Replicate Bioscience Announces Publication of Promising New Phase 1 Durability Data for Its srRNA Vaccine Candidate RBI-4000

• Eight month follow-up data published in Communications Medicine, a Nature portfolio journal
• Full clinical dataset supports further development of RBI-4000 as a next generation vaccine approach for rabies, an ongoing global public health concern
• Optimized RNA vaccine demonstrates ability to generate protective immunity with potential for superior durability compared to traditional vaccine technology

SAN DIEGO, Sept. 24, 2025 /PRNewswire/ -- Replicate Bioscience, a clinical-stage company pioneering novel self-replicating RNA (srRNA) technology for applications across infectious disease, immunology, and other therapeutic areas, today announced that long term immunogenicity data from the Phase I trial of its srRNA-based rabies vaccine candidate, RBI-4000, have been published in Communications Medicine, a Nature portfolio journal.

The article, "Durability of next-generation self-replicating RNA vaccine RBI-4000: a Phase 1, randomized open label clinical trial," includes long term immunogenicity data from the company's rabies vaccine candidate, RBI-4000. The data reinforce previously published Phase I data, which demonstrated improvements in clinical safety and immunogenicity using Replicate's optimized srRNA platform compared to existing conventional linear mRNA and srRNA technologies.

Continuation of this Phase I trial for up to 8 months, including 5 months of additional durability data, showed that RBI-4000 elicited long-term immune responses to rabies at all dose levels and regimens tested. Following two administrations of RBI-4000 at 1 or 10 microgram dose levels, 100% of participants retained detectable rabies virus neutralizing antibodies (RVNA) at 6 months. Within those respective dose cohorts, 61% and 88% of the participants exhibited persistent antibodies above the WHO-defined metric of seroprotection for rabies.

Post-hoc analysis using eight different statistical decay demonstrated that the immune responses elicited by RBI-4000 were equal or superior in durability to the standard-of-care commercial, inactivated rabies vaccine comparator. Importantly, half-lives of RVNA responses in RBI-4000 treatment cohorts were extended by at least 6-fold compared to those in the commercial, inactivated rabies vaccine cohort. 

"These remarkable durability results position Replicate's srRNA technology as an advantaged, promising alternative to both mRNA and conventional vaccine platforms. This goes beyond RNA's inherent advantages in speed and manufacturability," said Parinaz Aliahmad, Ph.D., Head of Research and Development at Replicate. "The complete clinical data package supports continued development of RBI-4000 for induction of protective immunity against rabies at unprecedentedly low doses and with a single dose approach."

About the Phase I trial of RBI-4000

The Phase I randomized, open label clinical trial (NCT06048770) enrolled 89 healthy volunteers, age 18-45 years. Safety and immunogenicity of RBI-4000 was evaluated across three dose levels including 0.1, 1, and 10 micrograms (mcg) in a prime-boost regimen, along with a prime only (10 mcg) cohort to assess single dose feasibility. RabAvert, an approved inactivated virus vaccine, was included as a comparator arm.

All dose levels of RBI-4000 tested, including those as low as 0.1 mcg, elicited de novo protective immune responses through Day 85, with the majority of participants across all dose cohorts achieving the WHO-established threshold of a protective RVNA response when administered in a prime-boost or as a single (10 mcg) dose schedule. The trial participants were followed through 8 months after initial vaccination (study termination).  

RBI-4000 demonstrated good tolerability, with no dose-limiting adverse events, and a maximally tolerated dose of RBI-4000 was not reached. There were no serious adverse events nor discontinuation due to treatment-related adverse events experienced by any participants through study termination.

Key  takeaways from the Ph1 trial continuation data

• RBI-4000 elicits durable immune responses at all doses and regimens tested (including a single-dose regimen), demonstrated by detectable RVNA responses out to 8 months from initial vaccination
  
  
• Two doses of RBI-4000 administered at 1 or 10 mcg resulted in 100% of participants with detectable RVNA at 6 months, of which 61% and 88% were above the WHO defined metric of seroprotection for rabies, respectively compared to 58% in commercial, inactivated virus vaccine comparator.
  
  
• Post hoc statistical decay analysis of cohorts followed for 240 days demonstrated that RBI-4000 generated RVNA responses of equal or superior durability compared to an approved inactivated rabies vaccine, with extended half live of antibody titers.
  
  
• Data is the first demonstration that an RNA vaccination can elicit protective immunity with comparable or superior durability to an approved traditional vaccine platform

About Rabies
Endemic in over 150 countries, rabies is a deadly disease with a 99% mortality rate if left untreated, causing 59,000 deaths annually. Deaths due to rabies are fully preventable if exposed individuals receive an effective vaccine before the virus spreads to the central nervous system and clinical symptoms appear. Rabies is most frequently addressed through post-exposure prophylaxis including a course of human rabies vaccine. Although effective, current rabies vaccines require 3 to 5 doses and are subject to supply shortages due to complicated manufacturing processes, limiting accessibility and increasing complexity of administration in resource-limited settings. Rabies is included in WHO's 2021-2030 Roadmap for the global control of neglected tropical disease. And as part of the 21^st Century Cures Act, the U.S. Food and Drug Administration (FDA) included rabies in its Tropical Disease Priority Review Voucher Program List.

About Replicate Bioscience
Replicate Bioscience is a clinical-stage company amplifying the power of RNA therapeutics by pioneering its novel self-replicating RNA (srRNA) technology to overcome the shortcomings of existing mRNA approaches, with potential improvements in bioactivity, induction of more potent immune responses, and improved therapeutic index. RBI-4000, the company's clinical-stage srRNA rabies vaccine, has demonstrated protective levels of immunity at doses lower than any other reported mRNA or srRNA vaccine in Phase I trials. Funded by Apple Tree Partners, Replicate is advancing a robust pipeline of srRNA vaccines and therapeutics, fueled by its proprietary library of customizable viral vectors. With deep expertise in srRNA and end-to-end development capabilities, Replicate is uniquely positioned to expand the reach of RNA treatments toward widespread use in infectious disease, immunology, immuno-oncology and more. Visit us at www.replicatebioscience.com.

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SOURCE Replicate Bioscience