Founder-CEO Interview Series

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Stefanie Flückiger-Mangual

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Stefanie Flückiger

Stefanie Flückiger-Mangual, Chief Executive Officer, is one of TOLREMO’s scientific founders and expert in the field of drug resistance in cancer therapy.

She is a biomedical scientist and biochemist by training (University of Fribourg and ETH Zurich) and holds a Ph.D. in Molecular and Translational Biomedicine from ETH Zurich.

Stefanie led the team of scientist who discovered novel molecular mechanisms that can be exploited to prevent the development of resistance to cancer therapies.

Founder-CEO Interview Series

With: Stefanie Flückiger-Mangual

Can you tell us more about TOLREMO and why did you found the company?

TOLREMO is a cancer drug resistance company which uses a screening and drug development platform based on non-genetic drug resistance and cancer cell plasticity, to develop companion inhibitors that prevent resistance development.

TOLREMO is based on academic research that I did as a postdoc at ETH in Zurich where we identified novel ways of how cancer cells become resistant to cancer drugs. We found that drug resistance, even though in a clinic, is a long-term problem. The trigger is almost immediate with the first dose that patients receive.

We developed a screening technology of how we use this cancer cell plasticity to develop new drugs against new targets to prevent resistance development. TOLREMO is really the entrepreneurial translation of our science into a clinical solution, which is the next logical step and what we believe to be future blockbusters.

What is the percentage of patients who are resistant against cancer drugs?

A majority of them. People don’t really realise that the problem we face is not that there is a lack of cancer drugs. There are many cancer drugs out there and often times, they work really well for about a year, until the tumours return. The limitation we have in the clinic is a lack of durable responses, rather than cancer drugs per se.

We combine our lead asset which is called TT125 with epidermal growth factor receptor inhibitors (EGFRis) and KRAS inhibitors (KRASis). For each inhibitor you see a resistance developing within a year and a half in most patients. So, it is a huge problem.

Can you share a snapshot of how the company has progressed in the last 4 years?

In the beginning, it was just me. I was still in the lab, trying to raise funds and write a business plan.

The first year saw us establishing the screen platform. In the second and third year, chemistry was really important to actually develop a first candidate. The team grew.

Last year was a big step for us when we moved out of ETH into our headquarters in Muttenz. With our own offices and our own labs, it really feels like an established biotech now. It’s not a start-up anymore, but more in the growth phase.

Did you always know that you would be an entrepreneur?

Absolutely, not. I did research because I loved science and I thought it was fantastic what these cancer cells are able to do. We had all these interesting results and one day towards the end of my PhD, my PhD supervisor sat me down and asked me what my plans were in life.

I said that I didn’t know, and he asked if I had ever thought about founding a company. My first response was well, no, because how does one turn science into a company.

He urged me to go and figure it out. That triggered something in me. I started realising that maybe we can actually use this science to help patients. I really needed him to trigger that in the beginning.

It takes courage to take that step to become an entrepreneur. Where did this courage come from?

As I was a postdoc back then, there was not a lot to lose. I was not risking a fantastic, great career somewhere.

Either it works and it’s brilliant because you can actually use the science to help people, or if it doesn’t work, it would have been an amazing experience because you learn so much about many different aspects of what it’s like to lead and grow a company.

When you look at it from that perspective, you can only win.

What has been challenging in this journey so far?

Recruiting for me has been the most challenging, to build a team that invests their hearts and souls into making the company work.

You’ve won some awards. Tell us about them.

We won the Swiss Innovation Challenge, and it was surreal to have been on stage, receiving a check from a Federal Council member, looked on by around 3,500 people in the stadium in Basel.

Thinking back that just a couple of years beforehand, we were these lab rats, trying to figure all this out and then to actually stand on the stage with a Federal Council member was very rewarding. It was great for my team especially, to see this kind of external validation for TOLREMO.

Most recently, we made it to the top three of the Swiss Technology Award.

Where do you get your energy from?

I think I’m a naturally energetic person. I just love what I do.

The potential of the technology when we started this was a totally crazy idea. Now we actually see that this works and the clinical potential we have is absolutely amazing. That is a big driver for me.

What has been a highlight so far?

We are just about to nominate a clinical candidate which will be of a big highlight for all of us, as it marks the next phase for TOLREMO.

We have been in the start-up phase so far, having to validate the technology and show people that what we do and promise, is something that we can actually deliver on. With the nomination of the clinical candidate, this start-up phase really ends, triggering the next development phase which is to enter into the first clinical trials.

We are now in growth mode and ready to do business development as we have the validation for the platform that it works.

We have been talking to Pharma Partners from the very beginning and they have always said that although it sounds fantastic, we needed to show them preclinical proof of concept that it is actually true. Now, we have that and with this validation, we can have a very different conversation with Pharma partners.

Best part about being a CEO?

The best part is having the resources to set the direction and follow my vision for the company together with a fantastic team of dedicated people.

Any lessons learned along the way?

I was always somebody who asked a lot of questions, but I would certainly ask even more. I would also try to connect to yet more people who have gone through this path.

Any advice for scientists who would like to become entrepreneurs?

I would say “Just do it”. Especially if you are trained as a scientist, you are trained to doubt and to question. But as an entrepreneur, you have to switch gears a little. You have to be able to deal with a certain degree of risk.

You can never totally de-risk a project which is what you are trained to do as a scientist. So, you have to overcome your scientific heart a little.

What is your view on failure?

A big part of drug development is failure which is why we need clinical trials. You have a certain scientific hypothesis and you see if it works. But this sort of failure is up to biology, there is nothing you can do about it. What is important is to de-risk your asset as much as possible, and to do everything that is in your power to succeed. You then have to leave it up to science.

There is, however, failure that is more preventable than others. Our job as entrepreneurs is to try to see these pitfalls and try to navigate them as well as we can. It is important to know that failure is always a possibility. But somebody has to test it. If you fail, it’s fine, then you know that it doesn’t work. But somebody has to do it.

It’s important not to be paralysed by the idea of failure. It’s intrinsic to what we do.

What is your hope for TOLREMO?

When thinking about drug resistance and realising that it is a problem, I would like people to think about TOLREMO, for us to become part of their “resistance” thinking. TOLREMO will be the company to show that there is a different, smarter way to deal with drug resistance in cancer. We will show that targeting non-genetic mechanism is a viable way to create novel therapeutic options for patients. I hope we can thereby help usher in a new area of precision oncology.

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