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Not long until the AGM. I wonder whether it’ll be in person this year.

Caveat to this is that we are witnessing RBD mutations more - which could remove one of our weapons. So would mean we rely predominantly on T cells to clear infected cells instead of having both antibodies to prevent infection and T cells to clear anything that gets past that line of defence.

I’m of the opinion that we shouldn’t need to. If we can generate high avidity T cells to the Nucleocapsid protein, we know most variants of covid pick up mutations more in their spike protein rather than the more conserved N protein. As such, if the virus managed to evade the bodies B cell response through mutating the spike protein, the nucleocapsid protein should theoretically remain unchanged and therefore T cells come to the rescue by continuing to recognise this.

Instead of vaccinating with full length spike protein, we have opted to immunise with a region focussed only on the receptor binding domain. Whilst mutations may be picked up here by the covid-19 virus, the RBD region of the virus shouldn’t change as much due to this region being critical to the virus being able to bind the ACE2 receptor and infect cells. So the hope is any neutralising antibodies Covidity generated through this arm of the DNA vaccine, target B cells to generate antibodies against a region which hopefully mutates slightly slower than the rest of the spike protein.

Time (and data) will tell if Scancell were correct in this assumption.

Highly recommended reading

https://twitter.com/ellingulrich/status/1571051885506985984?s=46&t=9ZqTOdbMsXvLU-IEjOEYSQ

Yup basically! Covid is a moving target and vaccines are playing catch up. What we need is to get one step ahead.

Lots of publications and chatter about the new variants and how convergent evolution is helping with immune escape.

BA.2.75.2 for instance evades BA.5 immunity and seemingly evades all licensed monoclonal antibody therapeutics and is spreading quickly in India.

A really interesting pre-print. Recent evolution of Omicron has led to many subvariants that exhibit high growth advantages over BA.5. Interestingly, mutations on their receptor-binding domain (RBD) converge on several hotspots, including R346, R356, K444, L452, N460 and F486. https://www.biorxiv.org/content/10.1101/2022.09.15.507787v1

Pseudovirus neutralisation assays suggested variants in this paper were able to bind ACE2 and so could circulate the population, infect and spread.

Covidity targets the RBD as well as the N protein. It’ll be interesting to see how these variants stand up to the vaccine in the lab and in the real world.

C7

If Covidity data is positive and demonstrates that we are able to generate a lasting immune response both against a viral target and variants of then this could open a range of doors of different size. Especially given the fact that a) we know that stability of these DNA vaccines is long (years), and b) can be delivered by needle-free mechanisms.

The first one that comes to mind is influenza. The flu vaccine market was valued at $5 bn in 2020, and is projected to reach $10 bn by 2030. Every year the flu strain changes, so we are constantly trying to guess what the next season will be and manufacture doses for this. Scientists have for years tried to generate a pan-flu vaccine but so far none have been successful. There's a great article here which summarises some of the reasons why https://www.pnas.org/doi/10.1073/pnas.2123477119. Being able to generate both virus neutralising antibodies against a specific target AND potent T-cells targetted to the appropriate regions to provide pan-strain immunity in a similar manner to how covidity works would be attractive to many pharmaceutical companies.

Another that comes to mind, though a smaller target market would be something like ebola. From both a human disease and a defence angle. Being able to vaccinate against both of these would be good. Though target market is small and there are a number of different vaccines either in development or allowed under compassionate use. Being able to store vaccine for long periods with limited refrigeration would be one of the beneficial angles which a DNA vaccine could have the edge especially in areas where filovirus outbreaks tend to occur. Furthermore, studies have shown that CD8 T cell responses are targeted towards the nucleoprotein of the virus in ebola survivors (https://www.pnas.org/doi/10.1073/pnas.1806200115). So again, combining multiple T-cell epitopes into a single vaccine could be very pivotal in generating consistent and sustained responses, in a vaccine which is easy to store and easy to deliver.

These are just two examples where the immunobody platform could be utilised towards other infectious diseases. So covidity could open many doors for use in other diseases if the data is positive and if SCLP want to either go alone, license or sell the platform as a whole.

https://www.pharmamanufacturing.com/articles/2022/10-tips-for-improved-drug-development/

Updated link. The parenthesis caused a hyperlink error

TF

Inan and I had our fair share of disagreements. But one in particular I will always push back on is this idea of ‘no risk’. It’s utter codswallop and should be called out.

Look at success rates in drug development (see funnel diagram https://www.pharmamanufacturing.com/articles/2022/10-tips-for-improved-drug-development/)

Preclinical - 10-20 candidate therapies
Phase 1 - this drops to approximately 6
Phase 2 - this drops again to approx 4
Phase 3 - this drops again to around 2
Market

So just because we have seen SCIB1 working in the clinic - absolutely does not mean it is no risk and will be successful through to market.

Investing in pharma is not without risk. Any one of our therapies may fail. But equally any one of our therapies may succeed. Indeed, the more shots on goal we have the more chance we have of being one of the successful ones.

But to say no risk, is dangerous and shouldn’t be taken as gospel.

Great to hear from you LL, I hope you’re keeping well.

II (Interactive Investor) I’ve found to be very good, especially with respect to corporate actions. They’re very prompt at sending details of AGMs, voting etc and it’s incredibly easy to do on their platform.

You can currently get 6 months free, then £12.99 flat fee a month after that. Trades are £5.99 each.

I guess with many of these things it’s horses for courses, I know some platforms allow certain funds, ETFs, foreign investments etc to be traded. Others are more restrictive. So (and I know I’m probably preaching to the converted) definitely don’t your homework and choose something which is right for you.

Good luck! And look forward to hearing you’ve rejoined the 1m+ club!

I can appreciate the sentiment, but if you look at a single drug like keytruda, that in 2020 had sales exceeding £14bn.

$200m for SCIB1 - I could get behind. But $200m for worldwide exclusivity on Immunobody, which could potentially lead to any number of $bn drugs for cancer or infectious disease targets. IMHO is worth a lot more than just $200m.

Others may disagree but for a modular platform, I personally would be wanting either non-exclusivity or individual targets or ideally a far higher value than $200m, especially when you see what some other platform technology acquisitions have gone for recently. Sanofi for instance spent $3.2bn on an mRNA platform company Translate Bio. BMS purchased MyoKardia for $13bn odd for their clinical stage platform technology.

There definitely seems an appetite for platform technologies at the moment (see https://www.fiercepharma.com/pharma/ma-landscape-tilting-away-late-stage-buys-and-toward-platform-strategy-analysts), plus with Immunobody latent being extended by the incorporation of Avidimab into it, could be far more attractive to a potential purchaser who is prepared to pay a premium on that.

Genetech/BioNTech recently posted positive phase 1 results for their mRNA based individualised cancer vaccine. https://investors.biontech.de/news-releases/news-release-details/positive-phase-1-data-mrna-based-individualized-neoantigen. So they're obviously a logical collaboration partner.

Something stood out for me in this piece - 'feasibility of the process of profiling each patient’s tumor to inform individualized vaccine design and on-demand manufacturing of iNeST in a clinically relevant timeframe was confirmed.'

Just remember the immunobody platform (SCIB1 etc) - doesn't require individualised vaccine design and manufacturing. Neither does moditope. That led me to do a bit of digging and I found this interesting, Roche/Genetech entered into a worldwide agreement for Nykode's vaccibody technology in 2020. Vaccibody is a DNA based cancer vaccine technology which functions in a very similar way to the Immunobody platform. https://nykode.com/innovation-and-research/technology-platform/

Thinking aloud and I would welcome others input. I highly doubt Roche would purchase two of the same thing - though that's not to say they wouldn't to stop other people from getting their hands on something. Especially if one turned out better than the other.

Which leads me to wonder whether scancell have interest from someone other than Roche. Or Is Roche/genentech interested in moditope having got their hands on a worldwide exclusive immunobody equivalent for $200m. Could SCLP have turned down an offer of that amount?

Great find Bermuda!

No worries! :) thank you for the apology. I’m sorry I didn’t post my workings beforehand. Would have removed any ambiguity in my initial comment.

Ok, Matt, so yes my comment was incorrect because the source I was referencing was their measured amount https://twitter.com/annaalbecka/status/1565005630515060736?s=21&t=9PBfBVXcNBE37bBEziOAtw

However a more scientific test done at the Crick has details and comparisons. https://www.scientificlabs.co.uk/file/1060/Shaking%20Incubator%20Energy%20Consumption%20Case%20Study

Either way, the sentiment remains. Running a lab is costly in terms of energy usage, especially when you have multiple machines running constantly or intermittently through the day. Hence my comment that if energy prices rise (and businesses as we know have no price caps), the amount to just keep the science going will increase as energy prices go up.

Also factor in the new business rates on electricity mean the financial runway will be significantly shorter - electricity costs for running a lab will be steep and getting steeper!

For example, I found out the other day a single shaking cell incubator running for a day costs more than an entire house consumes in electricity.

Thanks for this! Good to see that patents have been filed, this always adds value to these!

Two things that are interesting about the PEGS conference attendance.

- if presenting at PEGS (a very high profile conference), there’s obviously good data available on the bispecific antibodies already. So things have been happening for a while in this field.
- it also suggests patents have been filed for this as they wouldn’t be presenting data on it without it already having some form of patent pending

Fantastic post Bermuda, that’s my morning reading over coffee.

Interesting they talk about deep immune monitoring and validating vaccine candidates early to get rid of the less effective ones. This reminded me of one of LD’s most recent papers which is well worth a read (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8630742/).

https://twitter.com/shaun_day_/status/1562697205009756160?s=21&t=nRFJZULRgJJYqSdW3zH1YA