The One-Stop-Shop for oligonucleotide drug development

Oligonucleotide development is a complex process, where many hurdles have to be overcome and topics have to be addressed including:

• Scientific aspects (target gene identification, oligo activity, target gen specificity, delivery)
• Pharmacological aspects (biodistribution, side effects, dose finding, toxicity, etc.)
• Preclinical regulatory aspects including Tox-study program, definition of manufacturing and analytical acceptance criteria, material planning for clinical trial, stability study, etc.

• Manufacturing aspects (e.g. method development for synthesis and purification, upscaling analytics, scalability, formulation, Fill&Filish)
• Regulatory aspects (Scientific advise, clinical program, Investigational Medicinal Product Dossier (IMPD) and other regulatory documents)

During this process, strategic decisions in early development could have dramatic impact on later clinical development, time lines and costs.

XNApharma can support your oligonucleotide development – if it is an ASO, siRNA, Aptamer, CpG or other short oligonucleotide as well as  gRNA, mRNA or a delivery approach.

We offer lab services, consulting as well as network and support for the whole process.

• ASO, siRNA, CpG, mRNA Sequence design and optimization by considering specificity, side effects, species cross-reactivity  
• Pharmacological lead optimization
• Design of ligand conjugation chemistry, e.g., GalNAc, cholesterol, peptides
• Optimization of formulation and transfection
• In vitro and in vivo efficacy analyses on mRNA (qPCR) and protein level (Western blot, ELISA, Fluorescence microscopy, etc.)

• Cytotoxicity (MTT/XTT)
• Apoptosis assays (TUNEL, cleaved PARP, etc.)
• PBMC cytokine response assay (ELISA)
• ADME, biodistribution, Dose finding
• Clinical chemistry from biological fluids
• Support regarding authority communication and Scientific Advice Meeting

Oligonucleotide manufacturing and GMP method development is a critical step in therapeutic oligonucleotide projects. The design and strategy of clinical studies massively influence requirements of your GMP project as well as GMP project time lines and costs. We provide support in the design of your GMP project including calculation of GMP material amount, acceptance criteria, work flow, stability studies, definition of validation criteria, risk management, review of documents and reporting, set up of regulatory documents (IMPD), communication with the authorities.

For oligonucleotide GMP manufacturing XNApharma collaborates with CDMO partners. For very long oligonucleotides and mRNA molecules we established synthesis, purification and analysis as well as process upscaling.