Member Info for sadoldgit

Solubility can apply to alcohol . if we dissolve a tablet i water is it totally soluble? I can disolve a tablet yet still residue at the bottom by definition is not soluble.

Apologies for appearing pedantic HBD.
My understanding is the benefits of of crystalline structure. is that the crystal is totally dissolved in a solution. This is not to be confused with emisable in water.

I must confess not to reading your attachment in its entirety.

However. as you have raised ths issue and I have mentioned many time before the importance of the formation of a crystallisation of a compound.
Should the patent be granted for this invention then it gives additional benefits of patent protection extending patent protection to 20 years above application date.

regards

Very good question fearg. If it is to do with crystallisation of a compound then my opinion FWIW is that it should solve solubility issues. Sareum were experiencing problems with larger than research doses of our Tyk 2 Jak 1 inhibitors which stem from the same family of compounds. effectively if this were the case then our Aurora plus FLT3 would in effect be covered with the same period of patent protection. I may be wrong, if I am not, then Tim and co have worked a blinder.

All will come to fruition in next couple of weeks. My opnion most of work is done to pre on license, just a matter of crossing the tee's and dotting the eyes. You would think this can be done quickly in reality it is not, delays happen.

The unkown Chinese pharma was never interested in taking our Aurora FLT + 3 forward to be taken as an oral route. It was taken to see effect on Covid 19. That is my most honest opinion. What the hell are you going to get for 50k ffs.

With regards Covid is it coincidental that the Chinese government opened up the 3 Gorges dam to flood Wuhan 5 days before expected rises. Sufficient enough to prevent investiagation by WHO but not enough to damage PLA or their missile base also located in Wuhan. Surely this must be more than coincidence. What is the probability of such an event.

Perhaps ask potnak as he is very good at providing info onshort notice of pessimistic results.

Regards

I will add I am not to ramp or deramp based on my investments. I will call a spade a spade. I will research as much as I can not only for my benefit but also the newer investor. I have been posting on this board since Sept 12th 2012. Longer than most on here. There are a very few posters I respect, very few indeed.

i will look at the science, if not happy I would have effed off years ago. Some good newcomers and i value their comments too.

Regards and keep the faith. Am tired and emotional now and off to bed.

Regards

Very good question Potnak.
Either the patent that was formerly rejected after 3 atempts for 1802 as were classed as similar compound. But then again would have thought that would have been announced.
The patent may well be for crystallisation of a compound. Crystallisation of a compound will offer many benefits, The two main benefits would be maintaining compound structure and solubility. Effectively crystals can be dissolved so we can take up via injection through a solute or through the oral route. Storage times should increase along with temperature and humidity restraints.
additionally and of course financial importance would be the added benefit of patent protection. ie if and when granted the procedure cannot be copied to produce our compounds rendering copies when other patents expire. Effectively start from 2020. I f this proves to be the case then Tim an co have worked a blinder.

Cannot see an additional compound in immuno although in reality the selection of molecules they have can inhibit not only Jak 1 Tyk 2 but also jak2 and Jak 3. No need to worry as guessing that should a compound need to be modified , but prefer to use the word enhanced, these could be added if so required, but would require declaration of new candidate and compound.

Regarding a specific compound. This is interesting and at end of preclinical, is when submission of a candidate is made for trials. Once started here no turning back, i see no reason why they would need a new candidate as was stated by Tim '1802 may work but we think 1801 is better.' I would give my hind teeth to know the difference between 1801 and 1802 as both are Tyk2 and Jak 1 inhibitors.

i would deduce that 1801 is sufficient for Covid treatment as it is. Downside is that the molecule can be made available at a price if we progress through AGILE platform. The financial gain from other targets would be well marked down. hence now time consuming negotiations. They will want as Covid treatment ( big bucks short term at least) but must also pick up remainder of targets Sepsis to MS ( many many times greater long term).

First things first is that 1801 need be pot through stage 1 trials. I f all ok, and am 80% certain myself that it will be, then world becomes our oyster.

Regards

Potnak what out of interested is your probability of failure on this on SDC1801.

My opinion for what it is worth is there cannot or never will be an SDC1803 as 1801 is immuno and SDC 1802 is oncology.

Regards

Punters back a 100 to 1 horse knowing it is very unlikely that it will win.

Potnak. Do you back 100 to 1 horses? Do you think you have backed one here.?
Your original quick look Google gave you 5 in 5000 success ie one tenth of a percent success that equates to 1000 to 1
What is this to to with a probability of success in fields of oncology and immuno treatment?

It is possible to have a horse rated at 100 to 1 and only 10 horses in a race.

You state the probability of success as 5 in 5000 for a success of new drugs. In this case you are inferring there are 5000 drugs and only 5 will reach full success.

Now a horse may be at 1 to 10 odds on? lets take a 10 horse race. By the nature of the odds it is implying that this horse at 1 to 10 on has 10 times chance of winning and only one of failing to win.

Why should this horse carry these odds if there are 10 horses in the race?

It inplies that this horse has a greater chance of success, therefore there must be characteristics based on its ability to gain these odds. Would that derivation be any different than a pharmaceutical company developing a compound for the treatment of various diseases.

The point I make is you cannot argue a horse being 100 to 1 to substantiate an argument of a pharma compound succeeding.

If you apply such odds where the number of subjects is irevelant to the probability then that also must bode to the probability of success with a pharma.

Good post Aberystwyth I concur 100%.

No news of advancement by the BOD with regards to 1801 is correct. It does not mean there is nothing going on. Negotiations will be going on in the background. Unfortunately we will not get to hear until a deal has been formerly proposed. Negotiations take time. From very early stages 12 to 18 months. Hazard a guess started around a year ago when we went into investigations for Covid. Clearly has much potential in this target alone and indeed any other similar virus that rears its ugly head. As a complication 1801 has vast potential in a range of auto immune diseases. My opinion it will be on licensed when SDC 1801 is taken on as a whole and not just for Covid 19.

Phase 1 trials will go ahead along with a licensing partner after pre clinical stages have been completed in their entirety. This is my opinion. Others will have their opinions. Lets look at it. science aside, probability of success in its entirety in immuno is only 15.1 percent. 69.8 % chance of going from phase 1 to phase 2. As each phase is reached the probability of success goes up.

Can offer no more on this.

Regards

As for dates I can offer no guidance on this as in the hand of the BOD and interested parties.

Sad as I am I will consume my beers and very slowly digest your attachment Thoth.

Regards

Afternoon Thoth, Yes Jak 1 is desirable. Jaks work in pairs. the only pair that does not work is Tyk 2 and Jak3 as not compatible. Not probability I might add but fact.

I maintain that for effective IL-6 regulation you need Tyk2 Jak1. As I posted earlier IL-6 in the treatment of a cytokine storm is not new.

. Now if we look at probability by definition than as one compound fails it therefore must give a higher albeit minimal higher probability of success.

In reality it is the science and its advancement in modern day which will decide.

Regards

whhops missed out quantum theory and quantum dynamics.

beer is rather strong today me thinks

Reggards

Our little gem is superior. They are trying to tackle a virus. A virus will mutate in its effort to survive. Sooner or later resistance develops. our immune systems are capable of so much, but at times need help in limiting its over reactions.
One aspect if ind intriguing is the non increase in viral load. This would indicate regulation of cytokine storm and at the same time not interfering with complex CD4 and CD8 cells. A finely struck balance of which interferons have been suitably regulated must be more than sheer luck.

I spend hours on end looking at the compounds, kinase inhibitors and their effect. Even the makeup of molecules. i dont just find out how things work but also how they can fail.

Probability is one thing but science is something else.

if we delve deeper into science, especially nuclear then we rely very much on probability. Mafuta will know. Way beyond the comprehension of many here.
De broglie wavelength and Heisenbergs uncertainty principle, just to start with. You can do a quick Google or you can spend years studying.
The breakdown of Newtonian mechanics where it is proved wrong only to be succeded by quantum

Thanks Mafuta. Be good to meet up for a beer and chat sometime. 20 p party would seem good. Or 10p come to that.
Nuclear Physics is a fascinating subject. I bought a book many years ago. Arthur J Beiser A Concept in Modern Physics.
It took me well over a year to go through in depth.
Martin and Harbison edition 3, and originally had edition 2.

good you are still going strong sir!

Al the best

SOG

Small world indeed Mafuta. Went to Berkeley ( certain it was there and Oldbury) for a first Aid competition. We came 6th. 6 teams entered.
Berkeley closed as the top ducts were exposed to the atmoshere. Should a duct go pop it would not be contained. Sizewell A we had a big outage. Gas blow out ducts. it was envisaged that if a duct went then the pressure release would bloe the concrete roof off and land on the main control room. Effectively they cut out vast swathes of concrete ( 10 feet thick reinforced concrete) in places. In effect created the same problem as to the reason they closed Berkeley.

As a nice side effect it wacked neutron doserate levels circa 300 micro Sievert per hour in areas which were nil. Concrete had high levels of H3 in it too. Chaos is cash they said. how right they were.

Regards as i am having a beer or two. A night off for me as just done 13 X 12 hrs night shifts. 12 months work will be turning into 2 years at least by the look of it.

We had a couple from berkeley ( Ops lads one of them a Phil Webb a complete and utter nut case).

Regards

Great days and good people. I am now at Vulcan NRTE now. Will retire when finish there next year i hope.

Hi Potnak
What were my figures based on? 3.4% is start to finish. I will add
(1) The same drug can go through multiple clinical trials.

(2) Typically, the overall probability of success is calculated by multiplying the probability of success for transitioning from Phase 1 to Phase 2, Phase 2 to Phase 3, and Phase 3 to Approval. However, the methodology used by the authors does not necessarily make that true in this case.
The probability of Phase 1 to phase 2 is 57.6%
Probability of phase 2 to phase 3 is 32.7%
Probability of Phase 3 approval 35.5%

Potters I am not trying to convince anybody sonny. However I am of the opinion as you have stated that you have already sold and invested that you would buy in should the price drop. I therefore suspect this is the reason of your negativeness.

SDC is the priority for Sareum at the moment. if we take a look at probability of that it is 15.1 %.

I will add the probability based on the figures you supplied are a factor of 30 times lower than those I stated. That gives your probability of failure at 99.9%. On that figure you must be pretty optimistic.

However the probabilities of going to phase 1 trials are much higher than this. if not both you and I would not be here.

Regards

Worked in the Nuclear Industry for over 35 years, working in Occupational Health, Health Physics and Engineering. A science degree is required for two of these positions. As much as we do look very deeply into worse case scenarios, it is something we take into account to resolve completely. it becomes a way of life, Anything less than complete 100% being resolved is neither acceptable or a win.

However, you have your outlook in life and I have mine and as such each of us are entitled to our opinions.

Wishing you all the best with your investments here and anywhere else.

Regards.

As shown, the overall probability of success for all drugs and vaccines is 13.8%. (If oncology drugs are excluded, the figure is 20.9%.) But this number masks a wide variation by therapeutic area. Oncology drugs have a puny 3.4% success rate, while vaccines for infectious diseases have a 33.4% success rate.

Oncology at 3.4% indicates for every 5000 there would be 170 successes.

if we take an assumed figure ( non inclusive of oncology) of 20.9% that would give us a success rate in 5000 of 1045.

That makes a quick look on Google figures of 5 in 5000 look very pessimistic.

Regards.

Potnak. i did not say SDC 1801 are tox free. I stated that no toxicity worthy of note has been mentioned so far.

Phase 1 trials take place in healthy humans. This is an indication that the drug in this stage can be deemed suitable with regards to safety enter stage 2. Should Phase 1 trial be completed this in itself is no guarantee that the drug is tox or serious side effect free. It can also continue into stage 3 trials whereby much larger numbers of patients are used. Unacceptable toxicity and safety concerns can also rear their ugly head here.

Whilst many drugs have failed in the past, we need to look at the reasons why. Once we understand the reasons why then adjustments to designs and make up of compounds can be altered. When hew compounds are developed we do not only look at what they can treat, but also limit or eradicate the symptoms we dont want.

Until convincing data can be produced to demonstrate or confirm aspects of a safety profile then it cannot progress further to a later phase to demonstrate its effectiveness.

I would find it hard to believe that there have been 5000 JAK inhibitors produced to enable a figure of 5 in 5000 success rate that you are applying to your argument. I maybe wrong, but I have never seen this or any information regarding this. Perhaps you could steer me in this direction whereby the relevant information exists

Immuno and cancer treatments typically spend 10 to 15 years in development as we know. As stages are reached the probability of failure goes down. But I will be the first to admit that it most certainly at any stage rule out failure 100%

Such as are their safety concerns with JAK2 and JAK3 what company or pharma are going to develop these types of drugs nowadays? Many of these are ageing first generation inhibitors. Their failure has lead to the design of better safety profiling of new molecules. It does not mean that a drug cannot fail just the chances of it failing nowadays are less.

What we do have ( referring to sareum) is very few dedicated professionals designing new drugs. They have worked in conjuntion with the ICR one of the most respected cancer institutions in the world.

Regards

Good morning Potnak.
Just a question here. May i ask why you have concluded that you are under no illusion that the chance of failure here is still really high? What is a really high failure rate? In what areas would you expect failure?
Then you then state the value is in the science and the protection we have in the patents.
It don't sound to me that you have much faith in our science.
Pharma's are most certainly not wanting to get in on the action if they share the same illusion as you ie very high chance of failure.
As I see it. We are approaching the end of preclinical studies in 1SDC1801 and 1802. No toxicity worthy of note, has been mentioned so far.
No toxicity noted at 30 x treatment dosage.
Problems overcome to enable manufacture of large quantities of compound.

Following in-vitro and in-vivo experimentation there is nothing to indicate that there should be a failure with regards to either compound in their safety profiles. There are no indications that SDC1801 has any of the side effects or toxicities associated with pure TYk2, Jak 2 and in particular Jak3.

Tyk 2 is not compatible with Jak3 as you are probably already aware.

Historically there have been no safety concerns in any Sareum compounds.
SRA737 is lacking in development, but this is not attributable to its safety, its compound or Sareum.

SDC1801 has been identified as a potential treatment from targets such as Sepsis through to MS.

Following human trials to establish a tolerable safety profile, all that is then required, is to produce a compound that is more effective than current treatments presentlyin place.

I am not saying it cannot fail, all I am saying is as I see it the chance of success far outweigh the risk of failure. These are my opinions and of course you have yours.

Regards

Thanks Ahfam. Post folllowed mine, just seen MattyBoys post.

Apologies AgentB for my abrupt reply.

Regards

Feel free tp post Tjb68. much better to see than some of the drivel posted here.

SRA 737 was shown to have excellent results when used in conjuction with other treatments. gemcetabine being one of them,
Cancer cells, apoptosis individuals ( no programmed cell death.) After chemo for example which destroys cancer cells ( our good cells also) the cancer can and normally does go throufg a state of replication stress, ie it multiplies rapidly and in certain types of cancer this can be prevented by sell cycle arrest of the P53 checkpoint.

Good post that submitted as info for reference shown below.

Stewart A, et al. A study of combinatorial growth inhibition, cell death and DNA damage repair caused by CHK1 inhibitor SRA737 and WEE1 inhibitor adavosertib in TP53 mutated cell lines. Abstract: 1010. AACR Annual Meeting. 2021.

It is unfortunate that Sierra oncology are dragging their heels on the devekopment of this one.

Regards