Member Info for Burble

In the guardian today. https://www.theguardian.com/business/2021/feb/09/ba-plans-transatlantic-flights-partially-fuelled-by-recycled-waste-in-2022?CMP=Share_iOSApp_Other

Would I be right in thinking that should the Aries case go our way, we could see more interest from the US on the deployment of EQT technology outside of the forestry side of things?

I’m just curious as to whether they have been in discussion with others stateside which can’t be finalised until the case is put to bed.

Thank you to each and everyone of you for your kind words. It's tough going at the moment, but we will survive and I'm sure what comes out the other end will be stronger.

I hope that the pandemic makes people realise what they truly value in life and advocate for these things rather than taking them for granted!

Anyway, onwards and upwards.

Which makes it 1630 GMT for the hearing. I wonder when we will hear results - same day? Same week? Longer time scale?

WF.

Sadly this is very much the case. Due to CR.UK cuts I am now currently sat on redundancy notice. Decades of investment into rare cancers with significant unmet research needs may end up being mothballed if myself and colleagues do not find a way to
remain funded. Thankfully we have some cash funds we can stretch a little further, but have a grace period to try and work out an alternative which may keep us in business, but the impact of Covid on research is far reaching and for many it will be the end of the road for their work.

The sad fact of the matter is this government and many past governments have failed to appreciate the role that the charitable sector plays and what they provide for this country which should be provided by central government. Rather than funding things properly, the third sector has taken up the slack which was fine when charitable donations were generously coming from the public....but unfortunately charities have been thrown to the wolves during this pandemic. I dread to think what the knock on effect for cancer research over the next few decades will be.

But we are where we are. Like you said in the context of SCLP, we will move forward and our time will come.

Ivy,

Agree, not entirely unexpected given what’s going on in the charitable sector. For me, the big question is definitely what progress has been made? It’ll be a bit gutting if the answer is none. We can live in hope that there has at least been something done and that it hasn’t been sat on a shelf for all this time.

Debs,

Immunotherapy is the broad term used to describe any treatment which helps your immune system fight cancer. The type or brand of immunotherapy is dependent on cancer being treated. Whilst scancell are working in the field of harnessing the immune system to target cancer, I would hazard a guess to say this probably isn’t scancell given what we know about the current state of play with our portfolio.

https://www.nihr.ac.uk/news/nihr-issues-final-update-on-implementation-of-the-restart-framework/26717

Some data on clinical trials restarts

C7

It wouldn't surprise me if these companies have built up quite a repertoire of data regarding where exactly the immune response from patients both vaccinated and naturally infected is focussed on the surface of the Covid-19 spike protein and in the case of naturally infected, probably the other viral proteins. As such, using computational modelling, they would be able to generate heat maps of key areas on the spike protein which could render a virus capable of vaccine escape.

As new variants became known, it would then be relatively easy to see whether these were located within these 'hot spots' and have an idea whether or not they would have a biological effect. This would reduce the amount of time needed to screen these new variants as it could be done computationally.

Another benefit of doing it computationally is that vaccine manufacturers would be able to do run these computationally using patient stratified heat maps - e.g. immune response from patients 90yrs +, 80 yrs +, with a particular comorbidity. As more data comes in both from immune responses of patients and naturally occurring infections the models could be refined accordingly.

An example of this type of work - this time in HIV, can be seen here in the paper titled 'Human anti–HIV-neutralizing antibodies frequently target a conserved epitope essential for viral fitness' (https://www.researchgate.net/figure/Mapping-of-the-HIV-1-gp120-core-epitope-A-Heat-map-summarizes-the-binding-of-the_fig3_45461541). It wouldn't surprise me if this is the type of surveillance that is ongoing and with probable collaborations between the vaccine companies, Public Health England and the COVID-19 Genomics UK (COG-UK) consortium.

For the 2nd gen vaccines, they have the time to adjust accordingly - we see this with the Covidity news today and the realisation that the SN15 may be better than SN14 given the changing situation. The benefit for us and the mRNA vaccines is the ease at which we can change the nucleotide sequence according to the changing situation on the ground. It will be interesting to see how the MHRA see changes to these vaccines - whether they are happy to approve changes without the need to do full trials.

C7 what time was your post? I’ll go back and find it and respond in a bit.

Bermuda,

You are indeed right. My pre-coffee brain wasn’t thinking properly when I typed that!

The thing that stood out for me was no mention of the lipid nanoparticle delivery system. It’s all well and good having SN14 and the new SN15, but not being able to deliver them complete hampers moving this into trials. I appreciate that their partners may be working on this and as they are not a company they won’t need to report, but it surprises me that there isn’t even a simple sentence saying ‘our partners are progressing well with delivery formulation’. Maybe it’s the pessimist in me, but it’ll be interesting to see when I’m 2021 they initiate the P1 clinical trial of Covidity. I wouldn't be surprised if it’s far later in the year than people expect. Ah well, onwards and upwards.

Some interesting information and I’m glad they have already identified another construct which could be used against new variants. That’s promising.

Another thing that struck me is the CRUK collaboration seemingly is still not decided. I wonder when CRUK will make those decisions or whether it’ll be kicked down the road for longer.

Unsure whether this has been posted before, apologies if it has.

But this is on the Guardian atm. https://www.theguardian.com/us-news/2021/jan/23/boeing-says-it-will-make-planes-able-to-fly-on-100-biofuel-by-2030?CMP=Share_iOSApp_Other

It mentions ‘ Boeing first must determine what changes to make to enable safe flight on alternative fuels derived from used vegetable oil, animal fats, sugar cane, waste and other sources.’

So seems the big guns are also looking at sustainability for their planes.

This is a nice paper, but if you look at Figure 6A - you can see that of the spike protein sequence, amino acids 314-543. Only four of these show good binding (344-363, 454-473, 464-683 and to a lesser extent 524-543). Of the mice which did respond, you can draw the conclusion that of these peptides, the immunodominant one is 464-483.

Out of the 6 mice immunised, 4 generated an immune response to this general region. Now imagine if this was mutated and therefore these mice lost immune binding capability. The immune response raised by a vaccine wouldn't work any longer and so that mouse would be able to be infected again.

https://www.nature.com/articles/s41392-020-00402-5

Hi C7

In response to your question regarding vaccine efficacy against new mutations. As you probably know the Pfizer, AZ and the Moderna vaccines all cause an immune response against the full-length Covid-19 spike protein. As such, you end up with a ****tail of antibodies and T-cells being raised by the patient's immune system against the spike protein (a polyclonal immune response). In most people, there will be immunodominant epitopes on the surface of a foreign body - which in this case is the SARS-COV2 spike protein. Whilst the immune response initially raises a large number of different low affinity antibodies, over time we see selection of specific antibodies which target these immunodominant epitope regions on the spike protein.

The worry for vaccine manufactures and governments is if one of those mutations is in a region to which most peoples immune responses are targeted. If so, their immune response is diminished and the vaccine fails to work or fails to work well enough to prevent infection/severe symptoms.

There are a number of ways to check vaccine efficiency. You can take blood samples from Covid survivors and screen these for binding against the normal spike protein. Then repeat that same assay looking for binding against the mutant. If the results are the same, then the mutation has no effect because antibodies are able to detect both proteins. However, if the antibodies present in the patient sera can only bind the wild-type protein rather than the mutant, that is worrying and suggests the vaccine may not work.

This can (depending on the mutation) be done computationally. If you know the patches where most patient antibodies bind (ie the immunodominant epitopes) you can simulate these new mutations to see whether they may have a detrimental effect.

Furthermore, for many patients you will find more than one immunodominant epitope, so a mutation in 1 does not mean game over for being able to neutralise the spike protein. It's the combinations which are worrying, especially if those combinations occur within multiple key epitopes on the surface of the spike protein.

TF,

You're right, my apologies for the confusion. I forgot that it was the combo part of SCIB1 which was the part which needed ICU beds, not the original arm.

I do therefore agree with you, if this gave them an opportunity to recruit more patients and generate more data then that might work. I wonder whether they could put it as two arms for a trial. You can always open one arm and then the other at a later date.

You may be right there, in a way a backlog of cancer referrals may mean that there is more pressure to get SCIB1 back up and running, and possibly SCIB2 off the ground. Especially as we have a small cohort worth of results that show promise - would mean that it isn't a completely unknown entity. There would also be data which suggests patient benefit to recruiting onto this trial rather than a complete unknown. Plus I would assume that the data that was generated from the initial cohort of SCIB1 patients will have been analysed at least partially.

Not a problem in the slightest.

Whilst there was impacts to research and clinical trials during the first two lockdowns, there is a general consensus across departments that if capacity is there, then they should aim to continue. As such, speaking to friends who work at clinical trials units across the country, there are some new trials being submitted and opening as we speak.

The main problem comes if the clinical trial needs ICU space in case of a serious adverse effect. For many trials, especially P1, this may be one of the criteria - hence if ICUs are full of Covid patients, the oncology trials won't go ahead as planned. Depending on R&D departments, they may have the full sign off at Trust level, such that they can hit the ground running in due course when things settle down, but the physical dosing may not begin if covid pressures are too great.

Didn’t LD mention during her AGM talk that the FG2811 antibody may be able to be used as a therapy for autoimmune diseases by dampening down autoimmune responses.

I wonder whether this is a patent for use of this antibody. The anti SSEA4 antibodies have been patented but I wonder whether this is now a patent for use rather than the actual physical antibody itself.

I guess we will find out in due course.