H4
ComboMiR: Combinatorial microRNA Therapeutics for Diabetic Complications
Prof. Stephan Herzig, Helmholtz Munich; Dr Manuel Gil-Lozano, Helmholtz Munich; Dr Estefania Simoes Fernandez, Helmholtz Munich; Dr Ana Jimena Alfaro Nuñez, Helmholtz Munich
Helmholtz Munich
Challenge
Diabetes affects nearly 589 million individuals worldwide, significantly raising the risk of severe, life-threatening metabolic complications. Recent studies have shown that diabetes is a heterogeneous and complex disease comprising at least five distinct subtypes, each associated with distinct clinical features, disease progression, and risks of complications. These include Severe Autoimmune Diabetes (SAID, traditionally known as Type 1 Diabetes), Severe Insulin-Deficient Diabetes (SIDD), Severe Insulin-Resistant Diabetes (SIRD), Mild Obesity-Related Diabetes (MOD) and Mild Age-Related Diabetes (MARD). Accordingly, modern diabetes management requires comprehensive control of key metabolic parameters, varying in relevance across subtypes, rather than focusing solely on glycemic control or body weight loss. Yet, today’s therapeutic options remain constrained by heterogeneous responses, tolerability limitations, and insufficient personalization to distinct patient profiles and subtypes.
Technology
Through our research, we have identified that microRNAs (miRNAs) from the miR-379/miR-410 cluster are dysregulated in the livers of patients with diabetes, and have demonstrated that inhibition of specific miRNA candidates from this cluster results in significant improvements in key metabolic parameters in diabetic mouse models, including enhanced insulin sensitivity, improved glucose clearance, and restoration of circulating cholesterol, triglyceride, and ketone levels, independent of body-weight loss.
Commercial Opportunity
The therapeutic approach pursued by our team is based on a novel combination of miRNA targets involved in metabolic control. The resulting miRNA-targeting drug candidate (“ComboMiR”), currently under optimization at Helmholtz Munich, is being advanced as a weight-stable insulin sensitizer with potential both as a stand-alone therapy and as combination therapy, particularly alongside incretin-based treatments such as GLP-1 receptor agonists, to enable patient-tailored treatment of diabetes and related complications such as cardiovascular disease. We strongly envision the creation of a spin-off company to secure follow-up funding for future preclinical development (e.g., CMC and GLP toxicology) and subsequent clinical development of a nominated candidate. Strategic partnering (licensing and/or collaboration) with biotech or pharmaceutical companies is also under consideration.
Development Status
With the support of significant governmental funding, the team has designed novel candidates combining oligonucleotide-based inhibition of the selected miRNAs with an alternative delivery vehicle, enabling liver-selective delivery and subcutaneous administration with minimal side effects. As part of an ongoing multidimensional lead optimization program, those candidates will be assessed for their ADME/PK-properties, efficacy and toxicity in relevant preclinical models and benchmarked against current standard-of-care therapies.
Patent Situation
• WO2015/063081 “MicroRNAs modulating the effect of glucocorticoid signaling” (assigned to Helmholtz Munich; priority date: 29.10.2013; see: patentscope.wipo.int/search/en/detail.jsf;
• WO2020/053186 "MicroRNA inhibitors for use in treating metabolic diseases" (priority date: 11.09.2018; applicant: Helmholtz Munich; see: patentscope.wipo.int/search/en/detail.jsf;
• PCT/EP2025/085707 (undisclosed international PCT-application; applicant: Helmholtz Munich; priority date: 06.12.2024).
Further Reading
De Guia RMet al.EMBO J. 2015. doi: 10.15252/embj.201490464.
Ahlqvist E et al. Lancet Diabetes Endocrinol. 2018.
