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Here we go. These are the exercise criteria for the BOD's 2013 share options according to post from Paraty. .

Scientific Criteria

receive approval to commence a programme of Clinical Trials of a defined Moditope product following submission of a clinical trial authorisation request to the Medicines and Healthcare products Regulatory Authority (“MHRA”);

or an Exit

Commercial Criteria

the entry, no later than the third anniversary of the Grant Date, by a Group Company into an unconditional contract

(a) if the Relevant Product is a Moditope Product – the sum of Ten Million Pounds (£10,000,000);

(b) if the Relevant Product is an Immunobody Product – the sum of Fifty Million Pounds (£50,000,000); or

an Exit

Yes - will try to post tonight

Sorry, really not with you, thought you were saying that Scancell had got to this stage on a total of £25m capital - did you mean something else?

Where did you get the figure of £25m from? Hope you're not posting fake news:)

posts had crossed again.

Re. the quality of life issue, I can see how it would be really useful in clinical trials to know more about patient outcomes. QOL is quite far reaching - it's all about the complete wellbeing of the patient whilst on treatment - their ability to carry on functioning, working, socialising, pain, side effects - just everything. I can see how it might make a difference when it comes to approval, especially to the breadth of the labelling and especially if you have 2 drugs with similar survival results but one with a poor QOL and the other an excellent QOL. Think it's a good thing and it is only a secondary outcome measure.

QOL assessment is great for products like SCIB1 which have no toxicity. I remember reading about Tom, from the first SCIB1 trial who was able to carry on with his normal life and studies all through treatment and is now a successful barrister. Imagine his QOL score.

For reasons given in my 21.53, I'm not sure you can rule out a placebo effect on some of the endpoints.

Secondly if I'm understanding you correctly, you're suggesting the use of historical data for the control arm. Think they already do that with some of the very rare cancers where it would be impossible otherwise to recruit enough patients. If you google historical data for control groups you'll get loads of arguments for and against. Fact is though, at the moment, the FDA require at least one but usually 2 well controlled, randomised trials before they will even consider approval.

Think there is potential for significant placebo effect when it comes to adverse events.

Also from memory the 21st Century Cures Act in the US enshrined into law the need to involve patients more in drug development. One way that's happening is that many trials now measure quality of life as a secondary outcome measure and that also has potential for placebo effect.

Finally, I would have thought it also has a role to play in patient retention. Am sure that if patients were told they'd been allocated to a control group they would be far less likely to complete treatment.

I'm not sure I've ever seen a randomised trial for late stage cancer (or any stage for that matter) where the control group was treated with placebo only. It's usually new drug versus a control group treated with the standard of care treatment. So you're actually looking to see new drug is better (or in some cases non-inferior) to SOC treatment.

https://onlinelibrary.wiley.com/doi/abs/10.1002/cyto.a.23571

The following paper has been published in the peer-reviewed Cytometry Journal - it's the official journal of the International Society for Advancement of Cytometry. Article is all about Parsortix and well worth a read, you can download the full text by following the links. Very positive, mind you it should be - it was written by Angle:)

hxxps://onlinelibrary.wiley.com/doi/abs/10.1002/cyto.a.23571

Have just got in from a very long, stressful and tiring day and caught up on the bb - wow!

What a shame that rather than debate in an intelligent and respectful manner you have to resort to attempts to belittle and discredit posters that you don't agree with.

Wild, I would happily allow Inanaco his opinions if only he would extend the same courtesy to other posters, I've lost count of the number of times I have suggested that we agree to differ only for Inanaco to claim this as some sort of weakness in my viewpoint and victory. Each and every one of us has something to offer this bb but these attempts to control what's posted and dismiss any post /poster or shut down any subject that isn't considered worthy is stifling.

I will leave it at that.

Botski - good spot. More details in link below.

BioNTech seem to be attracting lots of attention with their mRNA vaccines - now have deals with Genentech for mRNA cancer vaccines, Eli Lilly for TCR therapies and Pfizer for mRNA flu vaccine - well done them! Wonder whether they'll now be planning IPO?

https://endpts.com/pfizer-hits-the-gas-pedal-in-the-mrna-flu-vaccine-development-race-inking-a-425m-investment-pact-with-biontech/

Botski, interesting isn't it?

Haven't followed them closely but know their SP collapsed a few weeks ago. They obviously needed cash and issued RNS which implied they had been unable to get an equity funding away (at least on acceptable terms). At that stage they were looking at raising cash by selling on entitlement to future royalties for some of their products. Not sure whether those discussions came to nothing or they simply had a better offer for complete sale of the Company.

Seems to be same old issue of a market cap which had possibly got ahead of itself, funding issues and deals not coming in at rate/level hoped for but there could be more to it.

Rather than telling me the problem with how I research, perhaps better to respond to some of my points.

Can you guarantee that every patient who on paper should respond will actually respond in real life?

Can you confirm that your previous statement was correct and that 100% of patients respond to SCIB1?

Can you confirm that there isn't some as yet, poorly understood immunosuppressive mechanism that could result in patients failing to respond?

Can you confirm that a 25 patient trial doesn't leave more room for bad luck when it comes to patient recruitmet? ie. a higher than expected rate of non-responders?

If the answer to even one of those questions is no then it's impossible to say that the trial can't fail.

By the way, the only reason I used that article is that Scancell clearly feel it has merit as they retweeted it - rather than looking at the author, why don't you google Jason Luke who was quoted in the article? He most certainly has heard of Scancell as he's corresponded with RG and there was some talk of his joining the SCIB1 study.

If it was possible for anybody, let alone a lay person to research on google and have sufficient knowledge to predict that a new treatment will definitely work or that a trial can't fail then not only would we all be rich but also much better placed to help to any loved ones who are suffering.

I should add that I fully expect the trial to be successful but that's not the same as can't fail, no risk.

Haven't forgotten - I'll try to find the exercise criteria for directors share options that you asked for yesterday and post here.

Inanaco,

It's too late and I'm too tired to get into this debate tonight. I didn't suggest for one second that PD-L1 directly stimulates an immune response - expression of PD-L1 is one end of the PD-1 / L1 checkpoint inhibitor pathway.

As for the use of the word stimulating versus generating - it's semantics but stimulating is the word used by LD so it's good enough for me.

Your point about PD1 blockade preventing turning off of the T cell response - you're firstly assuming the CI works and how do you know that there aren't other immunosuppressive mechanisms that might also turn off the T cell response?

Finally, I'm afraid you're mistaken, not every single patient has responded to SCIB1 and those with heavy tumour load had the weakest responses.

I wouldn't be invested here if I didn't feel there was a good chance of success but it isn't guaranteed and there is risk. If it was as simple as 'we know why it should work therefore it must work' then there would never be any clinical trial failures.

No, I can see where you're coming from but.... - it is still not known exactly why some patients respond to PD-1 and some don't. There seems to be no doubt that PD-L1 expression by the tumour plays a role but it's by no means the whole story. There are patients with very low PD-L1 expression that respond and those with high that don't. In phase III trials even when Keytruda was restricted to patients with high PD-L1 expression, only a percentage of patients respond. There are all sorts of theories as to why those with high PD-L1 don't respond, most of which seem to revolve around the tumour micro environment and a general consensus that stimulating the immune response will help, however. they simply don't yet fully understand.

So it is fact that not all patients respond to Keytruda, regardless of PD-L1 expression and it's fact that not all SCIB1 late stage patients with tumour load responded to SCIB1. Hopefully, SCIB1 will make enough of a difference to show that it increases response rates to Keytruda BUT with only 25 patients it will have to be good and good enough to convince future backers that it's a better bet than any of the other hundreds of treatments currently being tested in combination with PD-1's. As I mentioned before - with such low patient nos., just 1 patient failing to respond could make all the difference.

Would strongly recommend that anyone invested here reads the article below, which incidentally was tweeted by Scancell. It's a great article and helps to appreciate the scale of the field Scancell are operating in. This quote from the article is from Jason Luke:-

Even now, as a community, we don’t understand why anti-PD-1 antibodies like pembrolizumab and nivolumab work'
'

So rather than saying what mechanism will cause it to fail, I would throw back at you what mechanism will guarantee success?

https://cen.acs.org/content/cen/articles/96/i23/difficult-search-right-recipe-cancer.html

It was posted by Paraty - will try to find it.

As for SCIB1 combo trial - of course it can fail. It it wasn't possible for it to fail then they wouldn't need to run the trial. Unless things have changed in the last couple of weeks, we know the trial has been scaled back to 25 patients. Just one patient's response or lack of response could make the difference between success and failure. Even it if meets the endpoints, it will still need to be taken into a much, much larger randomised study so not only does the trial need to be successful but results need to be good enough to secure either a licensing deal or the investment to fund larger studies.

Article on Amryt published yesterday

http://www.evaluate.com/vantage/articles/interviews/amryt-awaits-crucial-readout-it-prepares-rare-disease-push

Jeez - shudder to think what Ofsted report would be like, no doubt be put on special measures

Thanks for your 23.50. Yes, I do understand the usual meaning of due diligence but it is a term that can be applied to any investigation or evaluation.

Scancell's deal with the CRUK for SCIB2 was announced via RNS in December 2017 and was unequivocal - Scancell and CRUK had entered (past tense) into a partnership. I can't understand why you would now suggest that
in April 2018, 4 months after that RNS they were still carrying out due diligence. Are you seriously suggesting that Scancell would issue such a misleading RNS, that CRUK would be party to it and that the deal may still fall through due to due diligence?

It's highly likely that the CRUK team carrying out due diligence ahead of the deal were different from the team who will actually be working on and developing the drug. It is entirely reasonable for CRUK's R&D team to carry out a full appraisal of the drug and all data in advance of making critical decisions regarding its development path. That also can be termed due diligence.