Member Info for sadoldgit

At the moment as l see it to carry out phase 2 trial in Psoriadus would be fir 16 weeks to enable PASI score.

Pointless a phase 1b for a month for proof of concept.

Hence long term tox studies to enable this is 4 months. You cannot shorten this.

Clinical trial tox safety requirements look as if the goal posts have been moved over past fee years as phase 2 was efficacy and toxicity yogether.

There will be some correlation with animal testing.

However we as yet have not established a dose limiting toxicity.

Neither have we attempted dosing at maximum therapeutic dose of 1000 mg per day.

Regards

It were stated at 2022 AGM that interested parties said well give us some data.

I don't think this data much use to a finance institution.

2 raises recently now enough funds to take 1801 through tox studies and get the 1802 candidate to end of pre clinical.

Tim.been stood down to concentrate on pipeline.

That is only 1802.

I would suggest in light of re igniting development of 1802 we are being set up for takeover.

How else would you maximise the value of a company if you leave such a potentially promising immuno oncology compound like 1802 sitting on the shelf.

We may well receive news within the next 6 weeks or so with regards to 737.

Regards

It would not be out of the question that pharma can already achieve Indications themselves on SDC1801.

They can do as many as they want.

Unfortunately it all comes downs for use in humans in one guise or another, and that ain't going to happen until progression to phase 2 clinical.

https://www.abmole.com/products/sdc-1801.html?srsltid=AfmBOorserD1rZKSD4_M1aj8vDDFsIAqM0Vv7stgnf14ev_ZaHAQr_XU

Looks like Merck hedging their bets here.

If it works they have a slice of the cake if ot fails ot us a pittance to the 25 billion a year it rakes in from keytruda.

Regards

Welcome back to the chatboard C79 your input has been very much missed

Absolutely not and clearly nothing to fear as Sareum fo indeed appear very confident.

Safety aspects have been further improved by controls put in place by authorising bodies.

No indication to myocardial or adverse events affecting major organs.

This is in human trial which we know was short time but escalated up to 300mg per day.

Nothing untoward.

Originally maximum therapeutic dose put at 1000mg per day ( seems a magic figure by Sareum as 737 was set at the same)

We are at 30% of that

Higher doses for longer duration may indeed lead to an incidence of adverse events but would reckon to come into effect at high dosage levels.

Bare in mind that testing was done at over 30x maximum therapeutic levels with no observed adverse dose limiting events.

Capsule formulation looks to have been of condiderable benefit.

LADMET looks good as was reported in preclinicsl

Liberation

Absorption

Distribution

Metabolism

Excretion

Toxicity

All reported good at preclinical stage.

I am sure one ot two here think they know better.

Go to the AGM and ask Tim.

All looking very good.

Only downside is of course the further delay

On the bright side it will enable advancement to phase 2.

At end of phase 2 Deucravacitinib was licenced for 4 billion dollars plus a further 2 billion on commercialisation milestone payments.

That the arena we are in!

Deucravacitinib will be bettered in efficacy in Psoroasis alone is my betting.

Regards

Nothing of any much interest that we don't already know.

Indications are that it is safe.

I posted a link.

Suggest a read of that it explains a lot.

This is mainly associated with early first generation inhibitors.

So let's all concentrate on making inhibitors which have the same associated problems as with first generation inhibitors.

That not going to happen.

Then we look at claimed safety profile which is derived from data.

Some of this testing is not a requirement of GLP.

However when you look at in depth any information you supply with regards to resting it must be compliant with GLP.

The other option and indeed far greater cost is to repeat the whole testing process from scratch.

Development work was done on 1801 and 1802 prior to GLP being introduced in mid 2016.

How long was the transition period and was there notification of?

Tell me what the worst case scenario is.

No good saying it oooohhh er er er it could fail.

How can it fail?

Has the Edison report stated that it may fail in toxicology testing?

Who was the bright spark who suggested it has a risk of failure?

A poor result here of which l 100% doubt still leaves a product with value.

We are better than Baricitinib A product with boxed warnings which had a turnover of 922 million dollars in 2023.

We may be as good as or even better than Deucravacitinib with regards to safety and definitely better in efficacy in some Indications as with the dual benefit if zTyk2 and Jak1.

Creatinine levels of no observed increase postulated by Tim and Co to be better than Beprocitinib.

Regards

Https://pmc.ncbi.nlm.nih.gov/articles/PMC5188860/

Good evening PC1954.

A good link to toxicology testing below.

Very in depth and very informative.

GLP good laboratories practice.

Some preclinical work is not required to GLP standards.

However, to continue through different stages of clinical trial, information and data must be gathered and used that is classed as precise and accurate and on compliance with GLP.

It does appear that this GLP which was put into effect in 2016 has become increasingly instrumental in allowing the progression of clinical trials.

May have caused some of the problem with MHRA unable to approve CTA.

GLP intended to prevent fraud initially but grown into other areas.

Looking through the link which takes considerable time albeit fairly easy to understand, does give a sense of reassurance to the toxicology testing.

If we take into consideration that much of this testing can be done at early stage it is still a requirement involved in decision making.

Effectively the new toxicology study will supply data in accord with GLP compliance.

Much of these changes would gave happened post 2021 when it was being found out that pharmaceutical companies were supplying false and doctored information

The use of pencil

Altered documents and records

Missing documents

Persons not following GLP procedures.

Regards

Worth a read.

Although specifically requirement for FIH trials does indicate conditions for phase 2.

https://labtesting.wuxiapptec.com/2024/02/05/toxicity-data-before-first-in-human-trials/

16 weeks will enable PASI score to be derived in Psoriasi.

Phase 1b would have been virtually pointless as too short a trial time. Proof of concept yes but then back to proper clinical trial.

If we then establish safety over a 4 month period does that then enable to carry out linger term safety or efficacy studies in human trials?

I would suggest that it does.

Good evening PC1954.

Interesting links.

There is a lot that Chk1 inhibition has to offer.

If we look at broadly p53 it allows a cell to divide and replicate but also control or induce apoptosis in a mutation of the parent cell.

Many many different mutations cause different ailments ie cancer. But, also cell mutation linked to many other debilitating diseases.

It is indeed a very complex issue.

Overview of P53 below

AI Overview

+3

p53 is a protein that regulates cell division and cell death, and is a key factor in preventing tumors:

Function

p53 is a tumor suppressor protein that regulates cell division and DNA repair. It's found in the nucleus of cells and responds to cellular stress by inducing cell cycle arrest, apoptosis, or DNA repair.

Role in cancer

Mutations in the p53 gene can cause cancer cells to grow and spread. The p53 gene is the most frequently mutated gene in human cancers.

Nickname

p53 is known as the "guardian of the genome" because it's essential for regulating DNA repair and cell division.

Inheritance

Inheriting only one functional copy of the p53 gene from a parent can predispose someone to cancer.

Associated cancers

Mutations in the p53 gene are associated with a variety of human cancers, including hereditary cancers like Li-Fraumeni syndrome.

Whether Chk1 inhibitor can be used in some of these solvents l have no idea.

It would depend on doseage as off target effects increase.

However, what l would suggest is probably one of the largest pharmaceutical markets in the early to arise from this should a suitable treatment be found.

Alzeimers is being looked at with SMKI's.

However we look at it, it cannot be bad for Sareum.

Regards

Correct me if l am wrong Krone but after tweaking of the molecule bioavailability was reported at 100% for CCT245737.

There are lots of developments on going albeit painfully slow

Most effective reports of combo which is preclinical on combo therapy of SRA737 in combo with LDG and PD-1 inhibitor

PD-1 inhibitions are monoclonal antibodies and the drug name ends unsurprisingly in mab.

Regards

Good trades this morning.

Is news of some sort on the horizon that people have caught wind of?

Looks like wolfie bringing good fortune to the board.

Regards

Morning wolfing, trust you had a good sleep.

A good read below.

Indicative of being better than the rest on current data supplied and interpretation thereof.

I cannot see it failing my self.

At the very worst case and that is all but impossible is a tad better than Baricitinib.

That pulled in 922 million in revenue in 2023.

Take a long read and read again.

It is not ancient as only a few days out. Clearly l think you have missed it, fo l have copied and pasted for your benefit.

'The Phase 1 trial of SDC-1801, which concluded in July 2024, demonstrated a favourable safety profile and achieved blood plasma levels significantly exceeding the predicted therapeutic exposure, with a long half-life of up to 20 hours. No serious adverse events attributable to SDC-1801 were observed.

Based on the unblinded data now available, the Company is pleased to report that the frequency of adverse events (all mild or moderate) was similar in the active and placebo groups. No clinically significant effects were observed on any component of blood (including red blood cells, haemoglobin, reticulocytes, platelets or neutrophils) which have been affected by earlier generation JAK inhibitors.

Analysis of blood samples from subjects who received SDC-1801 for 10 days in the multiple ascending dose cohorts demonstrated clear, dose responsive, reductions in three biomarkers of JAK1 and/or TYK2 activity. This provides strong evidence that safe blood levels of SDC-1801 were able to significantly inhibit major inflammatory pathways.

The planned toxicology studies are designed to further validate the safety and tolerability of SDC-1801 over an extended period, providing essential data for regulatory submissions to conduct future clinical studies.'

Regards

One for you here wolfie.

https://www.icr.ac.uk/news-archive/pronai-licenses-oncology-drug-targeting-dna-damage-response-checkpoint-kinase-1-(chk1)-from-crt-pioneer-fund-uk

No Funnyguy, they do not deliver news as they are chemists and not paper boys

Https://pmc.ncbi.nlm.nih.gov/articles/PMC10115327/

Worth a read as an overview.

Reading these types of reports points very favourably in benefit to 1801.

Unfortunately as a Jak inhibitor the NIH associate Tyk2 Jak in this class irrespective of selectivity.

Olumiant (Baricitinib)

Revenue generated in 2023 was 922 million dollars.

An ageing first generation inhibitor.

Full of boxed warnings.

In addition it should make its way into journals.

Good morning Celtic007,

The peer review will be pretty much in line with the data supplied.

Review will be supplied as an external unbiased account of data provided.

It will carry more clout of course than a manufacturers claim.

So it is important that this review is undertaken.

Preferably by those with no conflict of interests.

Will give far greater in depth detail too.

Regards

Regards