CALYXHA Biotechnologies GmbH is a product development company in the preclinical stage and also applies its drug discovery technology in industry partnerships. CALYXHA was founded in 2019 by Eszter Nagy MD PhD, Founder and CEO of CEBINA GmbH (Central European Biotech Incubator and Accelerator), Co-founder and President of Eveliqure Biotechnologies GmbH, previously Co-founder and CSO of Arsanis Inc, Vice President and Global Head of Research at Intercell AG (now Valneva SAS); Prof Robert Konrat, PhD (University of Vienna, Max F. Perutz Laboratories) and scientists Marco Sealey, PhD and Tanja Gesell, PhD; Wolfgang Friedl and CEBINA GmbH. CALYXHA is incubated and accelerated by CEBINA GmbH.

Tanja and Marco – you both have been to Summer School – could you share a little bit your story how your path from researcher to entrepreneur happened to be as well as what role Summer School took over?

Marco

You’re certainly right that it’s an interesting situation! Both of us participated in the Summer School: I was one of the first participants in the “2015 experiment,” meaning it was the first year of the summer school; Tanja followed in 2016 with Lea (our daughter) and me backstage.

Making the transition from the academic environment to start a venture, and become an entrepreneur…well, it’s not easy. During our studies and while pursuing various degrees, especially in the scientific environment, we are “programmed” to follow mainly one path – that leading to a professorship. This pathway seems to be too narrow and limiting sometimes, and it’s clear to me that we need more alternatives. Luckily, the academic community is slowly changing and providing more entrepreneurial programs and options in the curriculum.

Early in my career, I was fortunate to work on research projects focused on understanding trypanosomes, a group of unicellular pathogens. These are parasites that currently affect many people and cause significant morbidity and mortality in the developing world, and there are very few therapies available. Working to understand the molecular and cellular biology of these organisms, and thereby provide tools for diagnostics and chemotherapy was always a motivation for me. During this journey, I got to observe and experience the interface between basic and applied research.

At the Konrat group in the department of Computational and Structural Biology at the Max Perutz Laboratories in Vienna, Austria, I coordinated interdisciplinary projects that combined cell biology with atomic-resolution studies of protein binding using NMR. I also assisted in the development of in vitro disease models for studying the mode of action of small molecules.

In 2015, following a suggestion by the Technology Transfer Office at the University of Vienna, I attended the summer school to present one of the projects that I was working on. Six years ago, I did my first “elevator pitch”, built a business plan and after an intensive week of work, finally pitched in front of real investors. It was truly exciting, and after that experience it was clear to me that to be an entrepreneur you need to have passion, confidence in your project, and a willingness to adapt to change. And after five years, working on the future CALYXHA projects, collecting data, filing a patent, and believing in it, I decided to change my academic path and focus on CALYXHA.

Tanja

Today, as a couple, we are fortunate – since our trajectories are connected, but we have different paths and complementary expertise. Indeed, the CALYXHA project has two seeds, which were growing more and more together along their paths.

I am a Molecular and Computational Biology scientist as well as a trained artist. Both fields are united by the underlying question: what is a structure? Yes, it’s a deep academic question, but one that turned later into a business.

In a first step, I have defined a phylogentic definition of structure, then with international collaborators, I found various extensive sets of functional transcriptomic annotations associated with complex diseases.

In my career, that underling question about structure developed into the questions: what is a disease, and what is behind a disease?

With Professor Robert Konrat at the University of Vienna, I also started considering structural features of small molecules (drugs). We strongly believed that new structural models allow exploration of new approaches in medicine.

In Alpbach I presented our in silico drug discovery platform based on unified structure definitions, which can be used for both repurposing existing drugs and identifying possible disease applications for novel chemical compounds. The drug development platform was a starting point for the discovery of the molecules used by CALYXHA.

After Marco established different in vitro and in vivo experiments in the lab, I started and coordinated bioinformatics projects that combined next-generation sequencing techniques, metabolomics, and image analysis with big data to identify and understand the mode of action (MoA) of our new compounds. Starting with a bottom-up approach to find different potential candidates, I switched to top-down approaches to characterise these molecules. From this point onwards we have focused together on future CALYXHA projects.

Marco

What I think has been essential to CALYXHA is how we complement each other based on our professional expertise. The different knowledge and expertise that we can combine, and use to design together experiments that combine in vitro and in vivo disease models with sophisticated experimental readouts and deep bioinformatic analysis, is a real plus.

 

Regarding COVID-19 we all currently face challenging and volatile times. How is Calyxha doing?

Marco

It’s hard to imagine who is not affected today by COVID-19. We, like many of the startups located at the Vienna Biocenter, were directly affected by the shutdown.

In our case, we have a very close collaboration with the laboratories at the University of Vienna and the university closed on March 15th. Since then, we have had no access to infrastructure, machines, services and the collaboration with the university labs stopped. It’s the moment when we all realised how much we depended on but also profited from the location at the Vienna Biocenter.

At the beginning, I contacted colleagues at the campus who are running cell culture experiments to ask how and what they were doing. For all of us responsible for the labs, it was a hard call to balance the risk of infection for us or one of the employees with the need to keep the experiments running. I was delighted to experience the very collaborative environment on campus during these difficult times, however: we all have a willingness to help, to share lab equipment, instruments, and reagents.

Tanja           

For CALYXHA, the COVID-19 crisis changed our perspective in different ways. On the one hand, it is hard to fulfil some of our milestones in time. On the other hand, with our tissue degeneration approach we pivoted to COVID-19 as well, hoping to contribute. Drug repurposing has of course become a well-known phrase during this crisis. Our drug development platform has the potential for different partnerships. With CALYXHA, we have the advantage that the drug discovery platform is already on track.

Marco

Regarding funding, we were lucky to get support at the beginning of the year from Austrian VC as well as international investors, which will accelerate the preclinical development of our lead candidate. It will also broaden the scope of proof-of-concept studies in disease areas where we expect efficacy from our radically new disease-modifying approach.

 

Would you like to share another shaping situation you faced on your path of entrepreneurship?

Tanja

The Summer School was an important step and experience for both of us. We still profit today from a fantastic network that originated from it.

Last year, we were pleased to get an invitation to give a talk at the 5^th anniversary.

There, I spoke about the movie “Solaris” by Andre Tarkovsky.  The film is a science fiction epic that sends a person into the unknown. It is not only a beautiful metaphor about our situation, but there is also a personal coincidence which connects “Solaris” with the Summer School.

A year later, Herman Hauser gave a talk at a research institute in Vienna. After his talk, we decided spontaneously to present him “Solaris”, to share and to continue a discussion from the school. At that time, we couldn’t have known that today our company CALYXHA would be sitting in a building at the Vienna Biocenter, called Solaris – what a fantastic coincidence!

Marco

One clear memory was when an outsourced animal experiment didn’t work out. It was an unfortunate and disappointing moment.

Weeks later, I got a call to say there had been a power cut in one deep freezer in the facility, and we had lost our tissue samples.

Following this bad news, we discussed the possibilities and options. Finally, they agreed to repeat the experiment. We increased the dose, and guess what? We got a dose-response!  Thanks to the accident, we got a second chance! Without that positive experiment, and that moment of serendipity – I think CALYXHA wouldn’t exist today.

This moment I refer to as ”The call”. For me, it represents the “uncertainty-risk” that we all take when we start the journey with a startup.

Tanja

Looking back at the summer school, we learned a lot, and in particular we learned entrepreneurship. Now that I am an entrepreneur I understand things better, and in particular the importance of the team.

The project was accelerated when Dr. Eszter Nagy joined the team as a CEO. Eszter has over 20 years of biotech experience in discovery, preclinical, and early clinical development. When we met Eszter, she had just founded CEBINA, a Central European Biotech Incubator and Accelerator.

Now, CALYXHA is in partnership with CEBINA, renting offices and laboratory space in the CEBINA facility, and is supported by its business development, R&D, and its operation team.

We continued to work with Prof. Robert Konrat. Since he is an entrepreneurial academic, the continued intense interaction with him has been very supportive and comforting in the transition process and bridging the two worlds.

The CALYXHA team is marked by critical but effective discussions from all angles in a productive and time-efficient manner.  The team also includes our main investors with whom we meet frequently to discuss progress and strategies.

We have the vision to bring our molecules to the market.  Along this line, I did the logo and the website.  Retrospectively, at the early stage of the company, discussions about the logo were essential for the team to align claims and values.

Terms such as “milestones, deck, scientific-deck, business-deck, one pager, undisclosed, kick-off meetings, burning-rate, align, team, TC (teleconference), etc…. ” are now in our daily vocabulary.

 

Congratulations to your currently announced first patent grant as well as you secured seed funding – what are your next steps on your entrepreneurial road? 

Marco

We are lucky to have supportive and engaged investors.

Tanja

CALYXHA’s claim is revolution in targeting tissue degeneration, visually pointing to a process of de- and re-generation. Indeed, our approach is a radical new way to consider different diseases targeting tissue degeneration. This gives us the opportunity to contribute to the drug development against COVID-19 and other diseases while we fulfill our current milestones.

Marco

Today, scientists have a global responsibility regarding the COVID-19 crisis to consider every possibility to help. Along this line, we will keep our initial goals the development of drugs for treating tissue degeneration.

 

Thank you very much for sharing your story and we are looking forward to meeting you soon again.