Thymosin beta-4

Research overview

Key studies

1. Sosne et al., Int J Mol Sci (SEER-1) (2022)

   Randomized, double-masked, placebo-controlled phase 3 (terminated early)
   Model: Humans (18 people with stage 2-3 neurotrophic keratopathy)

   Complete healing at 4 weeks in 6 of 10 RGN-259 versus 1 of 8 placebo participants (p = 0.0656); some comfort scores differed; sponsor employees co-authored ^10.

2. Sosne and Ousler, Clin Ophthalmol (2015)

   Single-center randomized, double-masked, placebo-controlled phase 2, 28 days
   Model: Humans (72 adults with moderate to severe dry eye)

   Neither primary endpoint differed from placebo at day 29; several secondary endpoints, including central corneal staining, differed ^8.

3. Ruff et al., Ann N Y Acad Sci (2010)

   Randomized, placebo-controlled single and 14-day multiple ascending-dose phase 1
   Model: Humans (40 healthy volunteers)

   No dose-limiting toxicities or serious adverse events; exposure was dose-proportional and half-life rose with dose ^6.

4. Bock-Marquette et al., Nature (2004)

   Cell culture and coronary-ligation model
   Model: Cells and animals (mice)

   Tβ4 formed a complex with PINCH and ILK, activated Akt, and was associated with improved cardiac function after ligation ^3.

5. Banerjee et al., Circ Res (2012)

   Global and cardiac-specific gene knockout
   Model: Animals (mice)

   Knockout mice were born at Mendelian ratios with normal heart and vessel formation and normal adult cardiac function ^5.

Doses used in published trials

What investigators administered in the cited studies, recorded as a fact about those studies. Not a protocol and not a recommendation.

• In SEER-1 (NCT02600429), people with neurotrophic keratopathy received 0.1% RGN-259 or placebo eye drops five times a day for 4 weeks ^10,20.
• In ARISE-3 (NCT03937882), adults with dry eye received RGN-259 or placebo eye drops four times a day for 14 days ^11.
• In a phase 2 severe dry-eye trial (NCT01393132), 0.1% RGN-259 or vehicle was instilled 6 times daily for 28 days ^9.
• In a phase 1 study, healthy volunteers received single intravenous doses of 42, 140, 420 or 1260 mg synthetic Tβ4 or placebo, then the same dose daily for 14 days ^6.
• In the NL005 phase IIb myocardial infarction study (NCT05984134), arms received recombinant human Tβ4 intravenously at 0.5 or 1.0 µg/kg per the arm descriptions, or placebo, for 7 days after PCI ^14.

Published adverse-event data

Reported in the cited trials or product labels. Frequencies apply to the stated population and do not transfer to other settings.

• Any non-serious adverse event (registry tally)
  47 of 350 RGN-259 versus 31 of 349 placebo; no serious adverse events in either arm
  Adults with dry eye, ARISE-3 (NCT03937882) ¹¹ · As posted in registry results
• Serious adverse events (registry tally)
  3 of 299 RGN-259 versus 2 of 302 placebo
  Adults with dry eye, ARISE-2 (NCT02974907) ¹² · As posted in registry results
• Adverse events after intravenous dosing
  Described as infrequent; no serious events
  40 healthy volunteers, phase 1 ⁶ · Mild or moderate

What is not known: Long-term human safety, systemic pharmacokinetics in patients, and whether results from the topical eye-drop trials apply to any other route are not established ^6,8,10. The biological necessity of endogenous Tβ4 for cardiac repair is disputed by knockout data ^5. Detailed ARISE-2 and ARISE-3 efficacy results were not located in a peer-reviewed publication in the sources reviewed ^11,12.

Regulatory status

Status

Not FDA-approved; no Drugs@FDA application was located as of 2026-10-24 ^17. The RGN-259 eye drop has completed phase 3 dry-eye trials and a second neurotrophic keratopathy phase 3 trial (SEER-2) was listed as recruiting ^11,12,19.

United States (FDA)

No FDA-approved thymosin beta-4 product was located in Drugs@FDA as of 2026-10-24 ^17. FDA's compounding safety-risk page (current as of April 22, 2026) addresses the TB-500 fragment, not the full-length protein ^15.

Sport (WADA)

The 2026 Prohibited List names 'Thymosin-β4 and its derivatives e.g. TB-500' under S2.3 (growth factors and growth factor modulators); S2 substances are prohibited at all times and are non-Specified Substances ^16.

Status varies by country and changes over time. How we describe regulatory status.

References

1. UniProtKB P62328 (TYB4_HUMAN): Thymosin beta-4 UniProt. 2026
2. Thymosin beta 4 sequesters the majority of G-actin in resting human polymorphonuclear leukocytes J Cell Biol. 1992
3. Thymosin beta4 activates integrin-linked kinase and promotes cardiac cell migration, survival and cardiac repair Nature. 2004
4. Thymosin beta4 induces adult epicardial progenitor mobilization and neovascularization Nature. 2007
5. Thymosin beta 4 is dispensable for murine cardiac development and function Circ Res. 2012
6. A randomized, placebo-controlled, single and multiple dose study of intravenous thymosin beta4 in healthy volunteers Ann N Y Acad Sci. 2010
7. A first-in-human, randomized, double-blind, single- and multiple-dose, phase I study of recombinant human thymosin beta4 in healthy Chinese volunteers J Cell Mol Med. 2021
8. Thymosin beta 4 ophthalmic solution for dry eye: a randomized, placebo-controlled, Phase II clinical trial conducted using the controlled adverse environment (CAE) model Clin Ophthalmol. 2015
9. Thymosin beta4 significantly improves signs and symptoms of severe dry eye in a phase 2 randomized trial Cornea. 2015
10. 0.1% RGN-259 (Thymosin beta4) Ophthalmic Solution Promotes Healing and Improves Comfort in Neurotrophic Keratopathy Patients in a Randomized, Placebo-Controlled, Double-Masked Phase III Clinical Trial Int J Mol Sci. 2022
11. Assessment of the Safety and Efficacy of RGN-259 Ophthalmic Solutions for Dry Eye Syndrome: ARISE-3 (NCT03937882) ClinicalTrials.gov. 2026
12. Assessment of the Safety and Efficacy of RGN-259 Ophthalmic Solutions for Dry Eye Syndrome: ARISE-2 (NCT02974907) ClinicalTrials.gov. 2026
13. A Study of the Safety and Efficacy of Injectable Thymosin Beta 4 for Treating Acute Myocardial Infarction (NCT01311518) ClinicalTrials.gov. 2026
14. Efficacy and Safety Study of Thymosin Beta 4 in Patients With Acute Myocardial Infarction (NL005 phase IIb; NCT05984134) ClinicalTrials.gov. 2026
15. Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks (content current as of 04/22/2026) FDA. 2026
16. Tractatenblad 2026 Nr. 25: Anti-doping convention (ETS No. 135), amendment to the appendix - The 2026 Prohibited List, World Anti-Doping Code (English text; entry into force 1 January 2026) Tractatenblad van het Koninkrijk der Nederlanden (official government publication). 2026
17. openFDA Drugs@FDA query for 'thymosin' (no matching applications) FDA (openFDA Drugs@FDA). 2026
18. PubChem compound record for thymosin beta 4 (CID 45382195) PubChem. 2026
19. Assessment of the Safety and Efficacy of 0.1% RGN-259 Ophthalmic Solution for the Treatment of NK: SEER-2 (NCT05555589) ClinicalTrials.gov. 2026
20. Assessment of the Safety and Efficacy Study of RGN-259 Ophthalmic Solutions for Neurotrophic Keratopathy: SEER-1 (NCT02600429) ClinicalTrials.gov. 2026