Our Scientific Approach
Many diseases are caused by multiple abnormalities rather than by a single defect. In these cases, the traditional single-target approach to drug discovery and development may be less effective because a single target may not address the multiple underlying defects causing the disease. Use of a single, broadly targeted drug can lead to off-target toxicities, side-effects and tolerability issues, and co-administration of two or more drugs can be confounded by differences in the pharmacokinetics and tissue distribution of the drugs, thereby reducing the likelihood of each agent being simultaneously active in the same cell.
Our scientific approach is to leverage the growing body of knowledge associated with disease pathways and to rationally design orally bioavailable product candidates that simultaneously interact with multiple biological targets within one or more related disease pathways.
Our SMART Linker Technology Platform
We have developed our SMART linker technology platform to engineer molecules that simultaneously modulate multiple biological targets within one or more related disease pathways. The linkers used in our technology platform are small chemicals designed to join two separate bioactives into a single conjugate molecule. In systemic circulation, our SMART linker conjugates are stable and inactive, potentially reducing off-target toxicities and side effects. The conjugates are designed to be cleaved by specific enzymes exclusively within cells in order to release the two bioactives inside the cells. By releasing the bioactive components of the conjugate molecule only inside cells, the SMART linker allows the bioactives to reach their targets more efficiently and have greater efficacy than if the bioactives were dosed independently or in combination. The stability of our SMART linker conjugates outside of cells and the release of the bioactives exclusively within cells are differentiating features of our SMART linker technology platform.
Potential Benefits of our SMART Linker Technology Platform
We believe that our SMART linker technology platform provides substantial improvements over previous approaches to bioactive conjugation and has the potential to:
- Enhance activity on disease pathways through modulation of multiple biological targets
- Improve efficacy by matching the pharmacokinetics and tissue distribution of the component bioactives
- Improve safety and tolerability by releasing the component bioactives only within cells
We have observed in multiple preclinical studies that our SMART linker conjugates achieved greater efficacy than administration of the two bioactives either independently or in combination. In clinical trials, SMART linker conjugates have demonstrated significant improvements in activity on disease pathways and tolerability relative to equivalent doses of the two bioactives delivered in combination. We also have observed statistically significant efficacy with SMART linker conjugates at dose levels significantly lower than the prescribed doses of the two component bioactives.