Beta-cell recovery to counter diabetes

Project Information

DiogenX

Grant agreement ID: 190133766

DOI

10.3030/190133766

Project closed

EC signature date 30 November 2023

Start date 1 October 2023

End date 30 September 2025

Funded under

• The European Innovation Council (EIC)

Total cost

€ 5 673 000,00

EU contribution

€ 2 500 000,00

Coordinated by

DIOGENX SAS
France

Periodic Reporting for period 2 - DiogenX (Beta-cell recovery to counter diabetes)

Reporting period: 2024-10-01 to 2025-09-30

Summary of the context and overall objectives of the project

Globally 20 M of T1D patients rely on exogenous insulin administration as the only treatment to manage their disease. The treatment is complex to follow since it requires not only to inject insulin (2-4 times/day) but to adhere to a restrictive lifestyle (e.g. following a strict diet) reducing patient QoL. An additional problem is that insulin can drive to poor glucose control which is associated with many complications (e.g. stroke, renal disease) reducing life expectancy 10-15 years.

DiogenX aims to withdraw insulin dependency and cure T1D by protecting and regeneration of pancreatic beta-cell able to produce insulin according to glycemia levels.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

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.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

The results obtained over the past year confirm the relevance of DiogenX’s scientific approach, targeting the Wnt pathway with RSPO1 analogues to regenerate pancreatic beta-cells. Extensive nonclinical data demonstrated that DGX-01 restores beta-cell mass, improves glycemic control, and shows a favourable safety and PK profile, supporting its progression as a potential first-in-class, disease-modifying therapy for people with type 1 diabetes—ultimately aiming to reduce or eliminate dependence on exogenous insulin.
The project also delivered a complete CMC package: a stable cell line, a qualified GMP Master Cell Bank, robust perfusion-based manufacturing, a multi-step DSP achieving >99% purity, qualified analytical methods, and a stable formulation.
These achievements position DGX-01 for IND/CTA submission and entry into first-in-human clinical trials. Key needs for further uptake include continued financing, regulatory engagement, GMP manufacturing campaigns, partnership building, and sustained IP and market access strategy.