Approach

Despite therapeutic advances made in the last decade, there remains a high unmet need for new cancer treatments. Radiation therapy is a proven approach to treating many cancers and is typically administered by an external beam of high energy rays. In contrast, radiopharmaceutical therapy (RPT) selectively deliver radioisotopes to tumors via the bloodstream.

RPT represents one of the most promising new modalities for the treatment of solid tumors. Radiopharmaceuticals have the unique advantage of being both diagnostic and therapeutic. The same drug conjugate could be used for both diagnostic imaging and therapeutic use by switching out the radioisotope. Direct visualization of drug conjugate uptake by tumors with imaging allows for proper patient selection to receive the therapeutic radioisotope (e.g. Actinium-225).

RPTs have several similarities to antibody drug conjugates (ADCs). However, several aspects of RPTs offer advantages over ADCs, potentially offering patients and physicians viable treatment options. 

We believe RPT represents one of the most promising new modalities for the treatment of solid tumors.

Conceptually, antibody drug conjugates, or ADCs, and RPT are similar in that they both consist of a binder recognizing a cancer protein target, linker, and payload to attack cancer cells. However, we believe certain aspects of RPT may offer advantages over ADCs on both efficacy and safety that could result in a higher probability of success in identifying and advancing RPT drug candidates in a shorter timeframe. These include:

• Radioisotopes are more potent than chemotherapeutic payloads of ADCs;
• Our RPT drug candidates use binders smaller than antibodies, which can allow for deeper and broader distribution in the tumor;
• With RPT, cellular internalization is not necessary to cause cancer cell killing, whereas most ADCs are dependent on cellular internalization for efficacy;
• Stable linkers can be used with RPTs, whereas customized cleavable linkers are used for ADCs;
• RPTs can avoid drug resistance mechanisms that ADCs face such as drug efflux transporter-mediated resistance; and
• RPTs utilize a theranostic approach in which the same binder for therapy can also be used for diagnostic imaging to better select patients for treatment as well as dosimetry to help identify a maximal safe dose to administer.