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Almas,
Thanks for that.
If nothing else it would be good to at least get a clear picture on how recruitment is going across the board but particularly for Modi1 - which cohorts are still recruiting and how many recruited so far. If you have the time I'd be interested to hear any feedback or comments from you on the presentation and I'm sure others would appreciate it too. No problems though if it's not possible.
Hi Bermuda.
Thanks.
The Proactive presentation on Wednesday, 29th May is to be given by Lindy herself.
Bookings are open; places were still available when I made mine last week.
It will be around six months since the last update by then, so I am obviously hopeful (I wish I could write "confident") that Prof Durrant will not be re-presenting that information on the 29th...
Almas
From a few weeks back on Macmillan:
“ I also assumed that because my treatment was now a combination trial; modi-1 plus nivo, that I couldn’t stop the nivo and continue with the modi. This was confirmed.
My last discussion with S, he thought the modi vaccines were complete (after 9 months) and just nivo remained. But when I had a different view, he looked it up and confirmed they continued. Therefore, I concluded they didn’t know the optimum timeframe for the modi either. To be fair, it’s a phase 1 trial so that is not the objective. On this basis the initial trial timeframe was for fewer injections, and I’d had them all, it was logical to conclude I’d had the benefit from these as well. Oncologist nodded.”
…..would have continued with Modi-1 on its own but figured that the benefit had been obtained.
Looks like Scancell are doing another Proactive One2One event on 29th May. It'll be interesting to see who is presenting.
https://www.proactiveinvestors.co.uk/register/event_details/444
Can't read the full article? What does it say?
But if you also can only read the same vague headline I can, then your interpretation of it RE Genmabs specific relationship with Scancell is more than a bit of a stretch. IMO.
Https://www.ft.com/content/2f3caeee-ff64-47eb-b00e-6568ad1f1858
Hope they're still interested in more from Scancell.. but it looks like they have headed to China to find more innovation.
That's Inanaco on the other side. The research and time put Into the Information he produces and shares Is mind blowing. I don't understand most of It myself. With all the positive large positive %ages produced In the SCLP Trials you have to wonder why the Co hasn't been bought out
Sarah Danson also referenced this in her recent presentation at the Melanoma patient conference
https://www.google.com/search?client=safari&sca_esv=73778d81cd87c189&hl=en-gb&sxsrf=ADLYWIL6OsT1cntPtbrbd-fE_2cdETt6lQ:1715672278957&q=sarah+danson&tbm=vid&source=lnms&prmd=invmbtz&sa=X&ved=2ahUKEwiX0POl0YyGAxVrVEEAHRazCR0Q0pQJegQICBAB&biw=393&bih=656&dpr=3#
Not really directly related, but some interesting sidebar comments in this article, suggesting that Scancell and others in this field may be on to something bigger re targeting the immune system…..
Richard Scolyer: Top doctor remains brain cancer-free after a year https://www.bbc.co.uk/news/world-australia-69006713
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.
burble,
regarding your cd8+ /cd4+ t cell comment. scancell published some research back in september showing they had identified a cd8+ t cell response to some ****citrullinated peptides:-
'there is ample evidence suggesting an important role of cd8 t cells in eradicating tumor cells. here we present data for a novel class of antigens recognized in the tumor microenvironment by cd8 t cells. our previous studies have demonstrated that ptm specific cd4 t-cell responses provide survival benefits against aggressive tumor models in mice and suggest the presentation of modified epitopes in the tumor environment. in this study, we have shown the first evidence of cd8-mediated responses to hcit peptides and demonstrated that these are capable of selectively recognizing the modified but not the wt epitopes.'
https://jitc.bmj.com/content/11/10/e006966
Hi Burble,
Appreciate you taking the time to share your thoughts which have helped me focus on relevant points. So early data shows Moditope has demonstrated potential in humans. Not getting carried away but this is encouraging.
The bit that attracted my attention re poster 1 was a bit that was cut off the end of your copy, Burble: viz “…..complete regression of 70% of established tumours”
Also, no copy or comment re the 3rd poster on SCIB1? Or is there nothing new there?
Excellent technical summary Burble, thank you.
I asked about BionTech and the Moditope 'T' Cells back at the 2022 AGM. A that time LD was very positive that BionTech were still very much interested and those cells were being harvested at that time. So as you say its quite puzzling why we are going ahead with this research on our own.
Could it be that our price as gone to high !!
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
Looking at the series of tiny trades at the start and end of the day, I can't help wondering if someone gave their lottery numbers to their stockbroker by mistake.
Thanks Bermuda. When you have had time to rake through, it would be good to know . . . anything you find. Come on you Techies !
The CIMT Annual Meeting abstracts have now been published in full - just click the '2024 Meeting Abstracts' tab towards the top of the page in the link below.
https://www.meeting.cimt.eu/call-for-abstracts
BASEL, 15 - 17 OCTOBER 2024
https://www.terrapinn.com/conference/festival-of-biologics/agenda.stm
The Festival of Biologics is your opportunity to hear from industry leaders, global regulators and world-renowned academics at the forefront of innovation. Join us for 3 days of cutting-edge insights into the latest industry developments.
October 16 th at 17:30
Reserved for Scancell
Therapeutic Vaccine Development
immunotherapy
Lindy Durrant,
Joint CEO and CSO,
Scancell Lt
ModiFY Trial, We await the following:
1 ) Mono-therapy Update
2 ) Modi1 + CPi 1st Full Data Report
3 ) Modi1 - Harvested Moditope T Cells as requested by BionTech.
4 ) Modi1 + CPi in Renal Cancer Upgraded to a 1st Line Treatment : Awaiting Approval
5 ) Modi1 + Duplet of CPi’s : Awaiting Approval to start a new cohort in Renal Carcinoma.
6 ) Neo-Adjuvant Arm where the resected tumour is analysed for the Ingress and Impact of the ModiTope generated ‘T’Cells.
7 ) Will Modi1 be linked up with a Duplet of CPi’s to target Ovarian Cancer. This would have to be fully funded with a partner as the cost of the Checkpoints would not covered by the NHS.
ModiFY is a very diverse Trial with many possible trajectories.
It is worth mentioning that "Extensive preclinical testing" of Novavax's vaccine was done at Texas Biomedical Research Institute:-
https://www.txbiomed.org/news-press/news/novavax-covid19-vaccine/
The last we heard about Covidity on 1 October'23 was that the research team at Texas Biomedical was waiting for official approval to move into primate studies, hopefully followed by FDA human clinical trials:-
https://www.ksat.com/news/local/2023/10/02/new-type-of-covid-vaccine-showing-promise-at-texas-biomed/
I'll probably emit something when it hits 50p as well to be fair.