Les RDV Santé et Numérique : Interview with Nathalie and Gregory Maubon from HCS Pharma

[Emmanuel Mawet]: Hi Nathalie, you are the CEO of this innovative French start-up, before talking about HCS Pharma, could you give us a quick overview of your background?

[Nathalie Maubon]: I did a PhD in basic research in cancer, molecular and cellular biology and then worked in the pharmaceutical industry, a biotech company for 12 years. I was in charge of developing new in vitro models, miniaturizing them and industrializing them on robotic platforms in order to test molecule libraries on a large scale. I was in parallel member of research projects or research project leader for the research of new drugs from hit research to clinical drug candidate.

[EM]: What were the driving forces behind joining the HCS pharma adventure?

[NM]: I created HCS Pharma based on 3 observations:

1. Thanks to industrialization and medical progress, the life expectancy of the world’s population has increased significantly over the last 30 years. Unfortunately, certain so-called complex diseases such as cancer or neurodegenerative diseases such as Alzheimer’s or Parkinson’s have also increased significantly. And the drugs currently available for these diseases are still not very effective. It is therefore necessary to increase efforts to find new treatments for these types of diseases (new drugs, cell therapy, etc.)
2. The pharmaceutical industry is not innovating with the current drug discovery process. Drug candidates that are to be tested in humans are chosen based on results from simplistic in vitro or animal models that are not predictive of what will happen in humans. As a result, 90% of drug candidates fail in the human clinical phase, and 97% fail in oncology.
3. Due to this lack of innovation, pharmaceutical industries are closing their research centers, with a transfer of risk to academic research, which is not trained for the industrialization of in vitro tests.

It is therefore essential to relaunch innovation in the search for new treatments, which is why I created HCS Pharma with the objective of changing the process of searching for new drugs to obtain more effective treatments.

[EM]: Historically HCS Pharma, what are its activities?

[NM]: Coming from the private sector, I created HCS Pharma as a CRO. We are specialized in cell imaging. We started with classical in vitro tests in 2D culture and we very quickly set up a partnership with another start-up, Celenys, which was developing a 3D culture technology, the BIOMIMESYS technology, which made it possible to reproduce the extra-cellular matrix of any type of organ. Celenys developed cell culture products with BIOMIMESYS technology and within HCS Pharma, we developed and validated cell models based on BIOMIMESYS products. Unfortunately Celenys went bankrupt in 2017 and we bought back the patent and internalized the technology within HCS Pharma. Since then, our business model has changed in the development of BIOMIMESYS products. This technology being a disruptive technology, it requires more financial and human resources than previously. We develop products based on this BIOMIMESYS technology and we also use it internally to research new drugs/cell therapies alone or in partnership with other biotechnology or pharmaceutical companies…

[EM]: How Biomimesys® represents a real breakthrough and what added value for your customers?

[NM]: BIOMIMESYS® is the only technology that faithfully recreates the environment of any type of organ, also called the extra-cellular matrix (ECM). An organ or tissue is created from cells that are attached to a solid scaffold by means of adhesion proteins. Currently, there are three types of 3D cell culture systems: matrix-less systems that form a compact cell aggregate, solid plastic-like scaffolds without adhesion proteins that also form a cell aggregate in the cavities of the plastic, and hydrogels without solid structure. In the BIOMIMESYS creation process, a hydrogel is created from the solid structural elements of the ECM on which the adhesion proteins are grafted and then a physical process is used to change the state of the hydrogel into a solid structure. As we can play on the composition and the modification of the state change process, we can recreate matrices in a specific way with the same chemical, physical and biological properties as the ECM in vivo.

[EM]: Your Biomimesys® technology has been recognized as DeepTech by BPI France?

[NM]: The impact is mainly more visibility. We are also part of a community of deep tech entrepreneurs with the same constraints, the same issues and the same problems, such as high financing needs, multi-market possibilities, difficulties in selling disruptive systems…

[EM]: Can we say that this breakthrough is also due to digital technology, which is becoming more and more important in the pharmaceutical and scientific fields?

[NM]: Yes, testing 100s of thousands of compounds on biochemical tests was still relatively simple because 1 tested molecule gave a numerical result. Since the testing of molecules is done on cellular tests in 2 dimensions by cellular imaging with an analysis of the images giving numerical results, a tested molecule can give 1 to a few images which will give 10 or even 100 numerical results. But when we move on to testing molecules on a mini-tissue or organ recreated using BIOMIMESYS®, we have to make a stack of 3D images, reconstruct the object by filling in the gaps between 2 images and then analyze the objects to obtain quantified results, and all this at high speed to test the same libraries of molecules. Digital technology is therefore at the heart of pharma.

[EM]: What digital bricks are needed to carry out a project like yours?

[Grégory Maubon]: To analyze the effect of molecule libraries on tissues reconstructed with BIOMIMESYS, we use big data, object analysis by image stack reconstruction then data analysis by machine learning, deep learning and/or AI

[EM]: There are many biotech companies developing 3D printing technologies, especially for artificial skin reconstruction. What are the differences or similarities with your Biomimesys® technology? Are there any points of convergence ?

[NM]: There are indeed several companies that develop bioprinters and/or bioinks like Cellink or service or cell therapy like poïetis in Bordeaux for reconstructed skin and liver or organovo which on liver. In my opinion, there are several problems with bioprinting. The first problem is the time needed to print the cells which allows to make micro-tissues but cannot be used at high speed or to recreate complete organs as organovo is trying to do. The second major problem is the use of bio-inks which are hydrogels without solid structure. These hydrogels encapsulate the cells and reduce gas and nutrient exchange. Nature being well done, the cells self-organize when put in BIOMIMESYS. For example, the differentiation of stem cells in BIOMIMESYS® has made it possible to obtain complete organoids architected with all of the functional liver cells.  On the other hand, BIOMIMESYS being very porous, about 100 µm, it is possible to make large structures without having cell death in the heart of the structure.

[EM]: HCS Pharma was born in France with its two sites in Lille and Rennes and is incorporated in France. Is it also a French company in the composition of its capital?

[NM]: For the moment, yes. But raising funds for this type of disruptive technology is difficult, while the financing needs are substantial.

[EM]: The health crisis has highlighted France’s major industrial dependencies in the health field. What do you think about the aspects of industrial sovereignty? How does HCS Pharma contribute to this sovereignty?

[NM]: This is a wishful thinking of the French government and also supported by Europe with the EIC but in my opinion, the financial means are not there. While we are struggling to raise a few hundred thousand euros, start-ups in the United States are raising several million. After the seed stage, raising funds for development is very difficult in France. With the EIC, deep tech start-ups can raise up to €15 million, but this is still not enough with a long 3-step process that is not in line with the timing of a start-up. I hope to be able to keep this BIOMIMESYS technology in France, but in view of the problems of raising funds, like many start-ups, there will certainly be an obligatory move to the United States or Asia, if only to launch the business.

[EM]: IT tools and the move to the cloud have become unavoidable, including in the life sciences. As a company director, are you aware of the security issues surrounding data?

[GM] : From the very beginning of the company we have based our strategy on a hybrid vision of IT services. Part of our tools are hosted in the cloud to facilitate their development and scaling. A second part is located on our premises for security and data volume reasons. We take the security of our infrastructure very seriously because we have already protected both our data and our customers’ data. I would like to make it clear that this security issue is only a matter of technology. We regularly train internally so that everyone is aware of the “computer security gestures” because today, social engineering is the greatest danger.

[EM]: Do you know that choosing American technological solutions puts you at risk due to the extraterritoriality of their laws? And that they have already used this weapon in an “economic warfare” context?

[GM]: We are fully aware of this problem, and we are keeping up to date with the current negotiations of the European Community with the USA. We try as much as possible to use European solutions for our IT needs, but it is sometimes complicated to find the right solution for small and medium sized companies like ours. Fortunately, there are more and more possibilities like the Dolibarr ERP or the CryptPad co-creation tool and we see with hope initiatives to structure offers like Euclidia.

[EM]: Do you think that digital sovereignty is an important dimension for a business leader?

[GM]: Technological and digital sovereignty are very important dimensions at HCS Pharma. In order to find effective therapeutic solutions for the diseases of our century, such as cancer or neurodegenerative diseases, innovation must take place at all levels: from the reconstruction of relevant cellular models that can be used in high throughput screening using disruptive technologies such as BIOMIMESYS, to the analysis of images and data using digital tools.

On the other hand, the notion of digital sovereignty might seem secondary for a company with less than 20 employees, but it is indeed a fundamental strategic issue. Today, digital technology is at the heart of all companies, regardless of their size. Unfortunately, it is the smallest ones that, due to a lack of skills, time and means, are the most ill-equipped to put in place the right tools. We take this concept very seriously by trying to make an “informed” choice (the very principle of sovereignty) for every decision involving digital technology. Sometimes, as we mentioned earlier, it is complicated and we have to apply a reality principle, which is often related to a question of cost! But, once again, we are not fooled by this weakness, and we are working to quickly regain our ability to choose.

[EM]: Coming back to HCS Pharma, what are your ambitions for the next 5 years?

[NM]: The ambition is to make BIOMIMESYS technology known internationally and thus to be able to develop internationally by setting up new sites in the US and in Asia, to continue the research and development of BIOMIMESYS for internal use in order to find new drug candidates against cancer or neurodegenerative diseases that are much more effective than those currently on the market. In Asia, we also want to develop the technology for cell therapy and regenerative medicine.

[EM]: We are coming to the end of this interview, what would be your conclusion?

[NM]: My conclusion is that it is important to reindustrialize France and to do so through disruptive technologies such as BIOMIMESYS is an excellent idea to move towards technological sovereignty. I see things evolving in the right direction in France but also in Europe, but it is necessary to go faster in these changes and to increase the financing because the reindustrialization of France is still far from being a success.