At Highlight Therapeutics, we continue advancing toward our goal of turning research into real therapeutic options. For this reason, we are pleased to share the follow-up results from our phase IIb clinical study, in which we evaluated the combination of BO-112 with pembrolizumab (the anti–PD-1 therapy developed by MSD) in patients with advanced melanoma resistant to immunotherapy.

The data, presented at the 2022 Annual Meeting of the American Association for Cancer Research (AACR), confirm the potential of BO-112 as a new second-line therapy with high efficacy for these patients.

A major clinical challenge

Advanced melanoma remains one of the most aggressive and difficult cancers to treat. Although treatments based on PD-1 inhibitors have revolutionized immuno-oncology, fewer than 20% of patients achieve a durable benefit from these therapies.

This means there is still a significant unmet medical need: developing treatments capable of overcoming resistance to anti-PD-1 therapy and offering a new opportunity for patients who no longer respond to standard immunotherapy.

BO-112: reactivating the immune response

BO-112 is a double-stranded RNA agonist designed to activate the immune response against tumors.

Its objective is to resensitize tumors that have stopped responding to anti-PD-1 therapy, improving antigen presentation, promoting T-cell infiltration, and increasing the expression of molecules such as MHC-I and PD-L1 on tumor cells.

In this way, the immune system regains its ability to recognize and attack cancer, even in cases where it had previously lost this capacity.

Results exceeding the current standard

The study, conducted together with Merck (MSD outside the United States and Canada), included 42 patients with cutaneous, mucosal, and acral melanoma in France and Spain. All participants had experienced disease progression after previous treatment with PD-1 inhibitors.

With a median follow-up of seven months, the results show:

• an objective response rate (ORR) of 30% and a disease control rate (DCR) of 65%, compared with the 8–13% typically observed with second-line therapies
• 15% complete responses and durable responses in the majority of responding patients
• in cases of mucosal melanoma, a particularly difficult subtype to treat, a response rate of 66% and disease control of 100%
• a manageable safety profile, with no treatment discontinuations due to adverse events

These results represent a significant improvement over the current standard and reinforce the potential role of BO-112 as a reference second-line therapy for advanced melanoma.

A new opportunity for patients who had stopped responding

Our CEO Marisol Quintero highlighted the significance of these findings: “These data confirm that BO-112 is effective in resensitizing tumors and helping overcome resistance to anti-PD-1 therapy, opening the possibility of treating many more patients with immunotherapy. It is important to note that BO-112 achieved improvements even in patients who had initially responded to treatment before relapsing, and that in mucosal melanoma—a particularly complex form of the disease—we observed response and disease control rates that far exceed the current standard.”

What comes next

The potential of BO-112 extends beyond melanoma. Its mechanism of action suggests possible applications in other solid tumors resistant to immunotherapy, broadening its clinical relevance.

In this context, Highlight Therapeutics plans to initiate a new randomized phase II study in second-line melanoma in 2023, and has already begun discussions with other companies working in the PD-1 inhibitor field to explore strategic partnerships that could accelerate its development.

Moving forward

Each positive result brings us one step closer to our purpose: making immunotherapy an option for more patients.

With that goal in mind, we continue advancing with the same conviction that has guided us from the beginning—awakening the immune system to transform the treatment of cancer.