Member Info for Burble

Remind me was the AGM last year an in person event?

Also remember we are talking about two different diseases.

Cancer vaccines can show results relatively quickly - either tumour shrinkage, tumours disappearing etc. plus stage 3 or 4 melanoma patients have relatively low 5 year survival rates (63% and 22% respectively). So results may come quicker the longer patients are on trial.

Compare that to covid-19, are you interested only in whether it prevents serious disease? Serious disease against more than one variant? Lower overall infection rates? There are so many variables in what questions want and need to be asked. So doesn’t surprise me that the trial goes on longer and that there hasn’t been a eureka moment announced just yet.

5th of July was their last post. Maybe they’re on holiday?

It’s what the people in white coats refer to as keeping me out of trouble for the next 30 years.

If that’s you spending pocket money, I really should consider my life choices when it comes to employment!

*Dame

This caught my eye in the guardian article.

‘ With some data suggesting Omicron-specific vaccines offer little advantage over current jabs, [Dams Kate] Bingham said there was a need for those that tackle multiple variants, adding it was also important to move away from needle-based vaccines due to cost. “Whether it’s patches, sprays, pills, implants, whatever they may be, I think we’ve got to go there,” she said.’

https://www.theguardian.com/society/2022/jul/17/uk-missed-chances-prepare-future-pandemics-vaccines-kate-bingham

LD ahead of the curve again?

Thanks RR,

I’ll have a look.

Being a notable company won’t be a problem in a few months time when we have Moditope results, an Avidimab license with big pharma, Covidity being given to the general population, SCIB1 curing melanoma and GlymAbs going forward at light speed.

Maybe I’m just premature in writing this. ;-)

Unsure.

It’s weird because I copied an existing Wikipedia page for ITM power, changed the different aspects and we already have pages for SCIB1 and Lindy.

It’s also asking for additional sources. But if you look at many of the sources they’re not all just Scancell related, there are journals, news articles etc. so I thought it was relatively level and not self promotion, but obviously Wikipedia thinks differently.

Bad news folks. The reviewer of the wikipedia page decided to decline the publication of a dedicated Scancell wikipedia page. Despite there being one for SCIB1 and one for Lindy Durrant.

Submission declined on 11 July 2022 by Stuartyeates.

General information:
This submission's references do not show that the subject qualifies for a Wikipedia article—that is, they do not show significant coverage (not just passing mentions) about the subject in published, reliable, secondary sources that are independent of the subject (see the guidelines on the notability of organizations and companies). Before any resubmission, additional references meeting these criteria should be added (see technical help and learn about mistakes to avoid when addressing this issue). If no additional references exist, the subject is not suitable for Wikipedia.

Reviewers comments:
Largely based on primary sources, sponsored links and marketing material. Some claims not sourced at all.

Going to have a rethink, dig out some more references and resubmit.
https://en.wikipedia.org/wiki/Draft:Scancell

You’d get it for the first dose, but the second unfortunately you’d have to pay more for.

As this has a two-part vaccination schedule - we consider it a prime/boost vaccine candidate. You get the first on overnight shipment, the second you have to pay carriage for.

So looking at the clinicaltrials.gov website it seems the following route is being taken.
- identify and make multiple patient specific neo-antigen peptides
- deliver these to the patient along with an immune stimulatory adjuvant (poly ICLC)
- alongside this also treat patients with nivolumab (PD1 inhibitor) immunotherapy

Theoretically this could work.

However, this throws up some critical drawbacks for me mainly around the 'Identify and make multiple patient specific neo-antigen peptides'
How long does the manufacturing and formulation for this take. As we have seen with our peptide based modi-1 drug manufacturing, this isn't as straight forward as many would hope. Individual peptides may be relatively easy to manufacture, but may be an absolute mare to get into a formulation fit for administration. Will these peptides then be mixed together? If so, what common components will you need to get those all into solution in a single tube to deliver to the patient. If administered separately - that means five different solutions, which could theoretically be thought of as five individual drugs - this could bring with it regulatory, GMP manufacturing and supply chain hurdles.

Patients on this trial have stage 3 or stage 4 disease. Any delays in manufacture or formulation would be at the detriment of the patient.

If you are looking for T-cell specific epitopes, we also know that for many MHC Class I peptides there is a bias towards hydrophobic amino acids at T-cell receptor contact residues. This makes formulation slightly more difficult trying to keep peptides from not sticking together or dropping out of solution. Also as we have seen from Moditope papers, not all T-cell epitopes make good vaccines.

On top of all of this the cost both in time and reagents to manufacture bespoke products on an individual patient by patient, disease by disease basis is high. Whilst I appreciate peptide manufacture isn't anywhere near as high as autologous T-cell therapy manufacture, personalised medicines can cost upwards of £280,000 per patient (cost to NHS for tisagenlecleucel for example is £282k per patient).

Now let's compare.
- Immunobody platform - DNA based, cheap to produce, quick to modify, long term stability, standardised formulation, good safety profile, able to be an off the shelf product, patient agnostic.
- Moditope platform - peptide based, slightly more difficult to produce and formulate, broad targets, stability unknown, slightly more complex formulation, assumed good safety profile (no adverse effects reported so far in trial), able to be an off the shelf product, patient agnostic.

IMHO both Immunobody and Moditope cancer vaccines excel in comparison to this trial and many other cancer vaccine trials. So good luck to Amazon and the patients treated by this trial, but I'll stick with my decision to invest here.

An interesting paragraph.

‘ In recognition of the fact that the Lanespark Project will supersede any pre-existing arrangements between HUI and PHE, the parties have agreed that on entering into the definitive agreements, the existing exclusivity agreement between PHE and HUI's UK operating subsidiary, as well as the related existing collaboration agreement, will each be mutually terminated without any further obligation on either party.’

I wonder why? Does PHE have better options on the cards but can’t bring them to fruition because of this legacy agreement?

Dracula

I would say in order my guess would be
- Covidity next few weeks
- moditope - before September
- Avidimab licensing - by December
- GlymAbs data - Q4 2022-Q1 2023

Good for NeoTX if their trial is going well.

I however am happy with my investment here for a number of reasons.

Dosing for naptumomab estafenatox (the NeoTX compound) is a multi-step infusion given back to back over consecutive days and the dosing schedule is then repeated a few weeks later.

In comparison dosing for Immunobody and Moditope are single injections given a few weeks apart. Meaning patients have less time in hospital (patient and healthcare service therefore benefits)

Naptumomab estafenatox has to be given in multiple smaller doses due to the risk of massive cytokine release. SCIB we have shown the limiting factor is the amount you can get in a needle (if using Trichor) but this will change going forward with needle free. Even upto 8mg we haven’t seen any major toxicities in the Ph1 SCIB1 trial.

Being protein based, naptumomab estafenatox has the risk of anti-drug antibodies being generated. Hence the more you get given the drug the more chance there is of your immune system mounting a response against either the super antigen itself or the antibody end. Whilst the company can make different flavours of the compound targeting other antigens apart from 5T4, it would limit how often you can dose the same patients as over time (and as we have seen with naturally occurring immunity to the super antigen may limit the cohort of patients it may work properly on.)

Immunobody hasn’t got that drawback being a DNA based drug and moditope is a short peptide based drug, which you’re wanting an immune response against the peptide. You won’t mount an immune response against any scaffold regions of this because there aren’t any.

For those reasons. Whilst I wish NeoTX the very best in their trial. I suspect our platforms will be of more value to patients, and of more interest to potential investors or pharma companies in the long run.

Chester 5T4 has limited expression in cells, but is expressed widely in a large number of cancers. Hence many have tried (and failed) to target this protein due to its confined expression in malignant cells.

Chester - good post. However, I hope you don't mind me offering a minor correction.

Covidity itself doesn't ever need to see the nucleocapsid. In some essence it *is* part of the nucleocapsid (i.e. there is a short section of the nucleocapsid encoded within the covidity DNA coding sequence. When covidity is transcribed and then translated, the final functioning protein (which includes this fragment of the nucleocapsid) is presented to dendritic cells). It is this which in turn results in the generation of specific T-cells which recognise and target cells infected with Covid-19. The surface of these infected cells are decorated with fragments of the virus and will include sequences from the spike protein, the nucleocapsid protein, and any of the other 27 proteins from the virus. It is the nucleocapsid sequences which decorate the surface of the infected cells which are then recognised by the T-cells produced by covidity. These then target and kill the cells including the viruses inside. As such, covidity/the T-cells generated by this never need to infiltrate the nucleocapsid to function.

The two pronged approach SCLP have taken with covidity means covidity also generates B-cells which will generate neutralising antibodies. In this case, these B-cells target the receptor binding domain. Antibodies produced by these bind onto the receptor binding domain of the covid-19 virus particles. These viruses are outside of cells (either because a person has been newly infected or because they have actively replicating virus inside them). These antibodies bind onto the RBD and in doing so prevent the free virus from latching onto other cells and infecting them.

When the trial opened we had Nottingham and Edinburgh open (07/04). the most recent change was added on the 17/05 which showed Imperial opening.

CleanerWorld
Yes Imperial covers five hospitals across North West London, however patients would only be treated with Modi-1 at Hammersmith as this is where their clinical research facility is located and given this is a phase 1 trial the additional facilities that this specialist unit has would be a requirement of the trust to run the trial.

‘ Scancell pushes on in the shadows …’

Scancell now are both an oncology and infectious disease focussed company…I wonder whether a monkeypox product is the next Immunobody to be added to the list.

That would really put the goods in the shop window so to say. It would fit with CEPI’s 100 days for a vaccine drive. It would highlight the versatility of the platform over and above oncology.

Yes it would be spreading company assets thinner, but from a scientific perspective it would be v.interesting. Even if it didn’t get to preclinical and just was published as a scientific manuscript it would be a powerful reminder of adaptability of the platform.

Obv. Drawback is there is already an effective monkeypox vaccine, so sales probably wouldn’t be high unlike say a flu vaccine or HIV vaccine.

Oh no, what a nightmare Roses. I hope it passes quickly, treats your kindly and that you and the family recover swiftly and with no long lasting problems.