An oncolytic virus for tumors of different etiology presenting defects in interferon signaling, designed as a potent, specific and safe therapy.  Promising in-vivo murine melanoma model shows potential for development as a mono or an add-on to chemotherapy or check-point inhibitors.

UNMET NEED
On Nov. 2015 the FDA approved the first oncolytic virus based treatment. Oncolytic viruses are a promising category of anti-cancer therapeutic agents that have a dual action: 1) kill cancer cells directly and specifically and 2) stimulate of anti-tumor immunity. Viral characteristics such as size, genome composition, lytic abilities etc. determine the interactions of oncolytic viruses with cancer cells. There is a need for an oncolytic virus with markedly different characteristics to target tumors which do not respond to current viral- and/or immune-therapies.

VIRUS DEVELOPMENT
Directed evolution enabled to develop the oncolytic virus, EHDV-TAU. A clone of the epizootic hemorrhagic disease virus selected on interferon-defective human prostate cells. The directed evolution process increased the viral replication by 10E7 (10 million fold) on this subset of human prostate cancer cells. Virus was tested on multiple tumor models. Infection of tumors is inversely correlated to IFN/JAK/STAT signaling.

INTELLECTUAL PROPERTY
On June 2017 Ramot filed a provision patent application on the novel viral agent and its use in the treatment of cancer, specifically cancer presenting a defective antiviral response.

DIFFERENTIATION FROM THE ONCOLYTIC VIRUS GOLD STANDARD
EHDV-TAU has some unique immunological and molecular features in comparison to the oncolytic virus gold standard:

REFERENCES
In vivo studies showing abscopal effect, virus-induced secretion of immunostimulatory chemokines, increased tumor infiltration of cytotoxic T cells. In addition to analysis of susceptibility determinants to EHDV-TAU. Dellac S, Ben-Dov H, Raanan A, et al. Constitutive low expression of antiviral effectors sensitizes melanoma cells to a novel oncolytic virus. Int J Cancer. 2021;148(9):2321-2334. doi:10.1002/ijc.33401

Two modes of cell death induction: Interleukin-6 and Interferon-α Signaling via JAK1-STAT Differentially Regulate Oncolytic versus Cytoprotective Antiviral States. Danziger O, Pupko T, Bacharach E, Ehrlich M. Front Immunol. 2018 Jan 30;9:94. doi: 10.3389/fimmu.2018.00094. eCollection 2018.
Viral Selection: Combined genetic and epigenetic interferences with interferon signaling expose prostate cancer cells to viral infection. Danziger O, Shai B, Sabo Y, Bacharach E, Ehrlich M. Oncotarget. 2016 Aug 9;7(32):52115-52134. 
Manipulation of cells by virus: Shai, B., et al., Epizootic hemorrhagic disease virus induces and benefits from cell stress, autophagy, and apoptosis. J Virol, 2013. 87(24): p. 13397-408.