BY OUR PLATFORMS
BY THERAPEUTIC AREA
01 July 2022
As part of our SLAS Europe 2022 coverage, we speak to Dr. Javier Terriente, Co-founder and Chief of Drug Development at ZeClinics, about how zebrafish could be the future for discovering new therapeutics.
Please could you introduce yourself and tell us about your role at ZeClinics?
My name is Javier Terriente, and I have a PhD in molecular biology. I spent 15 years in academia, and in 2013 we founded ZeClinics. I am the co-founder of ZeClinics, but I have also been leading the scientific side of the company. I was the scientific director until a couple of years ago, and today I am the chief of drug development.
Essentially, my role now within the company is to lead theour internal drug development programs, that we have in the company, our internal programs in drug development, and I also help with the implementation of new technologies like artificial intelligence and so on. In a way, I would say that I am the chief innovative officer in the company.
Image Credit: Kazakov Maksim/Shutterstock
ZeClinics is a contract research organization (CRO) specializing in zebrafish research. Why was ZeClinics founded, and what are some of its core missions and values?
First and foremost, ZeClinics was founded on the basis of our expertise, which we felt could bring something new to the industry. As an academic, I had a lot of experience working with zebrafish. I was very much focused on basic research problems, but we understood from early on that the zebrafish could bring a lot of biological and experimental advantages to the industry that may be useful for drug discovery, target discovery, and understanding the safety of new compounds and more. So, we thought, ‘Why not?’. Why not create a company that can bring that expertise to the industry? Our company started small and has grown to 40 people – and we hope to grow more in the future.
In terms of core missions and values, I would say that our main mission is excellence and quality. We think - and hope - that we are always providing the best scientific output with the best quality, in terms of data management, in terms of scientific quality, and in terms of translatability of the results to humans.
I would say this excellence is what really drives us. The second mission that we have is to accelerate research. Within everything that we do, we seek to get drugs to patients earlier and at the lowest possible cost.
Your solutions focus on zebrafish as its model. Why are zebrafish such an excellent model to use for drug discovery research?
The first thing to know about zebrafish is that typically, we work with larvae, which are not considered animals until they reach around the day 5 mark. Essentially, you operate with an in vitro system that has all the biological features of an animal: gaining all the advantages of working with an animal, like complex biology.
For instance, there is organ physiology, and the biological processes happening therein are remarkably similar to those occurring in a human being: 80% of the genes in zebrafish are echoed in humans, so researchers can understand and model disease; understand the role of genes in the context of disease; and of course, look for drugs that are modulating these targets.
From an experimental point of view, a zebrafish is a small animal. This means that, for like for any in vitro model, you use multiwellple plates to test hundreds of drugs per week. Essentially, it is an animal in vitro system that brings the best from animal models, and, at the same time, facilitates the obtaining of big data and high biological translatability. All in all, we believe that it is a very good animal model with which to perform this research and accelerate the field.
By using zebrafish as models for research, this also reduces the use of experimental animal models. Why is this important to consider when conducting new research?
There are two dimensions that are interlinked. The first one is obviously ethical: of course, the aim for all researchers – and society in general - is either not to use animals in research or to minimize the use of animals in research as far as possible.
By using zebrafish embryos that are five days post-fertilization, researchers are not using an animal, as it is considered by regulatory bodies. This facilitates all the advantages of working with an animal without actually having to work with an animal.
This approach allows the user to find the best drugs - or make most of the experiments required to advance a drug in terms of safety, efficacy, or any other criterion without having to use an animal. This means that if it later becomes a necessity to use animals, researchers can use their best candidate.
All things considered, users see reductions in time, money, and the use of animals.
The second dimension is regulatory: given that zebrafish embryos five-day post-fertilization are not categorized as animals, this will avoid the imminent regulatory restrictions within the chemical industry, eliminating all animal research.
This means that zebrafish will become even more of an ideal alternative to the use of animals in research because they provide largely the same information that can be obtained from a rodent or a dog but are not classified as animals.
Image Credit: Micha Weber/Shutterstock
You currently offer three service platforms (ZeTox, ZeGenesis, and ZeEfficacy). Can you tell us more about these platforms and their applications within research?
The three central platforms we offer are ZeTox, ZeGenesis, and ZeEfficacy. Within ZeTox, what we have is a portfolio to analyze the toxicity of drugs from a general point of view but also to understand cardiotoxicity and other types of organ-toxicities. This platform is always evolving, so we are always generating new validations and proving the translation ability of this, the creativity of the animal experimental model, and also the implementation of new tests.
Next, we have ZeGenesis, which is essentially the creation of new genetic models. These are models that facilitate the understanding of the biological process within disease, which is typically coupled with ZeEfficacy (the use of zebrafish for understanding the efficacy of drugs in the context of disease). Within ZeEfficacy, there are a lot of different disease models that we can offer our clients, and but which are also customizable phenotypic screenings including complex behavioral analysis.
For instance, if a client wishes to study diabetes, we can create a model that suits the needs of this client and characterize it phenotypicallywe work with it.
forWe also do a lot of target discovery, as well as drug discovery purposes. This is so, because
iIt is also important to understand the role of things genes in the context of disease, and this is a very important point when you have a wealth of data like genomic data coming from patients: to really be able to pinpoint which genes are important associated with in disease. This is something that we do a lot with our clients.,
but iIn addition to theseis there three platforms, we also develop our own drugs, so we have a form of dual business model. This means that, on the one hand, we develop products and services for our clients, but on the other hand, we also use these technologies that we are developing to discover our own drugs in different applicationsindications.
You are talking at SLAS EU 2022 about your ZeBYTE platform, which is currently in development. Can you tell us more about this platform and how it works? How will this new platform differ from the other platforms you currently have available to clients?
ZeBYTE is not going to be a separate platform. Essentially, it is a holistic platform: something that allows us to undertake all the work currently taking place at the company. It is more than a platform: I would say that it is an initiative. This It is something that is always evolving, and essentially, what it does is implement artificial intelligent technologies all around the experimental and research process pipeline that we perform do at the company.
As such, wWe are implementing deep learning algorithms for extracting data from our images and videos obtained from experimental samples. BSo basically, for to streamline phenotypic extraction and phenotypic analysis. Then, wWe are using artificial intelligence, machine learning, and deep learning to analyze the related data that we generate: to understand and find casualties between our data, to find new targets, discover new hits, and so on.
It is a holistic way of going or transitioning from only a wet lab to a digital or a combination of wet lab and dry lab. Something I think is interesting about this platform is the fact that we can create generate the biological data from disease models, then we can treat this data through artificial intelligence to generate new hypotheseshypothesis, and then we can go back to the lab the next day to prove our hypothesisthose hypotheses experimentally. It is a cycle that we think is going to be very interesting for our clients and for our own research.
By giving this talk at SLAS, you are able to highlight the continued scientific advancements we are seeing in the industry. How vital are in-person conferences and exhibitions, such as SLAS, in accelerating new ideas and creating important discussions?
I think they are vital. The point about in-person meetings is that there is a level of spontaneity: things simply happen in a different way than they do in a video conference. During the pandemic, all of us have gone digital, and conferences and meetings which were in person can be done via video conference, but it is very difficult to substitute that intangible quality of a conference with a video conference.