I2
Lipidera
Prof. Petr Pávek, Charles University; Dr Radim Nencka, Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences
IOCB Tech
Challenge
Severe lipid-related and cholestatic diseases such as HoFH, cholestatic liver diseases, and MASH remain inadequately treated, particularly in patients who are statin-intolerant or refractory to existing therapies. Current approaches are largely LDLR-dependent. Additionally, cholestatic diseases lack effective disease-modifying oral therapies, and novel mechanisms face high regulatory and translational risk. The challenge is therefore to develop a first-in-class, orally available therapy with a differentiated mechanism that delivers clinically meaningful lipid lowering or cholestatic benefit while maintaining an acceptable safety profile.
Technology
The LipidEra project is based on modulation of nuclear receptors governing lipid and bile acid metabolism, specifically constitutive androstane receptor (CAR) and pregnane X receptor (PXR). The lead compound, MI-883, is a dual CAR agonist and PXR antagonist that reduces cholesterol synthesis, enhances bile acid elimination, and lowers circulating cholesterol independently of LDL receptor activity. This represents a first-in-class mechanism with potential applicability across multiple metabolic and cholestatic indications. The broader pipeline includes selective CAR agonists, PXR antagonists, and intestine-specific CAR modulators, all covered under a shared patent family.
Commercial Opportunity
The commercial opportunity lies in addressing high-unmet-need indications, including rare (orphan) cholestatic diseases and genetically driven dyslipidemias such as HoFH, as well as broader metabolic diseases such as MASH. An LDLR-independent mechanism provides differentiation from statins, PCSK9 inhibitors, and emerging oral PCSK9 agents. Orphan indications offer additional incentives, including market exclusivity (7 years in the US, 10 years in the EU). In broader dyslipidemia markets, the program is positioned to focus on selected niches where differentiation, combination strategies, or non-LDLR biology provide strategic value.
Development Status
MI-883 is the lead candidate with completed pharmacodynamic profiling and an advanced non-GLP ADME/Tox package. Non-GLP 7- and 28-day repeat-dose toxicity studies in rats have been completed, along with studies in PBX mice and proof-of-concept work in humanized PXR–CAR–CYP3A mouse models. These studies confirm target engagement and biological activity in relevant systems. Ongoing development focuses on optimization and translation, with remaining CTA/IND-enabling activities including final formulation development, GLP toxicology in two species, definitive PK studies, genotoxicity testing, and completion of DDI assessments.
Patent Situation
All lead and pipeline compounds are protected under the patent family WO2020221380. The application entered national phase in the EU, USA, Canada, and Australia in 2021, with patents granted in Australia (2022) and the EU (2024, Unitary Patent). Applications in the US and Canada are pending, with active prosecution ongoing. If granted, compound protection extends until 2040. Additional follow-on strategies, including deuterated analogs and selection patents, are under evaluation to further strengthen long-term exclusivity.
Further Reading
Scientific validation of the LipidEra approach is supported by a 2025 publication in Nature Communications describing CAR/PXR modulation and its impact on lipid metabolism (https://doi.org/10.1038/s41467-025-56642-y). Further technical and strategic context is available through publicly accessible patent documentation (WO2020221380).
