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Professor Karl Karlsson, CSO & Co-founder and Perla Björk Egilsdóttir, CEO Putting an end to their quest is 3Z Pharmaceuticals, a CRO revealing new dimensions in the rapidly growing realm of drug development. Changing the industry narrative in early drug development, 3Z is transforming the conventional drug development process, which is constantly getting longer and increasingly expensive. In doing so, the company utilises zebrafish for drug screening, and combines pharmaceutical research with software development, presenting a new way of approaching the zebrafish research model. “We do not use rodents. Instead, we perform in vivo assays using zebrafish, providing speed and cost-effectiveness similar to cell-based assays, with unprecedented accuracy and scalability,” says Professor Karl Karlsson, co-founder and CSO, 3Z Pharmaceuticals.
For pre-clinical drug and toxicity screening, 3Z Pharmaceuticals uses 2500 zebrafish larvae in separate containment wells as its primary animal model. The behaviour recordings of these shoals of fish—that bear 85 percent genetic resemblance to humans—are leveraged by 3Z’s in-house developed software and advanced data processing methods for behavioural modelling and data analysis. The behavioural information is used as a detailed readout, which is sensitive to all kinds of perturbations and broken down into different parameters, driving early decision-making in drug development. These zebrafish models from 3Z also have been instrumental in dramatically increasing cost-effectiveness in the early phases of drug development and the speeding up of the drug pipeline.
According to Karlsson—a highly experienced neuroscientist with an extensive background in behavioural neuroscience—the separate assays enable companies to start investigating compounds that they could not have done previously, which, in turn, increases the number of compounds in their pipeline.
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We perform in vivo assays using zebrafish, providing speed and cost-effectiveness similar to cell-based assays, with unprecedented accuracy and scalability
Another key differentiator of 3Z’s zebrafish platform is how it stores and generates a comparative database, and provides comprehensive insights into zebrafish research outcomes. 3Z has been successful in assisting companies in achieving economies of scale, equipping them with massive datasets that help compare a new compound with the immediately-collected control groups, as well as, a dataset of normative values that reveals any difference that the compound might produce. Moreover, 3Z has invested significant time in working out different behavioural parameters. The behaviour repertoire of a fish is so rich that plenty of information might get lost if a single parameter is focused upon. While other companies and researchers working with fishes are focused on simple metrics like the velocity of their swim, 3Z’s rich behavioural datasets include long-term recordings, revealing circadian rhythms, different stimuli responses, alongside the swimming speed and location.
While 3Z allows parallel screening of 2,500 zebrafish larvae that result in high throughput, the solutions’ benefits do not end there. “Our zebrafish platform offers high flexibility and scalability that allow us to provide tailor-made solutions and develop customised assays to suit our clients’ needs in screening for particular compounds,” says Perla Björk Egilsdóttir, CEO, 3Z Pharmaceuticals, who is also a biochemist and has a proven track record as an entrepreneurial business leader. Born with a focus on sleep research, 3Z has now expanded its service to multiple drug discovery and efficacy and toxicity assays, including disease models to mimic Parkinson’s disease, motor neuron disease, epilepsy, and sleep disorders.
Paving the way towards rapid growth and innovation, 3Z has worked closely with several pharmaceutical companies to provide cost-effective solutions for fast and precise drug development. In an instance, 3Z worked with a pharmaceutical company that discovered a novel human mutation linked to severe disease. Having affected only a handful of patients, this rare mutation had the potential to revisit new novel targets. As the biological material from the human patients cannot be accessed directly, the client was in dire need of tissue samples whereon they could recreate the mutation. Post a refined market analysis, 3Z Pharmaceuticals was an obvious choice for them. 3Z helped the client regenerate the rare mutation in a zebrafish and discover its genetics control, how it changes with age, what downstream effects it has on other species, and more. Additionally, this approach turned out to be valuable in revealing novel genes and routes. The zebrafish used for behavioural assays weathered the storm for the client, helping them quickly screen new compounds.
3Z is currently amassing large databases to utilise AI for reviewing behavioural trends in the future. Moving ahead, the folks at 3Z are also focused on making their business model better, moving from a pure fee-for-service model into an IP sharing model, and finally, to in-house drug discovery programs.
Company
3Z Pharmaceuticals
Management
Professor Karl Karlsson, CSO & Co-founder and Perla Björk Egilsdóttir, CEO and Haraldur Thorsteinsson, CRADO and Co-founder
Description
Changing the industry narrative in early drug development, 3Z is transforming the conventional drug development process, which is constantly getting longer and increasingly expensive. In doing so, the company utilises zebrafish for drug screening, and combines pharmaceutical research with software development, presenting a new way of approaching the zebrafish research model. For pre-clinical drug and toxicity screening, 3Z Pharmaceuticals uses 2500 zebrafish larvae in separate containment wells as its primary animal model. The behaviour recordings of these shoals of fish—that bear 85 percent genetic resemblance to humans—are leveraged by 3Z’s in-house developed software and advanced data processing methods for behavioural modelling and data analysis
3Z specializes in the creation of genetically modified models related to disorders of the central nervous system. They have made notable progress in the identification of potential treatments for ADHD using their innovative zebrafish screening method. The primary therapeutic candidates, initially uncovered using engineered zebrafish, have been subjected to thorough testing in mammalian models to affirm and broaden their therapeutic viability. Of particular importance, these groundbreaking ADHD treatments are not stimulants, presenting a promising alternative with fewer side effects than current therapies. This addresses the requirements of individuals who do not respond well to existing treatments.
The collaboration between 3Z and biotx.ai has the objective of establishing a robust connection between research on animals and eventual human clinical trials. Through the utilization of advanced AI-driven human genetics-based modeling, the involvement of key therapeutic targets in ADHD will be exhaustively investigated. This comprehensive analysis will shed light on the impact of these targets on the disorder, predict potential effects on other diseases or conditions, and evaluate metabolic alterations. The accuracy of these predictions will be verified by comparing them with real-world measurements from zebrafish studies, effectively emulating a Phase II clinical trial.
The results of this pioneering AI-driven investigation will provide predictive insights into the potential success or failure of the upcoming trial, thereby reducing the risk associated with the primary compound as it progresses to an actual clinical trial. Through the application of AI modeling, this collaboration is geared towards expediting the drug development process and enhancing the efficiency of translating outcomes from animal models to human trial settings.
Dr. Karl Karlsson, CEO of 3Z and a distinguished authority in behavioral neuroscience and biomedical engineering, has underscored the importance of this partnership. He has noted, "We are embarking on a novel era in the realm of drug discovery and development, one in which AI holds the promise to transform the industry. The animal models we devise are centered around disorders and conditions that arise from imbalances within neuronal networks, arguably one of the most intricate aspects to accurately simulate. Nevertheless, we can model the effects of the drugs we pinpoint on specific genetic targets, equipping us with crucial information and significantly mitigating the risk of setbacks moving forward."