Across the duration of the project, DiogenX completed all scientific and technical activities required to advance DGX-01 toward IND/CTA readiness. The first year focused on the comparison and selection of RSPO1 analogues, using a comprehensive panel of efficacy models. Several Fc-bearing RSPO1 analogues demonstrated strong, reproducible activity in vitro and ex vivo consistently inducing beta-cell proliferation. These analogues also showed meaningful in vivo efficacy in the Non-Obese Diabetic (NOD) mouse model, widely used in academic and pharmaceutical research. All candidates were able to improve glycemic control and reduce diabetes incidence after weekly dosing.
Based on the totality of these data, one analogue—DGX-01—was selected as the Lead. Subsequent studies established its pharmacokinetic profile, confirming exposure suitable for human administration, and demonstrated a favourable non-clinical safety profile across mice, rats, and cynomolgus monkeys, with no adverse findings precluding further development.
In parallel, extensive effort was dedicated to the industrial development of DGX-01. Early upstream and downstream development delivered consistent, high-quality material.
WP4 completed full cell line development. After two rounds of cloning, the project selected a stable, high-producing monoclonal clone, subsequently used to generate the GMP Master Cell Bank, which passed all ICH Q5A/Q5D characterisation and viral safety testing and is now released for GMP manufacturing.
Downstream development (WP5) established a robust purification cascade achieving >99% purity at toxicology-scale (250 L) and acceptable overall yield for Phase I supply. All associated analytical methods (identity, purity, charge variants, potency, and safety assays) were developed, qualified, and transferred to QC laboratories for release testing.
Finally, formulation development delivered a clinical formulation compatible with global distribution and long-term stability.
Overall, the project produced a complete, coherent, and high-value non-clinical and CMC package, enabling smooth regulatory progression toward first-in-human trials.
