Combining AI and Zebrafish to Accelerate Drug Discovery

Combining AI and Zebrafish to Accelerate Drug Discovery
Insights from IndustryDr. Javier TerrienteCo-founder and Chief of Drug Development at ZeClinics

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 our internal drug development programs, 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, like for any in vitro model, you use multiwell plates to test hundreds of drugs per week. Essentially, it is an 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 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 experimental model, and also implementing 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 custom 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 phenotypically for target discovery, as well as for drug discovery purposes. This is so, because it is also important to understand the role of 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 associated with in disease. This is something that we do a lot with our clients.

In addition to these 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 indications.

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. It is something that is always evolving, and essentially, what it does is implement artificial intelligent technologies all around the experimental and research pipeline that we perform at the company.

As such, we are implementing deep learning algorithms for extracting data from our images and videos obtained from experimental samples. Basically, to streamline phenotypic extraction and phenotypic analysis. Then, we are using 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 generate biological data from disease models, then we can treat this data through artificial intelligence to generate new hypotheses, and we can go back to the lab the next day to prove those 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.

I think that it is very important to come to in-person meetings: to meet people; to meet friends; to find new collaborations; to find new providers, and of course, to find new clients. It is vital for the survival of the company.

You are also working on the intersection between laboratory research and artificial intelligence (AI). How important is adopting emerging techniques such as AI to life sciences research? What are some of the advantages of combining AI techniques into your solutions?

Rather than ‘important’, I would consider this adoption as essential. To put it another way, I do not believe that any company will survive the next 10 years without using artificial intelligence. Artificial intelligence is just a better way to extract meaningful information from your data: it is a way to accelerate and accommodate your research, and it provides a competitive edge that is vital to the continued survival of a company.

From a research point of view, by analyzing data with AI we might find genes connected with diseases that were uncovered. That is likely going to provide competitive solutions to our company. In other words, we will not follow the same hypothesis as others (work on the same targets), but we hope will create new biological hypotheses, which is going to be great for research and, eventually, great for patients.

Image Credit: Gorodenkoff/Shutterstock

Are you hopeful that your ZeBYTE platform will help to accelerate the discovery of new therapeutic targets and drugs? What would this mean for global health?

In this type of work, we are already seeing the use of artificial intelligence and how it is accelerating research by uncovering things that were previously hidden.

In terms of how this is going to translate into human health: if the technology and the platform are adopted by many people – which is what we hope – we will definitely help other companies as well as ourselves to find targets and eventually cure diseases that are currently untreatable. This could really cause a paradigm change.

You partner with a large variety of research areas, including pharma, agrochemical, and cosmetic companies. How important do you believe collaboration is to science and ZeClinics?

It is very difficult for any small company like ourselves to do everything right. It is important to focus on what you do right and try to find the best partner for these other areas where you cannot be the best – letting your organization be the best when you partner with another.

This is happening both for small companies like ours and larger pharmaceutical companies. Across the field, we see larger companies working with smaller companies: buying or collaborating to get better solutions or better technological advancements. This is going to happen and, in the end, will benefit both the sector and the patients.

What’s next for ZeClinics? Are you involved in any exciting projects?

For me, the most exciting imminent project is the full implementation of ZeBYTE. In addition, we have several different drug discovery programs that we hope will spin out next year into new companies as we did with the cardio programs that we began in 2019 within a company called ZeCardio Therapeutics.

On the other hand, from a service point of view, we are offering more and more new services within the metabolic area and in the neuro-degeneration area. We are hoping that we will cover more areas for our clients and be increasingly innovative in what we do in the future.

What are you excited for about SLAS 2022?

We are currently seeing lots of interesting technologies and the rise of organoids and organ chips, which can be great models to complement what we do. We are also seeing lots in terms of automation. In general, I think that the sector is thriving.

We see people coming from different sectors here: mathematicians, big pharma, and small biotech scientists and engineers. In general, it is a very good place to merge different sensitivities.

Something else I have seen in this conference that I have never seen in other conferences within the sector is a focus on diversity and inclusivity, which I think is hugely important: considering diversity in terms of gender, race, sex, and more.

Of course, that is not technology, but it is important for our day-to-day work and another key takeaway from this conference.

Where can readers find more information?

  • ZeClinics: www.zeclinics.com
  • ZeCardio Therapeutics: www.zecardiotherapeutics.com
  • Read more about the development of ZeBYTE: https://www.zeclinics.com/science/zebyte-platform-to-predict-the-effect-of-drugs-based-on-the-use-of-zebrafish-and-artificial-intelligence/

About Dr. Javier Terriente

Dr. Javier Terriente is a biochemist with a PhD in developmental genetics. He has more than 20 years of research and managing experience in the Academy and the Biotech industry.  

In 2013, he co-founded ZeClinics (www.zeclinics.com), a vibrant biotech that exploits zebrafish as a research model for performing drug and target discovery, chemical assessment and understanding human disease. ZeClinics provides research services to third companies and academic groups, while it develops internal drug discovery programs.

More recently, Javier co-founded ZeCardio Therapeutics (www.zecardiotherapeutics.com), a spinout from ZeClinics that focuses on the discovery of therapies to treat cardiovascular diseases. From 2013 to 2020 he acted as Chief Scientific Officer at ZeClinics.

He now plays the same role in ZeCardioTx, while acting as Chief of Drug Development at ZeClinics. Per his role in both companies, Javier manages a growing scientific team, has directed several PhD theses, and published multiple research articles on the use of zebrafish for addressing drug toxicity and discovering new therapeutic drugs and targets.   

In addition to these roles, he serves as Vice-President at Asebio, the Spanish association of biotech companies. 

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