TB-500 (Thymosin Beta-4)

Thymosin beta 4: A potential novel adjunct treatment for bacterial keratitis

Sosne G et al. · International immunopharmacology · 2023

Reviews thymosin beta 4 as an adjunct in bacterial keratitis, covering the corneal models in which it has been examined and its reported effects on inflammation and repair.

Context: Concerns one ocular indication. It does not generalise to systemic tissue repair.

RGN-259 neurotrophic keratopathy phase III

0.1% RGN-259 (Thymosin ß4) Ophthalmic Solution Promotes Healing and Improves Comfort in Neurotrophic Keratopathy Patients in a Randomized, Placebo-Controlled, Double-Masked Phase III Clinical Trial

Sosne G et al. · International journal of molecular sciences · 2022

Population: Patients with Stage 2 or Stage 3 neurotrophic keratopathy and persistent corneal epithelial defects; 10 subjects assigned to the active arm and 8 to placebo

A phase 3 randomised, double-masked, placebo-controlled trial compared a 0.1% thymosin beta-4 ophthalmic solution with vehicle placebo in 18 patients with stage 2 or 3 neurotrophic keratopathy. The investigators measured closure of persistent corneal epithelial defects at four weeks, Mackie classification disease stage, time to closure, patient-reported ocular symptoms and adverse events.

As reported by the study

Route reported

Topical ophthalmic solution applied to the eye

Schedule

Administered under the trial protocol across a 28-day treatment period, with assessments continuing to day 43; the abstract does not state the daily instillation frequency

Duration

28 days of treatment with follow-up to day 43

Treatment arms

0.1% RGN-259 (thymosin beta-4) ophthalmic solution · Placebo vehicle

Context: Eighteen subjects in total, so the trial is very small for a phase 3 label and its primary comparison did not reach the conventional significance threshold. It studies the full-length thymosin beta-4 protein applied to the ocular surface, and says nothing about the TB-500 fragment, about injected or systemic administration, or about any tissue outside the cornea.

The effect of thymosin treatment of venous ulcers

Guarnera G et al. · Annals of the New York Academy of Sciences · 2010

Population: 73 randomised patients with venous stasis ulcers of the lower limb, recruited across eight European sites in Italy and Poland

A multicentre, double-blind, placebo-controlled, dose-escalation phase 2 trial randomised 73 patients with venous stasis ulcers to topical thymosin beta-4 or placebo alongside standard ulcer care. The authors assessed safety and tolerability at each dose level and recorded complete wound closure over the study period.

As reported by the study

Route reported

Topical application to the ulcer

Schedule

Applied under the trial protocol in a sequential dose-escalation design, with dose levels including 0.03%

Duration

Healing assessed over approximately three months as reported by the authors

Treatment arms

Topical thymosin beta-4 at ascending dose levels, including 0.03% · Placebo

Context: Reported as a short conference-proceedings summary rather than a full trial report, so randomisation detail, per-arm numbers, comparative closure rates and statistical testing are not presented. Dose-escalation designs spread a small sample across several dose levels, the topical route to an open ulcer is not comparable to injected use, and the product tested is full-length thymosin beta-4, not TB-500.

A randomized, placebo-controlled, single and multiple dose study of intravenous thymosin beta4 in healthy volunteers

Ruff D et al. · Annals of the New York Academy of Sciences · 2010

Population: Healthy adult volunteers in four cohorts of 10 subjects each (40 subjects in total)

A randomised, placebo-controlled phase 1 study gave 40 healthy volunteers ascending single intravenous doses of synthetic thymosin beta-4 (42 to 1260 mg) followed by the same daily dose for 14 days. The investigators recorded treatment-emergent adverse events, dose-limiting toxicity and pharmacokinetic parameters including half-life and dose proportionality.

As reported by the study

Route reported

Intravenous

Schedule

Under the study protocol each cohort received a single intravenous dose and then, after safety review, the same dose once daily for 14 days

Duration

Single dose followed by 14 consecutive daily doses

Treatment arms

Synthetic thymosin beta-4 42 mg · Synthetic thymosin beta-4 140 mg · Synthetic thymosin beta-4 420 mg · Synthetic thymosin beta-4 1260 mg · Placebo

Context: A first-in-human tolerability and pharmacokinetic study in healthy volunteers with no disease endpoint and no efficacy measure; 40 subjects and 14 days of exposure cannot characterise uncommon or delayed harms. It uses the full-length 43-amino-acid protein given intravenously, so its pharmacokinetics do not transfer to the TB-500 fragment or to subcutaneous or intramuscular use.

Simultaneous quantification of TB-500 and its metabolites in in-vitro experiments and rats by UHPLC-Q-Exactive orbitrap MS/MS and their screening by wound healing activities in-vitro

Rahaman KA et al. · Journal of chromatography. B, Analytical technologies in the biomedical and life sciences · 2024

Population: Human serum and isolated in-vitro enzyme systems, cultured fibroblasts, and rats dosed with TB-500 with urine collected over time

This study developed and validated a mass-spectrometry method to quantify TB-500 and its breakdown products simultaneously, then tracked its metabolism in human serum, in isolated enzyme systems and in the urine of dosed rats. The authors separately compared the parent peptide and each identified metabolite in fibroblast cytotoxicity and scratch-wound migration assays.

As reported by the study

Route reported

TB-500 administered to rats with urine sampled thereafter; the abstract does not state the administration route

Schedule

Rat urine collected under the study protocol from 0-6 hours and out to 72 hours after dosing

Duration

Metabolite sampling to 72 hours

Treatment arms

TB-500 (Ac-LKKTETQ) parent peptide · Identified metabolites including Ac-LK, Ac-LKK and Ac-LKKTE · Untreated control (in-vitro assays)

Context: Entirely analytical and preclinical: the biological readout is a cultured-cell scratch assay, not a wound in a living animal or person, and there is no human pharmacokinetic data. The authors explicitly frame their own metabolite finding as a challenge to the assumption that the parent peptide is the active species, which is a hypothesis raised by this work rather than a settled question.

Synthesis and characterization of the N-terminal acetylated 17-23 fragment of thymosin beta 4 identified in TB-500, a product suspected to possess doping potential

Esposito S et al. · Drug testing and analysis · 2012

Population: Not applicable — the materials examined were a commercially obtained TB-500 formulation, a synthesised reference peptide, and spiked human plasma and urine

An analytical study used high-performance liquid chromatography with high-resolution Orbitrap mass spectrometry to determine which peptide is actually present in a commercial TB-500 formulation, and independently synthesised that peptide by solid-phase synthesis as a reference standard. The authors then proposed a triple-quadrupole method for detecting it in plasma and urine.

As reported by the study

Route reported

Not applicable; no administration to humans or animals

Context: This is a laboratory identification and detection-method paper with no biological, animal or clinical component, so it reports nothing about what the peptide does in a body. It characterises one sourced product at one point in time and cannot speak to the composition, purity or content of any other material sold under the same name.

Effects of BPC-157 and TB-500 on Achilles tendon healing in rats: A histopathological and biomechanical study

Biçer O et al. · Joint diseases and related surgery · 2026

Population: Thirty-two male Sprague-Dawley rats, approximately 12 weeks old, following standardised Achilles tendon transection and surgical repair; eight animals per group

Thirty-two rats undergoing standardised Achilles tendon transection and repair were randomised to control, BPC-157, TB-500 or the combination, given intraperitoneally daily for four weeks. The investigators measured maximum load to failure biomechanically and graded tendon histology using Bonar and Movin scoring, Sirius red birefringence and immunohistochemical collagen type I and III expression.

As reported by the study

Route reported

Intraperitoneal injection

Schedule

Administered daily for four weeks after surgery under the study protocol

Duration

Four weeks post-operatively

Treatment arms

Control · BPC-157 10 µg/kg/day · TB-500 60 µg/kg/day · BPC-157 plus TB-500 combined

Context: An animal study with eight rats per group and a single four-week endpoint, described by its own authors as exploratory and preliminary; rodent tendon healing, a surgically transected model, an intraperitoneal route and a weight-scaled rodent dose do not translate to human injury or human dosing. Multiple histological and immunohistochemical comparisons were made without a stated correction, and no human evidence for TB-500 in tendon injury was identified.