On September 28, 2021 Precision Molecular (PMI), a clinical-stage company with the mission to develop imaging biomarkers and targeted alpha therapy (TAT) for patients with cancer, reported publication of preclinical data in Proceedings of the National Academy of Sciences (PNAS) detailing development of PMI06 and its use to quantify accessible levels of programmed death-ligand 1 (PD-L1) in solid tumors (Press release, Precision Molecular, SEP 28, 2021, View Source [SID1234590423]). The study also demonstrated how accessible target levels can be used to derive insights into pharmacologic activity of antibodies in tumors and elucidate therapeutic response. The study was led by researchers at the Johns Hopkins University School of Medicine.
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
PMI06 is a radiolabeled peptide that binds to PD-L1, marking the ligand for visualization using positron emission tomography (PET) imaging.
In the paper entitled "Pharmacodynamic measures within tumors expose differential activity of PD(L)-1 antibody therapeutics", the authors report on development of PMI06 and its evaluation in tumor models with variable PD-L1 expression. The authors note that rapid quantification of PD-L1 pharmacodynamics to interrogate the pharmacologic activity of antibodies offers the potential to select drugs with desired tumor penetration and targeting properties and optimize dosing to reduce therapeutic resistance. In addition, quantification of pharmacokinetics and pharmacodynamics of PD-1/PD-L1 therapeutics at the tumor site could advance the development of personalized therapies tailored to the unique properties and needs of each patient.
"There are several approved immune checkpoint inhibitors currently available to patients and more in development," said Seulki Lee, Ph.D., CEO of PMI. "Unfortunately, it has been difficult to predict which patients may benefit from which drug – which is determined, in part, by the presence of PD-L1 on the surface of their tumors. With PMI06, we can measure baseline PD-L1 levels in the whole body and follow the interaction between PD-L1 and a PD-L1 inhibitor, measuring how quickly and effectively the drug engages with the target. We can also measure how PD-1 inhibitors change PD-L1 levels in the tumors. In doing so, PMI06 offers the potential to guide selection of more targeted therapy, optimize the therapeutic dose, and avoid treatments that are not likely to work. Given the potential of this noninvasive biomarker, we look forward to studying it in patients and evaluating its potential to help direct personalized doses of immunotherapy."
Currently, the only registered biomarker to guide checkpoint inhibitor selection is immune histochemical analysis of PD-L1 expression. Unfortunately, this approach has limited predictive value and correlates only moderately with patient survival and response to PD-L1 based treatment.
Changes in PD-L1 levels could be measured using PMI06 without a biopsy during immune checkpoint therapy. Importantly, preclinical studies showed that PMI06 did not alter or interfere with the binding of the PD-L1 inhibitor to its target; PMI06 does not replace the checkpoint inhibitor once the inhibitor has bound to its target on the cell surface. Structural studies have shown that PMI06 binding to PD-L1 is similar to other approved checkpoint inhibitors which target PD-L1, suggesting its use as a biomarker could be translated to other immune checkpoint drugs.