Engineering the future
of RNAi-based medicine

Leading the next generation of RNAi therapeutics

Unlocking the full potential of RNAi

City Therapeutics™ was founded by the pioneers of RNAi with a clear vision: to lead the next generation of RNAi therapeutics. Our approach is built on four principles: differentiated science, a strategic and diversified R&D pipeline, sustained momentum and unrivaled RNAi expertise. Together, these define how we create and advance best-in-class RNAi medicines.

Our platform is redefining what’s possible in RNAi. We engineer trigger molecules with unmatched potency, specificity and durability and pair them with precision targeting ligands that deliver siRNAs to a broader range of cell and tissue types, expanding RNAi’s reach beyond the liver and fueling a new era of therapeutic discovery.

Our leaders helped build and shape the RNAi field and bring deep experience across research, development and regulatory strategy. That expertise extends throughout our organization, where scientists with decades of hands-on RNAi experience drive our programs forward with precision, speed and insight.

A vast opportunity ahead

siRNA engineering platform to deliver disruptive medicines

RNAi has come of age yet has significant room to grow. With seven FDA-approved therapies since 2018, it has transformed the treatment landscape for rare, specialty and prevalent diseases. Yet the runway ahead remains vast—more than 200 cell types have yet to be targeted and thousands of diseases remain untreated. We are uniquely positioned to lead the next wave of RNAi breakthroughs with our unique and differentiated platform.

RNAi-based medicines possess high biological specificity, can directly target and degrade messenger RNA to silence gene expression and block protein production, and have the potential to address a wide range of diseases.

Leveraging next-generation trigger molecule engineering and novel extra-hepatic targeting capabilities, City Therapeutics is building a sustainable product engine of RNAi-based medicines to make a significant impact for patients.

Better triggers

Creating novel RNAi trigger molecules with improved potency and foundational intellectual property.

City is designing various trigger molecules with enhanced potency, specificity and cellular uptake driven by chemistry, sequence and length. Our proprietary cleavage-inducing tiny (city) RNAs that cleave target messenger RNA to silence gene expression are just one example.

Better delivery

Developing purposely tailored targeting ligands to reach more cells and tissue types.

These novel targeting ligands enable robust delivery of RNAi therapeutics to treat a broader range of human diseases than what is possible with the current generation of RNAi-based medicines. Our pipeline spans foundational hepatic delivery and proprietary extrahepatic delivery for ocular, CNS and additional tissue types.

Best-in-class molecules

Engineering the future of RNAi-based medicine.

City is uniting powerful RNAi trigger design with advanced delivery capabilities to create best-in-class molecules that redefine what RNAi therapeutics can achieve.

Our pipeline & programs

CITY-FXI:
A potentially best-in-class RNAi therapeutic targeting coagulation factor

Blood clots can cause serious conditions like stroke, deep vein thrombosis (DVT) or heart attack. Current blood thinners can help, but many people stop taking them due to bleeding risks or daily dosing challenges — leaving them unprotected.

CITY-FXI is a next-generation RNAi therapy candidate in development at City Therapeutics, designed to prevent dangerous clots without increasing bleeding risk. By targeting a key protein called Factor XI, CITY-FXI aims to keep patients protected from thrombosis while reducing the bleeding risk.

Based on the duration of effect observed in preclinical studies, supporting a simple dosing schedule, CITY-FXI has the potential to meet an unmet need by potentially making clot prevention safer, easier and more convenient for patients.

CITY-RBP4:
A promising RNAi therapeutic to prevent vision loss in Stargardt disease

Stargardt disease is an inherited retinal disorder affecting more than 30,000 people in the United States (1 in 8,000 individuals globally). Stargardt disease causes progressive vision loss, typically beginning in childhood, and often leads to legal blindness by age 25. There are currently no approved treatments.

CITY-RBP4 is a next-generation RNAi therapy candidate being developed as a potentially transformative therapy to slow or halt Stargardt disease progression. The treatment uses RNAi to decrease expression of a liver-produced protein, RBP4, that plays an important role in the Stargardt disease mechanism.

Where curiosity meets commitment

From the very beginning of City Therapeutics, we knew building the right culture mattered. Our employees defined City’s core values to showcase what drives us, what we expect from one another and the kind of company we want to create. The result is distinctly our own — a reflection of what drives us and how we work together.

Courage

We explore the unknown in service of patients.

Innovation

We push the boundaries of what is possible.

Tempo

We move decisively — fast, focused and with purpose... but not frantic.

Yes

We embrace optimism and celebrate our team and journey.

How we work

WFC (Work from City)

We’re building a company in the heart of Kendall Square where we come together every day to collaborate, ideate and inspire one another. Our choice to be an in-person company is intentional – for us, being together fuels creativity, deepens connection and accelerates scientific discovery. We believe working side by side not only benefits our people but also propels our momentum, driving faster decisions and meaningful discoveries.

At the same time, we recognize that life doesn’t always follow a plan. When flexibility is needed, we make it possible because we believe the best work happens when people are supported, connected and inspired.