AP-002 is a novel, orally bioavailable gallium based small molecule NCE. In contrast to currently available bone modifying agents, AP-002 uniquely has both anti-bone resorption and direct anti-tumor cell killing activity. This positions it ideally to treat cancer metastatic to the bone. Bone metastases often result in severe pain, spinal cord compression and cancer-induced bone fractures, collectively referred to as skeletal related events (SREs). A life threatening consequence of cancer induced bone resorption is hypercalcemia of malignancy.
The present treatments for cancer-induced bone resorption conditions are either bisphosphonates (e.g. zoledronic acid; Zometa®) or the anti-RANKL MAb, denosumab (Xgeva®). Both have undesirable side effects, both need administration by healthcare professionals (intravenous or subcutaneous), and neither of them have direct anti-tumor activity. In a recent large (4,500 patient) placebo controlled trial in breast cancer, denosumab failed to improve survival.
Preclinical studies show that AP-002 selectivity inhibits osteoclast differentiation and bone resorption, with a different mechanism of action from other anti-bone resorption agents. In addition, the preclinical studies have also shown that AP-002 promotes the growth of osteoblasts (the bone forming cells). Unlike other anti-bone resorption agents, AP-002 has been shown in in vitro and in vivo studies to have direct anti-tumor activity. Additionally, studies demonstrate that AP-002 is synergistic in combination with a range of other anti-tumor agents. Therefore, AP-002 is ideally positioned to be developed as an oral anti-cancer drug that inhibits bone resorption, that could be adjunctive to other anti-cancer therapies. Altum also intends to develop AP-002 in non-cancer bone resorption indications, such as severe osteoporosis.
The AP-002 US IND is approved and its Phase 1-2 trial in solid tumors with bone metastases or at risk of bone metastases is planned to start Q1 2019. Focus in the Phase 2 part of the trial will be on breast, lung and prostate cancers.
- Wang et al. 2018: AP-002: A novel inhibitor of osteoclast differentiation and function without disruption of osteogenesis. American Society Bone & Mineral Research (ASBMR) Annual Conference 2018