Member Info for HotblackDesiato

Came across a Chinese patent granted in March to Shandong University (see link below) where CHK1 inhibitors are used to improve early embryo development (I was just as amazed at this as you are). US and Europe applications are also on file.

https://worldwide.espacenet.com/publicationDetails/description?CC=EP&NR=4330376A1&KC=A1&FT=D&ND=3&date=20240306&DB=EPODOC&locale=en_EP#

'The general inventive concepts are based on the discovery that mammalian fertility and embryo development can be enhanced by a CHK1 inhibitor. A method for treating human infertility is disclosed. The method comprises identification of an individual having altered CHK1 function and administering a therapeutically effective amount of a CHK1 inhibitor. Further, embryonic development can be enhanced by the use of a culture medium comprising CHK1 inhibitor.'

If you scroll right down to the bottom of the page in the above link, table 9 lists the inhibitors covered and their source:

UCN-01 Phase 1, 2 US; Canada General I inhibitor

Prexasertib (LY2606368) Array/Eli Lilly Phase 1 US General I inhibitor

IC-83 (LY2603618) Array/Eli Lilly Phase 1, 2 US General I inhibitor

MK-8776 (SCH 900776) Merck Phase 1, 2 US General I inhibitor

AZD7762 AstraZeneca Phase 1 US; Japan General I inhibitor

CBP501 CanBas Phase 1, 2 US General I inhibitor

XL844 Exelixis Phase 1 US General I inhibitor

PF-477736 Pfizer Phase 1, 2 US General I inhibitor

SRA737 Sierra Oncology Phase 1, 2 UK General II inhibitor

GDC-0575 Roche Phase 1 US General II inhibitor

LY2880070 Esperas/Eli Lilly Phase 1, 2 US; Canada General II inhibitor

M4344 Merck Phase 1, 2 US; Canada

BEBT-260 BeBetter Medicine

CCT245737 MedChemExpress

CHIR-124 MedChemExpress

SAR-020106 InvivoChem

PD0166285 MedChemExpress

SB-218078 MedChemExpress

Chk1-IN-5 MedChemExpress

CCT244747 MedChemExpress

What will they think of next?

Hi Aber - I believe the BoD's plan is to look for non-dilutive funding e.g. give us £Xm and you get a % ownership of 1801.

I don't think Tim & John have worked on their compounds for so long to effectively give away the company for peanuts. They'll want a big payday more than any of us. Looking at their ages, they'll be more inclined to go for, say, £4+ a share for the whole company rather than some sort of lowball £1.50 per share and some sort of lucrative post working at the Big Pharma for a few years.

With 1801/2's potential we should be worth more than we were at peak covid prices.

Whilst out for a wander I was thinking over my first point re deliberately shelving 737 and as others have suggested, if the licensee intended stopping development, why would they offer shares in themselves as part of the deal? CPF would have known the rough value of the company prior to signing the deal so either they couldn't care less about the money side (as Meg points out) or they've been told the bigger picture e.g. Company X is currently of little material value however once they've developed 737 they'll be worth a fortune therefore shares will be of greater value in time.

Though I agree with the notion that CRUK aren't interested in money as such, the greater the financial income from any deal means the more they can spend on research into other types of cancer therefore they walk a bit of a tightrope between giving something away for peanuts to see it advanced quickly but they wouldn't say no to a billion pound deal as they could put that to very good use.

So the supplementary question is, are CRUK at odds with their financial arm, the CPF? CRUK needs funding and the CPF are the tool to make it happen through license agreements.

Hi Warthog - it's the mystery that keeps on giving. Almost 9mths down the road since the license deal and complete radio silence. The question we have to ask is who benefits from 737's removal from public scrutiny?

Possibilities -

1. Company with similar drug wants 737 off the market. For a relatively low price they've shelved the opposition and used up some of the 737's patent protected lifespan.

2. It is actively undergoing development but for unknown reasons the licensee wants to remain anonymous for now. Nothing nefarious, just someone keeping their powder dry.

3. It's part of some larger game being played. Once 1801 data is released, will 737's licensee come out of the shadows to make a T/O bid?

Hope you're back to normal after your op.

Regards.

Just wondering if 1801 could be used to tackle the cytokine storm caused by Mpox. A study on its pathogenesis, prevention, and treatment (link below) notes, '...severe Mpox infection often leads to a cytokine storm in later stages. This results in an increase in Th2-associated cytokines and a decrease in Th1-associated cytokines, characterized by increased expression of IL-2, IL-4, and IL-8 and a reduction in TNF-α, IL-2, and IL-12'.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10751291/

Just as a reminder from the 3/12/20 RNS (link below), "Covid-19 is caused by the virus SARS-CoV-2 and usually results in a mild disease that resolves on its own. However, some patients develop a potentially fatal severe disease due to inflammation arising from an overreaction of the immune system, known as CRS or a 'cytokine storm', leading to Acute Respiratory Distress Syndrome (ARDS), requiring intensive care. A major inflammatory pathway mediated by TYK2/JAK1 - the Interferon Type 1 pathway (Type 1 IFN) - is over-activated in severe Covid-19 patients and this pathway may be able to be blocked by SDC-1801.

Recently, researchers have observed the similarity between severe Covid-19 and the acute flares of lupus, an autoimmune disease characterised by overproduction of Type I IFN1. As Sareum reported in July 2020, SDC-1802, a close analogue of SDC-1801, demonstrated encouraging results in a disease model of lupus. The Company believes that SDC-1801 could potentially benefit severe-phase Covid-19 patients by blocking signalling along this inflammatory pathway and therefore reducing the 'cytokine storm'."

https://www.lse.co.uk/rns/SAR/covid-19-research-grant-confirmed-jl5vz09rz1662oy.html

Can't be long until the wider pharma community wakes up to what we have.

Regards.

I've read that vaccines cause adults. Though perhaps some would prefer smallpox to be just part and parcel of daily life.

It baffles me why those subscribing to conspiracy theories would invest in a sector so riddled with evil companies. Who's to say Sareum aren't part of the plot? I mean Tim once farted and blamed it on a nearby dog so, you know, it's a slippery slope from there. #justsayin'

I see we're off to Amsterdam next month for the European Academy of Dermatology & Venereology Congress - https://eadv.org/

https://sareum.com/events/

Just in time for the P1a results to be announced.

Not quite, Jinky. Just head north from there until you reach civilisation.

Hi Delta - I'm about halfway between Edinburgh & Glasgow so I'm a sort of Weegie with an Edinburgh accent. A mixture of Tongs ya bass and you'll have had your tea (two phrases that will be meaningless to our chums south o'ra border).

Lashing rain forecast for tomorrow so normality returns.

That's actually an interesting point, SOG. Now here's a nice problem to have - if you have a molecule that could target cancer AND autoimmune diseases, which road do you initially take it down? This is where a big enough deal for 1801 could give us lots of options for 1802's progress.

Just for info -

Chemotherapy Drugs Used for Autoimmune Diseases:

Methotrexate: Approved for treating rheumatoid arthritis, psoriasis, and various forms of cancer, it's also used for managing multiple sclerosis, lupus, sarcoidosis, and ectopic pregnancy. Its effectiveness in autoimmune diseases is attributed to its immunosuppressive properties.

Cyclophosphamide: Frequently used for rheumatoid arthritis, multiple sclerosis, lupus, and sarcoidosis. It requires careful monitoring due to potential side effects like hemorrhagic cystitis.

Mercaptopurine: Utilized for inflammatory bowel diseases, including Crohn’s disease and ulcerative colitis. It may cause significant malaise and myelosuppression, necessitating regular blood counts and liver function tests.

Mitoxantrone: Commonly used for MS and certain cancers. It can cause unique side effects like bluish-green urine discoloration and cardiotoxicity with long-term therapy.

Biotherapy Drugs Used for Autoimmune Diseases:

Infliximab: A biotherapy drug that, when combined with methotrexate, can effectively treat rheumatoid arthritis. It works by inhibiting tumor necrosis factor, a key factor in autoimmune inflammation.

Immunotherapy for Both Cancer and Autoimmune Diseases:

Nivolumab (Opdivo): An immune checkpoint inhibitor approved for various cancers. There's anecdotal evidence suggesting it can be safely used in patients with both cancer and autoimmune diseases, though further research is needed to confirm its safety and efficacy in this population.

Using drugs originally intended for cancer treatment in autoimmune diseases can lead to side effects typical of chemotherapy, such as neutropenia and immunosuppression (which is the whole point of the exercise!).

It would appear summer has finally reached my part of Scotland so off for a long walk.

Hi Aber - Not all potential oncology drugs go through Phase 1 trials (as SOG reminded me). Phase 1 trials are primarily focused on assessing the safety of a new drug or treatment in humans for the first time. They aim to determine the maximum tolerated dose, identify potential side effects, and understand how the drug behaves in the human body.

That said, drugs that might skip Phase 1 trials altogether typically fall into categories where preliminary evidence suggests they are highly unlikely to cause significant harm or where their mechanisms of action are so well understood that their safety profile can be reasonably predicted. From what I gather 1802 is very similar to 1801 and so there may well be some 'carry over' from 1801's safety profile to 1802. The decision to enter 1802 into P1 trials though will depend on several factors; its mechanism of action and potential effectiveness based on preclinical studies - this is where the translational studies and toxicology report will come in to play.

Regards.

Hi C79 - not sure if this link is of any use to you in your who-owns-what search: A Comprehensive Overview of Globally Approved JAK Inhibitors https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9146299/

Yes SOG, when I've been poking about on the US clinical trial register I'd noticed quite a number of studies had Chinese sponsors.

Nothing though leaps out at me when I do a search for trials registered since 1/1/24 that utilise Gemcitibine and/or Cisplatin so I think I've exhausted all avenues of investigation for now. Even if we knew if 737 has been renamed (without knowing what that name is) would be some sort of progress for those of us who like to dig.

Mind you, I also wouldn't be surprised to eventually discover 737 has been hiding right under our noses all this time.

Hi SOG - aha, good point re there being no requirement for a P1 trial in oncology. All that women's beach volleyball has fogged my brain somewhat.

Regards.

Hi SOG, I agree that 737 should be in P3 trials by now having completed two P1/2 trials via Sierra but the internet isn't able to pin anything down.

Am I right in thinking a P3 trial would have to be a continuation of the Gemcitabine & Cisplatin or Gemcitabine alone trial, otherwise any other combo trial would be back to square one i.e. a phase 1 trial?

Just on the off-chance a study was quietly getting under way in China, I looked at their trial register but found no reference to 737 (perhaps the name has changed?). Also there're only 6 trials since 2009 utilising Gemcitabine (see lengthy link below).

https://www.chictr.org.cn/searchprojEN.html?title=&officialname=&subjectid=®status=®no=&secondaryid=&applier=&studyleader=&createyear=&sponsor=&secsponsor=&sourceofspends=&studyailment=&studyailmentcode=&studytype=&studystage=&studydesign=&recruitmentstatus=&gender=&agreetosign=&measure=Gemcitabine&country=&province=&city=&institution=&institutionlevel=&intercode=ðicalcommitteesanction=&whetherpublic=&minstudyexecutetime=&maxstudyexecutetime=&btngo=btn

Perhaps a 7am RNS tomorrow will reveal all!

The number of papers to have referenced SRA737 is encouraging despite any visible progress from the current license holder. This time it's the 'Pivotal Role of Preclinical Animal Models in Anti-Cancer Drug Discovery and Personalized Cancer Therapy Strategies'.

https://www.mdpi.com/1424-8247/17/8/1048

"In preclinical studies for neuroendocrine prostate cancer (NEPC), Nest et al. found an increased expression of WEE1 and CHK1 in NEPC cell lines, leading them to explore the potential treatment using a synthetic lethal combination of Wee1 and other inhibitors. Their experiments using NEPC transgenic mouse models demonstrated that treatment with the Wee1 inhibitor AZD1775 and CHK1 inhibitor SRA737 effectively inhibited tumor growth, providing a promising approach for NEPC treatment."

Although it's really only a passing reference to 737 here, I can't be alone in noticing that there are quite a few papers coming out of China that either used 737 directly in their research or make some other reference to it. Dang frustrating to read positive comments on a global level yet the drug appears in limbo.

I wonder if the private US biotech holding 737 is owned by a Chinese pharma. Now there's a thought.

Hi SOG - I'll trade you one long read for another, though you may have already seen it:

Novel Therapies in Plaque Psoriasis: A Review of Tyrosine Kinase 2 Inhibitors - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9884727/

Hi Krone - I don't think any of their various subgroups have an oncology interest, instead they seem more focused on immunology therefore 737 might not be on their radar. As their Priovant website says, '... is developing brepocitinib across multiple severe autoimmune diseases with few approved therapies and pathobiologies aligned with the distinctive benefits of dually inhibiting both TYK2 and JAK1.'

However they'll no doubt have one eye on 1801.

Regards.

Hi Leggster - I think you can only develop a very loose strategy simply because there are so many possibilities and variables. A bit like a General having a battleplan. As soon as the first shot is fired the plan goes out the window.

Much would depend on the nature of any on-license. Is the licensee relatively unknown or a global player? What are the terms of the deal - small upfront payment but vast milestones? Maybe a larger upfront payment but they want a seat on the Board. What if the deal was with the same anonymous biotech that has 737? Now that really would raise eyebrows.

If a big enough pharma was serious about 1801 would the BoD chance their arm and ask if they'd be interested in acquiring the whole company?

For all we know the BoD are already considering one pharma's license deal against another's informal offer of a T/O. Then again, maybe the office phone hasn't rung in weeks!

Regards.

Hi Andy - nice to know there are proactive shareholders who are willing and able to engage as best they can with the BoD. It'd be good to remind the BoD that they have a number of ways to keep us informed of progress that don't require an RNS e.g. they could Tweet/X when the data has been unblinded or if the data package is nearing completion - I don't think either would be considered shareprice critical (if that's the right term).

Since we appear to have completed P1 as far as it'll ever be (assuming no P1b), they could update the Pipeline graphic on the website too.

I'm sure they're all quite busy at the moment but these relatively minor points would go some way to let us know they're on top of things and progress is being made.

Regards.