Member Info for HotblackDesiato

Hi Hopkirk/SOG - the referenced paper was funded by two Oz charities -

https://fundraise.mater.org.au/event/smilingforsmiddy/home

and

https://www.ocrf.com.au/

The Zuckerberg link is that they (and many others) help finance the archive for the papers so not a direct link as such.

Hi Hopkirk - looks like that's a companion piece to the one I contacted SP about and he subsequently tweeted. Both papers from Oz with some overlap in contributors where they use 737+hydroxyurea. Nice find though!

https://www.mdpi.com/2072-6694/17/11/1817

Now we just need T&J to have a chat with Dr. Meldal about solubility issues and our little shop of wonders would be complete.

With advances in AI, for all we know they could tweak Flt3+Aurora with the press of a button.

For those who thought trips to Boston were just junkets for the BoD, I presume that's where they were introduced to the Receptor.AI team.

The article below was published 6/8/25 by their CEO & founder. Worth a read to understand what they do etc.

AI models hope to provide accurate predictions of ADMET properties, which remain a major bottleneck in drug discovery - https://www.technologynetworks.com/analysis/blog/beyond-black-box-models-advances-in-data-driven-admet-modeling-403114

Onwards!

Hi Mafuta - with this being a collaboration rather than SAR employing the company as they would with a CRO etc., it might be a case of both sides cover their own costs as each company will reap benefits albeit in different ways. Just a thought.

Just had a look at some of Physiomics' deals to try to gauge a cost of the venture since they're another AI research company -

"In this new project, Physiomics will apply PK/PD modelling and simulation expertise to support preclinical-to-clinical translation for one of the client's lead candidates and inform selection of human dosing schemes for a First in Human clinical trial.

This contract, which supports the development of a non-oncology therapeutic, highlights the value of Physiomics' integrated modelling and simulation approach across the drug development lifecycle - from early discovery through translational planning and into clinical development. The contract is valued at £98,600 and will be delivered over the next 18 months."

and another

"The project will involve the application of modelling and simulation techniques to support the development of a first-in-class bifunctional antibody therapy designed to target multiple solid tumour indiciations. More specifically, Pharmacokinetic modelling approaches will be utilised to predict the human PK of the molecule in order to support the client to progress this new therapy into their first-in-human study. The project is valued at £47,600 and is projected to complete over the next three months."

I wonder if the BoD poked the warrant holder with a stick and suggested their £125k could go to good use.

Hi SOG - re the dosing for the extended tox, from what I can find a possible approach might be:

Low Dose: Start at or slightly below the no-observed-adverse-effect level (NOAEL) established in dogs from prior studies to confirm safety.

Mid Dose: Select a dose that achieves plasma exposures 1.5–2 times the NOAEL or matches the highest well-tolerated dose from the Phase 1a SAD study.

High Dose: Use a dose that produces exposures 2–5 times the NOAEL or exceeds the maximum human exposure observed in the Phase 1a trial (noted to be significantly above predicted therapeutic levels). This dose should aim to induce toxicity to identify the maximum tolerated dose (MTD) or reveal dose-limiting effects.

The other thing to keep in mind is the extended tox study should also include a recovery period i.e. once you stop taking 1801 for an extended period, how long do the effects remain and does it get flushed from your system 100%?

Thankfully our furry friends shouldn't get themselves involved in hedge strimmer incidents unlike one of the human volunteers!

Time for a long walk.

Regards.

Hi SOG - IF 1801 does turn out to be best in class re tox then that would certainly attract more than one interested party. I presume the BoD are receiving data from the CRO as and when each step of the study is completed rather than having to wait 'til then end for a bulk data package. If so, they might be able to RNS mid-Sept to say if all endpoints were achieved although a complete picture perhaps won't be known for another 2mths thereafter.

Although we'll never find out, it'd be interesting to know if data is being shared with a 'preferred' potential partner as it comes in but another potential partner is having to wait for the complete results. Business in never a level playing field so I imagine there may be a pecking-order re who sees what and when.

Regards.

Hi Matty - and for all we know there could be a pharma with their own current TYK/JAK program looking for a backup plan, especially if 1801 proves to have a better tox profile than their own drug.

The next few weeks will be interesting (and quite telling!) if we see an outbreak of naysayers, doomsters and other wombles flood this board. No, we're not home and dry just yet but the science and P1a results suggest things are looking good for SAR: we just need the sp to wake up.

I'm wondering who might be a potential partner/owner for 1801 so I asked the AI bot, Grok, "Which international pharmaceutical companies do not have a TYK2/JAK1 compound in their current pipeline?"

see complete reply here: https://grok.com/share/c2hhcmQtMw%3D%3D_493c90df-1bbe-495f-9e50-687351fecd62

If the link doesn't work, an extract is below:

Major international pharmaceutical companies not mentioned in these sources as having TYK2/JAK1 inhibitors include:

1. **Merck & Co.** - While Merck has invested in immunology (e.g., Prometheus acquisition), no specific TYK2/JAK1 inhibitors are noted in their pipeline. Their focus appears to be on other mechanisms or therapeutic areas like oncology and vaccines.[](https://www.fiercebiotech.com/biotech/jpm-24-how-takeda-beat-almost-every-biopharmaceutical-company-win-nimbus-tyk2-med)

2. **Roche** - Roche acquired Telavant for immunology assets, but no TYK2/JAK1-specific programs are highlighted in the provided data. Their pipeline emphasizes biologics and other targets.[](https://www.fiercebiotech.com/biotech/jpm-24-how-takeda-beat-almost-every-biopharmaceutical-company-win-nimbus-tyk2-med)

3. **Novartis** - No mention of TYK2/JAK1 inhibitors in the provided sources. Novartis focuses on other immunology drugs (e.g., IL-17 inhibitors like Cosentyx) and broad therapeutic areas like oncology and neurology.

4. **Sanofi** - Not listed in the TYK2/JAK1 pipeline data. Sanofi’s immunology efforts lean toward biologics (e.g., Dupixent) and other pathways rather than JAK/TYK2 inhibitors.

5. **Johnson & Johnson (Janssen)** - While active in immunology (e.g., Stelara), no TYK2/JAK1 compounds are noted in the provided references.

6. **AstraZeneca** - Although listed in JAK inhibitor pipelines, their focus is on JAK2 or other mechanisms, not specifically TYK2/JAK1 dual inhibitors.[](https://www.globenewswire.com/news-release/2025/03/03/3035899/0/en/JAK-Inhibitors-Clinical-Trial-Pipeline-Appears-Robust-With-50-Key-Pharma-Companies-Actively-Working-in-the-Therapeutics-Segment-DelveInsight-DelveInsight.html)

7. **Eli Lilly** - While involved in JAK inhibitors (e.g., Baricitinib), no specific TYK2/JAK1 dual inhibitor is mentioned in their current pipeline.[](https://www.globenewswire.com/news-release/2025/03/03/3035899/0/en/JAK-Inhibitors-Clinical-Trial-Pipeline-Appears-Robust-With-50-Key-Pharma-Companies-Actively-Working-in-the-Therapeutics-Segment-DelveInsight-DelveInsight.html)

8. **Gilead Sciences** - Not referenced in TYK2/JAK1 development. Their focus is primarily on antivirals, oncology, and other inflammatory pathways.

**Caveats**:

- **Incomplete Data**: Pipeline information may not be exhaustive, as companies may have undisclosed or early-stage programs not reflected in public sources.

- **Dynamic Pipelines**: Pipelines evolve, and companies like Merck or Roche could acquire or develop TYK2/JAK1 programs not captured in the 2025 data.

- **Focus on Other JAKs**: Some companies work on other

Hi SOG - I think you mean 30mg rather than 300mg. The highest single dose was cohort E at 150mg and the highest MAD was cohort D at 70mg twice daily (the highest single dose in the MAD study was cohort B with 100mg daily).

Regards.

Keeping in mind how positive the BoD were about the Australian authorities, I presume they're working with them again for the toxicology trials. Interesting link below, one major highlight is Sareum Australia PTY should be able to claim up to 43.5% cash rebate for R&D expenses. Ker-ching!

https://www.agilexbiolabs.com/benefits-of-conducting-your-tox-studies-in-australia/

Hi Aber - whilst the BoD obviously can't manufacture good news if there's nothing to report, I presume they've been getting regular updates from the CRO and a positive RNS is almost within reach. I just hope that if we do get a boost from news it isn't torpedoed by the takeup & sale of warrants.

I think with TM taking a backseat he'd prefer one momentous final payday so that he can get on with the rest of his life rather than continue to take flak from shareholders (irrespective of whatever salary he may be on).

Regarding news, if the BoD don't understand the expectations of shareholders by now (more ra-ra-ra!), then they never will. At least 1801 is all ours and any deal will benefit even the weariest LTH.

Hope all is well at Aber towers.

Regards.

Approx. 6wks left to go on the toxicology study. Although the BoD have said they'd need a couple of months from that point to review and fully understand the data, I'd expect a mid-Sept RNS to at least say the study is complete and early indications are that it went better than hoped or that it underlines their belief in 1801 or that it's not that great but 737 might still save the day.

If good news doesn't get the sp moving then nothing will.

Hi SOG - "Deucravacitinib at multiple doses did not demonstrate significant clinical benefit versus placebo in patients with moderately to severely active CD or UC. Deucravacitinib was safe and well tolerated."

I get the feeling that the last sentence was added just to throw them a bone.

For all we know Warthog's neighbour was just acting dumb and the pharma they work for is poised to buy SAR for zillions.

I think we're all approaching the point in SAR's journey known as squeaky bum time.

Hi Warthog - when you say, 'a neighbour works for a big pharma: he had no idea what Sareum are up to', it'd help to know what their role is - are they involved in mergers & acquisitions or do they work in the canteen?

That's my thinking/hoping too, BenH.

At the ProActive event SP said they'd been talking with key opinion leaders re 737 and he hoped they'd be able to announce a plan not too far from now (that being 4wks ago).

It's a difficult one for sure - what would you do if someone only wanted 737 today but another party wanted the whole company as long as 1801 gets a clean bill of health in the tox study? Not an easy decision.

Hi SOG - I asked IR@SAR earlier in the month if we could get an update on 1802 and the reply was, "As a small company we have to prioritise where our limited cash is invested and in recent times that has been the clinical studies and now extended toxicology of SDC-1801. We are continuing to look at SDC-1802 and will report once we have meaningful progress towards the clinic to share with shareholders and the wider market."

Regards.

Hi PCS - as one recent presentation noted, '1801 is potentially a pipeline in a pill'. Quite a bold statement from people who strike me as cautious, measured and not given to hyperbole.

Whilst part of me is given to thinking this could still all go pear-shaped, everything I've read suggests the science is on the right path so our time will come.