Our Approach

A bold vision

Thousands of genetically defined diseases have a known root cause. Our product engine enables us to systematically approach drug discovery in genetically defined diseases. We aim to discover and develop disease modifying therapies that result in meaningful outcomes for patients and families.

Our vision is to treat genetically defined diseases by addressing their root cause.

An integrated, patient-driven approach

Disease modeling in relevant human cells & tissue

Fully differentiated patient-derived or other relevant human cells from genetically defined disease populations

Scalable cell biology with custom robotics

Long-term culturing of human cells to enable comprehensive target identification
Robust assays using relevant models

Identification of cellular drug targets to modulate gene expression

Multiple chemogenomic and genomic screening approaches
- Proprietary annotated, pharmacologically diverse small molecule compound library
- Customized CRISPR-Cas9 guide libraries

Unique biology pathway insights to inform target identification and biomarker strategy
Proprietary database (FulcrumSeek)

Demonstrate functional benefit and maintenance of cell health
Genome-wide profiling to understand full impact of drug/target interaction

Profiling of development candidates across multiple patient-derived tissue-relevant cells

In vitro analysis of a product candidate to ensure target is representative of disease across populations
Provides increased confidence in breadth of therapeutic applicability
Generates insights around patient stratification

Biomarker-driven drug discovery and development

Biomarker strategy enabled and guided by data from patient-derived cell models

Our product engine in action: Addressing the root cause of FSHD

FSHD, a rare, progressive and disabling disorder, is caused by aberrant expression of the DUX4 gene in skeletal muscle resulting in the inappropriate presence of DUX4 protein. Normally, DUX4-driven gene expression is limited to early embryonic development, after which time the DUX4 gene is silenced. In patients with FSHD, the DUX4 gene is unsilenced as a result of a genetic mutation. The result is death of muscle and its replacement by fat, resulting in skeletal muscle weakness and progressive disability.

We utilized patient-derived FSHD muscle cells, known as myotubes, and screened them with our small molecule probe library to identify drug targets that reduced DUX4 expression. One of those drug targets was p38α/β MAPK (mitogen activated protein kinase). We evaluated multiple small molecule p38α/β inhibitors and observed a consistent reduction of both DUX4 expression and DUX4-driven gene transcripts with each inhibitor.

As a result of our evaluation, we identified losmapimod as our preferred development candidate based on substantial and attractive preclinical and clinical data regarding safety, pharmacokinetics and target inhibition.

We announced results from our ReDUX4 trial with losmapimod in June 2021. We believe the same approach we used to develop our FSHD therapeutic can be applied to many other genetic diseases where the root cause of the disorder is known. Read more about our pipeline.