MK-1942

Merck has bet tens of billions of dollars on antibody-drug conjugates in the last year through a couple of partnerships. Much of the fervor around Merck & Co.’s work with antibody-drug conjugates has centered on partnerships, namely the most recent $4 billion collaboration announced last week with Daiichi Sankyo. But that’s not precluding the company from building its own internal capabilities, Head of Merck Research Labs Dean Li, M.D., Ph.D., said Thursday on the company’s latest earnings call.  “We have built and we continue to build that expertise within the company, and we hope to see those internal programs peering its clinical head in the next couple years,” he said.  Li’s comments further illuminate Merck’s level of investment in the class which was the talk of the town in Madrid during the recent European Society for Medical Oncology Annual Congress. Merck’s collaboration with Daiichi follows a biobucks-laden deal with Kelun Biotech announced in December 2022 worth more than $9.3 billion in total. But Merck has been disciplined even as it's stacked on the deals. Kelun revealed earlier this week that Merck recently axed two preclinical candidates.  Li said that the data generated from the existing collaborations, in addition to others that are in combination with Keytruda, have built “a wall of data” informing where the field is headed. He noted that there will be improvements and changes to antibody structure that can impact tissue targeting in addition to the linkers between the antibody and payload. Li also suggested that there could be advancements in the kinds of payloads attached to the antibody, with just two types of chemotherapies currently used.  Merck has made ADCs a focal point of its future oncology strategy, but that hasn’t stopped the company from investing heavily in other therapeutic areas, namely the cardiometabolic and immunology space. Merck CEO Rob Davis said the company’s confidence that it will reach at least $10 billion in revenue from its cardiovascular franchise is “higher today” than it was when the goal was first announced in April 2022. That bullishness is thanks to sotatercept, which is under review by regulators as a treatment for pulmonary arterial hypertension.  Elsewhere, Merck is making cuts. The company has discontinued a couple of phase 2 trials testing MK-1942 for mild-to-moderate Alzheimer’s disease and major depressive disorder. The company says that the decision followed an unblinded review of the data indicating that the med was “potentially associated with observations of liver toxicity.” “This review was triggered by the identification of abnormalities in liver function tests for several study participants,” according to a statement provided by Merck. No related serious side effects were reported.

Merck & Co. has terminated two Phase II studies of the experimental drug MK-1942 after liver abnormalities were seen in a number of patients. The company confirmed the news to FirstWord on Wednesday, with the halted trials first disclosed on ClinicalTrials.gov.One study was investigating the small molecule in nearly 100 patients with difficult-to-treat major depressive disorder (MDD) on a stable course of antidepressant therapy. Subjects were randomised to daily dosing with MK-1942, intermittent treatment with the drug or placebo.The second trial was evaluating MK-1942 as a potential adjunct treatment in around 100 patients with mild-to-moderate Alzheimer’s disease. Participants were randomised to receive one of two twice-daily doses of the drug or placebo.According to Merck, the decision to halt the studies followed an unblinded review of data suggesting that MK-1942 was potentially associated with observations of liver toxicity. The review had been triggered by the identification of abnormalities in liver function tests for several study participants. However, the company noted that no related serious adverse events were reported.