Member Info for sadoldgit

I look forward to meeting some long term holders too Enki.

Have you been on day release from the ADVFN chatboard since 24th Aug. The utter garbage you write indicates a similar level of intellectual stupidity as one or two others that have posted over there.

Regards

Colbaltblue, with your pessimistic downbeat attitude on life, no one would ever invite you.

AI Overview

+6

Janus kinase (JAK) inhibitors are a promising treatment for systemic lupus erythematosus (SLE), and selective JAK1 inhibition may be especially effective for skin lesions:

JAK inhibitors

These small-molecule compounds can regulate cytokines and inflammatory mediators, and are already approved to treat other inflammatory autoimmune diseases. JAK inhibitors can block the JAK-STAT pathway, which is responsible for signaling from activated interferon receptors to the nucleus.

JAK1 inhibition

Selective JAK1 inhibition may be a promising treatment for SLE skin lesions.

JAK inhibitors in SLE trials

Several JAK inhibitors have been studied for SLE, including:

Tofacitinib: A JAK1/3 inhibitor that reduced cholesterol levels, improved vascular function, and decreased the type I interferon signature in SLE patients

Baricitinib: A JAK1/2 inhibitor that improved lupus rashes and arthritis in some trials

Deucravacitinib: A selective tyrosine kinase 2 (TYK2) inhibitor that yielded greater response rates than placebo in a phase 2 trial of SLE

SLE is currently treated with corticosteroids and immunosuppressants, but these treatments can have adverse reactions and poor efficacy. JAK inhibitors may be a safer and more effective treatment option for SLE.

Https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(22)02607-1/abstract

Rates of adverse events were similar across groups, except higher rates of infections and cutaneous events, including rash and acne, with deucravacitinib treatment. Rates of serious adverse events were comparable, with no deaths, opportunistic infections, tuberculosis infections, major adverse cardiovascular events, or thrombotic events reported.

Conclusion: Deucravacitinib treatment elicited higher response rates for SRI-4 and other end points compared with placebo, with an acceptable safety profile, in adult patients with active SLE.

Https://pubmed.ncbi.nlm.nih.gov/36369798/

Have a read through and see what is deemed acceptable as to safety.

Two things here FTC

On good long term toxicity results the compound ie 1801 will be worth around 4 x higher than current figures gained from informal discussions.

If Sareum had a market cap of 300 million the commercialisation value to a pharma will be no different than at 30 million.

End of phase 2 you are looking approx 4 x value of compound at end of phase1

Take into consideration we did not complete phase1b and hence gain any indication of efficacy or proof of concept in Psoriasis.

Safety profile similar to Deucravacitinib would put us at around 750 million plus l feel prior to completion of phase 2 trial results.

Even this figure may be well short if a company or companies recieve the right data results.

Me thinks it will go to a clinical trial stage development company already lined up by a pharma. I may be wrong, we may have been approached by a well heeled clinical trial development company looking to pass onto pharma.

On good long term tox results then commercialise the hell out of it, maybe to surpass the expectations of the heady heights predicted for Deucravacitinib.

BMS for one, are not going to want 1801 as a competitor.

As from what l have put we have around 200 to 250 million inclusive of milestone fees up to around 800 to 1 billion and of course anywhere in between dependant on news.

Odd that we are pushing to enter phase 2 trials and yet at around 30% of market cap prior to RF finance and phase 1a commencement.

Where has the lost value gone? Or has it not?

You will get those that think they are clever state if the 1801 was that good why is the SP at 25p instead of at least 150p?

No one made the offer so it is worthless.

People will pay up to what they think based on a value to them when commercialised.

However, they will offer initially what they think they can get away with.

It is up to them then to wait out a company seeing if they may suffer due to lack of or poor finance.

3 years ago company worth 300 million.

Now market cap.pf 30 but much further forward and funded to end of tox studies.

Tom.and Co will know better than l do,

In a sense it is reassuring that that they have chosen to pursue longer term toxicity investigations as shows great confidence in 1801.

Clearly no doubt in their mind.

Question now is does the pharma up the offer bow or risk losing out to another pharma once results are confirmed?

Regards

as dual inhibition with tyk2 and jak1 inhibitor efficacy should be pretty well guaranteed.

long term use for psoriasis but treatment period over many years, will be determined by toxicity effects.

are we ok for 5 years, 10 years or longer?

sle l believe we will give good results in efficacy but at the same time not suffer the adverse events that caused the cessation after phase 3 3 trials with baricitinib a jaj1 jak 2 inhibitor.

similar profile yes to us with regards to on target effects but we have tyk2 instead so removes the risk of ****dimerisation.

would suggest that we will carry out further studies to prepare phase 2 readiness for 1801 fo on licence to an interested party.

at the moment it's all about establishing long term safety which does in effect continue post commercialisation.

The FDA since around 2022 have placed importance on toxicity issues of typical inhibitors.

Adverse events especially serious adverse events have been on the increase.

The US market! I round hazard a guess I that that is where one of our major interested parties are.

Regards

Clearly there are people that know more than we do.

Outside players now involved.

Sp has been suppressed ever since RF came aboard and remained low after they have left.

Too much concentration here on the current SP.

We have funding now and can develop both compounds further.

I see no reason for the requirement of further tox studies to enable phase 2.

What has happened over the past 2 to 3 years is long term adverse events some serious as in major adverse cardiologist events.

These problems have not resulted in any suspension of any inhibitors currently in use.

Restrictive use as not used as first line of treatment and only where pervious treat Is showing of no benefit.

Pharmas wil want some degree of information supporting longer term toxicity effects as close as they can get to guarantee.

If we licenced now we at the low end with regards offers.

On good long term toxicity study news the price will increase several fold.

Take Deucravacitinib as an example. It gained its 4 billion upfront payment not on its mediocre Psoriasis results but completely cleared and put into a different class as not associated with the typical Jak1, jak2 and jak3 adverse events.

Whilst failing miserably in Ulcerative colitus this does not prevent Deucravacitinib being used and at the current time being declared as satisfactorily safe gor long term use.

Pharmas want revenues from commercialisation

For that they need compounds thst can be used over many years fo a patient. At the same time increasing commercialisation over other as yet unknown Indications.

Phase2 is normally where a larger part of the longer term toxicity studies come in.

No where in the RNS does it state that further long term toxicity studies are required as a prerequisite to phase2.

If you think l am wrong please indicate as to where.

As l see it an interested phsrma wants additional data with regards to toxicity.

The only realistic way this can happen where there is any degree of integrity is to use this information in the phase 2 application study package whereby it is accepted by the regulating body.

That my belief as to where we sit.

Regards

Big trade at 10.34.

That shows interest to me.

Many red trades corresponding to a 4 % rise.

Something brewing me thinks.

A change of sentiment too.

Since as SDC1802 is now receiving patent protection for use in immunotherapy then it may well be they can carry out similar testing on both compounds.

SDC1802 primary intent of indication is T cell lymphoblastic leukemia. Studies carried out so far express compelling efficacy.

Long term affects in cancer treatments tend to have a higher threshold of adverse events.

As the preservation of life takes major prioroty over adverse events.

All 30 odd molecules which are protected by patent are utilised whether partially or wholly by Sareum.

Chemically how the react or to be more more precise bind to a target will be the same.

The only difference is the corresponding Jak selectivity. Primarily still Tyk2 selective over Jak1.

That my understanding.

Minor differences in GM -CSF activity may be present between compounds as well selectivity on different Jak Stat pathways.

Questions l would put forward is how far is 1802 from end of preclinical and how long will this take to complete with no financial restraints.

Do you intend undertaking similar long term toxicity studies in 1802 and if not the reasonings behind this?

Is the company still focused on licencing 1801 to provide funding for development of 1802?

What is the priority with regards to providing increased value to shareholders over obtaining a licence deal?

What is your expectation of a possible on licence being completed within next 12 months?

Is there interest from pharmas with respect to 1802?

How long do you envisage further tox testing to take and when will this be implemented?

Some of the questions above are a little leading as many will realise.

Regards

'has entered into a development and commercialisation licence agreement for SRA737 (the "Licensing Agreement") with a private biopharma company based in the United States (the "Licensee Company").'

EP

'However … is there not also the scenario that the toxicity results prove to be a no go for a licensing partner?'

Toxicity results are not the be all and end all as can indicate good safety or poor safety and be incorrect both times.

Even early clinical is by no means conclusive.

Safety is most realised over 2nd and 3rd phase trials results involving hundreds of patients in Phase 2 and potentially thousands in phase3.

It is true that we are looking at phase 2a with 10's of patients but all boils down to adverse events and how serious they are. To give a good statistical analysis giving a high confidence factor requires data of many patients over a long time.

We had achieved very satisfactory results albeit short time frames and few people.

We could have done phase 1b, but as we know have decided to pursue into phase2a.

Clearly Sareum are pressing the safety aspect of SDC1801.

Funds on board achieved.

News on development of 737 would certainly be an added bonus but at the moment not part of the equation.

the safety of jakis or to be more precise associated adverse effects have been known gor ages.

we are primarily tyk2 selective over jak1

our jak1 also has selectivity over jsk2 and jak3

we therefore have very little jak2 adverse event risk by definition.

jak2 ****dimerisation is problematic as can alter red and white blood cell.production.

blood clots and deep vein thrombosis

i believe from memory there is a tyk2 jak2 inhibitor ropsacitinib that is in development for psoriasis and early stage investigations encouraging as great efficacy and claimed no serious adverse events.

it may well be that the tyk2 has preference to heterodimerise in this case with jak2 resulting in 2 advantages greater il-22 or il-23 whilst atvthe same time removing the problem of epo associated with jak2 inhibition.

we may well benefit from this pairing on our owns compound as jak1 and tyk2 both hetrodimerise ie pair up with jak2.

no maximum tolerated dose was established in preclinical with 1801 at over 30x maximum therapeutic dose.

it does appear that some compounds may well have an affinity for heterodimerisation of jak2 over jak2 dimerisation and if this should prove to be the case then a mighty step forward and of significant great value.

moderate adverse events may be experienced at higher doses and with older people.

baricitinib a jak1 jak2 inhibitor has mace events and data has disappointed eli lilly as they have decided to cease development in phase 3 for sle.

still approved for use in already granted authorisations for clinical use it already holds l might add.

sareum do appear confident enough to address long term safety concerns at this moment in time.

this does indicate a considerable degree of confidence in their sdc compounds.

the establishment of a decent safety profile will dependant on data either severely limit restriction as to indications of use or remove restrictions completely. the second of course is tall order but not unachievable.

it will certainly add considerable value to commercialisation up front payment and also milestone payments and royalties.

the pharma needs adequate reassurance from such investigations to safeguard as much as they can their investment which can run into hundreds of millions very easily.

my opinion fwiiw, is sareum are looking at a higher up front fee.

regards and a link below on jaks and concerns

https://ard.bmj.com/content/80/7/865

Worth a read in the link below

https://www.dovepress.com/jak-inhibitors--a-story-of-success-and-adverse-events-peer-reviewed-fulltext-article-OARRR#:~:text=However%2C%20the%20escalating%20clinical%20utilization,US%20Food%20and%20Drug%20Administration%20(

Good post Krone

Modifi has raised $10.7 million to date in seed funding and is backed by investors including American Cancer Society's investment arm, BrightEdge.

Merck has been in pursuit of eligible candidates that could potentially make up for a loss of revenue from its aging blockbuster cancer immunotherapy, Keytruda, which is set to lose its patent protection by the end of the decade.

Interesting link k below worth a read

https://www.medscape.com/viewarticle/989840?form=fpf

Good evening Lazarus, you beat me to it, as l were about to post something similar.

In addition to what you have posted, for the further tox studies the object is long term effects.

In itself difficult to obtain as long term effects are by nature very much of what they are. Effects are monitored at all stages even post commercialisation.

We have observed no serious adverse events.

We still have not reached an MTD!

Baricitinib is Jak1 Jak2 inhibitor with associated

adverse events but is okayed for use for up to 6 years.

This safety toxicity further studies looks to be taking the pi55 a bit.

Phase 1 data results that we have so far indicate safe for use at the current levels administered.

Perhaps Potnak could as he postulates either success or rapid failure on further toxicity results give his reasonings as to what type of result is likely to lead to failure as the only sure way is gaining data through successive trial stages.

Stage 2 is more about efficacy

I believe it us more about if we fit into the Allosteric Tyk2 safety class or the boxed warning class associated to earlier 1st generation and dome early 2nd stage inhibitors.

Its a deep subject with which we have been provided with no in depth explanation of what is required and why

Regards