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That's right Potnak, T & J will probably only know if there's been any major adverse effects. Since 1801 did well in the preclinical tox report, I doubt we'll see anything that would prevent 1b taking place.

Hi Potnak - as far as I'm aware both 1a & 1b are double blinded so the doctors handing out the medication don't know if the patient is getting a placebo or the real drug. Only a couple of people at the dispensary will know what they are handing to the doctor. It's only once the trial is complete that the results become unblinded and they know who took what. That way there can be no influence on the patient or doctor i.e. they've given some pills to a patient who then begins to feel unwell but they won't know if it's down to 1801 or some placebo effect until the trial is over.

As far as placebos go, the mind can play many tricks on our body. Studies have shown the colour of a pill has an impact on efficacy e.g. people respond better to red pills over yellow pills and 2 pills must surely be better than 1 pill etc. An injection is perceived to be more potent than a pill and so on. There are also studies that have shown that even when someone knows they are taking a placebo, they feel it has a positive impact.

When I posted that link a couple of days ago I meant to also include the one below on JAK inhibitors & the herpes virus as one of the doctors in the original article noted a patient developing the viral infection.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7328488/

It looks like JAK1 might be the pick of the bunch as the paper notes, "Emerging and pooled data may suggest that inhibition of JAK 2 and JAK 3 may be associated with a higher risk of VZV infection, while selectivity for JAK 1 may be associated with a lower risk of zoster infection."

Still all to play for and P1b results (if we ever get there!) should catapult us forward.

Hi SOG - the unfortunate thing is that since there is so much money to be gained or lost by big pharma, industrial espionage and other cloak and dagger shennanigans is almost common practice. I've mentioned a book, Bad Pharma by Ben Goldacre, before and the wiki link below is certainly worth a read if people don't have access to the book (especially the Bad Regulators section that talks about the MHRA).

https://en.wikipedia.org/wiki/Bad_Pharma

Regards.

Just had a look at what Sotyktu (deucravacitinib) costs and it's eye-watering. I know pharma has to recoup costs etc. but I didn'r realise it was so expensive -

"BMS has set a list price of $6,164 for a 30-day supply of the new drug, which is around 42% higher than the $4,344 Amgen charges wholesalers for a 30-day supply of Otezla, ahead of any discounts or rebates."

https://pharmaphorum.com/news/bms-scores-first-approval-for-psoriasis-therapy-sotyktu

And sur le continent it's 10,000 euros for 30 tablets - https://everyone.org/sotyktu-deucravacitinib

IF 1801 can equal or better it in the clinic then it could be a nice little earner. Surely funding can't be too difficult!!

Not a single comment re this over on the RGO board - must tell you something about the company.

Thanks for the update, chaps.

I hope the BoD can pull a rabbit out of the hat next week when they publish the first half results which should hopefully also outline their plans for the immediate future. With the new tax year just a fortnight away I'm expecting them to announce a public offer to help get 1801 across the line.

Hi SOG - just as a sidenote, it's sometimes interesting to learn about the patient's experience of a new drug and since Deucravacitinib/Sotyktu seems to be the current yardstick, the link below might be of interest -

https://www.dermatologytimes.com/view/deucravacitinib-a-year-in-review

Hi SOG - the paper certainly gives a good indication that 1801 (formerly SAR-20347) should perform very well in the clinic when compared to other compounds.

"Both Tyk2 mutant mice and mice treated with SAR-20347 showed significant reduction of IL-6 and IL-17 in imiquimod-induced skin lesions, but only SAR-20347-treated mice presented reduced levels of IL-23, decreased keratinocyte proliferation and improved clinical score."

and

"Blocking both Tyk2 and Jak1 in this study was more effective than inhibition of Tyk2 alone at reducing psoriasis-like disease severity, keratinocyte proliferation, as well as IL-23, IL-17, IL-6, IL-22, and antimicrobial peptide gene expression, and the authors postulate that targeting a combination of Jak1 and Tyk2 using an orally available inhibitor may be a viable approach for treating psoriasis."

Yes, the proof will be in the pudding but the smell coming from the kitchen in Oz is very good indeed.

If the BoD do read this board then they might all mysteriously have dental or hair appointments to go to later this morning.

On the other hand they might be quite happy to meet with just a couple of concerned but level-headed investors. If they are there at least try to find out who has 737!

Hi C79, apart from a bad case of the AIM blues all is well here, thanks.

As Potnak speculates on another thread, 737 might be in the hands of someone looking to quickly move it on to a bigger player. Since 737 has shown promising results when combined with PARP1 inhibitors (demonstrating synergistic effects in killing mammary and ovarian cancer cells), it might be worth looking at the current PARP front runners -

Olaparib: Developed by AstraZeneca. It has been approved for the treatment of patients with deleterious or suspected deleterious germline BRCA (gBRCA)-mutated advanced ovarian cancer who have been treated with three or more prior lines of chemotherapy, as well as for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, who had a complete or partial response to platinum-based chemotherapy.

Rucaparib and Niraparib: Developed by GSK. Rucaparib has been approved for the treatment of ovarian cancer associated with HR deficiency and for patients with deleterious BRCA-mutated metastatic castrate-resistant prostate cancer. Niraparib was initially approved for ovarian cancer associated with HR deficiency but later expanded to patients with ovarian cancer regardless of their HR-deficient status.

Veliparib: Developed by AbbVie. It is undergoing phase 3 clinical trials as a combination therapy for breast, ovarian, and lung cancers. Veliparib is an effective PARPs catalytic inhibitor with low IC50 values and increases sensitivity to treatments with DNA-damaging reagents, such as chemotherapy and radiation therapy.

Talazoparib: Developed by Pfizer. It was approved for advanced breast cancer patients with gBRCA mutations. Talazoparib is known for its potent PARPs trapping ability and is the largest in size among the PARP inhibitors.

Since these drugs are targeting various types of cancer, including ovarian, breast, and pancreatic cancers maybe a 737 combo could be an option.

Regards.

Indeed, Potnak. As CPF were in the driving seat for 737 I wonder if they just used the quick 'cookie-cutter' Sierra type of arrangement to get 737 moving rather than spending much more time to arrive at an albeit potentially better financial deal.

So from a certain perspective our current woes are maybe directly related to CPF not being able to maximise the 737 deal? Who knows?

Morning Potnak - I think the BoD expected a better 737 deal rather than a carbon copy of the Sierra one. They probably hoped our upfront payment would cover liabilities to RF and see us in the clear.

I suspect the BoD mainly work from home and only show up at HQ when they need extended face to face meetings. This would presumbly result in a lower cost on office rental though they'll still pay to have a sign outside the door.

Unless a source of funding shows up in the next week or so I think they might go for a public offering to raise about £3.5m in April. It might do the BoD well to also reduce their salaries and take bonuses based on share performance, that might help focus their 'business' minds.

If the sp falls much further, would they consider suspending the share whilst they seek alternative funding?

Regards.

Not quite, Krusty. As of 2016 HMRC classified anyone with assets valued in excess of £10 million as a HNWI. Prior to that date it was £20m. The people you describe are merely wealthy.

Hi C79 - I'm not sure NuMedii fits the bill as they seem more about using AI and Big Data to look for new treatments in general rather than being the "...company that is committed to advancing promising oncology programmes." (That's a quote from the answer to Q19 from the Dec AGM.)

As for ProLynx, an interesting possibility if they went for a triple combo e.g. 737+PLX038+chemo. Perhaps one to watch.

Regards.

As a slight aside since people have mentioned the MHRA - The latest issue of New Scientist has a 2-page advertising feature from the Dept for Business & Trade and the MHRA that tells us all how vital clinical research is etc. etc. Anyway, it says that by the end of June '23 although the statutory timeline for initial review was 30 days however some trials were waiting 150 days. The plan is now to double the number of clinical trials by 2027.

Regards.

Hi Blue - big pharma might be smelling blood in the water but that doesn't mean we'll be sold cheap. With patent protection on 1801 and good results we'll be worth more than £100m+ so let's not think about selling that large diamond we've got in our back pocket for the price of a Big Mac just 'cos we're a bit peckish.

I forget the name of the biotech who were offered about $600m but kept saying no and finally got about $6bn. Not saying that will happen to us but our IP is worth way more than our current m/cap.

Andy - I posted this the other day (and elcap, I suspect the BoD are busy with other things at the moment)

Hopefully this may reassure folks in the event things go bad to worse but please remember I'm not an expert, just a punter. I'd appreciate if someone can reply to this thread to either confirm my understanding or not.

Looking at who owns the intellectual property, the link to the various patent applications indicates Sareum Ltd.

https://worldwide.espacenet.com/searchResults?submitted=true&locale=en_EP&DB=EPODOC&ST=advanced&TI=&AB=&PN=&AP=&PR=&PD=&PA=Sareum&IN=&CPC=&IC=

So who owns Sareum Ltd? Companies House says there is just one individual with significant control - Sareum Holdings PLC

https://find-and-update.company-information.service.gov.uk/company/04863659/persons-with-significant-control

Sareum Holdings PLC is what we're invested in and no individual person has significant control i.e. the company cannot be sold off cheap without shareholder agreement.

https://find-and-update.company-information.service.gov.uk/company/05147578/persons-with-significant-control

So if I'm correct then we all own a share in the IP. The BoD will know they're outgunned in terms of not being able to accept any offers unless enough of us also agree.

Thank you for spotting this, Krone. At least it's a bit of good news for 1801 and it might've come at just the right time too.