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I know not I'm know

re. this comment from your 8.28:-

'I'm guessing Scancell wouldn't have bothered if BioNTech were not there'

I'm know you didn't mean it in this way but that comment is slightly insulting to LD. She's not there hanging on BioNTech's coattails but in her own right as an internationally recognised cancer vaccine expert. She was chairing the session on cancer vaccines and presenting a case study - highly likely SCIB1 or possibly Modi1.

With so little news coming out of Scancell at the moment, it's easy to forget that the BioNTech TCR collaboration is a side show here - Moditope and ImmunoBody are the stars of the show and worthy of presentation at these conferences in their own right.

No problem

I got the information from the link posted by TF yesterday. As the thread started off with that link and we were all replying to the thread, I assumed you/folks would have read the link. Just in case here it is again.

http://www.pnas.org/content/early/2018/08/22/1809232115

I'm still not with you, if you google ovalbumin you'll find links to all sorts of research for all sorts of diseases - it's used all the time as explained in my previous posts so still don't understand the asthma link.

RuckRover asked what vaccine had been used with Diprovocim and whether it could have been SCIB1. I simply answered his question - that it wasn't SCIB1 but was ovalbumin.

No, not any vaccine will do - just for clarity.

This study was to evaluate the performance of the adjuvant (Diprovocim) so all that was important in this particular case was the ability to stimulate an immune response and be able to objectively measure and compare the performance of the different groups. To achieve this the researchers created a vaccine using ovalbumin - an antigen that is known to be immunogenic and so is often used as a model antigen in research in mice. In order to make sure that the vaccine is effective they engineer the melanoma in the mice to ensure that it expresses ovalbumin - so they use mice with tumours expressing ovalbumin and a vaccine targeting ovalbumin.

Clearly in real life and in the human setting you can't dictate protein expression on patients tumours. So in real life the right vaccine is a crucial part of the combination.

Sorry, don't understand this from your previous post:-

'Ovalbumin which is "induced experimental asthma" but no link included in his post

the vaccine of interest to you TF was the melanoma vaccine ... '

What's the relevance of asthma?

As Steve mentions, the team in Scancell's labs have been working on identifying, evaluating and selecting the best adjuvant for Moditope. Below are links to some of their research, the first in particular demonstrates just how much work has gone into finding the right adjuvant. You can see that different adjuvants produce different responses with different peptides, it's not just about dose but the type of immune response. Their conclusion - 'adjuvant choice has a profound effect on the dose required and the response profile following immunisation with a self CD4 epitope peptide'.

Back in 2015 we were told that the adjuvant had been finalised but subsequently we were told that there would be a delay in manufacture of Modi1 as they were working on linking tech. for the new adjuvant. Pure speculation on my part but I have often wondered whether as a result of their research they changed their mind and selected Amplivant as it was superior to a previously selected adjuvant and that this is partly responsible for the delay in manufacturing Modi1.

We will never know but it's vital to get it right before manufacture and before Moditope enters the clinic. The great advantage Scancell has over other 'virtual biotechs.' is that they carry out all of their own research, using their own scientists in their own labs. Although it may be frustrating for shareholders, they have the capacity and resources to carry out the research they need to do just that.

http://www.scancell.co.uk/file-manager/scientific-papers/adjuvants-for-moditope.pdf

http://www.scancell.co.uk/file-manager/PDFs/poster-1-conference-mainz-sept-17.pdf

Ruck,

Like Amplivant, Diprovocim is a TLR1/2 agonist. They are both used as adjuvants to enhance the immune response. The vaccine used alongside Diprovocim was simply targeting an antigen called Ovalbumin - it's a common antigen that is known to be immunogenic and so consequently is often used for research purposes.

The purpose of the research was to highlight the efficacy of Diprovocim and the vaccine element is not significant.

That's completely different from accepting the trial protocol.

lol, you wouldn't have seen it as a bit of fluff if the FDA had refused to accept the IND.

It's important that Amryt have study centres in the US, especially if/when it comes to submission of the NDA. Easy to be cynical but RNS is good news.

DA

Although 560k sounds impressive, it amounted to less than £70k in trades which is probably a better measure of sentiment.

Afternoon leas,

Good to hear from you and hope all goes well this afternoon for Mrs Leas.

bigdouble, yes absolutely tragic.

Hope everyone will just take a couple of minutes to read the following entry in her blog in which she describes the stark reality of clinical trials from a patient's perspective.

https://www.bigclittleme.co.uk/blog/trial-and-error/

Completely agree - one to shove in the bottom drawer and forget about for a good while.

When a clinical trial has been on hold due to treatment related side effects, it's a big deal when the regulators confirm that they agree in principle to the Company's clinical development plan to resume the trial. It's a significant development and much more worthy of an RNS than half of the announcements we see on bios.

They now have the green light from the MHRA and can finalise detail of the trial design to obtain CTA. It's been a long time coming and hopefully will draw a line under this dreadful period in the Company's history.

Steroid use was a separate measure in the Lupuzor trial but as far as I know Immupharma haven't yet released any data on the results.

Agree. I would also add that the placebo issue is not just one of adherence to treatment but also access to treatment. I believe that on average, patients may see their rheumatologist once every three months at which time their condition is reviewed and any adjustments to treatment will be made. During both the Lupuzor and Anifrolumab trials, they were seen every 4 weeks and constantly monitored with far more testing than a normal patient would receive. This allowed for constant adjustments (if necessary) to SOC treatments and potentially greater control over the disease for patients.

Interesting suggestion re. future trials - surely something has to change? Perhaps exclude steroids completely from SOC treatment and if a patient experiences a flare that requires steroids then they're taken off the trial and counted as a non-responder. Measurement of patients dropping out due to requirement of steroids then becomes an outcome measure in itself as you would hope to see a lower drop off rate from the treatment arm. But wdik?

Richardo,

The failure announced yesterday by AstraZeneca was just the first of 2 large phase III trials for Anifrolomab. Results from the second trial are due later this year. The first trial split patients into low and high dose treatment arms but the second trial is only using the higher dose. It's therefore still possible that the second trial might be successful.

Anifrolumab targets the type 1 interferon system by inhibiting the interferon receptor. It may be that when AZN drill down into the data they find that patients with a high IFN gene signature responded better to Anifrolumab and that there is still the potential to take the product to market for this subset of patients. It's worth noting that the Anifrolumab trial in rheumatoid arthritis which began only a few months ago, will only recruit patients with high type 1 interferon gene signatures.

In other words, I think it's far too early to think that AZN may be interested in Lupuzor as we don't yet know of their intentions for Anifrolumab. You also have the issue that AZN recently offloaded most of its autoimmune pipeline to a new venture backed by Chinese investors. Their reason was that the drugs didn't fit in with its 3 core research areas which are oncology, cardiac and respiratory so they're unlikely to be in the market for any new autoimmune drugs. Think we should look elsewhere for a partner for Lupuzor.

Just IMO of course.

Thanks, but all Lupus trials must be carried out with both treatment and control arms continuing to receive standard of care therapy - the FDA and appropriate ethics committees wouldn't allow the trial to go ahead otherwise. Also if Lupuzor ever made it through to approval, the labelling would be as an additional treatment to SOC - it wouldn't be instead of so obviously needs to be tested in that setting.

Clearly the nature of the disease, difficulties with trial design and lack of biomarkers are making it very difficult to achieve success in the clinic. On the one hand you have a growing pile of drugs that have shown early stage promise but have failed at the last hurdle and on the other hand you have patients relying on steroids and antimalarials. Surely something has to give.