Getting to know... Césaré Cejas

In this team interview, we get to know MFX's Co-founder and VP R&D, Césaré Cejas.

Tell us about what you do here at MFX.

I head research and development?-?so what that entails is on the engineering side is the engineering prototyping and micro-fabrication of the bioreactors, then on the biology side is the internal validation with necessary cell culture data, bringing in necessary input from the other members of the company and also from consultants, and then making sure that the core technology works for relevant applications.?

Tell us a little bit about your background and what you did before this.

So,?I have a hard science background, mostly material sciences, engineering, physics and chemistry, with a bit of biochemistry peppered in. After finishing my PhD in 2013, I was an academic before setting up the company.?

So - you’re one of the MFX Co-founders -?what on earth led you to decide to found a company?

I think it was partly that, at that time,?I was disillusioned by the bureaucracy around academia.?In the sense that?early on I thought I wanted to go into the professor track, but eventually I felt discouraged. And then it seemed there was a choice whether you're going into a traditional large industry career or kind of starting something on your own, trying to start up your own adventure.?I guess the appeal of being in control of what the outcome is - the appeal of entrepreneurship was really high and that's thanks in large part to a?summer programme I had attended in Cambridge prior to making that decision.?

Also the promise of the technology was very much attractive, at that point I was working in the microfluidics domain and at that time, startups had sprouted left and right on different aspects of using microfluidics technology, but for different applications, things like using droplets for DNA sequencing or core-shell emulsions for cosmetics purposes. So I was already surrounded by a lot of entrepreneurial spirit around microfluidics and there was a real appeal to do something using that technology.?So then when I met Antoine, we hit it off right away and the discussion was not a hard one. Although it was hard to eventually quit academia at the end, but I did!

It’s always hard to leave academia?- have you looked back at all?

In a way, I still have one foot in the door because I still occasionally publish (mostly previous collaborative research). In the context of the company, we have different priorities as publications have less of an impact “traditionally”, but we do have collaborations and partners with academics that will definitely also lead to publications. These collaborative efforts provide credibility into what we do scientifically. So in a way, I get to continue some of the aspects of working in academia by continuing collaborations with them.?One good example is our sponsorship of a PhD student at King's College London.

So, tell us about the history of MFX. How has the company changed since you founded it?

So from a technology perspective, the core technology principles remain the same, but in terms of the footprint of the bioreactor it has really been adapted based on customer expectations in terms of its design and cell output.?We started with the conventional microfluidics dimensions, but realised we needed to work with larger cell numbers so the dimensions of our bioreactors have largely increased, but we've maintained some of the principles of microfluidics, especially relevant in the complex processes.??Also, since our first hire in around late 2019.?We've grown from two to three to five to nine. And now, we're at 17 (including our PhD student).??So, we haven't grown too fast, but we’ve progressed quickly.?I think our growth is proportionate to our funding, I would say and relevant to where we are today as a company.

So what's been the best thing at MFX so far?

The best thing is our approach to work, I wouldn't say we’re relaxed as we move at a fast pace but we’re flexible about things like leaves and working from home.?I think it's a very interesting concept because a lot of companies are very strict with how many days leave you have or where you work, but I think in a way it actually fosters trust, more cooperation and better time management between team members because you know that you are in control of your time. From how it’s going, people seem to deliver more effectively because they are able to optimise their time and sometimes eliminate long commutes especially if the focus is intense data analysis and processing. In addition, this flexibility also ensures that there is ample space for people to detach themselves from work and not get too tired.

I know these days, there's a lot of talk about mental health especially in the workplace. Post pandemic, people have largely benefited from working from home. So I think people have really been pushing around that flexibility.?Our flexibility in terms of working culture is, I think, the best thing in our company that I haven't seen elsewhere.?

Your teams are developing some really quite novel technology for cell culture. So what is the big difference between our bioreactors and the more traditional cell culture tools that people are using basic biology research?

The main difference is volume -?a number of academic papers have been published showing how cells grow better in a micro- (or smaller) environment because that's closer to how they grow in the body?- their processes are more efficient, when they're more compact or closer to each other. Studies have shown better/improved cell to cell signalling and communication, which then translates into better growth. But traditionally because microfluidics cell culture is conventionally done in a really small scale, traditionally it has been focused on single cell analyses. At first glance, one might see a disconnect between microfluidics and high-throughput cell culture because traditional cell culture (especially for CGT)?uses larger volumes. There is definitely a way, through multiplexing,?to take those principles and maintain some of those advantages in a relatively smaller scale such as better control of that microenvironment for the cells to grow in a more homogeneous manner, in contrast?to what you see in much larger bioreactors. You also have an additional component of lesser reagent costs, because now you only have to fill a relatively smaller volume around the cells.

What advantage do you think these kinds of bioreactors will provide to a cell therapy process?

So if you take as an example CAR-T,?the therapeutic dose is defined by the number of CAR-T cells that have been successfully infused with the viral vector. The aim is to increase the percentage of T-cells (immune cells) to become CAR-T, which are genetically modified cells that recognise and then eliminate cancer cells.

A big part of that process’s success is therefore the uptake of the viral vector and making sure the viral vector successfully interacts with the cells.?In a small volume environment (such as can be created in our bioreactors), it's easier for the viral vector to diffuse or to go into the cells as you increase the probability of contact between the viral vector and the cell.?So by increasing that probability of contact, you increase the probability of the T-cells becoming CAR-T's, which means that with such a high efficiency, you can potentially reduce the amount of vector that is used. Therefore, you reduce your reagent costs and shorten the length of the expansion culture ex vivo. As a result, you potentially hit therapeutic doses sooner in a given time frame.?

So what does the future of cell and gene therapy technologies look like to you?

I think the future, particularly for autologous CGT, is having the flexibility to scale processes up-and-down easily to understand the biology in greater detail and then translate faster to manufacturing.??There are a lot of startups setting up in this industry. And we’re also seeing much-established legacy companies that have started to divert their resources into scaling down or reducing the size of the bioreactor to accommodate the demand for more efficient process optimisation.

Indeed, process optimisation in cell and gene therapy is a crucial step in manufacturing a therapeutic dose. And the “trend” (so to speak), is to do it in volumes smaller than conventional ones since this allows for more precise and faster DOE (design of experiments).?From there, then you go and scale up for therapeutic doses - ideally using the same technology so as to minimise and eliminate problems with CGT translation. Cells can be finicky and so it is important that their environment is maintained, as much as possible,?whether culturing on a smaller scale or culturing for manufacturing. Currently, the industry widely uses different technologies for process optimisation and cell manufacturing - and the challenge is that this affects cell growth and homogeneity. Ensuring that you’re using one technology contributes to improving CGT translation.

So what excites you about cell and gene therapy?

In terms of it as a treatment? I think it’s because we know it works - we've seen it in the news and?we've heard about successful treatments.?Currently it's just really expensive.?I am excited about the opportunity, I believe, to kind of “democratise” it and to make it more accessible to a lot of people. As someone with a hard science background, I’m also excited by the innovation being built around scaling down these processes, allowing real process optimisation then scaling up while still maintaining process efficiency.??Currently the industry uses one type of system for process optimisation and then uses another for scaling up and that change in system or technology may or may not impact the cell manufacturing, but it certainly is time consuming to re-optimise it.

So, outside of work, you're studying for an MBA?- that seems like a lot of work. How is your MBA helping with the day job?

So I have been doing an Executive MBA at the Cambridge University Judge Business School since September 2022.?It's a part-time MBA - this means one full Friday and Saturday per month plus a few full-week commitments through-out the 20-month programme - and I’m already a year in!?I am expected to finish in April 2024.

So for MFX I've always been very comfortable with the science and Antoine (MFX, CEO and fellow co-founder) has always been the business mind around the company since we started. So it has helped me understand a lot of the concepts or?things that he does (or used to do when the company was not yet this size) such as corporate finance, share valuations, balance sheets, forecasting.?

I've also learned concepts that we've adapted to the company. One example is operations management where initially, we had the microfluidics engineering separate from the bioprocessing - but then from an operations perspective, it made sense to fuse them to get iterations and internal feedback on biological data more rapidly (the study group really helped!)

Timewise, I will admit it's been a difficult lesson in time management. I have my normal work responsibilities and with the MBA, there are obviously assignments dotted throughout the course of the program. A number of these assignments are done with study groups, and often your classmates are people from all over the world, so it's often difficult to find common time to work on it together. Sometimes you do late calls in the evening (UK time) because that's the only time that's available for everyone (especially if you have classmates from Asia and North America).

I had to adjust, understand and accept that no time is off limits - there's time for work, and then the MBA, but it's just for 20 months. I’m about to start my MBA thesis soon so my time will be even more stretched. This will be my fourth official academic thesis after my Bachelor’s, M.Sc and my PhD. While I have done such things before, the difference, aside from the subject matter, is that back then I was a full-time student, and now there is a company that I help run.?

I remember Antoine did warn me that I would probably struggle “balancing”?especially towards the final stretch of that MBA but I've committed to it and so far I've been doing well. I've had some really good grades on the assessments and I've also established some great connections, both professional and personal.?I can say that I never expected that I would grow much closer to people I have only met in the MBA - as if I have known them for much longer!

Pursuing an MBA is important to me because it improves how people perceive me as not just as a science person, but also someone who understands business and entrepreneurship.

Be careful you don’t become too much of a business person!?So do you have time for anything else outside work?

I love art. I once thought that if I wasn’t doing science, I would have preferred to pursue a career in the art world - whether that’s curating, conservation, provenance investigation or appraisals/auctioneering. I once joked with my friends that, if the stars align,?the last degree I’d like to pursue is an MFA! (and I would have one in each major discipline). When I do find the time, I like going to museums and visiting exhibits and reading about the history of old and contemporary collections. I have a predilection for 16th century mannerism and early 20th century fauvism. Both the UK and France have excellent collections.

Outside of that I like to travel, which I regularly do cross-channel and once-in-a-while, extended weekends in a European city with my partner. During long breaks, we like to visit places farther away.

Currently, aside from personal commitments, my time is very limited to work and the MBA.?

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