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The DNA Damage Response (DDR)

  • Protects healthy cells from DNA damage
  • Prevents DNA damage from accumulating to toxic levels
  • Is required for normal cell survival and prevention of cancer-causing mutations

Targeting the Totality of the DDR in Cancer

Loss of DDR Pathways: Synthetic Lethality
  • HRD tumors
  • PARPi resistance
Higher Levels of DNA Damage: Replication Stress
  • Small cell lung cancer
  • Combination therapies
Dependence on DDR Driven Processes: ALT
  • 10 to 15% of all cancers
  • High prevalence in sarcomas
DNA Damage Induced Immune Stimulation
  • Activation of cGAS/STING
  • IO combination

Inhibitors of the DDR

Tumor cells require DNA mutations for disease progression and switch off DDR components to promote cancer development. However, this makes cancer cells reliant on remaining DDR pathways to keep DNA damage below the toxic levels that trigger cell death.

This delicate balance makes tumor cells much more vulnerable than normal cells to inhibitors of DDR proteins. In this way, by targeting selective DDR processes, our technology aims to kill cancerous cells and treat malignant disease while leaving healthy cells intact.

Unmet Need

Despite significant advances in oncology therapeutics, DNA-damaging modalities, such as chemotherapy and radiation therapy continue to be the most used treatment strategies across a wide range of cancer types. Unfortunately, these treatments come with limitations and a substantial proportion of cancers either fail to respond or acquire resistance over time.


Current DNA-damaging therapies are toxic to normal tissue

An inability to distinguish between cancerous and normal tissue yields toxicity, limits ability to dose, and compromises efficacy


Resistance to current anticancer agents, including PARP inhibitors

Up to 50% of patients with BRCA-deficient tumors fail to respond to PARP inhibition, the standard of care in many advanced cancers. Those who initially respond will eventually develop acquired resistance and the treatment will ultimately fail


Dependence on DDR-driven processes

In approximately 10% to 15% of all tumors, telomeres—specialized structures that protect chromosome ends from progressive degradation—are extended through the DDR-driven ALT pathway and are able to achieve replicative immortality. Many ALT-positive tumors are associated with poor prognosis and have a lack of targeted therapies


Limited ability to reach the immune system

A substantial portion of malignant disease is not amenable to immunotherapy, a strategy that has been proven to be highly effective in treating select cancers

Our portfolio exploits the totality of the DDR to address cancers with significant unmet needs.



Our DcoDeR platform allows us to exploit the totality of DDR opportunities through:

  • Understanding disease biology
  • Identifying novel targets
  • Developing new medicines
  • Selecting and treating patients who will benefit most

DcoDeR: A World Class DNA Damage Response Discovery Platform