Innovation

We’re pursuing innovative science with antibody-drug conjugate (ADC) research

Merck scientists are evaluating ADCs to explore novel treatment approaches in both solid tumors and blood cancers

May 19, 2025

Share this article

3D depiction of an antibody-drug conjugate molecule

What are antibody-drug conjugates (ADCs)?

ADCs are a targeted means to transport and deliver chemotherapy to tumor cells. More than two decades since the first approval of an ADC, scientists continue to explore how, by leveraging novel scientific advancements, they can find new ways to better design and develop these molecules in order to better address current unmet needs in cancer treatment.

ADCs are made up of three distinct yet equally important elements — an antibody, a linker and a cytotoxic drug/chemotherapy payload. These elements work together to transport the chemotherapy payload to a specific target expressed on the surface of a cancer cell, bind to the target and then be absorbed into the cell to release the chemotherapy.

Anatomy of an ADC

• The antibody serves as the targeting mechanism, like a zip code helping to direct the delivery of the chemotherapy agent to cancerous cells.
• The payload, or the chemotherapy agent, is responsible for working to destroy the cancer cell when it’s released.
• The linker attaches the chemotherapy agent to the antibody and triggers the release of the chemotherapy agent once inside a cancerous cell.

Watch an animation of an ADC in action

Advancements in the scientific research behind ADCs

Since ADCs were first introduced in 2000, the chemistry and science behind these molecules has advanced significantly, and scientists have developed a greater understanding of what makes a good ADC target and how to design ADCs more effectively.

Tumor antigens, or proteins expressed on the outside of a cancer cell, are what an antibody initially binds to. Scientists now know that characteristics like how quickly an antigen is brought inside the cell and whether an antigen is recycled back to the cell surface are crucially important.

“Imagine ADCs as specialized agents that recognize and bind to specific tumor antigens on cancer cells. Once they attach to these antigens, ADCs are internalized by the cell, allowing the chemotherapy agent to be released directly inside, delivering the treatment where it’s needed most — at the core of the cancer cell.”

• Dr. Omobolaji Akala
  Associate vice president of oncology early development, Merck Research Laboratories

There have also been notable advancements in both linker and payload chemistry. Scientists have been focused on improving the stability of linkers and reducing the risk of payload release in the body, as well as evaluating where and how many molecules can be incorporated into the payload. Combined, these advancements may help in reducing damage to nearby healthy cells, while releasing a potent payload precisely within a cancer cell.

This evolving understanding of the science is fueling innovative research efforts with the goal of bringing more effective ADCs to patients.

“We’ve learned that designing ADCs is about balancing the right level of tumor antigen expression, the right potency of a cytotoxic agent in the payload, addressing the cell biology through that payload and engineering a payload to release at the right time and in the right place.”

• Dr. Marjorie Green
  Senior vice president and head of oncology, global clinical development, Merck Research Laboratories

Exploring ADC targets

We’re focusing on proteins associated with poor prognosis across both solid tumors and blood cancers to expand the impact of ADC therapies and address the needs of more patients. Our scientists are also combining ADCs with other innovative treatments such as immunotherapies and T-cell engagers.

By exploring the potential of a broad range of ADC targets and applying new technologies — such as novel linker chemistries, optimized payloads and combination strategies with other therapies — we aim to deepen our understanding of these complex molecules and work to identify and develop new meaningful therapeutic options for patients, aligning with our purpose of using the power of cutting-edge science to save and improve lives around the world.

Learn more about our work in oncology.

Innovation

TL1A: Exploring a potentially important target for inflammatory bowel disease

Our scientists are investigating ways to modulate TL1A to potentially address inflammation and fibrosis associated with inflammatory bowel disease

October 9, 2024

Share this article

Picture the immune system as a carefully orchestrated network of organs, cells and molecules working together to protect your body from foreign invaders. Normally, this system operates smoothly, identifying and then fighting off microbes. However, in the case of inflammatory bowel disease (IBD), a person’s immune system can mistakenly attack their own tissues, causing chronic inflammation and tissue damage.

Nearly three million people in the U.S. live with Crohn’s disease or ulcerative colitis, the two most common forms of IBD. Patients with IBD experience symptoms such as diarrhea, blood in the stool, abdominal pain, unintended weight loss, fatigue and impaired sleep. In 25-40% of patients, IBD may affect organs and tissues outside of the gastrointestinal system, including the joints, skin, bones, eyes, kidneys and liver. When IBD is uncontrolled, it can lead to hospitalizations and surgery.

Despite available therapies which have helped improve patients’ symptoms over the last two decades, many patients do not achieve a state of sustained remission.  

“People with IBD often struggle to find a treatment that works for them because each individual’s disease is different,” said Aileen Pangan, vice president and therapeutic area head, immunology clinical research, Merck Research Laboratories.

“With a better understanding of the biology of IBD, medicines have begun to emerge that aim to change the way we approach treatment. We’re investigating ways to modulate targets, including TL1A, that have been implicated in IBD and other immune-mediated inflammatory diseases.”

• Aileen Pangan
  

Our TL1A research

Our scientists are investigating tumor necrosis factor-like ligand 1A (TL1A), which has been shown to be increased in inflamed intestinal tissue and in the systemic circulation of patients with IBD.

TL1A is a cytokine, a protein functioning as a chemical messenger, that acts as a regulator of cellular immunity. In healthy people, levels of TL1A increase to help immune cells fight infections effectively, with levels going back down after the infection is gone. However, in IBD, TL1A levels are chronically elevated, leading to an excessive buildup of immune cells in the digestive tract, chronic inflammation, tissue damage and fibrosis.

Teams at Merck are evaluating the potential role of TL1A across immune-mediated inflammatory diseases, including Crohn’s disease, ulcerative colitis and systemic sclerosis-associated interstitial lung disease (SSc-ILD). Learn more about our research in immunology.

Innovation

What is One Pipeline?

How we’re advancing the best internal and external science to progress our pipeline for patients

May 30, 2024

Share this article

Drug development is a long and difficult endeavor. It can take more than 10 years to bring a new medicine to market. So how does our company think about developing new medicines and vaccines to help save and improve lives? The answer: through our One Pipeline strategy, where we complement our internal innovation and discovery efforts with the best external science through business development.

“Our One Pipeline strategy enables us to advance breakthrough science, whether it comes from our own labs or from our partners’ labs, and make medicines and vaccines for patients,” said Dr. Dean Li, president, Merck Research Laboratories (MRL). “Every day, we’re pushing scientific boundaries in research. Business development and external partnerships are integral to help drive our internal pipeline and to provide access to assets that are important for our discovery and clinical development groups.”

To achieve that balance, MRL works in lockstep with our business development and licensing (BD&L) team. “I want to emphasize how integrated BD&L is with MRL. This is hand in glove,” said Li.

Business development augments our pipeline

Our BD&L team is committed to securing scientific and commercial collaborations, licensing agreements and acquisitions from discovery to late-stage candidates and new technologies to help build our robust portfolio. We have a legacy of successful collaborations and are among the most active dealmakers in the biopharma industry.

“We match our strong scientific conviction with bold investments in novel, cutting-edge science to advance new options for patients,” said Sunil Patel, senior vice president, head of corporate development and BD&L. “We’re focused on bringing in the best external science to complement our internal efforts to deliver on our purpose and sustain our company for the next 130 years.”

The BD&L team members focused on our pipeline are embedded with scientists across our research network and, in addition to our New Jersey and Pennsylvania sites, they’re strategically located in key epicenters of innovation including Boston, Cambridge, London, South San Francisco, Shanghai and Tokyo. The team searches the globe for cutting-edge science and works alongside our research team to evaluate opportunities built on strong scientific principles, regardless of location or origin.

Creating a sustainable innovation engine

As part of our One Pipeline strategy, we ensure a smooth transition when bringing in external science and leverage our clinical development and manufacturing expertise to advance each program with speed and rigor. This strategy is helping to build and maintain the flow of novel candidates through clinical development to patients, enabling long-term, sustainable growth for our company.

“Strategic business development focused on the best external science remains an important priority for our company. We’ve demonstrated that we can leverage our deep discovery prowess to identify important acquisition targets and then add significant value through our powerful clinical research engine, our regulatory expertise and our commercial scale, which together can serve to accelerate development and enable broad global access to important medical discoveries for patients in need,” said Rob Davis, chairman and chief executive officer.

Pipeline

We’re focused on discovering new medicines and vaccines for today and the future. View our pipeline.

Business development and licensing

We work with many partners, from early-stage science to clinical-stage programs, to deliver life-changing therapies. Learn more.