Peptide News Digest

Foundayo Week 4 IQVIA 7,335 Scripts + Citi Telehealth Caveat, Merck Enlicitide Biocatalytic Science Paper, Rhythm Q1 IMCIVREE $60.1M, Vertex VX-670 GALILEO H2

Foundayo Week 4 IQVIA, Merck enlicitide biocatalytic Science paper, Rhythm Q1 IMCIVREE $60.1M + EMANATE miss, Vertex VX-670 DM1, PolyPeptide credit.

10 stories · Covering industry, research, clinical-trials

Editor's Note

May 9 brings the first full read on Foundayo's fourth commercial week and a different kind of milestone for macrocyclic peptide synthesis. Citi's morning note pegged the IQVIA Week 4 Foundayo tracker at 7,335 prescriptions and called it a 'modest uptake,' flagging the meaningful gap between IQVIA retail data and the roughly 35% of launch volume Lilly attributes to telehealth — a caveat that probably understates Foundayo's true volume but does not close the comparative gap to Wegovy pill, which Citi pegged at 440,410 scripts in the week ending May 1 with oral semaglutide accounting for 33% of all obesity referrals. On May 7, Merck published in Science the biocatalytic cascade route to enlicitide decanoate, an investigational oral PCSK9 inhibitor — a tailored enzyme suite that handles peptide fragment formation, coupling, and macrocyclization in a protecting-group-free sequence and cuts steps by more than half versus prior chemistry, with implications well beyond cardiology for any large macrocyclic peptide program. On the non-GLP-1 commercial side, Rhythm Pharmaceuticals' Q1 print (May 5) showed setmelanotide net product revenue of $60.1M (up from $37.7M YoY) on hypothalamic-obesity expansion plus EU authorization, even as the EMANATE Phase 3 program missed its primary endpoint across all four MC4R-pathway substudies. Vertex's Q1 update reaffirmed VX-670 — an oligonucleotide linked to a cyclic peptide that addresses the underlying CUG-repeat splice defect in myotonic dystrophy type 1 — is on track for GALILEO Phase 1/2 results in H2 2026. PolyPeptide expanded its credit facility to EUR 200M to support the strategic plan to double 2023 revenue by 2028. Two fresh AI-driven cyclic-peptide papers — CycloPepper in Nature Communications and the AI-designed CD28 antagonist CIP-3 on bioRxiv — show how computational design is moving past GLP-1 mimetics into immune-checkpoint and synthesis-optimization territory. A Frontiers in Endocrinology multicenter retrospective study mapped semaglutide use in T2D + ESRD, the population systematically excluded from FLOW. Hims & Hers prints Q1 May 11.

Industry

Citi (May 8): Foundayo Week 4 IQVIA Tracker Hits 7,335 Prescriptions, Telehealth Gap May Mask Real Uptake

In its fourth commercial week (April 27–May 1), Eli Lilly's Foundayo (orforglipron) recorded 7,335 prescriptions per IQVIA, Citi told clients May 8, calling the early launch 'off to a solid start' and modeling $146M in Q2 revenue and $1.6B for full-year 2026. Citi flagged that IQVIA captures retail and partial telehealth data but likely understates Lilly Direct and the 12+ telehealth firms representing roughly 35% of launch volume; Lilly executives have cited 20,000 patients now on Foundayo. For comparison, Citi's same note pegged Wegovy pill at 440,410 prescriptions in the week ending May 1, with oral semaglutide accounting for 33% of all Novo obesity referrals.

#foundayo #orforglipron #eli-lilly #iqvia #citi #telehealth #wegovy-pill #oral-glp-1
Research

Science (May 7): Merck Publishes Biocatalytic Cascade Route to Enlicitide Decanoate, the Investigational Oral PCSK9 Inhibitor

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 #enlicitide #pcsk9 #macrocyclic-peptides #biocatalysis #oral-peptide #synthesis-chemistry #science-journal
Clinical Trials

Rhythm Q1 2026: IMCIVREE Net Revenue $60.1M (+59% YoY) on Hypothalamic Obesity Launch — EMANATE Phase 3 Misses in All Four MC4R Substudies

Rhythm Pharmaceuticals reported Q1 2026 results May 5: setmelanotide (IMCIVREE) net product revenue of $60.1M, up from $37.7M a year earlier ($36.9M US, $23.2M ex-US), driven by 150+ new US start forms in acquired hypothalamic obesity following the FDA approval and the EU Marketing Authorization for the same indication; Japan's PMDA accepted the NDA for review. The MC4R-agonist peptide is the only commercial therapy for hypothalamic obesity. Offsetting the topline beat: the Phase 3 EMANATE trial in genetically caused MC4R-pathway diseases failed its primary endpoint in all four independent substudies, narrowing the indication-expansion runway. Net loss was $56.7M; cash $340.6M for 24+ months runway.

#rhythm-pharmaceuticals #setmelanotide #imcivree #mc4r #hypothalamic-obesity #emanate #q1-2026 #rare-disease
Clinical Trials

Vertex Q1: VX-670 Cyclic-Peptide-Oligonucleotide DM1 Conjugate On Track for GALILEO Phase 1/2 Readout in H2 2026

Vertex Pharmaceuticals' Q1 business update confirmed continued enrollment and dosing in the multiple-ascending-dose portion of GALILEO, the global Phase 1/2 study of VX-670 in adults with myotonic dystrophy type 1, with results guided for H2 2026. VX-670 is an oligonucleotide linked to a cyclic peptide endosomal-escape vehicle from Entrada Therapeutics' EEV platform; the oligonucleotide engages CUG-repeat RNA to liberate bound MBNL1 splicing factor and correct the upstream missplicing that drives DM1 pathology. The trial is the first clinical readout for the Vertex–Entrada DM1 collaboration, originally signed February 2023 with $250M upfront. DM1 has no disease-modifying therapy.

#vertex #vx-670 #myotonic-dystrophy #dm1 #entrada-therapeutics #cyclic-peptide #endosomal-escape-vehicle #galileo-trial
Industry

PolyPeptide Group Expands Credit Facility to EUR 200M to Fund Strategic Plan Through 2028

PolyPeptide Group AG announced that it has expanded its existing credit facility to EUR 200 million in support of growth ambitions and progress toward doubling 2023 revenue by 2028. The Swedish-Belgian peptide CDMO is one of the four large dedicated peptide manufacturers — alongside Bachem, CordenPharma, and Sun Pharma's Hyderabad PolyPeptide platform — and has previously announced a EUR 100M expansion in Malmö plus large-scale SPPS production in Braine-l'Alleud, Belgium that started in late 2024. The credit move heads into TIDES USA 2026 (May 11–14, Boston), where capacity, GMP investment, and large-scale SPPS economics will dominate the panel agenda.

#polypeptide-group #peptide-cdmo #manufacturing-capacity #credit-facility #tides-usa-2026 #spps
Industry

Hims & Hers Q1 2026 Preview: May 11 Print Tests GLP-1 Pivot After FDA Compounding Tightening

Hims & Hers reports Q1 2026 after market close May 11, with consensus revenue at $616-619M and EPS at roughly 3-4 cents — a 90% YoY decline. The investor question is whether the legitimate Wegovy/Ozempic distribution channel from the Novo Nordisk partnership (signed April 2026) can offset the wind-down of the compounded semaglutide business. Novo's branded products were not on the platform until March 26, with Q1 books closing March 31 — meaningful Wegovy revenue contribution likely lands in Q2. Subscriber count above 2.5M and ~82% three-month retention remain the standing benchmarks. The April 30 FDA proposal to remove semaglutide, tirzepatide, and liraglutide from the 503B bulks list raises the medium-term bar for any compounding-driven model.

#hims-hers #q1-2026 #novo-nordisk #wegovy #ozempic #compounding #503b #fda
Research

Nature Communications: CycloPepper ML Platform Predicts Cyclization Outcomes and Optimizes Synthesis of Therapeutic Cyclopeptides

A Nature Communications paper (2026) introduces CycloPepper, a machine-learning-guided platform for predicting cyclization outcomes and accelerating automated synthesis of therapeutic cyclic peptides. The model addresses one of the persistent bottlenecks in cyclic-peptide drug development: many promising linear sequences fail at the macrocyclization step or yield poorly under standard conditions, requiring expensive iterative chemistry. CycloPepper trains on a curated dataset of cyclization outcomes and integrates with automated synthesis platforms to enable closed-loop design-make-test cycles. The work joins CyclicMPNN (a fine-tuned ProteinMPNN derivative for cyclic peptide sequence design) and AfCycDesign as part of a fast-maturing computational stack for cyclic-peptide therapeutics.

#cyclopepper #cyclic-peptide #machine-learning #ai-drug-design #nature-communications #automated-synthesis
Research

bioRxiv Preprint: AI-Designed Cyclic Peptide CIP-3 Achieves Nanomolar Antagonism of CD28 Immune Checkpoint

A March 2026 bioRxiv preprint reports an AI-guided strategy for the discovery of cyclic peptide antagonists targeting the CD28 immune checkpoint, with the lead candidate CIP-3 binding the CD28 extracellular domain at nanomolar affinity and producing controllable modulation in cellular assays. CD28 is the principal T-cell co-stimulatory receptor and a high-value target for autoimmunity and transplantation, where current biologics (abatacept, belatacept) are large fusion proteins with associated dosing and immunogenicity tradeoffs. CIP-3's small cyclic-peptide format opens the prospect of subcutaneous dosing with a different PK profile. The work illustrates how AI-driven cyclic-peptide design is expanding beyond GLP-1 mimetics into immune-checkpoint pharmacology.

#cd28 #immune-checkpoint #cyclic-peptide #ai-drug-design #cip-3 #biorxiv #preprint
Clinical Trials

Frontiers in Endocrinology: Multicenter Real-World Cohort Maps Semaglutide Use in Type-2 Diabetes Plus End-Stage Renal Disease

A Frontiers in Endocrinology multicenter retrospective cohort study (2026) reports real-world safety and effectiveness of semaglutide in patients with type 2 diabetes and end-stage renal disease — the population systematically excluded from FLOW (which capped at eGFR ≥ 25) and the SELECT pre-specified kidney composite analysis. ESRD patients comprise roughly 1% of the diabetic population but 7% of US healthcare spending; their cardiovascular event rates are among the highest documented. The cohort fills a clinical gap: prescribers managing dialysis-dependent patients have had to extrapolate from outcome trials that explicitly excluded the population. Work joins the SOUL oral-semaglutide CKD analysis as the fastest-growing GLP-1 evidence stream beyond obesity and T2D.

#semaglutide #esrd #type-2-diabetes #real-world-evidence #kidney-disease #frontiers #novo-nordisk
Research

Drug Discovery World (May 2026): The Art and Science of Cyclic Peptide Drug Design — Experimental Discovery Meets AI Computation

A May 2026 Drug Discovery World feature consolidates the case for cyclic peptides as a distinct therapeutic modality: larger and more selective than small molecules, more permeable and cheaper to manufacture than antibodies, and uniquely suited for protein-protein-interaction targets that have resisted traditional drug discovery. The piece traces the recent algorithmic stack — RFDiffusion adaptations for cyclic backbones, AfCycDesign, ProteinMPNN-derived sequence design — alongside the synthesis chemistry advances (one-pot ligations, photo-redox macrocyclizations) that turn computational hits into tractable scaffolds. Over 40 cyclic peptide drugs are now FDA-approved across endocrine, oncology, and antimicrobial uses, and 6+ peptide-drug conjugates sit in Phase 3, per the late-April PDC market analysis.

#cyclic-peptide #ai-drug-design #macrocyclic-peptides #drug-discovery #rfdiffusion #afcycdesign