Advancing Research in Hepatocellular Carcinoma

HCC is the sixth most common cancer worldwide and the fourth leading cause of cancer-related death.¹ It accounts for roughly 80% of all primary liver cancers, and the number of new cases is expected to double between 2022 and 2050 — a trajectory driven largely by the persistent global burden of hepatitis B and hepatitis C, along with rising rates of obesity, tobacco use and alcohol consumption.^2,3

But scale alone does not explain why progress has been so elusive. HCC develops within a uniquely immunosuppressive tumor microenvironment that can prevent immune cells from mounting an effective response. At the same time, many patients have underlying liver dysfunction, narrowing the therapeutic margin and making broad immune activation especially difficult to manage.

This has created a persistent scientific challenge: how can a treatment distinguish liver tumor cells from healthy tissue, direct immune activity into the tumor, and limit activation elsewhere in the body? It’s a question the field is still working to answer — and one that is shaping how new approaches to HCC, including BeOne’s own investigational work, are being designed.

Meaningful progress will require sustained investment in understanding the tumor microenvironment, in designing therapies with the full clinical reality of liver disease patients in mind, and in generating the rigorous clinical evidence needed to determine what actually works — and for whom.

BeOne approached this question by first asking what a therapy would need to do differently in HCC specifically, rather than starting from a modality already validated in other tumor types and adapting it to liver cancer. That thinking shaped one investigational approach: a bispecific antibody designed to simultaneously engage a tumor-selective antigen and a co-stimulatory immune receptor, with molecular features intended to limit the systemic immune activation that has affected the safety profile of earlier immunotherapy strategies in this setting. It is administered intravenously, which is an important practical consideration for patients with HCC (who are often treated in community settings rather than specialized academic centers, and for whom complex or intensive administration procedures may not be feasible). It reflects one hypothesis about what HCC may require, grounded in the broader idea that progress here is more likely to come from approaches purpose-built for the disease’s biology than from strategies proven elsewhere.

BeOne is pursuing these questions in HCC as part of a purpose-built solid tumor strategy that matches scientific approach to disease need.

Across the portfolio, that means concentrating on areas where differentiated biology, modality and development capabilities may create meaningful possibilities for patients. The work is still evolving, but it represents the kind of disease-specific thinking needed to challenge a cancer that has repeatedly resisted innovation.

The path forward for HCC will be built through sustained oncology research, rigorous clinical evidence, and a willingness to pursue difficult scientific questions, ultimately building an evidence base that will determine whether a new generation of therapeutic strategies can change what an HCC diagnosis means for patients.