In cancer treatment, the challenge has always been how to destroy cancer cells without causing significant harm to normal cells. Is there a treatment approach that can achieve both effective tumor destruction and minimal collateral damage?

Over the past decade, antibodies targeting PD-(L)1 have ushered in an era of cancer immunotherapy. At the same time, antibody-drug conjugates (ADCs), often referred to as “intelligent biological missiles”, are reshaping the landscape of cancer treatment.

What happens when the two are combined?

HLX43 Phase I clinical data from Henlius, a biopharmaceutical innovation platform under Fosun, revealed that PD-L1 ADC demonstrated impressive anti-tumor activity and manageable safety in patients with advanced or metastatic solid tumors. The results were especially encouraging in patients with non-small cell lung cancer (NSCLC) and thymic squamous cell carcinoma (TSCC), showing promising initial efficacy.

So, what are PD-L1 ADCs, and what make them so special?

PD-L1: The Master of Disguise

To understand PD-L1 ADCs, it’s important to first know tumor immunotherapy.

T cells act as immune defenders, attacking abnormal or foreign cells. PD-1, their commander, decides whether to launch an attack.

Tumor cells use PD-L1 to camouflage themselves by binding to PD-1, preventing T cells from receiving attack signals and allowing tumors to grow unchecked.

PD-L1 inhibitors work like a security scan—unmasking PD-L1 and reactivating T cells to eliminate cancer cells.

ADCs: Intelligent Biological Missiles

ADCs, or antibody-drug conjugates, are a form of targeted therapy composed of three parts: an antibody, a linker, and a toxin.

What sets ADCs apart is their precision—they attack cancer cells while sparing healthy ones, greatly reducing side effects.

That’s why they’re called “intelligent biological missiles”: the antibody guides the drug to tumor cells, the linker carries and releases the payload, and the toxin acts as the warhead, delivering a lethal strike.

When PD-L1 Meets ADC

ADCs have long been seen as advanced versions of chemotherapy. But when combined with PD-L1, they offer something truly game-changing.

PD-L1 ADCs are like upgraded smart missiles, with stronger and more accurate “warheads” that combine the strengths of immunotherapy and targeted delivery.

Why is this pairing so effective? Because PD-L1 is a pan-tumor target found in many cancer types but rarely in normal cells, limiting off-target effects.

Moreover, PD-L1 can be internalized by tumor cells—meaning the ADC’s toxic payload can reach inside the cell for a more effective hit.

Can HLX43 transform the cancer treatment landscape?

Neither immunotherapy nor ADCs are new concepts. However, according to the Insight database, to date, there are only two PD-L1-targeted ADCs in the world that have entered clinical stage.

This is because developing a PD-L1 ADC is not as simple as just combining the two. It requires strong innovation capabilities and long-term accumulation of experience in pharmaceutical research and development (R&D).

Henlius’ HLX43 project was launched in May 2022. In just one and a half years, it produced clinical data that attracted worldwide attention. It is also the world’s first PD-L1 ADC to enter Phase II clinical trial.

At this year’s American Society of Clinical Oncology (ASCO) annual meeting, HLX43’s Phase I clinical data was released for the first time, demonstrating the molecule’s high efficacy, low toxicity, and manageable safety profile. The comprehensive technical advantages it has demonstrated, from antibody, linker to payload and drug loading, give HLX43 the potential to benefit patients who are unresponsive or resistant to Keytruda and Opdivo, as well as those who have failed chemotherapy and other treatments.

A differentiated strategy drives multiple “world’s first” achievements

HLX43’s impressive results are a testament to Fosun’s robust innovative R&D capabilities in the field of biopharmaceuticals.

Focusing on tumors and autoimmune diseases, Henlius’ current pipeline covers more than 50 molecules, including monoclonal antibodies, polyclonal antibodies, ADCs, fusion proteins, small molecule drugs and more.

A differentiated innovative R&D strategy, combined with efficient independent innovation capabilities, has enabled Henlius to achieve repeated breakthroughs in innovative drugs.

For example, Henlius’ flagship innovative product HANSIZHUANG has achieved a breakthrough in the treatment of small cell lung cancer treatment with a differentiated indication. It is the world’s first anti-PD-1 monoclonal antibody for the first-line treatment of small cell lung cancer, and has received orphan drug designations in the U.S., the European Union, Switzerland, and South Korea. In June this year, HANSIZHUANG was also approved for the first-line treatment of extensive-stage small cell lung cancer in both the U.K. and India. HLX22 is designed to address the clinical challenge of treating highly heterogeneous gastric cancer. By developing different binding epitopes, HLX22 represents a novel HER2 dual-targeted therapy for gastric cancer that could redefine the first-line treatment landscape for advanced gastric cancer.

The foundation of differentiated strategy is to identify “unmet” clinical needs. This approach reflects Fosun’s patient-centric philosophy and its commitment to developing high-quality, more accessible biologic medicines through innovative R&D. In addition to Henlius’ focus on prevalent cancers, Fosun Pharma is also expanding into areas such as rare diseases, severe malaria, and chronic diseases, striving to fill treatment gaps and collaborate with industry funds to invest in cutting-edge technologies such as nuclear medicine, RNA, gene therapy, and AI drug discovery. Perhaps the next globally recognized innovative drug will emerge from one of Henlius’ more than 50 pipeline candidates.