The EDV is a platform technology and has the potential to address multiple solid tumor indications. Currently EnGeneIC is conducting clinical studies in the following areas.
- Cerebral EDV for Recurrent glioma. A recent Phase 1 trial in recurrent glioma has shown safety and promising increased overall survival using EGFR targeted EDVs carrying doxorubicin. Subsequently, an IND has been accepted by the FDA to initiate a Phase I/IIa trial at major hospitals in the US.
- Mesomir Advanced mesothelioma (malignant pleural mesothelioma, MPM). A Phase I study is currently underway in Sydney, Australia. The EDVs are targeted with EGFR and carrying a microRNA, called mir-16a. This RNA molecule which is a regulator of gene expression and cell growth, is lost in MPM, and replacement therapy with mir-16a has the potential to normalise aberrant cell growth.
- Tailored EDV trial. This “intention to treat” trial is aimed at better informing us as to which tumor indications will respond best to EDV-based therapeutics. Patients who have run out of curative treatment options can be treated with EDVs carrying different payloads. For example, Adrenal Cell Carcinoma (ACC) which occurs in young adults, is unresponsive to chemotherapy and has a very grim prognosis. In pre-clinical animal studies, we found that ACC tumors are sensitive to a gene silencing molecule, siRNA, which turns off Ribonucleotide reductase M1 (RRM1) and subsequently prevents DNA replication and cell division. Other tumors that will be considered include metastatic colorectal cancer and triple negative breast cancer.
- Kid EDV trial. This Phase I trial in children with recurrent or refractory neurological or solid tumors will test EGFR-targeted EDVs carrying mitoxantrone. It is expected to commence in Sydney, Australia, in early February 2016.
Proprietary drugs. In early stage trials most patients enrolled have had multiple lines of chemotherapy and are generally chemo-resistant. We are developing our own drugs which are highly toxic and cannot be given systemically but are safe when delivered via the EDV. In laboratory tests and in animal models, these drugs prove to be up to 1000x more potent than conventional chemotherapy and are able to totally overcome drug resistance. One of these drugs is undergoing toxicology screens and if safe will be committed to the tailored EDV trial.
Next generation EDV-therapeutics. We and our collaborators are working on a number of product candidates for intractable tumors such as pancreatic cancer, as well as new antibodies to target tumors other than EGFR. We are also investigating ways in which to enhance the EDV-stimulated adaptive immune response in the majority of patients.