A study by Cima University of Navarra and the biopharmaceutical company Highlight Therapeutics demonstrates in animal models that co-injection of the drug BO-112 and a STING protein agonist achieves local and distant antitumor efficacy. This is the conclusion of a preclinical work published in the scientific journal Journal for ImmunoTherapy of Cancer (JITC).

The results of an in vivo study in mice of intratumoral co-injections of BO-112 and the DXMAA agonist STING conducted by Cima confirm a synergistic efficacy capable of eradicating non-injected distant tumor lesions. data "These results are very encouraging and are in line with the positive results obtained in Phase II with the combination of BO-112 and anti-PD1 therapies," says Dr. Marisol Quintero, CEO of Highlight Therapeutics.

"For several years we have been collaborating with Dr. Ignacio Melero to better understand the mode of action of BO-112," notes Dr. Quintero. "The main goal is to achieve both local control of the disease and, more importantly, efficacy against distant tumor lesions. The work published in JITC sample that co-injections of BO-112 and a STING agonist make it possible to eradicate untreated distant tumor lesions. But there may also be other opportunities involving irradiation of locally injected lesions, so we hope to continue with this work".

Clinical application

"The combined intratumoral approach should be clinically feasible for application in patients, as both BO-112 and several STING agonists are being injected into patient tumors in various clinical trials. We have consistently observed synergistic therapeutic effects in a variety of transplantable mouse tumor models, showing complete regressions of injected and non-injected tumor lesions," confirms Dr. Ignacio Melero, researcher senior in Immunotherapy at Cima and co-director of department Immunology at the Clínica Universidad de Navarra.

The results published in Journal for ImmunoTherapy of Cancer add to the preliminary data presented at the Society for Immunotherapy of Cancer (SITC) in Washington, D.C. last November 12, on a Phase II study focused on intratumoral administration of BO-112 with pembrolizumab in patients with advanced melanoma presenting with progressive disease on anti-PD-1-based therapy.

Next steps in the clinical development of BO-112 include:

- The initiation of a pivotal Phase 3 study in 2nd line metastatic melanoma is planned for 2022 following discussions with US and European regulatory agencies.

- Highlight Therapeutics has initiated strategic association discussions with anti-PD1 companies interested in increasing their market potential with anti-PD-(L)1 agents in attempts to extend clinical benefit to new indications and lines of therapy.

- Initial data from a Phase 1B essay initiated by sponsor and conducted by UCLA evaluating BO-112 + pembrolizumab in anti-PD1-resistant hepatocellular carcinoma that is currently recruiting patients is expected in 2022.

-The Clínica Universidad de Navarra, at partnership with Highlight Therapeutics, will develop in 2022 a pioneering investigator-driven clinical essay combining intratumoral injection of BO-112 with radiotherapy in patients with metastatic lung cancer.

reference letter bibliographic

• J Immunother Cancer. 2021 Nov;9(11):e002953. doi: 10.1136/jitc-2021-002953.
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