Member Info for sadoldgit

Not good MattyBoy1965.
If it is any consolation I sat on a loss for a while of around 9k on a tranche of shares years ago as added on a spike. I added at around 1.8 to 2.1p. I added continuously through a period from 0.22p to 0.6p per share.
When it drops you feel you have too many and when it goes up you dont think you have enough. Whilst healthy overall as still have a quite a few at low price I do sit on losses of around 45k on my higher buys . Overall around 60k up on what I now hold.

I do feel the current SP is like it was years ago at less than 0,3p per share old money.
Not a case of if it will move up just a case of when I feel.

Why did I invest in the first place?
Sister died of cancer. Diagnosed breast cancer 2006. Died January 1st 2010. Less than 4 stone in weight, bones crumbling and basically bleeding out of every orifice at the end.
That was my justification for investing.

My mother was diagnosed with cancer April 2021. Died July the 3rd 2021 covid not help as delay after delay. Nothing I could do to save either.

It will all come good I feel as been here over 10 years now. You can't bring someones life back. But you can become involved in a treatment that prevents or at least prolong the life of someone that dies.
There lies my interest.
Regards

I will go along with your 6o days Gunner. I think l had forecast 29th Sept. Sareum will know now of any potential problems within 30 days as previously posted by FATI.. Not sure when they will have or had had ethics committee meeting. Typical of Sar since the transformational deal that never took place years ago they most likely not release the outcome until final confirmation and official granting of clinical trial.

Regards

Do you understand the science yes ir no? I have never used the science to shout down the negative posts.

The science is not proven yet? If the science don't work sonny we will not be selling anything.

How can you state we are past the science bit after stating that the science is not proven yet.

The corporate finance guys on the board are the ones that will make the deal.

How are they going to make a deal ? What do they compare it against? The science has to proven to reach certain milestones. From lead candidate to commercialisation there are milestones in the development.

Do you understand that advantages of capsulisation and the crystallisation of a compound? What are the benefits? Do you understand anything about the science?
Rather than dismiss science they should try to understand it if they do not? At least make the effort. Much better to try an understand the science and listen to those that know a little more than we do rather than condescendly try to undermine them.

Then you use the word fact in some vain attempt which in your mistaken belief will give your argument some form of crediblity , then in the same sentence the word ' should.'. The relevance of the word fact here is meaningless.

As for buying in 2020. I added considerably. I sold some in 2021 around 9.4 pence. Some at much lower. I have bought back considerably more since. Remember the sub pound a share just under 2p in old money.

Made around quarter of a million since have been here and have just south of 200k shares now.

I can find no reason for myself to be negative. My belief in the science has never altered.
I will also point out to you here, that if the compounds do not prove to have a good safety profile they ain't going anywhere. So you need believe in the science and or the people that are trying to market it.

I

If you do not believe in the science then why are you here?

Regards

Good afternoon Potnak. What on earth has people posting science pertaining information to the benefit of those invested have to do with trying to convince themselves that they made the right call? For what purpose do you feel it necessary to post such garbage?

If people want to hold for gold then surely it is up to them. Likewise there are those that buy and sell and adjust their tone accordingly.

We have had delays although Sareum have stated this has had very little impact due to covid. The upside of Covid and the nature of our compounds helped increase our SP significantly. I am sure you took advantage.

Good post Aber.
My thoughts on Sareum.
We know our compounds or the compounds we are involved in have potential. Potential is a maybe and maybe not.

We have or had involvement in 737. &37 a checkpoint kinase inhibitor. Oh ish on its own. Slight improvement in combo. Outstanding in combo gemcitabine and a PD1 inhibitor. I will add to this in a mo and try and be not long winded.

Much uncertainty developed under the helm of Sierra. They did not have the funds available but did do some sterling work. CHK1 put on the back burner. Effectively the SP falls over a period of time as no progress updates. No news is not good news in this instance.
We now have 2 Sareum owned compounds with phenomenal potential.
To take them through to commercialisation we do not have the funds.
Options are to raise funds surely. one option is share dilution. Not saying we are going down this route but is a possibility.

Share dilution and investors nigh 5 hit a brick. They dont know how much but they are under the impression it will devalue shares.

Option 2 licensing on. The further we get down the road, achieve milestones , the risk of failure subsides and hence due to calculated probability of sucess the value rises. Interested Pharma's are no different to the investor.

Partnership, runs a similar path as risk associated with on licensing.

Biggest problems in pharma is a safety profile. Boils down to ( especially the USA) can the compound be elevated to the clinic for a specific indication? If it aint considered safe it aint going into the clinic.

Some of the uncertainties will now have been partially removed due to TYK2 ( deucravacitinib) approval and no black box ie severe safety concerns.

Behind the doors we have Tim and co in communications with interested parties. The higher the risk the less they will want to pay. That is understandable.

What we do not know for sure is the exit point for our compounds with regards to deal and size of payment.

Ab element of uncertainty exists.

This must now be changing very soon. Indications that TYK2 is indicating low toxicity with little to no serious side effects.

TYk2 is therefore looking a safe bet. Albeit it may not be effective in many indications ( on its own)

We have Tyk2 and Jak1 which in pre clinical results does suggest a far greater efficacy in other immuno therapies apart from Psoriasis. We have not, and can not really put the hammer down until we have competed a dose escalation study.

Until confirmed that we have an excellent safety profile then I do not see a significant many fold rise in SP.

Saying that however, I would not rule out an acceptable deal of some sort prior to results from a dose escalation trial. The very nature that the CTA has been accepted should further reinforce our potential to be commercialised. Then we can command the best possible deal

Just my thoughts on this.

Regards

Good morning Blastoid. I am pleased the all clear with SOTYKTU with regards to safety and no black box. I will admit to having slight concerns. I would pretty well.lay myy life down and say we will have better efficacy than SOTYKTU. We are also Jak1 essential for control of keratinocyte inhibition essential for extreme effictive control of Psoriasis. Pfizer were showing improvement in 14 days. There are reasonings to dare l say use pure Tyk2 in combo ( this may or may not involve Jak 2, I don't know). To me this indicates an admission that potentially there is a more effective form of treatment than pure Tyk2. Perhaps we could call ours JAKITYKTU.

Yes Il-12 and IL 23 good from Tyk2. Lot of apprehension with Tyk2 as basically un trialled in humans. No black box warning nod greatly underestimated.
We are in a sweet spot. We are also the only Tyk2 Jak1 gunning for oncology. Clearly we are more selective over ordinary Jak inhibitors and perhaps heading towards more specific.

Looking forward to next few months.

Regards.

Do not underestimate the increased value of no black box warning on a Tyk2 inhibitor.

I agree Gunner68. £pounds per share is low. I reckon should be sitting around 7 to 8 p per share old money as we stand. However, lots of AIM companies been hit hard over this year due to current events going on in the world. Investment has moved away from pharma but very soon the neglect will give way to investment due to the barrage of patent expiries coming up. Big pharma's not make much when generic drugs hit the market.

There are not many earth shattering, small molecule inhibitors coming onto the scene.

if GSK looking at lung cancer then 737 as it stands is vital. They will push into development and into clinic to gain revenue. There are a variety of treatments, all will eventually lose their efficacy due to antibody resilience in some cancers ( the difficult buggers ie Ovarian and Pancreatic to name just two. Combo therapy is the only way forward in many diseases, both immuno amd oncology.

A gi normous market exists and we need get a foot in the door.

Regards

A good long not too a difficult read for IBD Crones Disease and Ulcerative Colitus

https://academic.oup.com/rheumatology/article/60/Supplement_2/ii45/6265521

Plenty of space for our SDC compounds to make an entry. Phase 1 clinical trial results will be the price driver. ought to get updates too of dose escalation studies.

Still maintain we are better than deucracitinib with 1801 and we have 1802 in addition for oncology. Similar but not identical compounds.

Oct 2021

'Bristol Myers Squibb’s deucravacitinib has hit its first bump in the road. After blowing Amgen’s Otezla away in psoriasis, deucravacitinib went into a phase 2 readout in ulcerative colitis flying high—only to fail to meet the primary or secondary endpoints.

The clinical trial randomized 131 patients with moderate to severe ulcerative colitis to receive the oral TYK2 inhibitor deucravacitinib or placebo for 12 weeks. Deucravacitinib failed comprehensively, missing the primary clinical remission endpoint and the secondary efficacy endpoints. The secondary endpoints in the study looked at clinical and endoscopic responses along with histological improvement.

BMS downplayed the setback, reiterating its forecast that deucravacitinib will rack up sales of more than $4 billion in 2029 and pointing to the drug’s raft of opportunities. Deucravacitinib may even bounce back in ulcerative colitis, with a second study of a higher dose yet to deliver data.

Even so, the failure in the first midphase ulcerative colitis study is a setback for a drug candidate that was thrust into the spotlight by BMS’ decision to offload Otezla. As it assessed BMS’ takeover of Celgene, the Federal Trade Commission made the sale of Otezla a condition of the closing of the deal to ensure the Big Pharma remained incentivized to develop its own oral psoriasis prospect, deucravacitinib.

RELATED: BMS' deucravacitinib beats out exiled Otezla, plots 2022 launch

BMS’ faith in deucravacitinib was rewarded with phase 3 wins over Otezla in psoriasis. But any hopes the candidate would enjoy a smooth run to market in other indications have been hit by the failure in ulcerative colitis. The question now is whether the failure is a blip or an omen of more efficacy shortcomings as development expands beyond psoriasis.

Investigators are now enrolling patients with conditions including Crohn’s disease, psoriatic arthritis and lupus in phase 2 and 3 clinical trials. The roster of clinical trials will deliver a series of data drops over the coming years that will define the future of deucravacitinib outside of psoriasis.'

Would hazard a guess at Chk1 memcitabine and a PD1 inhibitor in combo WIP. Results are oustanding so far and patentented combo. sooner or later the cat will come out of the bag.
SDC1802 also compatable as a supportive treatment with CHK1 and PD1. Also reputed to increase sensitivity to Gemcitabine which is in our patent.
Good quality updates from you WIP
Regards

Good morning Aber. I think it just a part of life nowadays. Everything seemingly put back or delayed. Almost a continuation of Covid. There are still people working from home up here. Takes them 2 weeks to reply to Emails.

Enough of that. Day traders may be around and the slightest whiff of increase they sell ( people are getting short of money due to inflation and energy prices.
The good side is that Tyk2 has been validated as safe by NDA approval. In psoriasis we will be better and more effective than Tyk2
Tyk 2 on its own l see as inferior to Tyk2 with Jak1.
Tyk 2 basically not worth a toss on its own with regards to IBD as overly selective.

Yes Tyk 2 good but not on its own. That my opinion and am sticking with it until find news to the contrary.
One thing l do note is big pharma really big their products up.
We are dwarfed by big companies like BMS but l believe we have a a superior inhibitor. Unfortunately not reflected in the SP at the moment.
Imagine a big pharma with Sdc 1801 and 1802. They put their spin on a greT product reviewed and reported by people who may have a conflict of interest. It would be on sale now!

Regards

I think Warthog slight difference with initiation if trial and dosing.
Suitable healthy volunteers need recruiting and would estimate around 4 weeks for this. Should have decision on CTA end of month. But yes l did note myself it had crept into next year. A sareum trait l feel.

Regards

HbD As you correctly point out TYk2 will not be effective against cytokine storms. A dab of Jak 1 required for that.

Also we have a further advantage over SOTYKTO as we have 1 compound for auto immune and one for oncology.

Yes they are further ahead and just the start of the later generation of Tyrosine kinase inhibitors that are as effective but with a greater safety profile.

So many of the older medications and treatments will become obsolete very very soon.

Regards

Note also PASI Psoriasis Area Severity Index ( basically the severity of the lesions and the area covered by the body, a maximum Index of 72)
Now to be taken onboard a treatment is required to reduce this PASI by 75% over a 12 week period. Yes achieved By deucracitinib which is good ( Tyk2 only)

Pfizer Tyk2 Jak1
In contrast to this single-kinase inhibitor, PF-06700841 is a potent dual inhibitor of both TYK2 and Jak1. PF-06700841 is expected to inhibit Jak-dependent signaling at multiple points in the pathogenic cycle, including keratinocyte signaling, maintenance of inflammatory T-cell infiltrate, and direct inhibition of TYK2-dependent IL-23 signaling (Fensome et al., 2018). In this in-human, phase 1 study, PF-06700841 100 mg and 30 mg daily dose levels improved disease activity over 4 weeks, as measured by PASI in patients with moderate-to-severe plaque psoriasis.
Now it does state improved disease activity over 4 weeks as opposed to 12 weeks with pure TYk2. What we do not know is the reduction in PASI score for Tyk2 Jak1.

All looking very good.
I am sure I read somewhere that the clearance was achieved over an 8 week period for Tyk 2 Jak1 inhibitor. Bare this in mind but do not take as gospel until I find link to.
Regards

Year old news
'Psoriasis is a common, chronic inflammatory skin condition that impairs patients’ physical health, emotional well-being, work performance, and overall quality of life. Psoriasis and related conditions such as psoriatic arthritis are caused by abnormalities in the immune system. Various drugs are used or explored to treat these conditions, including Janus kinase (JAK) inhibitors; however, JAK inhibitors are associated with a range of side effects such as abnormal changes in blood cell, cholesterol, and triglyceride levels, as well as liver and kidney dysfunction. Deucravacitinib is a new oral drug in development that blocks a key molecule involved in the pathogenesis of psoriasis known as tyrosine kinase 2 (TYK2). This analysis compared the selectivity of deucravacitinib versus approved JAK 1/2/3 inhibitors (tofacitinib, upadacitinib, and baricitinib) for TYK2 and JAK 1/2/3 in whole blood assays, using therapeutic doses of each drug. The authors reported that deucravacitinib inhibits TYK2 with minimal or no inhibition of JAK 1/2/3. In contrast, tofacitinib, upadacitinib, and baricitinib inhibit JAK 1, JAK 2, and/or JAK 3 to various degrees but do not inhibit TYK2. These results demonstrate that deucravacitinib is a distinct class of drug compared with the JAK 1/2/3 inhibitors. The results of this analysis are consistent with those of two recently completed phase 3 trials in patients with moderate-to-severe plaque psoriasis (POETYK PSO-1 and PSO-2), as well as a phase 2 trial in psoriasis, in which deucravacitinib was efficacious and well tolerated, without clinical or laboratory abnormalities suggestive of JAK 1/2/3 inhibition being observed.'

https://pubmed.ncbi.nlm.nih.gov/34471993/

from Aug 20
TYK2 and Jak1 are critical for signal transduction of many key cytokines driving psoriasis. TYK2 is mainly associated with IL-23 and IL-12 signaling (Tokumasa et al., 2007) in T cells (Ishizaki et al., 2011), whereas many other cytokines signal through Jak1 in keratinocytes (Sohn et al., 2013). Hence, dual blockade of TYK2 and Jak1 has the potential to rapidly attenuate both the immune and epithelial components that create the psoriasis phenotype. Similar Jak/signal transducer and activator of transcription signaling pathways are also implicated in the pathogenesis of other autoimmune diseases including rheumatoid arthritis and inflammatory bowel diseases, but psoriasis is the most accessible disease for mapping molecular disease responses to Jak inhibitors

There exists another IL-1B inhibitor Anakinra. That has severe side effects too. (Orphan Biovitrum)

Psoriasis + Tyk2 and Jak1 all the way. Head and shoulders above anything else out there at the moment.

Good afternoon Benzo. Nice to see a new face.
What is your opinion regarding CHk1 in combination therapy with PD1, PARP and chemotherapy treatments? Since GSK have now bought Sierra outright and now the owners of a Chk1 compound, what is your opinion regarding the likely hood of GSK accelerating development of CHK1 combo therapy and the timescales involved?

Regards

Good news for Cineworld given their badly needed lifeline. Should have a good increase of 20% plus today once the news has sunk in.

i think you are right Silverfoil. 75 years at the helm. Truly a very sad time approaching I feel. God bless her Majesty.