Betapharma’s Pipeline

Betapharma's vision is to become a leading drug discovery and development company by building a proprietary product pipeline of a pipeline of high-quality drug candidates to move into clinical development. We dedicate our research taking the full advantage of Betapharma Chinese drug R&D centers to complete pre-clinical and early clinical studies.

Mechanism of Action

Epidermal growth factor receptor (EGFR) signaling pathways consist of four known cellular receptors: HER1 (also known as EGFR), HER2, HER3, and HER4. Normally, these HER pathways are tightly regulated. In cancer, signaling through these pathways can increase, resulting in growth, proliferation, migration, and survival of cancer cells. This correlates with disease progression and poor prognosis.

Sheddases are enzymes, specifically ADAM enzymes 10 and 17, that promote growth activity through all four HER pathways. Several marketed therapies that target individual EGFR family members have demonstrated that inhibition of HER signaling is an effective mechanism for treating certain solid tumors.

Potential Benefits

Sheddase inhibition blocks two different pro-oncogenic mechanisms, generation of active EGFR ligands and generation of a constitutively active HER2 kinase.

Inhibition of additional and/or common HER pathways is expected to be synergistic with currently approved EGFR inhibitors and improve patient outcomes.
Sheddase can activate HER3 through generation of the HER3 ligand, heregulin. As this pathway is involved in resistance to current EGFR targeted therapies, decreasing the activity of this pathway with inhibitors of sheddase may be beneficial.

Our lead compound: INCB7839

Novel, potent, orally bioavailable.
In preclinical models: single agent efficacy; synergistic with other EGFR therapies; and synergistic with chemotherapy.

Clinical Status

Phase I completed in healthy volunteers:

INCB7839 was well-tolerated.
In a dose-dependent manner, INCB7839 decreased HER2 ECD levels, a clinically relevant biomarker.

A Phase II trial in HER2 positive breast cancer has begun and will be used to determine the effectiveness of INCB7839 in combination with Herceptin. Results from this trial are expected in the second half of 2009.