Ann: Quarterly Activities Report and Appendix 4C, page-50

Can I ask why you're comparing HEK293 with MSC for the production of exosomes?

Sure, I hold CYP shares. CYP's supposed value proposition was to be able to produce large numbers of MSCs for therapeutic use. Ian Dixon was a CYP founder and 'platform technology' seemed to be a phrase he used in getting funding etc for CYP.

Chris Baldwin if I recall correctly in some of his presentations or public statements spoke of Ex1 as eating the mesechymal stem cell companies lunch.

I'm a retail shareholder I can and would change my holdings if I saw better value. But my approach is to try to understand the underlying technologies. I'm genuinely interested in the underlying technologies and so try to understand what is going on in the cell and cell-free (exosomes being cell-free) therapy (at this stage they are just potential therapy) spaces.

I believe it's been established that different cell lines will produce exosomes with different characteristics. And even exosomes derived from the same cell line can be (in fact, will be) heterogenous.

To me that makes sense - it accords with what I either know or think I know of cell biology. I think, naturally, different types of cells produce different lipids (these are not just little particles of fat always, though sometimes they might be in effect and in function) and gene-products (like cell surface receptors will be actively functional receive communications from other cells and effect what happens in the cell - so cell surfaces aren't just soap bubbles) that get transferred to the cells surfaces that are related to the functions of the different cell types and I think when exosomes are naturally formed in the doing of what natural cells normally do the surfaces of the exosomes are essentially made up of what were the surface constituents of the host cell they came from.

From a Feb 2022 paper -

HEK293-derived exosomes show a remarkable ability to carry and deliver chemotherapeutic drugs, such as doxorubicin, in such a manner that the drug causes minimal toxicity to non-targeted cells.

Sounds interesting. And logical. And plausible. But its still at a remote (high) level of abstraction.

I'd need to read the article to decide whether I'd agree it was also 'remarkable' in my own opinion, though clearly others have found it to be so.

Ohno et al. demonstrated the tumor-targeting property of exosomes isolated from HEK 293 cells by decorating them with the GE11 peptide or epidermal growth factor (EGF) on their surface, and then used them to deliver let-7a miRNA to EGFR-expressing breast cancer xenograft tissues leading to an enhanced therapeutic effect.

Ah, now that's getting more specific and so less abstract. When specific peptides and microRNA's and growth factors are named I feel like what is being described is almost the very particular features of nature, sort of nature's own, nano scale engineering, and when humans get real specific like that then I think we can sometimes change things naturally and do some natural re-engineering. We aren't just doing high level hand waving only anymore.

https://www.sciencedirect.com/science/article/pii/S1044579X22000475

Thanks for the link, thanks for the question. Don't have a lot of time to dig into this right now but I'm glad you are interested in this stuff as well.

My sense of things is that for EX1 to be a for profit business it needs to have some practical for profit use cases. Now if engineering a HEK line to produce exosomes to carry any specific drug to any specific cell target rather than have the drug get dispersed to useless or even harmful collateral damage sites - that's good. That's progress.