Pipeline
Turning “cold” tumors “hot”.
Stimulation of the immune system using anti PD-1 antibodies, known as checkpoint therapy, significantly improves survival in some cancers, e.g. melanoma and NSCLC. However, most tumor types don’t respond to checkpoint therapy, with a best case single agent response rate of between 20% and 40%. Activating the immune system can stimulate tumor neoantigens and the priming of T cells, turning “cold” tumors “hot”. Highlight believes BO-112 has a unique ability to modify tumor-intrinsic pathways and the immune system to make tumors more sensitive to IO therapies. BO-112 in combination with anti-PD1 antibodies has shown potent & durable clinical responses in patients not responding to anti-PD1 antibodies.
Infographic: Fundamentium
BO-112 - a potent Immunotherapy
BO-112 is a synthetic dsRNA complex targeting dsRNA-binding proteins like cytosolic helicases MDA5 and RIG-I and toll-like receptor TLR3. It has a unique, multi-target approach to turn cold tumors to hot and therefore visible to the immune system.
Compelling preclinical data has shown evidence of superiority as a single agent in several tumor models, with meaningful responses across several indications in hard-to-treat patients. It has demonstrated a favorable safety profile both as a monotherapy and in combination with anti-PD1 antibodies.
Extensive development program in wide range of tumors
BO-112 is being explored as a monotherapy and in combination as part of an extensive development program, both in-house and led by external investigators in different settings.
A successful Phase 1 clinical trial as monotherapy and a successful phase 1b clinical trial in combination with anti-PD1 have been completed. A Phase 2 combination trial is expected to begin in 2020. Highlight has signed a collaboration with Merck & Co for the Phase 2 evaluation of combination therapies of BO-112 and KEYTRUDA® in patients with select advanced stage solid tumors with liver metastases.
A number of investigator-led trials to explore combinations of BO-112 with checkpoint inhibitors in other indications are planned or underway, with partners including UCLA, California; Manchester University Christie Hospital, UK; and Clinica Universitaria Navarra, Spain. Initial clinical results were presented by Dr. Marquéz-Rodas at the 2018 Congress of the European Society for Medical Oncology.
Highlight Therapeutics is working to understand the key aspects of the mechanism of action of BO-112, particularly in settings where immune checkpoint inhibitors are not effective. Results showing that BO-112 restores sensitivity of JAK1-deficient tumors to adoptive cell transfer were presented by the research group of Dr. Toni Ribas at the 2018 Congress of the Society for Immunotherapy of Cancer.
