Aptamers represent an emerging class of therapeutics that can be applied to a variety of human diseases and have distinct advantages over other drug classes.
Aptamers use their three-dimensional
structure to bind to specific targets with high specificity and
affinity in a manner similar to monoclonal antibodies.
Unlike
monoclonal antibodies, aptamers are synthetically derived, making
production predictable, reproducible and cost-effective. Aptamers
are also chemically stable and do not generate an immune response
that could limit efficacy. Based on preclinical and clinical
data, we believe that aptamer therapeutics combine many of the
beneficial characteristics of small molecules and biologic drugs
and other classes of oligonucleotides, such as antisense and
siRNA, without exhibiting many of their disadvantages.
Aptamer therapeutics can potentially offer the following benefits:
- Attractive drug-like properties.
- Ability to disrupt interactions between proteins. The large surface area of interaction between aptamers and their protein targets makes aptamers well-suited to block interactions between proteins. Because abnormal interactions between proteins are involved in many disease processes, the use of aptamers to inhibit these interactions may have meaningful clinical significance. Furthermore, since aptamers interact with proteins found on the surface of and outside cells, aptamers do not have to cross the cell membrane, which may make it easier to deliver an effective quantity of aptamer to the target.
- High affinity binding and specificity. Aptamers have well-defined, three-dimensional shapes, which allow them to interact with a folded, three-dimensional protein target, like a key in a lock. The complementary structure of an aptamer and its protein target allows aptamers to bind to their protein targets with high affinity and specificity.
- Rationally designed duration of action. Aptamers can be rationally designed with an optimized duration of action necessary to achieve a desired effect. We use proprietary chemical stabilization and conjugation techniques to prevent or reduce the metabolism of the aptamer and its elimination from the body, which may permit aptamers to be used in treating both acute and chronic diseases. (See Drug Metabolism & Pharmacokinetics)
- No observed immunogenicity. Because nucleic acids are not typically recognized by the human immune system as foreign agents, aptamers do not generally trigger an antibody response to the aptamer. To date, we have not observed an antibody response to any of our aptamer product candidates in our preclinical studies or our Phase 1 clinical trials.
- Rapid in vitro discovery and chemical synthesis. Discovery of aptamers is an entirely in vitro process that does not rely on biological organisms. This allows for rapid and reproducible discovery compared to biologic drug products. Using our proprietary process called Systematic Evolution of Ligands by EXponential expression, or SELEX, we can select aptamers that bind to a selected target in vitro with high affinity and specificity in approximately one month. Then, using our proprietary post-SELEX modification processes, we engineer desired characteristics and functionality into each aptamer such that it is ready for preclinical animal testing in approximately 12 to 15 months. (See Aptamer Discovery)
- Ease of manufacturing. Aptamers are chemically synthesized allowing for rapid, scalable and reproducible production at lower costs. (see Chemistry, Manufacturing, and Controls)
|
