Jennerex
Jennerex Biotherapeutics, Inc. was an American private biopharmaceutical company that developed the oncolytic viruses JX-594 and JX-929 among others. By creating oncolytic viruses that can kill tumor cells directly through lysis, activate the immune system by delivering genes that encode immunostimulants and by overcoming tumor cell-induced immunological tolerance, and reduce tumor nutrient supply through the destruction of blood vessels, Jennerex aimed to create a novel approach to treating and possibly curing cancer.
Company
Jennerex received its name in honor of Edward Jenner, the pioneer of the smallpox vaccine and "the father of immunology".Locations
Headquarters are located in the Financial District, San Francisco. R&D and manufacturing operations are located at the UCSF Mission Bay campus in San Francisco, at the Ottawa Hospital Research Institute in Ottawa, Ontario, Canada, and at SillaJen, Inc. in Busan, South Korea.Company History
2003. Jennerex, Inc. was established.2007. Jennerex completed Pexa-Vec Phase 1 clinical trial.
2008. Jennerex initiated Pexa-Vec Phase 2a clinical trial.
2009. European Medicines Agency designated Pexa-Vec as an orphan drug for Live Cancer.
2011. Jennerex initiated Pexa-Vec Phase 2b clinical trial for Liver Cancer.
2013. US FDA designated Pexa-Vec as an orphan drug.
2014. SillaJen acquires Jennerex, Inc. SillaJen changed its name after the acquisition to SillaJen Biotherapeutics.
Pipeline
Oncolytic viruses developed by Jennerex are based on the vaccinia virus.Pexa-Vec (Jx-594)
Pexa-Vec is an engineered oncolytic virus that selectively destroys cancer cells and induces tumor immune response. Uncontrolled cell division, inactivation of the interferon pathway that is necessary to defend against viral infections, and constitutively active EGFR-Ras signaling pathway, are common features of cancer cells. These features enable rapid replication of the JX-594 virus and lysis of the host cancer cells. Deletion of thymidine kinase from the JX-594 genome prevents virus replication in normal cells. The immunostimulatory cytokine GM-CSF is produced from the JX-594 genome following infection, inducing immune response against both the virus and the tumor and enabling lasting tumor immunity. Finally, JX-594 reduces nutrient supply to tumors through blood vessel destruction. Because JX-594 is based on the Wyeth strain vaccinia virus that is commonly used for vaccination, it is well tolerated by rats, rabbits, and humans.Design
To engineer JX-594, human GMCSF gene and lacZ gene were inserted into the TK gene in the J segment of the Wyeth strain vaccinia virus. Elimination of TK from the JX-594 genome restricts viral replication to tumor cells, whereas GM-CSF production facilitates tumor immune response against, and β-gal is included for virus tracking purposes.Efficacy
Initially, it was demonstrated that patients with refractory melanomas who received intratumoral injection of JX-594 had mixed, partial, or complete responses.Upon comparison of intravenous delivery of JX-594 to intratumoral injection in immunocompetent liver cancer model in rabbits over 7 weeks, it was found that the i.t. treatment reduced the average primary tumor volume from 425 cm3 in control animals to 20 cm3 in i.t.-treated animals, and to 35 cm3 in the i.v. treatment group. Furthermore, the average number of lung metastases was reduced from 17 in control animals to 0.5 in i.t.-treated animals and none in the i.v.-treated animals.