Understanding Expression to Control Disease

When genes are expressed at the wrong time or in the wrong amounts, it alters the function of a cell, leading to disease. Our pioneering gene control platform provides a unique lens for understanding these disease-driving changes in gene expression to diagnose and treat disease.

Our Gene Control Platform

Ours is the first platform dedicated to the regulatory genome to systematically identify disease-causing alterations in gene expression and create medicines that control the expression of genes with the aim of providing a profound and durable benefit for patients with diseases that have largely eluded other genomics-based approaches. While much of targeted drug discovery has focused on inhibiting or otherwise changing the function of abnormal genes and proteins, many more diseases could be addressed by modulating the expression of both abnormal and normal genes, turning them on, off, up or down. Our unique ability to elucidate regulatory regions of the genome allows us to home in on which genes to control, in which cells, for which patients, and how best to modulate the expression of those genes to maximize the chances of providing a profound benefit and durable for patients.

Our approach begins and ends with the patient and harnesses the collective power of regulatory genomics, disease biology and small molecule transcriptional chemistry.

  • Patient Tissues
  • Regulatory Genomics
    +
    Disease Biology
  • Drug Targets and
    Patient Subsets
  • Small Molecule
    Transcriptional
    Chemistry
  • Patient Benefit

Regulatory Genomics

Regulatory regions of the genome control the expression of genes, turning them on, off, up or down like genomic dimmer switches. Through the coordinated activation and repression of genes, these genomic dimmer switches determine how a cell behaves, whether it is a skin cell or a lung cell, whether it is diseased or normal. Our gene control platform allows us to systematically analyze regulatory regions of the genome, identifying a very small subset of these genomic dimmer switches, known as super-enhancers, that control the expression of genes most critical to a given cell. By comparing super-enhancers and their associated genes in healthy and diseased cells from patient tissues, we can identify disease-causing alterations in the expression of critical genes and home in drug targets that we believe provide the best chance of providing a therapeutic benefit for patients. Because our approach starts in patient tissues, we can also identify subsets of patients whose disease is driven by distinct alterations in gene expression and are therefore most likely to benefit from a particular therapeutic approach.

Disease Biology

We integrate our understanding of the regulatory genome with deep expertise in the biology of the diseases that we aim to treat, including cancer, autoimmune disorders and genetic diseases. Our understanding of disease biology helps focus our discovery and development efforts in areas where we believe we can have the most impact. It also allows us to place our novel findings into the broader context of the disease, weaving together our insights with what is already known about the disease to further inform our decisions about which genes to control in which patients and how best to modulate those genes to discover and develop medicines most likely to provide a profound and durable benefit for patients with diseases that have eluded other approaches.

Small Molecule Chemistry

We have a unique expertise in creating small molecules to selectively modulate
transcription factors, transcriptional kinases and other regulatory proteins to control the expression of genes. Although our gene control platform can identify drug targets across a range of therapeutic modalities, we have focused our internal discovery efforts on targeting transcriptional and regulatory proteins for three reasons. Transcription factors, transcriptional kinases and other regulatory proteins represent among the most promising and high-potential gene control targets for therapeutic intervention because of the central role they play in carrying out the process by which genes are expressed. These specialized proteins have been historically difficult to drug, representing a largely untapped opportunity to bring novel and differentiated therapies to patients. And, through significant investments in our capabilities in biochemistry, structural biology and medicinal chemistry, as well as in building a sophisticated suite of proprietary assays to measure the biochemical, biophysical, cellular and genomic activity of known and novel compounds against transcriptional targets, we are uniquely positioned to leverage that opportunity to advance a new wave of medicines that selectively target transcription to control the expression of disease-driving genes.