NB-A002

Targeting DNA Repair Vulnerabilities in Cancer

NB-A002 is a potentially first-in-class small molecule designed to target cancers that resist today’s standard treatments.

Built for DNA damage response (DDR)–deficient, especially homologous recombination deficiency (HRD) tumors, it introduces a groundbreaking strategy to selectively eliminate cancer cells while sparing healthy tissue.

The Challenge — HRD-Positive Cancers Remain Difficult to Treat

Cancers with homologous recombination deficiency (HRD) often develop resistance to:

PARP inhibitors
Platinum-based chemotherapy

This leads to limited treatment options and poor patient outcomes.

The Approach — Synthetic Lethality

NB-A002 Targets ILF2 to Disrupt Cancer Cell Replication

NB-A002 is an orally active small molecule that:

Binds to the ILF2 protein
Disrupts DNA stability mechanisms
Increases stress during cancer cell replication

This triggers transcription–replication conflicts, pushing already vulnerable cancer cells beyond repair.

Why It Matters — Selectivity by Design

Targeting Weaknesses Unique to Cancer Cells

Cancer cells with DDR and HRD defects:

Cannot repair additional DNA damage
Become highly sensitive to NB-A002

Preclinical models show:

Selective tumor cell killing
Minimal impact on normal cells with intact repair systems

In-vitro response of HRD-positive lung cancer cells to NB-A002 and talazoparib

In-vitro colony-formation in HRD-signature lung cancer cells.
Left: representative plates after 7 days’ exposure. Right: quantified colony counts and colony area. Talazoparib (0.1–10µM), a potent PARP inhibitor, showed no reduction in colony number; NB-A002 (0.1–10µM) reduced colonies in a concentration-dependent manner; n= biologic replicates

Progressing Toward the Patients

NB-A002 is currently in IND-enabling studies, including

Pharmacokinetics

ADME profiling and drug metabolism studies

Toxicology

GLP-compliant safety assessments

Dosing Studies

NOAEL determination for clinical trials