Merck's peptide story is anchored by enlicitide decanoate, a macrocyclic peptide oral PCSK9 inhibitor that reported 57% LDL-C reduction at 24 weeks in the Phase 3 CORALreef trial (NEJM February 2026) and would be the first oral PCSK9 inhibitor if approved. The molecule is also notable for its manufacturing chemistry: the May 7, 2026 Science paper from the Merck process group described an engineered-enzyme biocatalytic cascade that cuts synthesis step count by more than half.
The broader peptide footprint includes the April 2025 Cyprumed deal worth up to $493M in milestones for oral peptide delivery platform access, the longstanding peptide-drug-conjugate research program, and a Q1 2026 Keytruda revenue baseline of $7.9B — recently overtaken by Eli Lilly's Mounjaro ($8.66B) as the world's top-selling drug per Bloomberg May 6. Merck's Q1 oncology cycle also included new ASCO-GU bladder and kidney cancer data plus continued peptide-radioligand work.
Stories here cover trial readouts, partnership economics, and the broader macrocyclic strategy. See #enlicitide, #pcsk9, and #keytruda.
ASCO 2026 abstracts will release on asco.org/abstracts beginning 5:00 PM ET on Wednesday May 21, ahead of the May 29-June 2 Chicago meeting. The peptide-oncology slate is substantial: Pfizer announced 40+ company-sponsored, investigator-sponsored, and collaborative oncology abstracts including three late-breaking sessions; Bicycle Therapeutics has an oral and four poster presentations on zelenectide pevedotin (BT8009, nectin-4 PDC) with Duravelo-2 interim data; Avacta has Phase Ia/Ib data on AVA6000 (FAP-Dox PDC) in salivary gland cancers; BioVaxys's MVP-S survivin peptide vaccine PESCO trial data; BriaCell's six Bria-IMT/Bria-OTS+ presentations on metastatic breast cancer; and Replimune's RP1 + nivolumab 3-year melanoma OS data. Crinetics CRN09682 SSTR2 NDC BRAVESST2 update expected.
Bloomberg reported May 6 that Eli Lilly's Mounjaro displaced Merck's Keytruda as the world's best-selling pharmaceutical in Q1 2026 — $8.66B Mounjaro Q1 sales vs Keytruda's $7.9B Q1 sales. The Mounjaro+Zepbound combined tirzepatide platform generated $36.5B in 2025, outpacing Keytruda's $31.6B. Keytruda had held the #1 ranking since Q1 2023, when it displaced AbbVie's Humira. The shift is the first time a peptide therapeutic has taken the top spot since the historical run of insulin biosimilars. The narrative also frames Lilly's $4.5B Lebanon Indiana manufacturing recommitment and the broader $21B Indiana capital plan as the supply-chain answer to demand at that scale.
Joelle Pelletier's perspective in Science (volume 392, pages 582-583, published online May 8) accompanies the Merck enlicitide biocatalytic synthesis paper and frames the enzyme-cascade route — engineered enzymes plus chromatography-free crystallization to cut step count by more than half — as a template that goes well beyond enlicitide. The piece argues that the limiting step for oral macrocyclic peptide therapeutics has been the manufacturing cost of multi-step protected-residue chemistry, not pharmacology or pharmacokinetics; biocatalysis collapses the cost curve and unlocks a pipeline of oral peptides at large molecular weights that have been quietly stuck in preclinical or Phase 1 economics. The framing matters as enlicitide (oral PCSK9 inhibitor with 57% LDL-C reduction at 24 weeks) heads toward NDA filing.
Merck scientists published in Science a convergent biocatalytic synthesis of enlicitide decanoate, an investigational oral PCSK9 inhibitor and macrocyclic peptide. A tailored suite of engineered enzymes catalyzes selective peptide fragment formation, coupling, and macrocyclization in a protecting-group-free sequence; combined with chromatography-free crystallizations, the route reduces step count by more than half versus prior state-of-the-art methods. Enlicitide is in Phase 3 (CORALreef, with –55.8% LDL-C reported earlier in 2026) and would be the first oral PCSK9 inhibitor if approved. The paper matters beyond enlicitide: protein-engineering-led cascades shift the cost basis for any large macrocyclic peptide program facing peptide-CDMO bottlenecks.
Merck's investigational oral macrocyclic peptide PCSK9 inhibitor demonstrated significantly greater LDL-C reductions at 8 weeks vs guideline-recommended oral non-statin therapies, delivering injectable-level cholesterol lowering in pill form.