(652b) Cancer Immunotherapy with PLGA Microparticles: Product Development from Benchtop through IND-Enabling Studies

Qrono's mission is to revolutionize cancer treatment with low toxicity therapies that build anti-tumor immunity and protect against distant metastases. At the foundation of this aim is a new drug delivery platform based on widely used poly(lactic-co-glycolic) acid copolymer microparticles that enable the local immunomodulation of the tumor microenvironment (TME) over time. Working with proven polymers allows Qrono to build concepts from published mathematical models into its formulation design process, ultimately creating a platform that provides the on-and-off release of multiple drugs or antibodies in a predictable fashion. Qrono hypothesizes that the on-off delivery of multiple active agents over time can mimic or superseded the signaling used by tumor and immune cells changing the TME to promote a lasting anti-tumor immune response compatible with existing immunotherapies.

Qrono’s lead product, QR206 uses PLGA microparticles to target highly potent tubulin inhibitor directly to treatment resistant tumors and their protective macrophages. QR206 incorporates multiple PLGA polymers to provide up to 50 day of drug release. This extended release performance has been maintained through the transition from benchtop testing through GMP production by mathematically correlating the timing of drug release to the polymer properties of initial molecular weight and degradation rate, which allowed continuous development with off-the-shelf GMP-grade polymers.

Qrono is developing QR206 in collaboration with the University of Pittsburgh and has progressed from in vivo proof-of-concept testing into IND-enabling studies in established head and neck cancer (HNSCC) models. These studies began in vitro, comparing the activity (IC50) of drug before and after microencapsulation. Once consistent nanomolar activity was confirmed, proof-of-concept for in vivo activity was established in mice bearing Cal-27 HNSCC xenograft tumors. Researchers at the University of Pittsburgh monitored tumor growth for four weeks, documenting a statistically significant (p<0.05) reduction in tumor volume relative to drug-only and vehicle-only controls at two consecutive time points. Animals were then euthanized and tissue samples were used in preliminary biodistribution and immune histology analysis to evaluate QR206’s mechanism of action. Tumor and serum drug concentration quantified by HPLC against naive tissue and serum standard curves documented elevated intratumoral, but not systemic drug concentrations from QR206 relative to controls (p<0.02). Tumor associated macrophage levels, which are correlated with suppression of the adaptive anti-tumor immune response, were quantified by F4/80 histology in multiple slices of tumor tissue and found to be significantly lower in QR206 treated tumors than in controls suggesting QR206 might have an positive impact on cancer immunotherapy.