Merck, a leading science and technology company, today shared updates on the company’s oncology pipeline and focused approach to the research and development of potential new medicines designed to improve the futures of people with cancer. This year, the company plans to open multiple new Phase Ib and II clinical studies for tuvusertib and M9466, key assets from its broad portfolio of DNA damage response (DDR) inhibitors; has advanced its lead antibody-drug conjugate (ADC), M9140, to Phase Ib based on positive signs of clinical benefit, and plans to expand to additional tumors; and progress M3554, its next ADC based on the company’s proprietary exatecan-payload platform, into clinical development. These and other updates were shared at the company’s Oncology R&D Update Call.

“The advancements in our strong early-stage clinical pipeline of ADCs created with our in-house platform and DDR inhibitors are grounded in encouraging data, particularly for M9140 and tuvusertib. The addition of M9466 to our pipeline further supports our focus on synergistic approaches in oncology, with the potential for combination with tuvusertib as well as with multiple other modalities,” said Danny Bar-Zohar, Global Head of Research & Development and Chief Medical Officer for the Healthcare business sector of Merck.

"With our preclinical research programs in ADCs, DDR inhibitors, next-generation immuno-oncology compounds and oncogenic signaling assets, we are well-positioned to continue to fuel our clinical development efforts as we work to improve the futures of people touched by cancer.”

The company’s leading pipeline of DDR inhibitors is being investigated across core hypotheses including synthetic lethality, activation of immune response, and synergy with cytotoxic drugs, to identify relevant combinations and understand which cancers are most likely to respond to different treatment regimens.

The company has developed a proprietary technology platform for the creation of exatecan-based ADCs, with M9140 the first of these to enter clinical development. M9140 utilizes an antibody specific for CEACAM5, which is highly expressed in several tumor types, and an exatecan payload joined by a β-glucuronide linker that is specifically cleaved in tumors, releasing the cytotoxic agent into the cells.

In preclinical research, M9140 has shown high bystander activity, as exatecan released in the target tumor cells can kill these cells and also permeate the cell membrane to induce cell death in neighboring cells. First-in-human data from the PROCEADE-CRC-01 clinical trial presented at the 2024 ASCO Annual Meeting show encouraging clinical activity and a manageable and predictable safety profile for M9140 in this population

Recent agreements continue to support the company’s oncology strategy, guided by focus areas across research, development, and commercialization. These collaborations align with the company’s goal of driving over 50% of launches in the coming years with external innovation. In addition to the agreement with Hengrui for M9466, the company has executed agreements with Caris Life Sciences to support target discovery that may accelerate discovery and development of first-in-class ADCs; with Inspirna, for ompenaclid, a first-in-class compound being investigated in colorectal cancer, complementing the company’s expertise in this tumor type; and with Abbisko Therapeutics Co. Ltd., for pimicotinib, for which the Phase III study in tenosynovial giant cell tumor recently completed enrollment.

At Merck, we strive every day to improve the futures of people living with cancer. Our research explores the full potential of promising mechanisms in cancer research, focused on synergistic approaches designed to hit cancer at its core. We are determined to maximize the impact of our standard-of-care treatments and to continue pioneering novel medicines. Our vision is to create a world where more cancer patients will become cancer survivors.