Oncology Venture - Irofulven
This drug candidate is a synthetic drug candidate based on a naturally occurring substance that exploits a deficiency in the DNA repair mechanism of cancer cells in a manner similar to a PARP inhibitor.
Therapeutic Target Annual Diagnoses (est.)
Metastatic castration-resistant prostate cancer TBD

How it Works

Irofulven alkylates DNA and protein macromolecules, forms adducts, and arrests cells in the S-phase of the cell cycle. This agent requires NADPH-dependent metabolism by alkenal/one oxidoreductase for activity.

The compound is more active in vitro against tumor cells of epithelial origin, and is more resistant to deactivation by p53 loss and MDR1 than other alkylating agents.

Clinical Trials

OV is running a single arm, open label Phase 2 Study of Irofulven for treatment of metastatic castration-resistant prostate cancer.  This study aims to enroll up to 27 men with metastatic castration-resistant prostate cancer who have previously been treated with docetaxel and who have been identified by the DRP as having a high likelihood of response to Irofulven.

Irofulven has been evaluated in 19 clinical trials, predominantly in refractory prostate and ovarian cancer patients and all conducted without DRP-guided patient selection. Results were positive, including a 10% response rate in patients with prostate cancer previously treated with docetaxel and 13% in ovarian cancer patients relapsing between 6 and 12 months after standard treatment with carboplatin and paclitaxel, but were not deemed sufficient for regulatory approval by the previous owner of the drug.

The ongoing and planned studies using the Irofulven DRP are expected to significantly improve response rates seen in prior studies.

A molecular model of irofulven. Irofulven is a semisynthetic sesquiterpene derivative of illudin S, a natural toxin isolated from the fungus Omphalotus illudens.

Irofulven DRP

Oncology Venture has developed an irofulven responsive predictor which is based on gene expression data by comparing associations between gene expression profiles and growth inhibition in a panel of cell lines treated with irofulven. A second step has included filtering the identified gene expression profile against mRNA expression from a collection of 3200 human tumors. Only genes being differentially expressed in the clinical tumor material were retained in the model. A total of 205 mRNA’s were selected for the final irofulven responsive profile. The profile can be converted to a single score of predicted irofulven responsiveness, which allows Oncology Venture to track, match and treat the patients who are most likely to benefit from the drug.


Oncology Venture in-licensed irofulven from Lantern Pharma in May 2015. The irofulven project was granted $800,000. USD from Massachusetts and the Danish Swedish Medicon Valley Alliance.