Member Info for sadoldgit

CB, I totally agree with your post. These powerful forces are becoming all the more powerful.

Worth a read

https://www.svb.com/industry-insights/healthcare-life-science/the-advantage-of-oz-offshore-tax-rebates-for-lshc-rd-in-australia

Warthog4.

Easy gaff to make. It is no problem. People understand the gist of your post.

Edison rectified report yesterday which shows 46% increase in SP.

Most if not all are aware that funding will need to be raised at some time in the future and has been pointed out many times before that we will require additional funds to take 1801 past phase 1a ie dose escalation.

Acrivon obtained prexasertib. In addition to this Acrivon were over subscribed on a 100 million dollar fund raise.

The pivotal point will be the outcome of dose escalation results. Investors. pharma partnerships, on licence or even buyout is not going to happen until the data i from such a trial is known.

Edison:-

'Sareum will need to raise additional funds before end-CY23 (H123 cash balance of £2.9m).

For accuracy I would have used the term ' will require additional funds'.

Now additional funding may come from 'on licence ' of 737. In this instance Sareum will not have raised funds.

Therefore the use of the word 'raise' implies share dilution. Therefore the Edison report may be construed as misleading.

A little pedantic of me but does point out the connotation of words used by Edison in the presupposition of the use of certain wording for a desired objective.

Regards

Time for a beer. A very long read on item 3 and have skipped through a lot of it. Will take deeper look later.

Indicative of yet more in combo effectiveness.

No indications of any clinical approvals.

5-Ph-IAA is a derivative of IAA. 5-Ph-IAA, a ligand, establishes the auxin-inducible degron 2 (AID2) system together with an OsTIR1 (F74G) mutant. AID2 induces rapid and efficient depletion of mAID-fused proteins to study protein function in living cells, causing tumor suppression.

Together, these results suggest that a DNA-PK-CHK1 axis is engaged at stalled forks in response to ATR and TIM deficiency to promote replication catastrophe, which is separable from the initial role of CHK1 under the canonical ATR-CHK1 checkpoint to counteract the replication damage triggered by acute TIM loss. In this sense, CHK1 plays a dual role, i.e. fork protection and fork destabilization, depending on the status of ATR at TIM-deficient stalled forks.

ATR-CHK1 is indispensable for preventing fork breakage at unchallenged forks and replicating fragile sites (50–52). Our TIM-mAID model reflects the physiological infliction of endogenous replication stress, such as stochastic replisome dysfunction, progression through difficult-to-replicate regions and DNA repeats, and oncogene activation during which replication forks could be challenged, thereby underscoring the coordinated efforts between the FPC and ATR to guard the replicating genome in a collective way.

Very promising indications for a vital ATP inhibitor in the DDR pathway, I will add. Very recent released literature too.

Good find C79.

Good afternoon C79 no surprises with Acrivon developing ACR-368 (prexasertib.) Fast tracked too.

We await news from whatever the CPF decide on 737.

The window for news is open on this one.

Regards

I think we pay them 60k a year. Plus more on top for the extras

We estimate the company may require additional funds to start the Phase Ib study planned for CY24, given our expectation (refer to our previous note) that it will need to raise additional funds before the end of CY23.

What a cobblers of a statement.

'Estimate ',then 'may require 'then e'xpectation' then i't will need.'

Basically they dont know. The importance is, clinical trials can go ahead. The other pertinent point is 43.5% tax. rebate. Dose escalation trials prove favourable , thenthere will not be a problem obtaining funds. If they are not favourable we aint going to need the funding.

Accuracy of content: All information used in the publication of this report has been compiled from publicly available sources that are believed to be reliable, however we do not guarantee the accuracy or completeness of this report and have not sought for this information to be independently verified. Opinions contained in this report represent those of the research department of Edison at the time of publication.

With statements that Edison have made up and not surprised they do not guarantee accuracy of report.

Ah , the dreaded opinions.

Tim an co are better versed than any of us here. They will know what else is out there and more importantly what we have.

737 we carry no sway but SDCcompounds are wholly ours

Regards

Some indications in the link below albeit a little different that what i have posted

https://www.nature.com/articles/d43747-021-00024-y

It will also pave the way for 1802 Ahfam.

Sareums compounds have so far had very favourable toxicity outcomes compared to the competitor.

Aurora +FLT3 had good preclinical toxicity but had a problem manufacturing of the oral compound with subsequent solubility issues.

Remember also that the big pharma at some stage will come under the fear of missing out. It will take a while for the news to sink in of trial approval. Then the wait for dose escalation results. Phase 1 b and results in psoriasis if good plus prospect of wider identifiable indications with high chance of favourable outcome ought to give around triple the value of dose escalation good results.

100 to 150 million on good escalating dose results. 300 to 450 million around phase 2 and 900 million to 1.5 billion on successful phase 3

Are the figures plucked out of the air? No.

I posted around 18 months ago a info from data of early stage, mid stage and late stage phase 3 expected valuations of drugs and corresponding market access value. Based on done deals around 2019 /2020. Somebody has to place a value!

Pre clinical was circa 10 to 30 million phase 1 around 50 to 75 million, phase 2 around 300 to 400 million and phase 3 around 700 to 1.2 billion. Dollars here

This was an average and also need take into account patent protection and market size. So dont take figures as gospel just a rough ball park figure at each stage of succesful development. in addition this is compound valuation and not a valuation of the company. I will see if I can dig it out again in the very near future.

if and a very challenging if is that should SDC1801 blows Deucravacitinib out of the water in psoriasis then you would be looking at a very healthy Mcap indeed. We are likely to be better on efficacy but need keep wattchful eye on tox and safety profile. Be good to get decent results in UC and CD too which Deucra has not done so far.

Regards

In all honesty I believe SDC1801 will not be around long after phase 1a dose escalation studies. At the latest phase 1 b in psoriasis.

Pharmas have got a desire for the Tyk2 programmes.

Enough then to take 1802 well into stage 2 clinical if not also bought out by then.

It does look like the preferred option of the big pharma to buy out. No milestone payments and no royalties. But they will require credible data. As Tim stated it is a very competitive market.

Partnering is also an interesting option.

Discussions need replacing with signed agreements me thinks.

Regards

Yes tis an exciting time. Sareums wholly owned SDC1801 to enter clinical trial.

Regards

A few months old but the folowing does give an indication of the interest in TYk 2 in psoriasis.

https://www.biopharmadive.com/news/tyk2-inhibitors-jak-protein-startups-biotech/633635/

As for 737 a good report in the link below.

https://www.nature.com/articles/s41416-023-02279-x

Regards to all.

Thoth2 stated that we are non allosteric.

I have disagreed with him on this.

Tyk2 can only signal via the JH domain 2 by definition. JH2 effectively can control to an extent JH1 the active site.

Jak1, Jak2 and Jak3 can only signal directly the active site.

Hence Tyk2 signals via JH2 and the other Jaks via JH domain 1.

Just to complicate things further here, from memory there are 7 JH domains.

Basically it is the first 2 domains which are of interest to us.

Tyk 2 can be considered as a regulator of the JH1 domain by signalling via JH2 domain.

Furthermore all molecular structures in the makeup of Tyk2 by different pharmas are not the same. That one of the main reasons why all our molecules around 30 in total are protected by patent.

Thoth was adamant that our Tyk2 was non allosteric. I don't believe he fully understood the meaning of allosteric and JH2 domain.

Tyk 2 is definitely more selective and may be regarded as specific. There is a big difference between selectivity over and specific.

Deucravacitinib is Classed as Tyk2 only, but in fact has selectivity of over a thousand times greater over the the other Jakis.

Apart from that Jakis are more effective in pairs.

There is an exception here in that Tyk2 does not work with jak3.

However to complicate things further tyk2 via the JH domain 2 it can regulate jak3.

All very complex indeed.

Regards

Absolutely Silverfoil. It took the MHRA over 3 months to respond.

As a minimum value l would place 400 million at the very least for 737.
It was licensed at 320 million dollars 7 years ago with low up front and high backend payments.

Possible outcomes are on licence, partnership or buyout of 737.

With regards to buyout this is mainly done by acquisition.
Pharma's with deep pockets will pursue this route.
Discussions although informal will go on for months before notifiable formal offers are made.

A pharma in this instance still has to assign a value to the pipeline.

But sareum only has 27.5% financial interest in 737.

Slight complications here but will come down to the evaluated data available.

Tim and Co have put much effort into getting SDC1801 into clinical trials.

Many people here critiscised Tim and Co after the AGM. They know who they are and should know better. Majority of it caused by sheer ignorance.

The only beef l have had is that more communications to be made and that it may have been better to consult outside body on CTA as this area is not in the field of Sareum expertise.

Aside from all this the current SP is still low. Many have taken advantage of the recent rise and sold.
Shown buys are only around 30k higher than shown sells. 14% rise ok in the current financial climate.

A gradual rise should continue as many will not be aware of recent developments.

I believe enrolment finishes 9th May for healthy volunteers for 1801 trials.
The CRO have proven to be pretty top notch in their communications and have exceeded expectations of many here including myself.

The biggy at the moment will be news of 737 development. Any positive news on this will propel sp North especially with regards to upfront payments.

Bare in mind also, the real Jewel in the Crown is SDC1802.
Should all go well then 2 billion is most certainly not out of the question for thiscompound alone. Again you are looking at phase 2 data here.

Onwards and upwards

Regards

Price is still very undervalued at the moment.

I can not foresee a takeover until SDC 1801 has at least reached dose escalation reports and news of developments of 737.

Goodmorning SCHeckler.
From memory AZ5153 became SRA 515.
Primarily taken on according to SO to increase efficacy of momo. Not 100% on this.

Yes the pharma industry very incestuous.

My thi ki g for what it is worth is 737 to be on licensed where it will be trialled in combo outside of what we k ow so far. Not by a biggy pharma but a pharma that will take a compound from early to mid clinical and develop into commercialisation.

Phase 3 trials LDG and early stage trials in other combo

You can bet your bottom dollar that Michelle Garrett and Co will be involved at some stage if not already.

Ask yourself who would you get in contact with regards to 737? The people who work in the admin side at CPF will be clueless. MG and UB!

Most of this work outside of SO will be the property of the CPF.

May take a little while to come together and whilst Sar can surprise any time with RNS l reckon we are looking at early to mid July.

On any sort of an on on licence we are looking at 100 million plus to market cap. That is more than the current MC and related SP.
Edisons last valuation placed a value of 120 million dollars with a 1 in 4 chance of success of trials basically with mono and LDG alone.

A lot involved. Plus we do not want another SO fiasco.

Jeez even the MD resigned
I would say that was forced too. When resignations are handed in it is normal to work the notice period. Negotiable but normally around 6 months to a year. He resigns and recieves a years salary.
Shareholders were up in arms about the Co.pany being sold at too lower price.

Back to 737.

From the very early days 737 was developed to be used in combo.However you will need toxicity studies done as in a mono therapy. How else would you determine what toxicology is due to whT in a combo therapy trial?

Regards

Mattyboy1965.
News on 737 developments are encouraging. I posted around 6 months ago developments with 737 and resistance to CHK1 inhibitors.Much of the work was carried out by Michelle Garrett diciples for want of a better phrase. Particular attention to AKT and P13k pathways. Chk1 inhibitor strongly suggested for studies with these type of inhibitors.

Note the following link

https://www.kent.ac.uk/biosciences/people/1185/garrett-michelle

Carefully note her pedigree,

Note also AZD5363

The diciples on recent research work had propesed the notion of cHK1 inhibitor with either AKT or P13k inhibitors.

Now MG has a vested interest in development of not only 737 but also AZD5363.

Development was halted end of 2019/20 for 737.

Further development work was carried out with Prexasertib.

Udai Banerji and Michelle Garrett heavily involved in the design and development of these 2 biological requirements. ie 737 and AZD5363.

The only real advancement made is Acrivon acquiring Prexasertib CHK1 inhibitor. This CHK1 inhibitor ceased development with toxicity issues related to heart problems.

As much as SO advanced 737 until lack of funding and subsequent they have basically choked any development since 2020. ( over 3 years)

AZ had developed their own CHK1 inhibitor. The development of this inhibitor was discontinued.

More research has been done on 737 and CHK1 inhibitors outside of SO than SO have carried out themselves. MG was also an advisor to SO. Areas looking at are breast cancer and high grade serious ovarian cancer and both these have high unmet needs.

There is still much goings on that we do not know about.

i will post over the weekend after digging into old research reports.

Regards

Good morning Ahfam. That were around 2012 from memory to do with our Aurora + FLT+3. The transformational.deal that never took place.

Good morning SCHeckler. Appallling performance by the maritime.
Yes most government departments are abysmal. I took identification into doctors here at Thurso to register. 8 months ago. Yes l am told being processed. We will email you they say. No email. I phoned my local doctors last week l am still registered with them. No approach to them to register any where else.

Onwards and upwards with Sar.

Regards

I woud hazard a guess that the MHRA debacle was all about dose escalation trials in healthy patients. No MTD was established.
I remember a couple of years or so Tim talking to the smooth Aussie Andew Scott. Now Tim stated in the interview at the time difficulty in obtaining an MTD which might come back and bite us, but it is a problem but a nice problem to have.

Now if we look at the CRO statement recently provided by the CRO down under we see an escalating dose from 5mg to 300mg per day which is somewhat below the 12.5mg per kilo of bodyweight up to a maximum of 1000 mg per day.

They have given a very cautious approach by taking into consideration other Jak 1nhibitors and their safety profile.

This must surely address any problems that were causing issues with the MHRA if this was the problem. Clearly whilst Tim an Co are excellent scientists they are likely to full short of a top class CRO with regards to resolving this type of problem.

Clearly they have been in consultation with the CRO and given greater detail as to the problem experienced with the MHRA.

Nothing is ever 100% but at the moment the future development into clinical trials looks very rosy for all concerned.

News of an on licence and commencement of dose escalation clinical trials should send market cap around the 400 million mark as Num4's recent post suggests as reminded by fearg. It is not the actual up front payment amount but just the on licence and development of 737 that should propel the SP to new highs.

20 to 30 million as a minimum up front payment based on where we stood with SO and the next stage milestone of 19 million dollars. This of course does not take into account the reduction of 7 million to 2 million on dosing of the first patient in the USA.

737 has progressed and there is growing interest. The future for 737 is in combo therapy with at least gemcitabine. preclinical testing has also shown very promising results with PD-1 inhibitors and even better results in triple combo with LDG and a Pd-1 inhibitor.

737 produced stability in most indications and by the nature of how a CHK1 inhibitor works it has not failed in this respect. Comb treatment is the way forward as indicated by Tim at the AGM.

Great to see positivity returning to the board and comments too from very long term holders.

Regards to all.