Replicate Bioscience, a clinical-stage company pioneering novel self-replicating RNA (srRNA) technology to expand applications of RNA vaccines and other treatments, today shared positive results from the Phase 1 trial of RBI-4000, its srRNA-based rabies vaccine.

In this clinical trial, evaluating safety and immunogenicity of RBI-4000, participants received one or two doses of srRNA vaccine at low doses (0.1 mcg, 1 mcg or 10 mcg). At all assessed doses, RBI-4000 achieved a strong immune response with protective virus-neutralizing antibody titers above the World Health Organization (WHO)-defined immune surrogate level of protection against the rabies virus. RBI-4000 was well tolerated at all dose levels tested, effectively broadening the therapeutic window for the srRNA technology.

“These results have exceeded our expectations and show the power and potential of our srRNA technology  and, we believe, de-risk our platform, manufacturing processes, and pipeline,” said Nathaniel Wang, Ph.D., CEO of Replicate. “Achieving a broad therapeutic window is an important step-up from other existing mRNA and srRNA approaches, which allows us to expand applications of our self-replicating RNA to complex infectious diseases, off-the-shelf cancer vaccines, and as a platform for protein production.”

Preliminary data show:

• The surrogate metric of protection (RVNA≥0.5) was achieved in most subjects in the ultra-low 0.1 mcg cohort; this is the lowest dose of any RNA technology reported to achieve surrogate of protection in humans.
• Single administration met the surrogate metric of protection for a majority of subjects in multiple cohorts.
• Favorable tolerability across all dose levels tested, with no severe adverse events.
• Superior therapeutic index with clinical bioactivity and tolerability at all doses tested (0.1 – 10 mcg).

Data from this study are being prepared for publication and will be shared at upcoming scientific conferences.

”When we founded Replicate, we envisioned a class of RNA therapeutics capable of treating many more diseases and reaching many more patients.  These data represent exciting progress towards realizing that vision,” said Replicate co-Founder and Board Chair Michael Ehlers, M.D., Ph.D., Chief Scientific Officer and Venture Partner at Apple Tree Partners (ATP).

About rabies, RBI-4000 and the Phase 1 trial: Rabies remains a public health threat in several geographical regions and is designated an FDA Tropical Disease and NIAID Priority Pathogen. A next-generation rabies vaccine with improved immunogenicity and simpler manufacturing represents an opportunity to broaden access to rabies prevention worldwide. Replicate’s first vaccine product candidate, RBI-4000, is an srRNA vaccine developed to stimulate virus-neutralizing immune responses to rabies for prophylactic use. The Phase 1 trial (NCT06048770) is evaluating the safety, tolerability, and immunogenicity of RBI-4000 in 84 participants in the U.S. In preclinical studies, intramuscular administration of RBI-4000 provided durable protection against the rabies virus, inducing antibody production and robust virus-specific T cells. For more information about the trial, please visit clinicaltrials.gov.

About Replicate Bioscience

Replicate Bioscience, an Apple Tree Partners portfolio company, 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 at lower doses, induction of more robust and durable immune responses, and improved tolerability. Replicate’s off-the-shelf srRNAs contain two components: virally derived genetic code to drive controlled and self-limiting amplification, and the RNA encoding therapeutic proteins. The company’s library of viral vectors, selected for driving robust and sustained protein expression and orders-of-magnitude improved performance over linear mRNA, allow for the development of treatments in applications including oncology, infectious disease, and autoimmunity. Differentiated by a team of srRNA experts, a customizable library of synthetic srRNA vectors, and end-to-end development capabilities, Replicate is uniquely positioned to finally expand the reach of RNA treatments toward widespread use in infectious disease, immuno-oncology, autoimmune disease, and more. Visit us at replicatebioscience.com.