RX-5902

Potential First-in-Class Inhibitor of a key Protein that modulates Wnt/β-catenin

RX-5902 is a potential first-in-class small molecule inhibitor of phosphorylated-p68, which is selectively over-expressed in cancer cells and modulates the activity of the β-catenin/Wnt pathway which is involved in cancer cell growth and proliferation, oncogene expression and in the immune response to cancer.

Phosphorylated p68, which is highly expressed in cancer cells, but not in normal cells, results in up-regulation of cancer-related genes and a subsequent proliferation of cancer cells and tumor growth. RX-5902 selectively blocks the interaction of phosphorylated p68 with beta-catenin, thereby decreasing the proliferation or growth of cancer cells in preclinical models. Apart from its direct antitumor effects, RX-5902 is immunomodulatory and multiple preclinical models suggest that RX-5902 enhances the efficacy of immunotherapy. Rexahn has evaluated RX-5902 in a Phase 1 dose escalation study in patients with a diverse range of metastatic, treatment-refractory solid tumors, including breast, ovarian, colorectal, and neuroendocrine tumors. In February 2017, Rexahn initiated a Phase 2a clinical study of RX-5902 monotherapy in patients with metastatic triple negative breast cancer (TNBC). In August 2018, we announced a collaboration with Merck to evaluate RX-5902 in combination with Keytruda® in TNBC.

Candidate & Indication Collaborators Preclinical Phase 1 Phase 2

RX-5902

Metastatic Triple Negative Breast Cancer

Merck & Co.
Preclinical complete
Phase 1 complete
Phase 2 in progress

RX-5902 Mechanism of Action

Phosphorylated p68 (P-p68) is a key protein that modulates the Wnt/β-catenin pathway, a key biological pathway that promotes cancer cell growth and metastasis. P-p68 is abundant in tumor cells.

P-p68 plays a key role in promoting the transport of β-catenin from the cell cytoplasm into the nucleus. P-p68 forms a complex that 'chaperones' β-catenin across the nuclear membrane.

Once inside the nucleus, β-catenin turns on oncogenes (cancer genes) that promote proliferation and metastasis of cancer cells.

RX-5902 binds to P-p68 and disrupts the formation of a protein complex with b-catenin. This inhibits the transportation of β-catenin across the nuclear membrane and leads to a reduction in β-catenin in the nucleus.

With markedly reduced nuclear β-catenin, oncogenes are turned off in cancer cells, inhibiting tumor growth. Immune cells are then activated against the tumor cells - providing a two-pronged attack on the cancer cells.

Taking a Stand against Breast Cancer

~10-20%

Of breast cancer is triple-negative, testing negative for both hormone receptors and HER2.1

22 out of 10,000

Women ages 50-54 will be diagnosed with breast cancer in the next year.1

12%

Chance of Diagnosis of breast cancer within the lifetime of a woman living in the US.1

1 American Cancer Society

Clinical Development

Phase 1

RX-5902 was evaluated in a Phase 1 dose-escalation clinical trial in cancer patients with solid tumors designed to evaluate the safety, tolerability, dose-limiting toxicities and the recommended Phase 2 dose. Secondary endpoints include pharmacokinetic analyses and an evaluation of the preliminary anti-tumor effects of RX-5902. We completed enrollment in this study in 2016.

Updated results from the Phase 1 clinical trial of RX-5902 were presented in October 2016 at the 2016 European Society for Medical Oncology Congress.

The results showed evidence of single-agent, clinical activity of RX-5902. In this study, RX-5902 preliminarily appeared to be safe and well tolerated at the doses and dosing schedules tested with no dose-limiting toxicities or treatment-related serious adverse events. The most frequently reported drug-related adverse events were mild nausea, vomiting, and fatigue. Initial signs of clinical activity have been observed. Twenty-four subjects were enrolled (11 female, 13 male), and seven subjects experienced stable disease in breast, neuroendocrine, paraganglioma, head/neck or colorectal cancer. Three subjects received treatment for more than one year. Approximately 55% of the subjects had received four or more therapies prior to their enrollment in the Phase 1 clinical study.

Clinical Trials

Triple Negative Breast Cancer

The purpose of this Phase 2 portion of the study is to use the dose and schedule of RX-5902 identified in Phase 1 to treat subjects with triple negative breast cancer.

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Partnerships

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Publications

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