ADOUT MultisiRNA

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What is MultisiRNA?

It is a novel siRNA-based anti-HBV therapeutic which is being developed by Biomics. It consists of two components:

  • • multiple specific siRNA molecule(s) targeting the HBV mRNA [1]; and
  • • a novel lipid nanoparticle (LNP) formulation. The LNP serves as the delivery vehicle to take the siRNA into infected liver cells resulting in silencing of or “knocking down” the HBV mRNA.
The combination molecule is named “MultisiRNA”. The design of the siRNA component takes advantage of the structure of the HBV genome. The hepatitis B virus is a small DNA genome with four overlapping open reading frames, meaning several genes are produced from the same viral DNA sequence by shifting the starting point of the translation process. Thus one siRNA molecule has the potential to silence more than one HBV gene.

What is the current stage of development?

Biomics has completed high-throughput target siRNA screening in vitro and discovered five novel siRNA sequences that are highly effective against the four major HBV subtypes . Biomics’ preliminary data has shown that theMultisiRNA design is effective and safe in both in vitro and early stage in vivo studies (in an HBV-infected mouse model).

The efficacy of the approach has been demonstrated against subtype D using one of the identified sequences targeting the HBV polymerase gene, and the Company is ready to expand its studies to subtypes A, B and C. The Company’s goal is to validate the efficacy in vivo for all four subtypes. Further evaluation and optimisation is needed to confirm the optimal siRNA drug candidates to achieve this.

The Company also has generated in vivo data demonstrating the safety of the new generation LNP delivery vehicle. Further development is being undertaken to ensure compatibility with the multi-target siRNAs.

When the preclinical development program is complete, Biomics plans to commence clinical studies in China and Australia.

What is the competitive advantage of MultisiRNA?

  • • MultisiRNA utilises multiple siRNAs to target the HBV RNA at several sites to reduce the possibility of development of resistance.
  • • High silencing efficacy of multiple sequences, each of which individually can knock down HBV mRNA by more than 80% in vitro.
  • • Highly efficient liver delivery system with low liver toxicity as demonstrated in an in vivo mouse model of HBV infection.
  • • Relatively low development cost compared to the novel small molecule development due to the demonstrated targeted efficacy in the siRNA screening system developed by Biomics.

[1] Li T, Zhu YY, Chen L, Sun Y, Yuan J, Graham M, French P. Size unbiased representative enzymatically generated RNAi (SURER) library and application for RNAi therapeutic screens. Nucleic Acid Ther. 2015;25:35-46

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