Technology
Dark Antigens®
Dark Antigens® are a new class of tumor-specific targets from the dark genome, with potential to reshape the future of cancer treatment.
Dark Antigens arise from diverse sources within the dark genome, providing a large untapped reservoir of potential targets
Enara Bio is shining a light on the vast untapped potential of the dark proteome, enabling us to develop first-in-class immunotherapies that transform patient care.
One of the most surprising findings from the Human Genome Project was that just ~2% of our DNA was annotated as genes that code for proteins.
For decades, drug discovery has focused almost exclusively on this small fraction of the genome. The vast remainder, known as the dark genome, has been largely unexplored.
Previously undiscovered polypeptides and proteins
The dark genome includes a wide range of elements that were originally thought to be “non-coding” or lacking function. However, these sequences perform essential roles in normal biology, from regulating gene expression to shaping chromosome stability. Importantly, it is now widely understood that many of these sequences also encode previously undiscovered polypeptides and proteins with wide-ranging functions. Collectively, this emerging dark proteome is increasingly linked to human disease pathology and represents a major untapped opportunity for new targeted therapeutics.
Discovering and validating hidden antigens
In cancer, the dark proteome is a rich source of novel tumor-specific antigens, including both cell-surface proteins and intracellular-derived peptides presented at the cell surface by HLA molecules. While today’s established cancer antigens are derived from the traditional protein-coding genome, recent research has shown that the majority of cancer-specific antigens originate from the dark genome.
By discovering and validating these hidden antigens, we are addressing the longstanding unmet need for new cancer targets in solid tumors. This is enabling us to build a pipeline of first-in-class treatments that can unlock the full power of cancer immunotherapy and deliver transformative benefit for patients.
Enara Bio is pioneering the discovery of Dark Antigens® – novel tumor-specific antigens from the dark genome.
During tumorigenesis, cancer cells undergo widespread epigenetic and translational dysregulation. These altered cellular processes result in the transcription and translation of previously silenced regions of the dark genome, leading to the production of Dark Antigens®.
Therefore, unlike many conventional tumor antigens, Dark Antigens® are tumor-specific by origin, with little or no expression in normal healthy tissues.
We have discovered large numbers of Dark Antigens® across all major cancer types, laying the foundation for Dark Antigen® therapeutics to have a broad role in the future treatment of cancer.
Many Dark Antigens® are expressed at high prevalence across multiple tumor types. Therefore, in contrast to mutation-derived neoantigens – which are either patient-specific or shared by small subsets of patients – much larger patient populations can benefit from Dark Antigen® therapeutics.
Our initial therapeutic focus is on first-in-class T cell engagers (TCEs). We have discovered Dark Antigens® with the hallmarks of ideal targets for this modality:
- Minimal or no expression in normal healthy tissues
- Robust presentation on the tumor cell surface
- Homogeneous expression within tumors to support strong and durable efficacy
- Shared across broad patient populations