Member Info for Burble

Ross. That is up to you to decide. If you brought in at 4.8, then you're looking at approximately a 50% return on your investment. If that is enough for you, then cash out and leave. Nobody can tell you what to do with your money. Also welcome to the LSE share boards, as a newly registered account as of today it's good to see you start your posting journey on the VLS chat board. Good luck with your investment whichever way you decide to play it.

Am I right in thinking that if SCLP had submitted to the CEPI funding call, it was for the proposal titled 'Broadening protection against SARS-COV-2 and new broadly protective Betacoronavirus candidate vaccines'?

If so I was looking through the call for proposals (https://cepi.net/wp-content/uploads/2021/03/CfP-BPCV-Call-Text-FINAL.pdf) for which the expression of interest window closed on the 1st October 2021.

Review process starts on the 15th and 30th of the month (or the following business day). So based on that, if we have submitted something, then EOI has likely has already been reviewed already. Applicants passing the EOI stage will then by invited to submit a full proposal and have six weeks to submit a full funding proposal. So again that might already have happened.

If that's the case and the final date for EOI date was October 1st 2021. Then if anything that came in last minute is reviewed this would occur either on the 15th October or the 30th. I would therefore think we would hear news soon! I wonder whether SCLP will notify us either way or whether we will only hear if we have been successful.

Another publication that highlights the need for second generation vaccinations. Whilst this suggests a 16 month reinfection rate for the unvaccinated, we are seeing waning protection in the vaccinated community too. Hence, the hope for positive Covidity data over the next 6 months or so. Plus we may hear if we have applied or been successful from CEPI soon by the sounds of their tweet.

https://www.theguardian.com/world/2021/oct/19/without-covid-19-jab-reinfection-may-occur-every-16-months-say-scientists

Ray

No head and neck cancers area classified separately to CNS tumours. The classification of cancers usually come from what cells are involved - brain tumours come from cells of the central nervous system. Head and Neck cancers generally begin in the squamous cells that line mucosal surfaces (as well as a few other cell types including lymphomas, adenocarcinomas and sarcomas).

Head and neck cancers therefore includes cancers of the mouth, tongue, throat, as well as those of the nasal cavities, sinuses, salivary glands, tonsils etc. Are linked to alcohol and tobacco consumption as well as infection with HPV.

Sadly for many of these cancers, the drop off is quite stark. 1 year survival for hypopharyngeal cancer in adults is 60.5%, but drops to 27.8% 5-year survival and then 19.1% 10-year survival. Hence why this new combo-immunotherapy trial is so exciting and moditope even more so!

Also to add - the HRA have a policy that they will give ethical opinion within 60 calendar days if the receipt of a valid application.

Roses

As a HRA REC member, we’re doing all meetings by Zoom now. It works really well to be honest with you.

Chester - it depends which committee they have submitted to. Most sit monthly for 10 months a year, so our REC had September off and return next week. Others it’s slightly different.

It will also depend whether they have chosen to submit to a specific REC or whether they have chosen ‘next available slot’. Obv the latter is quicker, but as different RECs have different characters and experience of the people sat on them, some people will choose to wait for a specific REC. Also other things to factor in when choosing where to submit is how efficient the approvals team are. Some are better than others at responding to queries, so you find researchers will apply for ethics from the ones which are easier to communicate with. This is important if you think there may be amendments added in the future.

I saw this. Fantastic news for a difficult time treat disease.

Will be good to see how Moditope fares against that drug combo,

Was an interesting piece on Covid vaccines targeting the S and N protein. Sadly mention of other clinical trials (I.e. SCLP) we’re not named in person, but was still good to hear the talk around S and N protein targeting vaccines - especially in the context of variants.

Roll on First patient dosed

https://www.medrxiv.org/content/10.1101/2020.08.14.20174920v2.full.pdf

This is the pre-print of this - so may not be the fully peer-reviewed one, but it has probably got 99% of the text that is published in.

Something also to bear in mind is that
submissions don’t mean a binary approval. Ethics/Regulatory committees may provide provisional approval subject to changes - these can be as minor as a change to wording to patient information leaflets, or additional data required. So whilst we have an idea of where in the process we are by the mile stones reported in RNSs, we’re not privy to any of this background movement. Hence first patient recruited may come anytime soon, or alternatively there may be a longer period of quiet before we get that news. Difficult to really gauge.

Chester

When applying you can apply in two manners - either for a specific committee or you can request any committee. Many projects are choosing the latter because the pandemic has offered flexibility and agility - making approvals a bit smoother.

Some people are prepared to wait for their specific local committee. So just because SCLP is based in Nottingham/Oxford doesn’t particularly mean that they will be getting approval from these.

Powerhouse signs binding exclusivity agreement to deploy technology in Poland, Greece and Hungary

Powerhouse Energy Group plc (AIM: PHE), the UK technology company commercialising hydrogen production from waste plastic, is pleased to announce that it is has entered into a binding agreement (the “PGH Exclusivity Agreement”) with Hydrogen Utopia International PLC (“HUI”) under which HUI has been granted an exclusive non-transferable licence for the application of Powerhouse’s DMG® technology in Poland, Greece and Hungary. HUI’s corporate mission is to create a project pipeline for Powerhouse’s DMG® technology in these regions through seeking funding from and partnering with states, regional authorities and the private sector in targeted regions to facilitate the deployment of DMG® technology.

Just catching up on posts.

I'm sorry to hear of your loss Ratcliffe. My thoughts are with you and the family at this difficult time.

Taverham,

Preclinical models are the experiments conducted directly before a drug goes into humans. So generally animal models, but may also be additional lab based experiments.

Generally these are looking for off target toxicity, efficacy, drug metabolism, distribution, delivery mechanisms, bioavailability for example. So in a nutshell gaining as much data to support the move into patients.

Interesting point to note is that the enolase peptide may be added at a later date if no safety issues with the vimentin peptides. Am I right in thinking that the enolase peptide was the one giving us grief in manufacture?

From a patient perspective, this is such a milestone, four groups of patients, all with difficult to treat cancers may have a lifeline thrown to them. Even more exciting is the fact the results should be known in the next nine months. I hope so very much that the preclinical results translate through into the clinic and that patients enrolled on the trial benefit from this first-in human trial.

Ivy,

Pharmjet will help get DNA into the cells. In one of their other Covid vaccine studies, the delivery method was important for the DNA vaccine.

Needle-free systems like this have a number of advantages. The high pressure which delivers the vaccine results in the vaccine to be dispursed over a larger area than would be found through a traditional needle route( https://pubmed.ncbi.nlm.nih.gov/11251382/). This results in greater and enhanced update of plasmid DNA. In a study looking at the injection of rabbits with a malarial DNA vaccine using an intramuscular needle-free system, the NF delivery resulted in upto 10-fold increase in anti-parasite antibodies as compared with the standard needle injection (https://pubmed.ncbi.nlm.nih.gov/11567774/).

In a separate study looking at a dengue virus DNA vaccine, monkeys vaccinated using a NF delivery system developed higher antibody titres and these levels were stable for longer, than those compared with standard needle injection of the DNA vaccine (https://pubmed.ncbi.nlm.nih.gov/14585337/).

As for the former question - unsure. The dermis has a number of different subtypes of antigen presenting cells which may be better at cross-presentation than other routes of administration. There is a subtype of cells called the langerhans cells. The dermal subset of Langerhans cells which are found in human skin have been reported to be specialised in the induction of cytotoxic T-cells and in addition to that the human CD14+ dermal dendritic cells can promote antibody production by B-cells.

In the case of Covidity, we obviously want to produce Viral neutralising antibodies - i.e. from B-cells and then also the induction of cytotoxic T-cells. So this route might augment the immune response further and increase the efficacy of the vaccine.

I beg to differ.

If this trial were being run here in the UK, we would have had to submit a clinical trial application to both the MHRA and the HRA for approval. This would have to detail things like the delivery method, formulation, dosage, trial design, endpoints, samples taken from trial subjects. Hence this would have been known months ago when submission to appropriate authorities was completed.

The fact that they are announcing this to the market now, suggests that things are soon to go live!

https://www.theguardian.com/world/2021/aug/15/new-covid-variants-will-set-us-back-a-year-experts-warn-uk-government

I hope we get some good PR when first patient dosed and then subsequently interims come out. That would really light the blue touch paper beneath the Scancell rocket

So needle free is going to be either intradermal or intramuscular (slide 7). Interesting. Especially given this could then expand to any ImmunoBody DNA based vaccine.

Also nice to have a date put on the new patent lifespan. Another 20 years adds value to the platform as a whole.

https://www.cell.com/cell/fulltext/S0092-8674(21)00701-7

Lay summary: https://www.broadinstitute.org/news/researchers-identify-potential-new-targets-next-generation-covid-19-vaccines

Interesting finding - ‘ Surprisingly, we detected only one HLA-I peptide from N’… ‘ The N protein remained the most abundant viral protein in both cell lines.

An alternative hypothesis for lower N representation could be that the protein harbors fewer peptides compatible with the HLA binding motifs.’

‘Notably, N had fewer than expected presentable peptides than most SARS-CoV-2 proteins in both cell lines’

‘ Our results hint that N might be less presented than expected.’

‘ Thus, integrating T cell epitopes into the design of next-generation vaccines has the potential to provide prolonged protection in the face of emerging variants’

So we know Immunobody as a vaccine platform can generate high avidity T-cells against a presented target. This got me thinking, maybe compared to other N protein targeting vaccine candidates, we hold a trump card in the way these are presented to the immune system and the T-cell response generated. Exciting times!

I’m now curious which exact epitope LD has targeted in the N-protein.