EXHIBIT No. 03 // ON THE RECORD

TB-500 Benefits for Tissue Repair and Wound Healing in the Research Literature

The strongest exhibits in the file are wound and epithelial findings — measured, cited, and tagged for the molecule they were actually run on.

The headline wound finding

TB-500 Benefits for Tissue Repair and Wound Healing in the Research Literature begin with the clearest exhibit on the record: a rat full-thickness wound model in which topical or intraperitoneal thymosin beta-4 increased re-epithelialization by 42% at 4 days and up to 61% at 7 days versus saline, increased wound contraction by at least 11% by day 7, and raised collagen deposition and angiogenesis [3]. As little as 10 picograms stimulated keratinocyte migration 2-to-3-fold in the same work [3].

Those are precise, reproducible animal numbers. They are also on the full-length parent protein — the ~4963 Da Tβ4, not the ~889 Da TB-500 heptapeptide. The benefit case for the fragment in humans inherits these figures without yet earning them.

Does TB-500 help wound healing?

In animal and topical models, thymosin beta-4 accelerated dermal and corneal re-epithelialization and increased contraction, collagen, and angiogenesis [3]; a 2016 review summarized its promotion of dermal healing [8]. Human efficacy of the 7-mer is unproven. The wound-healing evidence is strong in rodents on the parent protein and absent for the fragment in controlled human trials.

How long does it take for TB-500 to work for injury healing?

No human timeline is established for the fragment. In a rat wound model, full-length thymosin beta-4 raised re-epithelialization by 42% at 4 days and up to 61% at 7 days [3] — an animal-model time course, not a human dosing schedule. Translating those days to a person is not supported by any controlled human data.

Does TB-500 help corneal or eye healing?

Topical thymosin beta-4 promoted corneal wound healing and decreased inflammation in a murine alkali-injury model [7], and the clinical-grade ophthalmic formulation RGN-259 improved dry-eye signs in placebo-controlled trials. A 2025 engineered tandem thymosin peptide also promoted corneal wound healing [12]. The ophthalmic evidence is among the most developed, but it is on Tβ4-based formulations, not the TB-500 fragment as marketed.

The mechanism behind the wound numbers

The re-epithelialization figures are not a black box; they follow from the protein's cell biology. Thymosin beta-4 mobilizes and migrates keratinocytes and endothelial cells, which is why a wound resurfaces faster and vascularizes more [3][5]. The picogram potency in the migration assay — ~10 pg stimulating keratinocyte migration 2-to-3-fold [3] — points to a signaling effect rather than a bulk structural one.

That migration activity traces back to the actin-binding core, the LKKTETQ motif that the TB-500 fragment carries [1]. It is the strongest mechanistic reason to think the fragment might do something in a wound. It is also why the question is genuinely open rather than settled: carrying the motif is not the same as reproducing the 43-residue protein's full program at a tolerated dose, and no controlled human wound study of the fragment has tested it.

Extracellular-matrix remodeling and scarring

Beyond resurfacing the wound, thymosin beta-4 shapes how the matrix is rebuilt. The protein promoted matrix metalloproteinase expression during wound repair, supporting extracellular-matrix remodeling [9], and reviews credit it with reducing myofibroblast number, which lowers scar formation [5].

Recent biomaterials work pushes the same angle through delivery systems: a 2025 study combined thymosin beta-4 with selenium and improved diabetic-ulcer healing [11], and a separate 2025 study loaded Tβ4 into a hemostatic, antibacterial exosome hydrogel that improved vascularized wound repair [15]. These are animal and engineered-construct studies on the parent protein, illustrating where the research is heading rather than establishing the fragment in humans.

What the tissue-repair file does and does not show

On the record: accelerated re-epithelialization, increased contraction, raised collagen and angiogenesis, and reduced scarring in animal and in-vitro wound models — all on full-length thymosin beta-4 [3][5][7][9]. The effect sizes are large and the picogram potency is striking [3].

Not on the record: a single controlled human trial of the TB-500 heptapeptide for wound healing or any tissue-repair endpoint. The benefits described here are the parent protein's, demonstrated in animals; the fragment's human benefit remains an open question. The TB-500 references and citations list every study behind these figures.