3D In Vitro MASH Screening for Lead Selection
A human-relevant, de-risking efficacy and safety screening program enabling selection and advancement of anti-steatotic and anti-fibrotic drug candidates for MASH drug discovery (formerly NASH)
Innovative therapies for MASH (Metabolic Dysfunction-associated Steatohepatitis, renamed from NASH) remain a critical unmet medical need. Our MASH Screening Program is designed to support your MASH drug discovery and developmental pipeline in identifying, prioritizing, and de-risking MASH drug candidates early on, using a robust, human-relevant 3D liver MASH model.
By enrolling your lead candidates into our established 5-week screening program, you can:
- Identify and prioritize promising MASH candidates cost-effectively
- De-risk go/no-go decisions with multiparametric analysis of MASH hallmarks in a single screen
- Accelerate translational confidence with clinically relevant dose–response insights
- Generate reliable, decision-driving pre-clinical data to support your IND-enabling studies
- Save millions by discarding early on unsuccessful drug candidates with a 3D in vitro human translational screening
Join the 3rd edition of our MASH Screening Program by March 27
or discuss a customized MASH screening at your convenient timeline
MASH Screening Program‘s impact in numbers
Pharma & Biotech participants
customer compounds tested
customers identified their positive candidates
success rate in lead identification
Why MASH Screening with InSphero?
We inspire researchers, worldwide, to reach their full potential so that life changing therapies can ultimately make it into the hands of patients.
Fast, scalable phenotypic screening
Screen up to 50 compounds with 5-week turnaround, fitting seamlessly into MASH lead selection discovery workflows.
Reduce translational risk early
Evaluate lead candidates in a primary human, multicellular 3D MASH liver model that recapitulates key disease hallmarks.
Benchmark against clinical candidates
Objectively compare your lead candidates with clinical-stage drugs to support your go/no-go decisions for prioritization
Entry to advanced phenotypic characterization
Start with a standardized screening program and progress selected candidates into advanced phenotypic follow-up as needed
From lead selection to confident decisions: Your partner in MASH drug discovery
Our MASH Screening Program (formerly NASH) supports teams from early lead prioritization through to in-depth phenotypic validation. Phase 1 enables scalable selection of the most promising lead candidates, while Phase 2 supports in-depth analysis for prioritized candidates
Phase 1: Multiparametric screening and clinical benchmarking to prioritize MASH lead candidates
Actionable insights into your lead candidates’ safety and efficacy profiles
Screen up to 50 lead candidates per program in a human-relevant 3D MASH liver model to generate multiparametric efficacy and safety data. Evaluation based on established MASH hallmarks: extracellular LDH to assess hepatotoxicity, intracellular triglycerides to quantify steatosis, and secreted pro-collagen I to monitor fibrotic activity- supporting your early lead prioritization and risk assessment for confident go / no-go decisions in MASH drug discovery.
Figure: Effect of clinical candidates on steatosis and fibrosis in the 3D MASH model. Ervogastat reduces intracellular triglyceride (TG) content and lowers Pro-Collagen I secretion after 10 days of treatment. PLN-1474 decreases Pro-Collagen I secretion in a concentration-dependent manner.
Benchmark performance against clinical-stage MASH candidates
Evaluate your lead candidates side by side with a curated panel of up to 10 clinical-stage MASH drugs and reference compounds, enabling objective comparison to industry benchmarks. This approach strengthens translational relevance of your findings, supporting data-driven early benchmarking.
Figure: Efficacy results of 10 clinical MASH drugs or tool compounds. Scatter plot comparison of 5 concentrations comparing PC-1 versus triglycerides values. Anti-steatotic or anti-fibrotic effects are shown as percentage versus MASH control over the Y and X axes, respectively.
Phase 2: De-risk and validate selected MASH candidates with advanced phenotypic insights
Achieve disease-relevant phenotypic validation of selected lead candidates
Advance prioritized MASH candidates into a multidimensional phenotypic follow-up study to confirm efficacy and strengthen translational confidence using clinically relevant endpoints:
- Steatosis: intracellular triglyceride quantification
- Fibrosis: clinically relevant biomarkers (PIIINP, TIMP1, HA)
- Inflammation: cytokine and chemokine profiling
- Phenotype confirmation: histological assessment of steatotic and fibrotic features
Figure: Sirius Red staining demonstrates enhanced fibrosis in the MASH liver model compared to the Lean model. FFA + LPS induction in 3D human liver spheroids generates a MASH-like pro- inflammatory phenotype with elevated TNF-α, MCP-1, and MIP-1α secretion versus LEAN control. Selonsertib (ASK1 inhibitor) served as anti-inflammatory reference
Mechanistic insights to support confident candidate advancement
Extend phenotypic findings with advanced mechanistic and molecular analyses to understand how your lead candidate drives phenotypic outcomes:
- Quantify lipid and fibrotic MASH phenotypes and evaluate drug efficacy by benchmarking against clinically observed pathology using an AI-powered image analysis solution
- Assess molecular responses via single-spheroid transcriptomics
- Explore pathway involvement and combination strategies to guide differentiation and advancement
Figure: AI-based image analysis of the fibrotic phenotype in the MASH 3D liver model
Evaluate drug responses across patient-derived MASH models and genetic diversity
Assess lead candidate efficacy in patient-derived 3D MASH liver models generated from primary hepatocytes of steatotic donors or diverse genetic backgrounds (SNPs). This enables evaluation of inter-patient variability and supports informed patient stratification and risk-mitigation strategies.
Join the MASH Screening Program by March 27 or at your convenience
Your lead candidates are evaluated in our validated 3D InSight™ Liver MASH model, built from primary human hepatocytes and key non-parenchymal cells, including Kupffer, endothelial, and stellate cells - to deliver robust, human-relevant safety and efficacy data.
Phase 1: Study design and treatment schedule
- 10-day co-treatment during MASH induction
- Treatment strategy: 4 applications per compound across a 5-point dose-response.
- 3 replicates per endpoint in 3D human liver spheroids
- Selected endpoints for quantitative assessment of steatosis, fibrosis, and hepatotoxicity
After phase 1 screening program, meet with InSphero’s scientific experts to review the results and discuss next steps for prioritized candidates - optimizing study design and building a robust, decision-ready data package for efficient progression.
Why our customers joined the MASH Screening Program
“For our lead target at Inipharm, a human-centric system is extremely important for proof of concept. InSphero’s primary human liver spheroids under culture conditions that resulted in fibrotic and inflammatory processes was able to reproduce known human genetic phenotypes relating to our target of interest. Additionally, the MASH Screening Program testing platform was an efficient way for us to assess multiple leads for potential efficacy.”
