We would love to hear your thoughts about our site and services, please take our survey here.
London South East prides itself on its community spirit, and in order to keep the chat section problem free, we ask all members to follow these simple rules. In these rules, we refer to ourselves as "we", "us", "our". The user of the website is referred to as "you" and "your".
By posting on our share chat boards you are agreeing to the following:
The IP address of all posts is recorded to aid in enforcing these conditions. As a user you agree to any information you have entered being stored in a database. You agree that we have the right to remove, edit, move or close any topic or board at any time should we see fit. You agree that we have the right to remove any post without notice. You agree that we have the right to suspend your account without notice.
Please note some users may not behave properly and may post content that is misleading, untrue or offensive.
It is not possible for us to fully monitor all content all of the time but where we have actually received notice of any content that is potentially misleading, untrue, offensive, unlawful, infringes third party rights or is potentially in breach of these terms and conditions, then we will review such content, decide whether to remove it from this website and act accordingly.
Premium Members are members that have a premium subscription with London South East. You can subscribe here.
London South East does not endorse such members, and posts should not be construed as advice and represent the opinions of the authors, not those of London South East Ltd, or its affiliates.
Https://x.com/edison_inv_res/status/1742576663190225271?s=46&t=_cUs6qcowyQbbF4MoPYSCw
Hi August it would be great to see movement on 1802 full stop as long as we see it going forward I’m sure would make everyone happy and add value to the SP hopefully being first in class ,interesting times ahead with 1801/737
GLA
News due soon for the single ascending dose (SAD) part of P1a should be completed now and data finalising, let's see if the bod capitalise on the opportunity and RNS to gain some attention.....
Sareum Holdings plc today announces Positive Topline P1 SAD Study Results for SDC-1801
Hi Gunner,
My understanding, from one of the presentations, I think it was Tim that mentioned that successful P1a progression of 1801 through the safety part of the trial , would negate the need for same with 1802 and that administration could proceed directly with patients . That’s my recollection, I stand open to correction though.
Good post AugustDestiny - hopefully the link says it all especially the pipeline
https://sareum.com/research-development/
Hi August are you sure 1802 can go into patients just on 1801 safety results ? Do we not need to do the toxicology studies first ?
GLA
Some decent postings over the last couple of days.
After patiently attending the AGM and following the SRA737 RNS, I'm none the wiser of where we are at the moment - given the various snippets I picked up from the meeting, I continue to be optimistic but go back to the step by step analogy and await the next news.
@ SOG I didn't realise home was just across the border in Suffolk, plenty of breweries for a decent pint for when hopefully we can celebrate Sareum - presume Sizewell is a vocation hub?
GLA
Evening all,
Just a few munterings as T2 used to say.
I’m here invested here approaching 4 yrs now, a ‘newcomer’ some might say ! Average buy-in about the 1p mark, old money. My initial investment was made on the basis of the value I saw then for a company involved in studies in both autoimmune and oncology research. I took a medium term view, prepared to await the opportunity to get into trials.
The company have stated, in my time invested anyhow, that the aim was to deal/ licence at pre/ early clinical. If I was willing to invest back then, with the molecules only at lab stage then with the progress to clinic now, I’m more comfortable now with P1a at /nearing it’s completion, before the data readout. As SOG has clearly highlighted the importance of this final Biomarker part of the phase, in a recent post, we eagerly await the successful conclusion and hopeful progression to P1b.
The BOD still advise that the trial is proceeding so, as the SP hovers at these levels,given where we are now, I believe the disconnect to be greater than ever before and hence I’ve been a buyer over the last fortnight, at levels I honestly didn’t think I would get to avail of again.
I also believe interest from prospective partners/ suitors and will increase markedly if the safety box has been ticked.Remember that 1802 can be administered to patients with confirmation of 1801 safety.How much extra value does that bring ? Finally, I’m always conscious of the fact that there are relatively few shares in SAR at the 72m mark or thereabouts (albeit some more will duly be allocated to RF ) So as daily volumes are tiny at present, positive 1801 safety news will IMO bring new levels of interest and hopefully the SP moves accordingly. 737 is at last licensed and we await news on both the licencee and the pathway forward . Maybe the next piece of news on that front could be receipt of the initial payment due under the terms of the agreement.
GLA, onwards and hopefully soon,Upwards !
About 1 in 44 men will die of prostate cancer
In our study, SRA737 exhibited significant single-agent activity in suppressing CRPC tumor growth and metastasis in a TRAMP mouse model. It was also well-tolerated in the 4-week treatment study, with no consequential body weight loss or gross toxicity. These preclinical data support the potential of SRA737 as a treatment for CRPC. CHK1 inhibitors have been investigated in many clinical and preclinical studies. Despite their promising therapeutic potential [12], the low selectivity and toxicity often associated with CHK1 inhibitors have been the primary roadblocks for translating these agents to the clinic [32]. SRA737 is a newer generation and highly selective orally available CHK1 inhibitor that exhibits >1000-fold selectivity against CHK2 and CDK1 (IC50: 0.32 nM for CHK1 and 697 nM for CHK2) [33, 34]. SRA737 demonstrated favorable safety and efficacy when combined with gemcitabine in preclinical non-small cell lung cancer (NSCLC) and MYC-driven B-cell lymphoma mouse models [33]. Importantly, recent reports from the only two clinical trials on SRA737 in advanced cancers (NCT02797964 and NCT02797977) demonstrated unique features of this drug, including lower myelotoxicity and higher but manageable GI toxicities that are distinct from other CHK1 inhibitors examined in the clinic [18, 35]. Particularly, despite no complete or partial RECIST responses were observed in one trial that included 13 mCRPC patients, 8/13 (61.5%) mCRPC patients showed stable disease after four cycles of therapy, demonstrating its potential for use in combination therapy.
In summary, our study identified WEE1 and CHK1 kinases, two critical DDR and G2/M checkpoint regulators, as potential novel therapeutic targets for CRPC. We further demonstrated the efficacy and tolerability of the WEE1 inhibitor AZD1775 and CHK1 inhibitor SRA737 as single agents and in combination for CRPC/NEPC treatment in a transgenic mouse model of advanced prostate cancer. Our findings provide solid preclinical support for the further evaluation of these agents for the treatment of lethal prostate cancer.
Elcap - absolutely!
Well it does demonstrate that SAR737 works really well in a combo. Just have to find a partner drug that is tolerable.
AZD-1775 (adavosertib), was discontinued by AstraZeneca, due to its low tolerability…..unlikely therefore that this paper furthers the aims of SRA737.
Interesting to see Nature posting up a paper that came out back in November '23 - was posted here on Nov 13th :)
ATB
Great find Damion
Someone will need to wake them up first .. God knows how they are managing to fill their days at the moment with no more development work and all progress being undertaken by 3rd parties .....
Feels like something SAR should at least tweet.
Https://www.nature.com/articles/s41388-024-02939-z
WEE1 and CHEK1 (CHK1) kinases are critical regulators of the G2/M cell cycle checkpoint and DNA damage response pathways. The WEE1 inhibitor AZD1775 and the CHK1 inhibitor SRA737 are in clinical trials for various cancers, but have not been thoroughly examined in prostate cancer, particularly castration-resistant (CRPC) and neuroendocrine prostate cancers (NEPC). Our data demonstrated elevated WEE1 and CHK1 expressions in CRPC and NEPC cell lines and patient samples. AZD1775 resulted in rapid and potent cell killing with comparable IC50s across different prostate cancer cell lines, while SRA737 displayed time-dependent progressive cell killing with 10- to 20-fold differences in IC50s. Notably, their combination synergistically reduced the viability of all CRPC cell lines and tumor spheroids in a concentration- and time-dependent manner. Importantly, in a transgenic mouse model of NEPC, both agents alone or in combination suppressed tumor growth, improved overall survival, and reduced the incidence of distant metastases, with SRA737 exhibiting remarkable single agent anticancer activity. Mechanistically, SRA737 synergized with AZD1775 by blocking AZD1775-induced feedback activation of CHK1 in prostate cancer cells, resulting in increased mitotic entry and accumulation of DNA damage. In summary, this preclinical study shows that CHK1 inhibitor SRA737 alone and its combination with AZD1775 offer potential effective treatments for CRPC and NEPC
And conveniently being shown as a sell - likewise the previous 10k trade at 50.11 is a buy by me.
Happy days with the usual MM's shenanigans!!
GLA
Exactly 50p per share when I just topped up another 600 SAR shares to make my holding a nice round number. Dummy sales shows 48.9p to sell shares - closely squeezed...
My young son's favourite TV programme... I am hoping for the reveal to turn us into a blue day today, just like the hope of a blue number that everyone has when they pick a box on the TV show... GLA!
I noticed that today on Endpoints a survey by Harris has shown that oncologists want more options for treating late stage NSCLC (Non Small Cell Lung Cancer). SRA737 went up against NSCLC when with Sierra. Just wondering if it will be further advanced with the new licencee. The oncologists stated than none of the current immuno therapies were rated as excellent. Maybe we can change that??
For the point of view of investors potnak it boils down to how much faith we have in the Compound.
I am 100% in faith with Compound
Bringing an investor on board with no understanding of the history is extremely difficult in current financial climate.
Phase1 data being good we will get an update on the most important aspect is how interested perceive and interpret this data with corresponding informal discussions.
Tyk2 compounds are a hot topic. Tyk2 with corresponding addition of Jaki inhibitors even hotter , but safety profile here is of paramount importance
Your 2 billion valuation at later stage is achievable on good results.
As I have said before we do not k ow what is going on in the background.
Deals are not made overnight. It takes years sometimes to reign in a reputable company to invest or whatever means to come to mutually agreeable financial arrangement.
Tablet formulations while less expensive to produce run the risk of a percentage of the tablet running through the entire gastrointestinal tract undigested and the administration and up take to the body is compromised.
Pit a value on this at end of phase 1 a trial. Any upfront significant payment or partnership contribution will remove the need for the parasitic life blood sucking effects of the likes of RF. A smaller up front payment and financial deal may be the downside, the upside of course would be the removal of the vital but poor finance package with RF.
Easier said than done, bit we need to produce satisfactory safety data from dose escalation to get the ball running.
Regards to all.
Some decent posts and contributions of thoughts today here on the whole.
No way will Sareum say they will licence at end of phase 1a. As stated by the board before they are looking to on licence at end of stage 1b.
If we look back close to 3 years ago Tim stated it was their objective to licence 1801 to raise the funds to develop 1802.
The number one problem exists as to funding. Sareum cannot continue on its present course of funding by the likes of sharks like RF. Disastrous!
However, has been stated by the board that interested parties are saying give us some data.
That data is in the process of being derived ie safety profile data plus biomarker data.
Without doubt the most important data is this safety date as that is required as a precursor to enable the selection of Indications that SDC1801 can treat, psoriasis being a minimum.
Various other Indications of potential can then be selected by the information of biomarkers.
This has a 2 pronged approach. Safety profile and efficacy are very closely correlated.
Many compounds can have efficacy in various Indications and when entered into clinical trial end objectives may or may not be met on efficacy but the down side is toxicity and off target side effects. That is it in a nut shell. Deucravacitinib is not as far as l am concerned ever going to make headway into UC.
Initial dosing strategy resulted in end points not being met. They were then evaluating higher dosaging but concerns as to compromising safety profile. Clearly pure allosteric Tyk2 is not in line with all the hype made by BMS.
Once a compound shows a promise in an indication and is granted to be used for treatment a company will look to commercialise it in other Indications. Some will work and many will not and that is why there are so many late failure stage results pointinting to poor statistical failure rates.
Correct me if l am wrong but l believe SDC1801 dose escalation taken up to 300mg per day.
Sareum originally stating that the treatment range would be up to a maximum of 1000 mg per day. Dosing in pre clinical gave no adverse effects up to 30 times treatment dosesge.
A nice problem to have said Tim but it may come back to bite us. We'll it did with the MHRA.
Back on course, now should the results of the clinical dose escalation data prove no adverse events then it will be game on. Our compound will then have a value. This value can then be significantly enhanced by clinical.data in an indication.
You are looking at approximately 3 to 5 times an increase in value by going from phase 1 success to either phase 2 or a phase 1b.
So at what point l ask does an interested party chose to become involved?
As the compound achieves milestones then so does the value go up significantly.
On top of this we have excellent long life patent protection, and a capsule as a method of oral administration. A capsule has significant advantages over tablet formation with regards to uptake of co