MOTS-c Enters Its First Human Efficacy Trial: Inside the 2026 Phase 2a Study
TL;DR: MOTS-c enters its first human efficacy trial in 2026 — Hudson Biotech Phase 2a tests insulin sensitivity in prediabetes.
What Is the New MOTS-c Human Trial Testing?
ClinicalTrials.gov registry NCT07505745, sponsored by Hudson Biotech, describes a Phase 2a randomised, double-blind, placebo-controlled study of investigational MOTS-c in adults with prediabetes and overweight or obesity.[1] It is the first registered trial to dose MOTS-c — a 16-amino-acid mitochondrial-derived peptide — directly in humans and measure a clinical efficacy endpoint, rather than simply observing correlations between circulating MOTS-c levels and metabolic markers in existing cohorts.
Design: Participants are randomised 1:1 to investigational MOTS-c or placebo. After a screening period of up to 4 weeks, both arms receive a 12-week double-blind treatment period plus standardised lifestyle counselling, followed by a 4-week post-treatment safety follow-up (through week 16). Primary efficacy endpoint: change from baseline in oral-glucose-tolerance-test (OGTT)-derived insulin sensitivity, measured by the Matsuda Index. Primary safety endpoint: treatment-emergent adverse events through week 16. Secondary endpoints: HbA1c, fasting glucose, 2-hour OGTT glucose, and immunogenicity.
Source: ClinicalTrials.gov, NCT07505745
The trial is currently recruiting and has not read out. As with any Phase 2a study, it is designed primarily to establish an efficacy and safety signal in a defined patient population, not to support a regulatory filing on its own.
Why Is This a Milestone for MOTS-c Research?
Preclinical interest in MOTS-c has been building for over a decade. In rodent models, MOTS-c has been reported to activate AMPK, the cell's central energy-status sensor, largely in skeletal muscle, by interfering with the folate cycle and driving accumulation of the AMPK-activating intermediate AICAR — a mechanism covered in more depth in our MOTS-c research overview. Whole-animal studies have also linked MOTS-c to improved insulin sensitivity and reduced diet-induced weight gain, even with ageing or a high-fat diet.
What has been missing is a registered human trial that doses MOTS-c itself and measures a clinical outcome. The existing human literature is limited to small observational work — for example, a cohort of ten adults in which circulating MOTS-c levels correlated with insulin-sensitivity markers (HOMA and the Matsuda Index) only in lean individuals — which is associative, not interventional. NCT07505745 changes that: it is a controlled, dosed, prospective test of whether the rodent AMPK/insulin-sensitivity signal translates to people.
What Happened to the Last Attempt to Develop a MOTS-c Drug?
This is not the first company to try to turn MOTS-c biology into a drug candidate. CohBar Inc. developed CB4211, a MOTS-c-derived analogue, and in August 2021 reported topline Phase 1a/1b results in adults with NASH (non-alcoholic steatohepatitis) and obesity, showing reductions in markers of liver damage alongside lower blood glucose and modest weight loss over four weeks.[2]
The programme did not progress smoothly. CohBar disclosed in November 2018 that the study had been temporarily suspended to address persistent mild injection-site reactions, restarted with an adjusted formulation, and was further delayed by the COVID-19 pandemic. Ultimately, CohBar determined that the formulation used in the Phase 1b stage was not suitable for further development, and its efforts to produce an improved formulation were unsuccessful.[3] In 2023, CohBar's board approved a merger with Morphogenesis, with CohBar shareholders ending up with roughly 15% of the combined entity, which became TuHURA Biosciences.[4] The CB4211 programme effectively ended there.
Hudson Biotech's NCT07505745 is a separate, newly registered programme testing MOTS-c in a different indication (prediabetes and insulin sensitivity, rather than NASH), with no public link between the two sponsors. It represents a fresh attempt at human MOTS-c drug development roughly five years after the field's only prior clinical dataset.
How Does the New Trial Compare to the Last One?
| Programme | Sponsor | Phase / year | Population | Status |
|---|---|---|---|---|
| CB4211 (MOTS-c analogue) | CohBar Inc. | Phase 1a/1b, topline Aug 2021 | NASH + obesity | Discontinued; CohBar merged into TuHURA Biosciences, 2023 |
| NCT07505745 (MOTS-c) | Hudson Biotech | Phase 2a, registered 2026 | Prediabetes + overweight/obesity | Recruiting; no results reported yet |
CB4211 and the compound tested in NCT07505745 are separate development programmes from different sponsors. This table is for contextual research reference only.
How Does This Fit With MOTS-c's Regulatory Status?
Two separate tracks
NCT07505745 is a sponsor-led investigational drug trial working toward possible future drug development. It is entirely separate from the FDA's Pharmacy Compounding Advisory Committee (PCAC) meeting on 23–24 July 2026, which is reviewing whether MOTS-c and six other peptides should be added to the Section 503A Bulk Drug Substances List for compounding.
Evidence gaps remain in the compounding review
FDA briefing documents ahead of the PCAC meeting flagged evidence gaps across several of the peptides under review; our coverage of that briefing explains what agency scientists found and did not find for each compound. A single newly registered Phase 2a trial does not resolve those gaps.
Neither process changes MOTS-c's current status
MOTS-c remains an unlicensed, unapproved investigational peptide. It is not an approved medicine in the US, UK, or anywhere else, and no interim result from NCT07505745 changes that while the trial is ongoing.
What Should UK Researchers Take From This?
For context, this kind of transition — a compound moving from preclinical/observational human data into a registered, dosed efficacy trial — is the same step retatrutide (LY3437943) took years before it reached its current, much more advanced Phase 3 TRIUMPH programme. MOTS-c is at a considerably earlier stage: one recruiting Phase 2a trial, from one sponsor, in one indication, with no results yet reported. Researchers should treat this as an early-stage development signal, not evidence of clinical efficacy.
Velox Peptides supplies MOTS-c strictly as an HPLC-verified in vitro research reagent, with batch-specific certificates of analysis. It is not licensed for any indication, including insulin sensitivity or metabolic disease, is not a medicine under the Human Medicines Regulations 2012, and Velox Peptides makes no therapeutic or efficacy claims for it, including in connection with NCT07505745 or CB4211.
MOTS-c is supplied as a research reagent only. It is not a medicine and has not been evaluated by the MHRA or FDA for use in our products. Not for human or veterinary use. See our Research Use Policy and MHRA Statement.
References
- MOTS-c for Improving Insulin Sensitivity in Adults With Prediabetes and Overweight/Obesity. ClinicalTrials.gov, NCT07505745, sponsor Hudson Biotech. clinicaltrials.gov
- CohBar Inc. New Data Available on CB4211 for NASH and Obesity, topline Phase 1a/1b results, August 2021. patientworthy.com
- CohBar, Inc. CB4211 programme overview and formulation status. cohbar.com
- CohBar, Inc. SEC Form S-4/A: merger of CohBar and Morphogenesis Holdings to form TuHURA Biosciences, 2023. sec.gov
- U.S. Food and Drug Administration. Pharmacy Compounding Advisory Committee; Notice of Meeting, 23–24 July 2026 (docket FDA-2025-N-6895). fda.gov
Frequently Asked Questions
What is the new MOTS-c clinical trial testing?
NCT07505745, sponsored by Hudson Biotech, is a Phase 2a randomised, double-blind, placebo-controlled trial of investigational MOTS-c in adults with prediabetes and overweight or obesity. Participants are randomised 1:1 to MOTS-c or placebo for a 12-week double-blind treatment period, with a screening period of up to 4 weeks and a 4-week post-treatment safety follow-up. The primary efficacy endpoint is change from baseline in OGTT-derived insulin sensitivity, measured by the Matsuda Index; safety is also a primary endpoint, tracked via treatment-emergent adverse events through week 16.
Has MOTS-c been tested in humans before?
Not as an administered investigational drug tested for efficacy. Prior human data on MOTS-c is limited to small observational studies correlating circulating MOTS-c levels with insulin-sensitivity markers (such as HOMA and the Matsuda Index) in existing cohorts, and to the separate CB4211 programme, which tested a modified MOTS-c-related peptide rather than MOTS-c itself. NCT07505745 is the first registered trial to dose MOTS-c directly and measure a clinical efficacy endpoint.
What happened to CohBar's MOTS-c drug programme, CB4211?
CohBar Inc. developed CB4211, a MOTS-c-derived analogue, and reported topline Phase 1a/1b results in NASH and obesity in August 2021, showing reductions in liver-damage markers alongside lower blood glucose and modest weight loss over four weeks. However, CohBar determined that the formulation used in the Phase 1b stage was not suitable for further development, and efforts to produce an improved formulation were unsuccessful. In 2023, CohBar's board approved a merger with Morphogenesis, forming TuHURA Biosciences, which effectively ended the CB4211 programme.
Does this trial change MOTS-c's compounding legal status in the US?
No. NCT07505745 is a sponsor-led investigational drug trial, unrelated to the FDA Pharmacy Compounding Advisory Committee's (PCAC) review of MOTS-c on 23–24 July 2026, which concerns whether MOTS-c should be added to the Section 503A Bulk Drug Substances List for compounding. The two processes run on separate tracks: one is drug development toward a possible future New Drug Application, the other is a compounding-eligibility recommendation. Neither currently makes MOTS-c an approved or prescribable medicine.
Is MOTS-c available for research use in the UK?
Yes, for in vitro laboratory research only. Velox Peptides supplies MOTS-c as an HPLC-verified research reagent for qualified researchers. It is not a licensed medicine, has not been evaluated by the MHRA or FDA, and is not for human or veterinary use. Velox Peptides makes no therapeutic or efficacy claims for MOTS-c, including in relation to insulin sensitivity or the trial discussed in this guide.