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Hi Ben - just to clarify, the max dose in Oz was Cohort F at 300mg. JR compared the results for Cohort D (75mg) with brepecitinib at 100mg.

As for not going with even higher doses, I think it comes down to what the body can absorb and effectively use. You can eat oranges all day but the body only uses the vitamin C that it needs and you pee out the rest. No sense taking 1000mg of 1801 per day if max benefit is at, say, 75mg per day.

Hi BenH - the highest level of SDC-1801 used in preclinical toxicity trials was approximately 30 times the efficacious dose level, though importantly, a Maximum Tolerated Dose was never actually reached. The baseline efficacious dose is the lowest dose that produces desired therapeutic effects (I don't know if SAR published what that exact level is).

Anyway, this means that even at 30x the lowest intended dose level, the compound continued to show excellent tolerability without reaching a point where toxicity became limiting. That suggests to my untrained mind that a 1g dose (as you propose) wouldn't show much in the way of toxic effects. Remember that MAD cohort D was just 75mg hence the need to create a less pure batch to try and induce the issues that would appease regulators. Or we could just make each pill the size of a small child's fist and tell patients just to get on with it.

Hi Ben - I'll try to answer your questions but keep in mind I'm no expert.

I'm guessing that the patents will outline a number of routes that can be taken in order to manufacture 1801. A chemist could probably look at any formula and tell you a number of ways that you could make it - different paths, same destination. JR will know methods that stay within the current scope of the patents that optimize the process. A bit like you're making a cake and it requires flour - do you add self-raising or do you use some other type and then add a raising agent?

The whole point of the remanufacturing is as JR said during the meeting, that regulators often like to see definite tox issues. I presume they like certainty it gives and this would allow them to state on the bottle, "Do not exceed more than 2 tablets in 24hrs" or whatever. This gives the consumer some sort of confidence that regulators know where the red line is as opposed to "hey kids, you can eat these things like Smarties!"

Hope that helps.

Hi LJ - I don't think there's anything suspicious re the delay to the next tox trial. JR stated their own risk management review suggested it'd be prudent to use a fresh batch of 1801 with intentionally greater levels of impurities in order to maximise the possibility of inducing a tox response. He also stated they wanted to tweak the formula slightly to improve the absorbtion. These things don't happen overnight.

None of my predictions have ever been right but I reckon this'll be NT to buy first thing on 7th April.

Hi SOG - yes, very interesting for those who like a bit of science. Just looking back at the IM presentation and JR points out that MAD cohort D (75mg) is equivalent to 100mg of brepocitinib yet they plan on going to higher doses (and with a less pure formula of 1801) in the tox study in an effort to get some sort of tox reaction just to please regulators! Is it safe? You bet'cha!

I just hope I can fill my ISA at these prices in April!

Hi Elcap - just my own thoughts on the PR side of things. The key is getting our IP & trial results to the right audience in the right format. For example how many people who watched yesterday's presentation know what interferon gamma is? Or rather, after the meeting how many did a quick internet search just to get the gist of it? They say you should never invest in something you don't understand (like crypto!)

I'm sure the BoD will be contacting many scientists who understand what they have and who can feed that up to those who initiate mergers and acquisitions. Show us the data etc. Ultimately these are the people the BoD need to impress.

The other side of the PR coin of course is engaging with punters. Without us to churn shares and get involved in IPOs, a company can flounder. However a steady stream of good news can only occur if there is news to share (no shyt, Sherlock). I posted on another thread about the number of 737-specific RNS detailing great progress. They can't announce success until a trial is complete hence the periods of radio scilence. Whilst it would be great to see an interview with JR on the BBC talking about 1801, how many people would decide to invest in the company as a result? I doubt more than a one or two. Also bear in mind that a science-heavy two minute interview has to jockey for position with news about a footballer's girlfriend - what's more in the public interest?

Instead of rambling further here, I'll now go for a ramble in the great outdoors...

Regards.

Hi SOG - just on the subject of 737, I've done more digging to try and find out who the mystery bio is/was by taking a different angle and searching for the name of the IND sponsor. Nothing! It's clear that whoever it is, they want to remain anonymous. Ah well, at least we've got £5m in the bank and a roadmap for our pipeline.

Just a bit miffed that if yesterday's presentation had lasted the full hour (as scheduled!) they could've answered 2 more of my questions - are they looking to extend 737's patent protection sooner rather than later and which two species will be used in the 1801 tox study?

I know you're of the opinion that one will be primate but it'd be interesting to know for certain - European regulations require demonstrating that Non Human Primates are essential and that no alternatives exist. There are also some drugs that appeared safe in primate testing that later caused severe toxicity in humans such as TGN1412 (see link).

https://pmc.ncbi.nlm.nih.gov/articles/PMC2964774/

Regards.

There are 23(!) RNS specific to 737 available here https://sareum.com/regulatory-news/

Just a sample -

https://otp.tools.investis.com/clients/uk/sareum_holdings_plc/rns/regulatory-story.aspx?cid=2841&newsid=1674371

https://otp.tools.investis.com/clients/uk/sareum_holdings_plc/rns/regulatory-story.aspx?cid=2841&newsid=1674376

https://otp.tools.investis.com/clients/uk/sareum_holdings_plc/rns/regulatory-story.aspx?cid=2841&newsid=1674379

and

https://www.newswire.ca/news-releases/sierra-oncology-announces-late-breaking-oral-and-poster-presentations-at-aacr-2019-for-sra737-and-sra141-preclinical-data-887036703.html

People need to remember that when it was with Sierra, it was up to them to market it. SAR were just junior partners with little to no say. If someone contacted SAR re 737, all the BoD could do was point them towards Sierra. We all know when GSK merged with them that everything other than Momo was handed back so it wasn't just 737 that was victim to this action.

Now that we're in the driving seat, let's see what transpires.

Probably standard part of any license deal that the licensee gets first refusal.

At least the sp hasn't slumped quite as much as I thought it might. Although I've submitted a number of questions ahead of the IM event, I'll ask another one during it though I don't think they'll get round to answering it, "If the Board were inclined to do so, would they be able to buy shares on the open market or are they currently prevented from doing so due to having insider knowledge of forthcoming news?"

For those on the trail of 737, the following two websites might be worth refering to now and again:

https://pubchem.ncbi.nlm.nih.gov/compound/72165232

https://evsexplore.semantics.cancer.gov/evsexplore/concept/ncit/C129580

An interesting piece about how one biotech company sifted through 7 potential suitors before making a deal. Not saying we're in the same position but it makes you realise what can be required to get things over the line.

https://www.fiercebiotech.com/biotech/chimerix-engaged-7-other-biopharmas-choosing-jazzs-935m-deal-heres-why-jazz-won

It's only a matter of time until one of our trolls appears and accuses AI of ramping!

Hi PCS, yes, it's a bit tricky asking questions ahead of a presentation knowing that there will be a trading statement shortly before it. Although we hope many of our concerns will be answered within the body of the 6mth statement, there are no guarantees so we need to hedge our bets and make the most of the communication channels available to us; better to be proactive than reactive!

We all know getting a response from their IR person is a lottery so I prefer to submit questions well in advance and hope the hour is long enough to get direct replies.

Regards.

No problem, PCS. Clearly anyone and everyone can submit whatever questions they want. I imagine some may want SP to justify whatever salary he is on and ask what a typical week looks like for him now that he has exec powers. That may be an important question for them but it perhaps assumes every hour in the week must have equal productivity e.g. are 4 days reviewing competitors' compounds more worthy than a day spent shmoozing with a interested party?

For clarity, I only give the above as a potential example. If he's just wandering around the office with his shirt hanging out and asking where the biscuits are is another matter.

I've modified my question re 1802 - "Is there any end in sight for 1802's translational studies? What has been learned so far from these studies and can 1801's toxicity profile inform expectations for 1802?"

Onwards!

Hi PCS - sorry, I submitted the questions below to the IM platform ahead of reading this board but feel free to add!

1. In taking over the license for 737, was it by mutual agreement with CPF or did they approach Sareum with the desire to relinquish control? Presumably we had to pay to have the larger stake.

2. Does the BoD believe the mystery US-bio had honest intentions or do they feel 737 was deliberately shelved?

3. With 737 patented to 2034, does the BoD consider that is sufficiantly long enough for 737 to currently be an attractive proposition or will they have to start work sooner rather than later to extend the patent life?

4. Is there any end in sight for 1802's translational studies?

5. John Reader had suggested that a paper on 1801 would be submitted for publication. What's the current position?

6. Which two species will be used in the extended tox studies for 1801 and when do you expect them to be completed?

Morning Laz - I'm only guessing here but if the MMs are supposed to match buys to sells in order to keep things roughly balanced, those 4m shares dumped the other day will have kept the sp low to deter further sells and once they've been soaked up by punters the sp might rise slightly as the pressure comes off - just in time to catch the new tax year buyers in a few weeks! As long as I can lower my average at the start of April, I'll be happy though I doubt I'll be able to buy at today's levels.

MMs may be running out of cheap shares, add in any good news from the mid-year report and the sp might start to crawl back to where we should be.

Hi Bailiff - think of it this way, if you get £40k at 12.5p a share, the sp only needs to reach 13.44p a share for you to max out your CGT allowance of £3k profit if you sold the lot.

Depending on your strategy and views on paying tax, it might be better to follow Aber's suggestion and wait 'til the new ISA allowance kicks in. I'm just holding on for the start of April myself.

This is not investment advice, just an observation.

Cheer up Aber - I'm sure I'll be paying more than 12.5p per share in 3wks time. Them's the breaks.

Hi Laz - for all we know the institution dumped half their shares onto the market the other day with those huge sells and passed the rest to thier clients. Mysteries of the universe etc.