HeartBeat.bio AG and Cubase Bio are joining forces to develop a more detailed way of studying cardiovascular disease in human cardiac tissue, combining organoid models with three-dimensional spatial transcriptomics.

The companies have secured approximately approximately $116 million through the Eurostars program for a joint research initiative known as FACTS-3D, or “Fibrosis Analysis in Cardioids via Transcriptomic Spatial-mapping in 3D.” The project is supported nationally by Sweden’s Vinnova and the Austrian Research Promotion Agency (FFG), with additional funding from the European Union through Horizon Europe.

At the center of the collaboration is an effort to better understand how myocardial fibrosis develops and responds to treatment. Fibrosis, characterized by excessive deposition of connective tissue in the heart, contributes to structural remodeling and impaired cardiac function across a range of cardiovascular diseases.

The companies say the project is intended to address limitations associated with widely used preclinical approaches. Animal models and conventional two-dimensional cell cultures can provide valuable biological information, but neither necessarily reproduces the cellular complexity and three-dimensional organization of human cardiac tissue. That distinction becomes particularly important when studying diseases in which interactions between different cell types and their location within tissue influence disease progression.

HeartBeat.bio will contribute its Cardioid platform, which uses human cardiac organoids as a model for investigating cardiac biology and drug responses. Cubase Bio will apply its three-dimensional spatial transcriptomics technology to characterize molecular activity throughout intact organoid structures. Rather than relying on thin tissue sections, the approach is designed to preserve the three-dimensional context of the cardiac tissue being analyzed. Cubase Bio’s technology is also intended for scalable workflows compatible with 96- and 384-well plate formats, potentially making spatial molecular profiling more suitable for higher-throughput drug discovery applications.

The FACTS-3D project will focus on the molecular and cellular changes associated with myocardial fibrosis. By mapping gene expression and cellular states across intact cardiac organoids, the researchers aim to determine how disease-associated changes are distributed within the tissue and how those patterns change following treatment. The resulting data could help researchers distinguish disease-relevant cellular states, investigate mechanisms driving cardiac remodeling and evaluate pharmacological responses. The partners also expect the work to support the identification and validation of potential therapeutic targets.

For HeartBeat.bio, the collaboration expands the potential applications of its Cardioid technology beyond phenotypic screening toward deeper investigation of disease mechanisms. “FACTS-3D brings together two highly complementary technologies to address one of the major challenges in cardiovascular drug discovery: understanding disease biology in a physiologically relevant human context while retaining the spatial information that is essential for complex cardiac phenotypes,” says Michael Krebs, CEO of HeartBeat.bio.

He added that the collaboration could help the company use Cardioids to investigate and validate mechanisms and targets involved in heart failure, with an initial focus on fibrosis and cardiac remodeling.

Cubase Bio sees cardiac tissue as a particularly strong application for three-dimensional spatial analysis because tissue architecture is closely connected to both normal cardiac function and disease. “The way cells organize in three dimensions is central to how a heart chamber is built, what happens when fibrosis occurs and how the heart remodels itself,” says Malte Kühnemund, CEO of Cubase Bio.

According to Kühnemund, conventional section-based spatial transcriptomics cannot fully capture intact three-dimensional structures, while imaging approaches capable of preserving that spatial information can present challenges for high-throughput applications.

The companies intend for FACTS-3D to bridge those limitations by combining intact human cardiac organoids with scalable molecular profiling. If successful, the platform could provide drug developers with a more comprehensive view of how cardiovascular disease develops at the cellular level—and how candidate therapies alter those processes in human-derived tissue.

For further information, please visit www.heartbeat.bio or www.cubasebio.com.