Member Info for Burble

You and me both! It would be exciting to be part of the Scancell journey!

CW's post earlier saying 'For me the biggest take away from the government ‘funds’ is the inclusion of Cancer Vaccines in the story .. We all know they have been out of favour so it’s good to see !'

In the post-covid world, there is a vast amount of interest from government in nucleotide based technology - with a high emphasis on mRNA technology and there is a lot of interest in how this can be deployed for other illnesses/diseases. It seems the government is interested in expanding the UK capability in the nucleotide therapeutic space, with a large focus on how nucleotide based therapies can be developed and utilised. As such it doesn't surprise me that there is an inclusion on broader cancer vaccine technology, however I would highlight that the spotlight in a lot of the work I'm involved in is mRNA based therapeutics, delivery mechanisms and analytics etc.

As such, whilst this funding is important and should be welcomed, I will be intersted to see what cancer vaccines are in scope/out of scope. Fingers crossed they are open to both DNA and peptide based vaccines as well as mRNA technologies and aren't blinkered by the success of the mRNA covid vaccines. Especially given the government overtures for enticing mRNA based companies to invest in the UK (https://www.gov.uk/government/news/moderna-to-open-vaccine-research-and-manufacturing-centre-in-uk). Having said all that, recent funding calls within the manufacturing space for nucleotide based technologies have included DNA as one of the 'in scope' grant funds (https://apply-for-innovation-funding.service.gov.uk/competition/1356/overview/685e8ab1-88ff-481c-8200-618811d7f6a8#scope). It will be interesting to see whether further funding in this space is open to other cancer vaccine technologies or whether non-mRNA tech will be considered (stupidly IMHO) out of scope.

I second that opinion. It’s wrong and manipulative to be probing for information, especially so that she probably doesn’t know this site and share bulletin boards exist and that people are freely discussing her cancer journey.

Just go and be as casual as this guy was! https://youtu.be/e6Y2uQn_wvc What’s the worst that can happen?

Ivy,

Do you have a name that is common with someone who works in this field? I could only imagine that the organisers have got wires crossed. Normally when organising speakers to be invited to conferences it’s because someone on the organising team knows personally or has read something of the speaker and have interest in that. I wonder what list you’re listed on!

Yeah all good, just now got to find the finances to pay for it all - it's not a huge budget, but at this time with cost of living crises and everything else going on in the world, scraping together some money for that is not easy (though I did still manage to find some £££ to buy more SCLP shares this month). But got a year to go, so that should hopefully be plenty of time.

CW beat me to it! Apologies didn’t see your post

Non paywall version https://www.icr.ac.uk/news-archive/scientists-plot-extinction-of-cancers-by-disrupting-their-ecosystems

Re Covidity - results expected approximately January time. So not long to wait.

Konar

1 - playing devils advocate, a follow-up question would therefore me 'How many days between naive patient immunisation and them being infected by omicron?' For many patients, immune response to a vaccine takes 3-4 weeks post vaccine to start working. So highly likely if they were vaccinated during the omicron surge, their immune response didn't have a chance to kick in before they were infected. Hence the follow-up on those patients will probably be more in depth.
2 - agree, not great at face value but if you look at the PH1 trial protocol it states the following:

'When the study commenced in 2021 there were significant numbers of unvaccinated individuals who also had no known exposure to SARS-CoV-2; however as the epidemiology rapidly changed with most people having either been vaccinated, or infected with SARS-CoV-2, or both, the use of SCOV2 only in these populations made rational sense, particularly as it has more mutations in common with the Omicron variant. A protocol amendment submitted in February 2022, permitted the enrolment of participants irrespective of their previous COVID-19 vaccination and/or SARS-CoV-2 infection status, amended the treatment regimen to SCOV2 only, and aligned the administered dose with the doses employed for other DNA vaccines. Immunogenicity analyses will be performed separately for the vaccine-naïve, previously vaccinated and previously infected immunogenicity analysis populations.

This study is expected to enrol up to 80 participants at a single centre in South Africa. Enrolment will attempt to continue until at least 10 evaluable participants receive all protocol-required SCOV2 vaccinations for each immunogenicity analysis population. However, should the epidemiology be such that certain populations cannot be enrolled, the Safety Review Committee may determine that enrolment for that population be considered complete.'

So considering that you have the following
18 patients in vaccine-naïve
?10 previously vaccinated
?10 previously infected immunogenicity analysis populations.

Given some people dropping out of the trial, technically 40 is the minimum needed. So without further information to support the opposite, I'm not worried about either of these.

Some absolutely fantastic questions - well done all who managed to get to the AGM and ask them.

BioNTech - still interested, but more so in the platform rather than the T-cells that come with it - cheaper and easier to deliver.
More PR needed - but will only happen when they're certain that responses are correct - not wanting to jump the gun.

Organisation to do deals in future - this has been tough this year. Several lined up, better offers, couple of candidates for CFO. Moment LD doing it, but needs support.

New budget R&D credits - potentially this will be a cut and this will be taken into account.

Focus on moditope, current seems on antibodies. LD loves Modi-1 - long road to get that validated. Like antibodies - easier to do deals at easier stage. Redmile money has helped get antibodies into the clinic. Preclinical mAbs worth something but not huge amounts, once clinical validated thats worth more.

John/Richard moving on - how much does Martin Diggle/RedMile get leaned on for help - Board supportive. Negotiations are done by C-suite, so helpful and supportive. Martin Diggle - collegiate and supportive board, Redmile and MD have relationships with strong contacts in pharma. 'SCLP exciting we have ever seen'

Glymab deals/avidimab deals - any deals next year front loaded enough? Cant promise - how many we do, what stage we do them. Will they be enough unsure - might need to ask further money.

Recruiting campaign for new chair person - non-executive chairman? Plan at the moment is a Non-exec chairman.

2/2

mAb stimulates T-cells within tumours which then target tumour. This has avidimab - so will also take to the clinic.

Also this mAb enhances adoptive T-cell therapies (and this is the bit that peaks my interest) and I think has a real opportunity for commercial success.

In cell therapies (CAR-T etc) 'they give a billion T cells to patients, they grow them in the lab and give them a billion T cells. Thats very expensive and very time consuming and the majority of those T cells probably 90% of them never get to the tumour and never do anything. By giving this antibody, we get much better adoptive transfer, so you get more T cells that actually adopt. So you could go with fewer cells in essence and still get the same effect, the other thing which is even more important, once they have put a billion cells into somebody, most of them get switched off very quickly and are not very effective. They are what we call exhausted, being overstimulated. If you do that in the presence of our antibody, the majority of them or at least sort of 30-40% of them remain active and really potent. So not only could you give less T cells, the T cells you give become more active and we think this is a really good licensing opportunity for some cellular company and we are talking to people as we speak'.

First time listening to this - some interesting tidbits.

Cash runway to Q1 2024 - have money for pre-clinical work but not clinical work for some products (Modi-2 being one of the stand outs). But lots of talk about deals and licensing technology - so this could be extended and we could see other products in trials ourselves if stars aligned.

mAb licenced to Genmab give them the rights to develop into standard mAb, antibody drug conjugate, radiotherapy etc but not cell therapy as they don’t have expertise and so would have sublicenced. LD said ‘we kept those rights and will do a separate deal ourselves on a validated target’ - interesting - suggests to me that they know there is an opportunity for this in CAR-T type technologies, so another deal on the cards either now or in the future?

CD4 T cells (i.e. moditope platform) - novel nobody else really doing this.

Checkpoint+Modi-1 - lower dose than monotherapy arms because checkpoints have own toxicity and this is a double agent study.

H&N cancer diagnostic biopsy before treatment, then treat with CPI or CPI+Modi-1, then surgery 6 weeks later. Tumour cell will be studied - see exactly where T-cells are and what is happening (and if tumour shrunk before surgery). This is what pharma are looking for - proof of regression and mechanism of action and how things are working. So should provide far more information.

Modi-2 works in particularly supressive environments, so could be used as a CPI equivalent or in combo with Modi-1 in a dual therapy.

Sally: - peptide synthesiser and formulation brought in house - cheaper and easier to do multiple experiments and tweak experiments.

SNAPVax - manufacture Modi-peptide with one end being coupled to a high hydrophilic peptide sequence at one end and a high hydrophobic at the other. Hydrophobic tails then bind together and you get a ball of peptide with hydrophilic outer and hydrophobic inner. All Modi-2 peptides mixed together and form these spheres. Some minor tweaking to buffer needed to form injectable solution which can be sterilised. Material being made for toxicology.

SCIB1 - 10 patients on vax alone still alive 7 or so years later. 4 patients received SCIB1+CPI - still doing well. Some sadly have passed away despite everything.
iSCIB1 - already manufactured, MHRA need to sign off on amendment. In pre-clinical now curing 50% - so more potent than SCIB1.

GlymAbs - take two into clinic.
Bristol Myer Squibb have an anti-fucosyl GM1 antibody in clinic - doesn't bind well and binds to other GM1 targets. SCLP mAb super specific to fucosyl GM1 only, highly selective to SCLC and to no normal tissue so far. LD 'cautious about this but could be the holy grail of a completely cancer specific antibody'. This is why kept in house, not for sale.

Second mAb is a 'checkpoint inhibitor antibody' but targetting glycan so unique... 1/2

Kash.

Oh no, what a nightmare. Rest up, get well soon and fingers crossed C19 treats you kindly.

Konar

PBMCs will have been harvested from healthy donors. Then they have been analysed to see whether there is a native response to the peptides - so no dosing of patients. Just taking blood from the general population and seeing if some already have circulating T-cells recognising the peptides.

I used to donate a pint every quarter when I worked at Pfizer. Phlebotomy used to take blood from willing victims…I mean colleagues, for use in many of these types of experiments. It then generally sits under a broad ethics approval for the use of blood products in unspecified research. Many universities and companies operate a similar model.

Also on the Evitria website it says 'Antibodies with reduced Fc-effector functions are essential for therapeutic applications where activation of the host’s immune system would have negative effects, such as when an antibody is used to neutralize a binding interaction.

We hold a licensing partnership to offer antibodies with truly silent Fc domains, using mAbsolve’s STR technology. STR-modified antibodies show no binding or activity above background noise across the Fc gamma receptors, far surpassing all previously described modifications.'

So that's another piece added to the puzzle. Link between SCLP, mAbsolve, and Evitria.

Evitria (a service provider for recombinant antibody expression) tweeted this earlier from PEGS Europe https://twitter.com/evitria_ag/status/1592444513225957380?s=20&t=u-kJL-brccND-ApcAMjv3A

Seems the bispecific antibodies are being produced by Evitria.

Evitria (a service provider for recombinant antibody expression) tweeted this earlier from PEGS Europe https://twitter.com/evitria_ag/status/1592444513225957380?s=20&t=u-kJL-brccND-ApcAMjv3A

Seems the bispecific antibodies are being produced by Evitria.

Ahead of next weeks AGM, what kinds of questions do people think we should be asking?
For me a big one is what’s happening with SCIB2, has that been parked permanently? Is any work going on since we took it back in house? We saw only three weeks ago GSK walk away from a NY-ESO-1 candidate, others are still busy working in this area. Does SCIB2 have a place in the Scancell repertoire or has the research focus shifted to Moditope/GlyMAbs first?

‘Transforming T-cells into a form that can hunt cancer requires considerable genetic manipulation to both remove the genetic instructions for building their old receptors, and give them the instructions for the new ones.’

This highlights why modi-1 and Immunobody could be so valuable! They’re patient agnostic, they do not require custom produced products to be made, which are expensive and have long supply chains to produce. They both could be off the shelf products. You also don’t need to be engineering old T cells and giving them new functionality, you’re just coaxing them along inside the patient.

‘The disease continued to get worse in 11 patients, but stabilised in the other five.’

Soon we get the data to show whether both Modi-1 and SCIB1/Covidity are superior in a range of different cancer types. Melanoma (SCIB1), Head and Neck, Triple Neg Breast Cancer and Renal.