PIPELINE

Other assets

Oncology Venture - LiPlaCis

Other pipeline assets

Besides Dovitinib, 2X-121, and Ixempra, Oncology Venture has several other pipeline assets as listed on this page.
  • LiPlaCis® 
  • 2X-111
  • Irofulven
  • APO010

LiPlaCis®

LiPlaCis® is an intelligent, target controlled liposome formulation of one of the world’s most widely used chemotherapeutic agents, cisplatin, which has documented efficacy in numerous tumor types.
The specific LiPlaCis formulation allows delivery of LiPlaCis directly to the tumor site where is it needed.
Therapeutic Target Annual Diagnoses (est.)
Metastatic breast cancer
Prostate cancer 1.3 million (worldwide)
Lung cancer 2.1 million (worldwide)
Head and neck cancer 865,000 (worldwide)
Bladder cancer 549,000 (worldwide)
Ovarian cancer 295,000 (worldwide)

How it Works

LiPlaCis, a target controlled liposome, enables a more selective up-take of cisplatin at the tumor site. Once it has accumulated in the cancer tissue, the drug is broken down by secretory phospholipase A2 (sPLA2), an enzyme present on tumors. The lipid composition of LiPlaCis is tailored to be specifically sensitive to degradation by the sPLA2 enzyme and thereby for release of the encapsulated cisplatin.

Clinical Trials

A Phase 2 clinical trial of LiPlaCis is ongoing in Denmark for the treatment of metastatic breast cancer. In October 2018 this trial was expanded to include prostate cancer patients, increasing the planned study cohort from 30 to 50 patients. The aim of this study is to identify the breast and prostate patient populations relevant for submitting a Marketing Authorization application. 

Response to a registration route has been received by FDA (505(b)(2)). OV has received IDE approval and are in discussions of the clinical trial design of the IND.

References
  1. A partial remission is defined as a >30% reduction in tumor size as measured in one dimension by CT scan. A 30% reduction measured in only one dimension is equivalent to an estimated 66% reduction in total tumor size, since the tumor will not only have been reduced in length (one dimension) but also in height and depth. Thus, on average the tumor is reduced to 34% of its initial size, or less (0.7 x 0.7 x 0.7 * 100% = 34%).

LiPlaCis DRP

The Cisplatin DRP was validated in multiple studies, including:

On 15 August 2018, the LiPlaCis DRP was granted IDE approval by the FDA.

History and Funding

Oncology Venture in-licensed LiPlaCis from LiPlasome Pharma in 2016.  The technology behind this product candidate was originally developed by scientists from Danish Technical University (DTU).

Development of LiPlaCis is funded in part by a 2016 EUROSTARS grant, with additional funding from Smerud Medical Research.

Equipment from Oncology Venture’s labs.

2X-111

2X-111 (Glutathione-enhanced, PEGylated Liposomal Doxorubicin)
Therapeutic Target Annual Diagnoses (est.)
Brain metastases from breast cancer TBD
Glioblastoma multiforme 50,212

How it Works

This novel drug candidate is designed for the liposomal delivery of the anti-cancer drug doxorubicin directly to a tumor, with a glutathione coating added to exploit active endogenous transporters, allowing the drug to cross the blood-brain barrier.

Doxorubicin is an anthracycline that inhibits the growth of many cancerous cell lines, including glioblastoma and breast cancer cell lines.  It is among the most widely used anti-cancer agents.

Clinical Trials

Phase 2 clinical studies have been prepared, using a validated DRP companion diagnostic in patients with brain metastases from breast cancer and recurrent glioblastoma multiforme (GBM).

2X-111 has been granted orphan drug designation by the U.S. Food and Drug Administration.

In a prior clinical trial conducted without a DRP, 2X-111 demonstrated encouraging efficacy and safety. Observed response rates in this Phase 2 study in brain metastases from breast cancer included 67% disease control.  Use of the validated DRP for 2X-111 in future trials is expected to result in improved efficacy.

2X-111 DRP

An abstract on the predictive ability of the DRP in treating advanced breast cancer with a similar anthracycline, epirubicin, was presented in a poster session at the 2017 American Society of Clinical Oncology Annual Meeting. The abstract describes a retrospective-prospective blinded study which evaluated the ability of the DRP to predict the efficacy of epirubicin in a cohort of 135 metastatic breast cancer patients.  The DRP was significantly associated with progression free survival in this study.  The estimated median time to progression for a patient with a DRP value of 25% was 7 months, versus 13 months for a patient with a DRP value of 75%.

History

2X-111 (formerly 2B3-101) was in-licensed from 2-BBB Medicines B.V.

A molecular model of doxorubicin. 2X-111 is is designed for the liposomal delivery of doxorubicin directly to a tumor.

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.

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.

History

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.

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

APO010

APO010 is a novel, investigational systemic chemotherapeutic treatment targeting multiple myeloma,  a systemic malignancy in the blood that affects plasma cells.

This recombinant, soluble, hexameric fusion protein consists of three human Fas ligand (FasL) extracellular domains fused to the dimer-forming collagen domain of human adiponectin. It has potential pro-apoptotic and antineoplastic activities.
Therapeutic Target Annual Diagnoses (est.)
Multiple myeloma 160,000 (worldwide)

How it Works

The human immune system can kill cancer cells using a certain type of white blood cells called cytotoxic T lymphocytes (CTLs). One way CTLs kill cancer cells is programmed cell death (apoptosis). A Fas ligand (FasL) on the CTL binds to a death receptor (CD95) on the target cell. This triggers apoptosis. 

APO010 is synthesized as a mega FasL consisting of six FasL.  The target cell recognizes this as if it were a CTL that binds to the death receptor, triggering apoptosis of the target cell.

APO010 is expected to act in synergy with other cancer immunology agents such as ipilimumab and PD-1/PD-L1 inhibitors.

Clinical Trials

A Phase 1/2 clinical trial of APO010 is ongoing in Multiple Myeloma (MM) according to plan. In MM, the tumor cells are only available by laboratory separation from other bone marrow cells. The APO-010 DRP® result is influenced by the tumor cell collection procedure, which varies across hospitals. Oncology Venture is currently comparing these collection methods to get the right calibration. No responders have so far been identified in the trial.

In a Phase 1 study in 25 patients with solid tumors, APO010 was well tolerated.

APO010 was found to be highly efficient in multiple myeloma in pre-clinical studies.

APO010 DRP

Validation of the APO010 DRP is underway in the ongoing Phase 1/2 clinical trial. 

History

Oncology Venture in-licensed APO010 from Onxeo (previously TopoTarget) in 2012. The drug candidate was originally designed by professor Jurg Tschopp in Lausanne and developed by Apoxis SA. 

Publications

Equipment from Oncology Venture’s labs.