Member Info for sadoldgit

A link with slightly more info from Fierce Biotech below.

of relavence here is Early clinical and the ASCO meeting in June 2020 I feel.

I would not be surprised if Sareum will end up going the same route. 25 million up front and possible 1 to 2 billion buyout within next 18 months.

Dose escalation good results will be a pre requisite to this of course.

Regards

A good link Krone and reinforces the importance of getting the data evaluated and receiving dose escalation results in phase 1a. It also applies to 737 too, albeit a little more complex.

Great unbiased posts from you as usual C79.

It is not a case of CHK1 inhibitors do nor work it is the way they work or need to work effectively requires in combo therapy.

It is realised the CHk1 in mono does not warrant mono therapy continuation. However in combo with a chemo or ionising radiation therapy far more effective. with other inhibitors even more so.

Deduce that Chk1 inhibitors are not effective on their own ie mono therapy. For DDR to work, DNA damage needs to be created. CHK1 cannot create DNA damage. Repair cell or create apoptosis yes it can do.

Regards

PT.

Strange time to sell as after 16,30 hrs as a UT (Uncrossing trade )transaction. Could be perceived as deliberate. Personally i see no problem other in slight scare tactic. 15k shares is all.

Not sure as to when we will receive an update, I certainly would not expects any adverse effects on the piddly little daily dosage at the moment. Well neck deep in the excreta if we did. I see no problems at all right up to 300 mg per day which is 70% less than Sareums intended maximum dosing regime.

if we take 737 in phase trials then the MTD / maximum treatment dosage of 1000mg per day matched around about the same as was predicted as a maximum in post Sareums pre clinical studies. Doses had been carried out up to 1400 mg per day in mono. Reduced dosages in combo therapy but that is the nature of the game as is also the reduction of chemo which has toxicity in itself and heavily dose dependant.

SDC1801 in mono therapy max therapeutic dose of 1000 mg per day. 300 mg is sweet FA.

Only very slight concern is we are treating healthy people with healthy immune systems.

For actual indications there is no reason not to believe that the dose per day can be increased to maximise efficacy and at the same time minimising adverse side effects if indeed there are any at all at a derived safe determined dose per indication.

Whether the price goes up or down in the meantime does not change a thing.

Has selling 15000 shares made any difference to the effectiveness of SDC 1801 and 1802?

People that post the most rubbish are those that know very little about the science and how the pharmas work irrespective of how many years they have been here.

They knock the BoD.

How many of the recent setbacks can be laid at the feet of out BOD? The MHRA still not know the difference between their ar5e and their elbow, Not sure if you would ask them that question they would ever be able to put an answer to.

Thoth 2 God bless his soul would agree on that one.

Good name for a beer in a microbrewery.

Regards

Progress being made with Acrivons CHK1 inhibitor.

https://www.pharmaceutical-technology.com/data-insights/prexasertib-mesylate-monohydrate-acrivon-therapeutics-peritoneal-cancer-likelihood-of-approval/

Clearly they are pushing CHK1 into Phase 3 trials pretty quickly.

Regarding timelines of which we are in the driving seat have you taken into consideration that prexasertib was on licenced with timelines and milestone payments although actual dates and amounts not disclosed in the readily available contract?

With regards to a takeover I cannot envisage that happening as there is no indications at this moment in time with developments on the 737 front. How on earth do you place a value on this part of a business acquisition?

Dose escalation studies are the way forward at the moment. These results will open the doors for any on licence or partnership.

A deal of some sort with 737 can materialise anytime as the CPF hold the reins on this one.

Regards

Good evening corcs

Extract below from Feb 2023 s(o before we have been granted clinical trial approval.) indications are that Tyk2 Jak1 (especially our 20347)are more efficacious in Psoriasis than TYk 2 alone

'SAR-20347 is an oral inhibitor of Tyk2 and Jak1 with selectivity over Jak2 and Jak3. Preclinical assays demonstrated that SAR-20347 inhibited IL-12, IL-23 and IFN-α signaling [22]. Both Tyk2 mutant mice and mice treated with SAR-20347 showed significant reduction of IL-6 and IL-17 in imiquimod-induced skin lesions, but only SAR-20347-treated mice presented reduced levels of IL-23, decreased keratinocyte proliferation and improved clinical score [22]. In addition, SAR-20347-treated mice manifested lower IL-17 gene expression compared to Tyk2 mutant mice [22]. In this model, Works et al. demonstrated that SAR-20347 treated mice showed an almost complete loss of IL-22 gene expression in skin lesions, and they postulate that SAR-20347 would impair the ability of Th17 and γδ cells to induce IL-22 [22]. IL-22 is required for development of autoreactive Th17 cells [77,78]. However, not only IL-22 production was impaired, since IL-22 signaling was also affected in vitro in a human colonic cell line, and STAT3 phosphorylation dependent of IL-22 was completely blocked [22].

Blocking both Tyk2 and Jak1 in this study was more effective than inhibition of Tyk2 alone at reducing psoriasis-like disease severity, keratinocyte proliferation, as well as IL-23, IL-17, IL-6, IL-22, and antimicrobial peptide gene expression, and the authors postulate that targeting a combination of Jak1 and Tyk2 using an orally available inhibitor may be a viable approach for treating psoriasis, but currently there are no ongoing or completed clinical trials for SAR-20347'

There will be indications where we are better tha pure Tyk 2 and indications where we may not be as good. IBD I believe we will prove successful. Deucravacitinib failed in the primary endpoints in UC. Back to the drawing board for them as increased dosaging is the only option they have.

Regards

Gsk gobbled up and shelved 737? To use your phrases Funny boy. It does not work like that.

Clearly you have no idea Funnyboy. Are you aware of the contractual obligations and conditions in the original on license agreement between the CPF and Pronai Therapeutics.

Due to the conditions in the contract Sierra Oncology could not continue their period of non development. It were covered by a clause of which the CPF were very lenient in enforcing.

Effectively SO delayed development of 737 as much as they could.

Perhaps you could provide in future some factual or documentated information we can relate to when posting such absurd opinions on this board.

Regards

Good evening Salfordred. You have cost me a small fortune on the Glen Turret. I worked a few hours over the weekend at a decent rate. Dedicated the total amount to Glen Turret in the Bin ends establishment in Thurso. 4 bottles all i can afford. There is a heavily peated and 2 others.

Deposit paid 200 pounds and will pay remainder on collection. Woman next door to me who works there said she would have a look at what they have, these are no longer available from distillery. As she works there she gets 5% discount. Gave her the cash to collect and said take the purchase as her own. Interestingly they have Old Pultney at 5 pounds a bottle less than local Tesco. Money well spent I think.

Back to Sar and all looks fine tom me. As we progress there will be those thgat will sit up and take notice. personally i do not see us going into Phase 1b. Once phase 1 a trials competed with no adverse effects from the Jak1 side then we will be on licensed or partnership.

Attention to detail will eventually pay off.

Pretty certain that at 300 mg per day absolutely nothing of any concern.

Regards and been some good posts over past few days and more importantly lack of the claimed long term investor scaremongering ones negative ones.

Good morning Salfordrd I will indeed give the Glen Turret a try. A good whisky shop in Wick which has a truly massive selection, and will give them a visit later. Will pass through Perth on way home if not stocked in Wick.

Regards

Some great scenery about. been up in Caithness around 5 years. Weather here cooler today at around 22 deg and past few days hit high of 28 deg. Some really phenomenal views and good distilleries too especially if you head West , then South.

Camper vans can be annoying. There are also some maniacs that drive the NC500. Should be back home in a month or so will be topping up on some whiskies. Old Pultney 15 year old good and and 18 year old very good but pricey so will limit myself to a couple of boxes.

Tim and co feeling good about 1801 in trials and why not as spent over 10 years in development of.

Regards to the truly invested.

Latest news

https://www.businessweekly.co.uk/news/biomedtech/sareum-trial-sdc-1801-gets-underway-australia

Funnyguy. I know one thing that does not add up.

Your statement

'GSK not purchase Sierra when they had the license'

Can you post the dates that GSK completed the purcase of SO and the date of the announcement that SO intends to return the rights of SRA737 to the CPF?

GSK stated their primary objective was to purchase SO for the commercialisation of momo.

As they stated primary objective this infers there were secondary objectives. No information has been given at to what the secondary objectives were.

GSK would gain a BET inhibitor SRA515 that may prove friutful in combo with momo (BETi pelabresib and ruxolitinib already in development giving far better results than momo)

Secondly GSK bought the Tesaro pipeline in 2019 to commercialise.

737 in combo would pose serious threat to gsk commercialising the Tesaro pipeline in areas of high unmet need. Ie HGSOC to name but one indication.

Development of 737 was halted due to all funding neing diverted to the progression of momo. SO claimed they were exploring options to provide funding further development of 737. One thing that SO did not state as far as I know, is they were seeking funding, only exploring options, but happy to be proved wrong on this.

Had continuation of development continued on 737 it is very likely it would have posed a threat to the GSK gaining a foothold on the tecently purchased Tesaro pipeline. It were rapidly pushed into SCLC as an area with an urgent unmet need, especially in Europe albeit a close eye kept on with regards to safety profile.

From GSK point of view ,why spend further money on development of a drug, leading to milestone payments to be made to the CPF along with associated royalty payments if successful? If on licensed to a competitor you risk severe competition and a threat to commercialisation of your own pipeline, In addition you are paying for this privilege.

Far better to delay the development which SO have proved extremely successful in. A delay of 3 years including reduced milestone payment. About a year they were looking at final design of combo alone.

At the time the share holders of SO were in uproar over the 1.9 billion accepted by SO. The director resigned shortly afterwards with a years salary paid and numerous financial benefits totalling well over a million dollars.

Exactly who was the directors allegiance to?

No need sit behind the sofa.

Sareum have completed preclinical and successfully entered clinical trial.

Take into account the success already gained in 737 with a good safety profile. No cardiac problems that prexasertib experienced with cardio issues.

It is evident that Sareum have not only taken into account in their inhibitors the efficacy of their formulated compounds but also endeavoured to make the compound with considerable consideration with aspects to safety.

737 mtd was established in monotherapy with a maximum dose of 1200 mg per day in clinical trial. ( Close to Sareums predicted safety and treatment dose in preclinical) In use with LDG the 'optimum amount was found to be around 500mg per day.

In this instance the amount of Gemcitabine required ( normally 500 mg plus )was at least halved ie to 250 mg.

Therapeutic doses of SDC compounds were put at maximum of 1000 mg per day per person.

Preclinical trials established no MTD at 30 x the therapeutic dose.

MTD of course is only one way way of assessing a drugs safety profile and indeed different from a continual long term therapeutic dose.

Sit back on your sofa ,as with a maximum dose based on being a Jak1 / 2/3 inhibitor ( derived from dosages from wholly Jak 1, 2 and 3 compounds) albeit primarily Jak1 , at around 30% of Sareums maximum intended therapeutic dose rate and wait for the long anticipated very good safety profile obtained from escalating doses in healthy individuals that will allow SDC1801 to advance into later stage trials.

Remember that Sareum entered the Jak inhibitor programme long after the earlier broad stream approach of Jak inhibitors ( one size fits all approach) and their associated toxicities especially those related to Jak2.

All sareums individual molecules are protected by rigorous patents. Further patent protection is also provided by Crystallisation structure of a compound ( this is not new) which covers the actual manufacture and quality control of the compound.

Not quite War and Peace just an overview of what we have.

Regards

Ahfam I do not for one moment expect any indications of adverse toxicity at 300 mg.

Sareum initial planned dosing was up to 1000mg max per day.

Effectively the dose allowed for these phase 1 dosage trials has been reduced by 70% by the ERC.

What is of the upmost importance is the efficacy of these dosages in psoriasis or any other indication which Sareum choose to commit to.

Squeaky bum time as Thoth2 would call it. However,as Tim and co believe we can perform better than Deucravacitinib in Psoriasis then I will take that as a good indication. It has taken longer than most of us here expected to get to this stage.

The 'Optimum amount of Jak1' as Tim quoted around 3 years ago. Cant be far out as never reached a maximum tolerated dose at 30 times treatment regime.

Regards

I do feel for you Surfie1961,

AIM pharma taking a hammering since early 2022.

Many pharmas peaked around 2021 due to Covid.

However, we have our 1801 and 1802 compounds. Myself i dont see a probem with dose escalation and we ought be top notch in Psoriasis.

The question is what other indications are we likely to be to be better than current treatments ?

Inflammatory bowel disease would be great and we cannot do worse than Deucravacitinib.

First hurdle is good toxicity results.

2nd hurdle good results in Psoriasis.

At some point funding will be required for phase 1 b.

We are awaiting news of any developments with 737. Ideally a deal of some sort will conclude within next couple of months.

Sareum will know more than we do and they will be aware of any progress the CPF and 737.

A complex issue indeed with regards to patent protection and combo therapy.

We do need news and good news being a partnership or on licence of some sort with either or both 737 and 1801.

Keep the faith and am certain you will be well rewarded.

it were around 6 months that CPF licenced to Pronai Therapeutics. 737 much further forward. Unlikely to be used in monotherapy but plenty of ever increasing scope to be used in combo with a multitude of other inhibitors and treatments.

I am of the firm belief of an absolute minimum of 20 million upfront to CPF which would give an approx 6 million to Sareum. Would take us well into phase 1 b and prep 1802 for clinical.

1802 is the real biggy and there is a risk here. However, should it do well then at least a 2 billion MC is not out of the question.

Regards

Good evening C79

informative posts from you as always.

Why use deuterium as a hydrogen atom instead of hydrogen?

It will make no difference with regards to reactivity.

I have always pondered as to why it is used ( it exists in our SDC molecules)

I will shed some light. It is used to determine up takes and also excretion rates. Therefore it is possible to determine uptake, concentration in plasma and body organs as well as the excretion rates.

Deuterium being part of our compounds can therefore be used to determine uptake distribution and excretion from our bodies. ( LADMET). Here I will add it does not in itself relate to toxicity as that is a result of the total compound.It will however be of fundamental importance with assessing risk to specific organs.

Measured by femtosecond infrared spectroscopy. No need go in to detail but can be used to identify organs that may retain compounds that may lead to damage ie toxicity. Hence the identification of organs treated by a molecule that may retain longer than therapeutically beneficial and lead to toxicity and consequent adverse effects in vital organs.

Deuterium is not new to medical science having been around for about 40 plus years.

No idea of cost but would hazard a guess by the non use in clinically approved compound would constitute a considerable saving.

Our Sar developed molecules will contain the same make up used in final candidate preclinical to those used in human trials and into clinical use. i do not have the same level of faith in a Chinese developed product.

I replaced some light bulbs with LED's around 7 months ago. 6 of them at around 5 pound each. All made in china. 5 year guarantee. Not used much at all but have replaced them with original tungsten bulbs as soon flicker and fail. Same country supposedly developing world class inhibitors.

On that note I perceive very little threat from Chinese competition to our inhibitors both wholly owned and those we have a financial interest.

regardst o all

Slight foopah in presentation, there C79 i am certain they did not just add Jak2 to Jak1. Tyk2 to Jak1 yes.

Adding Jak2 would have been disasterous.

Very encouraging all the same. Chinese are not renowned for quality control to say the least. it does how however the dual inhibition approach to have far greater efficacy than than Tyk2 alone.

i would put the ratio of selectivity of TYk2 over Jak1 to be of extreme importance.

I am also sure that our attention to detail with rrgards to translational studies will perform better that the Chinese inhibitor.

Regards

Very nice tick up. Mafuta. Next week Sareum will be in clinical trial.

First reports back in a few weeks and anticipation of god safety reports will hold the momentum. Each increase in dose escalation should add value to SP. Expect a few sells but overall expect a steady rise over next few weeks.

Approaching 3 months since all data back for 737 from SO. I am of the firm opinion that an on licence will take place as we have heard no news with regards to further development prior to on licensing of 737.

3 months is more than adequate on receipt of all data to decide on the strategy for moving forward on 737. 737 a tad complex as preclinical indicates a multitude of combo therapies in addition to the original 737 and LDG that other competitors are heading into. May take a while for CPF and interested party to reach a mutually agreeable contract prior to finalisation.

In an ideal world:- 737 on licensed for circa 25 million upfront payment soon. 7 million to Sar

pave the way for financing phase 1b continuation of translational studies for 1802 and a very considerable SP lift for the truly invested here.

For where we sit at the moment, entering clinical trial (a Sareum first,)with our wholly owned and wholly developed Tyk2 Jak1 inhibitor, with what else we have, 2.6p in old money is peanuts.

A super few weeks coming op I feel whilst the pharma industry ,can only but watch the fruits of our labours unfold.

Great to see decent sentiment return to this BB.

Regards to all, and that means all and that includes those I have irritated at times.