Radio DARPin Therapies: DLL3 and more

Molecular Partners has developed an in-house Radio DARPin Therapy (RDT) Platform that represents a unique and innovative delivery system for radioactive payloads to solid tumors. Radioligand therapies have proven potential but with technological limitations that DARPins may address. Molecular Partners’s first disclosed target for its in-house RDT programs is Delta-like ligand 3 (DLL3). Expression of DLL3 is low in healthy tissue but significantly increased in certain tumor types, providing an opportunity for selective targeting through the high-affinity and specificity offered by DARPins. Molecular Partners is exploring additional targets amenable to Radio DARPin Therapies internally and in its collaboration with Novartis and potentially others.

Need

Radiation therapies are a well-validated approach to treating cancer. However, the treatment often also affects healthy cells, resulting in harmful side effects. This limits the amount of radiation patients can receive, which can leave hard-to-reach tumor lesions untreated. This encourages relapse and ultimately limits therapeutic potential.

Rationale

The unique nature of DARPins as an engineered protein drug class may allow Molecular Partners to overcome the limitations of other radioligand therapies. DARPins have great potential to enable robust, tumor-specific delivery of therapeutic radionuclides owing to their small size – allowing for great tumor penetration – high specificity and long tumor residence time. The DARPin scaffold is highly customizable allowing a range of additional features tuned to an indication. Ultimately this may enable more effective treatment of small or hard-to-reach tumors.

Solution

Preclinical data shows that Molecular Partners’ proprietary Radio DARPin Therapy Platform can deliver high amount of radioactivity to tumors without accumulating in other tissues. Further data shows that Molecular Partners has been able to engineer the surface of RDT candidates to dramatically reduce accumulation in the kidney which is a historical challenge for small protein-based delivery vectors. In preclinical models, this surface engineering did not affect tumor uptake or uptake in other healthy organs and combination with another kidney reduction strategy provided a cumulative benefit.