PO0017 - Essential Biomarkers for a Clinical Study of a Novel Allogeneic Cell Therapy for Acute Graft-versus-Host Disease

Background: Allogeneic cell therapies require screening and monitoring biomarkers to ensure a precision medicine approach that personalizes treatment. The standard procedure of stem cell transplantation imposes toxicity and immune-related concerns, which are evidenced by the development of acute graft-versus-host disease (aGVHD). The availability of live human placenta-derived as a source of Decidua Stromal Cells (DSCs) has shown encouraging efficacy and safety profiles in many diseases, including aGVHD.

Aims: A limitation of using DSCs in aGVHD is a lack of understanding of how the cells behave in the body and how they affect the immune system of the host. ASC Therapeutics has developed ASC930, an allogeneic cell therapy consisting of DSCs for the treatment of patients with Steroid Refractory aGVHD (SR-aGVHD) and concomitant biomarkers to profile therapeutic screening and monitoring.

Methods: In the prospective study (NCT04883918), the safety and efficacy of ASC930 is being evaluated. Disease response will be assessed using surrogate safety and efficacy endpoints. To better understand the relationship between established biomarkers and DSCs, the study will include quantification of donor-derived cell-free DNA and flow cytometry to measure the immune response. In addition, two biomarkers of endothelial dysfunction, predicting long-term outcomes, will be evaluated: suppressor of tumorigenicity-2 (ST2) and regenerating islet-derived protein 3-α (REG3α), which have been identified in high concentrations in the blood of patients with aGVHD and are predictors of increased mortality.

Results: Preliminary clinical work using labeled DSCs showed that the cells travel to the lungs, then to the spleen and liver (Erkers 2015). These results are being assessed in vivo with the methodology described above, focusing on DSC pharmacokinetics and pharmacodynamics, as well as immune and therapeutic response.

Conclusion(s): The introduction of selective biomarkers of cellular, immune, and disease response to DSCs can help select the right patient, the right treatment, and the right monitoring in the treatment of aGVHD.