Member Info for sadoldgit

Whoever gets involved will be dealing with the CPF

There is much research taken out after Michelle Garrett formerly project lead at CRT in the development of SRA737.
As I have stated before this work has included in the field of CHK1 using the earlier CCT244744 compound. Earlier work was done with SRA737.

Potential is huge to say the least and negotiations with an interested party will take some time.

Does the interested party want the lot ie complete buyout or on license?

737 was valued at around 120 million by Edison circa 2018 with no data results and a 15% chance of success as a mono and in combo with LDG

Pre clinical has worked well hence 2 patents ie Pd-1 and Wee 1
Much more effective with LDG

If we remove the risk factor of 15% alone for just CHK1 ie 737 that give a price of around 700 million dollars. That excludes inflation.
It also excludes the patented combo and further development work on CHK1 inhibitor resistance pathways.

Absolute minimum must be around 700 million dollars.
On licence would be considerably more due to further indications than just NSCLC and anal cancers. Upfront milestone payments tend to be on the low side but considerable on commercialisation.

Potential here with HGSOC, Breast and pancreatic.

It is important to remember that CHK1 to be effective will require combination therapy and these combination compounds also have a price.

Ideally a deal to be done before Sareum intend to raise more funds.

I cannot see another Pronai Therapeutics ( now Sierra Oncology) type deal happening.

A downside is there is much lesser investment recently in pharmaceuticals. At the same time there are some massive deals that go through.

It is not in anyway owned by Sareum it is that we have a 27;5% interest. Ultimately the decision is with the CPF but we will have a voice and that is about all.

There other options of course but these are the main two. Partnership and or co development.

We can only wait and see what transpires.

Regards

There will be interested parties of course.
There are not many later generation CHK1 inhibitors selective over CHK2 with low to mid toxicity and taken via the oral route.
Chk1 and chemo
Chk1 and either PARP or PD-1 inhibitor
CHK1 PD-1 and chemo
CHK1 P-13 /AKT inhibitor in combo.
Chk1 and Wee1
CHK1 and WEE1 with chemo.
Even less that have patent protection in combo therapy.

Some say the science dont matter. Science is the compounds. A chemical structure addressing a biological problem.

It does it is that they just dont understand and hence never make a valid argument.

Look at what we have and what competition there is around.

Yes it is a competitive market.

Oh some will say but they have returned it ( not rejected).
SO did some sterling work then prioritised momo which was a bit of a pigs ear they purchased for a very low upfront fee from Gilead. Made a 1.9 billion purse out of it.
Developed 737 in human trials with Chemo which gave good results, preclinical with PD-1 and Wee1 inhibitor patented.

More development work done outside of SO.

Put a price on it!

It is not a case of if but a case of when

Regards

Very true KS. I doubt that you are invested,
Looking to buy in maybe

Well Surfie, I do hope this evolves as it should over the next few months, then we will both be happy.

We may have a slight retrace.

Pharmaceuticals way down in past 12 months.

All down to timing here, as in how long do Sareum wait for CTA approval via MHRA?

We have ( well 27.5% financial interest) SRA737. Can allow 3 months minimum as I see for major development with suitably interested party.
Return of 737 mid Jan then around 4 weeks to glean through SO data on.
CRT carried out more research work than SO with respect to CHK1i resistance.
Pathways hypothesised to limit/prevent resistance. Michelle Garrett who was formerly involved in development of CHK1 with Sareum has continued investigational work into this. Of an extreme high calibre here. Even using CCT244744 which was the untweaked candidate in investigational studies.

SDC1801 CTA approval, anyones guess to timeframes, but delay is not good and Sareum will be burning funds whilst delay continues.

2 very promising compounds that ought to generate considerable shareholder value.

Yes, we all get a bit peeved with SP. I have been here since 2012. I bought at 0.3p and less when people posted that it would be down to 0.1p. Continued to add. Sold a few when reached a high and bought back more when much lower.

Very little we can do apart from wait. From an original investment of around 12k I amassed a tad under 600k.
Now have left around 150k and have taken several k out a while back.

It is not an easy share. I feel we are much near the bottom at the moment as we will get, I may be wrong. if it does go lower I am in the position to buy more.

I will take this opportunity to wish everyone a happy new year and a very prosperous 2023 however you choose to look at things.

Regards

C'mom Surfie. This share could go up 500% in 6 months as has done before. Then you can at least get your less than measly 15k back plus a bit.
I am not overly interested in what it can go down to. I am more interested of what it can go up to.

Regards and chill out man.

OECD input.
Together with governments, policy makers and citizens, we work on establishing evidence-based international standards and finding solutions to a range of social, economic and environmental challenges. From improving economic performance and creating jobs to fostering strong education and fighting international tax evasion, we provide a unique forum and knowledge hub for data and analysis, exchange of experiences, best-practice sharing, and advice on public policies and international standard-setting.

Fairly recent addition to GLP, or to be more precise a modification to include,

Bare in mind we have had Covid 19, people working from home and bl00dy big backlog.

'o Data Integrity
1. In the last few years, guidance on data integrity has been developed in the fields of Good Manufacturing Practice (GMP) and Good Clinical Practice (GCP). Could similar guidance on data integrity in GLP be developed?

The OECD Working Group on GLP is currently developing a document regarding data integrity in the context of GLP. Once ready, a draft will be posted on the OECD GLP website for public comment. (Posted on 15 June 2020).

I can find no implementation date on this.

;One of the fundamental purposes of the Principles of Good Laboratory Practice (GLP) is to ensure the quality and integrity of test data related to non-clinical safety studies. The way in which study data, supporting human, animal and environmental safety assessment, is generated, handled, reported, retained and archived has continued to evolve in line with the introduction and ongoing development of supporting technologies. However, the main purpose of the requirements of the Principles of GLP remains the same in having confidence in the quality, the integrity of the data and being able to reconstruct activities performed during the conduct of non-clinical safety studies. This OECD Advisory Document on GLP Data Integrity provides guidance for test facilities or test sites that conduct GLP studies and aims to promote a risk-based approach to the management of data.'

Regards

PCS1954 I agree fully.
Complain if no Director investment, and when they do invest they mock. Clearly the Director is confident. It is not as if it will go up 10% and he will sell.
Tim has over a million and has not sold.

There are no pleasing some.

2023 coming soon and good news should flow.

Regards

Good evening Julie1.
CTA not resubmitted. A review by the GLP authority requested by the MHRA.
The board looked as though they were getting a little peeved by the MHRA. Typical indications of an under experienced and under staffed workforce.
No timelines as to how long it will take to resolve, as out of the hands of Sareum BoD.

Government institutions/bodies and that includes local council authorities are a nightmare to deal with.

Regards

BB
I fully agree with your post Thursday 16.25hrs
I should have read that first.
Regards

BB
They have four patents in total.
Two patents are for further SRA737 as protection In North America and somewhere else.
Yes SO will have these two patents plus the 2 for in combo patents.

I am saying that the patents have to be returned to CPF as part of intellectual property.
SO can destroy all IP property at the request of CPF if they deem fit to. That is my understanding.

How can SO 'on license' these 2 in combo patents to another party? They would not be able to continue development as not have a license granted by SO.

Had sierra oncology developed 737 in combo and then chosen to on license to a third party then I would see no reason they could not include that in part of the on license agreement. There is no breach of license agreement here.

However due to lack of development SO have chosen to return the license to CPF. They have not kept to the agreement.
A new negotiated contract was made with respect to milestone payments . Still no development apart from 'looking at funding options'

Basically a breach of agreement . I would hazard a guess that the CPF have pressed them on this issue hence their decision to return.
These agreements are complex at the best of times.

With regards to license yes they still have subject to the 90 day notice of intent.

' But, the agreement does explicitly provides the CPF a sub-licensable license to them. Its the presence of this automatic license that allows the CPF to do what they want.'

I think we looking at two different sides of the same coin

Regards

My opinion for what it is worth is there will be no problem with the patents in combo. It forms part of the intellectual property. Worse case scenario would be cancel the patents which costs money.

If it were a patent outside licensed use then yes a problem, But in a combo therapy for same indications I do not see as a problem.
SO own the two patents which have been approved. They no longer have the license. They cannot therefore keep the patents to prevent development work whether on its own or in combination therapy, The CHK1 737 is developed and named in the patent protection. PARP, and WEE1 candidates are not named.

It were discussed on here many moons ago and was done to death.

The conclusions were
Patents will form part of the IP.
Unless 737 were used outside of the licensed indications.

Tim stated that IP and patents will be returned and he is far higher up the knowledge tree than us that post on this BB.

In a sense a great shame that SO did not continue as committed to Momo.

Only a couple of weeks away and then we will know for sure if Tim is correct or not.

Regards

Good morning HbD.
The results if satisfactory or better should allow stage 3 trials. As long as the phase two trial met its end points. Phase1 would be establishing a safe dose and a dose toxicity threshold. Phase 2 is treatment of indicated cancers in small numbered trial.

The compounds cannot be tweaked at this stage. The compound candidates can only be tweaked at preclinical. The CHK1 compound was tweaked in pre clinical and improved over earlier candidate.

Target to beat for SDC1801

the achievement of PASI75 response at week 12, while secondary endpoints consisted of PASI50, PASI90, PASI100,
PGA 0-1 score, and DLQI 0-1 score at week 12. Primary endpoint was obtained in 7% of placebo-treated patients,
9% of patients treated with 3-mg BMS986165 every other day, 39% of patients treated with 3 mg BMS986165 daily, 69% of patients treated with 3 mg BMS986165 twice daily group, 67% in 6 mg BMS986165 twice daily group, and
in 75% of patients treated with 12 mg BMS986165 daily.

The percentage of patients reaching PASI90 response was
2%, 7%, 16%, 44%, 44%, and 43%, respectively. PASI100 was detected in 0%, 2%, 0%, 9%, 18%, and 25%, respectively.
The percentage of patients obtaining sPGA score 0-1 were 7%, 20%, 39%, 76%, 64%, and 75%, in
the placebo group, 3 mg every other day group, 3 mg daily group, 3 mg twice daily group, 6 mg twice daily group,
12 mg daily group, respectively; while DLQI 0-1 was

achieved in 4%, 16%, 16%, 42%, 60%, and 64%, respectively.56

Adverse events were reported in 55-80% of patients across the BMS986165 groups compared to the 51%
of the placebo group. The most common adverse events
were nasopharyngitis, headache, diarrhea, nausea, and upper respiratory tract infections

July 2021.

Recent findings: Although several clinical trials have shown that WEE1 inhibitor can be safely combined with different chemotherapy agents as well as radiotherapy with concurrent chemotherapy, its clinical development has been hampered by the higher rate of grade 3 toxicities when added to standard treatments. A few clinical trials had also been conducted to test WEE1 inhibitor using TP53 mutation as a predictive biomarker. However, TP53 mutation has not been shown to be the most reliable predictive biomarker and the benefit of adding WEE1 inhibitor to chemotherapy has been modest, even in TP53 biomarker-driven studies. There are ongoing clinical trials testing WEE1 inhibitor with novel agents such as ATR and PAPR inhibitors as well as anti-PDL1 immunotherapy, which may better define the role of WEE1 inhibitor in the future if any of the novel treatment combination will show superior anti-tumor efficacy with a good safety profile compared to monotherapy and/or standard treatment.

To be approved to go into clinic WEE1 need have more efficacy. Chk1 way more effective in triple combo.
The least toxic CHK1 which is 737 will be available for license.

Patents give us an idea of indications.
Actual clinical and pre clinical data will surely indicate effectiveness and safety profile.
Whilst not guaranteed to be most effective in every indication there is plenty of room for areas where there exists an urgent need for new treatments.

I would not rule out serious interest by Astra Zeneca as their WEE1 inhibitor quite recently reported as the most developed and effective WEE1 inhibitor.

The only thing that in a sense concerns me is ownership. Large companies like to own as opposed to be licensed to.
Whether or not the CPF would be open for a direct buyout would remain to be seen. Much here will rely on the data. What happens to the later investigational work carried out by Michelle Garrett ( formerly of ICR) and co.
How much is this worth?
The advantage here is that all this material will belong to the CPF via ICR/CRT.
They can further develop in trial prior to on license or sale.

As for valuation before any trial data result Edison put a value of circa 120 million dollars on 737 alone circa 2018.
This was based on a 15% chance of success in combo with LDG and a possibility of having wider application in combo.
At 15% of the then estimated available market with a turnover if successful of close to 1 billion in its final year.
This is pre patent. Originally looking at patent expiry of circa 2023. Combo increases to 2037.

Original license agreement circa 320 million with milestones and 27.5% financial interest to Sareum

Any future on licence agreement must be well in excess of at least twice ( ie greater than 30% chance of success) this original figure due to risk reduction.
Likewise the current value placed on 737 must be in line for similar ratio increase in worth.

Not going to happen over night.

Best informative post at the end of this year HbD.

CHK1 and Wee1.

I think from around 2021
Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer with high incidences of p53 mutations. AZD1775 (adavosertib, previously MK-1775) is a small molecule WEE1 inhibitor that abrogates the G2M checkpoint and can potentially synergize with DNA damaging therapies commonly used in PDAC treatment. The purpose of this study was to identify combination partners for AZD1775, including standard chemotherapy or targeted agents, in PDAC preclinical models;
Adavosertib (development codes AZD1775, MK-1775) is an experimental anti-cancer drug candidate. It is a small molecule inhibitor of the tyrosine kinase WEE1 with potential antineoplastic sensitizing activity.[1] It is being developed by AstraZeneca.[2] It is being investigated as a treatment for pancreatic cancer with phase 1 trial.[3][4] University of Michigan researchers are as of 2019 planning a phase 2 study.

Originally it was the CHK1 route that was being investigated and the WEE1 route was chosen. Both are effective at TP53 checkpoint, but early CHK1 inhibitors had very poor toxicity,

From late 2019.
Conclusion: AZD1775 in combination with gemcitabine and radiation therapy was well tolerated at a dose that produced target engagement in a surrogate tissue. The overall survival is substantially higher than prior results combining gemcitabine with radiation therapy and warrants additional investigation.

Patent protection SRA737 and Wee1
In one aspect, the present disclosure provides for methods for inhibiting the growth of a tumor by slowing or stopping cancerous tumor cells from replicating. Herein disclosed the combination of a Chkl inhibitor and a Weel inhibitor are shown to arrest the reproduction of cancer cell lines indicative of bladder, colorectal, lung, ovary, pancreas and head and neck cancer cancers. Accordingly, provided for are methods for inhibiting the growth of a tumor, the method comprising contacting cancerous tumor cells with a combination of a Chkl inhibitor and a Weel inhibitor, where the cancerous tumor cells include: bladder cancer, breast cancer, colorectal cancer, esophageal cancer, gastric cancer, head and neck cancer, hepatocellular cancer, leukemia, lung cancer, lymphoma, mesothelioma, melanoma, myeloma, ovarian cancer, prostate cancer, pancreatic cancer, renal cell cancer, small cell lung cancer, or squamous cell carcinoma of the head and neck cancerous cells.

737 0nly oral available CHK1 inhibitor available to licence,
Wee 1 inhibitors increased efficacy in combination with CHK1 inhibitor.
Similar with PARPi
Results way way further improved when used in combo with LDG of which WEE1 and PARPi are compatible.

No wonder they said form an orderly queue at the AGM.
This does nor even take into account further work undertaken on CHK1i resistance by Michell Garrett and crew.

Good afternoon HbD,
Very interesting PARP and Wee1 !
Opens the doors with either or both especially with a chemo.
Will look further into this.
Bare in ming that dear Michell Garrett has been using CCT244747 which is the precursor of CCT245737 in preclinical investigations for CHK1 inhibitor resistance. The biggy would be HGSOC and breast cancer.
A new door opens here as early CHK1 inhibitors experienced very poor toxicity.
Most are shelved nut a couple are available for research work.

Both Wee 1 and PARP will increase efficacy of CHK1, These were the original options to SO prior to running out of funds due to momo. Both can be much more effective when combined with chemo should toxicity be kept low.

SO turned a sows ear into purse with momo.

Give SO their due they carried out some sterling work with SRA737. Funding withdrawn to support momo.
Shareholders not happy at takeover price of 1.9 billion. Previous MD resigns with over 2 million dollar package.
He resigned. he did not give a years notice but received a years salary.

Clearly he has not been a good little boy in some peoples eyes.

Biggest potential here without repeating myself too much is HGSOC and breast.

It is a massive market for a top notch treatment and I dare say knock the 5hit out of GSK pipeline.

I do spare a thought for those in China suffering and indeed soldiers of both sides in the war in Ukraine. As we speak many will be alive now but not by the New Year.

On that note I wish you a Merry Christmas and prosperous New Year.

That will include all on here whether I agree with your opinions or not.

https://patents.google.com/patent/EP2634185A1/en

Worth reading BMJ Molnupiravir authorisation premature.
It will not allow me to copy link and post here.

Merck happy to rake in 6 billion dollars per annum for something they stated reduced hospitalisation and death by 50%

Be interesting to see if any legal battles ensue.
The MHRA authorised its use.

Mulnupiravir, not living up to expectations.

UK government had purchased over 1 billion pounds for this treatment.

New pandemic escalating in China. Some are forecasting a million deaths plus 2023. Likely new variants.

Perhaps the MHRA could take this into consideration when delaying applications/approvals

https://www.dailymail.co.uk/health/article-11565947/Covid-drug-DOESNT-cut-risk-dying-help-recover-quicker-home.html

A few years old from circa 2014.

One strategy to improve the efficacy of RT is to target signaling pathways activated by radiation. Chk1 is one of the main regulators of the G2/M checkpoint and an essential signal transducer in the cellular response to DNA damage and replication stress [3, 4]. Therefore, this kinase represents an attractive target for sensitizing cancer cells to both RT and chemotherapy. Previous studies have shown that selectively targeting the G2/M cell cycle checkpoint can improve cancer cell sensitivity to RT [5, 6]. A number of Chk1 inhibitors have demonstrated tumour-specific radiosensitization in preclinical studies [7–9]. However, their translation into clinical trials has been limited by difficulties with pharmaceutical formulation and toxicity. Here, we present data on CCT244747, a potent, non-toxic, orally bioavailable Chk1 inhibitor [10] that mediates in vitro and in vivo radiosensitization by modulating G2/M checkpoint control. We show that death occurs through mitotic catastrophe and/or apoptosis in cells cycling with unrepaired DNA damage.

Note from the above abstract
' However, their translation into clinical trials has been limited by difficulties with pharmaceutical formulation and toxicity. Here, we present data on CCT244747, a potent, non-toxic, orally bioavailable Chk1 inhibitor [10] that mediates in vitro and in vivo radio sensitization by modulating G2/M checkpoint control'