AB001: A Quantum Leap in Cancer Therapy

Pioneering a new wave of gene silencing immunotherapy:
tumor-agnostic, orally delivered, and clinically proven
to shrink tumors in 14 days.

AB001 is a tumor-agnostic, investigational small molecule currently in Phase II clinical trials.  AB001 introduces a multi-dimensional attack on cancer, integrating:

  •                                                               •  Pan-mutant KRAS inhibition
  •                                                               •  MicroRNA-based gene silencing and mRNA transcriptional repression
  •                                                               •  PD1-PDL1 inhibition

Pan-KRAS mutant inhibition

AB001’s interaction with pan-KRAS mutations involves both direct and indirect binding mechanisms, depending on the specific mutation and conformational accessibility.

Key Mutations with Direct Binding: G12C, G12D, G12V, G13D, G12R

Mechanism:

    • •  AB001 binds allosterically to the GDP-bound (inactive) conformation of KRAS.

    • •  The binding site is distinct from the GTP/GDP active site (orthosteric) and does not require covalent attachment (unlike G12C-specific inhibitors).

    • •  This pocket is often referred to as the switch-II pocket, and AB001 binds with binding affinities around -7 to -7.8 kcal/mol, depending on the mutant

miRNA-based Gene Silencing

mRNA transcriptional repression

 At the transcriptional level, AB001 binds in the binding pockets of RNA and blocks its transcriptional activity which leads to prevention of tumorigenesis. At the molecular level, AB001 alters micro-RNA (miRNA) and regulates its gene function.

Pathways Inhibited by AB001

Being a small molecule it easily transverses through the plasma membrane and targets multicellular pathways such as WNT/β Catenin, PI3K, MAPK pathway, which are mainly involved in cellular proliferation survival and resistance.

None of the currently available chemo drugs target cancer stem cells due to their slow-growing ability, fast differentiation and expansion, which are responsible for relapse and recurrence.

AB001 is the first small molecule that eliminates cancer stem cells from the root via the beta-catenin pathway and degrades them. Furthermore, toxicity studies prove the safety of the molecule making it a promising alternative candidate for chemotherapy.

AB001 PD1/PDL1 Inhibition

Direct Interaction and Degradation

AB001 acts as a PD-L1 immune checkpoint inhibitor and degrader. It binds to PD-L1 on tumor cells, disrupting its interaction with PD-1 receptors on T-cells. This blockade releases the T-cells from suppression, restoring their cytotoxic activity against cancer cells.

More uniquely, AB001 promotes PD-L1 degradation, not just inhibition. This induces internalization or proteasomal degradation of the PD-L1 protein by: (1) Tagging PD-L1 for ubiquitination, (2). Disrupting stabilizing interactions (e.g., with CMTM6)  (3) Altering PD-L1 mRNA expression and stability

Blockage of PD-1/PD-L1 interaction results in the reversal of the exhausted T-cell phenotype and normalization of antitumor response, providing the rationale of targeted therapy. It also stimulates B cells to secrete tumor-eliminating antibodies and inhibits the suppression of regulatory cells by Inhibiting IL-10 and TGF beta.

AB001 Overcoming Resistance

of Immune Checkpoint Inhibitors