Nucleic acid therapeutics are poised to radically change the medical landscape, offering the potential to treat numerous serious, often devastating, genetically defined diseases that until now have proven “undruggable.”
To date, nucleic acid therapeutics have been comprised of complex mixtures of hundreds of thousands of chemical entities known as stereoisomers. Some stereoisomers in these mixtures have therapeutic effects, while others are less beneficial or contribute to undesirable side effects. Uncontrolled stereoisomer drug mixtures can lead to suboptimal efficacy and increased risk and safety concerns.
Our novel chemistry platform eliminates these complex chemical mixtures, giving us control over the pharmacology of our stereopure medicines in development. Rationally designed, our stereopure nucleic acid therapies precisely target underlying disease biology and in our proof-of-concept studies they have demonstrated improved activity, stability, specificity and immunogenicity compared with stereoisomer mixtures. As a result, we believe we will be able to maximize therapeutic effect while minimizing the potential for side effects and safety risks. By doing so, our goal is to unleash the true and vast promise of nucleic acid therapeutics to treat numerous diseases.
From complex to pure:
Our approach for designing exceptional nucleic acid medicines for patients
- Nucleic acid therapeutics are a large and innovative class of drugs that can modulate the function of target ribonucleic acid, or RNA, to ultimately affect the production of disease-associated proteins.
- Each nucleic acid therapeutic is made up of strings of nucleotides, each held together by chemical linkages.
- The orientation of atoms at each linkage occurs randomly using conventional synthesis, adopting either an “up” or “down” orientation.
- Because a nucleic acid therapeutic has multiple linkages, an enormous numbers of permutations are possible, often resulting in over half-a-million different molecules in every dose.
- WAVE is the first company to fully control the orientation of the linkages and develop stereopure nucleic acid therapeutics.
- Nucleic acid therapies employ various molecular mechanisms to carry out their function.
- These mechanisms include those that promote degradation of the target RNA, like antisense and RNAi, and those that involve binding to the target RNA and modulating its function, like exon skipping.
- Nucleic acid therapies that promote degradation of the target RNA utilize very specific, naturally occurring enzymes.
- For instance, antisense therapies rely on the enzyme RNase H, whereas RNAi therapeutics rely on Ago2. In each case the nucleic acid therapeutic makes specific interactions with the enzyme.
- By controlling the orientation of the linkages WAVE is able to optimize the interaction between a nucleic acid therapy and various enzymes to improve pharmacology.
OUR GOAL: Exceptional Outcomes for Patients
- We have shown in proof-of-concept studies that WAVE chemistry enables improvements in activity, stability and specificity compared to mixture-based approaches and that it can be utilized across any target sequence.
- At WAVE, we are focused on developing optimally designed nucleic acid therapies that will be safer and more effective for patients.
- Using our chemistry and approach, our aim is to develop targeted treatments for a broad spectrum of rare, serious and previously untreatable genetic conditions.