Solutions to address challenges in safety

1. Assessment of off-target toxicity (hybridization-dependent) using transcriptome analysis

In order to select sequences that have low off-target toxicity risk to humans, transcriptome analyses, using human cell lines, are conducted.
In cases where an off-target gene is detected, support is provided by evaluating the toxicological information of that gene and conducting a risk assessment.
Nucleic acid drugs with known clinical safety information are used as reference data in order to analyze transctiptome data of the client’s nucleic acid drug candidate, thus contributing to the selection of candidates with low toxicity risk to humans.

[Examples of off-target toxicity assessments of ASOs with known clinical safety information]
Presentation at the 6th Annual Meeting of the Nucleic Acids Therapeutics Society of Japan
『Evaluation of the extrapolation about the off-target effects of antisense oligonucleotides from in vitro to human』

2. Evaluation of off-target toxicity (hybridization-independent) using various toxicity assessment systems

In oligonucleotide drug discovery, by evaluating the effects on the blood and immune systems, and toxicity in the liver and kidneys, oligonucleotide candidates with low toxicity risk are selected.
At Axcelead, strategic proposals on the timing — and type — of toxicity studies that should be conducted for various toxicity profiles are provided, taking advantage of our extensive experience in drug discovery.
As shown below, we have various assessment systems for both in vitro and in vivo tests. In addition, upon consultation, we can construct bespoke evaluation systems for clients.

3.LNP formation and analysis of immunostimulatory activity

Axcelead support development of in vitro/in vivo platforms customized for a client for new modalities.