While Merck intends to maintain the output of its internal discovery engine, to meet its goal of delivering one new product or major indication every year and half, Bar-Zohar said more than 50% of its future launches will result from external co-development partnerships. These could include strategic in-licensing of assets for further in-house development.

“By building on our existing strengths and maximizing synergies within our in-house discovery pipeline and external assets, we will secure sustainable R&D productivity that leads to innovative medicines for patients in need,” he added.

Going forward, researchers will build on the company’s established expertise in the underlying biology of its therapeutic focus areas of oncology, neurology and immunology and will leverage its capabilities in such fields as antibody-drug conjugate (ADC) technology.

Hitting cancer at its core

Merck’s oncology R&D strategy centers on its capabilities in cancer DNA, in particular key types, such as head and neck, urothelial and colorectal carcinomas. The pipeline, the research chief explained, is focused on synergistic approaches targeting key pathways involved in cancer cell survival, deploying mechanisms to “hit cancer at its core.”

Here, the company’s approaches include delivering tumor DNA-damaging payloads directly to the cancer by utilizing the ADC technology, as well as preventing cancer cells from repairing DNA damage, through inhibition of the DNA damage response (DDR).

Lead asset in the oncology pipeline is xevinapant, an investigational oral small molecule inhibitor of apoptosis protein (IAP) that was licensed from Swiss biopharma Debiopharm in March 2021 and according to Zohar builds on Merck’s heritage and expertise. This is being evaluated as a treatment for locally advanced squamous cell carcinoma of the head and neck, an area that has not seen significant advances in treatment in the past 20 years.

The Darmstadt-based company’s portfolio of selective and potent DDR inhibitors also includes several agents under development that directly inhibit DDR pathways required for cancer cell survival and are said to “tip the therapeutic balance” in difficult-to-treat cancers.

Earlier this year, M9140, the first ADC developed using Merck’s own technology, advanced into human trials. The ongoing Phase 1a study is assessing the substance in patients with colorectal cancer.

MS portfolio is expanding

In neurology and immunology, Merck aims to expand its multiple sclerosis (MS) portfolio with evobrutinib, an investigational, oral, CNS-penetrating, highly selective inhibitor of Bruton’s tyrosine kinase (BTK) that it believes has the potential to become a best-in-class treatment option for relapsing multiple sclerosis (RMS).

The company also is seeking to expand in neurology by evaluating the potential of oral cladribine, a leukemia treatment, in neurological diseases such as generalized myasthenia gravis, where inflammation is a primary driver.

Immunology drugs for unmet needs

To diversify the pipeline with immunology and accelerate R&D, Merck is focusing on targets with “proven biology via novel modalities” and is currently conducting a Phase 2 study of the TLR7/8 inhibitor enpatoran in cutaneous and systemic lupus erythematosus.

Additionally, the firm’s researchers are initiating a proof-of-concept study with enpatoran in neuromuscular conditions dermatomyositis and polymyositis. Both conditions are seen as having a high unmet medical need.

Author: Dede Williams, Freelance Journalist