Member Info for sadoldgit

Krone, an interesting read from the link you posted

https://pharmaphorum.com/news/failed-ibd-trial-dents-confidence-in-bms-deucravacitinib/

The question is why has Sotyktu failed to meet its endpoints in ulcerative colitus?
We are informed that TYK2 only ( specifity and not selectivity) does not have any of the off target effects associated with Jak1, 2 or 3 and hence the horrid black box warnings do not apply to pure Tyk 2.

For ulcerative colitus

We have,
'Tofacitinib, a non-selective Janus kinase (JAK) inhibitor, is effective in inducing clinical and endoscopic remission in patients with active ulcerative colitis (UC). Tofacitinib inhibits cytokine signalling through blockade of JAK1, JAK2, JAK3 and tyrosine kinase 2 (TYK2). Adverse events including neutropenia and anaemia resulting from JAK2 inhibition have been observed in actively treated patients.

By selectively targeting JAK1, such adverse events could be expected to be avoided.

This open label study was designed to enrol 15 patients with UC, however the trial was discontinued after two inclusions due to safety concerns with the agent in a parallel trial for systemic lupus erythematosus. GSK2586184 was administered in two patients with moderate-to-severe UC.

The JAK1 selective inhibitor GSK2586184 was well tolerated and induced clinical and endoscopic response in two patients with moderate-to-severe UC. In addition, treatment with GSK2586184 decreased histology scores and faecal calprotectin levels at early withdrawal.

While JH1 is an active domain of tyrosine kinase, JH2 is referred to as a pseudokinase domain due to altered Gly-rich region and lack of catalytic Asp. JH2 has an essential role in regulating the basal activity of JAK2 and JAK3 tyrosine kinases through allosteric mechanisms and cytokine-inducible activation of signal transduction (Saharinen & Silvennoinen, 2002).

A conundrum is what we have by the looks of it.
As far as I can tell. Jaks 1 and 3 ( inhibitors that is) effective in treating UC. Safety concerns not so good as Jak2 also and compound is not selective.

Tyk2 via JH2 (allosteric site) regulates Jak2 and Jak3 in JH1

Allosteric JH2 domain regulating Jak2 and Jak3.
Regulating would indicate parameters ie basal loads ie too much or too little.

The point I make here is that it may well be that, sufficient inhibition of certain Jaks via allosteric inhibition to treat a certain target will not work irrespective of dosage.

Control of the active JH1 domain directly via Jak1 and Jak 3 inhibitor i guess would prove to be more successful. Maybe why Tim at the AGM stated there will be some indications more favourable to our inhibitor and other indications more favourable to Deucravacitinib.

I may be wrong but just my reasonings on this.

Lastly but not in the least Deuterium exists in our SDC 1801/1802 compounds.

Regards

Good afternoon Ahfam.
Interesting reads on Humira in the links below. Also a link regarding patent expiration. Some I am sure you will be familiar with, as you have posted relevant info pertaining to expiration of large pharma institution patents before.


https://www.pharmaceutical-technology.com/features/humira-biosimilars-set-the-stage-for-long-awaited-2023-us-launches/
https://www.pharmaceutical-technology.com/comment/abbvies-successful-hard-ball-with-humira/
https://dividendgrowthmindset.com/abbvie-the-2023-humira-patent-cliff-looms/

A link below of general info on patent expiries.
https://www.fiercepharma.com/special-report/top-15-blockbuster-patent-expirations-coming-decade

SRA737 has effectively been delayed for close on 3 years. Some push the 'GSK have returned it so must be something wrong with it argument'

GSK have pushed the commercialisation of the likes of Jemperli into the clinic to meet demands of high unmet need. It is extremely advantageous to get your foot in the door first. The only real competitor albeit still at clinical trial stage as I see it was SRA737. It would cost 300 million in milestone payments alone many more millions to commercialise and then pay approx 10% in royalties. Also take into account that it would take time to get clinical approval. GSK prime objective is the commercialisation of their own pipeline. GSK had already bought Tesaro for their pipeline which GSK are now pushing into other areas of oncology. Why would GSK want SO to on license such a competitor as 737, when they are already or in the process of commercialising their own pipeline into the same areas of oncology treatment that SRA737 has been found to have very favourable results ( in combo with other inhibitors) in preclinical investigations. Indeed, good results were also obtained with 737 and LDG in combo.

Regards

Apologies if shown before.

https://www.kent.ac.uk/news/science/24627/research-discovery-shows-potential-new-approach-to-cancer-treatment

It may not come as such a surprise to have a GLP review requested by the MHRA if one takes the following into account.

https://www.cbc.ca/news/health/drug-companies-caught-faking-data-1.3620483

I could post many more links but believe the post above will give a basic insight.

Regards

CircleOfLife.
I am 100% positive here, which is no different to the BoD or many investors on this BB. There is nothing wrong with being 100% positive, but must not be taken as 100% certainty. I am aware of the risks. If there were no risks the SP would be a many fold increase than what it sits at now. 2p in old money.

You have stated that you currently hold 3500 shares, of which some you claim to have held for 10 years plus.
You also stated 9th Nov 22 :-
'A lazy Google search didn't show anything previous so I assume this is Sareum's first phase 1 application as sponsor. Rejection is embarrassing but hardly terminal, clarify and modify the necessary bits then respond. One assumes the situation is recoverable and not e.g. due to to license issues or fallout from non-SAR activities.'

For someone that has been here 10 years and claims to know all the risks, why do you find the need to Google recently in an effort research any Phase 1 trial applications made by Sareum?

No point in adding any more as PC1954's post at 20.42 says it all

In my very honest opinion CoL, you just don't add up.

Regards

Yes it certainly does happen Ahfam. They can be spotted a mile off. One of the first things they try and do is con people into believing they have a balanced opinion.

Some, but l hasten to add not all, claim to have been invested years too. Their comments are not conducive of a long term investor. You just have to laugh at them. Snowflakes

Out for a beer or two when finish work. All the best to the genuine invested.

Yes you are correct Aber. After the 90 days to be handed back in a timely manner. 737 licensed to SO and will be handed back by SO.

The only work that SO have done according to their website was finalise trial design. Whilst this has not progressed to any great extent the data for this trial design should prove interesting.

There really are no difficulties to warrant return of IP.
It may well be that data is being sent in dribs and drabs and would expect an RNS at some time early Feb stating that we have now received all of the required data.
Question here is do the CPF wait a little longer to evaluate data, to put forward a plan or just inform Sareum that all relevant data received.

With regards to on licensing.
I do not think it would be the done thing to license to more than one pharma. Far too complex. One creates a patent that the other cant use unless royalties paid. How do you then sell the whole caboodle? Who gets what? Can of worms comes to mind.
Sareum pretty good with SDC1801 immuno and 1802 oncology.
Keeps it simple with two similar but not identical compounds.

A deal will not be made anytime soon ie within next month. This my opinion fwiiw and would be looking easter onwards on a daily basis. News could come at any time soon with CTA.
3 working weeks into this year and no indication from Sareum that they have applied for trials outside the UK.

Anyway enough from me. A pigs ear or two coming up.

Regards

Good afternoon SCHeckler.
Yes potential is massive.

Also disclosed herein, the methods of the invention include a combination therapy administering an effective amount of SRA737 and coadministering a second effective amount of a further treatment.'
Note the ' second effective amount'

As I see it, they have cleverly they have covered combo therapy by patenting CHK1 with any other form of treatment. In this sense the patent does not appear to cover triple combinations eg 737, LDG and niraparib. But then again these treatments are not all administered at the same time.

To confuse things here
'Further treatments also include, but are not limited to, administering any one of gemcitabine, olaparib, niraparib, rucaparib, talazoparib, cisplatin, a ribonucleotide reductase inhibitor, etoposide, SN-38/CPT-11, mitomycin C, and combinations thereof.'
' and combinations thereof'
It does state any one and not only one I might add.

A patent lawyer needed to decipher correctly I feel.

We do have the Chinese with their CHK1. I dont know what patents they have. Maybe in China yes

The Chinese with their version of CHK1 from their website indicates they have Global coverage.
http://www.bebettermed.com/goods-2-view.html

Regards

Of course we have the chinese with their own version.

https://topic.echemi.com/a/chk1-inhibitors-bibert-pharmaceuticals-class-1-new-drugs-were-approved-clinically_106314.html#:~:text=According%20to%20information%20made%20public%20by%20the%20Drug,that%20recur%20after%20at%20least%20two%20systemic%20treatments.

Of course we have the chinese with their own version.

https://topic.echemi.com/a/chk1-inhibitors-bibert-pharmaceuticals-class-1-new-drugs-were-approved-clinically_106314.html#:~:text=According%20to%20information%20made%20public%20by%20the%20Drug,that%20recur%20after%20at%20least%20two%20systemic%20treatments.

I may be wrong but look to have CHK1 in combo with anything that induces replication stress protected.

Administration

As disclosed herein, the methods of the invention include administration of the effective amount of SRA737. In an embodiment, the effective amount of SRA737 is administered as a monotherapy.

Also disclosed herein, the methods of the invention include a combination therapy administering an effective amount of SRA737 and coadministering a second effective amount of a further treatment. Further treatments include, but are not limited to, administering a chemotherapeutic agent, administering an antibody or antibody fragment (such as an immune checkpoint inhibitors), administering a radiation treatment, administering an external inducer of replication stress, and administering a combination thereof. Further treatments also include, but are not limited to, administering any one of gemcitabine, olaparib, niraparib, rucaparib, talazoparib, cisplatin, a ribonucleotide reductase inhibitor, etoposide, SN-38/CPT-11, mitomycin C, and combinations thereof.

Coadministered encompasses methods where SRA737 and the further treatment are given simultaneously, where SRA737 and the further treatment are given sequentially, and where either one of, or both of, SRA737 and the further treatment are given intermittently or continuously, or any combination of: simultaneously, sequentially, intermittently and/or continuously.

The skilled artisan will recognize that intermittent administration is not necessarily the same as sequential because intermittent also includes a first administration of an agent and then another administration later in time of that very same agent.

Moreover, the skilled artisan understands that intermittent administration also encompasses sequential administration in some aspects because intermittent administration does include interruption of the first administration of an agent with an administration of a different agent before the first agent is administered again.

Further, the skilled artisan will also know that continuous administration can be accomplished by a number of routes including i.v. drip or feeding tubes, etc.

Just a snippet

Regards

Looking at these patents it clearly indicates subject to normal patent lifespan times of 20 years it covers inventions up to 2040 as a minimum.
Prior to 1995 in the US patent coverage was 14 years.

In addition to HbD's reply

For in deep detail enter publication number and look at Justia for patents descriptions.
It will not allow me to post the links here
Regards

Sierra Oncology Granted US and EU Patents for Chk1 inhibitor SRA737
- Selection patent issued for SRA737 covers the compound explicitly and extends initial protection out to 2033 -

VANCOUVER, May 30, 2017 /PRNewswire/ - Sierra Oncology, Inc. (NASDAQ: SRRA), a clinical stage drug development company focused on advancing next generation DNA Damage Response (DDR) therapeutics for the treatment of patients with cancer, today reported it has been issued a selection patent for its Chk1 inhibitor, SRA737, from the U.S. Patent and Trademark Office. The patent explicitly covers SRA737 and extends its protection out to 2033 in the U.S., before any patent term extensions.

Methods of Treating Cancer Using CHK1 Inhibitors
Publication number: 20220226338
Abstract: This disclosure provides methods of using a checkpoint kinase 1 (Chk1) inhibitor in the treatment of cancer in a subject having at least an intermediate tumor mutational burden (TMB), or a genetic abnormality in one or more particular genes associated with replicative stress. Accordingly, methods of treating cancer in a subject having at least an intermediate tumor mutational burden (TMB-I) are provided. Also provided are methods of treating cancer in a subject having a genetic abnormality in one or more particular genes selected from cell cycle regulation genes, replication stress genes, oncogenic driver mutations and DNA damage response and repair network genes. Methods of selecting subjects for Chk1 inhibition therapy are provided. The methods can include administering to the subject an effective amount of a SRA737 compound, in some cases in combination with low dose gemcitabine.
Type: Application
Filed: May 13, 2020
Publication date: July 21, 2022
Applicant: Sierra Oncology, Inc.
Inventors: Christian Andrew Hassig, Bryan William Strouse, Ryan James Hansen, Kenna Lynn Anderes, Snezana Milutinovic, Angie J. You, Barbara Jane Klencke, Mark Kowalski

Patents normally run for 20 years from date of application. It does not always mean however that the patents expires after 20 years.
Take an example below

3. MEDICINAL PRODUCTS ARE AN EXCEPTION
A longer period of protection may be awarded for the protection of medicines based on the Supplementary Protection Certificate (SPC) which can be used to extend the validity of a patent by up to 5 years.

Before a medicinal product comes onto the market, a number of years will pass during which research is conducted into the safety of the product. The European Medicines Agency will only issue a marketing authorisation for the active ingredient if a medicinal product is safe and effective.

To compensate for this period, the term of protection of the patent can be extended by 5 years using an SPC. This gives the patent holder extra time to earn back his investment.

Regards

Warthog4. I really cant be ar5ed with the likes of 'Strictly' or other media peddled crap on TV either. The world is in a state for the benefit of the very few.

Never in the field of human wealth, has so much been taken off of so many by so few.

Sierra Oncology retains the global commercialization rights to SRA737. ( Not any more as notice given of intent to return)

However, we have
'Of note, we have recently received management support from a major immuno-oncology company to potentially supply their leading immunotherapeutic agent to run a combination study with SRA737. We will further analyze these opportunities and evaluate next steps with this asset over the coming months, exploring options to enable the continued
advancement of SRA737 in the context of our emerging pipeline.

Full link below.

https://www.bloomberg.com/press-releases/2019-06-01/sierra-announces-promising-preliminary-efficacy-in-sra737-clinical-program-outlines-potential-path-to-registration

Since this news. Developments have progressed, leading to 2 patents, one with WEE1 and the other with a PD-1 inhibitor.

Further developed had ceased due to funding being focused on Momo.
March April 2020 time the for sale sign for want of a better phase was taken down from the Sierra website.
The question here is for what reason was the opportunities for collaboration or on licence removed.

All quiet since.
There is increasing investigational activities and data thereof relating to CHK1 inhibitors over the past few months.

The CPF now retains the worldwide commercialisation rights.

Effectively the CPF has options

on licence
collaboration via a partner
sell outright all commercial rights.

An option of course is to do nothing, but i would suggest highly unlikely to be the case here.

In light of recent pharma pipeline perusal, all major companies own their own pipeline. I can find none that are under an 'on license' indicating a preference to own outright.

Although the latest valuation from Edison for Sierra oncology based on increase in value of the share price/market cap put a value of 120 million dollar increase due to SRA737 ( now at 25% as opposed to earlier 15% chance of success ) , it does not take into account the success in preclinical investigations resulting in patent protection covering these potential in clinic combo therapies.

We can interpret from data readily available that SRA737 has out performed ( taking into account efficacy and tolerability) all other CHK1 inhibitors with the added benefit of being an orally available CHK1 inhibitor.

With the exception of the Chinese, home grown approved CHK1 inhibitor there are no other CHK1 inhibitors approved for use in the clinic anywhere else in the world.

CPF and potential developments with SRA737 will take time.

Regards

Very recent AACR

https://aacrjournals.org/clincancerres/article/29/2/331/713982/A-Phase-I-II-Trial-of-Oral-SRA737-a-Chk1-Inhibitor

https://www.youtube.com/watch?v=FgLtdbQALC0&ab_channel=ecancer