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Bunsie,

The safety profile of anti PD-1's has probably been studied more than any other new drug on the market and the range and severity of adverse events is well documented. Far more toxic drugs than SCIB1 have been tested in combination with checkpoint inhibitors, indeed, one of the main advantages of Scib1 is the lack of toxicity. If the trial does produce high levels of severe adverse events, it should be obvious whether these are in line with Keytruda's safety profile or whether there's something else going on. So I don't think you need to be overly concerned about the risk of Scib1 being blamed for Keytruda's side effects.

From your previous post:-

'SCIB1 and PD-1 will have a control arm. '

It's a single arm, open label trial in 25 patients, no control arm.

Some perspective in the recently released video below. It's less than 10 minutes long and I really hope everyone will spare those few minutes to watch to the very end.

Hopefully AP101 will be approved and will help with wound management but ultimately, it would be fantastic if gene therapy can lead to a cure for these children. It could well happen within the next few years.

https://www.youtube.com/watch?v=x49zImaZe_8

Burble

Have finally had a chance to read and take in your post last night on the difference between chimeric and humanised mAbs and it's starting to make sense so thanks very much! Also helped to visualise the different types of antibody and the diagrams in the link below were useful alongside the one in your post.

Whilst I knew that the letters 'mab' at the end of a drug indicated that it was a monoclonal antibody, I hadn't appreciated that the letters immediately preceding 'mab' also had a meaning:-

chimeric = 'xi' ie. Ritu'xi'mab
humanised - 'zu' ie. Pembroli'zu'mab
human - 'u' ie. ipilim'u'mab

Going to use your post to now go and have another read and try to understand more from Scancell's recent paper 'Molecular and structural basis for Lewis glycan recognition by a cancer-targeting antibody'

https://absoluteantibody.com/antibody-resources/antibody-engineering/humanisation/

https://portlandpress.com/biochemj/article/doi/10.1042/BCJ20200454/226072/Molecular-and-structural-basis-for-Lewis-glycan

Bunsie,

Thanks for posting - it's a real concern that the reporting and media coverage of this issue is going to have a knock-on effect on recruitment for the other vaccines in clinical trials. There's no doubt that it's going to make people stop and think before volunteering and it's so important that the message in the final paragraph of your 13.50 gets through:-

'It’s not impossible the transverse myelitis — if confirmed as a diagnosis — was related to the vaccine. But it wouldn’t be possible for the vaccine to cause a COVID-19 infection, which could then spark the myelitis.'

A couple of points -

Just noticed that 100% of patients entered the open label safety follow up phase of the trial - that's very encouraging.

Second point is that the success of AP101 will possibly make for an easier journey with AP103.

Am hoping to see some media later on and will be interesting to hear from the Company.

https://www.nytimes.com/reuters/2020/09/09/world/europe/09reuters-amryt-pharma-drug.html

Great to see Redx finally starting to fulfil its potential.

https://www.londonstockexchange.com/news-article/REDX/research-collaboration-with-jazz-pharmaceuticals/14679410

https://www.rte.ie/news/business/2020/0909/1164084-amryt-pharmas-filsuvez-drug/

Fantastic news. There has never been an approved treatment for EB which is a truly dreadful disease causing unimaginable suffering to patients who are mostly children so today's RNS from Amryt is wonderful news:-

'Amryt is very pleased to announce positive top line results from its pivotal Phase 3 EASE trial of FILSUVEZ® (previously AP101 /Oleogel-S10) for the treatment of dystrophic and junctional Epidermolysis Bullosa ("EB"). The primary endpoint of the trial was met (p-value = 0.013). EASE is the largest Phase 3 trial ever conducted in EB.'

Moreover,:-

'Amryt intends to complete the submission of its rolling New Drug Application ("NDA") to the US Food and Drug Administration ("FDA") and request priority review for FILSUVEZ®. FILSUVEZ® previously received Fast Track Designation and Rare Paediatric Disease Designation from the FDA. This means that if an NDA for FILSUVEZ® is approved, the Company 'expects to be eligible to apply for a Rare Pediatric Disease Priority Review Voucher that can be used, sold or transferred. Amryt also intends to pursue an accelerated assessment in the EU. Regulatory submissions in the US and the EU are expected to be filed by late Q1 2021.

'

......and I guess this is exactly why these vaccines need to be tested in tens of thousands of patients. Remembering that this was a healthy person volunteering to do their bit, let's hope that he/she is now fully recovered.

Burble,

Firstly thanks very much for your mAb explanation, much appreciated and will reply fully in the morning.

Regarding the Oxford vaccine - what a shame. The anti-vax brigade are going to have a field day. What does this mean?

' A second individual familiar with the matter, who also spoke on condition of anonymity, said the finding is having an impact on other AstraZeneca vaccine trials underway — as well as on the clinical trials being conducted by other vaccine manufacturers.'

Back to Scancell - missed the 2 price monitoring RNSs. Anyone any clue about the 2 x 250k trades?

Crumbs -

Ouch! Not like you.

Crumbs,

You may well be right - hope so!

If the first deal is purely for glycan mAb (s) , it's not necessarily any reflection on Avidmab. We know that the 3 collaborators have been evaluating a whole range of uses and settings for these mAbs both with and without Avidimab. It may be that the first deal comes from a source that already has its own proprietary platform/tech. for re-engineering mAbs and so wouldn't/couldn't license Avidimab but is interested in the targets for use with their own tech.

Time will tell, but it's great to be having a discussion about the structure of Scancell's first deal.

Burble,

Thanks for your previous posts on Avidimab.

Just my opinion of course, but I think that Scancell's first deal is most likely to be for one of the glycan mAbs (without Avidimab) - possibly FG88? Looking at the Trinity Delta note on the glycan mAbs, there is a table (exhibit 6) which summarises 4 of the mAbs. If you look at the row with the title 'Human mAb', some are listed as chimeric and one is humanised. If and when you get a chance, could you explain the difference and the implications (if any) of the difference?

https://www.trinitydelta.org/research-notes/a-sweet-source-of-financing/

Burble

Thanks for another great explanation.

I'm being lazy here, but I'm sure from memory that SCIB2 (possibly SCIB1 or both lol) upregulated PD-L1 expression on the tumour cell surface which in turn potentially MAY increase response rates to the PD-1?

Awonda,

Just to be clear, nobody on this bb has ever suggested that synergy isn't possible, or even probable. However, to be 'proven' it needs to be tested in humans and so best to wait for the results of the SCIB1 combination study.

exfm

Thanks for your post which seems to have got a little lost. The link to the FT article is below.

Cancer vaccines: not such a long shot
https://app.ft.com/content/d0d26d4e-3514-4c3a-81f2-00bd1724d4a6

It starts with a little of the history of cancer vaccines and talks mainly about mRNA vaccines from BioNTech and Moderna. The following is relevant here and the whole article is a timely reminder that whilst we talk about the possibility of vaccines in other indications, Scancell's core business is in cancer vaccines.

'The latest generation of developers have advantages over the last. They can benefit from recent research helping them select effective targets. They can also team their vaccines with "checkpoint" inhibitor drugs, which stop cancer cells from applying brakes to the immune system'

'

Thank you!

So this related to Scancell's Covidity vaccine? ie. Taken from platform that has already proven to be safe and to generate potent immume responses with previous preclinical research highlighting potential in infectious disease.

Inanaco,

There are likely to be plenty of potential investors looking in here that won't understand what on earth your last two posts are saying. Can you perhaps explain in simple and plain english?