WBI-2100: A Novel Anti-cancer Compound with Neutropenia-prevention Activity

WBI-2100 is being developed by Welichem as a treatment for solid cancers both as a monotherapy and synergistically in combination with other chemotherapies. In addition, WBI-2100 boosts neutrophil levels and prevents chemotherapy-induced neutropenia (CIN). There are no other anti-cancer drugs possessing such dual activities.

Preclinical Anti-cancer Efficacy:

WBI-2100’s anti-cancer activity has been demonstrated in various mouse tumour models (lung, breast, kidney, liver, pancreas, ovarian cancers and melanoma) both as a monotherapy and as a synergistic combination-therapy with Cisplatin, Taxol, Gemcitabine, or Dacarbazine. In a melanoma model, more than 80% tumour growth inhibition was achieved when combining WBI-2100 with Taxol compared with approximately 40% with Taxol alone. More importantly, no obvious adverse effects, such as neutropenia was observed in the mice treated with WBI-2100.

Unique Modes-of-Action:

Cancer is a heterogeneous disease comprised of cancer cells that are themselves biologically diverse. Compounds possessing multiple modes of action can potentially be very effective anti-cancer drugs.

The cytotoxicity of WBI-2100 has been demonstrated to be selective for solid cancer cells over hematological cancer cells. When tested on the National Cancer Institute’s panel of 60 cancer cell lines, its LC50 was significantly lower (approximately 100 fold) for all solid cancer cell lines than that of leukemia and lymphoma cell lines.

WBI-2100 has been shown to be anti-angiogenic in vitro and in vivo. Angiogenesis plays a critical role in solid tumour growth and invasion. Various anti-angiogenesis drugs have been developed recently, and they all need to be combined with other chemotherapeutic drugs to be effective in the clinic. It appears that WBI-2100 possesses both anti-angiogenesis and anti-cancer activity. In vitro, WBI-2100 induces apoptosis in human umbilical vein endothelial cells (HUVEC) cells and inhibits vascular network formation (tube formation) of HUVEC cells at sub-toxic doses. Using an in vivo Matrigel plug assay, WBI-1001 was able to block FGF-induced angiogenesis in mice in a dose-dependent manner.

WBI-2100 has strong anti-metastasis activity. Metastasis causes more than 90% of human cancer deaths. In vitro, using Boyden chamber assay, WBI-2100 strongly inhibited tumour cell invasion at sub-toxic concentrations. In vivo, dose-dependent inhibitory effects on both lung and breast cancer metastasis have been demonstrated.

Neutrophil Stimulatory Activity:

Chemotherapy induced neutropenia (CIN), which refers to abnormally low levels of neutrophils in the circulating blood and creates a substantial risk of life-threatening infection, is a common side effect of cancer chemotherapy. When patients experience neutropenia during chemotherapy, their scheduled treatment may have to be delayed or the doses reduced, thus exposing the patients to a lower chance of survival or cure of the cancer.

In contrast to other chemotherapy drugs on the market, other than its anti-cancer activity, WBI-2100 has a unique property of boosting neutrophils in different animal species. Such stimulatory effects are specific for neutrophils, and other hematopoietic cells are not affected by the WBI-2100 treatment. More interestingly, when WBI-2100 is combined with the chemotherapeutic drug cyclophosphomide, chemotherapy-induced neutropenia is prevented. These combined activities of WBI-2100 as a novel cancer drug candidate that also stimulates neutrophils suggests that it has the potential of being a unique cancer chemotherapy that negates the serious side effects normally experienced by patients undergoing cancer chemotherapy. In theory, by having the unique dual activity, WBI-2100 can be combined with any chemotherapeutic cancer drugs to increase other drug’s anti-cancer efficacy and at the mean time to prevent or treat the CIN. WBI-2100 could potentially be developed as a small molecule treatment for CIN. The only drugs available on the market are the biologics, Neupogen and Neulasta. Both of which are recombinant hematopoietic growth factors. Depending on the receptors expressed by the target cancer cells, Neupogen and Neulasta may stimulate cancer cell growth and thus potentially reduce the anti-cancer efficacy of the chemotherapy drugs when treating CIN. As a small molecule and an anti-cancer drug, WBI-2100 is obviously advantageous to treat CIN.