Member Info for sadoldgit

I used to go to Upton Park regularly when younger and away games. back in the days of Trevor Brooking, Billy Bonds, Pop Robson. Mervyn Day and the likes. Not been for years but still keep an eye on. A few beers in the Boleyn as well.

Back to topic
Not long to wait however. for granting of CTA as sareum will receive preliminary decision this month.
Not sure if they will release info on this or wait until end of 60 days.

A little word here. Dont go looking up sar compounds. SAR20347 isa Sellick compound. Was confusing as is Tyk2 Jak1 Jak2 and Jak3 and the purity poor at 97%

A link below here of some compounds for those that may be interested in Kinase inhibitor make up of compounds.

https://www.selleckchem.com/products/sar-20347.html

in addition there is a bit of retrace in the bio market
https://www.fiercebiotech.com/biotech/kill-your-darlings-band-biotechs-cut-pipeline-prospects-focus-cash-priority-programs?itm_source=parsely-api

That is a patent for the compound itself I believe. Does not in anyway relate to the manufacturing of a compound as far as I can see.. Does correspond to autoimmune ie 1801

We have a patent grant circa Oct 21
https://www.lse.co.uk/rns/SAR/us-patent-granted-for-sdc-1802-tyk2jak1-inhibitor-9hk3sdpmxw35xkv.html

To answer your question it would appear that we have been granted patent protection regarding SDC1801

The patent (US 11,154,539) will grant on 26 October 2021 and will protect the SDC-1802 molecule and pharmaceutical preparations thereof as a therapeutic to treat cancer selected from pancreatic, colorectal and kidney cancers, melanoma, and B-cell lymphoma by inhibiting TYK2 kinase. This programme is in preclinical development.

It dose not relate specifically to crystallisation of a compound. Hence I would assume in the absence of any other factual reports we may not as yet be patent protected in this part of the invention in the USA.

From RNs Jan7th 2021
"The granting of this patent in the US completes the protection of the intellectual property for our proprietary SDC-1802 Programme across all major markets. The Board believes that the patent will enhance the value of its TYK2/JAK1 inhibitor programmes and the Company's negotiating position as it continues to engage in discussions with potential licence partners."

https://www.lse.co.uk/rns/SAR/us-patent-grant-for-tyk2jak1-anticancer-candidate-a8j5mz5b2ls6bxr.html

Certain we are patented up to the eyeballs.

Since both SDC1801 and 1802 are similar and crystallisation of a compound has been patented for 1802 I an contemplating as to why no mention of this or any indication that 1801 protected in same way.

It may well be from which group ie 0, 1 or 2 or combination thereof that 1801 is formulated by. There exists differing degrees of selectivity in these compounds.

Not entirely sure on this one.

Krone, good afternoon.
Patent for crystallisation of a compound was granted April 2022.
RNS
https://www.lse.co.uk/rns/SAR/european-patent-granted-for-sareum8217s-sdc-1802-jus0tdjz7hd5wzb.html

Olumiant (baricitinib) Jak 1 Jak2

I dare say that we are vastly superior to older 1st generation Jak inhibitors that have an ever increasing associated side effects. Mainly Jak2. Jak3 and Jak1.
Yes we have Jak1 but as TM stated an 'optimum amount'.
The difficulties in obtaining an MTD and of course at 30 times treatment dosages there were no adverse effects reported, it can only be taken that we are head and shoulders over anything else currently out there at the moment. Of course confirmation of this can only be achieved in our up and coming phase 1 trial.

Enough from me.

Regards

https://www.fda.gov/drugs/drug-safety-and-availability/fda-requires-warnings-about-increased-risk-serious-heart-related-events-cancer-blood-clots-and-death

The only slight concern i have is the development of heart problems with the use of inhibitors. I am fairly sure but not 100% certain that this is predominantly a Jak2 problem. But interesting that this has been known about for some time yet is only now being put under the microscope so as to speak. The older early stage Jaki's and even some of the 2nd generation inhibitors are not without problems.

The Janus kinases (JAKs) are a family of cytoplasmic tyrosine kinases whose function is to transduce cytokine-mediated signals via the JAK-STAT pathway. There are four JAK subtypes, each of which has overlapping receptor responsibilities. Inhibitors of this enzyme family (jakinibs) have shown efficacy in treating certain inflammatory and autoimmune diseases such as rheumatoid arthritis and Crohn's disease. However, the first generation of these drugs, tofacitinib and ruxolitinib, lacked subtype selectivity, affecting JAK1/JAK3 and JAK1/JAK2 respectively. This has led to dose-limiting side effects in this otherwise promising class of drugs.[13][14] Upadacitinib is a second generation Janus kinase inhibitor that is selective for the JAK1 subtype of this enzyme over the JAK2 (74-fold), JAK3 (58-fold) and tyrosine kinase 2 subtypes.[1

Upadacitinib is predominantly a Jak1 inhibitor.

https://www.ema.europa.eu/en/news/ema-starts-safety-review-janus-kinase-inhibitors-inflammatory-disorders#:~:text=In%20addition%2C%20preliminary%20findings%20from%20an%20observational%20study,Olumiant%20compared%20with%20those%20treated%20with%20TNF-alpha%20inhibitors.

https://www.fda.gov/drugs/drug-safety-and-availability/fda-requires-warnings-about-increased-risk-serious-heart-related-events-cancer-blood-clots-and-death.

Regards

Good morning Gunner68.
Only one trial in healthy patients would be required. A company would be in a position to trial then for efficacy in any other or all indications.

Worthy of note here ( although slightly off target is the following link with regards treatments and exclusion of patients with pre existing auto immune /cancer conditions.
https://pubmed.ncbi.nlm.nih.gov/32194150/

Back to original chain of thinking.
This is the importance of prior escalating dose toxicity and side effect studies to establish a maximum safe dosing limit to treat humans.
Some indications may/ will require higher levels than others.
As HbD has already pointed out 'The Phase 1a trial will also investigate the effect of SDC-1801 on certain biomarkers of autoimmune disease that could be predictive of efficacy when tested in patients."

Hence 1a is pivotal, very much so.

This would indicate areas of most potent efficacy and likely hood of success in a variety of indications of which we have many.
Many indications will be dose dependant.

There is plenty of room out there in this increasingly growing market.

Beer o clock time

Regards

Badsterman. I sincerely hope that new treatments are developed to combat spondyloarthritis.
I dont think we are far away with regards our inhibitor 1801. It would be fantastic to get a decent treatment into the clinic. Like most diseases it is not only the patient but also immediate family who suffer albeit not in the same way.

Too many treatments in use are outdated, yes may be relatively cheap but are ineffective with non tolerable side effects.

However they are still money spinners for the manufacturers.

Regards and sincerely hope that a more effective tolerable treatment come along for your better half.

Treatment targets for plaque psoriasis
An acceptable treatment response is either BSA = 3% or an improvement in BSA = 75% from baseline, 3 months after treatment initiation [18].

The ideal target for treatment response is BSA = 1% 3 months after treatment initiation maintained at every 6-month assessment interval during maintenance therapy.

Explains a lot of claims. Equal to or greater than 75% in BSA ( body surface area)
Tofacitinib, Jak1 Jak3
https://pubmed.ncbi.nlm.nih.gov/26875540/

Plenty of room and scope here for 1801!

At one time the at thront and most cost effective way of treating severe plaque Psoriasis.

Look at the side effects.

https://www.drugs.com/sfx/methotrexate-side-effects.html

Good post Ahfam. There is a lot going on behind closed doors that we are not privy too. Apart from that/

Note for psoriasis. This from 2020.

We do have competitors in this market, BMS Deucracitinib a TYk2 inhibitor
Phase 3 study from march 2021 to April 2024.
full info in link below
https://www.clinicaltrials.gov/ct2/show/NCT04772079

Since Deucracitinib is TYk 2 only and yet Tyk2 Jak1 are critical for signal transduction then surely SDC1801 would be vastly superior to Deucracitinib.

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.

Full link of the above given below
https://www.sciencedirect.com/science/article/pii/S0022202X20300270#:~:text=TYK2%20and%20Jak1%20are%20critical%20for%20signal%20transduction,through%20Jak1%20in%20keratinocytes%20%28Sohn%20et%20al.%2C%202013%29.

CB.
Renegotiation was somewhat a waste of time. Reduction in milestone payment did absolutely sweet fa. I think reduction was along the lines of 5 million. ie 7 miilion dollars for trial in first patient to 2 million. ( dollars) of which we were entitled to 27-5% of. Sierra gone through every loophole to delay.
What concerns me is the 'finalising design' which has been going on for around 8 months. What have they achieved? More importantly what have they done?
Have GSK made any reports or an update on the status of trials to the CPF? Must be due soon as was part of agreement.
GSK have clout so they will get their way.
Nigh 3 years of delay with development of 737 is not good however you look at it. Unacceptable I feel but very little can be done about it.
if successful to commercialisation then will equate to around 70 million total in milestone payments to Sareum plus royalties. Fast track is not out of the question but combo therapies need finalising. They are patented after all.

We may or may not hear news of development of SRA737 around same time as Clinical trial acceptance.
Correct me if I am wrong. but my understanding is we are funded through to end of phase 1 clinical trial in healthy humans but would only be progressing trials in patients with psoriasis subject to further fund raising.
When and how much funds are required is any ones guess. No indication as to the amount given. I believe we have funds sufficient to take sdc1802 to end of preclinical.
Not sure of our cash burn up rate at the moment but bound to increase on commencement of phase 1 trial.

Regards

Cobalt. Sareum would have had a voiced opinion and that is about all. They have a minor 27.5% financial interest in 737 and hence have no sway at all. They are part of yet have no control of.

Regarding 737 GSK will not be looking at alternative non dilutive solutions to finance 737. That problem no longer exist. It will depend much on how much of a priority GSK assign to 737.

Regards

A good read and will go through in depth later. That will take a day or so.

This high failure rate raises the question of whether certain aspects of drug development are overlooked? On the one hand, true target validation, which confirms the molecular target is the cause of human disease and drug's intended target, is still challenging for the success of clinical drug development. On the other hand, current drug optimization may have overemphasized one aspect but overlooked others that may mislead drug candidate selection and unbalance clinical dose/efficacy/toxicity.

The delicate balance of clinical dose/efficacy/toxicity of drug candidates in clinical trials is not only determined by their potency/specificity in inhibiting its molecular targets (through SAR studies), but also by their tissue exposure/selectivity in disease-targeted tissues and normal tissues (through STR studies). However, current drug optimization process overly emphasized drug's potency/specificity through SAR studies but overlooked drug's tissue exposure/selectivity in disease-targeted tissues vs. normal tissues through STR studies, which may have misled the drug candidate selection, impacted clinical dose optimization, and tipped the balance of clinical efficacy and toxicity.

We did experience difficulties in reaching a MTD. At 30 times treatment dose an MTD was not established.
Low treatment dose of 12.5 mg per day and a maximum of 1000mg per day.
MTD could not have been calculated on 12.5 mg per day as would only give 420 mg per day and hence 1000mg a day not possible. Now in this case as 1000mg treatment a day is maximum envisaged dose then we would be looking at a minimum of 30,000 mg a day ie 30 grammes. Yes it does appear a colossal amount. Interesting point is what a sareums intended dosing regime for an indication? This I would hazard a guess to be in the hands of the clinical trial experts ( experts in their field of a specific indication) that can establish a dose effective response .

Tim an co have avoided the 'too competitive' market ( as stated previously by TM and their intentions) and have aimed understandably at a market that best suits the capabilities of 1801 ie first indication of psoriasis. Not the biggest market but biggest chance of success.

Regards

Bobbler, firstly good afternoon.
We can look also as to why these drugs failed. Mainly due to toxicity and adverse side affects. if we remove or reduce the toxicity then we can increase the efficacy. Most drugs fail as due to the levels required for successful treatment are not reacted due to adverse side effects.

We are fortunate enough to have entered at a time where there are well known adverse effects associated with JAK 1, 2 and 3. This has enabled us to develop little to no toxicity compounds by selectivity over these early stage inhibitors.
Of course this has to be proven, hence we have clinical trials.

Of course some will say, well these companies had clinical trials too. Yes they did but were they aware of the toxicities and adverse side effects that are now well known and documented have since come to play such an important part. A case of the big pharm with plenty of clout claiming look what this can do. Not really looking at where it can fall down. Sareum have developed their drugs on these big pharma' s mistakes.

I am certain we will pass phase1 and psoriasis trial with flying colours.

Regards

One important thing I omitted is the word proven with regards to safe therapeutic dosages in clinical trial ascending dose
studies.

Sareum were and still are looking to license at end of preclinical/ early clinical. Nothing has changed. As for being long overdue I just do not see this being the case. We are approaching end of preclinical with 1801. Until we are granted CTA that is where we remain with 1801. There will always be doubts until a particular milestone is reached. Once reached the element of doubt is removed and the value of the commodity goes up in value.

CTA should and is a mere a formality. The crux here is to establish safe therapeutic treatment levels. Our capsules will be ready and in sufficient quantities for early stage trials.

The CTA is a waiting game of course. Nothing can proceed any further until granted. It is a vital milestone with regards to continuing development.
Does anyone here have serious doubts about the granting of the CTA?

Phase 1 trial and its results will be of paramount importance, not only to continue development of 1801 but also the financial value , it will add to Sareum based on the safe level of therapeutic dose that can be established via ascending dose escalation studies. Until a milestone is reached there will always be an element of doubt. The established safe level of dosages will have an effect on how much and which indications we can realistically treat. As dosage levels go up so does the efficacy of our compound corresponding to which indications it is theoretically possible to treat successfully.

Its value will rise accordingly.

In this instance how can you place a price on a compound if you have not established an accepted safe therapeutic level of treatment. Unless these are established you are going to have a hell of a job progressing to later stage clinical trials and that will include additional indications.

SDC 1801 around 8 years ( from memory) in development so far. 1802 not that far behind.

We may or may not have a clear decision after 30 days of application. In this instance, if there are any shortcomings then there is a time limit to respond to these shortcomings ie 14 days ( this follows the preliminary decision). You can with valid reasons gain a period of extension. Without a period of extension a final decision will be concluded at end of 60 days.
With regards to not saving a soul. CHK1 has been used in trials whereby the results were extremely encouraging. To such an extent that the treatment to those who benefitted from the trial were still being treated months afterwards. Not all I might add but a few which justified continued treatment.

All treatments have their downsides and there is not one treatment in oncology where the success rate is 100%. I doubt there ever will be, due to the nature and ability of the disease to mutate. it can be strived towards.

It is a waiting game proven by the many years it has taken us to reach this far. Most of the work, although not the most costly is done at preclinical stages.

Regards

I will add one further thing, although I have concerns this merely relates to how much longer we have to wait for on license or maybe a buyout even.
I am of the frame of mind to think that both our inhibitors may well be taken over just after the end of Phase 1 clinical with SDC1801. The concern many majors will have is side effects and toxicity issues, especially long term as are associated with JAK2 and 3. (they have short term ones too). Tim did state that if anyone wanted both they would have to pay the price. HNWI came in a very short while after this.

Regards

You are welcome Kat. You are not a troll in my view it is that you have concerns as many of us do. At times it is better to take a profit. Far better to be in a position of, I sold and made some money than kept and lost.
it will be worth keeping an eye on and my own view if it heads south to around 150 p then definite buy. I have funds to add at this price. Not a case of if all goes well, be more of a case of when. That we dont know, we dont know if Sareum intend to raise capital and when. All will hinge around phase 1 clinical trial. A slight trip south in the meantime may happen and cause concern for some. At the same time we may hear of developments with SRA 737 in next 6 or 7 weeks or so may be sooner. Half a million milestone not take us far but of more importance 737 kick started with a bl00dy big pharma in GSK pushing it. The big companies have far more political sway than the small company even if their compounds not as good.
Its a case of weighing outcomes up and seeing what options we have.
Long term excellent to outstanding. Next 6 months could be little volatile.
In no way was I trying to undermine you for selling. if appeared that way then please accept apologies.
There are people that buy sell at a profit then slate the share. that i do not agree with. You have not done that, you have been cautious and guarding your gains. Nothing I see wrong in that. Just a case of contemplating a good time to come back in.

Ps bare in mind that all stocks especially some of the smaller pharmas (AIM) ( covid expectations) have taken a real hammering over past 6 to 9 months.

Regards