BMS will carry out all clinical development of modified enadenotucirev virus therapy for solid tutors

Bristol-Myers Squibb (BMS) is paying PsiOxus Therapeutics $50 million upfront for exclusive rights to NG-348, the U.K.-based company’s preclinical-stage transgenic enadenotucirev virus candidate for treating solid tumors.

Under terms of the deal, which is still subject to antitrust clearance, BMS will shoulder global clinical development of NG-348, together with commercialization activities, and provide PsiOxus with funding to support continued preclinical development. PsiOxus could receive up to $886 million in development, regulatory, and sales-based milestones, plus sales royalties.

The NG-348 deal follows on from the firms’ clinical collaboration, announced in June, to evaluate PsiOxus’s oncolytic adenovirus therapeutic enadenotucirev, administered systemically in combination with BMS’s nivolumab (Opdivo) for the treatment of a range of tumor types. A Phase I trial is under way.

PsiOxus has developed NG-348 using its proprietary tumor-specific immuno-gene therapy (T-SIGn) platform. The anticancer candidate is an “armed” transgene-modified variant of the enadenotucirev virus, which is engineered to encode two membrane-integrated proteins—full-length human CD80 and a membrane-anchored antibody fragment specific for the T-cell receptor CD3 protein. PsiOxus claims that when these two proteins are expressed on the surface of NG-348-infected tumor cells, they provide T-cell receptor and costimulatory signals, which studies in human tumor xenograft models have demonstrated activate both CD4 and CD8 human T cells. Expression of the transgenes is controlled by an endogenous virus major late promotor, which only allows expression of the proteins on the surface of virus-infected tumor cells, and prevents off-target expression in healthy cells.

“NG-348 represents the first of our T-SIGn armed-viruses,” stated John Beadle, M.D., PsiOxus CEO. “We are thrilled to partner once again with Bristol-Myers Squibb, a leader in immuno-oncology, to drive this program into clinical development with the aim of providing a potential treatment to cancer patients.”

“PsiOxus has developed a novel platform of tumor-targeted delivery with oncolytic viruses focused on cancer,” added Fouad Namouni, M.D., head of development, oncology, at BMS “We are excited to bring our deep expertise in immuno-oncology to the continued development of NG-348 and to better understand the potential role of oncolytic viruses in enhancing checkpoint blockade in multiple types of cancer in the tumor microenvironment.”

PsiOxus claims the T-SIGn technology offers the potential to generate a broad range of systemically delivered oncolytic immune therapeutics, including oncolytic viruses that express one or more antibodies, cytokines, immunomodulatory proteins, or RNA-based cargos.

While the T-SIGn platform is in preclinical development, early-stage clinical trials are ongoing to evaluate unarmed enadenotucirev in different tumor types, either alone or in combination with chemotherapy or conventional chemotherapeutics, including  paclitaxel