Member Info for sadoldgit

There is not a great deal of a connection between Sareum and the new drug that battles cancer death star

The new drug which has been pushed through rather rapidly VS-6766 in mono or with Defacitnib in combo therapies.

It is targeted at low grade serious ovarian cancer ( approx 1 in 6) for which the KRAS (kirsten -rat sarcoma virus) onco-gene needs inhibiting Dont worry about KRAS what it stands for. Importance is they exist in all animals. They are also proto-oncogenes.

A proto-oncogene is a healthy gene which resides within a cell. There are many of them, Each one is responsible for making a specific protein so it can make a new cell. The number of proto-oncogenes is controlled by the cell. So basically we have cells that control the amount of healthy genes that we have, to produce proteins to create new cells.

Unfortunately and for whatever the root cause , these proto-oncogene cells, via a mutation or error become a malfunctioning gene ie oncogene. They can be switched on when they should be off resulting in a proliferation of cells and a malfunctioning gene passed on to the new cell that we do not want. To make things worse these cells have no programmed cell death ie apoptosis.

Raf is the best characterized Ras effector and is a member of a family of serine/threonine kinases, ( That is what our CHK1 is, a serine/threonine kinase inhibitor) that includes Raf-1, A-Raf and B-Raf. Raf activation stimulates a signaling cascade by phosphorylation of MAPK which successively phosphorylate and activate downstream proteins such as ERK1 and ERK2).
MAPK brief explanation
A mitogen-activated protein kinase is a type of protein kinase that is specific to the amino acids serine and threonine. MAPKs are involved in directing cellular responses to a diverse array of stimuli, such as mitogens, osmotic stress, heat shock and proinflammatory cytokines.

I am rambling.

In a nutshell low grade serious ovarian cancer requires inhibition of KRAS
High grade serious serious ovarian cancer P53 checkpoint stop. Should prove much better in combo, ie 737 and 515 and
later an immuno checkpoint inhibitor.
My understanding for what it is worth especially after reading HBD post is that 737 is vital in the treatment where DDR (
DNA Damage Repair) comes into effect. 737 I cannot understand how it can kill a cancer cell as cancer sells have no programmed death. However in saying this 737 comes into its own whereby 50% of tumour cancers are TP53 dependant.

There are treatments that can kill tumour cells. Unfortunately we then get DDR basically metastase now( ie very rapid cell replication), this is where CHK1 comes into its own. It is this rapid replication of cells that SRA was invented to stop.
Interestingly our 1801 is compatible with many inhibitors and treatments including CHK1, yes that includes 737.

Call me mad but I am of the opinion that Gilead dont want Momo. If momo is sold, Gilead i reckon be in like a shot then after

I have many thoughts on this KRAS subject especially with CHk1.
A fairly recent report below

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8665414/#:~:text=CHK1%20protects%20oncogenic%20KRAS-expressing%20cells%20from%20DNA%20damage,and%20is%20a%20target%20for%20

Not sure of a smoke screen Mafuta.
Sierra not owned by GSK they have merely made an offer that the board have advised acceptance.

Sierra cannot lose in this situation.

The worst they can end up with is 1.9 billion from GSK.

Sierra merely advancing the promotion of Momo. Should a buyer offering sufficient payment for Momo alone then they can blow GSK out of the water. Will then leave more than sufficient funds for full steam ahead 515 and 737. A billion plus for Momo minus the 300 million for Gilead leaves them 700 million for development of the afore mentioned compounds which if successful will then have access to a multi billion pound market many times the size of the monetary value accessible for Momo. Sierra have been determined to keep SRA737 ever since removed the for sale sign early 2020.

Trying their luck? Maybe.

Either way good for us.

Regards

Good morning Gunner. My 6 months would start from granting of clinical trial. So yes l can be seen to look a bit optimistic by saying 6 months from now. I apologise for that.

Phase 1 trials for toxicity in humans should not take long . A small number of healthy volunteers given an escalating dose from 12.5 mg per day and then increased
Not sure how high the first recruitment will go to, maybe 50 to 100 mg per day. Short period of time then it is repeated with healthy set of new volunteers that start on maybe 50 to 100 mg per day then increase dose daily. This will continue until.toxicity develops or we have well exceeded 1000 mg per day.

These early tests take around 5 to 6 months l believe. Should not have to wait as long as we did for toxicity results of preclinical l am surmising.

Stage 2 trials will be the treatment of an indication in a small number of people with an ailment. First thing looked at is, is it more effective than current forms of treatment and are there any side affects? This one will take longer likely around a year.

Now if toxicity is not an issue and we can deliver to a human around 1000 mg a day with no adverse effects, then l believe we will have proven to have ****ed all over anything else currently out there

Toxicity will reduce the amount of a compound that can be administered to a human. It is ok to say a compound will treat Indications but to do so must be delivered in adequate quantities. Toxicity restricts that. Toxicity issues are a primary reason for a drug failure.

Apologies for rambling on. Should Sareum start early July we will know within 6 months if we have cracked it or not. Taking your CTA application and capsule formulation timescales along with the red tape of approx 3 months, that appear very realistic and down to earth, we are looking at 9 to 10 months from now.


So yes, 6 months from now rather optimistic. I will go for 9 to 12 months from now which is not far away from your 18 months.

Also bare in mind that anytime before this offers can be made for license or whatever.

Regards.
Ps if it seems a bit hickledy pickledy then I am blaming my little mob phone.

Regards

Good evening Elcap. I am of a similar opinion to yourself. GSK claim to have made offer to Sierra for Momo for 1.9 billion. In the pipeline they have 737 and 515.

The board of Sierra invested quite heavily at end of last year in shares. They are guaranteed a healthy profit from the circa 15 dollars per share they bought in at.
Directors will want deal to go through
Momo will be marketed in a comparatively small niche market. The market for a Chk1 inhibitor especially in combo with the likes of 515 is inherently much larger. Bare in mind that SDC 1802 can be used in conjunction with a CHK 1 inhibitor as well as also a myriad of other treatments to improve effectiveness and compensate for cancer that develops resistance to treatments.

That being said l can see no reason as to why Sierra/ GSK want to create positive publicity around 737 or to a lesser extent 515.

GSK/ Sierra will not want a competitor coming in and trumping their offer at the last minute. Hence l believe why the 737 profile has been kept so low for the past 6 months. Finalising trial design they say! You scratch h my back and l will scratch yours comes to mind here.

I don't see much happening with news of 737 or any change in the stagnant 55 dollar Sierra share price until deal is finalised. I would hazard a guess however, that the designs are in place and if and when deal is finalised 737 development will.be rapidly propelled forwards.

In all we have held up well with SP compared to many other companies. Yes we can drift down a tad on no news but can climb rapidly on good. The one to watch for is results for our SDC1801 phase 1 trial in human clinical toxicity studies. That is the biggy. As this milestone is reached, then we will be in a position to command licensing conditions and payments both up front and on royalties. What are we looking at for that to recevie positive news via an RNS updating progress.? 6 months or there abouts.

In the meantime all we can realistically do is wait.

From memory the US military funded investigations with SDC1802 for Lupus.

SDC1801 should prove more effective as is immuno therapy.

Morning WIP it should also be noted:=

Otezla is available in the U.S., but is dispensed only through a network of specialty pharmacies.[18] The estimated wholesale price is $22,500 for a year of treatment.[19] In Austria, the drug is available in all pharmacies, and a year of treatment costs health insurances about €11,000 as of 2018.[20] In India, the drug is available in all pharmacies, and a year of treatment costs about ?22,000. Celgene made Otezla available in the U.K. in May 2021.

Apremilast was approved for use in the European Union in January 2015.[7]

In 2019, Amgen acquired Otezla from Celgene for US$13.4 billion.[24]

In 2020, Otezla generated US$2.2 billion for Amgen

Regards

Clarification here. Deucravacitinib is pure TYK 2. Tyk2 is more selective than Jak2. Jaks work best in pairs.
Pure Tyk2 will not fully inhibit IL-10 as IL-10 inhibition is made up of 4 sub units. 2 sub units from Jak1 and 2 sub units for Tyk2.
Do not look at Jak1 being an inhibitor in its own right look at it more to enable full potential of Tyk2
Deucravacitinib flunked trials in inflammatory bowel disease. Me thinks this due to not fully suppressing IL-10 so reckon that will leave BMS with a bit of head scratching.

Our 1801 is a Tyk2 Jak1 (as TM stated circa April 2020 what they believe an optimal amount of Jak1.)

Likewise our SDC1802 should as from the same stable, be streets ahead of current competition not just on toxicity concerns alone.

Regards all

Childhood cancer outcomes being discussed HOC. Summary.
Poor prognosis.
Still using treatments designed in 1960's 70's and 80;s
Insufficient funding and research into new treatments.
Importance of early diagnosis.
importance of contribution of CRUK.
New treatments urgently required.
Specialist units to be set up for early diagnosis of child hood cancers.
Treatments abroad not available here.
Crucial to understand side effects ( some long term) and relapse
Access to funding for research. Great Ormond street contribution.
Approximately 200 childhood cancer fatalities a year.
10 year plan on investment to improve treatment of childhood cancers. ( motion passed)

Although primarily many of the indications associated with our TYK2 Jak1 are, for want of the word of it, adult cancers there are a remarkable amount of indications applicable to childhood cancers.

From WHO Dec 2021.
Each year, an estimated 400 000 children and adolescents of 0-19 years old develop cancer. [1, 2]
The most common types of childhood cancers include leukemias, brain cancers, lymphomas and solid tumours, such as neuroblastoma and Wilms tumours.

Wilms tumour (nephroblastoma) is a type of kidney cancer that most commonly affects young children.

The main treatments include:

chemotherapy for almost all children
surgery for all children
radiotherapy for some children.

We look that we have much value here as we have about every form of leukaemia and carcinoma covered but the degree of efficacy here I cannot find.. This may include as far as i can see those which are not TYk2 dependent.

regards

https://www.nasdaq.com/articles/4-biotechs-that-could-be-potential-takeover-targets-in-2022

Whilst Sareum are not mentioned here, it does give an indication as to the amounts that can be paid for a takeover.

But must take into account that these negotiations will go on for many months.

Note that very little info is available on our toxicity results. All very hush hush. Phase 1 clinical trial results will be the overriding decisive factor. If our tox issues are as good as we are led to believe then the efficacy in treatments will not be hampered by dose related problems.

Nothing much else to add.

You are welcome DP64 as others. I am not ramping as no need i we have the HNWI's having invested around 6 million of their own money have done that.

Regards

Market Cap of circa 200 million. 2 potential blockbuster 2nd generation little to no toxicity blockbuster therapies,
Phase 1 clinical trials in humans to start soon on SDC1801 followed by SDC1802 a little later.
Excellent LADMET properties enhanced by crystallisation of a compound to enable 100% purity and capsule formulation.

2 multi billion pound compounds at entering phase1 or ending pre clinical. The time and dedication to getting things spot on.

Offers made be made in informal discussions of 50% of current SP but do you seriously think any director would be even the slightest inclination of accepting such an offer with what they have in the pipeline?

As has been stated. have a good in depth look at our RNS history going back to at least 8 years. Read in depth, understand and take a look at inferior treatments, who owns them and how much revenue they bring in each year.

Nigh all drugs that are failing now are due to toxicity and severe side affect issues associated with dosage levels.

Our TyK2 SDC 1801/1802 compounds were invented to provide a treatment for immuno and oncology to treat many ailments that have no or no decent level of success. In addition 1802 and as per the recent EPO release may be used as a combination therapy as a minor player and may lead to the major treatment after resistance has been found to lessen efficacy of current treatments. Can be used on its own and or with a myriad of current and developing therapies.
There are many indications which both SDC 1891 and 1802 are aimed at.
Regards

It is uncanny the amount of drugs that fail due to toxicity issues, a milder dose to reduce toxicity effects also reduces effectiveness of these therapies.
Many companies now experiencing gaping holes in an expanding market.

CTA application or news of 737 combo and commencement thereof.

Capsule and formulation manufactured in sufficient quantity and to GMP.

News of granting of clinical trial.

News of progressing of clinical trial.

Clinical trial results, indications stated for 1801.

737 News in combo therapy. Milestone payments of 2 million paid and also 2nd milestone on top.

Offer of buyout for 1801 and 1802 at circa 2.5 billion dollars.

Revised offer accepted 2.75 billion dollars from.GSK.

That my prediction. Tin hat material.

Sierra stated some time ago that SRA737 could prove more commercially viable than Momo.
GSK will be very aware of our pipeline what is in it and the potential. Also be looking at our lack of toxicity. patent protection, last but not least compatability with other treatments. How many know here that 1802 can counteract the cancer resistance build up to Gemcitabine? So much has been done that we are not privy to.
GSK are big enough to buy 1801 and 1802 for which Tim was looking for. When asked by the smooth talking aussie Andrew Scott ' what if a company wants both? TM replies well they will have to pay the price then.
Tim had slight concerns, as difficult to find a pharma that wanted immuno and oncology. Not many companies do both.

All looking good, very good!

Finalising of combo trials most likely delayed if GSK in talks with Sierra. Any combo announced regarding a GSK compound would give the game away and result in speculation that may not materialise.
Clearly discussions been going on between GSK and sierra for some months. They will know exactly what is in the pipeline and its potential before making any offer.

Good post num4. GSK have bought Sierra which is not only their pipeline but also their obligations. Effectively they now have the money to progress 737. At the very least expect we should hear soon what Sierra's intentions are with regards to 'design' of trials/ therapies. It has been nearly 3 years of little to no development of 737. I cannot for the life of me see them stalling for at least another 6 months claiming we are waiting for finalisation of buyout.

Sierra have been given much leeway. Too much leeway some may say. GSK has made their move and now anything to do with NDA should be at an end.

Regards

As it stands with the licence agreement intestines alone 300 million in total, around 70 million of that for Sareum. Roughly 10% royalties on worldwide sales thereafter.

GSK would have to approach CPF
How much can we buy it for?
CPF. Well how much have you got? Ha ha.

Seriously now. The more they develop and establish combo therapy the more money CPF will want for buyout complete.

In this scenario it would be in the interests of GSK ( since they will be developing) to purchase 737 in its entirety ASAP
An absolute minimum of 1 billion l would guess. That give us 275 million
Enough to finance 1802 and 1802 into and through Stage 2 trials easily.

Just my thinking that is all.
It will depend how much value the CPF are prepared to accept either with royalty payments or without. One will be significantly higher than the other

Sierra did have a graph some weeks ago with CHK 1, Gemcitibine and immuno checkpoint inhibitor.
Looks like been removed as cannot find it. Results they obtained were phenomenal on the graph. Unfortunately l cannot find anything to post or take from website to substantiate this.

Regards

Good post WIP
Interesting and note, SRA737 already been explored in combo with Niraparib ( GSK PARP)
Regards

Afternoon WIP.

Looking fine for SRA 737 in combo with PARP inhibitor. Bare in mind that SDC1802 can be used should and when gemcitabine loses effectiveness in treatment as cancer does develop a resistance to it.Effectively now GSK own SRA737. They have bought Sierra oncology. The license agreement will remain the same.
Niraparib ( GSK PARP) in need of being partnered to increase effectiveness, otherwise GSK would not be going down this avenue. SDC1802 can be used in combo as either the minor or major treatment. We are fine to work with PARP and or CHK1. All 3 not out of the question.

Will have a look in depth at your posted material.

Regards