Professor Karl Karlsson, CSO & Co-founder and Perla Björk Egilsdóttir, CEO
With the advances in technology, the field of neurosciences is unlocking new opportunities to significantly reduce the burden of nervous system disorders. However, neuroscience drug discovery, which demands an understanding of disease biology, combined with innovative chemistry and neuropharmacology, can be a significantly challenging and complex process. While animal models have broadened the understanding of human nervous system disorders and their treatment, small and mid-sized pharmaceutical companies lack the budget and the expertise required to leverage these models for understanding disease biology, and testing the safety, toxicity and side effects of new drugs while also interpreting the relationships between genotype and phenotype. In fact, studying drugs can turn out to be significantly expensive for these companies when using traditional lab animals like mice or rats. Against this backdrop, small and mid-sized pharmaceuticals seek specialists for the drug discovery process, who can help find new drugs for CNS diseases through reliable techniques to speed up the process and allow evaluating multiple drug molecules within a short timeframe.
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.
We perform in vivo assays using zebrafish, providing speed and cost-effectiveness similar to cell-based assays, with unprecedented accuracy and scalability
In fact, the company has preset assays that present a cost-effective option for small pharmaceuticals, instead of building a new assay from scratch. That’s not all; 3Z also empowers budget-strapped small pharmaceuticals with a risk-sharing strategy, whereby 3Z reduces the cost of the assay in return for a part of the IP or revenue of the ensuing compound.
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.