Merck’s Innovative Oncology Pipeline of DNA Damage Response Inhibitors and Antibody-Drug Conjugates Poised to Advance Cancer Treatment
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.”
Realizing the Full Potential of DNA Damage Response Inhibition
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. Four investigational DDR inhibitor medicines in clinical trials include:
- Tuvusertib (M1774), a potentially best-in-class small-molecule oral inhibitor of the ataxia telangiectasia and Rad3-related (ATR) kinase;
- M9466, a next-generation potent and selective PARP1 (poly (ADP-ribose) polymerase 1) inhibitor, recently licensed from Jiangsu Hengrui Pharmaceuticals Co. Ltd. (Hengrui);
- Lartesertib (M4076), an ataxia telangiectasia mutated (ATM) kinase inhibitor; and
- Peposertib, a DNA-PK inhibitor.
Recently presented data lay the foundation for combination Phase II studies with tuvusertib. Data from DDRiver 301 Part B presented today at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting show the ability to combine tuvusertib at a predicted efficacious dose with the PARP inhibitor niraparib, as well as encouraging activity in PARP-pretreated ovarian cancer. These findings complement data for the first-in-class tuvusertib and lartesertib combination first presented at the American Association for Cancer Research (AACR) Annual Meeting 2024 in April. The company is exploring tuvusertib across three Phase II studies:
- Ongoing Phase Ib/II DDRiver NSCLC 322 study (NCT05882734) in combination with cemiplimab in ICI-resistant advanced non-small cell lung cancer (NSCLC) with biomarker stratification;
- Recently opened Phase II DDRiver EOC 302 study (NCT06433219) of tuvusertib plus lartesertib or niraparib in biomarker-selected PARP-resistant ovarian cancer; and
- Recently opened Phase II JAVELIN DDRiver Bladder study (NCT06424717), in combination with BAVENCIO® (avelumab) in ICI-resistant advanced urothelial cancer.
For M9466 (also known as HRS-1167), data presented during the 2024 ASCO Annual Meeting from Hengrui’s first-in-human clinical trial show a favorable safety profile and promising efficacy in PARP-naïve, PARP-sensitive tumors, supporting Merck’s plans to further develop this investigational medicine in various combinations. The recently opened DDRiver 501 study (NCT06421935) will evaluate M9466 in combination with tuvusertib in solid tumors with relevant mutations and/or prior PARP inhibitor exposure, with a focus on castration-resistant prostate and ovarian cancers. The clinical development program will build on the company’s expertise in genitourinary and gastrointestinal cancers and aims to expand the list of indications beyond the tumors shown to be sensitive to first-generation PARP inhibitors.
Driving Innovation in Antibody-Drug Conjugates
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. Following the completion of the ongoing dose-optimization part, the company plans to assess combinations in colorectal cancer with standard-of-care agents with alternative scheduling options. A basket trial planned to launch in early 2025 will further explore M9140 monotherapy in tumors with high CEACAM5 expression, with the potential for further exploration in various combinations.
M3554 is the next ADC based on the company’s platform, linking an exatecan payload with an anti-GD2 antibody. This potentially first-in-class ADC will enter its first-in-human study later in 2024. M3554 will be evaluated in patients with solid tumors with high GD2 prevalence, such as neuroblastoma, where GD2 has been validated as a target as a naked antibody, as well as soft tissue sarcoma, glioblastoma, and osteosarcoma.
ADCs are one of several modalities being explored in preclinical research. By maximizing the exatecan platform, delivering next-generation cytotoxins and targeted payloads, expanding into novel antigens, and discovering immune agonist ADCs, the company anticipates expansion in the organic clinical ADC portfolio over the next several years.
Guided Approach to External Innovation
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.
Advancing the Future of Cancer Care
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. Learn more at https://www.merckgrouponcology.com/en/home.html.
About Merck
Merck, a leading science and technology company, operates across life science, healthcare and electronics. Around 63,000 employees work to make a positive difference to millions of people’s lives every day by creating more joyful and sustainable ways to live. From providing products and services that accelerate drug development and manufacturing as well as discovering unique ways to treat the most challenging diseases to enabling the intelligence of devices – the company is everywhere. In 2023, Merck generated sales of € 21 billion in 65 countries.
Scientific exploration and responsible entrepreneurship have been key to Merck’s technological and scientific advances. This is how Merck has thrived since its founding in 1668. The founding family remains the majority owner of the publicly listed company. Merck holds the global rights to the Merck name and brand. The only exceptions are the United States and Canada, where the business sectors of Merck operate as MilliporeSigma in life science, EMD Serono in healthcare, and EMD Electronics in electronics.
All Merck press releases are distributed by e-mail at the same time they become available on the Merck website. Please go to www.merckgroup.com/subscribe to register online, change your selection or discontinue this service.
To view this piece of content from cts.businesswire.com, please give your consent at the top of this page.
View source version on businesswire.com: https://www.businesswire.com/news/home/20240531201218/en/
Contact information
Media Relations
Noelle.Piscitelli@emdserono.com
Phone: +1 (781) 427-4351
Investor Relations
investor.relations@merckgroup.com
Phone: +49 6151 72-3321
About Business Wire
Subscribe to releases from Business Wire
Subscribe to all the latest releases from Business Wire by registering your e-mail address below. You can unsubscribe at any time.
Latest releases from Business Wire
Daiichi Sankyo Shines a Light on Inequalities and Unmet Needs in Care as Part of Its Commitment to People With Cardiovascular Disease31.8.2024 17:00:00 CEST | Press release
Daiichi Sankyo Europe, (hereafter, Daiichi Sankyo) today announced its reinforced commitment to addressing key unmet needs and barriers in cardiovascular (CV) care, by shining a light on inequalities in treatment and outcomes experienced by various patient groups. The announcement follows the presentation of data from sub-analyses of the SANTORINI observational study and ETNA-AF (Edoxaban Treatment in routiNe clinical prActice in patients with nonvalvular Atrial Fibrillation) study programme, at the European Society of Cardiology (ESC) Congress 2024. Gender inequalities in CV disease treatment and LDL-C goal attainment Raised low-density lipoprotein cholesterol (LDL-C) is a key modifiable contributor to risk of cardiovascular major events. It has been shown that for every 1 mmol/L reduction in LDL-C, there is a 22% reduction in major cardiovascular events after 1 year.7,8 Female patients in Europe who are at high or very high CV risk were undertreated and less achieved guideline-recomm
Suzano completes purchase of 15% stake in Lenzing AG31.8.2024 00:40:00 CEST | Press release
Suzano, the world's largest pulp producer, today announces the completion of its acquisition of a 15% stake in Lenzing AG, the Vienna-listed leading global supplier of sustainable premium cellulosic fibres for the textile and non-wovens industry, from B&C Group. As announced in June this year, the transaction value is EUR 230 million (or EUR 39.70 per share). The agreement was subject to regulatory approval, which was granted without restrictions. The long-term partnership between Suzano and B&C Group establishes that Suzano has the right to hold two seats on Lenzing’s Board and the option to acquire an additional 15% stake from B&C Group until the end of 2028. Following the sale of the 15% stake, B&C Group now holds 37.25% of Lenzing’s share capital. Lenzing is a leading global supplier of premium wood-based cellulosic fibers (lyocell, modal, and viscose) for the production of clothing, home textiles, hygiene products, and non-woven materials. Beto Abreu, CEO of Suzano, said: “Lenzing
Ant International Collaborates with Brazilian Partners to Drive Financial Inclusion with Innovative Credit Tech Solutions30.8.2024 20:46:00 CEST | Press release
Ant International, a digital payment and financial technology leader, today announced its strategic initiative to provide AI-driven credit technology solutions designed to empower local partners and advance financial inclusions in Brazil. As a major milestone, Ant International has formed a strategic partnership with Dock, a leader in payments and banking technology in Latin America. This collaboration aims to enhance the credit management capability and infrastructure efficiency for Dock’s clients, which include financial institutions, retailers, fintech start-ups, etc. The shared vision is to make credit services more inclusive for market segments that are currently insufficiently served, such as micro, small and medium-sized enterprises (MSMEs). In the initial phase of the collaboration, Ant International’s AI-driven credit tech solutions, including an automated and intelligent risk management engine, will be explored for integration into Dock One platform. This initiative aims to s
Wipro Appoints Srikumar Rao as Global Head of Its Engineering Edge Business Line30.8.2024 16:20:00 CEST | Press release
Wipro Limited (NYSE: WIT, BSE: 507685, NSE: WIPRO), a leading technology services and consulting company, today announced the appointment of Srikumar Rao as Global Head of its Engineering Edge Business Line, effective from October 5, 2024. Srikumar succeeds Harmeet Chauhan, who is stepping down to pursue opportunities outside the organization. Srikumar will report to Srini Pallia. Srikumar has been with Wipro for 26 years and has grown with the organization, serving in various leadership roles. He was most recently the Chief Operating Officer (COO) of Wipro Engineering Edge (WEE) and Global Practice Head of Embedded Systems. His work has spanned several markets, selling and delivering specialized Engineering, Research, and Development (ER&D) services to Software & Internet, Semiconductor, Automotive, Manufacturing, and Communications clients. In his new role, Srikumar will continue to scale and strengthen Wipro’s engineering prowess. He will also be responsible for defining the vision
Alnylam Presents Detailed Results from the Positive HELIOS-B Phase 3 Study of Vutrisiran▼ in Patients with ATTR Amyloidosis with Cardiomyopathy at the European Society of Cardiology Congress30.8.2024 12:00:00 CEST | Press release
Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, today announced detailed results from the HELIOS-B Phase 3 study of vutrisiran, an investigational RNAi therapeutic in development for the treatment of ATTR amyloidosis with cardiomyopathy (ATTR-CM). The data were presented today in a Hot Line session at the European Society of Cardiology (ESC) Congress 2024, taking place August 30-September 2 in London, United Kingdom. Results from the HELIOS-B study were also simultaneously published in TheNew England Journal of Medicine. As previously reported, the HELIOS-B study met all 10 of its primary and secondary endpoints, across both the overall and monotherapy populations, with statistical significance. Enrolled patients were predominantly New York Heart Association (NYHA) Class I or II with wild-type disease and had been diagnosed by non-invasive methods, with substantial concurrent treatment with available standard of care treatments such as tafamidis and
In our pressroom you can read all our latest releases, find our press contacts, images, documents and other relevant information about us.
Visit our pressroom