CirCode Biomed’s HM2002 gets FDA green light: World’s first circular RNA drug to enter U.S. clinical trials for heart disease

In a landmark regulatory development for RNA-based medicine, Shanghai CirCode Biomed Co. Ltd. has received Investigational New Drug (IND) clearance from the U.S. Food and Drug Administration (FDA) for its flagship candidate, HM2002. This makes HM2002 the first circular RNA-based therapeutic approved for clinical trials targeting ischemic heart disease in the United States. Combined with a prior clearance granted by China’s National Medical Products Administration (NMPA) in January 2025, this dual approval positions CirCode Biomed at the forefront of the emerging circular RNA therapeutic category.

The clearance, announced late on May 30, comes at a critical juncture in RNA drug innovation. While messenger RNA (mRNA) gained prominence during the COVID-19 vaccine era, the limitations around mRNA stability and immunogenicity have prompted increased attention toward circular RNA (circRNA) technologies. Unlike mRNA, circular RNA molecules form covalently closed loops, allowing for more durable expression and reduced immune activation—two features that could unlock longer-acting, safer therapies for chronic conditions such as heart disease.

Why Is the FDA IND Clearance for HM2002 Significant?

HM2002 is designed to treat ischemic heart disease by delivering circular RNA that encodes vascular endothelial growth factor (VEGF), a protein that stimulates blood vessel growth in oxygen-deprived tissues. CirCode’s approach involves injecting HM2002 directly into the myocardium, where it induces VEGF expression long enough to promote angiogenesis, restore microcirculation, and enhance cardiac function—without lingering beyond its therapeutic window.

The FDA’s decision to greenlight human trials in the U.S. not only validates the preclinical and first-in-human data from China but also represents the first regulatory recognition of a circular RNA drug’s clinical promise in any Western jurisdiction. The U.S. clearance follows the successful completion of a small-scale investigator-initiated trial (IIT) at Shanghai’s Ruijin Hospital, where patients reportedly showed significant cardiac function improvement without adverse events.

What Is the Market Need for RNA-Based Treatments in Heart Disease?

Globally, ischemic heart disease remains the leading cause of death, claiming over 9 million lives annually, according to the World Health Organization. Despite medical advancements ranging from beta-blockers to coronary interventions, many patients experience inadequate microvascular recovery after ischemia. Current treatment regimens often fail to induce neovascularization—a critical factor in improving long-term heart function and survival rates.

CirCode’s HM2002 seeks to fill this gap by enabling localized, transient expression of VEGF, effectively regenerating blood flow without the side effects typically associated with gene therapy or chronic protein infusions. The company argues that its circular RNA approach strikes a vital balance between efficacy and safety—a claim early data appear to support.

How Fast Did CirCode Biomed Advance HM2002 to Clinical Trial Stage?

One of the most striking aspects of the HM2002 story is the pace of development. CirCode Biomed was able to move from concept to dual-country IND clearance in under 24 months—an unusually short timeframe in biotech drug development. This acceleration was made possible by the company’s AI-driven circular RNA platform, which optimized the design, translation kinetics, and preclinical safety profile of HM2002.

According to Dr. Yun Yang, CirCode’s co-founder and CTO, the platform leverages artificial intelligence to simulate RNA folding, predict immune responses, and rapidly iterate on vector designs. Yang noted that this proprietary system enables the company to prototype and de-risk candidates faster than conventional biotech workflows.

What Sets HM2002 Apart from Other Gene or Protein Therapies?

Unlike viral vector-based gene therapies or systemically administered biologics, HM2002’s action is designed to be local, time-limited, and self-terminating. Its circular RNA structure offers stability in vivo without invoking innate immune defenses, and the VEGF protein it expresses dissipates after initiating tissue repair. As explained by CEO Dr. Chenxiang Tang, the goal is to administer a single dose that expresses VEGF just long enough to re-establish microcirculation in ischemic tissue—without persistent expression that might lead to off-target effects or vascular overgrowth.

Tang added that the therapy’s design is informed by the understanding that angiogenesis is most beneficial during a narrow post-ischemia window. “Once that window closes and the vasculature has reformed, the job is done. You don’t need the drug to hang around,” he stated.

How Has the Investment and Regulatory Community Responded?

Though CirCode remains privately held, the FDA clearance is being closely watched by biotech investors, institutional analysts, and pharmaceutical companies exploring RNA-based innovations. Market observers have described the dual U.S.-China clearance as a validation not just of HM2002, but of the broader viability of circular RNA as a therapeutic platform.

Biotech analysts at Morgan Franklin Life Sciences noted that the move may drive renewed capital flows into the circular RNA space, similar to the surge mRNA companies saw after their vaccine successes. Meanwhile, early-stage venture arms of Big Pharma are reportedly assessing licensing opportunities or potential equity investments in the few firms operating at the cutting edge of this field.

What Is the Broader Pipeline Outlook for CirCode Biomed?

CirCode is not banking solely on HM2002. The company has disclosed a robust preclinical pipeline that includes circular RNA vaccines, autoimmune disease therapeutics, oncology drugs, and in vivo CAR-T cell therapies. Several of these programs are expected to reach the clinical trial phase by 2026. The firm’s portfolio diversity mirrors industry efforts to apply RNA tools across a wider range of indications, particularly where protein replacement or genetic modulation is beneficial.

The strategic focus appears to be on diseases with high unmet needs where existing therapies are either non-curative, difficult to administer, or carry high toxicity. By offering controlled protein expression with limited immune activation, CirCode is targeting areas where traditional gene therapy or biologics face hurdles.

Does This Signal a New Era for RNA Therapeutics?

The regulatory nod from the FDA marks a turning point for circular RNA as a modality. While mRNA has dominated public attention since the COVID-19 vaccine era, its inherent limitations—such as transient expression and instability—have become evident in post-pandemic use cases. Circular RNA, by contrast, offers a new toolkit for achieving sustained yet controllable expression, opening up therapeutic areas like chronic disease, oncology, and tissue regeneration.

CirCode’s clearance, therefore, may do for circRNA what Moderna’s COVID-19 vaccine did for mRNA: shift it from academic curiosity to clinical mainstream. The company’s success also adds momentum to an expanding field that includes academic labs and emerging biotechs in North America, Europe, and East Asia.

What Comes Next for CirCode and HM2002?

CirCode will now initiate formal U.S. clinical trials under the IND framework. The company is expected to begin patient recruitment by Q3 2025, with Phase I data potentially emerging in early 2026. Pending successful outcomes, HM2002 could progress into Phase II trials across multiple geographies—including joint U.S.-China sites—by the second half of 2026.

Looking ahead, CirCode may face growing interest from large pharmaceutical companies interested in acquiring or partnering on circular RNA platforms. Analysts believe that if early clinical data validate HM2002’s safety and efficacy profile, CirCode could emerge as a leading platform company, possibly setting the stage for a future IPO or strategic acquisition.

For now, the FDA’s endorsement of CirCode Biomed’s HM2002 represents more than a regulatory formality—it’s a vote of confidence in the next frontier of RNA science.