Merck joins a growing list of companies targeting lipoprotein(a), high levels of which are associated with an elevated risk of adverse cardiovascular outcomes.
Merck is fronting $200 million to partner with China-based Jiangsu Hengrui and develop its investigational small-molecule for cardiovascular care called HRS-5346, the pharma announced Tuesday.
The collaboration agreement will also see Merck put an additional $1.77 billion on the line for certain developmental, regulatory and commercial milestones. Meanwhile, Hengrui will be entitled to royalties on net sales of HRS-5346, in case of regulatory approval. Tuesday’s partnership will cover all worldwide territories except the Greater China region.
Merck and Hengrui expect to close the deal in the second quarter of 2025, subject to antitrust clearances and other customary conditions.
HRS-5346 is a lipoprotein(a) inhibitor. Also known as Lp(a), it is a type of low-density lipoprotein, high levels of which have been linked to an elevated risk of adverse cardiovascular outcomes. The molecule has emerged as an attractive target for pharma companies in recent years, especially given its ubiquity. According to Merck’s Tuesday release, roughly 1.4 billion people worldwide have heightened Lp(a) levels.
Details regarding HRS-5346’s specific mechanism of action remain sparse, but Dean Li, president of Merck Research Laboratories, said in a statement on Tuesday that the molecule is an “inhibitor of Lp(a) formation.” HRS-5346 is currently being assessed in a Phase II trial in China. Merck was also mum on specific development plans for the asset.
Among the gaggle of companies working on an Lp(a) therapies is AstraZeneca, which in October 2024 also partnered with a China-based company, CSPC Pharmaceutical Group, to advance YS2302018, an oral small-molecule disruptor of Lp(a). The pharma paid $100 million upfront and has promised up to $1.92 billion in potential milestones.
Eli Lilly, meanwhile, is working on its own oral candidate muvalaplin. In November 2024, the pharma unveiled mid-stage data for the candidate, touting an 81.7% decrease in Lp(a) levels versus placebo at the 60-mg dose level. A note from Leerink Partners at the time stated that muvalaplin has “megablockbuster potential.”
In partnering with Hengrui, Merck joins a growing industry-wide trend of looking eastward and tapping Chinese partners for new innovative therapies. Last week, for instance, AstraZeneca entered into two Chinese collaborations: one with Harbour BioMed to develop next-generation multispecific antibodies, and another with Syneron Bio to work on macrocyclic peptides.
In January 2024, Roche announced a licensing deal with Innovent, putting forth $80 million upfront and up to $1 billion in milestones to advance a DLL3-targeted antibody-drug conjugate (ADC). The candidate, dubbed IBI3009, entered Phase I trials in the U.S. in December 2024. GSK has also recently partnered with DualityBio, betting up to $1 billion to test an investigational ADC for an undisclosed gastrointestinal cancer indication.
