Member Info for HotblackDesiato

Hi Aber - I'm not surprised there was no mention of Sareum in the part you refer to. It's purely an ethics declaration from Udai Banerji saying that although he works for one of the developers he doesn't get any royalties and he spoke for free at some Sierra event. It would only mention Sareum if he carried out any paid or unpaid work for us during the development of 737.

The last update on their news tab is dated 8/2/22 so I think there's your answer :-(

Just to try and bring some clarity to the accrual figure, I came across this definition -

https://www.mayo.edu/research/institutional-review-board/definition-terms

"Accrual. The number of subjects who have completed or are actively in the process of completing a study at Mayo Clinic. This does not include screen failures. It does include withdrawals. Example: You enroll 100 to accrue 25."

So if the Oz clinic follows the same definition, the figure of 8 could be accurate either if it's the number of people who have completed their time on the trial (the first cohort) or the number in the process of completing the study. The key word there for me is 'completing' i.e. if you've been recruited but your cohort hasn't started yet or it's finished then you don't get counted - it's only the number of patients being dosed at any given time. So with only 8 people in each cohort, the figure might never change even though the trial is proceeding as planned.

What happens to ISAs when you pass on - https://www.gov.uk/individual-savings-accounts/if-you-die

Hi Ahfam - Once the BoD get results of blood tests etc. they'll have a clearer idea of what else 1801 may be able to treat. So whilst the company has declared initial interest in psoriasis and serious respiratory infections, they might be in a position to lure pharmas in with test results showing strong responses relating to other biomarkers too.

Mmmm, not sure. I'd guess psoriasis was chosen as it's pretty low hanging fruit with lots of potential patients and could be an easy win in order to prove efficacy. Reducing RTI's might just be a nice addition.

One of the factors that will be considered during the review of 1801's efficacy will be any adverse events. Searching for 'common adverse effects in psoriasis drug trials' brings up a recurring thing - an upper respiratory infection. Most of you will be aware that 1801 is also a potential candidate for the treatment of acute respiratory symptoms of viral infections so it'll be very interesting to see if 1801 reduces this type of adverse event in the current trial.

Just a few links below noting patients contracted colds or other respiratory infections -

https://journals.sagepub.com/doi/10.1177/24755303221142295

https://pubmed.ncbi.nlm.nih.gov/31046481/

https://www.nejm.org/doi/full/10.1056/NEJMoa1314258

https://www.nejm.org/doi/full/10.1056/NEJMoa1806382

Clearly there are coughs and wheezes going about all the time but looking at the percentages, it is remarkable how many people on the trials contracted something which 1801 may also treat or possibly even prevent.

(Disclaimer: I'm not a doctor so might well be talking cobblers.)

Hi Laz - with 8 participants per cohort in P1a and each cohort to start sequentially rather than in parallel (per the RNS), the only statement on progress we have is the trial doc update last Friday indicating an accrued population of 8 people.

So is it -

a) the first 8 people have completed their stint

b) only 8 people have been recruited so far

or

c) a typo and it should either read '48' for part 1 or '80' for the whole of parts 1&2?

None of us know the answer hence some frustration on my part. If they have all the recruits, why didn't they also change the doc on Friday to reflect 'no longer recruiting' instead of leaving it as 'recruiting' etc.?

Hi Sixth - I think it's just poor admin on the part of whoever is supposed to be updating the trial entries. The ethics approval was given on 4th May for the whole trial but it was just the record for part 3 that got updated to 'approved' on 25th May - parts 1 & 2 were only updated on the 7th June.

Presumably the clinic won't have enough bed space for all the volunteers at one time but if they've only managed to recruit 8 people so far out of 80 in the space of a month then we're miles off from any real news.

If it is just poor admin and the trial is slightly further along than is being reported, you'd have thought a wee RNS would be good just to say the first cohort has been completed and all is well.

Just had a look on the ANZCTR website to check if there are any updates and I see the 'Part 1&2' entry was updated yesterday (see link below). The first patient was dosed on 5th June and whilst the target sample size is 80, the accrual to date figure is just 8. The odd thing is the recruitment status is 'recruiting' however the Nucleus Network clinical trial webpage no longer shows the original details of the psoriasis trial - so are they recruiting or not? The ethics approval has also been updated to show it's been granted.

ANZCTR entry - https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=385555&isReview=true

Current recruitment webpage - https://www.nucleusnetwork.com/au/participate-in-a-trial/melbourne-clinical-trials/

Original recruitment page for psoriasis trial (presumably 1801) which is no longer available directly from the Nucleus Network site - https://www.nucleusnetwork.com/au/participate-in-a-trial/studies/the-regulating-study/

Perhaps the figure of 8 refers to those who have now completed their involvement in the trial i.e. those from the first cohort.

Anyhoo, just thought it worth a mention.

Evening Belhus - after reading an article about AstraZeneca (see below), I wonder if they'd be interested in 737 (or the whole company).

"AstraZeneca’s share price dipped 5% this week when drug trial results failed to meet investors’ expectations, says Hannah Kuchler in the Financial Times. While datopotamab deruxtecan, developed with Japan’s Daiichi Sankyo, was found to stall the progression of patients’ advanced non-small cell lung cancer longer than the current chemotherapy treatment, shareholders were disappointed AstraZeneca did not declare the results “clinically meaningful”. The Anglo-Swedish drug giant said further analysis was required and that clinical significance was anyway “subjective”. Some patients also suffered lung scarring, although AstraZeneca said this was “low grade”. Meeting expectations was always going to be a challenge, according to Credit Suisse’s analysts, because the patients in the late-stage phase-three trial had already tried at least two other drugs. The drug may yet prove to be more effective when taken earlier."

Hi Potnak - hang on a minute, you start with, "Had the deadline to progress or hand back already passed or did they know it would pass before the sale of Sierra..." but then you go on to suggest, "They literally could have on licensed or sold it on!" Ehh, not if the deadline to progress or handback had passed!

However I do agree that the sp does not reflect any potential for 737 but if we do get bad news the MMs will torpedo the sp.

Just musing so would welcome any thoughts - Sierra have one 737-related patent granted and another 5 in the system. Add our own patents to the mix and it would make for a dizzying read. I'm therefore wondering if this potential embarrassment of IP riches has a knock-on effect to 737 negotiations as any interested party will have to go over each with a fine tooth comb in order to fully understand 737's scope etc.

Negotiations will be a complex matter so it's maybe no wonder we haven't had any update on progress.

Hi C79 - and it's good to know Sierra's patent for CHK1 (SRA737)/PARPi combination methods of inhibiting tumor growth was granted on 7th March. That IP will now be in the hands of the CPF per the license agreement.

https://patents.justia.com/patent/11596637

Other Sierra patents for 737 in the pipeline - https://patents.justia.com/search?q=sra737

Plus, consider the potential market value of 1802 now that we have patent protection in the US - once we get 1802 into the clinic it could be a major money spinner. Sections 2.1 to 2.26 in the link below outline the various conditions that 1802 could potentially treat.

https://patents.justia.com/patent/11673870

So although it's our main candidate for cancer, it could perhaps also treat everything from asthma to MS.

I wonder how that queue is getting on.

Hi C79 - crikey, £690 per pack? Compare that to the approx. £2.50 per pack for Methotrexate and £18 or so per pack for Ciclosporin (see links below for pricing). No wonder the NHS consider it only in patients whose symptoms have not responded adequately to other systemic treatments.

https://bnf.nice.org.uk/drugs/methotrexate/medicinal-forms/

https://bnf.nice.org.uk/drugs/ciclosporin/medicinal-forms/

Now all we have to do is hope 1801 is more effective and/or cheaper.

Hi Bailiff - I agree the science can be pretty mind bending but the trial application itself is thankfully 99% plain English.

Yeah, at first glance it looks a bit much but it's pretty straight forward to understand. Assuming patients will read it, it has to be clear in what the objectives are and leave no room for ambiguity.

If you're smart enough to own shares in SAR, you're smart enough to understand the doc :-)

Jerry - It's all here https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=385555&isReview=true

BenH - it's also worth remembering that you can have multiple patents covering a single drug e.g. a patent for the new drug, a patent covering the manufacturing process and then a patent covering the theraputic uses of the drug.