The FDA has cleared Complement Therapeutics GmbH’s (CTx) investigational new drug (IND) application for CTx001, its lead gene therapy candidate under clinical development to treat geographic atrophy secondary to age-related macular degeneration (AMD).
First, a look at this company.
Headquartered in Munich, Germany, CTx is a biotechnology company that spun out from the University of Manchester in 2020.
- To note: The company’s subsidiaries are based in the United Kingdom and the United States (Boston, Massachusetts).
Its scientific focus: Involves researching and developing novel therapeutics within the complement cascade (system)—based on CTx’s founders’ pioneering research—with its lead investigational product targeting geographic atrophy (GA).
Talk about the complement system.
As part of the human body’s innate immune system, the complement system consists of an estimated 50 proteins and protein fragments that circulate in the blood and work together to help the body recognize, attack, and remove pathogens (bacteria and viruses) and damaged cells.
- The “cascade” component of this system refers to its ability to—once a protein is activated—trigger the next protein to then amplify an immune response.
In relation to disease: The system’s dysregulation is involved in the development of various diseases, including AMD and hematological conditions.
- As such: AMD is considered a “complement-mediated” disease—and a target for CTx to address.
Explain the company’s approach to this.
CTx has developed the Complement Precision Medicine (CPM) Platform to quantify systemic levels of over 30 complement proteins, including C3 (its central protein), to support patient stratification and disease monitoring.
- Specifically: This platform measures an array of complement proteins from just one blood sample.
And where does its lead asset factor in?
Consider GA, a late-stage presentation of dry AMD.
According to CTx: Dysregulation of a number of specific components of the cascade are implicated in this disease—including C3, C5, factor H, and factor I.
As such, the research reportedly conducted by the founders of CTx “ identified the pivotal role of factor-H-related proteins (FHRs) in the development of AMD.”
Quick rundown on FHRs, please.
FHRs are composed of five plasma proteins with similar structural properties to those of factor H, a protein that regulates one of the pathways (alternative) within the complement cascade.
What to know: FHRs (such as FHR protein-1 [FHR1], to be exact) promote inflammation—and potentially contribute to the inflammation observed in FHR.
- In regard to CTx: The company’s research into this area served as the foundational therapeutic strategy for its lead candidate.
So what do we know about CTx001?
CTx’s lead asset is an adeno-associated virus (AAV)-based gene therapy designed to deliver a truncated version of complement receptor 1 (mini-CR1).
The intended result: To enable long-term modulation of the complement cascade’s classical and alternative pathways.
- And the potential: For CTx001 to “deliver durable, one-time treatment benefits” for GA patients, according to CEO Rafiq Hasan, MD.
As for the future: Additional clinical programs are expected to evaluate the therapeutic potential for CTx001 to treat other complement-mediated conditions—such as renal and neurological conditions.
Gotcha. And in terms of this IND?
The FDA’s IND clearance paves the way for CTx to conduct an international first-in-human (FIH), open-label, phase 1/2 clinical trial.
Dubbed the Opti-GAIN (Optimized Geographic Atrophy INterventional) trial, the study is expected to evaluate the safety, tolerability, and preliminary efficacy of CTx001.
What do we know about its design?
Just that it’s informed by data from a 1-year natural history study (i-GAIN) that included 230+ participants (aged 18+) diagnosed with GA secondary to AMD.
Its purpose: Was to evaluate the relationship between genetics, blood biomarkers, and phenotypic changes in GA patients’ eyes.
- And its results: While not readily available to the public, CTx stated that the i-GAIN’s findings provided “valuable insights into disease progression, imaging biomarkers, and patient stratification in GA.”
Nice! So what’s the timeframe for the new Opti-GAIN study?
The company plans to begin patient enrollment at “leading retinal centers” across the United States in Q1 2026.