Adenovirus-based Cancer Immunotherapies: ONCOS-102

ONCOS-102 is Targovax’s lead adenovirus-based pipeline product – a purposefully engineered human serotype 5 adenovirus optimized to induce systemic anti-tumor T cell responses in cancer patients.

ONCOS-102 has completed a Phase I clinical study and is being tested in further combination clinical trials in several solid tumor indications:

  • Mesothelioma in combination with standard of care chemotherapy (enrolling patients)

  • Melanoma in combination with an immune checkpoint inhibitor (enrolling patients)

  • Ovarian and colorectal cancer in combination with an immune checkpoint inhibitor (enrolling patients)

  • Prostate cancer in combination with a dendritic cell vaccine (planned study)

ONCOS-102 showed encouraging Phase I efficacy data in a challenging patient population. In its Phase I clinical trial in heavily-pretreated patients with multiple types of solid tumors, ONCOS-102 demonstrated a stable disease (SD) rate of 40% in 10 evaluable patients.

  • Patient-level data demonstrate multiple immunotherapeutic mechanisms. The Phase I data showed a dramatic increase in tumor-infiltrating cytotoxic CD8+ T cells, innate immune system activation, and cancer specific CD8+ T-cells in blood indicating systemic activation of the immune system. Both the increase of innate immune cell infiltration and the increase of CD8+ T cells were correlated with overall survival.

  • Clean safety database in over 100 patients. A five-year compassionate use program has demonstrated an encouraging safety profile in 115 ONCOS-102 treated patients. Adverse events were mostly of grade 1 or 2. The ONCOS-102 Phase I study did not identify a dose-limiting toxicity.

  • Synergistic potential in combination usage. Preclinical data has shown synergistic effects between ONCOS-102 and chemotherapy (doxorubicin/ifosfamide). There is also compelling mechanistic rationale for combining ONCOS-102 with immune checkpoint inhibitors, which would benefit from ONCOS-102’s innate immune system activation, co-stimulatory effects and T cell activation, yielding a complete immunotherapeutic arsenal.

Magnus Jaderberg picture

Magnus Jaderberg
Chief Medical Officer, Head of Research & Development

We aim to develop ONCOS-102 in combination with standard of care chemotherapeutics in selected cancer indications. Combining ONCOS-102 with immune checkpoint inhibitors is also an intriguing opportunity which we are actively exploring.

Future development of Targovax’s Oncos oncolytic virus platform:

The Targovax team has significant experience in developing and manufacturing adenoviral constructs for clinical use.

When the development is completed, we will have an efficient discovery platform covering the whole path from construct design to clinical manufacturing using commercially validated methods. The Targovax platform provides unparalleled efficacy for taking constructs with novel engineered characteristics from sketch board to clinical development. When compared with the development of new antibodies, this Targovax discovery platform is much more time- and cost-effective.

Lukasz picture

Lukasz Kuryk
Director of Clinical Science

We have demonstrated that ONCOS-102 treatment can reinstate the immune system’s capacity to recognize and attack cancer cells, even in late stage cancer patients with low immunogenic tumor types.

ONCOS-102 & Its Mechanism of Action

ONCOS-102 is a purposefully engineered human serotype 5 adenovirus optimized to induce systemic anti-tumor T cell response in cancer patients.

In order to make ONCOS-102 even more powerful, it includes three engineered characteristics:

  1. The adenovirus knob protein targeting the virus into the host cells is replaced with a protein from different adenovirus (serotype 3) to facilitate the specific entrance of ONCOS-102 into tumor cells.
  2. One of the genes affecting virus replication in the host cells is inactivated (Δ24 deletion). As a result the virus cannot replicate in normal cells, but can do so in tumor cells.
  3. A gene coding for GM-CSF, a drug stimulating the immune response, is inserted into the virus genome and expressed during the virus replication in the tumor cells.
ONCOS-102 structure

Mechanism of action

ONCOS-102 MoA

Local ONCOS-102 treatment induces a unique, systemic anti-tumor immune response in patients. The mechanism of action has been established by systemically studying samples collected from patients before and after treatment with ONCOS-102.

  1. Local administration of ONCOS-102 in the tumor creates a danger signal inducing the production of inflammatory cytokines
  2. ONCOS-102 particles infect tumor cells and result in immunogenic tumor cell death and release of tumor antigens and new ONCOS-102 particles in the tumor microenvironment
  3. The combination of the production of inflammatory cytokines, release of tumor antigens, release of new ONCOS-102 particles and production of the co-stimulatory molecule GM-CSF attracts antigen-presenting cells to the tumor. These cells take up tumor antigens (and also ONCOS-102 antigens)
  4. Antigen-presenting cells (such as dendritic cells) migrate to lymph nodes with the antigens.
  5. In the lymph nodes, antigens are presented to T Cells. As a result the T Cells are activated to recognize cells expressing those antigens.

Activated T cells attack and kill tumor cells expressing the specific antigens. The effect is systemic.

Evidence for ONCOS-102 Mechanism of Action

ONCOS-102_MoA_1v2 ONCOS-102_MoA_2v2 ONCOS-102_MoA_3v2 ONCOS-102_MoA_4v2 ONCOS-102_MoA_5v2