Merck KGaA, Darmstadt, Germany, which operates its Healthcare business as EMD Serono in the U.S. and Canada, shared updates on its healthcare strategy, aimed at doubling R&D productivity. The goal is to introduce one new product or major indication every 1.5 years on average by focusing its expertise and capabilities and leverage synergies within the existing pipeline to deliver transformative medicines in Oncology, Neurology and Immunology, augmented by an increased focus on external innovation. The company expects to maintain the output of its internal discovery engine, while more than 50% of future launches will result from external co-development partnerships and strategic in-licensing of assets for further in-house development. 
 
“We are driven by our ambition to accelerate the discovery, development and delivery of innovative medicines to patients with cancer and neuroinflammatory and immune-mediated diseases,” said Danny Bar-Zohar, Global Head of Research & Development and Chief Medical Officer for the Healthcare business sector of Merck KGaA, Darmstadt, Germany. “With a mindset of design simplicity and resource discipline paired with agility of execution, we will speed the generation of high-quality data that will support our efforts to bring forth more medicines for more patients, faster.”
 
To increase R&D productivity, the company will build on the underlying biology of its focused therapeutic areas of oncology, neurology and immunology and will leverage technological capabilities, particularly its antibody-drug conjugate (ADC) technology.
 

Oncology: 

The company’s oncology R&D strategy centers on cancer DNA while building on existing leadership in key cancer types, including head and neck, urothelial and colorectal cancers. The oncology pipeline is focused on synergistic approaches targeting key pathways involved in cancer cell survival, deploying mechanisms to hit cancer at its core:
 
Delivering tumor DNA-damaging payloads right to the cancer with cutting-edge ADC technology
Preventing cancer cells from repairing DNA damage, through inhibition of the DNA damage response (DDR)
 
The lead asset in the oncology pipeline is xevinapant, an investigational first-in-class potent oral small molecule IAP (Inhibitor of Apoptosis Protein) inhibitor being evaluated in the curative setting of locally advanced squamous cell carcinoma of the head and neck (LA SCCHN). Xevinapant, which was in-licensed from Debiopharm in March 2021.
 
The company’s portfolio of selective and potent DDR inhibitors includes leading asset M1774, an oral ATR (ataxia telangiectasia and Rad3-related) inhibitor M1774, which has been designed as a potentially best-in-class molecule. The DDR portfolio also includes inhibitors of ATM (ataxia-telangiectasia mutated) and DNA-PK (DNA-dependent protein kinase) and has recently been complemented by a collaboration with Nerviano Medical Sciences with the option for a license agreement on the next-generation selective PARP1 (poly (ADP-ribose) polymerase) inhibitor NMS-293.
 
Earlier this year, M9140, the first ADC developed using the company’s own technology, advanced into a Phase Ia study in patients with colorectal cancer. M9140 is an anti-CEACAM5 ADC with a topoisomerase 1 inhibitor (exatecan) payload that has been rationally designed for stability in circulation and superior cancer cell killing activity with a broad therapeutic window. M9140 has synergistic potential with DDR inhibition as well.
 

Neurology and Immunology: 

In neurology and immunology, Merck KGaA, Darmstadt, Germany, aims to expand its multiple sclerosis (MS) portfolio with evobrutinib, an investigational, oral, CNS-penetrating, highly selective inhibitor of Bruton’s tyrosine kinase (BTK) with the potential to become a best-in-class treatment option for relapsing multiple sclerosis (RMS). In a Phase II study and follow-up, evobrutinib is the first BTK inhibitor (BTKi) to demonstrate sustained clinical efficacy for people with RMS through three and a half years and impact early biomarkers of ongoing central inflammation that correlate with disease progression, including slowly expanding lesions volume and levels of blood neurofilament light chain protein.
 
The company seeks to expand in neurology by evaluating the potential of oral cladribine in neurological diseases where inflammation is a primary driver, such as generalized myasthenia gravis.
 
The company focusing on targets with proven biology via novel modalities. A Phase II WILLOW study of the TLR7/8 inhibitor enpatoran is being studied in cutaneous and systemic lupus erythematosus.