City Therapeutics has emerged with $135 million in Series A funding, aiming to revolutionize RNA interference (RNAi) therapeutics. Spearheaded by John Maraganore, former CEO of Alnylam Pharmaceuticals, the company seeks to develop next-generation RNAi medicines with enhanced potency, specificity, and broader tissue accessibility. This initiative aims to expand the therapeutic potential of RNAi beyond its current limitations, potentially rivaling the impact of monoclonal antibodies.
Next-Generation RNAi Technology
City Therapeutics is focused on engineering small interfering RNAs (siRNAs) to create more effective and versatile therapies. Their approach includes:
- Novel RNAi Triggers: Designing smaller, more potent RNAi triggers, such as cleavage-inducing tiny RNAs (cityRNAs), that can induce mRNA cleavage through distinct proteins to silence gene expression.
- Targeted Delivery: Developing tailored targeting ligands to enhance siRNA delivery to a broader range of cells and tissue types, overcoming the limitations of current RNAi therapies that primarily target the liver.
- Human Genetics Integration: Leveraging advancements in human genetics to identify novel therapeutic targets and optimize clinical development strategies.
Clinical Development and Pipeline
The company anticipates its lead program will enter clinical development around the end of 2025, with plans to submit one to two Investigational New Drug (IND) applications per year starting in 2026. This fast-to-clinic strategy aims to build a sustainable pipeline of high-impact RNAi-based medicines.
Tracy Zimmermann, Chief Scientific Officer of City Therapeutics, stated, "Recent scientific advancements and technologies have opened the door to novel and improved engineering of RNAi trigger molecules, allowing this highly specific class of medicines to be better optimized and address more diseases."
Leadership and Investment
City Therapeutics boasts a leadership team comprising pioneers in RNAi therapeutics, including former executives from Alnylam Pharmaceuticals and other leading biotech companies. The Series A financing was led by ARCH Venture Partners, with participation from Fidelity Management & Research Company, Invus, Slate Path Capital, Rock Springs Capital, Regeneron Ventures, and AN Ventures.
Robert Nelsen, a managing director and co-founder of ARCH Venture Partners, noted, "The time to re-enter the RNAi revolution is now, and our investment in City Therapeutics is based on our conviction that RNAi therapeutics will expand as a major category of breakthrough medicines."
Broad Therapeutic Potential
Maraganore envisions RNAi's potential to silence disease-causing genes in various target tissues, including the central nervous system, eye, muscle, adipose tissue, lung, and tumors. This broad applicability underscores the significant unmet medical needs that City Therapeutics aims to address with its innovative RNAi platform.
