Wednesday, May 22, 2019
Gotham Therapeutics, a biotechnology company developing a novel drug class targeting RNA-modifying proteins, and ZoBio, the leading contract research organization in integrated fragment-based drug discovery, today announced significant progress made as part of their collaboration to identify therapeutic lead candidates for Gotham’s initial portfolio of epitranscriptomic targets. In the first project pursued within the collaboration, the initial phase for Gotham’s drug discovery project targeting the METTL3/METTL14 complex has been completed and a portfolio of small-molecule candidates will be further evaluated.
“In a sector that is still in its infancy, we have made tangible progress with our partner ZoBio to develop small molecule leads against a portfolio of epitranscriptomic targets just 14 months after initiation of the project,” commented Dr. Lee Babiss, Chief Executive Officer of Gotham Therapeutics. “Today’s news is also a validation of the semi-virtual model we use and the productivity of our network with best-in-class CROs.”
“With METTL3/METTL14 being among the more obvious approaches in epitranscriptomics, the quality of the chemical matter pursued is going to be a key differentiating factor,” added Dr. Gerhard Müller, Chief Scientific Officer of Gotham Therapeutics. “Together with ZoBio, we have not just successfully identified the initial candidates for Gotham’s first pipeline program but also established a robust process from gene to lead as a platform for additional projects to come.”
“The unique combination of our expertise and technologies allows us to initiate programs to pursue inhibitors of pharmacological targets that have been previously out of reach,” added Dr. Gregg Siegal, Chief Executive Officer of ZoBio. “We are pleased to have been able to use our intellectual and technological resources to enable Gotham’s drug discovery program and to further the newly developed field of epitranscriptomics. We look forward to continued work with the Gotham team and to continued advancements in this new field of biology.”
In January 2018, Gotham and ZoBio initiated a collaboration to develop small-molecule inhibitors of the “writer” protein complex METTL3/METTL14, a SAM-dependent methyltransferase that modifies mRNA encoded adenosine in the messenger RNA to m6A and thereby regulates protein expression. The collaboration aims to use ZoBio’s unique capabilities in biophysics-based drug discovery and structural biology to attack this novel target. Through extensive protein engineering, multiple forms of the complex have been generated that enable all of the planned studies. Using Surface Plasmon Resonance to screen ZoBio’s diverse fragment library, the collaboration has resulted in the discovery and validation of multiple, drug-like substances that selectively modulate the function of the METTL3/METTL14 complex and have the potential to be optimized towards pre-clinical candidates. ZoBio’s unique expertise in both Nuclear Magnetic Resonance spectroscopy and protein crystallography has enabled the deep understanding of the mode of action of these chemotypes at atomic resolution. With their combined arsenal of capabilities and expertise, Gotham and ZoBio are well positioned to generate in vitro and in vivo active inhibitors that will further Gotham’s programs and the field of epitranscriptomics.