“We help you investigate the toxicity or potential side effects of your drug - free of charge!”

InSphero originated from the Bio Engineering Lab of Andreas Hierlemann. Jan, can you briefly summarise what the company is doing and with whom you collaborate?

Sure. First of all, many thanks for inviting me to this Digital Campus and for the possibility to listen to the keynote by Caroline Uhler. I learned a lot about statistical methods on drug repurposing and I see some dots here for future collaborations…
About InSphero: we are a pioneer in engineering and producing easy-to-use and assay-ready 3D microtissue assays for predictive compound classification. And we are doing this both for in vitro drug safety and for drug discovery applications. Typically, we collaborate with large pharmaceutical companies, with smaller biotech firms as well as with some academic partners.

This year, InSphero celebrates its 11th birthday. In retrospective, how would you describe your development or your growth curve..?

The good news is that we are still alive after 10 years, this fact is already a good sign! This only happens to about 10% of the startups. And: we have grown: we started with three people and we are now 66 with our headquarter here in Switzerland, in Schlieren close to Zurich, and ten employees in the US. It has been an interesting and very rewarding time, although not always a straight up line. We had some challenges in 2015/2016 when we were under a lot of pressure by a US competitor that had some 120 million in funding who tried to break into our market. That was painful but it made us stronger in the end. This competitor is no longer in business and we are still growing. So, sometimes you need this kind of challenge in order to move forward at a faster pace.

Your area of expertise is in the field of pre-clinical research. An essential model in this context is the 3D Human Liver Model. Can you further explain this model? And: does this engineered liver model replace animal experiments…?

The liver is a really cool organ because a lot of the drugs that patients are taking are passing through the liver; some molecules get metabolised, and in some cases these metabolites cause a toxic effect. This means, the original parental drug was actually safe but the reactive metabolite which was generated by the liver has a negative effect, for instance, on the liver or on skin -- and we get a rash. The complexity here is really quite intriguing and that might be the reason why there was such a strong interest in industry to have an easy-to-use and more reliable liver model. Hepatocytes when they are grown in a classical 2D culture loose their liver-specific functionality after two to four days. By forming a 3D spheroid or organoid, however, we can extend that functional life-span to more than 60 days. That allows us to mimic the therapy, including redosing, of a human patient. We published a milestone external page paper in 2017 testing more than 100 compounds and we showed that this approach is by far more sensitive and specific than the current methods. It is a great tool for drug safety, and now we are also applying it as a disease model. There is a lot of interest in non-alcoholic steatohepatitis (NASH), a rapidly growing metabolic disease in the world, which could have a socio-economic impact similar to type 2 diabetes. So, now we can use this technology to identify new drugs. You already mentioned that we see a big movement in the pharmaceutical industry - at least for the past couple of years - to move away from animal testing into advanced human in vitro models, not so much driven by ethical concerns but driven by the understanding that these advanced human models are actually offering a lot more valuable data than the animal. They also have faster turn-around times (questions-to-answer time) and, in addition, many new treatment paradigms like CAR T cells {Chimeric antigen receptor T cells} and antibody-drug conjugates {both alternatives for treating various cancer types}, or mRNA therapies do not really work in animals.

InSphero is also contributing to the global race to find vaccines and treatments against SARS-CoV-2...? Can you tell us more about this initiative?

Yes. When the pandemic started, as an entrepreneur the first thing you do is to make sure that your operations remain viable and the staff is safe. But when we had this phase covered we discussed with the team: is there something we can do with our expertise to help finding new drugs or new vaccines for the coronavirus? Lung tissue is not one of our specialties due to the way how our technology works. But we are very good at predicting human safety of new drugs. This made us start a new initiative where we reached out to the community and offered: «independent of your status whether you are academic (i.e. non-profit) or a company, come to us and we help you investigate the toxicity or potential side effects of your drug - free of charge!». We had the capacity in the lab and we put this out to the community as our contribution to the global effort of studying and understanding this disease. I cannot say more about the projects arising from this initiative due to confidentiality, but this helped us to identify additional areas of research.

In what way does InSphero ‘feel’ the impact of the COVID-19 pandemic, economically?

First of all, in some ways organizationally. When the pandemic started we of course applied social distancing in our company, which was a little more difficult to execute in the labs. We also needed to secure protective garments and masks which were more valuable than gold at that time in March. We do 50% of our business for the US and very often ship our tissues to US customers. First, the flights stopped and that made it very difficult for us to get our products into the US logistically. Later, when the US also figured out that it was not a disease just affecting Europe and China, the labs of our customers started to close down, which reduced our business on the product side. But, we have very good relationships with our pharmaceutical partners, which allowed us to continue some of their research work in our labs. So, we have been very busy. But of course this whole story has not yet come to an end and we will see quite substantial effects, propagating in ripples throughout the economy over the next years. Many pharmaceutical companies had to stop clinical trials because the data was contaminated by the COVID-19 lung disease or clinics stopped contributing to trials because they were overrun by patients infected by SARS-CoV-2. I think, many of these trials will have to be restarted to a large extent, which will delay the introduction of new drugs by a year or two years. That is going to have an effect on the cash flow of the pharmaceutical companies and they will decide on whether they will slow down research and development or increase outsourced partnerships. So, the effect on us is still unknown, but step-by-step we are navigating with a little more visibility than we had two or three months ago which allows us to decide on strategy again actively instead of reactively.


Many thanks, Jan, all the very best to you and InSphero, we will be excited to hear more about you in the near future!