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Today's Chairman's Corner post reminds us that there is an IND for 737 in acute myeloid leukaemia and myelodysplastic syndromes - the links below outline the current players and market size etc. (plus who knew Sauron had any need for a Middle Earth-based market intelligence company?)

https://www.mordorintelligence.com/industry-reports/acute-myeloid-leukemia-therapeutics-market

https://www.mordorintelligence.com/industry-reports/myelodysplastic-syndrome-treatment-market

It did cross my mind though, what if a prospective owner/licensee isn't focused on those specific areas? It seems an IND can be amended fairly easily (well, there's always red tape to negotiate), so the current IND focus isn't too much of a drawback if it doesn't align with a company's immediate plans.

Regards.

Hi RV84 - see below (I've edited out the bit where he says HBD is a righteous dude).

"One of the pleasures in maintaining a portfolio of development-stage drugs is that news is spread around the various programmes. Recently, a peer-reviewed study was published in the British Journal of Cancer demonstrating that SRA737, our clinical-stage oral CHK1 inhibitor, in combination with low-dose hydroxyurea shows compelling efficacy in cellular and mouse models of high-grade serous ovarian cancer, one of the most lethal and difficult-to-treat gynaecologic malignancies, with a five-year survival rate of just 35-40%. The paper, by Gabrielli and colleagues, represents an important piece of independent academic validation of SRA737’s mechanism of action and potential as an effective cancer treatment.

This publication adds to a growing body of peer-reviewed evidence supporting the therapeutic potential of SRA737 as a monotherapy or in combination with multiple cancer drugs in numerous solid and haematological cancers. Two Phase 1/2 clinical studies highlighted the clinical safety and efficacy profiles of SRA737 as a monotherapy or in combination with low-dose gemcitabine – these studies and several others highlighting the potential of SRA737, including the recent paper mentioned above, can be found on our website under News & Events / Publications.

Such validation supports our business development activities for the asset, by providing independent academic evidence of activity in a cancer indication with significant unmet need.

As previously announced on 13 March 2025 and 12 March 2026 (HY25), we hold the licence for SRA737 on significantly improved economic terms, securing 63.5% of all future revenues, and we retain both an open Investigational New Drug (IND) with the FDA for a Phase 1 trial in acute myeloid leukaemia and myelodysplastic syndromes, and sufficient capsule stock to conduct such a trial. Our specialist US-based business development consultancy is actively pursuing partnering discussions, and this publication in a high-quality, peer-reviewed journal provides compelling third-party evidence that supports those conversations.

While this is early-stage translational research, we are pleased to see continued high quality and rigorous data providing a meaningful mechanistic rationale for SRA737’s potential to treat ovarian cancer.

Our primary focus remains on advancing SDC-1801 through its Phase 2-enabling toxicology programme and towards clinical development. We are equally committed to realising the value of the broader portfolio, and SRA737 remains an important part of that. I look forward to updating you as our business development efforts for the asset progress."

On the other hand, it could be linked in some way to a paper I was looking at the other day - https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/bph.70259

"The authors also show that inhibition of CHK1 with CCT245737 or that of JAK1 with upadacitinib limited hypertrophy, fibrosis and functional decline, even without lowering blood pressure. For the pharmacology community, this is a particularly notable finding because it places Ang II signalling in the heart, firmly beyond its haemodynamic effects."

and

"CHK1 inhibition with CCT245737 clearly improved outcomes in the study and earlier work has already described this compound as selective and orally active (McDonagh et al., 2021; Walton et al., 2015). But blocking CHK1 systemically raises predictable concerns about DNA repair in proliferating tissues. This suggests that CHK1 inhibition may be better suited for short-term use for example, in acute hypertensive stress rather than as a chronic strategy."

Hi Ben - oddly, I also had the same thought!

Abstract 5518 is "Population-based prediction of cardiovascular mortality in gynecologic cancer survivors using machine learning (RISKHEART)."

https://www.asco.org/abstracts-presentations/258101

Not sure where 737 fits into this presentation.

Hi Celtic - none of us know what the future holds so If someone says the whole company is worth X but another person says a single compound is worth twice that, who do you believe? Over the years many have put forward valuations and whilst they may have been notionally accurate, none have been realised through commercialisation.

You've been here a while now so I expect you have a few different exit routes for your investment based on your own experience.

All that said, I think we'll see a 737 deal before autumn with perhaps more to follow.

Just musing - I'm beginning to think the reason why the mystery US startup couldn't raise funds for 737 was maybe just down to the remaining patent life at the time, an issue that has since been addressed. Didn't TM mention something about £800m once upon a time? I forget the details surrounding the proposed figure but the landscape changes and with it, further papers appear suggesting 737-combos could be effective in more areas.

Could be a long hot summer.

Hi Elcap - the April Chairman's Corner should pop up this week so hopefully it'll confirm the tox study is on track. It'd be great if the BoD could report that interest in 737 is hotting up after that BJC paper was published earlier in the month. Question is, what if one party just wants 737 but another wants everything but only if 1801 tox is top-notch?

Regards.

I'm not saying it's like for like but Eli Lilly is paying $3.25 billion in upfront cash for Kelonia Therapeutics and its phase 1-stage myeloma therapy.

https://www.fiercebiotech.com/biotech/lilly-picks-another-vivo-car-t-company-7b-deal-kelonia

Now compare our pipeline with Kelonia's - https://keloniatx.com/pipeline/#pipeline

The money is out there.

Hi Celtic - there can be strategic reasons for wanting a paper to be published at the right time, either to get the jump on a competitor or to wait and see what a competitor announces re their own drug. If you can publish a paper to show your drug is superior to a competitor's own hot-off-the-press data then you'd possibly hold back your paper in order steal a competitor's thunder.

It could also come down to wanting to dovetail publication with a new round of funding e.g. if you can publish just before you seek funding for the next stage of development then it might be easier to get when your drug is the talk of the town.

JR has said the paper on 1801 has been submitted to a journal so the publishing is out of our hands. At least if it was rejected for not being novel enough we'd probably know by now.

A web search would suggets getting a paper published can be a long process: the Journal has to approach the right (unpaid) reviewers and hope they are available. Even if a reviewer accepts the invitation, they might not get round to looking at the paper. The Journal may then wait weeks before reassigning. If one reviewer says 'pass' but the other says 'fail' the Journal editor then has to step in etc. etc.

https://edinburghuniversitypress.com/publish-with-us/early-career-researcher-hub/authors-guide-to-peer-review/why-does-peer-review-take-so-long

I've looked at a few reviewer comments on random papers and and there can be an endless back and forth between reviewer and writer arguing over the minutiae of charts and tables. Then there's a reviewer who deliberately kicks things into the long grass in order to delay publication....

From our own perspective, I think JR may have preferred to have been able to include P1b data on psoriasis patients but things rarely go to plan.

Regards.

Article - How are global macro trends and pharma catalysts pushing Sareum Holdings higher?

https://kalkine.co.uk/news/general-news/how-are-global-macro-trends-and-pharma-catalysts-pushing-sareum-holdings-higher

I've e-mailed SP asking if he could maybe address the issue of establishing 1801's MTD in the next Chairman's Corner - if the current tox study can't define it then what steps might be taken to ensure it isn't a problem further down the road.

I also pointed out the Q&A has vanished from the IMC March event.

Regards all.

Hi DJ - Re MTD, didn't JR say it's a nice problem to have but it could come back to bite us?

If a drug trial cannot establish an MTD then it may lead to suboptimal/skewed dose levels in subsequent clinical trials, potentially compromising the safety and efficacy of the drug. This failure can hinder the drug's progression to later phases of testing and may result in the discontinuation of its development.

Alternative methods for determining safe dosage levels in clinical trials include parallel dose comparison studies, cross-over designs, and dose titration studies. Also, AI can enhance dose selection by predicting safety and efficacy, thereby reducing risks associated with human trials.

I presume the P1a trials in Oz wouldn't have gone ahead without the authorities knowing all the preclinical work and corresponding tox studies.

MTD studies define the highest dose of a drug or therapy that does not cause unacceptable side effects or toxicity. In the P1a trials the main side effects were headaches and/or dizziness. No idea if the headaches were mild or really bad. I suppose it could be a bit of a grey area to say although we couldn't find a toxic dose, enough people complained of really bad headaches so we'll use that as the limiting factor.

I'm not a doctor so take all the above with a pinch of low sodium salt however I'm sure JR & TM will know all the risk factors and will have taken advice at every stage of trying to establish the MTD.

Hi C79 - re 737, in section 8.1.2 of that link it notes, "Further trials are currently underway or scheduled in the future, encompassing combinations with agents such as the PARP inhibitor niraparib". I'm not aware of any current clinical trials so I presume they're more likely talking about preclinical research. As for "scheduled for the future", since the FDA doesn't publish any info on INDs I doubt the paper's authors would have any insider info unless this is again just an educated guess on their part relating to preclinical work.

Fingers crossed that official news on 737 isn't far away.

A steady 20% rise each day for a couple of weeks is just what we need.

Hi Celtic - will 737 be taken up by someone? My one concern was the remaining patent life however that has been addressed and now it's patented out to at least 2041 so 737 will have become much more attractive. Also note that Sierra applied for a number of '737 in combo' patents and all intellectual property was handed over when 737 was returned. Every cloud has a silver lining.

I believe a deal will be done this year but I've no idea what shape it'll take. I think the BoD alluded that they don't want to see any more share dilution (or at least keep it minimal), so that probably means some sort of deal where we give a decent percentage of 737 away but the partner/new owner carries the can on the funding of new trials .

SP has noted there's more than one interested party and I don't think anyone could make an offer that also prevents us from informing others that a deal is on the table - we have control so it's our perogative to start playing one off the other if there's equal interest. Bidding wars are a great spectator sport if you're the beneficiary. I just hope the BoD play hardball but not to the extent they put buyers off - step forward Michael Owen!

Just remember one thing though - I have never predicted anything correctly here in all my years.

Regards.

Hi Bailiff - I think once we get back into the 20s we might see a few mid-size sells as some hope to 'rinse & repeat'. Fingers crossed those days are finally behind us and any retrace will be a minor event ahead of greater gains - I don't breakeven until 32p!

Celtic - assuming the tox study gets completed in a couple of months time, it'll still take months thereafter to fully review the data ahead of prepping a P2 study package. At least we're beyond the previous point of failure so I presume the vehicle is working as intended.

Lots of news to come this year on all fronts.

Thanks Nav.

I don't have access to L2 but would that show any unfilled large orders?

An interesting read on manipulation - https://discoveryalert.com.au/automated-trading-dark-side-2025-manipulation/