Oxford Global24 Aug 2020 11:04
A really interesting talk, highlighting much of the scientifically published information that is out there on Modi-1 and Modi-2.
I quite liked the digital setup, you could see who was also in attendance which was helpful. Some big name pharma companies there including AZ, GSK, Sanofi, smaller biotechs, academia, CRUK etc. I might have a look at the actual names of people on LinkedIn later today and see whether they are just research staff or something a bit bigger.
It was promising the response rates and strength of binding of HLA-DP4 to the citrullated peptides in comparison to wildtype. This I think highlights just how key citrullation and autophagy are to Modi-1 working. The mouse work was pretty striking, especially the extended tumour growth work (4, 7, 10 and 14 days post transplant). Even the 14 day PT mice showed a statistically significant response (p=0.0012) at 40 days post tumour vaccination. It was also interesting to hear LD say control mice had to be culled early due to the size of tumours. The data that was presented on tumour regression was also interesting - a 50% reduction within 3 days (going from 500 mm3 to 250mm in such a short space of time is pretty incredible).
The work on mice tumour rechallenge was also promising - seeing a near 100% survival rate a second time around shows that this is not a one-shot vaccine and that it can continue to work after the event. This is good, especially for tumours that metastasis, though obviously with the caveats that continued expression of associated targets is required.
The Modi-1 work with PD-1 inhibitors was an interesting point, especially in so far as she said it was difficult to do the data analysis of the Modi-1+PD1, vs Modi-1 alone because the vaccine was having such an effect on it's own. But I'm happy with a statistically significant result from Modi-1 alone, and the combination therapy. This definitely I think helps build the case for interested parties with PD1 inhibitors, especially ones already in the clinic. Combination therapy could extend patents which would also be a benefit.
Modi-2 was interesting, different mode of action and the key player here is the myeloid-derived suppressor cells.
One take home from all of this though was that some most people already have a T cell repertoire to homocitrullinated peptides and interestingly there seems a loss of CD4+ cell response in some cancer types (ovarian specifically was highlighted). So more work seems to be needed to understand whether these patients will not response.
All in all, an interesting but v.highly technical presentation. The format at times I think was challenging, as the presentations were all pre-recorded.
Roll on Thursday for the next one this week!
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