Member Info for HotblackDesiato

Just looking at Google Finance and it would suggest 63k shares were sold at 12:01pm but the volume isn't reflected on LSE's share trades page. What the...?

I guess it's neither here nor there to those waiting for the endgame.

Looks like our CTN should be stamped 'fair dinkum' pretty soon. If it all goes pear-shaped then at least we'll have a base to go off opal mining or digging for gold :-)

Hi PCS - yep, a smart move by the BoD to register a business in Oz. I submitted the question below so expect they'll make some comment at the meeting.

Can you elaborate on the recent announcement regarding the setting up of a legal entity in Australia e.g. what is it called, where is it located and what type of entity is it i.e. a branch of Sareum or a subsidiary etc.?
(from poking around it looks like a subsidiary requires a paid member of staff to work in Oz whereas a branch just requires an office address. There doesn't appear to be a 'Sareum Australia' or whatever registered and I couldn't find any of the BoD named as business owners so it might be a case of they've got a local accountant to act as company secretary. The specific location in Oz is relevant as there are various grants and so on available to companies depending on which territory they are in. Also as far as I can tell, any CTN has to go through the local ethics committee. Now that I type this I wonder if they will accept the results from a UK ethics committee therefore saving time on the review - another question to ask!)

Evening SOG - yeah, I quite agree and only really pondered thoughts of a buy-out in a "what if..." scenario. I'm in this for a big payday so until we have the high value goods then, personally, I wouldn't be too interested at present.

I presume potential suitors would have done their homework by this stage and would know whilst SAR are a co-developer, we're probably not in a position to talk deals - unless the CPF have given us the go ahead to work/negotiate within certain boundaries e.g. SAR does the legwork but the CPF signs off on any deal and in return we may see a slight improvement to our own terms re royalties.

Regards.

Hi Fearg - regarding 1802, slide 13 in the link below notes, "Additional biomarker studies to better understand the mechanism of action" so perhaps they've decided to do further research in order to be more selective.

http://www.sareum.com/files/2616/7810/3880/Sareum_Company_Mar_23.pdf

Just some info re biomarkers:

https://md.catapult.org.uk/designing-a-biomarker-strategy/

https://www.fda.gov/drugs/biomarker-qualification-program/biomarker-qualification-program-educational-module-series-module-2-how-biomarkers-can-improve-drug

https://pubmed.ncbi.nlm.nih.gov/27249758/

It'd be great if they could tell us if talks with interested parties re 737 have started and maybe more importantly, why companies are queuing to speak to us when we don't own the compound. Are we're finally reaching a stage where a company might want to buy us out completely while we'd still be pretty cheap?

http://www.sareum.com/files/2616/7810/3880/Sareum_Company_Mar_23.pdf

(probably why website was down for Warty)

Sorry SOG, but not sure what you're getting at. I'm talking about the actual results of the study, not an overview of the trial.

Anyway, more detail on the trial here: https://beta.clinicaltrials.gov/study/NCT02797977?distance=50&term=SRA737&rank=2&tab=table

I don't know if folk at Sierra are incompetent or if the US authorities enjoy a bit of red tape as much as the MHRA but it looks like publication of the 737 combo trial results have hit a snag for the third time.

See entry below dated 16th March.

https://beta.clinicaltrials.gov/study/NCT02797977?distance=50&term=SRA737&rank=2&tab=results

Note - "The date on which the National Library of Medicine provided quality control (QC) review comments to the study sponsor or investigator. The sponsor or investigator must address major issues identified in the review comments. If there is a date listed for results returned after quality control review, but there is not a subsequent date listed for results submitted to ClinicalTrials.gov, this means that the submission is pending changes by the sponsor or investigator."

As some of the trials were in Spain, maybe something has been lost in translation. Maybe Sierra have 'accidentally on purpose' ballsed things up to slow progress or maybe there is something more fundamental. It might just be a jobsworth at the dept. and there is nothing to worry about.

I've submitted another question to Investor Meets - "The U.S. govt. website ClinicalTrials.gov was updated on 16th March to indicate that the results for Sierra's Phase 1/2 trial of SRA737 in combination with Gemcitabine and/or Cisplatin have failed a quality control review for a third time.
Are you able to provide any detail regarding this and what impact this might have on further trials of SRA737 or a potential on-license deal?"

You never know, we might get an update this week to say discussions are well underway and the above is of little consequence as the data is rock solid.

At the risk of boring you to tears, I thought I'd do some digging and so only post this to try and bring more clarity to the subject.

A very good overview for layman - https://www.dcatvci.org/sponsored/n-nitrosamines-in-drug-products-overview-challenges-and-lessons-learned-from-an-api-manufacturers-perspective/

It notes, "Nitrosamines can be eliminated by GMP, synthetic route modifications, elimination of nitrosamine formation sources, and a holistic understanding of the entire manufacturing process. As a result of growing knowledge about nitrosamines, some recommendation to process modification was published by regulatory agencies. The first of these possible mitigation strategies is derived from literature reports showing that commonly used antioxidants such as ascorbic acid (vitamin C) or alpha-tocopherol (vitamin E) inhibit the formation of nitrosamines in vivo based upon data from human gastric fluid in vitro studies. A second possible approach is based upon the fact that the formation of nitrosamines typically occurs under acidic conditions, whereas, in a neutral or basic environment, the kinetics of these reactions are significantly reduced."

A deeper dive - https://pubmed.ncbi.nlm.nih.gov/36736774/ and https://www.sciencedirect.com/org/science/article/abs/pii/S1083616021021551

And just to kill off the topic I've submitted this to Investor Meets: "There is a concern in some quarters that N-nitrosamines could potentially be a by-product during the manufacture of SRA737. As Nitrosamines can be eliminated by GMP, synthetic route modifications, elimination of nitrosamine formation sources, and a holistic understanding of the entire manufacturing process, can the Board assure shareholders that adequate steps been taken to mitigate such contamination?"

And now to turn my attention to some Chicken Tagliatelle sitting in the fridge...

Not that it matters at this point - https://www.hra.nhs.uk/planning-and-improving-research/application-summaries/research-summaries/a-fih-study-to-evaluate-the-effects-of-sdc-1801-in-healthy-adults-or-with-plaque-psoriasis/

I've just added - With regards to the CTA process in Australia, do you know how much of the UK application will be accepted by the Australian authorities or will elements such as the ethics review need to be examined again?

(I think the Oz ethics review can take up to 3mths from submission so accepting the UK review findings would save a great deal of time.)

I've submitted the questions below. The comments in brackets are only included here to let you understand my thinking.

Question 1:
Can you elaborate on the recent announcement regarding the setting up of a legal entity in Australia e.g. what is it called, where is it located and what type of entity is it i.e. a branch of Sareum or a subsidiary etc.?
(from poking around it looks like a subsidiary requires a paid member of staff to work in Oz whereas a branch just requires an office address. There doesn't appear to be a 'Sareum Australia' or whatever registered and I couldn't find any of the BoD named as business owners so it might be a case of they've got a local accountant to act as company secretary. The specific location in Oz is relevant as there are various grants and so on available to companies depending on which territory they are in. Also as far as I can tell, any CTA has to go through the local ethics committee. Now that I type this I wonder if they will accept the results from a UK ethics committee therefore saving time on the review - another question to ask!)

Question 2:
Can the board confirm if the SRA737 data package from Sierra Oncology met their expectations e.g. does it include patient genetic information etc.?
(It'd be good to know we got everything that JR hoped for and nothing has been left out.)

Question 3:
Is there any scope to renegotiate the terms of our agreement with the Pioneer Fund with the aim of improving our entitlement to a share of SRA737 milestone payments and royalties?
(I expect the answer is 'no' but things do change; afterall the original ProNai deal was renegotiated therefore there is a precedence.)

Question 4:
With a completed Phase II trial of SRA737, do you expect the next step in its development to be a Phase III trial or another Phase II trial but with new parameters?
(The value of a compound in P3 or one that is P3-ready is much much more than a P2 compound. Kerr-ching.)

Just on a sidenote, as I was switching off last night I thought I saw a post from CoL but it's now gone. Has he been rumbled?

Regards.

Worth a read http://www.austrade.gov.au/ArticleDocuments/2814/Clincal-Trials-Capability-Report.pdf.aspx

Page 11 - What makes Australia an ideal destination for clinical trials? A fast, pragmatic regulatory pathway.

Maybe I should send a copy to our MHRA, however I fear they'd just file it and hope to read it later...or never.

Looks like setting up a new business in Oz was a smart move as otherwise we'd need to find a sponsor.

https://www.australianclinicaltrials.gov.au/industry-and-sponsors/sponsorship

"International pharmaceutical and biotechnology companies and groups of researchers can conduct clinical trials in Australia. However, the trials must be sponsored by an Australian entity. The entity can be an individual, company, institution or organisation that takes responsibility for the initiation, management, provision of insurance and indemnity, and/or financing of a clinical trial."

I was also looking for info on our new legal entity but haven't found anything too useful yet. Perhaps we'll get more detail next week.

https://asic.gov.au/online-services/search-asic-s-registers/companies-and-organisations/

Bulp - if only you had access to a search engine ;-)

https://taxsummaries.pwc.com/australia/corporate/taxes-on-corporate-income

Hi SoG - I wonder if CoL will be submitting a question to Investor Meets asking for clarification on nitrosamines. No doubt he'll turn up here soon enough to say the move to Oz is good on the face of it but they have many nasty bitey creatures there so maybe not such a smart decision.

Morning Aber, what was it they said at the last meeting? You don't want to trip over the same rock twice?

Tie me CTA down, sport, tie me CTA down....etc.

CoL - although you say, "I have never said nitrosamines were a problem for 737", you have said, "...the 737 structure contains secondary amines, such functionality is known to be susceptible to nitrosamine formation, this is in addition to other formation pathways. Nitrosamines can be potent mutagens and are the subject of huge regulatory scrutiny. Hence, the structure is pertinent to nitrosamines, how can it be anything else?"

Most investors here are not scientists (myself included) so perhaps you can understand if readers interpret some of your statements to imply there are possible issues with 737.

You give the appearance of being someone working in the pharma world (I have no way of authenticating this) so it might be beneficial when you make such statements, that you explain in layman's terms exactly what the ramifications are. If someone purports to speak from a position of authority on a web forum then they shouldn't be surprised when others test their claims in the hope of bringing clarity to a complex subject.

As for filtering you, how would anyone test your claims then?

CoL - I did not suggest nitrosamines present no concern. I suggested their impact would be dependant on the concentration. You might want to reread what I wrote and note how it started with a big "if" -

"IF there is any chance of nitrosamines being produced in the 737 manufacturing process then how much would a patient consume during treatment? Without knowing the absolute figures, a complete course of 737 might be akin to eating 5 bacon rolls, therefore perhaps considered a moot point."

I hope you're not twisting things to suit an agenda.