The Story of NORGANOID - Where We Are Coming From And Where We Are Headed
The reality of today’s drug development industry is that the low-hanging fruits – drugs with significant effect on a large population - have all been picked and we are in need of new approaches to develop new drugs faster and thereby address the unprecedented health system challenges (Stott, 2017a, Stott, 2017b). Although, there has been a progressive change in the models and methods used in preclinical drug development, going from animal models, to cell culture models, to robotized systems for high throughput screenings, the available human-specific models have only changed and improved in the past 15 years, in their 70-year history of usage. The ground-breaking findings of (Takahashi & Yamanaka, 2006) enabled the reprogramming of human somatic cells into pluripotent stem cells. These induced pluripotent stem cells (iPSCs) enabled a whole range of new cell-based models. The promise was to create highly specific in vitro models to develop drugs targeted at the disease.
One of the cell-based models that Prof. Yamanaka’s discovery enabled, was the development of organoids (Shoji et al., 2023). Organoids are 3D cell culture models made up of multiple cell types that can self-organise to recapitulate complex structures of in vivo tissue . Therefore, organoids enable the replication of physiological processes in a more realistic manner than 2D cell-based models. This has been a fundamental leap in the cell biology field with the potential to transform the biotechnology and pharmaceutical industry (Homan, 2023).
Despite this technological evolution, the amount of capital needed to bring new therapeutics to market has steadily increased over the past 30 years. Unfortunately, the failure rate of drugs (ca. 90%) has not changed a lot during this period and the return on investment is approaching 0% (Deloitte, 2023; Biotechnology Innovation Organization, 2021; Pamolli et al., 2020). For a company developing a new drug this means that the indications would need to get narrower and narrower, leading to highly specialised therapeutics where only a subset of patients are eligible. Decreasing the market size already leads pharma companies to increase prices to the tens of thousands of dollars per month for a single patient, just to breakeven on their R&D cost. This is not sustainable for healthcare systems, especially not in Europe. In my view, the biotechnology and pharmaceutical industries do not have this luxury. There are patient lives at stake here.
Most drugs fail due to the poor translatability of experimental results from animal experiments to human trials. Despite mammalian physiology being similar, a mouse is not a human. Optimising drugs on animal models will continue to lead to drug failures together with a waste of economic and time resources, and in many cases will also continue to lead to animal suffering (Van Norman, 2019). A different approach to developing drugs is needed. At NORGANOID we envision a future where organoids reduce the cost of failure of preclinical studies and improve clinical outcomes, possibly leading to better and cheaper drugs.
My first encounter with the world of stem cells was when I worked for a company that stored stem cells derived from umbilical cord blood while studying molecular biology at the Technological University of Graz. I immediately became fascinated by the vast biological potential of stem cells and wanted to learn more about them. To do that, I spent 10 months as an intern at the Department of Neurosurgery in Graz where I cultivated nerve cells from adult stem cells and conducted research on neural stem cells in the hippocampus of mouse brain. After gaining experience with mouse models, I wanted to shift my focus to research which is closer to human maladies.During a research stay in the group of Jan Wijnholds (Leiden University Medical Center, 2015-2016), I became the first person in the Netherlands to establish a human 3D retina culture (Quinn et al., 2019). The more I immersed myself in the subject, the more excited I became about stem cells and their ability to model tissues and mimic diseases to find potential therapies for them. It was during my time in Leiden that I first encountered microfluidic technology. In the life sciences, precise liquid handling in small volumes is not just desired, but often essential. However, the challenge lies in handling small quantities accurately, which leads to increased usage of laboratory consumables, resulting in unnecessary resource consumption and waste generation. Microfluidics helps in this regard. Building on my experiences, I started to work in April 2017 on the first practical concept of NORGANOID at the startup incubator Science Park Graz. In February 2022, I founded NORGANOID with the goal of creating an automated system that produces human tissue from stem cells, with microfluidics as a core technology.
The Food and Drug Administration (FDA) allowed in November 2022 that methodologies other than animal testing can be used to show the preclinical safety and efficacy of new investigational drugs, with the aim of replacing animal testing in the future. Among these New Approach Methodologies (NAMs) organoids and organ-on-chip technologies play a crucial role (U.S. Congress, 2022). The European Medicines Agency (EMA) is following suit (European Medicines Agency, 2021). From a biomedical perspective this evolution of regulatory practice changed the world. Together with Phase 0 trials preclinical studies can move towards human-specific disease models and human subjects earlier (Burt, 2020). This represents a paradigm shift for the industry. Our vision is to create a world where 3D cell-based preclinical experiments are highly automated, scalable, that are as easy as pressing a button, all while keeping the cost of failure at a minimum.
The generation of organoids is however a tedious endeavour and requires expert knowledge. There is a shortage of scientists capable of establishing and maintaining organoid cell cultures. In my view, organoids are required to achieve, as an industry, the goal of true patient-centric drugs. At NORGANOID, we understand the challenges of organoid generation and how crucial it is to have realistic cell-based models for drug development & chemicals safety screening. At NORGANOID we us as being the next step after 2D cell culture experiments. We are developing tools to enhance the prediction of patient responses of drugs and chemicals screened in vitro. We are currently developing our NanoLab SYSTEM™ (NLS™). NLS™ is designed to be a plug-and-play, automated organ-on-chip platform and will handle everything from initial iPSC differentiation, to organoid culture and maintenance, and will be compatible with standard imaging systems to perform drug and chemical screening. We will support you during every step of the implementation stage of the organoids into your processes and help you to get the most out of your experiments. With NLS™ we aim to reduce the feedback cycle time, thus reducing the time-to-market and reducing the potentially harmful drug or chemical compound entering the market. With the help of our platform we will enable you to follow your curiosity to ultimately have an impact in the world.
Our efforts bridge the disciplines of life sciences, engineering, and data science, and will require significant innovation and collaboration from experts across these areas. We are grateful to have the strong support from FFG, aws, our scientific and industrial advisors — who will provide their experience, their networks, and their capital to this effort. At the same time, we also plan to enhance our remarkable team that embodies a new type of culture, one based on a true partnership between scientists, engineers, and data scientists, working closely together to define problems, design experiments, analyse data, and derive insights that will lead us to changing how drugs and chemicals are tested in vitro. We profit from being embedded within the ecosystem of the Medical University of Graz through collaboration with various preclinical and clinical teams. We believe that building this community and this culture is as important to the success of our mission as the quality of the science or the engineering that these different groups will create.
We do believe that the time is right to rethink the preclinical drug development process using a different and more modern toolkit, in the hope that a new paradigm may help us increase the health span of more patients, sooner, and at a much lower cost. We invite you to join us on this journey. Together, we can shape the future of preclinical experiments, drive innovation, and make a lasting impact on the world of healthcare.
Charlotte Ohonin
Founder & CEO
