Member Info for Burble

Berm, sadly I can't access this.

Let me try #ICanHazPDF on twitter.

Ciaskin,

29th May (next Wednesday)

https://www.proactiveinvestors.co.uk/register/event_details/444

Question - if the proactive one2one is at 1800, does that mean any news if announced would be announced earlier that day, or technically could they wait till the following morning given markets are closed at the time of the presentation?

Bojo,

I think the real excitement may come with the checkpoint inhibitor patients, if you look at things like Keytruda, it’s Ph1 trial wasn’t amazing but good enough to allow continuation of the trials. Larger cohorts then demonstrated clinical application and utility.

The fact modi is showing activity is good but I think the later cohorts will help demonstration further it’s clinical application.

Thanks Berm, that’s helpful to not take my inferences out of context. Both therefore also highlights that moditope is seen by both sides of the immune system which so good, especially if both can be harnessed.

Also to add 60% of patients showing stable disease with one patient showed (past tense) a partial response. That in itself is v.interesting addition. Curious how many people have been dosed so far and how many patients this 60% stable disease refers to.

Four observations for me are as follows:

Author affiliations - none of the people listed seem to have links to BioNTech - does this mean that the 2018 collaboration to identify TCRs from moditope vaccinated people has gone quiet? Does this mean we're exploring these ourself - if so, this can be value add?

CD4+ T-cell confirmed and mapped - this demonstrates that the underlying mechanisms behind moditope are working - we are able to generate CD4+ T-cells against the moditope vaccine in patients. This evidence in addition to the resected patient information may prove beyond all doubt that moditope works and is capable of generating CD4+ responses in patients - this was something LD highlighted was high on the list that potential pharma companies would want to see. Furthermore, they stress that there is little or no-recognition to wild type - highlighting how specific this TCR is to the siPTM modified peptides.

CD8+ T-cell confirmed and mapped - this is curious to me, as LD has been keen to stress that moditope targets CD4 cells and not specifically CD8 cells. So the fact they have identified this TCR is also interesting.

Finally, from a IP perspective, I wonder what work is being done to secure this? Given that it is being presented, I'm a bit stumped as to what the IP position is on this.

isolation and characterisation of tcrs that recognise citrullinated and ****citrullinated post translationally modified peptides

s. paston1 , r. choudhury2 , s. shah2 , g. cane1 , j. chadwick1 , r. metheringham2 , f. master1 , r. herbertson3 , l. durrant1,2

1 scancell ltd, oxford, united kingdom

2 scancell ltd, nottingham, united kingdom

3 brighton and sussex university hospitals, brighton, united kingdom

under conditions of cellular stress, proteins can be post translationally modified causing them to be recognised by the immune system. one such stress induced post translational modification (siptm) modification is citrullination, the conversion of arginine residues to citrulline by peptidylarginine deiminase (pad) enzymes. we have previously shown that targeting citrullination can induce cd4 responses that provides efficient tumour therapy in vivo in a process mediated by autophagy.

we are currently running a phase 1/2, multicentre, open-label study of modi-1 in patients with breast, head and neck, ovarian, or renal cancer (the modify study) study. the moditope® vaccine incorporates two citrullinated vimentin peptides (vim28cit and vim415cit), and a citrullinated a-enolase peptide (eno241cit), each conjugated to the toll-like receptor (tlr)1/2 ligand adjuvant amplivant®. sixty percent of patients receiving modi-1 monotherapy show stable disease and one patient showed a partial response. currently we are recruiting patients receiving modi-1 in combination with checkpoint inhibitors.

eighty three percent of patients make a t cell response to eno241cit, we have isolated a tcr from one of these patients. single-cell rna- & tcrseq was performed on sorted cd4+ ifnγ+. rnaseq analysis revealed these are cytotoxic cd4 t cells, using lentivirus-tcr transduced t cells we have successfully shown that two isolated tcrs react specifically to eno241cit peptide with little or no recognition of the wild type peptide. the epitope has been mapped and the presenting hla allele identified.

another post translational modification is the carbamylation of lysine to ****citrulline. this reaction occurs when isocyanic acid reacts with the amine (nh2) groups on lysine to yield ****citrulline. the carbamylation of amine groups leads to a change in molecular charge, which in turn alters antigenic properties and can lead to the generation of unique t cell and antibody epitopes. we have successfully isolated a cd8 tcr that specifically recognises a post translationally modified peptide from aldolase. the tcr recognises a 9mer peptide that has been modified with the conversion of lysine to ****citrulline at position 7 (vlaavy-hcit-al).

using lentivirus-tcr transduced t cells we have shown that the ****citrulline peptide is recognised and not wildtype, the epitope has been mapped and the hla restriction confirmed. t-cell based immunotherapy has achieved remarkable clinical responses in cancer patients. our own data in preclinical mouse models have sh

Did anyone see the northern lights last night? We spent three hours gazing at the sky watching it dance in front of our eyes.

It made me realise how insignificant we are in the grand scheme of things.

Interesting that there has been an uptick recently in tweets from SCLP. Another one on the need for more NHS clinical cancer vaccine trials.

https://x.com/scancellpharma/status/1788929381424844835?s=46&t=A6vOxblM5AgE5_ReawinRA

Oral presentation sounds interesting, but even more exciting will be the two posters.

- development of CAR-T from the GlymAbs

- isolation of TCR from Modi-1 patients

If my mind serves me correctly, didn’t LD say that they may look to go for renal cell carcinoma with doublet checkpoint therapy with modi-1?

RCC currently can have nivolumab (Opdivo) with ipilimumab (Yervoy) as front line treatment. So similar to SCIB1 in melanoma.

Agree excellent video, LD seems confident especially around Modi-1, SCIB1 and i SCIB1+.

So data Q3/Q4 - based on body language, I would hazard a guess that it’ll be Q4 for those. Interesting that the GlymAbs seem to be being explored in the ADC space - will be interesting to see what companies are hot in that area.

berm, you may be better placed to answer this but was there a slip of the tongue when she said cytokeratin being one of the targets for Moditope? Or is that in modi-2?

Doesn't surprise me, but these are generic titles so may present a more broad overview of cancer vaccines in the melanoma space. Especially as they cover different patient demographic groups.

It seems she also presented at the Association of Cancer Physicians event on the 1st March 2024 in the New Therapies session delivering a presentation titled 'cancer vaccines: trials and the future - where are we now?' Interesting tweet about it https://x.com/drlennardlee/status/1763629978430669099 'There was spontaneous applause when we heard what she was achieving in the #cancervaccine space!'

Bermuda,

Dr Shaw is also presenting at the Oncology Forum (https://oncology-forum.co.uk/wp-content/uploads/2024/04/2024-UK-Oncology-Forum_DRAFT-Programme-4.pdf) in a breakout session titled 'multidisciplinary challenges for modern melanoma clinical practice' with a half hour talk entitled 'vaccines in early and advanced melanoma'.

This meeting is only open to UK cancer healthcare professionals, and has breakout sessions for the main cancer types.

Can a more experienced investor explain to me how a closed period actually works? If they were in discussions with somebody, would they be able to announce anything new to the market at these events or would their hands be forced to regurgitate old data because of the closed period?

I'm just curious as to whether or not this is or isn't a sign we are in a closed period or whether there isn't actually any news to share?

I must admit I’ve been wondering if they’re in a closed period. Just a hunch and I may be wrong

EE,

I see this in a completely different light. If you have a product which can be used for the same target but across multiple indications in infectious disease and oncology, why wouldn't you want to validate it in each of those? Not only does that give you multiple opportunities to do deals, it also means that you can offer exclusivity in one indication but not another.

So in the case of the glymab antibodies, you have a number of different avenues for doing deals and generating cash flows.

- Oncology - different indications or use in different modalities

- Infectious disease - detection or targeted treatment

- Diagnostics - highly specific antibodies are valuable in this space too

- Discovery - whilst slightly niche, antibodies can be bound to solid materials and then used to capture specific analytes in complex mixtures.

Each of these could generate deals which reduces the likelihood of us as shareholders being diluted through further raisings. So to me, I think it only natural that a company which has developed something like the glymabs to be exploring what they do.

As Lindy is a middle author in the author list, I would pretty much guarantee that LD has had limited input on this bar providing materials and possibly the odd zoom call. Where you say 'the company itself should be ENTIRELY focused on developing intellectual property and monetising it for the benefit of its shareholders.' I would think this is exactly what they are doing. They are not doing these experiments themselves, but are letting others explore what the technology can and cannot do through scientific/academic collaborations. In turn this is passively developing the IP and in turn helping drive the monetisation of the product.

Dracula, I've slowly been averaging down over the years with a drip feed of purchases whenever I've had some spare cash. Still slightly underwater but it's not a crazy amount that it needs to climb to get back into a small profit. I'm hoping to hold out for when it does rise, but I've stopped making any major purchases as I feel there are other opportunities to invest in other companies where the returns will be greater/quicker than locking more money up here.