Gordon Stein, CFO of CleanTech Lithium, explains why CTL acquired the 23 Laguna Verde licenses. Watch the video here.
London South East prides itself on its community spirit, and in order to keep the chat section problem free, we ask all members to follow these simple rules. In these rules, we refer to ourselves as "we", "us", "our". The user of the website is referred to as "you" and "your".
By posting on our share chat boards you are agreeing to the following:
The IP address of all posts is recorded to aid in enforcing these conditions. As a user you agree to any information you have entered being stored in a database. You agree that we have the right to remove, edit, move or close any topic or board at any time should we see fit. You agree that we have the right to remove any post without notice. You agree that we have the right to suspend your account without notice.
Please note some users may not behave properly and may post content that is misleading, untrue or offensive.
It is not possible for us to fully monitor all content all of the time but where we have actually received notice of any content that is potentially misleading, untrue, offensive, unlawful, infringes third party rights or is potentially in breach of these terms and conditions, then we will review such content, decide whether to remove it from this website and act accordingly.
Premium Members are members that have a premium subscription with London South East. You can subscribe here.
London South East does not endorse such members, and posts should not be construed as advice and represent the opinions of the authors, not those of London South East Ltd, or its affiliates.
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“
TLL Pharma's JAK1/TYK2 looks to be competitive and well patented but there is limited data, its finished pre-clinical and is nearing the end of its P1 trial in healthy adults the same path as SDC-1801 should start next year, its IC50 looks good on paper. https://ard.bmj.com/content/79/Suppl_1/252.1 P1 Status: https://clinicaltrials.gov/ct2/show/NCT04243083
Hi Fadec. My point is it doesn't matter. We are not scientists, we are investors. We hope we have picked the right company but there is no doubt we are in a hot sector with a hot molecule. I don't doubt that TYK2 could be worth multiple billions one day. I do have my reservations that Sareum will be around to see it though. That's why I favour RMMs risk analysis with discounts accounted for valuations . At the end of the day, if Pfizer and BMS have potential blockbuster TYK2, you can bet the likes of Gilead, J&J and other will want in on the action. Even heavily discounted for risk, it could be worth more than multiple of today's sp. And We're not even talking about 737 and flt3 yet. I really want the science to come good but I'm in no doubt that I will have sold out by the time it does.
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!
Fadec - thanks for your response. It is much appreciated.
I think it's vital we can keep a balanced view on the board, even when it is negative for SAR. I think in the long term it can only help both shareholders and the company to have balanced effective research.
NUM4/Thoth2/Damion/RMM - it would be good to have your views on Fadec's take.
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!
Hi Fadec. What you say is all true or at least could be one version of what will happen. The clinics will decide which compounds will come out in top. The winning compound or compounds will be the ones that show efficacy, pure and simple. That doesn't mean there isn't a huge amount of money to be made along the way. Market sentiment will decide that. When you say you don't believe what companies say, I raise you Tim Mitchell. A scientist, CEO who had never ramped the science or John and his inventions, even though lots here wish he would. If he Says 'best in class' he believes it and that is good enough for me. Sareum are further behind the other TYK2 as development goes but that means we are further away from the binary win/lose decision too. The compounds won't be in sareum hands when they get to that point. I'm no expert in valuing companies and risk but the deals that Tim listed were actually made and there is no reason that it couldn't happen here. Its a bit about of a paradox. We say, its all about the science but really, it isn't about the the science at all. It's about what big Pharma is willing to pay to be in the game. And the price goes up with every hurdle jumped.
Thank you Fedec for your thoughtful and circumspect analysis of our Tyk CDC 1801 and 1802. You indicated in a previous post that a licencing deal was imminent after the awarding of the patent for CDC 1802. I would be very interested to know, if it is ok for you, the value you would place on such a licencing and at what stage one should consider a de-risking. We have already have had very comprehensive valuations from a number of other clued in posters on here and your assessment would certainly be valued.
Thank you bFedec for your thoughtful and circumspect analysis of our Tyk CDC 1801 and 1802. You indicated in a previous post that a licencing deal was imminent after the awarding of the
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!
Hi Fadec, so in your opinion, are you concerned about Nimbus/BMY tyk2? As a sareum shareholder?
I think this is a difference in how BMY and Nimbus are progressing their Tyk2 programs where their Tyk2 are classed as Allosteric inhibition, and are claiming this is the way forward, I’ve also put the link for the Catalytic site for other methods of inhibiting Tyk2, it would be good too look at this too see the difference in the development design between Tyk2,s other than selectivity profiles!
Important to understand this new class of TYK2 (only) inhibitors. Allosteric inhibition drives selectivity & the only 2 in the clinic are ours @NimbusTx and $BMY. These allosterics have distinctly different profiles from any other putative TYK2. Learn more at #ACR20 Nov 5th!
https://twitter.com/jebkeiper/status/1321816334393577473?s=21
https://en.m.wikipedia.org/wiki/Allosteric_regulation
https://en.m.wikipedia.org/wiki/Active_site