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Thanks very much

Bob, sorry I left you off my previous post (missed your 17.58)

Thanks very much

Great, thanks.

Would also be really grateful if you could keep your ears open for answers to the following:-

1) Is Modi1 manufacture complete (and if so when) ?

2) When exactly was the IND for SCIB1 submitted to the FDA?

Yes, homocitrullinated peptides are also associated with autoimmune disease. Worth remembering that the collaboration with the Karolinska Institutet is with the Rheumatology Department and not oncology as you might expect. Makes sense given the role of citrullination in autoimmnue diseases. It might well be that some of this research into MDSCs arose from the collaboration.

Will you please stop bringing me into your posts and arguments.

I believe they mean broaden in the sense of the cancers/patients that will respond. Citrullinated and homocitrullinated peptides are chemically very similar but triggered by different modifications - citrullination and carbamyation .

Scancell has previously presented research showing a connection between the presence of Myeloid derived suppressor cells (MDSCs) and carbamylation. MDSCs are bad news for cancer patients, they originate in the bone marrow and can strongly expand in the presence of cancer. They're still not fully understood but they're highly immunosuppressive (suppress T cell immune response). High levels of MDSCs are therefore associated with cold tumours that are unlikely to respond to immunotherapy and a very poor prognosis for the patient.

I can try to find a link to the paper but essentially they seem to be saying that MDSCs expressing a particular enzyme (MPO) trigger carbamylation. A vaccine that can take advantage of MDSCs might work where others don't and I think that's probably what Scancell mean by broadening the utilisation of Moditope. .

They've definitely tested homocitrullinated vimentin and aldolase peptides but I'm sure they've looked at others too.



Scancell have already tested homocitrullinated vimentin and aldolase peptides on mice and human blood or tissue and achieved a CD4 response.

Isocyanic acid is needed for carbamylation which is increased by the enzyme MPO. Myeloid derived suppressor cells (MDSCs) are cells that originate in bone marrow and are strongly associated with cancer and Scancell seem to be saying that MDSCs expressing MPO are found in the tumour microenvironment and that they cause the build-up of isocyanic acid which diffuses into the tumour itself. Carbamylation then takes place and homocitrullinated peptides are then presented on tumour cell surface ready for vaccine to come along and zap tumour!!

So basically MDSCs can be used to trigger modification –

Yep thanks for the reminder Konar. A great spot from you and thanks for sharing.

Absolutely Crumbs and no, TF there's no problem at all, it's good to be able to discuss openly.

'I feel I have exercised you here'

exercised????

wouldn't homocitrullinated epitopes and carbamylation require new patent application?

Haven't seen anything in this application that mentions either which is why am hoping/expecting that there are others lodged awaiting publication.

Ray - yes that was the European patent - both European and US patents have had claims deleted/amended. That's an entirely normal part of the application and examination procedure but would be interesting to know whether coverage of US patent differs in any way in terms of claims.

Either way - it's a good sign for the enolase patent application which is running along behind this one and might have an easier path now.

Have you looked at the claims in any detail, made any comparisons with European or original application?

Well spotted!

https://www.telegraph.co.uk/business/2018/10/29/angle-spies-opportunity-468m-pre-natal-screening-market-novel/

1) There is no positive way of saying we've replaced our Chairman and we've shut our US operations

2) Scancell aren't paying £225k pa for a non-exec chairman - that figure covers the period when he was exec. chairman. Check out salaries on other AIM bios - it's not out of line and if you want to recruit someone decent to replace him then you'll have to pay the going rate.

3) The point about Genentech was in relation to keeping the US office open, not JC

4) JC became an exec chairman while he was doing the rounds with potential investors in the US and the workload required it. The company was in a transition phase with new CEO and now he is up and running and the switch back to non-exec role makes sense.

I take your point re. making changes when things are wobbling but in my experience there's nothing the market likes less than perceived failed strategies, lack of direction and sudden changes in leadership. You may not have been mounting a campaign but you posted on 2 different sites calling for the closure of the US office and the replacement of the Chairman the day before the AGM.

Crikey, I completely share your frustration and I never thought I'd find myself defending JC but here goes!

The strategy to open a US office was to raise the profile of the Company, mainly to access capital but as JC said at the last AGM, institutions simply want to see more from Scancell before they invest. I'm sure we've all got our own opinions as to why that may be but IMO it would be far more damaging now to do a U turn and close the US office - what message does that give out to the markets?

It's easy to mix up frustration with the salary increases (which I very much share) and lack of progress with other issues. Everything is delayed, everything is bad and it must be JC's fault. However, the reason for nearly all of the delays we have experienced aren't down to funding, they're down to delays on the science side. Think it's important to separate the man from the role for a second:-

1) Does the US office add significantly to costs? Probably not.
2) If we want/hope/expect to do deals with the likes of Genentech, will it help to have a US office? yes
2) We have the salary/fees of a chairman regardless of whether they're US or UK based. The fact that it's a non-exec position means that there isn't really any reason why the Chairman needs to be physically in the same place as the CEO.

Even assuming you were able to find a suitable replacement (not as easy as you think) another change in leadership together with a U turn on US strategy and closing of the US office would send out a very strong, negative message that the company are not looking forward with a view to expanding but are contracting and insular in their thinking. So just too late IMO to reverse the situation.

Re. Moditope patent - how is that down to the US office? JC will have nothing to do with the patent - that's in LD's court.

Great RNS.

It would be interesting to know which company requested the study. I can't see that any abstracts from the conference have been published but worth keeping an eye on Angle's website. Anyone invested in Premaitha will know that IP is a real issue in the NIPT field and that the big players such as Illumina will robustly defend their position. So although it's clearly very early days, the commercial potential is obvious. Good to see that Angle have no intention of risking spreading themselves too thinly by developing this themselves.

Careful what you wish for TF!

Inanaco, I'm not sure I understand the question. They'll have plenty of experience of similar devices, similar drugs, similar trial protocols, the same manufacturing process, the same study centres.............................

Inanaco, re. your 16.27. Not sure if your reference to Barnier is appropriate although I guess that depends on your opinion of the man! The FDA clearly have found some deficiencies in the IND application related to the use of the Trigrid device - that's not to say that any of the products involved are deficient, just that they don't have the information/data needed to assess the risk and clear the IND.

The trial is for a drug (PD-1) with known immune related and potentially life threatening side effects, a vaccine (SCIB1) that generates a potent immune response and a device that amplifies that response by at least 100 times. It's a new device and a new combination of drugs that has never been tested in humans and it's only to be expected that the FDA will want to make absolutely sure that all bases are covered whether the issue lies with manufacturing, safety or simply lack of supporting data.

We have no idea when the IND was submitted but you would hope that it was several weeks ago. The fact that the latest estimate for commencement of the trial is H1 2019 (not even Q1!) suggests that the FDA may have asked for further studies. If so it would be useful to know whether these are down to Ichor or Scancell to complete.

As you say, hopefully a full explanation will be forthcoming at the AGM and all will become clear. It's not at all unusual for the FDA to request more information/further studies when assessing INDs and good job too really given the potential impact of their decision.