City Therapeutics Announces First Participant Dosed in Phase 1 Clinical Trial of CITY-RBP4 for the Treatment of Stargardt Disease

Initial CITY-RBP4 data are expected in mid-2027, with another program expected to enter an investigator-initiated trial by year-end.

Rhea-AI Summary

City Therapeutics (CTY) has dosed the first participant in its Phase 1 trial of CITY-RBP4 for Stargardt disease type 1. CITY-RBP4 is an investigational RNA interference therapy designed to reduce production of retinol-binding protein 4 (RBP4), limiting vitamin A delivery to the eye and potentially slowing retinal damage and vision loss. City expects initial data in mid-2027.

The first-in-human trial is randomized, double-masked and placebo-controlled across multiple centers. It evaluates safety, tolerability, drug exposure and biological effects of single and multiple doses injected under the skin in healthy volunteers and people with Stargardt disease. Assessments include RBP4 suppression and reductions in circulating retinol. CITY-RBP4 is City's second program in clinical testing; the company expects a third to enter an investigator-initiated trial by year-end.

Positive

• Minor pointFirst participant dosed in CITY-RBP4's Phase 1 trial, advancing City's second program into clinical testing.
• Minor point. Forward-looking: it has not happened yet and may not happen.Initial Phase 1 data are expected in mid-2027.
• Minor point. Forward-looking: it has not happened yet and may not happen.Third program is expected to enter an investigator-initiated clinical trial by year-end.

Negative

• None.

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Key Figures

First participant dosed: 1 participant Initial data expected: Mid-2027

First participant dosed

1 participant

Phase 1 CITY-RBP4 trial

Initial data expected

Mid-2027

Phase 1 trial

Key Terms

rna interference, first-in-human, double-masked, placebo-controlled, +2 more

6 terms

rna interference technical

"engineering the next generation of RNA interference (RNAi) therapeutics"

RNA interference is a natural cellular process that acts like a mute switch to reduce or silence the activity of a specific gene by targeting its messenger RNA, the blueprint used to make a protein. For investors, it matters because therapies and diagnostics that harness this mechanism can precisely block disease-causing proteins, creating new drug classes with high potential reward but also scientific, manufacturing and regulatory risks that affect company value.

first-in-human medical

"The Phase 1 trial is a first-in-human, multicenter, randomized, double-masked"

A first-in-human study is the initial test of a new drug, medical device, or therapy in people to check safety, side effects and appropriate dosing. It matters to investors because it marks a major development milestone: successful early human testing can reduce scientific and regulatory uncertainty, much like moving a prototype from the workshop to a real-world test drive, and often affects a company’s valuation and funding prospects.

double-masked medical

"randomized, double-masked, placebo-controlled study in healthy volunteers"

Double-masked describes a clinical study setup where neither the people receiving treatments nor the researchers who administer or assess them know who gets the active therapy versus a placebo or comparison. This reduces conscious or unconscious bias and makes results more reliable for regulators and doctors. For investors, double-masked trials carry more credibility—like a taste test where neither the tasters nor the servers know which sample is which—so positive outcomes and approvals are taken more seriously.

placebo-controlled medical

"double-masked, placebo-controlled study in healthy volunteers"

"Placebo-controlled" describes a testing method where one group receives the actual treatment or intervention, while another group receives a harmless, inactive version called a placebo. This approach helps determine whether the real treatment has genuine effects beyond psychological expectations. For investors, understanding this ensures confidence that reported benefits are real and not influenced by bias or false perceptions.

pharmacokinetics medical

"designed to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics"

Pharmacokinetics is the study of how a substance, such as a drug or chemical, moves through and is processed by the body over time. It tracks how it is absorbed, distributed, broken down, and eventually eliminated. For investors, understanding pharmacokinetics helps gauge the effectiveness, safety, and potential risks of new medications or treatments, which can influence a company’s success and valuation in the healthcare industry.

pharmacodynamics medical

"evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics"

Pharmacodynamics is how a drug actually affects the body — the strength, type and duration of its effects and the relationship between dose and response. Think of it like how turning a thermostat changes room temperature: it shows what the drug does and how much is needed to get the desired effect. Investors care because these properties drive clinical success, dosing convenience, safety profile and competitive advantage, all of which influence commercial potential and regulatory approval.

AI-generated analysis. How Rhea-AI works. Not financial advice.

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CITY-RBP4 is an RNAi therapeutic candidate designed to provide potent and durable suppression of RBP4, a clinically supported target in Stargardt disease

City’s second program to advance into the clinic, demonstrating strong momentum across the pipeline

CAMBRIDGE, Mass., Nov. 10, 2026 (GLOBE NEWSWIRE) -- City Therapeutics, Inc. (Nasdaq: CTY), a clinical-stage biotechnology company engineering the next generation of RNA interference (RNAi) therapeutics, today announced that the first participant has been dosed in the Phase 1 clinical trial of CITY-RBP4, an investigational RNAi therapeutic candidate for the treatment of Stargardt disease type 1 (Stargardt disease). CITY-RBP4 is designed to silence expression of retinol-binding protein 4 (RBP4) to reduce the delivery of vitamin A to the eye and potentially slow the progression of retinal damage and vision loss associated with Stargardt disease. City expects to report initial data from the Phase 1 trial in mid-2027.

“Stargardt disease is a devastating condition that can lead to significant vision loss early in life, yet there are currently no approved treatments,” said Andy Orth, President and Chief Executive Officer of City Therapeutics. “Advancing CITY-RBP4 into the clinic brings us an important step closer to addressing that unmet need, while also reflecting the significant progress of our pipeline. With two programs now in the clinic and a third program expected to enter the clinic through an investigator-initiated trial by year-end, we continue to leverage our City Platform to develop RNAi therapeutics designed to deliver meaningful and durable benefits for patients in need. We look forward to evaluating CITY-RBP4’s therapeutic potential in this Phase 1 study and reporting initial data in mid-2027.”

Stargardt is an inherited macular degenerative disease and the leading inherited cause of central vision loss in children and young adults. The disease is caused by mutations in the ABCA4 gene, which lead to the accumulation of toxic vitamin A byproducts in the retina and progressive, irreversible vision loss. RBP4 is the primary carrier of retinol, a form of vitamin A, from the liver to the eye, and published third-party clinical proof-of-mechanism data support RBP4 reduction as a potential therapeutic approach to slow disease progression.

The Phase 1 trial is a first-in-human, multicenter, randomized, double-masked, placebo-controlled study in healthy volunteers and people with Stargardt disease designed to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of single and multiple subcutaneous doses of CITY-RBP4. Pharmacodynamic assessments will include suppression of RBP4 and the associated reduction in circulating retinol. Participants with Stargardt disease in this study are eligible to be enrolled in a planned open-label extension study evaluating the long-term safety and preliminary efficacy of CITY-RBP4, including exploratory measures such as retinal imaging and visual function assessments.

About CITY-RBP4

CITY-RBP4 is a GalNAc-conjugated small interfering RNA (siRNA) therapeutic candidate designed to silence hepatic expression of retinol binding protein 4 (RBP4) for the treatment of Stargardt disease type 1 (Stargardt disease) and other retinal diseases. Preclinical studies demonstrated potent and durable suppression of RBP4 and corresponding reductions in circulating retinol, and pharmacodynamic modeling data suggest the potential for infrequent subcutaneous dosing. City is initially developing CITY-RBP4 for Stargardt disease and is also exploring its potential in geographic atrophy secondary to age-related macular degeneration, which shares pathology with Stargardt disease given the accumulation of toxic vitamin A byproducts in the retina.

About City Therapeutics

City Therapeutics is a clinical-stage biotechnology company engineering the next generation of RNA interference (RNAi) therapeutics, with the aim of delivering meaningful and durable benefits for patients in need. City’s lead development programs are CITY-FXI for thromboembolic diseases, CITY-RBP4 for Stargardt disease and other retinal diseases, and CITY-TFR2 for anemia associated with chronic diseases. The City Platform is the engine behind every therapeutic the company develops and integrates deep expertise in trigger engineering, including proprietary cityRNA triggers designed to address limitations of conventional RNAi approaches, tissue-selective delivery, and genetics-driven target selection. For more information, visit www.citytx.com and follow us on LinkedIn, X, and Bluesky.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended. All statements contained in this press release other than statements of historical facts are forward-looking statements, including, without limitation, statements regarding: the design, conduct, progress and timing of City’s Phase 1 clinical trial of CITY-RBP4, including the expected timing of reporting initial data from the trial; the planned open-label extension study of CITY-RBP4; the therapeutic potential of CITY-RBP4 for the treatment of Stargardt disease, geographic atrophy and other retinal diseases, including the potential for infrequent subcutaneous dosing; the expected timing of City’s third program entering the clinic; the potential of the City Platform; and City’s strategy, plans and objectives. In some cases, you can identify forward-looking statements by terms such as “aim,” “anticipate,” “believe,” “continue,” “could,” “designed to,” “estimate,” “expect,” “intend,” “may,” “plan,” “potential,” “predict,” “should,” “target,” “will” or the negative of these terms or other similar expressions, although not all forward-looking statements contain these identifying words.

Forward-looking statements are based on City’s current beliefs and expectations and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements, including, without limitation: City’s limited operating history and the early stage of its development programs; uncertainties inherent in the development of product candidates, including the initiation, timing, enrollment and completion of clinical trials; the risk that results of preclinical studies or earlier clinical trials may not be predictive of future results; the risk that initial or interim data may change as more data become available; the risk that City’s product candidates may cause adverse side effects or fail to demonstrate sufficient safety or efficacy to obtain regulatory approval; City’s ability to obtain and maintain regulatory approvals; risks associated with City’s RNAi approach and the City Platform; competition, including from other therapies for Stargardt disease that may be approved before CITY-RBP4; City’s reliance on third parties, including clinical research organizations and manufacturers; City’s ability to obtain, maintain and enforce intellectual property protection; City’s need for substantial additional funding; and general economic, industry and market conditions. These and other risks and uncertainties are described in greater detail in the section entitled “Risk Factors” in City’s final prospectus relating to its initial public offering filed with the Securities and Exchange Commission (the “SEC”) pursuant to Rule 424(b)(4) under the Securities Act of 1933, as amended, on October 16, 2026, and in City’s subsequent filings with the SEC.

Any forward-looking statements contained in this press release speak only as of the date hereof, and City expressly disclaims any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law.

Contacts:

Media Contact:

Katie Engleman, 1AB
katie@1abmedia.com

Investor Contact:

Stephanie Ascher, Precision AQ
stephanie.ascher@precisionaq.com

FAQ

AI-generated questions and answers. How Rhea-AI works. Not financial advice.

When does City Therapeutics expect initial CITY-RBP4 Phase 1 results?

City Therapeutics expects to report initial Phase 1 data in mid-2027. The study evaluates safety, tolerability, drug exposure and biological effects in healthy volunteers and people with Stargardt disease.

Can Stargardt participants in City's CITY-RBP4 trial enter a longer-term study?

Participants with Stargardt disease are eligible to enroll in a planned open-label extension study. That study will evaluate long-term safety and preliminary efficacy, including exploratory retinal imaging and visual function assessments.