Member Info for sadoldgit

Dickpuller,

It may or may not as the case may be of interest to you that one of the Indications applicable and in patent description to treat erythema.

Basically skin burns caused by ionising radiation especially beta radiation of where the skin is exposed. To a certain extent x rays will cause this although more penetration as is a photon but does not have higher energies that penetrate like gamma radiation.

A link below gives a general easily understandable overview.

Use of nuclear weapons with subsequent consequences do not bare thinking about.

Many shares hammered today with the small biotech sector taking the brunt.

As Damion pointed out we should recieve an RNS this month with an report of how we stand.

We are getting close now for the longest period of time without an RNS that l can remember

https://www.cdc.gov/radiation-emergencies/hcp/clinical-guidance/cri.html

Regards

Potassium Iodate tablets are not to reduce the effect of radiation they are administered to limit the uptake of radioactive iodine particular.

The thyroid gland is flooded with non radioactive iodine and hence prevents the thyroid gland up taking radioactive iodine.

Youngsters are way more succeptible and benefit far more than adults.

600,000 medical records destroyed in Kiev after the Chernobyl disaster. Dose rates in some of the streets in Kiev were around 2 milli sievert per hour at the time of the May day parades.

No they are not!

In an event of a Nuclear Emergency and when it is advised by a Health Physicist the use of Potassium will be administered.

I think you are just a tad out of your depth here

So whilst it is good to see development, interest and use of these inhibitors it is also very important to realise that we are close to the top with not just one but 2 compounds of which both are patent protected to cover auto immune.

I would hazard a guess 1802 would excel in UC and possibilty of combo use. reasons being a large amount of patients that have Ulcerative colitus and or Crohns disease develop into cancer.

Current treatment is mainly steroids which in turn have their own negative effects.

Continuation of last topic. Baricitinib will now be authorised for ues in Africa ti treat certain indications albeit at a reduced price,

Companies now are really trying to wring the last little bit of income from the rapidly failing inferior retrospectively prehistoric early generation inhibitors.

Regards

Good post Damion.

An interesting point to be made here.

Ritlecitinib/Litfulo made by Pfizer a US pharma.

A Jak3 inhibitor it is stated. No it is not, merely selective over Jak 2 and Jak1.

Incidently Jak3 Jak1 can prove effective in Ulcerative Colitus which I would hazard an educated guess as to what it was designed for in first place.

FDA approves Litfulo 23rd June 2023

NICE originally rejected Litfulo, but at a later date revised its decision following public consultation ( Never heard about that one, Helen Knight Director of Medicines Evaluation heard how severe Alopecia Areata can have a significant impact on peoples health and quality of life. I wonder who contacted her or lobbied her)) , more information and a reduced price. Priced at £ 949.41p. Discount not disclosed but now NICE recommending LitFulo for something little more than bald patches, it certainly not life threatening.

It contains a boxed warning, R

Risk of death in people 50 or over that have at least one cardio vascular risk factor and are taking a janus kinase inhibitor.

Litfulo is a Janus Kinase inhibitor full of Jak3 Jak2 and Jak1.

It has all the downsides of risk of serious infections associated with Jak3

Cardio vascular, numerous problems associated with Jak2 and of course problems associated with Jak1 albeit with not decent selectivity here.

Pfizer? NIH describe as having acceptable safety profile with long term treatment for Alopecia Areata and of course looking at treatment over 24 weeks and in effect another 24 weeks to expect results which are significantly better than placebo. 14k sufferers in England.

See how this is talked up. Designed for use to treat Alopecia Areata.

I dont think so by a long term, but i wont go on about this.

By having known serious problems including risk of Major Adverse Coronary Events it it has been approved for clinical use in non life threatening ailment.

Early first generation drugs are being repurporsed as are some of the later 2nd generation of which this is one with the likes of Breprocitinib and Rocsacitinib both ulimately controlled by Pfizer that own Priovant. Baracitinib on the move to Africa!

Excerpt below

'Pfizer’s corporate political contributions and lobbying activities are focused on promoting the interest of our company, without regard to the personal political preferences or affiliations of any of our employees, officers, or board members. The company’s corporate political contributions and lobbying activities are subject to robust internal procedures designed to align these efforts with our public policy priorities and applicable law. The company has an extensive training and reporting program in place to ensure compliance.'

Not eactly a level playing field, we exhibit no adverse off target effects in SAD and MAD studies greater than Placebo and we are required ,long term toxicology testing.

Tim put us at best in class and see nothing to dispute that.

Dick Puller, why would we need Potassium Iodide.

Just asking out of interest?

That good find \BoilB

I am wondering as to who carried out this research and when.

737 was on licensed with a milestone payment due on raising of funding by the US private pharma.

Clearly no money raised and whether they bothered to try we do not know.

But very interesting combo of which prexasertib now taken on by Acrivon also gets a mention.

Regards

'The numbers of monkeys used in research are increasing mostly because there are more biotechnology-derived drugs being developed, i.e. drugs that need to be tested in monkeys. For instance, out of 29 drugs that were approved by the US FDA in 2019, five drugs (17%) were biotechnology-derived products and all of those used monkeys to evaluate toxicity. The same trend occurs in Europe. Other factors include, an increase in the number of studies related to neurodegenerative pathologies, oncology, immune-inflammatory pathologies'

NHP or canine.

Still have strong belief that the toxicology studies will be carried out in primates.

There are reasons that are advantageous to drug development. Primates much more similar to humans than dogs.

A link below may be of interest to some while the 'odd' one or two will label bs.

Why use monkeys?

'The areas of research where monkeys are essential include the function of the brain and its disease, such Alzheimer's or Parkinson's, reproduction and susceptibility to certain infections where human biology is radically different from that of rodents. ​Research with monkeys also includes advances in transplantation techniques, the role of the Rhesus-factor in blood transfusions, development of in-vitro fertilisation techniques, and advances in stem cell development.

In 2017, the Scientific Committee on Health and Environment Risks (SCHEER), on the request of the EU Commission, published its final report on the need for monkeys in biomedical research, production and testing of products and devices. It recognised that limited use of non-human primates is imperative in particular biomedical research fields, such as immunology and neurodegenerative disease. It also recognised that replacement should be the ultimate goal, but that it is simply not possible at present.

​

What areas of biomedical research use monkeys?

Regulatory testing

The majority of procedures conducted on monkeys are to understand the toxicity of a new drug before it can be tested in humans/patients. Rats and dogs are the default species for this type of testing, but monkeys must be used if the drug is so specific to humans, that it does not have a pharmacological effect in a rat or a dog. This is the case for many biotechnology-derived drugs such as therapeutic antibodies, oligonucleotides (short DNA or RNA molecules) or gene therapies. Monkeys are also used in the earlier phases of drug discovery, e.g. when a specific receptor - like the one in humans - for a new potential drug, is only present in monkeys.

Vaccine testing

As seen throughout the Covid-19 pandemic, vaccine development often involves monkeys in the final stages of pre-clinical testing, to ensure safety and efficacy of any vaccines before human clinical trials.

All leading Covid-19 vaccine candidates (Moderna, Oxford/AstraZeneca, Pfizer/BioNTech, J&J) used rhesus macaques during preclinical testing.

Baboons were shown in a study to be a good model for studying the effects of Covid-19 and comorbidities such as diabetes.'

further info in link below

https://www.eara.eu/monkeys-and-animal-research#:~:text=Rats%20and%20dogs%20are%20the,a%20rat%20or%20a%20dog

By using non human primates a greater in depth knowledge can be gained not just on toxicology test due to the similarity with the human species.

There exists very relavent information within links.

From a previous link an extract below.

'Small molecule JAK inhibitors: is selectivity possible?

The idea of exploiting the therapeutic potential of JAK modulation was fostered by the discovery of JAK3 deficiency in patients with severe combined immune deficiency, while the later recognition of the frequent gain of function JAK2 V617F mutation in myeloproliferative disorders provided a further rationale for developing therapeutics to suppress exaggerated JAK-STAT signalling. Extensive preclinical and clinical research efforts eventually led to the development of the first JAK inhibitors, ruxolitinib and tofacitinib, which both inhibit multiple kinases although with different potencies.

Since then, a continuous strive for selectivity has characterized the development of JAK inhibitors with the overall aim of INCREASING SAFETY BY MINIMISING OFF TARGET EFFECTS WITHOUT LOSING EFFICACY. This aim is far from trivial.

First, the heterodimeric pairings and the involvement of a given JAK in several pathways complicate the selection of the best target. Even a highly JAK1 selective inhibitor will, due to the heteromeric JAK pairing, affect cytokine signalling that also depends on JAK2, JAK3, and TYK2. Further, mouse studies using both non-selective and next-generation selective JAK1-3 inhibitors demonstrate overlapping immunogenomic effects at the network level rather than blocking specific pathways. Second, the approach for all currently licensed JAK1-3 inhibitors has been to target the JH1 domain encompassing the ATP catalytic site, which is highly conserved across many kinases. Third, one such ATP competitive inhibitor will exist in equilibrium with the substrate and ATP implying that an increase in intracellular inhibitor dose, which is hard to control as it depends on patient-specific parameters such as age, sex, and co-medications, will likely affect the ATP binding to the other JAKs thereby causing loss of selectivity in vivo. Fourth, IN VIVO SELECTIVITY CANNOT DIRECTTLY BE INFERRED FROM IN VITRO STUDIES, IN VITRO AN EX VIVO DATA FROM ENZYMATIC AND BIOCHEMICAL ASSAYS VARY WIDELY ACROSS STUDIES AS THEY DEPEND ON THE SUBSTRATES CELL LINES USED,THE CYTOKINE AND OR STAT BEING MEASURED cell lines used, the cytokine and/or, and experimental dosages.Ultimately, JAK selectivity is relative, and the TRANSLATION INTO CLINICAL EFFICACY & SAFETY IS HIGHLY COMPLICATED.

Collectively, these complexities challenge the development and use of selective inhibitors yet represent a major therapeutical advantage for clinical efficacy in the treatment of complex diseases, in which multiple cytokines are typically involved, and for which the targeting of a single cytokine is likely insufficient.'

Note the 'TRANSLATION INTO CLINICAL EFFICACY & SAFETY IS HIGHLY COMPLICATED.'

Translational sudies still onging with 1802, the importance of which, attention to detail here cannot be over emphasi

Good afternoon luvleyjubley.

With regards to 737 it was developing fine in combination therapy up until 2019 until SO pulled the plug on financial support for 737 even to the point of robbing allocated funds, to fund Momelotinib prior to buyout by GSK.

A good report from 2019 is in the link below,

https://ecancer.org/en/video/7768-efficacy-and-immune-correlates-of-the-sra737-plus-ldg-regimen-in-combination-with-anti-pd-l1-in-an-sclc-model

I will certainly take a look at Facebook and i certainly do not mind contributing to relavent topics.

i do gey annoyed about the number of US pharma companies that sell drugs here via the NHS.

There were warnings/fears of this onslought 25 years ago relating to the cost to the NHS ( well tax payer) and the lack of development/research by UK companies.

Bill Gates provides funding to the MHRA, an excellent chap who i would think expects nothing in return.

The amount of funding is not disclosed.

Regards

Good morning.

Tyk2 allosteric inhibitors and variations.

Some allosteric inhibitors will work better in some indications than others.

In addition allosteric TYK2 inhibitors that bind to the JH2 pseudo domain and non allosteric inhibitors that bind to the ATP site each have different effects.

Interesting read in the link below, it does explain in depth objectives and complexites in compound design.

https://www.sciencedirect.com/science/article/pii/S2352396423004061

Indeed many bio companies are jumping on theTYK2 bandwagon, seemingly at an ever increasing rate.

There will never be a one size that fits all. Efficacy and satisfactory safety profile whether suitable for long term use or not will have significant impact on commercialisation and hence value.

Not wasting my time posting on here, it will come as a relief to a few, my game plan has not changed. been here since 2012. Unfortunately there exists a spiteful few that will have posts removed. They know who they are as well as i do.

It does not bother me as I see they have an ultimate agenda.

As for Nick Cotton, there are no shortage of Dot Cottons that post. One in particular comes to mind.

Regards to all genuine long term investors.

Before any T..t on here says I am ramping, what figure did Tim Mitchell put on SDC1801 and SDC1802 and my figure is nowhere near that.

We are also much further forward than when Tim made this remark and will be ready to progress into phase trials latter part 2025.

Tell me how many large pharmas take on an on licence,

Pfizer set up Priovant to develop Prexasertib and Ropsacitinib,

It is evident that large pharma will tend to buy out in preference to take an on licence. providing of course the product is good. Look at BMS with Deucravacitinib the first approved allosteric Tyk2 inhibitor that was supposed to 5hit miracless.

Somebody tell me the reasons why as 1801 should not prove better in some indications than Sotyktu.

What is the most valuable between the two?

Long term toxicology goes a hell of a long way to rival if not better on results should it duplicate results in SAD and MAD studies.

I agree B-B good long term toxicology report will put the compound in the hundred of millions valuation.

the figure i have put as total buyout of around give or take a bit 750 million and that is both compounds.

What is certain is the current market cap is grossly undervalued.

Regards

Good afternoon luvelyjubley.

GSK purchased Tesaro pipeline a few years back.

737 had some great results in combo including preclinical with a pd-1 inhibitor and parp inhibitor and low dose gemcitabine and great results in triple combo.

The way that the Checkpoint kinase inhibitor 1 works at the point of cell division, does well to stop cancer spreading but very little to destroy the cancer cells themselves.

Great results and very good reports which i will come to later.

Sierra oncology progressing 737 well.

2020 the 'for sale sign' as such came down, ie no mention of 737 in pipeline. RNS stating concentration of funds on Momelotinib a jak 1 Jak 2 inhibitor for myleofibrosis.

All funding was focused on momo including funds intended for 737.

Payment deferral of milestone and or reduction announced by Sierra. the only thing shown was a final design stage of 737 in combo therapy with either 737 and Wee1 inhibitor or immuno therapy ie PD-1 inhibitor.

(to the point here Triparna Sen gave a great presentation of triple combo 737, LDG and PD-1 inhibitor.

Involved as an author was John V Heymach.

John V Heymach is also an advisor to GSK.

GSK would know the potential of 737 with in combo therapy. certainly give Jemperli a run for its money in endometrial cancers as well as head and neck, anal and small cell lung cancer.

Jemperli is pushed into heavy commercialisation with approved for clinical use in Europe as in an area of unmet need.

effectively by mid 2019 737 ceased development. Bs given for further development of 737.

GSK had been in talks i would say from around early 2020 with SO.

No development for one of the most developed CHK1 inhibitors at the time. GSK did not want. They certainly did not want anyone else to have either. Why didn't SO sell to another pharma?

GSK not want.

GSK had just paid 5.1 billion for Tesaro pipeline so no need to buy an inhibitor which threatens commercialisation of jemperli. ( Dorstalimab) Any inhibitor ending in mab means mono clonal antibody. It works by identifying the cancer cell then destroys. PD-1, programmed death receptor 1.

Now in combination with a PD-! inhibitor and Low dose gemcitabine 737 began giving some excellent preclinial results.

Now tell me that GSK would be happy for a competitor to develop 737 in combo.

Jemperli was predicted for sales of over a billion dollars in Europe alone within a couple of years.

GSK, They are not like that?

Have a look at their previous history and out of court settlements that runs into billions and tell me I am wrong.

The benefits of getting their foot into the door first by fair means or foul.

Would i put it past GSK to stump up a measly couple of million to delay/ prevent developmentof such a promising treatment for hard to treat cancers. You bet I would!

i have posted about this in detail, the best argument I ever received was some clown telling me they could have used it as a back up.

How much money has Jemper

Good post Krone. CHK1 and Hydroxyurea not new in studies. Effective in some cancers. Never been in clinical trial in any form. Not all chkk1 inhibitors are the same as we know.

Combined use of subclinical hydroxyurea and CHK1 inhibitor effectively controls melanoma and lung cancer progression, with reduced normal tissue toxicity compared to gemcitabine This was around 2018/2019.

To fund 737 in a phase 2 or phase 3 runs into the hundreds of millions.

Only company in good development is Acrivon with Prexasertib using thier Onco signature platform. they raised 100 ,illionand in fact were over subscribed.

Which has the greater benefit 737 or prexasertib?

Answers on a post card. The use of crayons is not allowed.

Regards

Too much time on my hands?

I am at work Surfie1961. Work is so quiet as newly installed compenent failed and I ham at a loss at what to do. I get fed up watching you tube.

I notice you have not addressed my last post on commercialisation and valuation with regards to the importance of long term toxicology results.

it really is fun showing you up to be one of the most incompetent investment fools ever.

Knowledge is power.

To absorb knowledge you need a brain.

In this case there lies your problem.

Toodle pip.

I

Surfie1961.

Breprocitinib forecst to have arevenue of over half a billion in md 2030's

SDC1801 on current results indicates a far superior safety profile which removes it from restrictions placed on the family of Jak1, 2 and 3 inhibitors.

All Jak1 Jak2 and Jak3 will suffer this fate in auto immune but does not apply to the same extent in immuno oncology?

Are you able to comprehend this and the significance of?

Are you aware as to why Sareum designed 2 TYk2 Jak1 inhibitors?

The current safety data as a result of SAD and MAD studies confirms no short term treatment problems.

Now if you had something between your ears other than a vacuum you would realise the following

Associated problems with Jak1,Jak2 and Jak3 inhibitors that have been the cause of withdrawal mainly in phase 2 clinical trials.

Phase 2 clinical trials are about proof of concept efficacy and safety.

Now these early and to some degree later stage Jak inhibitors, went through and passed with what was considered at the time an acceptable safety profile from results from a phase 1 clinical trial. Off target effects and events at that time considered satisfactory in relation to efficacy V safety.

This is no longer the case. Allosteric Tyk2 inhibitors have a proven significantly greater safety profile to JAK inhibitors albeit can lack efficacy.

Hence between the two, allosteric TYK2 inhibitors will become first line of treatment over Jak inhibitors irrespective of selectivity, unless of course it can be proven, that there exists no significant off target effects restricting the use of an inhibitor.

This will be reflective in the commercialisation value which also includes tha amount of patent protection and lifespan of.

The above is not ramping, it is based on fact and a tad of logic.

Apart from moan about a falling SP just try to understand what you are invested in.

Regards

SAD and MAD dosing has confirmed the first part of this.

The second part will indicate effects and fit for usage of long term treatment

Surfie1961, how are your other shares performing. have you tried blaming sareum for their failure?

Worth a try you old Benghal lancer.

Surfie1961,

I have never stated or projected anywhere near 14 billion.

Pot kettle and all that. You need get off your backside pull your finger out and get a life. You do nothing but complain about something you know sweet FA about.

I cant be bother to read posts, You cant be bothered to attend the AGM. Well if I only had £7.50 invested I dont suppose i would bother taking the trouble to air my views at an AGM, Much better to moan on here, hey Surfie. I pity your wife if you have one.

Your posting history on sharechat boards clearly indicates what an absolute clueless buffon you are. In and out of a share for 15 years and never made a penny.

You buy at a peak then moan when the SP drops.

Let me tell you a little known fact, the idea is you buy at a low price and sell at a higher price. But dont be greedy like some.

Good to note that you have nothing of any value to contribute as usual.

Regards