Christopher Hart co-founded Creyon Bio after working at Ionis Pharmaceuticals where he built and led the functional genomics group. Before that he bounced between academia and industry with his background at the intersection of biology and computer science. Now he serves as Creyon’s CEO, using this background and experience to help the company engineer oligonucleotide-based medicines for gene-centric therapies.
Hart highlighted the difficulties facing drug development today that impact the speed at which new therapies are produced, the cost of development, and the failure rates of many candidates. Creyon therefore seeks to address these issues using oligo therapies.
For Hart, the opportunity for oligos lies in their ability to “engage with the molecular and genetic bases of disease by targeting effectively any aspect of the central dogma of molecular biology through Watson Crick Franklin hybridization to control gene expression that's underlying pathogenesis.”
Critical to capitalising on this ability is understanding how the interactions between sequence and chemistry impact the pharmacology of oligonucleotide-based medicines. This is particularly crucial for the development of safe and effective drugs.
A unique feature of oligonucleotides that sets them apart from other drug modalities is the fact that their pharmacophore and dianophore are separable, which allows for independent engineering of target recognition and drug properties. This separability allows engineers to improve ADME properties, PKPD distribution, and ultimately, safety.
However, as Hart points out, the vast design space for oligonucleotides presents a combinatorial problem that cannot be solved by traditional screening methods, requiring innovative approaches to identify optimal compounds. Creyon Bio uses a platform to connect base sequences and chemical modifications to biophysical properties and pharmacology, enabling the engineering of oligonucleotide-based drugs with high tolerability and efficacy.
Hart then presented the case of Leo, a newborn suffering from seizures caused by a rare genetic disease. After rapid whole genome sequencing, it was discovered that Leo had a variant in the TNPO2 gene, expressing a pathogenic gain of function on that protein. Creyon was able to successfully developed an oligonucleotide-based drug for Leo, demonstrating the potential for rapid drug development and personalised medicine.
Creyon Bio is working to extend the application of oligonucleotide-based medicines beyond the liver and brain to other tissues, using aptamer technology for targeted delivery. The company aims to address both rare and common diseases with their platform, leveraging their engineering approach to develop best-in-class oligonucleotide-based medicines.