Member Info for sadoldgit

The proof in the pudding 007 will be in the eating. Phase 1 dose escalation studies.

Sareum always had good toxicity or to be more precise better than all the rest.

Pharmas will take notice on result of our tox results. Eagerly awaited.

Tyk 2 Jak 1 and all of our makeup of 31 molecules are patented.

Gone very quiet on the Nitrosamine front I will add.

Next significant news to make a raise in the SP can only be 737 or maybe partnership for our SDC compounds.

We our now a company with its own wholly owned compound in clinical trial. A major milestone is an understatement. if a pharma does not want to get involved then all they can do is sit back and watch.

Tyk2 Jak 1 looking good, mighty good.

Astonished on todays RNS. Tim and Co deserve congratulations and the Aussie CRO deserve praise too.

Regards to all LTH.

I will 2nd that.

Come on you irons.

Many a beer in the Queens Head and the Boleyn years ago.

We have an avid Hammers Supporter up here in Thurso. When he travels to London always goes to the game.

Regards

Interesting link on Rinvoq there C79.

Jak inhibitor. Jak 1 with selectivity over Jak2 and Jak3.

No idea as just hoe effective but does show the efficacy of Jak1.

From memory our SDC1802 is TYK2 is five fold selective over Jakis. With our Jak1 one greater than 5 fold selectivity over Jak2 and Jak 3.

Now Tyk2 supposedly will regulate to an extent Jak2 and Jak3 and as far as I know not over Jak1.

All looks very good , but of course the proof of the pudding is in the eating.

Looking forward to the dose escalation studies ans confident myself we will not have any adverse issues even at the top 300mg per day. We are well below the initial Sar dosages of max 1000 mg per day treatment dose.

No maximum tolerated dose was reached at 30 fold treatment dose in preclinical.

The biggy of course is SDC1802,

Good results on escalation dose will pave the way for 1802.

They have experience of inhibitors in the treatment of AML with aurora but unfortunately development stopped with the solubility issues.

Similar problem occurred with out TYK2 compounds but these were resolved. They experienced difficulties in manufacturing in large quantities ( much larger than preclinical in mice) suitable to supply clinical studies.

Thankfully these issues with TYK2 Jak1 compounds were resolved.

Regards

I think recruitment all done and dusted by now.

I reckon the anticipated date of start as you state Potnak is the only realistic date we can go on.

Regards

Bare in mind that although the CPF will be well aware of further developments with 737 any potential on licensee will need to be made aware. This will take time. As I have said before they need communication with the likes of M Garrett and T Senn.

The compounds themselves cannot be changed but what they work best with can,

Regards to all.

The only thing I know is that if patients benefitted from the treatment then even at trial end they would still be able to receive the treatment.

It was mentioned in an RNS from memory. SO would continue treatment after this. Not 100% sure how long for.

Have no idea if it common or not.

Take into consideration that 737 was trialled on patients who had either become resistant to prior treatments or at very late stage progression. One criteria was patient has life expectancy of at least 3 months.

From memory there was one patient or somebody here that new a patient and had continued to take the treatment after trial end. It was difficult for him, some side effects, but at the very least it increased his survival time.

The potential is there in combo therapy.

There was a big jump to PARPi as was seen as the 'in thing'. But that has its own short comings. It needs combo to work. Now there is a dilemma pharmas were looking at PARPi as a replacement for \chk1 due to less toxicity. What they are finding is that just as CHK1 need in combo to work so does Parpi and even more so when used in combo with chemo such as gemcitabine. In effect CHK1 is critical when used in some combo therapy as act as a regulator.

In a sense combination therapy is the only logical way forward.

Early diagnosis and access to treatment is as vital as the treatment itself.

At one time it was what is suitable combo for CHK1 inhibitors ( basically to give it greater efficacy). Now on many reports they are suggesting that many inhibitors like PARP1 are best used in combo with a CHK1 inhibitor and you can include WEE1 in that also. The only viable candidates as I can see and both were worked with by Michelle Garrett is prexasertib and SRA737 ( well a log time back when it was CCT245737 and even the earlier pre clinical candidate CCT244747.

I had posted months ago excerpts which time consuming as copy and paste no good. Unfortunately this gets lost in the multitude of dross which manifests during times when the SP starts to slip and the doom and gloomers appear. Clueless but they appear all the same.

MG and co 2020 had this well understood unfortunately SO failed to provide funding. MG an advisor to SO too and when the for sale sign so as to speak came down from the front window further CHK1 development continued with prexasertib which is now on licensed to Acrivon. ( now I believe fast tracked or at least seeking fast tracking through the NDA ) into endometrial and HGSOC.

Prexasertib from memory is iv administered only.

CCT245737 is just far too good to let sit on a shelf.

Ramble a bit as usual but not have time to sit and compose a post.

Good morning HbD.

Yes you are correct as a trial was carried out in Spain

Check out the link below and click on more info.

https://ascopubs.org/doi/10.1200/JCO.2019.37.15_suppl.3095

I believe from memory there was a delay of some sort from data feed back from Spain. Nothing serious just a delay.

My own opinion here FWIIW, is I see no reason here for 737 not to be approved for fast track in some indications (especially endometrial cancer and HGSOC) in combo with LDG. We are ahead of prexasertib in development with no cardio concerns.

It is a very competitive environment.

Just a side step here.

'GSK is committed to disclosing the payments we make, as we work together with healthcare professionals.'

'Payments to doctors from GlaxoSmithKline have almost doubled since Dame Emma Walmsley became chief executive after the drugs company reversed policies introduced at the time of a bribery scandal in China.'

https://www.gsk.com/en-gb/responsibility/ethical-standards/engaging-with-healthcare-professionals/#:~:text=with%20those%20services.-,GSK's%20voluntary%20decision%20to%20publish%20our%20payments%20to%20HCPs%20is,777%2FHCP.

AS far as I can see very rarely does GSK take on an on licence however they do out licence.

https://www.thepharmaletter.com/article/gsk-in-out-licensing-deal-with-boston-pharmaceuticals ( look at the terms of the contract )

As an in license. Clearly to the benefit of GSK. Late 2022 acquisition.

https://www.gsk.com/en-gb/media/press-releases/gsk-and-spero-therapeutics-announce-exclusive-licence-agreement-for-tebipenem-hbr-a-late-stage-antibiotic-that-may-treat-complicated-urinary-tract-infections/

Announcement April 23 by AMR

https://www.gsk.com/en-gb/behind-the-science-magazine/amr-antibiotics-resistance-superbugs-new-medicines/

Regards

'A more rational application of CHK1i could represent monotherapy or combination with subtherapeutic doses of DNA damaging agents as with prexasertib or SRA737'

I will add here that prexasertib is CHK1 and CHK2.

737 is CHK1 with over a thousand fold selectivity over CHK2.

It still has 10 years of patent life remaining even due to delay of no further development by SO

Much of the link below will have been gleaned by investigational work by M Garrett et al.

Regards

An abstract from lin previously posted.

The major DLTs and SAEs G4 of ATR/CHK1/WEE1 inhibition were associated with myelosuppression, which is the most frequently occurring adverse effect with anticancer agents. CHK1i was found to be the most toxic of this trinity. Low selectivity of the first-generation CHK1i, imposing CHK2 inhibition as well, is one of the culprits of their escalated toxicity. Indeed, the nonselective inhibition pattern of AZD7762 and MK‑8776 is responsible for their significant cardiotoxicity [129,132,133]. The knowledge gained from the development of these agents resulted in the development of the well-tolerated SRA737 with prevailing CHK1 inhibition and mitigated severe myelosuppression [135,156]. On the contrary, even a selective CHK1 inhibitor combined with DNA-damaging agents could result in SAEs due to a significant effect on healthy cells [55,157]. A more rational application of CHK1i could represent monotherapy or combination with subtherapeutic doses of DNA damaging agents as with prexasertib or SRA737

A very long read. A little knowledge required here. A good account of the reasonings, beliefs and

https://www.mdpi.com/2072-6694/13/4/795

Our immune systems are compromised by excessive stress. It can manifest itself in many ways. Many will now of some ways of what stress can lead to. In the worst case scenarios it will end up in an ever decreasing circle. Long term stress is a killer. How our body and minds work are very closely related.

Below a link not to which I have stated above but will give some idea. My own thoughts on this is balancing of our immune system needs to be the case as opposed to a complete readjustment.

https://www.news-medical.net/health/How-does-Stress-Affect-Your-Immune-System.aspx

An overview of Oz clinical trials

https://www.australianclinicaltrials.gov.au/why-conduct-clinical-trial-australia

Straightforward

From NIH May 2022

A member of the Janus kinase (JAK) family, Tyrosine Kinase 2 (TYK2), is crucial in mediating various cytokine-signaling pathways such as interleukin-23 (IL23), interleukin-12 (IL12) and type I Interferons (IFN) which contribute to autoimmune disorders (e.g., psoriasis, lupus, and inflammatory bowel disease) ( NOTE THE eg ie example here)

As a critical intracellular component of the IL12, IL23 and type I IFN cytokine cascades, TYK2 plays pivotal roles in autoimmune disorders including psoriasis (Ps), inflammatory bowel disease (IBD), systemic lupus erythematosus (SLE), lupus nephritis, multiple sclerosis (MS), etc. ( Note pivotal roles )

The TYK2 inhibitor, Deucravacitinib (BMS986165), is currently the compound most advanced clinically, which selectively binds to the JH2 regulatory domain of TYK2 and suppresses TYK2 associated cytokine pathways (22, 27, 52, 56–59). Deucravacitinib was demonstrated to be highly efficacious in phase 2 and 3 psoriasis trials with good safety profiles (58)

From Journal of Crohn's and Colitus Jan 22 ( Oxford Academic)

Pharmacodynamic data suggest insufficient inhibition of TYK2 pathways with DEUC 6 mg BID. Incidence of adverse events (AEs) was 70.1% in the DEUC arm and 47.6% with PBO; rates of serious AEs were 9.2% (n=8) and 4.8% (n=2), respectively. Rash, acne, and worsening of UC were the most common AEs in the DEUC arm. No meaningful changes from BL in mean values of laboratory parameters were observed with DEUC treatment.

Conclusion

This Phase 2 study of DEUC 6 mg BID in moderately-to-severely active UC did not meet its primary or secondary efficacy endpoints at Wk 12. In biologic-experienced pts, response rates were numerically higher with DEUC compared with PBO. The safety profile was consistent with DEUC trials in psoriasis and psoriatic arthritis. ( Note numerically higher but not significantly higher)

In this instance TyK 2 ( Deucravacitinib) failed in meeting its end point. BMS were looking at addressing this issue with higher dosages, I have no idea how far they have progressed this.

in addition Circa May 21.

Tofacitinib, a JAK1 inhibitor, is now licensed for use in the induction and maintenance of ulcerative colitis. ( jak 1 more efficacious in this instance than 100% allosteric TYK 2 here!)

You can draw your own conclusions from this.

Regards

Num4

Always a pleasure reading your posts.

My chain of thought is to place yourself in the position of Tim and co

AGM with regards to 737.

Options of fast on licence or develop further the on licence. Predominantly in the hands of the CPF.

A day to a month to evaluate data.

Mid March all data returned. It is nigh two months since.

Now Tim and co cannot release any news on licensing apart from the granting of an on licence. They can issue news on furthe development but very much feel we have gone past that window.

I would hazard an educated guess that in the background there is interest in 737. Probable on licencing discussions in mid to late stage. Any interested parties would have had at least a month and most likely 2 months to evaluate the data.

If an on licence was not looking promising or financially lacking then I am certain that we would have heard by now.

Sooner or later Sareum will need funding to further develop 1801 in clinical and also 1802. That is inevitable.

We now have PH on board (the investment company.)

An option would be in the event of needing funding at a later stage is either wait for finalisation of an on licence or raise funding through PH investment.

No point in trying to raise funding before a deal for 737 can be ruled out. Any deal would increase the SP considerably with 737 and reliant on how much up front payment is offered.

In the event of requiring further funding via the likes of PH post positive 737 news, will lead to less dilution should further finances be required, as based on the SP/market cap at this time.

Sufficient funding we have to take us in to next year.

As I have said before it is ultimately in the hands of the CPF with regards to 737. We as well as the CPF do not want another Sierra oncology debacle.

As usual Tim an co will know more than us, but will as they always have done, with exception to the 'transformational deal ( that never materialised) remain tight lipped.

As a side point, it Interestingly that Acrivon deal for prexasertib was 5 million up front. there were also milestones and timelines specified. in contract but the actual dates and amounts were omitted No reason the CPF cannot do the same.

It is alsoencouraging to note that Acrivon as far as I am aware been approved by the FDA for fast track in some hard to treat indications.

Prexasertib has no patent life left, was stopped primarily due to cardio problems,n one have been attributed to 737 in phase 2 studies.

Chk1 is vital and success will be in combination type therapy. I think we can rule out as a monotherapy ( Tim AGM)

Those that claim to remember the 10 out of 10 days for the mice. Most don't know the relevance or what it actually relates to, or how defined and as such i suggest that any newbie should ask those that claim to remember I doubt if we would get an accurate factual response, let alone a correct answer from them.

I too were a disappointed on of

It is not a hollow victory Potnak it is a victory.

As for someone who does not read long rambling posts you have yet again contradicted yourself.

Unless of course you skim through and read if and they are of value to you. Clearly mine today have proved of value to you.

Personally l never posted that you have sold all your holding. I only stated ' l reckon you have sold some on a spike'. I see nothing ridiculous in that statement. Perhaps you could post something to the contrary.

As for the top of the tree? I don't see myself anywhere near it.

You seem to think l dislike you. Let me put your mind at rest. I don't dislike you It is just your agenda driven ramp and deramp you come out with l am not keen on.

Balls in your court now.

Regards

You still have not answered my question directly Potnak. Not the first time.

It is not sniping.

I will take your lack of a reasonable direct as an admission of defeat on this one.

I will spend what time l like reading through your ramping and deramping posts. You say one thing one minute then nullify it the next. I do find that amusing and indicates your transparency. Whether l am liked or not l will contribute what l feel valuable to this chat board.

As l have said many times before the share will have its ups and downs but the end game is getting a least one compound into clinic or at least an on licence on one if not two. Then l will sell a large chunk.

Unlike your self l have never ever made such a statement as you to discourage potential.new investors from investing. Neither such a statement to encourage investing either.

Regards

Cannot say for sure, but any tax rebates are reinvested for R&D.

There was one for 400k

I think another estimated at 280k

If Edison is an accurate account how can they speculate as all it is really on what the cash burn up rate is? Last 12 months much spent on R&D plus manufacturing of capsules.

Are Edison in the know how much phase 1a trial will cost? Have the factored in the tax credit of 43%?

'With burn rates likely to rise with trial commencement (c £0.5m/quarter currently), we expect Sareum will need to raise additional funds before end-CY23 (H123 cash balance of £2.9m).'

How does or would Edison know the burn rate for now until end of year? To the benefit of who is this report aimed? Any mention of cost savings? If not why not? What is the burn rate for SDC1802?

An excerpt from Sareum RNS

'The Directors consider that the cash held at the period end, together with that projected to be received, will be sufficient for the Group to meet its forecast expenditure for at least one year from the date of approving the interim financial statements. If there is a shortfall, the Directors will implement the required cost savings to ensure that the cash resources last for this period of time.'

Has Sareum anywhere stated they may need to raise funds by end of 2023?

Edison is an investment company so ask yourself exactly what is their agenda.

Something that is under priced will always sell. If it is sold there is a buyer. It is therefore in the interests for an investment research company to drive a price as low as they can get. Those that want to buy into will want the lowest price and ,support any type of slanted report that creates negativity.

Exactly what is your intention of your statement

'As its unlikely we will get a licence deal until we prove it then, for new investors, there is a compelling reason to wait for the first few patients to be dosed before pushing the button'

Are you dissuading potential investors not to invest now, or advising them in any way?

I reckon you sold a few on the recent spike Potnak and now looking to get back in. That seems a compelling reason for your statement. After all you do trade and that is by your own admittance.

Regards

ON AN ANNUAL BASIS, MANY REGULARLY OUTPERFORM THE MARKET BY A VERY WIDE MARGIN:

It then shows a section for Sareum showing up 92%. Where is the accuracy here?

Interesting point here. From Sareum end of year 6 monthly report ( up until Dec 22) Released 22nd of March 23,

The Group made a loss after tax for the period of £1.4 million (2021: £0.9 million), as it continued to progress its research and development activities. These activities, and the related expenditure, are in line with the budgets previously set and are funded by regular cash investments.

The Directors consider that the cash held at the period end, together with that projected to be received, will be sufficient for the Group to meet its forecast expenditure for at least one year from the date of approving the interim financial statements. If there is a shortfall, the Directors will implement the required cost savings to ensure that the cash resources last for this period of time.

For these reasons, the interim financial statements have been prepared on a going concern basis.

3. Taxation

No liability to for corporation tax arises for the six-months ended 31 December 2022. Research and development tax credits, receivable as cash, are estimated to be £285,000 for the period.