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Afternoon - hope you all had a wonderful Christmas and managed to switch off and spend time with loved ones.

Not sure whether this has already been posted, but I notice Lindy Durrant is presenting at PEGS Boston in May. She rounds of the session on 'NOVEL APPROACHES FOR NEXT-GENERATION ADC DESIGN' . In case anybody isn't sure, ADC = Antibody Drug Conjugate. Good to see her highlighting the potential of Scancell's suite of anti-glycan mAbs and Avidimab.

4:20 pm
Multi-Functional, Multi-Targeting Anti-Glycan Monoclonal Antibodies

Lindy G. Durrant, PhD, CSO, Scancell Ltd.
Glycans are excellent tumor targets. Notably, the same glycan expressed on a range of glycoproteins/lipids allows mAbs to target multiple antigens some of which can internalize whilst others are retained on the cell surface. Our mAbs can be potent ADCs but also retain ADCC/CDC activity and can cause membrane perturbation resulting in direct cell lysis. Additionally, Avidimab increases the avidity of any mAb and results in improved tumor killing

https://www.pegsummit.com/antibody-drug-conjugates

A cracking RNS to end the year with another miestone payment triggered. AZD5055 has clearly performed well in preclinical testing and let's hope it does the same in the clinic. Link to the clinical trial record is below - a 104 patient randomised study with single and multiple ascending doses.

https://clinicaltrials.gov/ct2/show/NCT05134727?term=AZD5055&draw=2&rank=1

https://www.news-medical.net/news/20211215/Cell-surface-expression-of-SARS-CoV-2-nucleocapsid-protein-and-its-role-in-immunity.aspx

https://www.biorxiv.org/content/10.1101/2021.12.10.472169v1

Interesting summary of research from the US National Institute of Allergy and Infectious Diseases (NIAID) looking at cell surface expression of the nucleocapsid (N) protein and its role in immunity to Covid. The conclusion:-

'N may be an Ab and T cell target for future “universal” vaccines offering broader protection against future SARS-CoV-2 strains as well as other human coronaviruses.'

Also worth noting the possible role of the N protein in long covid - very, very early days and clearly needs further investigation, much more research and clinical trials, but imagine a vaccine that acted as a booster and also helped with the symptoms of long covid.

roses,

What a crappy article from Claire Anderson in the Express. She could have opted to explain that we are entering uncharted waters with a new variant and 3rd boosters and it's only with the passing of time that we can possibly know when immunity will start to wane for each age group. Instead she opts for the lazy clickbait headline 'experts clueless'. Demanding instant answers when there are none to be had.

The performance from some quarters in the media has been abysmal from the outset of this pandemic. If only all reporting of covid related matters had been left to science/health correspondents things might have been very different.

The only similarities between DIOSynVax and Scancell is that they are both developing DNA vaccines and both are using PharmaJet.

DIOSynVax are using machine learning and algos to look at the structure of coronaviruses and predict how Covid will mutate in the future. They then pick a selection of eptiopes from various proteins that they believe will give the greatest protection. Clearly the end product is only as good as the data input and the accuracy of the algos. If you're going to use machine learning to make predictions on how a virus will mutate, then you need to build as much historical data as possible and that requires time for the virus and mutations to evolve.

Scancell on the other hand are developing an existing cancer vaccine which has already demonstrated in the clinic that it generates potent immune responses. They are targeting only the receptor-binding domain (RBD) - the key part of the Spike protein which allows it to dock and gain entry to human cells as well as the Nucleocapsid protein which is largely conserved, not only with new variants but also between different coronaviruses. On top of all that, Scancell's ImmunoBody platform has a dual mechanism of action and is enhanced with Avidimab which generates much more potent antibodies -it's more than just another DNA vaccine.

The interesting thing about DIOSynVax's approach is that once their algos have selected the epitopes, they can use any type of vaccine to deliver them and it's worth noting that they've decided to use a DNA vax with PharmaJet delivery system. Wish DIOSynVax well. We need as many 2nd generation vaccines to succeed as possible and it would be great to see more British bios up there.

WTP - Well spotted, thanks for posting.

Burble - do we have you to thank for alerting Julia Kollewe to Scancell?

Yes Ergomed has had a cracking run over recent years and has matured into a solid business with a fat order book in the safe hands of Richard Barfield.

Yet more good news from Redx. Milestone triggered by entering the second year of development which suggests that progress is at least satisfactory. Next milestone due on successful submission of an IND to the FDA. Excellent stuff and good to see Redx quietly getting on with the job in hand.

BOJO - there are a handful of others also targeting spike and nucleocapsid proteins and data from any of them validating nucleocapsid as a target can only make Covidity more attractive to potential partners.

burble,

Apparently ImmunityBio have circumvented the issue of anti vector immunity by genetically engineering to delete genes encoding for certain proteins - of course yet to be proven in the clinic.

Wild,

Yes, we really don't know for certain that those patients are alive today. However, what we do know is that the SCIB1 results were wonderful and they're in the bag, nobody can take that away. Looking forward to seeing more patients treated with ImmunoBody vaccines to build on the body of evidence.

roses,

She didn't use the word 'today, but she did say they are still alive and well and I agree that does suggest that they're alive and tumour free today. However, I believe that with the time constaints involved she may have forgotten to clarify that the survival data shown on the swimmer plot is up until the point that Scancell stopped collecting follow up data back in 2018. Otherwise they'd surely have updated the swimmer plot with longer survival times but they haven't - it's frozen at the 2018 stage with the remarkable survival data at that time.

I think we have to be a bit careful re. LD's comments on the SCIB1 swimmer plot slide. We know that according to the clinical trial protocol, patients were to be followed up for 2 years after their last dose and Scancell have confirmed that they stopped collecting ongoing survival data in Feb 2018 (2 years after last patient received final dose). Indeed if you look at the swimmer plots presented by Scancell in 2018 and the one presented last night, you'll find they're identical.

I think it's highly likely LD simply meant that at the stage Scancell stopped collecting data, all 10 resected patients were alive and disease free.

Just had another listen and LD clearly says:-

'As you're probably aware SCIB2 was partnered with CRUK and BioNTech'

Surely that's a mistake?

hasiba,

I'm not sure whether your comments about Scancell's labs are borne out of lack of research, malice or fundamental ingorance of biotech. and the drug development process.

Anyhow, just to reinforce Ray's comments, that Scancell's Nottingham labs are in the £100m brand new, Biodiscovery Institute, equipped with state of the art labs. Lindy Durrant's UoN role has given Scancell access to labs and equipment that most bios can only dream of. Have a read of the link below and you'll see there's not an inch or cardboard in sight. Anybody who has any experience of investing in bios. knows that at outset, many processes are outsourced. Baby bios simply don't have the funding or resources to do everything in-house. As companies grow and mature they will bring more and more functions in-house and that's exactly what the Oxford labs are all about.

As you're holding long and strong you should be thrilled to see that Scancell now have 2 state of the art laboratories, each performing different functions. It's great to see UK inovation being taken forward and that Scancell are now a step further ahead. I believe that you are very keen on another bio that doesn't have any labs or do any of its own research and development so I'm really not sure what your issue is with Scancell's.

https://www.nottingham.ac.uk/research/research-areas/biodiscovery-institute/infrastructure/infrastructure.aspx

Taverham,

All of the approved vaccines and the vast majority of those in development target only the Spike (S) protein. Scancell and a handful of others are targeting both the Spike and Nucleocapsid (N) proteins. Whilst the N protein can and does mutate, it does so at a much, much lower rate than the Spike and is highly conserved between different coronaviruses. For example, Scancell's preclinical research showed that Covidity recognised an N peptide from the original 2003 SARS coronavirus.

The fact that a protein has mutated doesn't automatically mean that the vaccine won't work - think of it as a really long sequence of code, imagine hundreds of letters and just one slightly changes - the vaccine may not even be targeting that particular bit of code and even if it is, it should recognise the other letters around it. Clearly the more changes and the greater the frequency of change, the greater the possible impact which is why the N protein has such great potential as a target.

Kashdog,

We really don't know what impact the new variant will have, but if nothing else it's a sharp reminder of the need for better vaccines. It's not going to be good enough to simply let Pfizer and Moderna continually boost the population (and their revenues) to protect against new variants and waning immunity. You're right about future speed of development and I think Scancell have already confirmed that they'll look for a partner after the current trial. In the meantime though the rapid emergence of the B.1.1.529 strain has heightened awareness of the risks of Covid and of new variants and this can only help with speed of recruitment to Scancell's trial.

Please ignore the rubbish at the end of the post - it was intended for elsewhere

Afternoon all.

Anyone have any thoughts on the new Modi1 clinical trial design? Worth having another look, there's the obvious addition of both monotherapy and checkpoint inhibitor combination arms for H&N cancer in the neoadjuvant setting but there are also other more subtle changes.

Interesting that when LD was presenting at the OXT shareholders meeting on 28th July (just 3 or 4 weeks before MHRA gave clinical trial approval), she was still presenting the old design and the combination arms were going to use Bristol Myers' Opdivo (Nivolumab) for the PD-1 checkpoint inhibitor. That's been dropped from the slide for new design and it no longer specifies which checkpoint inhibitor will be used, indeed they don't even specify that it'll be a PD-1. I assume we'll have to wait until the trial appears on clinicaltrials.gov to find out.

Pure speculation of course, but it would be great if Scancell were to run the combination arms of the study in collaboration with the pharma responsible for the checkpoint inhibitor.

https://www.youtube.com/watch?v=VprjClirb8k

https://www.scancell.co.uk/Data/Sites/1/media/docspres/agm-presentation-2021.pdf

3) The TNB and Ovarian monotherapy arms will then run in line with the previous design
4)