon figures which I’ve seen before on other sites, nothing is given remember it’s v.high risk, it’s prudent too take profits where you think is appropriate and de-risk your position too manage your investment, we have had some extraordinary gains of late so what I’m saying is even though the competition is strong derisk it so it shouldn’t effect you too much, as it’s only best in class when the clinic say it is, if and when there is a license deal for SDC-1801 then I guess we will not be taking that risk anyway!

We don’t know what indications Sareum is going for yet it would be good to know too see what is trying too be achieved Pfizer think the different selectivity between JAK/TYK2 denotes the indication, so in that there is no one glove molecule suiting all, so one molecule Tailored for an indication!

Sareum giving RA/Psoriasis data in their presentation/IP so could go for these, another thing to add is a comment in the SRI paper of SDC-1802 being a better molecule than SDC-1801 but they are trying too license SDC-1801 so I don’t know how that works licensing a lessor molecule in take data readout, I don’t know is the answe let’s see what the next 6 months hold, it isn’t exactly straight forward as lots are claiming here!