TB-500: Safety Profile & Research Summary

Preclinical Research Summary

Animal Studies (TB-500 Fragment Specifically)

Study	Model	Key Findings	Ref
Rahaman et al. (2024)	Rat / fibroblasts in vitro	Metabolite Ac-LKKTE showed wound-healing activity — parent TB-500 did not. Primary metabolite Ac-LK at 0-6h, Ac-LKK to 72h. No cytotoxicity.	[17]
Philp et al. (2003)	db/db diabetic mice, aged mice	LKKTETQ fragment promoted dermal repair comparable to full-length Tβ4. ↑ wound contracture and collagen deposition.	[8]
Sosne et al. (2010)	In vitro (LDH assay)	No significant difference between acetylated TB-500 and non-acetylated LKKTETQ on cell injury (LDH release).	[26]
Ho et al. / Kwok et al. (2012-2013)	Thoroughbred horses	10 mg SC single dose; detected at 0.02 ng/mL in plasma, 0.01 ng/mL urine. Detection: 11.3h plasma, 9.7h urine.	[27][28]

Studies Using Full-Length Thymosin Beta-4 (Parent Molecule)

Note: These studies used the 43-amino acid full-length Tβ4 protein, not the TB-500 fragment. Results may not be directly transferable to the 7-amino acid fragment.

Study	Model	Key Findings	Ref
Bao et al. (2013)	Rat myocardial ischemia	5.37 mg/kg IP, long-term dosing — 43% infarct volume reduction (p < 0.01)	[21]
Bock-Marquette et al. (2004)	Mouse cardiac cells	Tβ4 activates ILK → promotes cardiac cell migration, survival, and cardiac repair (published in Nature)	[11]
Smart et al. (2007)	Mouse epicardial progenitors	Tβ4 induces epicardial progenitor mobilization and neovascularization (published in Nature)	[29]
Malinda et al. (1999)	Rat dermal wound	Tβ4 increased re-epithelialization by 42% over saline at 4 days post-injury	[18]
Shah et al. (2018)	Mouse liver fibrosis	Tβ4 prevented oxidative stress, inflammation, and fibrosis in ethanol/LPS liver injury	[25]

Clinical Studies / Human Data (Full-Length Tβ4 Only)

No registered human clinical data exists specifically for the TB-500 fragment. The following are clinical data for the full-length Thymosin Beta-4 protein.

Study	Design	n=	Key Outcome	Ref
RGN-352 Phase I	IV in healthy volunteers	40	Safe, well-tolerated, no dose-limiting toxicities at doses up to 1260 mg cumulative over 14 days	[30]
RGN-259 Phase II (Dry Eye)	0.1% ophthalmic solution	—	Improved signs and symptoms of severe dry eye; no drug-related serious adverse events	[19][20]
RGN-137 Phase II (Pressure Ulcers)	Topical gel 0.01-0.1%	—	Accelerated dermal healing; no drug-related SAEs	[31]

Pharmacokinetic Parameters

Parameter	Value	Ref
G-Actin Binding	1:1 stoichiometric complex (LKKTETQ motif)	[6]
ATP Synthase KD	~12 nM (endothelial cell surface)	[10]
In vitro migration activity	~50 nM (identical to full-length Tβ4)	[26]
Plasma Half-life (SC)	~2.5–3 hours	[27]
Equine Detection	Plasma 11.3h, urine 9.7h (10 mg SC)	[28]
Primary Metabolite	Ac-LK (0-6h), Ac-LKK (up to 72h)	[17]
Acute Toxicity Threshold	No toxicity observed up to 20 mg/kg	[3]

Comparison: TB-500 (Fragment) vs. Thymosin Beta-4 (Full Protein)

Feature	TB-500 (Ac-LKKTETQ)	Thymosin Beta-4 (Full)
Length	7 amino acids (fragment 17–23)	43 amino acids
Actin Binding	✅ Retains LKKTETQ motif	✅ Full actin-binding domain
Anti-Fibrotic (Ac-SDKP)	❌ Absent (aa 1–4 not included)	✅ Present via N-terminal Ac-SDKP
Cell Migration	Comparable (~50 nM)	Comparable (~50 nM)
Wound Healing	Via metabolite Ac-LKKTE	Direct + via Ac-SDKP
Human Clinical Data	None	Phase I/II (RGN-352, 259, 137)
FDA Status	Category 2 (prohibited)	IND (clinical development)