At Highlight Therapeutics, we continue advancing our commitment to unlocking the full potential of immuno-oncology. On this occasion, together with the team at the Cima Universidad de Navarra, we have published positive results from a preclinical study in the journal Journal for ImmunoTherapy of Cancer (JITC) demonstrating the efficacy of combining BO-112 with a STING agonist.

These findings are particularly relevant because they show how this combination works synergistically to achieve both local and distant antitumor responses, further supporting the value of BO-112 as one of the most promising immunotherapies currently in development.

BO-112: awakening the immune response

Our investigational drug BO-112 is a double-stranded RNA agonist designed to activate the immune system and help it recognize and attack tumor cells.

In previous studies, BO-112 has shown efficacy when administered directly into the tumor—so-called intratumoral injection—and has been able to enhance responses in patients who did not respond to standard immunotherapy.

However, one of the limitations of intratumoral immunotherapy is that its effect often remains concentrated in the treated tumor, with less impact on distant lesions.

For this reason, in this new work we sought to explore how to enhance that systemic response by combining BO-112 with a second immune-activating agent: a STING agonist, a key molecule involved in the activation of innate immunity.

A synergistic combination

The study, conducted in preclinical models by the team at the Cima Universidad de Navarra, demonstrated that the coinjection of BO-112 and the STING agonist produced a synergistic effect capable of eliminating not only the treated tumor but also distant, non-injected tumor lesions.

This effect depended on the coordinated action of type 1 dendritic cells and CD8 T lymphocytes, as well as on the type I interferon signaling pathway and the function of STING in the host. Together, these mechanisms drive a stronger and more sustained immune response.

As our CEO, Marisol Quintero, highlighted: “These results, following the positive phase II data on the combination of BO-112 with anti-PD-1 therapies, are very encouraging. We collaborated with Dr. Melero to better understand the mechanism of action of BO-112. The main objective was to achieve both local disease control and, more importantly, efficacy against distant tumor lesions. The work published in JITC demonstrates that the coinjection of BO-112 and a STING agonist achieves synergistic efficacy capable of eradicating even untreated lesions.”

Dr. Ignacio Melero, senior immunotherapy researcher at Cima and co-director of the Department of Immunology at Clínica Universidad de Navarra, added:

“We believe this combined intratumoral approach is clinically feasible, as both BO-112 and several STING agonists have already been injected into human tumors in clinical trials. We have observed synergistic therapeutic effects in multiple animal models, with complete regression of both injected and non-injected tumors.”

Why this finding matters

These results reinforce the hypothesis that combining intratumoral immunotherapies can multiply their efficacy and offer a new therapeutic approach for resistant solid tumors.

The coadministration of BO-112 and a STING agonist could therefore become a strategy capable of inducing broader and more durable immune responses, with the potential to translate into future clinical applications.

Following this advance, we continue working to translate these preclinical findings into clinical studies in patients.

Our next steps include:

• The development of a pivotal phase III study in second-line melanoma
• The evaluation of new combinations with anti-PD-1 therapies in collaboration with strategic partners
• The publication of new clinical data from the UCLA trial evaluating BO-112 + pembrolizumab in PD-1–resistant hepatocellular carcinoma

Science translated into possibilities

Each discovery brings us closer to our purpose: awakening the immune system to transform the treatment of cancer.

In this regard, the joint work with the Cima Universidad de Navarra team is a clear example of how collaboration between basic science and clinical development can open new avenues for more patients to benefit from immunotherapy.