Replicate Bioscience Presents Positive Data from Phase 1 Trial and Preclinical Data with Novel Self-Replicating RNA at the 2024 American Society of Gene & Cell Therapy (ASGCT) Annual Meeting

Positive data from Phase 1 trial of RBI-4000 vaccine achieve WHO-established surrogate of protection across all dose cohorts

Vector improvements demonstrate broad potential of Replicate's srRNA for expanded indications in complex infectious disease and in situ expression of therapeutic proteins

SAN DIEGO, May 11, 2024 /PRNewswire/ -- Replicate Bioscience, a clinical-stage company pioneering novel self-replicating RNA (srRNA) technology for use across a range of infectious disease, oncology, autoimmune disease indications and beyond, presented new preclinical data and today will share interim clinical trial results from an ongoing Phase 1 study at the American Society of Gene & Cell Therapy (ASGCT) Annual Meeting, May 7-11 in Baltimore, Maryland.

"At ASGCT, Replicate is presenting two important breakthroughs in srRNA technology," said Nathaniel Wang, Ph.D., CEO of Replicate. "For vaccines, our clinical data demonstrate the induction of protective levels of immunity at doses significantly lower than any other reported mRNA or srRNA vaccine. This potency, combined with a best-in-class safety profile, demonstrates the capability of our technology to greatly expand the utility of RNA technology for vaccines. Beyond vaccines, further improvements to our library of vectors now enable us to control and prolong in vivo production of therapeutic proteins compared to circular RNA, linear mRNA, and current state-of-the art srRNA, opening up therapeutic areas such as immunology and metabolic disease."

RBI-4000's Phase 1 results will be presented on Saturday, May 11 at 10:15 a.m. ET by Replicate's Chief Medical Officer, Zelanna Goldberg, M.D., in an oral presentation titled "Single and Low Dose Self-Replicating RNA Vaccine Provides Effective Immune Protection Against Rabies in Healthy Volunteers." The results highlight the strong immunogenicity and favorable safety profile of RBI-4000 in the Phase 1 trial, which is the first clinical validation of Replicate's next-generation srRNA technology. Additional takeaways are as follows:

• Day 85 datasets for all cohorts met the WHO-established surrogate of protection at doses significantly lower than any other reported RNA-based vaccines;
  • Substantive majority of participants achieved metric in all dose cohorts.
• In the previously unreported 10 mcg dose cohorts:

• • 100% of participants achieved surrogate of protection after two vaccine doses.
  • 92% of participants achieved surrogate of protection after a single vaccine dose.

• Safety data from the interim dataset demonstrate RBI-4000 was well tolerated with no severe adverse events across all cohorts; reactogenicity was transient and self-limiting.
• No dose limiting toxicity (DLT) was observed; maximum tolerated dose (MTD) has not been reached, enabling further dose escalation.

On May 9, Parinaz (Paris) Aliahmad, Ph.D., Head of Research and Development at Replicate, delivered an oral presentation at ASGCT titled "Novel Self-Replicating RNA Vectors Broaden Therapeutic Window and Expand Use Outside of Vaccines." The results underscore the broad potential of srRNA as a new treatment modality across a wide range of disease areas. Additional takeaways are as follows:

• Vaccines using Replicate's optimized vectors achieve protective immunity at ultra-low doses (1 picogram) with minimal reactogenicity.
• Beyond vaccines, Replicate's novel srRNA vectors demonstrate >100-fold increased expression of encoded proteins and improved durability compared to circular RNA, linear mRNA vectors, and current state-of-the-art srRNA technologies.
• Replicate's novel srRNA vectors can expand utility of RNA technology for templated expression of biotherapeutic proteins for applications outside of vaccines, in areas such as immune disorders, metabolic disease, and cancers.

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 www.replicatebioscience.com.

SOURCE Replicate Bioscience