From Peptides to Genetic Medicine
Week Of January 10 – January 16, 2026
A quieter week on the press release front, with Viking’s main news being the publication of its Phase 2 VENTURE data for VK2735 in Obesity rather than new clinical readouts. The trial registry was more active, including Novo Nordisk’s AMAZE 1 Phase 3 for amycretin (their next-gen GLP-1/amylin combo) and a petrelintide PK study from Zealand.
For the Trial Spotlight and Mechanism Explained, I focused on CR059 — a circular RNA candidate encoding exenatide from a Chinese academic center. It’s an early Phase 1 with just nine participants, so not a trial that will move markets. But circRNA is a genuinely different platform than the peptide injections or small molecules we usually cover, and CR059 appears to be the first circRNA application targeting metabolic disease. The broader circRNA field is still nascent — the first circRNA drug (non-vaccine) to reach patients was CirCode’s HM2002 for heart disease in 2024, and only a handful of programs have entered clinical trials globally. The idea is that the closed-loop RNA structure resists degradation 2-5x better than linear mRNA (like the COVID vaccines), potentially enabling sustained protein expression from a single dose. Whether this “genetic medicine” approach offers meaningful advantages in durability or convenience is an open question, but it’s worth tracking as an alternative delivery paradigm.
🔥 THIS WEEK’S KEY DEVELOPMENTS
Viking completes enrollment for Phase 3 obesity trial of VK2735.
Viking Therapeutics announced the publication of its Phase 2 VENTURE trial results for the dual GLP-1/GIP agonist VK2735 in the journal Obesity. After 13 weekly doses, participants demonstrated statistically significant reductions in mean body weight from baseline of up to 14.7%, with no plateau observed. VK2735 is currently being evaluated in the VANQUISH Phase 3 registrational program for obesity.
Press | Mechanism: dual GLP-1 / GIP receptor agonist
🆕 NEWLY REGISTERED TRIALS (3 in last week)
Exenatide circular RNA (CR059) Early Phase 1 single ascending dose study in Chinese subjects with type 2 diabetes (First Affiliated Hospital of Henan University..., n=9)
[New Indications]
Trials: NCT07347080 (CR059101) | Mechanism: GLP-1 receptor agonist
AMAZE 1 Phase III investigating NNC0487-0111, a new medicine for weight loss in people with excess body weight (Novo Nordisk, n=1150)
[Weight Loss/Efficacy]
Trials: NCT07339423 (AMAZE 1) | Mechanism: GLP-1 + amylin combination (amycretin)
Petrelintide Phase I pharmacokinetic study testing different drug concentrations of the long-acting amylin analog for weight management (Zealand Pharma, n=48)
[Weight Loss/Efficacy]
Trials: NCT07338214 | Mechanism: Amylin receptor agonist
💡 TRIAL SPOTLIGHT
Educational spotlight selected by editors
A Single-Center, Open-Label, Single Ascending Dose Study of Exenatide Circular RNA-Lipid Nanoparticle Injection (CR059) in Chinese Subjects With Type 2 Diabetes Mellitus (CR059101)
This Early Phase 1, open-label study is designed to evaluate the safety and pharmacokinetics of CR059, a novel circular RNA (circRNA) candidate, in nine participants with Type 2 Diabetes Mellitus. Encapsulated in lipid nanoparticles, CR059 encodes exenatide—a GLP-1 receptor agonist—but leverages the unique closed-loop structure of circRNA to resist enzymatic degradation. This structural stability aims to prolong protein expression, potentially addressing the durability limitations often associated with linear mRNA and traditional peptide therapies. As an initial clinical test initiated by The First Affiliated Hospital of Henan University of Science and Technology, this trial serves as a strategic proof-of-concept for determining whether circRNA technology can successfully deliver sustained metabolic control in a human setting.
🔬 MECHANISM EXPLAINED
Understanding the science behind the therapeutics
GLP-1 receptor agonist with a unique delivery mechanism (Example drug: CR059/Exenatide circRNA)
CR059 represents a “genetic medicine” approach to GLP-1 therapy, utilizing circular RNA (circRNA) encapsulated in lipid nanoparticles (LNPs) rather than injecting the therapeutic peptide directly. Upon injection, the LNPs deliver the circRNA payload into the patient’s cells, where it serves as a durable template for the continuous intracellular production and secretion of exenatide (exendin-4). Unlike linear mRNA, circRNA forms a closed loop that evades degradation by exonucleases, significantly extending its intracellular stability and allowing for sustained protein expression over days or weeks. This mechanism potentially offers a “bio-factory” effect, reducing dosing frequency beyond what is possible with standard peptide injections or linear mRNA.
Why it matters:
Modality Shift: Moves beyond simple peptide replacement to instructing the body to manufacture its own drug, a key differentiator in a crowded market.
Durability: The stable circRNA platform enables prolonged protein production, potentially achieving ultra-long-acting profiles that could allow for less frequent dosing than standard peptide injections.
This newsletter compiles publicly available information from company press releases and ClinicalTrials.gov. Not investment advice.
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