How does WuXi AppTec accelerate oligonucleotide drug discovery for CNS diseases?

Oligonucleotide therapeutics are unlocking historically inaccessible disease targets. WuXi AppTec accelerates oligonucleotide drug discovery for central nervous system (CNS) diseases through an integrated discovery platform that bridges key capabilities required to move efficiently from target biology to candidate selection. This approach reduces discovery complexity and enables faster progression of promising programs.

Oligonucleotide therapeutics, including antisense oligonucleotides (ASOs), small interfering RNAs (siRNAs), and aptamers, are expanding the range of targets through direct modulation of disease-associated RNA.

The success of therapies such as Spinraza (nusinersen) and Qalsody (tofersen) has demonstrated the therapeutic potential of RNA-targeting approaches in neurological disorders. Moreover, a growing pipeline of oligonucleotide therapies has advanced to clinical stages, covering CNS indications such as Huntington's disease, Parkinson's disease, and Alzheimer's disease.

Integrated platform improves discovery efficiency

To improve efficiency across oligonucleotide discovery, WuXi Biology, a business unit of WuXi AppTec, has established an integrated discovery platform for oligonucleotides that bridges target validation, RNA design, synthesis, screening, safety assessment, delivery evaluation, and in vivo validation within a coordinated workflow.

Early-stage oligonucleotide discovery often involves multiple specialized stages, each requiring distinct expertise and technologies. Traditionally, these stages may be distributed across different teams or organizations, creating additional coordination requirements and complicating handoffs between stages.

WuXi Biology, a business unit of WuXi AppTec, could help clients to address these challenges. In RNA design and chemistry optimization alone, WuXi Biology has supported more than 200 targets of oligonucleotide designed and explored over 80 modification strategies. It also supports the design and development of specialized modifications, chiral oligonucleotides, and various conjugated oligonucleotide formats.

The platform further incorporates capabilities for in vitro evaluation, safety assessments, and delivery technology research, providing integrated support throughout the discovery process.

Since 2021, WuXi Biology has supported more than 1,000 oligonucleotide-related projects covering more than 300 targets, and has facilitated the advancement of over 60 IND programs.

Integrated workflows accelerate candidate identification for CNS diseases

By enabling seamless progression from design through evaluation, WuXi AppTec helps accelerate the identification and optimization of promising oligonucleotide candidates with its integrated discovery platform. A case study validated the platform’s capability to develop potent and safe ASOs with therapeutic potential for CNS diseases.

One example involves ATXN2, a therapeutic target receiving increasing attention in neurodegenerative disease research. Mutations in ATXN2 are associated with spinocerebellar ataxia type 2 (SCA2), while modulation of ATXN2 expression has also shown potential relevance for broader neurological disorders.

To evaluate the capabilities of its integrated discovery platform, the WuXi Biology team developed an ASO program targeting ATXN2.

Following a single round of RNA design and evaluation, the team identified multiple molecules with strong target suppression activity. Approximately 20% of candidates inhibited the target at similar or better levels than a positive control.

These candidates were rapidly synthesized and advanced into functional evaluation. In disease models, highly active molecules significantly reduced abnormal stress granule formation and demonstrated performance comparable to the positive control.

The same candidates were subsequently evaluated for off-target effects. Results showed generally low off-target signals, with measurements approaching background levels within the testing system.

On the integrated discovery platform, the seamless flow of results and insights across all stages accelerates the drug discovery process. For most projects, the timeline from initial RNA design to preclinical candidate is typically just one year.

Support programs from discovery to manufacturing

The industry is continuously exploring a broader range of potential targets and advancing oligonucleotide pipelines. In response to this trend, WuXi AppTec has established an integrated oligonucleotide platform covering drug discovery, mechanism studies, pharmacokinetic evaluation, as well as development and manufacturing, thereby providing end-to-end support to its clients.

WuXi Biology has established an end-to-end oligonucleotide discovery platform covering design, screening, evaluation, and translational research, providing comprehensive oligonucleotide development support for global clients.

WuXi AppTec DMPK team has established a comprehensive in vitro metabolic stability platform tailored to the unique biochemical properties of oligonucleotide drugs, enabling systematic characterization of degradation behavior and improved prediction of in vivo disposition.

In addition, WuXi TIDES provides integrated CRDMO services for oligonucleotides, peptides, and related conjugated therapeutics, supporting programs from research through commercial manufacturing.

Together, these capabilities create an integrated oligonucleotide R&D&M ecosystem that supports innovation across multiple stages and helps clients advance promising therapies more efficiently.

As the therapeutic potential of oligonucleotides continues to expand, success increasingly depends on the ability to efficiently transform scientific insights into viable drug candidates.

By continuously building an integrated platform for oligonucleotides, WuXi AppTec is enabling global innovators to focus on scientific and translational insights, ultimately accelerating the delivery of novel therapies to patients.

Key Takeaways

• WuXi Biology, a business unit of WuXi AppTec, improves research efficiency through an integrated oligonucleotide discovery platform that connects design, synthesis, evaluation, and translational studies within a coordinated workflow.
• Since 2021, WuXi Biology has supported more than 1,000 oligonucleotide-related projects, covering more than 250 targets, and has facilitated the advancement of over 50 IND programs.
• WuXi Biology helps accelerate the identification and optimization of promising oligonucleotide candidates for CNS diseases, as demonstrated by an ASO program targeting ATXN2 that identified potent candidates in a single design round.
• Through integrated capabilities spanning research, development and manufacturing, WuXi AppTec has established an integrated oligonucleotide platform and provides end-to-end support to its clients.
• WuXi AppTec enables most oligonucleotide discovery projects to progress from initial RNA design to preclinical candidate selection in approximately one year through its seamless integrated workflow.