Member Info for sadoldgit

Potnak l were referring to Damion panicking not yourself.

As for posting in the past week have posted mpst days. Have mobile phone only and not easy when working 260 mile away from home.

In addition not overly keen on reading unsubstantiated drivel by numerous posters with extreme negativity.

Yes we are all concerned

Stated several times before today not a problem with 1801 ie Tyk2 Jak1 active compound.

In my honest opinion for what it is worth is that the formulation has been made a little too dirty.

I were speaking very recently to a lad that worked at producing new drugs and compounds for companies and universities. Initially universities

L

I asked him without giving precise detail of problems with excipients. He has a masters degree in Chemistry and worked st producing varying amounts of different compounds for around 3 years

Toxicology halted near the end. I said

Tested in animals or humans, he asks

Animals l said

Ah rodents and canines. He replied

Liver toxicity ! He exclaimed

Extremely interesting chat for around half hour followed. With what can go wrong, why, and how. This was regards to excipients of which he told me are fairly simple to make. All important is how the metabolism can affect the recipient.

Downsides the 3 main ones he gave

Liver toxicity

Cancer

Heart problems.

Extreme precision is required in maintaining precise ingredient ratios as is the absence of impurities.

Off for a cuppa and a chat.

Regards

MattyBoy1965, the Bod font have to buy they can award themselves shares at the AGM unless enough turn up to vote against.

Potnak

'From the RNS

'Recent additional data has confirmed that the control group were not dosed with SDC-1801, and the findings are therefore considered unrelated to SDC-1801'

What have you learned over the past week from Damion that has proven otherwise?

Most likely panicked which is understandable.

The fear of losing grows and hence promulgation of a CRO admitting liability the only way that can save Sareum according to Damion.

Regards

There was a gun to fire it in phase1 a Sad and MAD trials. Hiw much adjustment was given to the gun in order to attempt perfection?

Or is it a case that the gun had a dirty barrel. Or that this particular gun had a barrel 10 thou oversize?

As you say still a way to go and of course this has a knock on effect to possible 1803 potential partnership or similar.

Similarities as worse case scenario would be identical excipient used in recent trial.

Whatever the problem it needs resolving before we can on licence 1802

1802 however a tad different as is to address oncology.

Interesting to note that the indications supposedly in areas of unmet demand for 1802.

Not the biggest of money spinner but we really ought to be getting our foot in the door even with a smallish upfront licence deal with higher end milestones.

Regards

A post ftom a so called knowledgeable poster?

'Whichever way this plays out it's a total mess now. More delays, extra costs, further dilution. The only thing that can help save the day is an RNS with a CRO admission of fault. Every other path is a rabbit hole and one that could be serious for 1801 / 02. The real question now is the one nobody wants to contemplate after Aurora, FLT3 is Sareums whole SKIL platform fundamentally flawed…,

One thing that os never done is to admit fault.

With regards to the Sareum Kinase Inhibitor library it is most certainly not flawed!

The kinase inhibitor library deals specifically with kinase inhibitors period.

The method or type of excipient used is outside the parameters of SKIL. Molecules and compounds are designed via i still computational chemistry.

Aurora FLT3 haha problem eith a solubility issue thst was to enable Aurora FLT3 to be taken orally.

Preclinical results were very promising

The Chinese medical company at Hubri Medical University did not manage to resolve this issue.

Sareum with limited funds were not able to fi once further as as pushing ahead with 1801 and 1802.

Since it is confirmed in the RNS that the problem does not exist with 1801 as not in the control group it just reinforces what prople do know as opposed to what they think they know.

Panic mode me thinks!

Regards

,The Company is in discussions with several contract research organisations (CROs) to restart the study as soon as possible, using existing cash resources.'

The question here is will sar continue with current excipirnt ir revert back to Phase1a formulation.

Good news !

Regards

The biggest faults of contract research organizations (CROs) often include poor communication and high staff turnover, which can lead to delays, cost overruns, and a loss of control for clients. Other major issues include inadequate patient recruitment and retention, data inaccuracies, and operational challenges like a lack of specialized expertise or resource misallocation.

Utah, as you have stated the company knows deep down it's not a goer, then why you buy more.

Until an investigation is completed no one can say for sure where and what the problem is. The company can not make a statement of who and where with regards to liability as without prior legal consultation and advice it amounts to nothing more than libel.

Sareum can make statements about 1801 but need be careful what they say about the CRO.

In my opinion for what it is worth is the active SDC1801 is OK but the 'tweaked' formulation in its current state may be the source of the problem

In this instance difficult then to explain why Sarrum looking for new CRO as is a formulation issue and not malpractices carried out by CRO.

They could revert back to the original excipient.

Regards

Until an investigation is completed relating to the cessation of trial is established, nothing can be stated written or orally that apportions failure to the 3rd party.

We all want to know what is going on.

With regards to records and procedures ensuring compliance and quality control you can take thst with a pinch of salt.

One of the first big issues the FDA had after covid.

Falsified records, records written in pencil. Qualification of staff.

Damion you need to lighten up

Yhe point l make has clearly gone over your head l feel.

If there is a problem with the formulation in this toxicology study then it matters not one iota as any CRO they use will mske no difference.

You can only pee out the cokk you have.

If there were no problems with the CRO you would work together and resolve surely?

Something very much amiss here Damion.

A decision had been made along the line with regards formulation normally just a tweak carried out in manufacturing process.

Clearly there was a reason and l don't think you are too far away from the point of the SAD and MAD dosing

A requirement now is to have toxicology studies carried out before phase 2 clinical trisl

Phase 2 vlinicsl trial was the stage where safety v efficacy determined whether a drill vould ho further. This has changed since around 2020.

2 in 3 drugs fail in clinicsl trials at this stage

Far better yp determine safety first hence long term toxicology testing bring mow a requirement before you can proceed.

We get t o a point in time when the drug is formulated it cannot be changed.

All efforts l believe are being made to maximise the potential of 1801.

Unfortunately at the moment it most certainly os not maximising the value

With regards to a sporting event

Ali v Foreman in Kinshasa Oct 30th 1974. Start of round 8 after being hammered by Foremsn in the previous 5 rounds.

I

Good evening DamionI agree with what you say in some aspect. Now l am not having a dig at you. Different aspects and opinions you put across very valuable. We font sll see things ftom tge same side

I do not agree firstly with the 14 to 31 hr crafting a regulatory problem.

All people are not the same

The minimum to maximum half life which in your opinion creates a regulatory problem? How do you work that one out?

Data is used to produce statistics.

In statistics we normally require a 95% confidence factor. The 95% confidence factor is generally what companies establish. That means statistically in 100 readings 5 will fall outside of the expected readings. Every oersons body will not react the same.

As people get older the liver and kidneys do not work as efficiently as when they were young.

This will slow down the half life down.

But of course data is taking people's details.

As long as they are fit, on no other medications and between the ages of 18 and 55 for the trial.

So that means some people are nearly 3 times older than others yet some may only be twice as old. They are not all going to be of the same age.

The trial only consisted of 80 people.

Data needs to be managed effectively and stating that a range of 14 to 31 hrs creates a regulatory problem is rather ill conceived.

I have not looked at the data results in depth.

Call it cherry picking or whatever you like but 17 to 20 hrs half life is very likely where most if the results sit.

As was once said 'There are lies, damn lies and then statistics"

Statistics are powerful when used correctly.

I tend to agree with you on reasonings of reformulation of drug.

Sareum had the new 'dirty batch" sent to the CRO.

Sareum and then the manufacturer was responsible for compound formulation and any adjustments. All quality control checks completed.

Now if there was a problem with this formulation why on earth would Sareum be looking to get trial done with another CRO?

There is much that just does not add up.

We require more information and that is understandable.

4 days to go until 23rd!

Regards to all

Difference in weights and people's build as well as lifestyle will.play a big part.

In support HbD someone who is 20 stone in weight and obese is not going to have the same metabolism as a 6 stone ballerina.

Therapeutic dose range by Sareum was stated as 2.5 to 12.5 mg per kilo up to a maximum of 1000mg per patient.

Sareum had previously stated that they had achieved over 30 times Therapeutic dose in preclinical with no problems. This was of course in the exploration to determine an MTD.

Sareum to carry out trial with another CRO would indicate not all is well between CRO and Sareum.

Another waiting game.

Long read and font gave tge time and inclination to copy and paste relavent parts.

Thankyou Num4 for the link to trial results.

To say that the interpretation by Damion is a tad skewed is somewhat of an understatement.

How we manipulate.

Empty stomach 3 hrs

Full stomach 6 hrs

100% increase in absorption peak time in full stomach as opposed to empty stomach.

Did not put 50% reduction in absorption peak time on empty stomach as opposed to full stomach.

In any case what does it matter? Directions are normally given at point of prescription at to whether there are restrictions to be taken on empty stomach.

With regards to compounds and adverse events difficult to get full description. However, much contained in the link below.

https://www.bmj.com/content/381/bmj.p917

https://www.bmj.com/content/381/bmj.p917

Agree entirely Andy that we need get 1801 off of the ground.

A major concern is that the compound performed admirably during SAD and MAD trials

Good Ladmet. Well impressive if we take into account no detected Jak2 activity.and no increase in creatinine levels

What else could we wish for ?

Then we spend nigh a year on a toxicology study that takes 16 weeks and us stopped close yo the end. That will have strained resources.

So we sit further back than we were 12 months ago.

Identify a plan and stick to it surely. Sareum are forever doing off piste.

Regards

AI Overview

+5

Yes, testing pharmaceutical excipients is a regulatory requirement because they are essential for creating safe and effective medicines. Regulatory agencies worldwide mandate routine testing to verify the identity, purity, strength, and quality of excipients and to ensure they meet Good Manufacturing Practices (GMP).

Why excipient testing is required

Patient safety: Excipients make up a significant portion of a medicine and improper or substituted excipients can have severe consequences. For example, a mix-up between glycerin and diethylene glycol (DEG) in cough syrup led to multiple deaths, as detailed in Pharmaceutical Technology.

Quality and efficacy: Testing ensures the excipients function as intended in the final drug product, which can affect drug release and overall performance.

Traceability and consistency: Testing verifies the traceability of excipient batches and helps maintain consistent quality from lot to lot.

Regulatory compliance: Agencies like the FDA and EMA require manufacturers to test incoming excipients and not just rely on the supplier's certificate of analysis (COA).

Risk mitigation: Regular testing helps manufacturers identify and mitigate risks associated with impurities or deviations in the excipient supply chain.

What testing entails

Identity and composition: Manufacturers must confirm the identity of incoming excipients.

Good hit Woodlands

A very very long read.

https://pmc.ncbi.nlm.nih.gov/articles/PMC7662502/#:~:text=The%20functional%20roles%20of%20pharmaceutical,preventing%20dissociation%20and%20aggregation%2C%20etc.

Damion the active ingredient ie Tyl2 Jak1 in the compound is most certainly not compromised.

The excepient as it stands is under scrutiny.

Just a recap here.

Toxicology study was stopped on tge 16 week trial due to issues in testing.

Effectively the compound exists of 2 parts.

The active ingredient and the excepient.

The active ingredient is Sdc1801 and as we know has performed exceptionally in phase 1a trials.

The excipient is an inactive ingredient in medications that serve various functions, such as improving taste, stabilizing the active drug, aiding manufacturing, and controlling how the drug is released in the body. While generally safe, some excipients can cause side effects or allergic reactions in sensitive individuals.

It is plausible that discussions took place with the CRO with regards formulation tweaking.

Tweaking in many cases done in the manufacturing stage.

In essence this would appear to be a formulation issue and no problem with 1801 but the excipient itself.

Given that the RNS indicates that SAR are looking at rapidly restarting trial with another CRO would suggest that the CRO are at fault here.

The all important recording of correct information by authorised and suitably qualified persons adhering to GLP is vital in ascertaining the origin of the problem.

I would like to think that we will be informed of the aforementioned by the 23rd of this month at the l

very latest.

Regards