Creating Multiplex Allogeneic Cell Therapies: Moving Beyond Editing with Sven Kili
For this snapshot Q&A, Phacilitate’s Ryan Leahy speaks to Sven Kili, CEO of Antion Biosciences, about the use of smart data for revolutionising cell therapies, promising areas for development within the industry and what challenges remain for providing long term efficacy for cell therapies.
During the interview, we learn a little more about the exciting development activities currently underway at Antion Biosciences and get a taster for what Sven will be presenting at Advanced Therapies Week 2022 in Miami.
Could you tell me a little about what you are working on at Antion Biosciences?
Yeah, absolutely! Antion Biosciences is a Swiss-based cell engineering company and we’re focused on developing next generation multiplex engineered allogeneic cell therapies, and these are for a variety of high unmet medical need diseases. We have a unique platform which we call the miCAR™ platform, and this allows us to silence or modulate the expression of up to six different genes plus an expressive component, such as a CAR or a TCR, and this is all done within a single construct delivered via a single transduction step. This is a much more efficient way of delivering a lot of guides and a lot of instructions to the cell. So our current focus is really centred on building out this platform and developing our first few indications, which are going to be in the oncology space.
How are you using a smart data approach to revolutionise your work?
Smart data is really a concept that we’re incredibly fortunate to be able to leverage at Antion, and we do this by the use of our proprietary in-house tool which we call, ‘Antion Design Studios’, and this revolutionary piece of technology allows us to define, refine and test our silencing constructs entirely in silico.
This allows us to enormously speed up the development process and to deliver the lab team sequences which are well validated for both on-target and off-target effects, as well as silencing efficiency. It also allows us to design and generate constructs which are able to modulate the expression of specific genes, thereby providing a lot more control to our constructs. So not only can we silence, but we can modulate – smart data really gives us this ability to be nimble and efficient.
In our research and design activities, we’re also developing additional functionalities for Antion Design Studio, and I’ll be more than happy to discuss those with you in the coming months as we validate the work that’s going on with them. So, very exciting times!
What do you see are the most promising areas for development in the industry, currently?
So the cell and gene therapy industry is evolving and growing at such a phenomenal pace, and there are so many very, very promising technologies. Thinking about that, I really don’t think I can pull out just one, but I’ll talk about a few.
I think some of the really exciting areas for development include the growing understanding of what’s really required to create a truly allogeneic therapeutic cell, and to be able to take this and treat patients effectively and safely at a much more democratic cost. So, how do we really make these therapies available to more and more patients? We need to do a number of things around this: we need to optimise the way we manufacture, we need to optimise the way we develop these therapies, and then we need to figure out exciting and appropriate ways of paying for them.
Another area is the profusion of vector technologies, moving beyond our reliance on purely viral vectors and into the realms of the various nonviral approaches, which will certainly help with the production bottlenecks that we’re seeing at the moment for viral vectors. This will also help certain therapies which require a different manufacturing approach, so I think this really offers a lot of alternatives to companies and opens things up, dramatically.
Finally, I think technologies that allow us to move from gene editing into the creation of truly multiplexed cells. Gene editing is an absolutely incredible ground-breaking technology that has opened so many doors for us and has allowed us to treat patients in very different ways, but what we’re seeing is that more than three or four edits becomes incredibly challenging. It becomes problematic for the cells, takes a long time, can potentially have problems for the patients is very expensive, so being able to carry out these multiple edits with high efficiency is becoming very challenging. New technologies are now coming in to take up that mantle, and these are particularly exciting. These especially include base editing, prime editing and, naturally, on the miCAR platform, so there’s a lot of really exciting stuff happening there.
What do you feel are the biggest challenges for long term efficacy of cell therapy and how are you overcoming these?
We are currently still trying to understand many of the mechanisms involved in ensuring long term efficacy, and when I say ‘we’, I mean the cell and gene therapy environment as a whole. These include things like cell survival, cell maturation, antigen escape, the hostile tumour microenvironment, the host immune factors, and many others. There’s currently an enormous amount of work going on in academia and industry to explore and to figure out how to mitigate these and other aspects which are limiting the long term efficiency or even the ability to re-dose, which may then negate that long term efficiency challenge.
At Antion, we’re working in-house and with collaborators on many of the approaches that I’ve talked about, and we really believe that the solution is unlikely to be a single gene or a single receptor. The body works with so many different mechanisms, and so we think an orchestrated approach is probably the most natural and efficient way going forward. Fortunately, this speaks very well to our technology, which is able to not only silence gene expression, but – as I mentioned before – to modulate specific genes as they’re expressed. This allows us to generate the most efficient therapeutic cells possible.
We’re very excited to have you back in January. What are you most looking forward to at Advanced Therapies Week 2022?
It really is the bright spot on the annual meeting calendar where we’re able to get together in sunny Miami and meet up and share information and knowledge with our colleagues. It’s one of those meetings where we can leave the dreary weather to go to where the sun is shining, where it’s warm, where the drinks are good, and where we can meet a lot of people.
I think 2022 is really shaping up to be an especially great year. We’ve been so limited in our face-to-face interactions over the last two years, and so much has happened medically and scientifically in this time. For many of us this is going to be the first face-to-face meeting that we’re being able to get back to, which is particularly exciting.
There are so many incredibly talented people that come to Advanced Therapies Week who speak, present, and who are just around. I’m really looking forward to, not only gaining amazing new knowledge and insights from these people, but also making new friends and colleagues at the same time.
Sven will be giving two presentations at Advanced Therapies Week 2022, first on a new approach to treating cancer with miCAR cellular engineering, and secondly on creating multiplexed allogeneic cell therapies: moving beyond editing. Find out more about joining us in Miami, here.