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.
Validated solid tumor targets
Numerous tumor targets have been clinically validated but have yet to be pursued as radiopharmaceuticals. RayzeBio focuses on biologically-relevant, tumor-specific targets suitable for targeted radiotherapy. These targets have high expression on solid tumors with little to no expression on normal tissues.
Binders to target
Several criteria are critical when considering delivery of a radioactive isotope. Molecular binders need to be designed to provide exquisite affinity and specificity to tumor targets to minimize off-target effects. At the same time, the binders should be small and agile to allow for deep tumor penetration and be tunable to create drug-like properties for proper clearance from the bloodstream.
Focused on therapeutics
We are focused on alpha and beta radioisotopes with a preference for using Actinium 225 (Ac225), an alpha radioisotope for therapeutic programs
Proactive investment to prepare for commercialization
We are completing the construction of an integrated GMP facility in Indianapolis, Indiana, which is being designed to manufacture our drug products, including commercial supply requirements, as well as Actinium-225. Currently, we source Actinium-225 from multiple third parties including the U.S. Department of Energy Isotope Program, managed by the Office of Isotope R&D and Production