Radiopharm Theranostics (ASX:RAD) has announced that preclinical data from studies with the Lu177-B7H3-monoclonal antibody RV01 demonstrated favourable biodistribution and showed that RV01 maintained high tumour uptake.
The company said that Fc region modifications of the monoclonal antibody (mAb) confirm a shorter half-life, compared to traditional mAbs. It said the shorter half-life and other Fc modifications have the potential to limit off-target exposure to the isotope and mitigate toxicities associated with traditional monoclonal antibody therapies.
RV01 is Radiopharm's B7-H3-targeted radiopharmaceutical therapy designed with strong affinity for the 4Ig isoform of B7H3 that is highly expressed in tumours and not in healthy tissues, which is being developed in partnership with MD Anderson Cancer Center.
The B7-H3 targeting mAb is designed to target various solid tumours that express the B7-H3 protein. High expression of this target is associated with a poor prognosis in many cancer types.
“We are especially pleased with these new preclinical data as they further validate earlier preclinical work that showed strong affinity to the target without the extensive circulation time of other monoclonal antibodies. Our mAb has been purposefully modified in the Fc-region with the objective of maintaining the same targeting capabilities together with a reduced half-life. Most mAbs have a typical half-life of over one week, whereas RV01 peaks within one to two days,” said Dr Dimitris Voliotis, chief medical officer of Radiopharm Theranostics.
“The antibody shows faster liver excretion in the preclinical experiments, allowing the isotope enough time to effectively target the tumour, potentially without the associated toxicities. Unlike peptides or small molecules, mAbs are excreted by the liver, the most radio-resistant organ. This, combined with the faster excretion due to the shortened half-life, potentially offers important advantages compared to excretion via the kidneys, where the elimination of radiopharmaceuticalscan result in a significant potential toxicities,” added Dr Voliotis.