Member Info for sadoldgit

It is comparatively recent WIP. However, a lot of this work will have been off of the back of the results of trials up to mid 2019.

We have US patent application for SRA737 in combo with PARP inhibitors by the look of it. That should secure that side of the market.

Am thinking a lot has been going on and kept very hush hush. Sierra will be privileged to much more of this info as will GSK.

If what is going through my head anything to go by then then it sint no surprise Sierra stated that SRA737 may be more commercially viable than momo. Looking here at the most effective long term control of HGSOC by the use of patented Combo with 737 as a treatment.

No surprise here then as to why Sierra took down the for sale sign of 737. Clearly aware of the potential and the monumental market it may prove to be a world leader in.

The power of Chk1 is in combo. What better way to protect than to apply for patent. 20 years protection from application date.

Regards

I would hazard a guess of GSK PD1 inhibitor, Gemcitabine and Chk1 as potential treatment also PD1 inhibitor platinum therapy and chk1 inhibitor.

Sierra oncology hold the key here, l believe
Yes ovarian is a bit of a f...er to treat effectively. Not always down to what we use to treat but also the rate and frequency of different treatments especially in combo. Of the opinion that Sierra can nail this one.

Regards

From memory l believe in Feb 2011 it rocketed 1100% from a low. Peaked at 4.2p.
Although we are still at pre clinical on reasonably good toxicity results in clinical trial then 1100% rise would not be out of the question.
Remember we have 2 Tyk 2 Jak1 compounds. Similar but not exactly the same.
I don't see much happening over next few months that will propel us rapidly northwards unless we receive a positive update with regards to decisive plan of action with SRA737.

Anyone else think it a little odd that GSK offer to buyout Sierra as opposed to just buy momo or the license for.
Normally prior to formal discussions, informal discussions tend to take place over many months beforehand.
A target price was put on Sierra towards end of last year of 55 dollars per share and along a couple of months later GSK offer the same price for a buyout.
GSk has PD 1 inhibitor. Although good and can work well with chemo uses different approach to destroy cancer cells. PD1 and chemo can destroy cancer cells. That is all they can do. Neither on their own or in combo with each other can stop Replicative stress or DNA damage repair. Hence we now have a situation that often arises in that we can kill cancer up to a point until develops resistance or the dreaded DDR of which similar outcome.
Interesting to note here also
Sierra have turned a sours ear into a purse on momo which failed stage 3 trial when owned by Gilead. Their work is first class. The drug was not given away for next to nothing. Gilead don't do that. It was a failed drug and hence the price reflected as such. Large milestone payments yes.

Secondly SDC 1802 is indicated for use in areas where current treatments in use become less effective due to the cancer developing drug resistance. 1802 can be used as a supportive or the major treatment. That laid out clearly in our patent application.

Regards

Relating here to SCLC only, an exerpt. From 2019.

Next, we expanded our study to an immunocompetent SCLC model to explore both the intrinsic and immune-mediated anti-tumor effects of SRA737+LDG regimen in combination with anti-PD-L1. We first determined that SCLC cell lines H209, H524 and RPP were resistant to monotherapy gemcitabine in vitro (Fig. S3B), with the RPP tumor model described above selected for further in vivo testing. RPP tumor bearing B6129F1 immunocompetent mice were treated with LDG (40mg/kg, 1/7, first day of week), SRA737 (100mg/kg, 2/7 first and second days of week) and anti-PD-L1 (300µg, 1/7, third day of week) as single agents or in combination. SRA737+LDG regimen mimicked the schedule currently being used in the clinical trial described above with or without anti-PD-L1 on the third day of a weekly cycle. We did not observe a significant anti-tumor effect with any single agent treatments (anti-PD-L1, SRA737 or LDG), and only a moderately delayed tumor growth with combined SRA737 and PD-L1 treatment (Fig 4A). However, we observed remarkable tumor regressions when we combined SRA737+LDG with anti-PD-L1. All mice achieved some level of tumor regressions and 80% of mice (8/10) had complete tumor regressions which were sustained up to 60 days post treatment

Given that anti-PD-(L)1 drugs have recently been approved as monotherapy and in combination with chemotherapy for the treatment of SCLC, and that the SRA737+LDG regimen is well tolerated in clinical trials in SCLC (NCT02797977), our preclinical data provide a strong rationale for combining this regimen with inhibitors of PD-(L)1 pathway in the clinic.

Regards

For a takeover to happen a value has to be placed on Sareums pipeline and economic interests.
Sdc 1801 ok
SDC 1802 ok
Aurora FLT +3 ok
SRA 737 a little difficult to fathom. It it worth a couple of million or a couple of billion to which we are entitled to 27.5%

On successful milestone payments circa 70 million. That around 1 pound per share minimum and of course royalties on top.
Selling the company at this moment in time l do not believe is delivering good share holder value.
6 months time l think completely different.

Regards

Also worthy of note is the following from April this year.
https://pubmed.ncbi.nlm.nih.gov/35259479/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7141083/

Not good info if l dont give a link!

Good info here for those that are interested in development with Chk1 Gemcitibine and PD1 inhibitor.

It is good to find this as is written as so many doubting Thomas's like to see for themselves and only then have a limited understanding.

It is lengthy. Very! But pay particular attention to Sra737 Gemcitibine and PD1 . When used separately or any combination of pairs and of course blow your socks off all 3 in combo.

Much of this info albeit not in as much depth, was on the Sierra website. No sign of it since just before GSk have become involved.

Designing of SRA737 in combination for clinical.trials they claim. They already know of the potential. About time they got a move on as GSK will have more than just a passing interest. Plus of course as Scheckler correctly stated GSK would have carried out all due diligence.

Regards.

I will add the link is a long read but provides some of the missing information or removed information from the Sierra website some time ago just prior to the GSK involvement.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7141083/

Good post Krone. I take it that designing combination trials for 737 which they have stated since at least January complies with terms set out in section 4.5.
Update must be do soon.
Dragged this on for approaching 3 years yet removed the for sale sign early 2020.

Good morning BB.
10 pounds a share in 18 months? Not out of the question as would put market cap at around 660 million.

With regards to 737, Chk1 inhibitors are not without thier problems mainly due to toxicity issues. Primarily heart problems albeit most non severe cases can be treated effectively.
Bare in mind that early clinical trial is to determine a level whereby a maximum safe dose can be used as a treatment.
As for a Chk1 inhibitor which blocks the multiplication following cell mitosis by inhibiting the P53 cell checkpoint.
Without this P53 also referred to as TP53 a cancerous cell cannnot replicate.
Cancer cells do not have a programmed cell death. Indeed there are other treatments that can cause sell death eg Chemo , PD1 (programmed death) and indeed PARP inhibitors. Most will prove effective. However over time drug resistance by the cancer becomes apparent. Furthermore, we also have the problem of DNA damage repair. In this instance we have now have a cancer that will massively replicate itself. Over 50% but not all cancers are reliant for cell multiplication on the P53 checkpoint.
If we look at what we have how can a Chk1 inhibitor kill a cancer cell that has no programmed cell death. It can only work on inhibiting new cancer cell growth. Clearly it needs work in combination with other therapies.
bare in mins also that our SDC1802 is compatible with PARP, Chk1 and many other inhibitors especially with the likes of gemcitabine which allegedly restore effectiveness of such chemo treatments following drug resistance.
We can look at SDC1802 for treatment of cancers. If we treat a cancer how can we stop the dreaded DDR process?

GSK are looking at increasing their pipeline in Oncology, especially in the areas of immunotherapy. IO they refer to as ie immunotherapy oncology.

I do not think we will hear much until takeover has begun later this year. GSK has some gaping holes in its oncology pipeline. These need to be filled.

Sareum are in discussions with potential partners. GSK state that they sre looking at combination therapies and make it clear that that is with their current pipeline. They also state that their intention is to look at other combination therapies and by definition omiting ' their current pipeline' would indicate that they have other compounds developed by other companies that they want to know a little bit more about.

Bit of a ramble, but just in after a busy nightshift,

Yes Citizen 79 does post good factual info. can be heavy reading at times.

The GSK Niraparib / Zejula from memory on small 100mg a day dose is around 8k dollars a month and not without some nasty side effects.

Regards

Outstanding post Num4 and very down to earth.

The only thing I will add is the emphasis on 'preclinical or early clinical' .
Tims belief is the greater value placed on a compound post preclinical offering substantial more value to investors.

We may have to wait a little while to perhaps end of phase 1 toxicity trial at the latest.

Tim and co been in discussions with potential partners and on licensees for ages. When milestones are met up goes the value. Interesting to know the content of the most recent discussions.

I dare say they have a very good idea of preclinical and and early clinical worth, otherwise the statements would not have been made by Tim. Just tie up the time the HNWI's came aboard providing much needed finance at a very convenient time. Yes and, they do have options to buy shares further down the line. Speaks for itself.

Regards

Good morning SCHeckler.
The licensing agreement is between CPF and Sierra and has nothing to do with an outside party. The contract will be legally binding between the 2 companies. Unless there is a serious breach/default of the agreement nothing changes. As it stands 737 is nothing to do with GSK. They do not own Sierra or any if its pipeline. They have made an offer, that is all.

Yes they will have carried out due diligence.

They may well know for what reason 737 was taken out of the ship window so as to speak on early 2020. Not long after trial completion l hasten to add.
Sierra want shot of momo as they are a late stage development company, that is the nature of their business.
Lots of work has turned Gileads phase 2/3 momo sours ear into a purse.
Look at the history and development as well as the institutions and people they contain involved in 737. Do you remember the likes of Michelle Garrett singing the praises and prospects for the cct245737?

737 has pedigree as developed in conjunction with the finest cancer research facility in the world.
Enough of my rambling. 737 will have its day but not may come as quick as people think. It if all goes as well as expected it will have access to a mega multi billion dollar market. Not happening overnight.
Keeping the faith in the science here and not forgetting we have two inhibitors entirely owned by us.
Regards

No it is not tosh you are saying Hbd.
We must fully understand the objective of a CHK1 inhibitor. In effect its object is to prevent rapid prolification of cancer cells via immobilising the p53 checkpoint.
Metastase, whereby after treatment, a DNA damage repair has taken place.
If we damage part of our body there exists a process whereby our body goes into overdrive to repair the damage that has been done. Cancer tumours are not recognised by our bodies as an invader. The tumour is in effect part of our body hence if it is damaged the body will go into overdrive to repair.
Hence we have early treatment of a cancer and then we have 3 outcomes
Cancer goes into remission. Cancer is not technically cured. After 5 years however, you are deemed free from.
Cancer develops resistance to treatments. This is an effing wide topic as to the whys
Cancer after a period of remission and returns metastase. Very common and increasing

It is this metastase which creates the biggest problem. Over 50% of cancer cell replication relies on the p53 pathway

Cancer cells are not apoptic ie have no programmed cell death. All our other cells in our bodies do.

Now if we take it that CHK1 stops cancer cell replication, but cannot effectively kill a cancer then we will realise the importance of just what it can do. In effect we are looking at combination therapy. look at early results with CCT245737
combined with gemcitabine ( a chemo) way better than 737 on its own.

We also have a problem here as with many chemotherapies a cancer will after time gain a resistance to types of drugs.

As a side step here, I did note that our 1802 may be used as a treatment in combination with gemcitibine as a means of overcoming cancer resistance to this particular form of chemo.

Call me mad but am of the opinion but on reasonable results of phase 1 human trials with either of our Tyk2 Jak 1 inhibitors then an astute pharma will want all 3 compounds.
GSK have made an offer for Sierra'
Yes Momo will give them an income. Primary reason for the offer they claim is momo. Well lets face it they sure aint going to say, what we really want is SRA737.
Sierra happy to promote and sell Momo. At the same time they are not prepared to sell 737 and this becomes apparent as
time goes on.
Take CHK1 and combine with a PARP inhibitor or even better with additional Immuno checkpoint inhibitor and you pretty well have 50% plus cancers sewn up. Sierra know of this.
You have sierra with 737 and our SDC1801/1802 inhibitors very much coming into the limelight.

Sure there will be toxicity issues and cardiotoxicity may well prove to be a minor issue.

Sierra have done a first class job of turning Gileads phase 2 or 3 failure into something.

They now have something with far more financial potential.

On the whole I see the stars aligning.

Our pedigree and the partners we have worked with, for example ICR are second to none.

Our patent protection is pretty t

Hbd
an interesting albeit very long read on cardiotoxicity with Small molecule kinase inhibitors.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7303342/#:~:text=Common%20toxicity%20presentations%20include%20the%20clinical%20signs%20and,ventricular%20ejection%20fraction%20%28LVEF%29%20%28Lamore%20et%20al.%2C%202020%29.
Regards

The only way a company can obtain a compound that another company will not sell is to buy the company.
interesting dosages from HBD's find of SAP of less than 800mg and greater than 800mg daily dose.
A considerable dose to say the least.

Regards

Good find Hbd
Spot on lad!

Hi HbD
At least 1 post baseline disease assessment OR discontinued treatment due to AE or disease progression or death Note: The median OS was not estimated in the mCRPC, HNSCC, or "Other" tumour type subgroups due to insufficient number of participants with events.
Unfortunately we do not know the exact cause of the adverse event.
1 case in a 107. statistics although a powerful tool it also requires sufficient numerical data. When percentages are used it implies figures of greater than 100.
Accuracy in statistics is related to the magnitude of count.
1 case in 107 implies 2 cases in 214 or 10 cases in 1070.
As is it a statistic and as such indicates random or chance it will also have a deviation value. on high numbers. plus or minus two standard deviations. Standard deviation being the square root of a number.
It may be one event that happen in a 1 thousand. Theoretically it is possible to have just done trial with 2 people and one person had an adverse event. Although highly unlikely if it were statistically validated at 1 in 1000.

As far as i know there were people that showed significant benefit in partaking in the trial who still continued to receive 737 after the trial was finished.

I dont think Sierra are wanting to sell it. They took it down from the 'for sale sign' early 2020.
As to value of 737 and 515 i would hazard a guess at several fold of what momo is worth.
Some have said if 737 is that good why has it not been sold?
My argument is that it is that much more commercially viable than momo. Momo will have access to a 2 billion dollar market per annum. It dont mean momo will rake in 2 billion dollars a year. By 2025 the drugs oncology market alone is estimated to be around 177 billion dollars a year turnover.
Bearing in mind that p53 is present in over 50% of tumours. Better results in combo we know. It is not beyond any reason that a pessimistic figure of 1% of this 177billion available market should not apply to a CHK 1 inhibitor. Sierra will know what they have. It is far too lucrative for them to sell as is. So as it stands my argument it is far too good for them to sell as is at the moment.
Their business is development of drugs to late stage or commercialisation.

Regards and beer oclock

HBD good afternoon.
Brief Summary:
The purpose of this clinical study is to establish the safety profile, determine the maximum tolerated dose (MTD) and recommend a Phase 2 dose and schedule of SRA737; and to evaluate the efficacy of SRA737 in prospectively-selected subjects with genetically-defined tumors that harbor genomic alterations linked to increased replication stress and that are hypothesized to be more sensitive to checkpoint kinase 1 (Chk1) inhibition via synthetic lethality. Specific cancer indications that frequently harbor these genetic mutations will be studied.

It is merely establishing a MTD. They would now have established this on completion of trial and vital to establish before progressing further. Nothing untoward here.
They can now plan later stage trials of treatment in patients. Even better to plan in combo.