Compounds for use in the treatment of a skin disease or skin condition, in reducing the amount of fluid exuding from one or more wounds or blisters, in promoting a healthy skin microbiome and in reducing scarring, and composition.

Abstract

The present invention relates to peptides for treatment of skin diseases and skin conditions. In particular, the present invention relates to peptide for treatment of wounds and / or blisters in patients suffering from a skin disease or skin condition selected from the group consisting of blistering disease, a disease or condition characterized by excessive wound exudate, a disease or condition characterised by a dysregulated skin microbiome and scars.

Description

131 Compounds for use in the treatment of a skin disease or skin condition, in reducing the amount of fluid exuding from one or more wounds or blisters, in Promoting a healthy skin microbiome and reducing scars, and composition. TECHNICAL FIELD

[001] The present invention relates to peptides for the treatment of skin diseases and conditions. In particular, the present invention relates to a peptide for the treatment of wounds and / or blisters in patients suffering from a skin disease or condition selected from the group consisting of bullous disease, a disease or condition distinguished by excessive wound exudate, a disease or condition distinguished by a dysregulated skin microbiome, and scarring. FUNDAMENTALS

[002] Under normal conditions, wounds heal sequentially and promptly, distinguished by four main phases (hemostasis, inflammation, proliferation, and remodeling). This is a complex process involving chemokines, growth factors, cytokines, proteases and antiproteases, and multiple cell types that act in a controlled manner during the healing process. If this process is interrupted at various stages and by different factors, a dysfunctional inflammatory phase occurs, which may be associated with the interruption of wound healing. Toll-like receptors (TLRs), crucial for normal wound repair, can be overactivated and induce local dysfunctional inflammation, which can delay healing.Some wounds, for example, epidermolysis bullosa (EB) wounds, are frequently complicated by bacterial infection or hypercolonization, where bacteria and their proinflammatory products (also called PAMPs), such as endotoxins (lipopolysaccharide / LPS) from Gram-negative bacteria, lipoteichoic acid. Petition 870260058481, dated 06 / 16 / 2026, p. 10 / 140 / 131 (LTA) and peptidoglycan (PGN) from Gram-positive bacteria activate TLR signaling and induce excessive and uncontrolled inflammation with high levels of tumor necrosis factor alpha (TNF-α), interleukin (IL)-6, and IL1β, resulting in a high level of proteolysis, which can lead to delayed wound healing. PAMPs can lead to TLR-mediated activation of nuclear factor (NF)κB, which in turn can induce local cytokine release and secondary tissue damage. Epidermolysis bullosa (EB)

[003] EB comprises a group of genetic disorders that manifest as mechanically induced blistering and fragility of the skin and other stratified epithelia. Four types are recognized, depending on the level of blistering in the extended zone of the epidermal basement membrane: simple EB, junctional EB, dystrophic EB with the subgroups dominant dystrophic EB and recessive dystrophic EB (DRE), and Kindler EB. EB is associated with a high wound burden and, therefore, wounds have served as a frequently used outcome in clinical trials.

[004] Inflammation is notable in the skin with EB and promotes pain and itching (Papanikolaou et al., 2021). There is evidence that a dysregulated inflammatory response may be involved in delays in wound healing and the promotion of fibrosis in recessive dystrophic epidermolysis bullosa (RDE) (Bernasconi et al., 2021). Another factor that may be involved in impaired healing and the promotion of chronicity of wounds is bacterial inflammation, which occurs in the injured skin of all types of EB (van der Kooi-Pol et al., 2012). Wound infections can promote wound-induced malignant transformation of keratinocytes and the development of cutaneous squamous cell carcinomas, which can occur in all types of EB and are the leading cause of death in severe RDE (Hoste et al., 2015; Robertson et al., 2021). In addition to being painful and debilitating, the high burden of wound care in EB constitutes an economic burden. Petition 870260058481, dated 06 / 16 / 2026, p. 11 / 140 / 131 considerable. In the EBDR, the annual cost of dressings ranges from US$4,000 to US$245,000 in the United States (Tang et al., 2021). Bubbles

[005] Blisters occur in all types of EB after friction and relatively mild trauma. They can be present anywhere on the skin and mucous membranes. The location of a specific blister may be specific to the type of EB. For example, in epidermolysis bullosa simplex (EBS), blister formation occurs mainly on the hands and feet. In other forms of EB, such as dystrophic EB, blisters occur in the most traumatized areas, such as bony prominences. Blisters may occur singly or in groups, depending on the initial degree of trauma, and may be filled with serous or bloody fluid. Blisters are not self-limiting and fill with serous fluid and expand rapidly if left intact. Blister formation in EB is the first sequence in wound formation. Blisters contain sterile exudate (Cutting, 2003; Adderley, 2008).Exudate formation in EB depends on epidermal loss combined with leakage through underlying capillaries. This characteristic is common in EB wounds and other acute epidermal wounds. Exudate

[006] Many factors can influence exudate production. In some cases, infection can increase exudate production. However, acute wounds, such as wounds caused by EB, that are not infected, also produce exudate.

[007] Exudation is a problem in wound treatment. Some wounds, for example, chronic wounds or EB wounds, often produce an excessive amount of exudate. If this is not controlled, the wound dressing becomes saturated and moisture can leak into the skin around the wound (i.e., the perilesional skin), which can cause Petition 870260058481, dated 06 / 16 / 2026, page 12 / 140 / 131 maceration and abrasion. Macerated skin breaks easily, which can result in an increase in wound size. In addition, blister formation can progress, increasing the size of the blister and the wound (Pillay and Clapham, 2018).

[008] Exudate can have a considerable impact on the quality of life of a patient with EB. Excess exudate can lead to problems such as discomfort, pain, foul odor, and leakage (e.g., dressing leakage). Wound exudate can therefore have a major impact on the life of a patient with EB, for example, making it necessary to change dressings very frequently. Pain and fatigue, as well as bulky dressings, can make bathing and changing clothes difficult for patients with EB (Pillay and Clapham, 2018).

[009] Inadequate wound management and inappropriate dressing selection can also contribute to the problem; for example, applying a dressing designed to absorb high levels of exudate to a wound with low to moderate exudate may cause intense pain or adhere to the wound bed, causing pain and trauma upon removal, as the delicate healing tissue is damaged.

[0010] If the dressing or therapy used does not control exudate and leakage occurs (leakage of exudate through the dressing), this can lead to an increased risk of infection. Additionally, when dressings are removed too frequently, due to increased change frequency, this can result in damage to the surrounding skin through epidermal shedding. Skin / wound microbiome

[0011] The skin is an ecosystem with multiple niches, each with unique physiological conditions and therefore hosting different bacterial populations. A dysfunctional skin microbiome has been implicated in the pathogenesis of EB (Levin et al., 2021), hereinafter referred to as Petition 870260058481, dated 06 / 16 / 2026, page 13 / 140 / 131 dystrophic epidermolysis bullosa (EB) (Bar et al., 2020). Other wounds

[0012] The complications mentioned above are also present in other wounds. In particular, inflammation, infection, wound leakage, microbial dysbiosis, and scarring are common complications in patients suffering from other types of bullous diseases besides EB, as well as in patients suffering from burn wounds, chronic skin ulcers, acute infected wounds, pressure ulcers, and chronic wounds such as venous ulcers or diabetic leg ulcers. Conclusion

[0013] Although advances are being made in the overall treatment of wounds, current treatment options for EB are limited to maintaining wound cleanliness through, for example, disinfectants (Octenisept, Prontosan, etc.), antiseptic baths, and silver-containing creams. However, these approaches present significant challenges and are inadequately effective (Pillay and Clapham, 2018; Pope et al., 2012; Prodinger et al., 2019). As antimicrobial resistance increases, common antibiotics and some antiseptics are becoming even less effective in treating wound infections. Furthermore, many existing treatments, especially silver-containing creams, are harmful to the environment and toxic to the patient if used long-term. Therefore, there is a great need for new and cost-effective treatments that improve healing in patients with EB.Regarding leakage in the absence of infection, there are currently no treatments that can combat excessive leakage in wounds with EB.

[0014] Thus, in summary, there is a great need for treatment that can specifically target wound leakage while preserving the commensal microbiome, as well as reducing and normalizing the dysfunctional microbiome, including excessive levels of S. Petition 870260058481, dated 06 / 16 / 2026, page 14 / 140 / 131 pathogenic aureus. In other words, there is a great need for treatment that simultaneously addresses wound leakage, microbial dysbiosis, and healing and scar formation in EB wounds, as well as in other wounds. SUMMARY

[0015] Surprisingly, the inventors discovered that C-terminal peptides derived from thrombin can be used in the treatment of various skin conditions and diseases. In particular, the inventors found that said peptides can be used to treat a disease or condition distinguished by blistering, a disease or condition distinguished by excessive wound exudate, a disease or condition distinguished by a dysregulated skin microbiome, and scarring.

[0016] It has been previously demonstrated that C-terminal peptides derived from thrombin can be used to treat inflammation and infection. The present invention demonstrates that thrombin-derived peptides are effective in the treatment of EB. The invention also demonstrates that thrombin-derived peptides are useful for the treatment of various symptoms that may be associated with certain skin conditions and diseases. Such symptoms include excessive exudate in wounds, dysregulated skin microbiome, and scarring.

[0017] Previous findings suggest the existence of a unique skin microbiome dysbiosis associated with EB (Bar et al., 2020; Levin et al., 2021). A similar dysbiosis has been found associated with other complex wounds, including burns and chronic skin ulcers (such as venous or diabetic ulcers) (Byrd, 2018). The inventors found that C-terminal peptides derived from thrombin can alter this dysbiosis, facilitating wound healing in patients with EB and other complex wounds.

[0018] All the symptoms mentioned above can be treated with thrombin-derived peptides in combination with any Petition 870260058481, dated 06 / 16 / 2026, p. 15 / 140 / 131 skin disease or condition associated with one or more, or even all, of the aforementioned symptoms. As the symptoms are different in their essence, they have traditionally been treated by separate treatment approaches. However, as the inventors have found, the peptides of the present invention provide, in a single treatment approach, a healing, improvement or relief effect on the symptoms, so that the individual needing treatment does not need to use several different medications or adjuvants.

[0019] Thus, the present invention relates to: a method of treating a skin disease or skin condition selected from the group consisting of a disease or condition distinguished by blistering, a disease or condition distinguished by excessive wound exudate, a disease or condition distinguished by a dysregulated skin microbiome and scarring, a method of treating a skin disease or skin condition in an individual who needs it, wherein the skin disease or skin condition is a wound or a disease or condition distinguished by blistering, and wherein the treatment reduces the amount of fluid exuding from one or more wounds or blisters, a method of reducing the amount of fluid exuding from one or more wounds or blisters in an individual who needs it, and A method for promoting a healthy skin microbiome in an individual who needs it, said methods comprising administering a compound comprising a peptide comprising or consisting of the amino acid sequence X1-X2-X3-X4-X5-X6-W-X8-X9-X10, where X4, 6, 9 is any standard amino acid. X1 is I, L, or V. Petition 870260058481, dated 06 / 16 / 2026, p. 16 / 140 / 131 X2 is any standard amino acid except C. X3 is A, E, Q, R, or Y. X5 is any standard amino acid except R. X8 is I or L, X10 is any standard amino acid except H, wherein the peptide has a length of 10 to 100 amino acid residues.

[0020] The invention also relates to compositions comprising said compound comprising a peptide for use in any of the methods mentioned above. DESCRIPTION OF THE DRAWINGS

[0021] Figure 1. Schematic illustration of a clinical study. Schematic representation of a randomized, double-blind FIH study.

[0022] Figure 2. Heat map of bacterial growth. The heat maps show the bacterial count in swabs and dressing fluids (DF).

[0023] Figure 3. Graph showing bacterial growth. Box plots show bacterial counts in swabs and dressing fluids (DF).

[0024] Figure 4. The bacterial level in the controls was normalized and the bacterial level after treatment with TCP-25 was expressed relative to the control. The results showed that TCP-25 reduced the bacterial count relative to the adjacent control at all three dose levels.

[0025] Figure 5. Illustration of the replication results and definition of the recorded areas. A Whatman paper is used to transfer bacteria from the wound and surroundings to an agar plate.

[0026] Figure 6. A replication method provides spatial data of bacteria in wounds. The classification from 1 to 4 represents the bacterial density. (A) TCP-25 gel reduced bacterial levels in the wound. (B) The Petition 870260058481, dated 06 / 16 / 2026, p. 17 / 140 / 131 TCP-25 gel reduced bacterial levels in the areas surrounding the wound. (C) Bacteria on the skin adjacent to the dressing remained unchanged.

[0027] Figure 7. Bacteria were identified on the wound surface and dressing on days 3 and 8 by MALDI-TOF. Results showed the development of a microbiome with generally 1 to 3 types present. Commensal bacteria predominated, and a correspondence was observed between the types found on the wound surface and dressing. Treatment with TCP-25 did not alter the overall composition of the commensal microbiome.

[0028] Figure 8. Treatment with TCP-25 reduced bacterial levels, particularly on the wound surface, and controlled excessive levels of S. aureus. A similar observation was made for wounds colonized by the Bacillus species.

[0029] Figure 9. Wound exudate was determined by analyzing the total protein content in the dressing fluid. The results showed that bacterial levels did not correlate with protein content on days 5 and 8.

[0030] Figure 10. Treatment with TCP-25 reduced exudation, particularly on days 5 and 8, in a dose-dependent manner.

[0031] Figure 11. The difference in exudation levels was calculated relative to the adjacent control wound. 2.6 and 8.6 mg / ml of TCP-25 reduced protein content and, notably, 8.6 mg / ml of TCP-25 showed significant reductions, with only 20-30% exudation compared to the control.

[0032] Figure 12. Illustration of the reduction in exudation on day 5 in wounds treated with TCP-25. Placebo gel dressings show greater exudation.

[0033] Figure 13. In a separate experiment, conducted in the manner described above, healing and pigmentation were analyzed. The results showed that TCP-25 reduced pigmentation on day 11. Petition 870260058481, dated 06 / 16 / 2026, page 18 / 140 / 131

[0034] Figure 14. A suture contaminated with S. aureus was implanted subcutaneously in mice. The suture coated with TCP25 did not show fibrotic scarring.

[0035] Figure 15. Cutaneous tissue of Lamc2jeb mice showing the therapeutic effects of topical treatment with TCP-25 gel. (A) Bacterial count on swab and (B) bacterial count on dressing. After treatment with TCP-25, a reduction in CFUs was observed in both swab and dressing samples. (C) Representative H&E-stained photographs show epidermis and dermis. Immature epidermis and dermis with deficient architecture are observed in the control area treated with gel. However, the skin treated with TCP-25 gel showed a comparatively mature epidermis with improved dermal architecture. The bar graph shows the histological score of the skin. An improved histological score of the skin was observed in the skin of mice treated with TCP-25 gel.

[0036] Figure 16. Cutaneous tissue from Lamc2jeb mouse wounds showing the therapeutic effects of topical treatment with TCP-25 gel. (A) Bacterial count on swab and dressing showing a reduction in CFUs after treatment with TCP-25 gel. (B) Bar graphs showing cytokine measurements in wound fluid. A decrease in pro-inflammatory wound cytokines was observed after treatment with TCP-25 gel. (C) Representative H&E-stained photographs show epidermis and dermis. Immature epidermis and dermis with deficient architecture are observed in the gel-treated control area. However, skin treated with TCP-25 gel showed comparatively mature epidermis with improved dermal architecture. (D) Bar graph shows wound histological score. An improved histological score was observed in mice treated with TCP-25 gel.

[0037] Figure 17. Cutaneous tissue from the wound of Lamc2jeb mice showing the therapeutic effects of topical treatment with gel. Petition 870260058481, dated 06 / 16 / 2026, page 19 / 140 / 131 TCP-25. (A) Bacterial count on swab and dressing showing a reduction in CFUs after treatment with TCP-25 gel. (B) Intensity of bacterial bioluminescence visualized using IVIS bioimaging. Representative heatmap overlays of light emission intensity are shown for 1, 3, and 6 h. The bar graph shows the intensity of bioluminescence emitted by the bacteria. A reduction in bacterial bioluminescence was observed after treatment with TCP-25 gel. (C) Wound healing rate showing an increase in healing after treatment with TCP-25.

[0038] Figure 18. There is a statistically significant reduction in the area of ​​the open wound between the baseline value and the last consultation, on day 29, in patients treated with TCP-25, both for primary wounds and for larger secondary wounds. However, the baseline wounds, corresponding to the primary wounds, which were treated with standard treatment (SOC), showed a reduction in the area of ​​the open wound that did not reach statistical significance. Paired t-test (two-tailed) with N = 4 (patients with DEB). Mean and standard deviation are shown in the graph.

[0039] Figure 19. Effects of TCP-25 on neutrophil-related proteins. (A) Median levels of neutrophil proteins NE, MPO, and HBP and (B) median levels of neutrophil chemotactic factor IL8 in wound dressing fluid samples by ELISA. In all graphs, the median is represented by a horizontal line, the interquartile range by a box, and the range by extension lines. The left (E) and right (D) wounds of each patient were plotted separately and treated as individual biological replicates (n = 16 wounds per group).

[0040] Figure 20. Treatment with TCP-25 reduces wound leakage in DEB wounds. Leakage (exudation score) was reduced after treatment with TCP-25 gel on day 29 compared to day 8. (A) Mean wound leakage from all primary (i.e., “plain”) wounds Petition 870260058481, dated 06 / 16 / 2026, p. 20 / 140 / 131 treated with TCP-25 (n = 3) on days 8 and 29 and for reference SOC wounds (n = 3) (bar graph on the left) and mean wound leakage from secondary (i.e., “complex”) wounds treated with TCP-25 (n = 3) on days 8 and 29 compared to additional untreated TCP wounds of similar size (n = 2) (bar graph on the right). Figure 20B illustrates wound leakage in primary, secondary, and reference SOC wounds for one of the treated patients.

[0041] Figure 21. Mean reduction (SD) of open wound area (cm2) from baseline (Day 1) on Day 29 for the matching wound pair: the primary wound treated with TCP-25 compared to the reference wound treated with standard treatment (SOC).

[0042] (n = 4 patients with dystrophic BE).

[0043] Figure 22. Levels of IL-1e, TNF-α and IL-6 in secondary wounds treated with TCP, observed after treatment for 15 and 29 days, compared with wounds not treated with TCP25 of similar size. DETAILED DESCRIPTION Definitions

[0044] In this specification, unless otherwise specified, “a” means “one or more”.

[0045] The term “amino acid”, as used herein, includes the twenty standard amino acids and their corresponding stereoisomers in the “D” form (as compared to the natural “L” form), omega-amino acids, other natural amino acids, unconventional amino acids (e.g., α,α-disubstituted amino acids, N-alkylated amino acids, etc.) and chemically derived amino acids (see below).

[0046] The term “blistering disease or blistering condition,” as used herein, refers to any disease or condition distinguished by one or more blisters, in particular one or more blisters on the skin. A blister is a pocket of bodily fluid, commonly Petition 870260058481, dated 06 / 16 / 2026, p. 21 / 140 / 131 located in the superficial layers of the skin. Blisters may be filled with serum, plasma, blood, or, if infected, with pus. When, or if, a blister bursts or ruptures, wounds may occur.

[0047] The term “dysregulated skin microbiome,” as used herein, refers to a skin microbiome distinguished by the overgrowth of microorganisms and / or by a disturbance and / or imbalance in the skin microbiome. For example, a dysregulated skin microbiome may exhibit reduced diversity of microbial species and / or an increased ratio of pathogenic or harmful bacterial species versus non-pathogenic or beneficial or benign species, compared to a healthy skin microbiome. The term is used herein interchangeably with “dysfunctional skin microbiome,” “dysbiotic skin microbiome,” and “dysregulated cutaneous microbiota.”

[0048] The term “EDTA”, as used herein, refers to ethylenediaminetetraacetic acid.

[0049] The term “excessive wound exudate,” as used herein, refers to a large amount of wound exudate emitted from a wound. In particular, excessive exudate (i.e., a large amount of) can hinder or delay wound healing. This can further result in the need for the individual suffering from excess wound fluid to change the dressing too frequently, for example, because the wound fluid quickly saturates or even leaks from the dressing. Leakage from the dressing can increase the risk of infection.

[0050] The term “hydrogel,” as used herein, refers to a continuous phase of an aqueous solution and a hydrophilic polymer capable of swelling upon contact with water. A “hydrogel” comprises nanostructures formed by said polymer and water and typically contains more than 90% water. Hydrogels are typically transparent or translucent, regardless of their degree of hydration. Hydrogels are generally Petition 870260058481, dated 06 / 16 / 2026, p. 22 / 140 / 131 distinguishable from hydrocolloids, which normally comprise a hydrophobic matrix containing dispersed hydrophilic particles. Hydrogels typically have a flow point of at least 10 Pa, such as at least 15 Pa, for example, in the range of 10 to 80 Pa, as in the range of 40 to 60 Pa.

[0051] The term “sequence identity,” as used herein, refers to the percentage of identical amino acids or nucleotides between a candidate sequence and a reference sequence after alignment. Thus, a candidate sequence that shares 80% amino acid identity with a reference sequence requires that, after alignment, 80% of the amino acids in the candidate sequence are identical to the corresponding amino acids in the reference sequence. Identity according to the present invention is determined with the aid of computational analysis, such as, without limitation, the Clustal Omega computational alignment program for polypeptide sequence alignment (Sievers et al. (October 11, 2011) Molecular Systems Biology 7:539, PMID: 21988835; Li et al. (April 6, 2015) Nucleic Acids Research 43 (W1): W580-4 PMID: 25845596; McWilliam et al.(May 13, 2013) Nucleic Acids Research 41 (web server edition): W597-600 PMID: 23671338, and the default parameters suggested therein. The Clustal Omega software is available from EMBL-EBI at https: / / www.ebi.ac.uk / Tools / msa / clustalo / . Using this program with its default settings, the mature A (bioactive) part of a query and a reference polypeptide are aligned. The number of fully conserved residues is counted and divided by the length of the reference polypeptide. The MUSCLE or MAFFT algorithms can be used for nucleotide sequence alignment. Sequence identities can be calculated similarly to that indicated for amino acid sequences. The sequence identity, as provided here, is calculated over the entire length of the reference sequence.

[0052] The term “standard amino acid” refers to any of the Petition 870260058481, dated 06 / 16 / 2026, page 23 / 140 / 131 twenty genetically encoded amino acids commonly found in natural peptides. Standard amino acids are referred to here by both their 1-letter and 3-letter IUPAC codes. The term “standard amino acid” is used to refer to both free standard amino acids and standard amino acids incorporated into a peptide. For the peptides shown, each encoded amino acid residue, where appropriate, is represented by a single-letter designation.

[0053] The term “topical administration” or “administering topically,” as used herein, refers to the application of a composition to the external surface of a patient, notably the skin or mucous membranes. Preferably, the external surface is the skin, and topical administration involves applying the composition to intact skin, damaged skin, raw skin, a blister, or an open wound.

[0054] The term “treatment,” as used herein, refers to any type of treatment or prevention of a disorder, including improvement of the individual’s disorder (e.g., in one or more symptoms), delaying the progression of the disorder, delaying the onset of symptoms, or slowing the progression of symptoms. Treatment may also be an augmaging or curative treatment. Thus, the term “treatment” also includes prophylactic treatment of the individual to prevent the onset of symptoms; however, treatment is preferably a curative treatment, an augmaging treatment, or a treatment to alleviate the effect of one or more symptoms.

[0055] The term “wound exudate,” as used herein, refers to any fluid that filters from the circulatory system into wounds or blisters. Wound exudate may be serous, serosanguineous, bloody, hemorrhagic, and / or purulent. It may comprise plasma, serum, and / or various cell types, such as neutrophils. The terms “exudate,” “wound exudate,” “wound leakage,” and “wound fluid” are used interchangeably herein. Petition 870260058481, dated 06 / 16 / 2026, page 24 / 140 / 131 document. Wound exudate can be quantified by visual inspection of the dressing; by weighing the dressing; and / or by measuring the total protein content in the dressing, for example, using the Bradford protein assay. Treatment method

[0056] The present invention relates to a compound for use in a method for treating a skin disease or skin condition in an individual in need thereof, wherein said skin disease or skin condition is selected from the group consisting of a disease or condition distinguished by blistering, a disease or condition distinguished by excessive wound exudate, a disease or condition distinguished by a dysregulated skin microbiome and scarring, wherein the compound comprises a peptide comprising or consisting of the amino acid sequence X1-X2-X3-X4-X5-X6-W-X8-X9-X10, where X4, 6, 9 is any standard amino acid. X1 is I, L, or V. X2 is any standard amino acid except C. X3 is A, E, Q, R, or Y. X5 is any standard amino acid except R. X8 is I or L, X10 is any standard amino acid except H, wherein the peptide has a length of 10 to 100 amino acid residues.

[0057] This further refers to a method for treating a skin disease or skin condition in an individual who needs it, wherein said skin disease or skin condition is selected from the group consisting of a disease or condition distinguished by blistering, a disease or condition distinguished by excessive wound exudate, a disease or condition distinguished by a microbiome Petition 870260058481, dated 06 / 16 / 2026, p. 25 / 140 / 131 concerning dysregulated skin and scars, the said method comprising administering a compound comprising a peptide comprising or consisting of the amino acid sequence X1-X2-X3-X4-X5-X6-W-X8-X9-X10, where X4, 6, 9 is any standard amino acid. X1 is I, L, or V. X2 is any standard amino acid except C. X3 is A, E, Q, R, or Y. X5 is any standard amino acid except R. X8 is I or L, X10 is any standard amino acid except H, wherein the peptide has a length of 10 to 100 amino acid residues.

[0058] The present invention further refers to a pharmaceutical composition for use in the treatment of a skin disease or skin condition in an individual who needs it, wherein said skin disease or skin condition is selected from the group consisting of a disease or condition distinguished by blistering, a disease or condition distinguished by excessive wound exudate, a disease or condition distinguished by a dysregulated skin microbiome and scarring, wherein the composition comprises a compound comprising a peptide comprising or consisting of the amino acid sequence X1-X2-X3-X4-X5-X6-W-X8-X9-X10, where X4, 6, 9 is any standard amino acid. X1 is I, L, or V. X2 is any standard amino acid except C. X3 is A, E, Q, R, or Y. Petition 870260058481, dated 06 / 16 / 2026, p. 26 / 140 / 131 X5 is any standard amino acid except R. X8 is I or L, X10 is any standard amino acid except H, wherein the peptide has a length of 10 to 100 amino acid residues.

[0059] The present invention further refers to the use of a compound in the manufacture of a medicament for the treatment of a skin disease or skin condition in an individual who needs it, wherein said skin disease or skin condition is selected from the group consisting of a disease or condition distinguished by blistering, a disease or condition distinguished by excessive wound exudate, a disease or condition distinguished by a dysregulated skin microbiome and scarring, wherein the compound comprises a peptide comprising or consisting of the amino acid sequence X1-X2-X3-X4-X5-X6-W-X8-X9-X10, where X4, 6, 9 is any standard amino acid. X1 is I, L, or V. X2 is any standard amino acid except C. X3 is A, E, Q, R, or Y. X5 is any standard amino acid except R. X8 is I or L, X10 is any standard amino acid except H, wherein the peptide has a length of 10 to 100 amino acid residues.

[0060] The present invention further refers to a compound for use in a method for reducing the amount of fluid exuding from one or more wounds or blisters in an individual who needs this, wherein the compound comprises a peptide comprising or consisting of the amino acid sequence Petition 870260058481, dated 06 / 16 / 2026, p. 27 / 140 / 131 X1-X2-X3-X4-X5-X6-W-X8-X9-X10, where X4, 6, 9 is any standard amino acid. Xi is I, L, or V. X2 is any standard amino acid except C. X3 is A, E, Q, R, or Y. X5 is any standard amino acid except R. X8 is I or L, X10 is any standard amino acid, except H, in which said peptide has a length of 10 to 100 amino acid residues.

[0061] The present invention further refers to a method for reducing the amount of fluid exuding from one or more wounds or blisters in an individual who needs this, said method comprising administering a compound comprising a peptide comprising or consisting of the amino acid sequence X1-X2-X3-X4-X5-X6-W-X8-X9-X10, where X4, 6, 9 is any standard amino acid. Xi is I, L, or V. X2 is any standard amino acid except C. X3 is A, E, Q, R, or Y. X5 is any standard amino acid except R. X8 is I or L, X10 is any standard amino acid except H, wherein the peptide has a length of 10 to 100 amino acid residues.

[0062] The present document further refers to a compound for use in a method of treating a skin disease or skin condition in an individual who needs it, wherein the skin disease or skin condition Petition 870260058481, dated 06 / 16 / 2026, p. 28 / 140 / 131, is a wound or a disease or condition distinguished by blister formation, and in which treatment reduces the amount of fluid oozing from one or more wounds or blisters, and in which the compound comprises a peptide comprising or consisting of the amino acid sequence X1-X2-X3-X4-X5-X6-W-X8-X9-X10, where X4, 6, 9 is any standard amino acid. X1 is I, L, or V. X2 is any standard amino acid except C. X3 is A, E, Q, R, or Y. X5 is any standard amino acid except R. X8 is I or L, X10 is any standard amino acid except H, wherein the peptide has a length of 10 to 100 amino acid residues.

[0063] The present invention further refers to a method of treating a skin disease or skin condition in an individual who needs it, wherein the skin disease or skin condition is a wound or a disease or condition distinguished by blistering, and wherein the treatment reduces the amount of fluid exuding from one or more wounds or blisters, said method comprising administering a compound comprising a peptide comprising or consisting of the amino acid sequence X1-X2-X3-X4-X5-X6-W-X8-X9-X10, where X4, 6, 9 is any standard amino acid. X1 is I, L, or V. X2 is any standard amino acid except C. X3 is A, E, Q, R, or Y. X5 is any standard amino acid except R. Petition 870260058481, dated 06 / 16 / 2026, pp. 29 / 140 / 131 X8 is I or L, X10 is any standard amino acid except H, wherein the peptide has a length of 10 to 100 amino acid residues.

[0064] The present invention further refers to a compound for promoting a healthy skin microbiome in an individual who needs it, wherein the compound comprises a peptide comprising or consisting of the amino acid sequence X1-X2-X3-X4-X5-X6-W-X8-X9-X10, where X4, 6, 9 is any standard amino acid. X1 is I, L, or V. X2 is any standard amino acid except C. X3 is A, E, Q, R, or Y. X5 is any standard amino acid except R. X8 is I or L, X10 is any standard amino acid except H, wherein the peptide has a length of 10 to 100 amino acid residues.

[0065] The present invention further refers to a method for promoting a healthy skin microbiome in an individual who needs it, said method comprising administering a compound comprising a peptide comprising or consisting of the amino acid sequence X1-X2-X3-X4-X5-X6-W-X8-X9-X10, where X4, 6, 9 is any standard amino acid. X1 is I, L, or V. X2 is any standard amino acid except C. Petition 870260058481, dated 06 / 16 / 2026, p. 30 / 140 / 131 X3 is A, E, Q, R, or Y. X5 is any standard amino acid except R. X8 is I or L, X10 is any standard amino acid except H, wherein the peptide has a length of 10 to 100 amino acid residues.

[0066] In some modalities, the individual suffers from a skin disease or skin condition selected from the group consisting of a disease or condition distinguished by blistering, a disease or condition distinguished by excessive wound exudate, a disease or condition distinguished by a dysregulated skin microbiome, and scarring.

[0067] In some modalities, the individual suffers from a skin disease or skin condition selected from the group consisting of burn wounds, chronic skin ulcers, acute infected wounds, pressure ulcers, and chronic wounds such as venous ulcers, for example, venous leg ulcers, or diabetic leg ulcers. In such modalities, the skin disease or skin condition is preferably any of those previously mentioned, wherein said skin disease or condition is associated with excessive wound exudate or associated with a dysregulated skin microbiome. Disease or condition distinguished by blisters.

[0068] A blister is a pocket of bodily fluid, commonly located in the upper layers of the skin. Blisters may be filled with serum, plasma, blood, or, if infected, with pus. When, or if, a blister bursts or ruptures, sores may occur. The disease or condition distinguished by blisters, as defined herein, may be any type of blistering disease or condition.

[0069] In some modalities, the disease or condition distinguished by blister formation is selected from the group consisting of: Petition 870260058481, dated 06 / 16 / 2026, p. 31 / 140 / 131 Epidermolysis bullosa (EB), burn-induced blisters, chilblains, cryotherapy-induced blisters, virus-induced blisters such as chickenpox, herpes zoster, herpes simplex, atypical enterovirus infection, hand-foot-and-mouth disease, herpetic eczema, bullous impetigo and staphylococcal scalded skin syndrome, pemphigus such as pemphigus foliaceus, pemphigus vulgaris, paraneoplastic pemphigus, pemphigus erythematosus or pemphigus vegetans, pemphigoid such as bullous pemphigoid, cicatricial pemphigoid, pemphigoid 200k or mucous membrane pemphigoid, linear IA bullous dermatosis, dermatitis herpetiformis, porphyria cutanea tarda, bullous lupus erythematosus, Hailey-Hailey disease and Stevens-Johnson syndrome (necrosis). toxic epidermal).

[0070] In some modalities, the disease or condition distinguished by blister formation is burn-induced blistering, such as blistering from superficial second-degree partial-thickness burns or deep second-degree partial-thickness burns.

[0071] In one embodiment, the disease or condition with blistering is distinguished by excessive wound exudate, such that leakage of wound fluid is a symptom of the disease or condition with blistering.

[0072] In one embodiment, the disease or condition with blistering is distinguished by a dysregulated skin microbiome, such that the dysregulated skin microbiome is a symptom of the disease or condition with blistering. Petition 870260058481, dated 06 / 16 / 2026, p. 32 / 140 / 131

[0073] In one embodiment, the disease or condition with blistering is distinguished by scarring, in such a way that scarring is a symptom of the disease or condition with blistering. Epidermolysis bullosa

[0074] In preferred embodiments, the disease or condition distinguished by blister formation is epidermolysis bullosa (EB). Thus, in a preferred embodiment, the present invention relates to the compound comprising a peptide described herein for use in a method for treating EB. Consequently, in one embodiment, the invention relates to a compound for use in a method for treating EB in an individual in need thereof, wherein the compound comprises a peptide comprising or consisting of the amino acid sequence: X1-X2-X3-X4-X5-X6-W-X8-X9-X10, where X4, 6, 9 is any standard amino acid. X1 is I, L, or V. X2 is any standard amino acid except C. X3 is A, E, Q, R, or Y. X5 is any standard amino acid except R. X8 is I or L, X10 is any standard amino acid except H, wherein the peptide has a length of 10 to 100 amino acid residues.

[0075] EB is a rare genetic disease, distinguished by the formation of blisters and wounds on the skin and mucous membranes after minimal trauma. It is estimated that there are 500,000 cases worldwide, caused by different mutations. At least 20 different genes encoding components that contribute to skin and mucous membrane adhesion and anchoring have been described as involved in different types of EB. There is no cure for the disease, and treatment may focus on wound care and Petition 870260058481, dated 06 / 16 / 2026, p. 33 / 140 / 131 regarding the treatment of symptoms associated with these, such as pain, itching, or infection.

[0076] There are several different types of EB. The peptides of the invention can be used for the treatment of any type of EB. Thus, in some embodiments of the invention, EB is hereditary epidermolysis bullosa. In other embodiments, EB is acquired epidermolysis bullosa. In some embodiments, EB is simple epidermolysis bullosa, junctional epidermolysis bullosa, dystrophic epidermolysis bullosa, such as dominant dystrophic epidermolysis bullosa or recessive dystrophic epidermolysis bullosa, Kindler syndrome, or acquired epidermolysis bullosa.

[0077] Blisters can occur in all types of EB after friction and / or relatively mild trauma. These can be present anywhere on the skin and mucous membranes. Commonly, blister formation in EB is the first sequence in the generation of wounds, with the blisters containing exudate. Wounds formed after the blisters open can produce an excessive amount of exudate. Dysregulated skin microbiome and scarring, as well as infection and inflammation of the wounds, can also be prevalent features of EB. The methods of the invention can be used to treat such blisters and / or reduce the excessive amount of exudate and / or restore a healthy microbiome in patients with EB.

[0078] In some modalities, the treatment method described here in the “Treatment Method” section reduces the size of one or more blisters or sores in an individual suffering from EB.

[0079] In some modalities, the treatment reduces the size of one or more blisters or wounds by at least 10%, such as at least 20%, such as at least 30%, such as at least 35%, such as at least 40%, such as at least 45%, such as at least 50%, such as at least 60%, such as at least 70%, such as at least 80%, such as at least 90%, such as where the treatment reduces the size of Petition 870260058481, dated 06 / 16 / 2026, p. 34 / 140 / 131 one or more blisters or wounds by at least 95%, compared to the size of one or more blisters or wounds before treatment, or compared to the size of a blister or wound that was not treated with the compound comprising the peptide, and which before treatment was of similar size and characteristics to one or more treated blisters or wounds.

[0080] In some modalities, the treatment reduces the size of one or more blisters or wounds by between 10% and 100%, as well as between 20% and 100%, as well as between 30% and 100%, as well as between 40% and 100%, as well as between 50% and 100%, as well as between 60% and 100%, as well as between 70% and 100%, as well as between 80% and 100%, as well as between 90% and 100%, as well as between 10% and 90%, as well as between 20% and 90%, as well as between 30% and 90%, as well as between 40% and 90%, as well as between 50% and 90%, as well as between 60% and 90%, as well as between 70% and 90%, as well as between 80% and 90%, just as between 10% and 80%, just as between 20% and 80%, just as between 30% and 80%, just as between 40% and 80%, just as between 50% and 80%, just as between 60% and 80%, just as between 70% and 80%, just as between 10% and 70%, just as between 20% and 70%, just as between 30% and 70%, just as between 40% and 70%, just as between 50% and 70%, just as between 60% and 70%, just as between 10% and 60%, just as between 20% and 60%, just as between 30% and 60%, just as between 40% and 60%,such as between 50% and 60%, such as between 10% and 50%, such as between 20% and 50%, such as between 30% and 50%, such as between 40% and 50%, such as between 10% and 40%, such as between 20% and 40%, such as between 30% and 40%, such as between 10% and 30%, such as between 20% and 30%, such as between 10% and 20%,

[0081] In some modalities, the treatment reduces the size of one or more blisters or wounds by at least 10%, such as at least 20%, such as at least 30%, such as at least 40%, such as at least 50%, such as at least 60%, such as at least 70%, such as at least 80%, such as at least 90%. Petition 870260058481, dated 06 / 16 / 2026, p. 35 / 140 / 131

[0082] In some modalities, the treatment reduces the size of one or more blisters or wounds by 100%, in such a way that the treatment results in one or more blisters or wounds being completely healed.

[0083] In some modalities, the size of one or more blisters or wounds is reduced after treatment for at least two days, such as at least five days, such as at least one week, such as at least two weeks, such as at least three weeks, such as at least four weeks, such as at least one month, such as at least two months, such as at least five months, such as at least six months, such as at least seven months, such as at least eight months, such as at least nine months, such as at least ten months, such as at least eleven months, in such a way that the size of one or more blisters or wounds is reduced after one year of treatment.

[0084] In some modalities, the size of one or more blisters or wounds is reduced after treatment between two days and two years, such as between five days and one year, such as between one month and one year, such as between two days and one month, such as between two weeks and six months, such as between one week and three months, such as between two months and one year, such as between one month and four months, such as between two weeks and eight weeks, such as between one week and five weeks.

[0085] In some forms, the wound or blister remains healed and does not reopen for at least two days, such as at least five days, such as at least one week, such as at least two weeks, such as at least three weeks, such as at least four weeks, such as at least one month, such as at least two months, such as at least five months, such as at least six months, such as at least seven months, such as at least eight months, such as at least nine months, such as at least ten months, such as at least eleven months, such as at least one year, such as at least two years, such as at least three years, such as Petition 870260058481, dated 06 / 16 / 2026, page 36 / 140 / 131 at least four years, as well as at least five years after the treatment is completed, such as when the wound or blister remains healed and does not reopen in any way after the treatment is completed.

[0086] In some forms, the wound or blister remains healed and does not reopen for between two days and five years, such as between one week and one month, such as between two months and eight months, such as between one year and five years.

[0087] EB may be associated with pain, such that pain is a symptom of EB. In some modalities, treatment reduces the pain experienced by the individual, such as when said treatment reduces the pain of one or more wounds or blisters.

[0088] Pain can be measured using a pain scale. In some modalities, pain is measured using a self-report scale. In other modalities, pain is measured using an observer pain scale. In other words, in some modalities, treatment reduces the pain felt by the individual, and this pain reduction is measured using a pain scale.

[0089] In some modalities, pain is measured using a pain scale selected from the group consisting of the Neonatal / Infant Pain Scale (NIPS), Children's Hospital of Eastern Ontario Pain Scale (CHEOPS), Face, Legs, Activity, Cry and Consolability Scale (FLACC), Faces Pain Scale (Wong-Baker Faces Pain Rating Scale), Color Analog Scale, Visual Analog Scale, Verbal Numerical Rating Scale and Wharton Pain and Disability Scale.

[0090] In some modalities, pain is reduced by at least one step or score on a pain scale, such as at least two steps or scores, such as at least three steps or scores, such as at least four steps or scores, such as at least five steps or scores, such Petition 870260058481, dated 06 / 16 / 2026, page 37 / 140 / 131 as at least six steps or scores, such as at least seven steps or scores, such as at least eight steps or scores, such as at least nine steps or scores, such as when pain is reduced by ten steps or scores on a pain scale, such as on any of the pain scales mentioned above.

[0091] In some modalities, pain is reduced between one and ten steps or scores on a pain scale, such as between one and nine steps or scores, such as between one and eight steps or scores, such as between one and seven steps or scores, such as between one and six steps or scores, such as between one and five steps or scores, such as between one and four steps or scores, such as between one and three steps or scores, such as between one and two steps or scores, such as between two and ten steps or scores, such as between two and nine steps or scores, such as between two and eight steps or scores, such as between two and seven steps or scores, such as between two and six steps or scores, such as between two and five steps or scores, such as between two and four steps or scores, such as between two and three steps or scores, such as between three and ten steps or scores, such as between three and nine steps or scores, such as between three and eight stages or scores,such as between three and seven stages or scores, such as between three and six stages or scores, such as between three and five stages or scores, such as between three and four stages or scores, such as between four and ten stages or scores, such as between four and nine stages or scores, such as between four and eight stages or scores, such as between four and seven stages or scores, such as between four and six stages or scores, such as between four and five stages or scores, such as between five and ten stages or scores, such as between five and nine stages or scores, such as between four and eight stages or scores, such as between four and seven stages or scores, such as between four and six stages or scores, such as between five and six stages or scores, such as between six and ten stages or scores, such as between six and nine stages or, Petition 870260058481, dated 06 / 16 / 2026, page 38 / 140 / 131 scores, such as between six and eight steps or scores, such as between six and seven steps or scores, such as between seven and ten steps or scores, such as between seven and nine steps or scores, such as between seven and eight steps or scores, such as between eight and ten steps or scores, such as between eight and nine steps or scores, such as when pain is reduced between nine and ten steps or scores on a pain scale.

[0092] EB can also be associated with itching, such that itching is a symptom of EB. In some forms, treatment reduces the itching felt by the individual, such as when said treatment reduces the itching of one or more wounds or blisters.

[0093] Itching can be determined using subjective patient reports or by objective measurement of scratching activity or scratch-induced skin changes. In some modalities, itching is measured using the Leuven Itch Scale. In some modalities, itching is measured using the 5-D Itch Scale.

[0094] EB may also be associated with excessive wound leakage, so that leakage from EB wounds is a symptom of EB. In specific modalities, the individual suffering from EB presents with one or more fluid-leaking wounds, that is, one or more wounds with excessive wound exudate, as described in the section “Disease or condition distinguished by wound exudate”.

[0095] Thus, in one modality, the treatment reduces wound leakage in a patient suffering from EB, for example, in the manner described in the section “Disease or condition distinguished by wound exudate”.

[0096] EB may also be associated with a dysregulated skin microbiome, such that a dysregulated skin microbiome is a symptom of EB. In specific modalities, the individual suffering from EB presents a dysregulated skin microbiome in one or more wounds, as described in the section “Disease or condition distinguished by skin microbiome” Petition 870260058481, dated 06 / 16 / 2026, pp. 39 / 140 / 131 "dysregulated". Such a dysregulated skin microbiome can hinder wound healing and increase the risk of infection or even sepsis.

[0097] Thus, in one embodiment, the treatment promotes a healthy skin microbiome in a patient suffering from EB, as described in the section “Disease or condition distinguished by dysregulated skin microbiome”. In one embodiment, the treatment reduces the total amount of microorganisms, such as the total amount of commensal microorganisms, present on the skin and / or in one or more wounds of a patient suffering from EB, as described in the section “Disease or condition distinguished by dysregulated skin microbiome”. In one embodiment, it increases the ratio of beneficial:harmful species and / or strains in the skin microbiome, on the skin and / or in one or more wounds of a patient suffering from EB, as described in the section “Disease or condition distinguished by dysregulated skin microbiome”.

[0098] EB can also be associated with scarring, such that scar formation is a symptom of EB. In specific forms, the individual suffering from EB presents one or more scars formed from one or more wounds, as described in the “Scars” section.

[0099] Thus, in one modality, the treatment reduces scar formation in a patient suffering from EB, for example, in the manner described in the “Scars” section. Disease or condition distinguished by wound exudate.

[00100] Wound exudate or wound fluid can be any fluid that filters from the circulatory system into wounds or blisters. Wound exudate can be serous, serosanguineous, bloody, hemorrhagic, and / or purulent. It may comprise plasma, serum, and / or various cell types, such as neutrophils. In certain wounds, the amount of exudate can be at such a high level that it impairs wound healing. In other words, the Petition 870260058481, dated 06 / 16 / 2026, page 40 / 140 / 131: Excess exudate can delay or worsen healing. Therefore, reducing the amount of exudate can improve healing.

[00101] The amount of exudate emitted by a wound can be independent of the amount of bacteria colonizing it. This is evident, for example, from the fact that the peptides of the present invention decrease bacterial levels in a wound in a dose-independent manner, while the reduction in wound leakage appears to be dose-dependent.

[00102] The amount of fluid leaking from a wound can be reduced in any individual who needs it, as in any individual suffering from a disease or condition distinguished by excess exudate. The individual may, for example, suffer from a disease or condition distinguished by blisters, as described herein in the section “Disease or condition distinguished by blisters”. In one embodiment, the individual suffers from epidermolysis bullosa, as described herein in the section “Epidermolysis bullosa”.

[00103] In some forms, however, the individual suffers from a skin disease or skin condition selected from the group consisting of burn wounds, chronic skin ulcers, acute infected wounds, pressure ulcers, and chronic wounds such as venous ulcers, for example, venous leg ulcers, or diabetic leg ulcers.

[00104] In some modalities, the treatment reduces the amount of fluid that exudes from one or more blisters or wounds, such as when treatment reduces the amount of wound exudate.

[00105] In some modalities, the treatment reduces the amount of fluid exuding from a wound or blister by at least 10%, such as at least 20%, such as at least 30%, such as at least 35%, such as at least 40%, such as at least 45%, such as at least 50%, such as at least 60%, such as at least 70%, such as at least 80%, such as at least 90%, as well as when the amount of exudate Petition 870260058481, dated 06 / 16 / 2026, p. 41 / 140 / 131, the wound is reduced by at least 95%.

[00106] In some modalities, the treatment reduces the amount of fluid that exudes from a wound or blister by between 10% and 95%, such as between 10% and 90%, such as between 15% and 80%, such as between 10% and 40%, such as between 30% and 80%, such as between 50% and 90%, such as between 20% and 50%, such as between 40% and 60%, such as between 10% and 25%, such as between 30% and 70%, such as between 80% and 90%, such as between 70% and 80% such as between 50% and 70% such as between 20% and 70%.

[00107] In some modalities, the treatment reduces the amount of fluid that exudes from a wound or blister by at least one step or score on an exudate scale, such as at least two steps or scores, such as at least three steps or scores, such as at least four steps or scores, such as at least five steps or scores on a wound exudate scale.

[00108] In one modality, the exudate score or scale, that is, leakage, is performed by visual inspection of the dressing after a certain period, for example, using a visual scoring scale from 0 to 5, where 0 represents “No exudate in the wound area” and 5 represents “Exudate soaking the dressing in an area that exceeds the wound area”.

[00109] In some modalities, the reduction is compared to the period prior to the start of treatment of the wound or blister. In some modalities, the reduction is compared to a wound or blister of similar size and characteristics that was not treated with the compound comprising the peptide and that, before treatment, had a similar amount of exudate to that of the treated wound or blister.

[00110] In order to quantify wound exudate, wound exudate can be collected on wound dressing(s) and the amount collected on the wound dressing(s) can be quantified.

[00111] In some modalities, the amount of wound exudate Petition 870260058481, dated 06 / 16 / 2026, page 42 / 140 / 131, is estimated by visual inspection of the wound dressing.

[00112] In some modalities, the amount of wound exudate is measured by means of images of the wound dressing.

[00113] In some modalities, the amount of wound exudate is measured by weighing the wound dressing.

[00114] In some embodiments, the amount of wound exudate is measured by measuring the protein content in the wound dressing, such as the total protein content in the dressing. Thus, the total protein content in a dressing is correlated with wound exudate and can therefore be used as a quantification of wound exudate. In some embodiments, the protein content is measured using the Bradford protein assay and / or any other method well known in the art.

[00115] Thus, in some modalities, the treatment reduces the total protein content that exudes from a wound or blister.

[00116] In preferred embodiments, wound exudate is measured in the manner described in Example 1 below.

[00117] In some modalities, the treatment reduces the amount of heparin-binding protein (HBP) in the wound exudate. HBP, also known as azurocidine or 37 kDa cationic antimicrobial protein, is an inflammatory mediator with the ability to induce vascular leakage. In one modality, the amount of HBP is reduced by at least 20%, such as at least 30%, such as at least 40%, such as at least 50%, such as at least 60%, such as at least 70%, such as at least 80%, such as at least 90%. In another modality, the amount of HBP is decreased between 20% and 90%, such as between 30% and 80%, such as between 50% and 90%, such as between 60% and 75%.

[00118] The amount of BPH in wound exudate can be determined using methods known in the art, for example, using the methods described in Example 1 or Example 5 of this application. Petition 870260058481, dated 06 / 16 / 2026, p. 43 / 140 / 131

[00119] Excessive fluid leakage from one or more wounds may cause the individual suffering from one or more wounds to need dressing changes at regular intervals. Dressing changes, particularly for individuals suffering from EB or other painful wounds, can be associated with a high degree of pain and distress. Reducing the amount of fluid leaking from one or more wounds may mean that the dressing does not need to be changed as frequently.

[00120] Thus, in one embodiment, the treatment reduces the number of times wound dressings need to be changed in a defined period of time, such as when the treatment increases the number of days that elapse before wound dressings need to be changed, such as when the treatment results in wound dressings that do not need to be changed as frequently compared to the beginning of the treatment.

[00121] In one embodiment, the treatment increases the number of days between dressing changes by half a day, as by one day, as by 1.5 days, as by 2 days, as by 2.5 days, as by 3 days, as by 3.5 days, as by 4 days, as by 4.5 days, as by 5 days, as by which the treatment increases the number of days between dressing changes by 6 days.

[00122] In one embodiment, after and / or during treatment according to the invention, the number of days between the need to change dressings is between one day and six days, as between one day and five days, as between one day and four days, as between one day and three days, as between one day and two days, as between two days and five days, as between two days and four days.

[00123] In one modality, the treatment results in changing the dressing only every three days, such as every four days, such as every five days, such as every six days, such as, for example, when the treatment results in changing the dressing only once a week.

[00124] The timing for changing a wound dressing can be determined by anyone familiar with determining this. Petition 870260058481, dated 06 / 16 / 2026, p. 44 / 140 / 131 moment, such as a caregiver, a doctor, a nurse and / or the individual suffering from the disease or condition. Thus, in some modalities, the moment for changing the wound dressing is determined by visual inspection of the wound dressing, such as, for example, by visual inspection by a person familiar with determining when the wound dressing needs to be changed.

[00125] In some modalities, the timing for dressing change is determined based on the amount of exudate present in the dressing.

[00126] In some modalities, the timing for changing the wound dressing is determined to reduce the risk of inflammation and / or infection, for example, when the timing is predetermined to reduce the risk of inflammation and / or infection. Disease or condition distinguished by dysregulated skin microbiome

[00127] The skin microbiome, also called skin flora or skin microbiota, refers to the community of microorganisms that reside on the skin. Commonly, the majority of the skin microbiome is composed of bacteria, such as approximately 1,000 species of bacteria from 19 phyla. A healthy skin microbiome is non-pathogenic and may include commensal and / or mutualistic bacteria. A healthy skin microbiome can prevent pathogenic bacteria from colonizing the skin, for example, by competing with these pathogenic bacteria for nutrients and / or stimulating the skin's immune system. In some cases, a healthy skin microbiome can promote and / or improve wound healing.

[00128] Many skin diseases and conditions are associated with alterations and changes in the healthy skin microbiome, that is, dysbiosis or dysregulation of the skin microbiome. A dysregulated skin microbiome can be distinguished by the excessive growth or overgrowth of cutaneous microorganisms and / or by an increased ratio of pathogenic, i.e., harmful, bacterial species compared to the ratio Petition 870260058481, dated 06 / 16 / 2026, pp. 45 / 140 / 131 of these species in a healthy skin microbiome. In some instances, dysbiosis is distinguished by the overgrowth of commensal and non-pathogenic bacteria. In some cases, bacteria colonizing the skin microbiome can become pathogenic and cause disease. In other cases, damaged skin can cause non-pathogenic bacteria to become pathogenic. Reversing skin microbiome dysregulation can help prevent and / or treat skin disease or conditions.

[00129] The present invention provides peptides to promote a healthy skin microbiome and / or to treat a dysregulated skin microbiome. Thus, in one embodiment, the treatment promotes a healthy skin microbiome.

[00130] A dysregulated skin microbiome can be treated and / or a healthy skin microbiome can be promoted in any individual who needs it, such as any individual suffering from a disease or condition distinguished by a dysregulated skin microbiome. The individual may, for example, suffer from a disease or condition distinguished by blistering, as described here in the section “Disease or condition distinguished by blistering”.

[00131] In some forms, however, the individual suffers from a skin disease or skin condition selected from the group consisting of burn wounds, chronic skin ulcers, acute infected wounds, pressure ulcers and chronic wounds such as venous ulcers, for example, venous leg ulcers, or diabetic leg ulcers, in which said wounds are distinguished by a dysregulated skin microbiome.

[00132] In other modalities, the individual suffers from eczema, such as atopic dermatitis. Thus, in some modalities, a healthy skin microbiome is promoted in an individual suffering from atopic dermatitis.

[00133] As previously stated, the dysregulated microbiome can be distinguished by an increased ratio of Petition 870260058481, dated 06 / 16 / 2026, page 46 / 140 / 131 harmful microorganisms compared to beneficial microorganisms, i.e., an increased ratio of (potentially) pathogenic microorganisms compared to non-pathogenic microorganisms. In other words, a dysregulated microbiome can be distinguished by a reduced ratio of beneficial microorganisms compared to harmful microorganisms, i.e., an increased ratio of (potentially) pathogenic microorganisms compared to non-pathogenic microorganisms. These microorganisms may be of a specific strain and / or microbial species.

[00134] Thus, in one embodiment, the dysregulated skin microbiome is distinguished by a reduced ratio of beneficial:harmful microbial species and / or strains compared to the ratio of beneficial:harmful microbial species and / or strains in an individual who does not suffer from a dysregulated skin microbiome, such that harmful microbial species and / or strains make up a larger portion of the total skin microbiome in the dysregulated skin microbiome compared to the skin microbiome of an individual who does not suffer from a dysregulated skin microbiome.

[00135] A dysregulated skin microbiome can also be distinguished by the excessive growth or overgrowth of cutaneous microorganisms. In such modalities, it may be important to reduce the bacterial load of the wound, for example, to prevent colonization of the wound or blister by pathogenic bacteria, such as to prevent, for example, wound infection. Thus, in some modalities, the treatment reduces the total amount of microorganisms, such as when the treatment reduces an excessive amount of microorganisms, for example, in one or more wounds or blisters, such as the total amount of bacteria present in one or more wounds or blisters.

[00136] In some modalities, the treatment reduces the amount Petition 870260058481, dated 06 / 16 / 2026, p. 47 / 140 / 131 total of skin microorganisms in the skin microbiome, such as when treatment reduces the total bacterial load in a wound or blister.

[00137] In some modalities, one or more skin microorganisms are resistant to one or more antibiotics. Thus, in some modalities, treatment reduces the total number of skin microorganisms in a skin microbiome comprising one or more skin microorganisms that are resistant to one or more antibiotics.

[00138] In some modalities, the treatment reduces the total amount of microorganisms present in one or more wounds or blisters by at least 10%, such as at least 20%, such as at least 30%, such as at least 35%, such as at least 40%, such as at least 45%, such as at least 50%, such as at least 60%, such as at least 70%, such as at least 80%, such as at least 90%, such as when the total amount of microorganisms present in one or more wounds or blisters is reduced by at least 95% compared to the amount of bacteria present before treatment.

[00139] In some modalities, the treatment reduces the total amount of microorganisms present in one or more wounds or blisters by between 10% and 95%, such as between 10% and 90%, such as between 15% and 80%, such as between 10% and 40%, such as between 30% and 80%, such as between 50% and 90%, such as between 20% and 50%, such as between 40% and 60%, such as between 10% and 25%, such as between 30% and 70%, such as between 80% and 90%, such as between 70% and 80% such as between 50% and 70% such as between 20% and 70%.

[00140] The quantity of bacteria can be measured using any well-known technique in the field. For example, the quantity of microorganisms is measured by measuring the number of colony-forming units (CFU) present in a dressing and / or in a wound or blister on the skin. In some modalities, this measurement occurs before, during, and / or after treatment.

[00141] Meanwhile, it may also be important to keep the bacteria Petition 870260058481, dated 06 / 16 / 2026, pp. 48 / 140 / 131, refers to beneficial, or non-pathogenic, bacteria in the wound microbiome. In other words, maintaining bacterial diversity in the wound may be important to prevent subsequent colonization by pathogenic bacteria after treatment is completed.

[00142] Thus, in some modalities, the treatment preserves the composition of the skin microbiome, such as when the treatment preserves the microbial diversity of the skin microbiome.

[00143] In some modalities, the treatment preserves the ratio between different microbial species and / or strains in the skin microbiome, so that the ratio between different microbial species and / or strains in the skin microbiome is the same or similar before, during, and / or after treatment. In other words, in some modalities, the treatment maintains the ratio of beneficial to harmful microorganisms in the skin microbiome, such as when the ratio of beneficial to harmful microorganisms in the skin microbiome is the same or similar before, during, and / or after treatment.

[00144] In some modalities, however, the treatment increases the ratio of beneficial:harmful microorganisms in the skin microbiome, for example, when the treatment doubles, triples or quadruples the ratio of beneficial:harmful microorganisms in the skin microbiome, so that the beneficial microorganisms, during and / or after the treatment, constitute a larger part of the total skin microbiome in relation to the harmful microbial microorganisms.

[00145] The ratio can be calculated by dividing the quantity of beneficial microorganisms by the quantity of harmful microorganisms. In some embodiments, the ratio is calculated by dividing the quantity of at least one beneficial microorganism by the quantity of at least one harmful microorganism, such as the quantity of at least two beneficial microorganisms by the quantity of at least two harmful microorganisms, such as the quantity of at least three Petition 870260058481, dated 06 / 16 / 2026, page 49 / 140 / 131 beneficial microorganisms with a quantity of at least three harmful microorganisms, such as a quantity of at least four beneficial microorganisms with a quantity of at least four harmful microorganisms, such as a quantity of at least five beneficial microorganisms with a quantity of at least five harmful microorganisms, such as a quantity of at least ten beneficial microorganisms with a quantity of at least ten harmful microorganisms.

[00146] In some embodiments, the ratio is calculated by dividing the quantity between 1 and 100 beneficial microorganisms by the quantity between 1 and 100 harmful microorganisms, such as the quantity between 1 and 50 beneficial microorganisms by the quantity between 1 and 50 harmful microorganisms, such as the quantity between 1 and 20 beneficial microorganisms by the quantity between 1 and 20 harmful microorganisms, such as the quantity between 1 and 10 beneficial microorganisms by the quantity between 1 and 10 harmful microorganisms, such as the quantity between 2 and 10 beneficial microorganisms by the quantity between 2 and 10 harmful microorganisms, such as the quantity between 2 and 5 beneficial microorganisms by the quantity between 2 and 5 harmful microorganisms, such as the quantity between 10 and 15 beneficial microorganisms by the quantity between Between 10 and 15 harmful microorganisms, just as between 2 and 50 beneficial microorganisms are present, with a quantity between 2 and 50 harmful microorganisms.just as the quantity of 3 to 10 beneficial microorganisms is balanced with the quantity of 3 to 10 harmful microorganisms.

[00147] In some embodiments, the ratio is calculated based on at least one beneficial microorganism, such as at least two beneficial microorganisms, such as at least three beneficial microorganisms, such as at least four beneficial microorganisms, such as at least five beneficial microorganisms, such as at least six Petition 870260058481, dated 06 / 16 / 2026, page 50 / 140 / 131 beneficial microorganisms, such as at least seven beneficial microorganisms, such as at least eight beneficial microorganisms, such as at least nine beneficial microorganisms, such as at least ten beneficial microorganisms, such as at least 15 beneficial microorganisms, such as at least 20 beneficial microorganisms, such as at least 25 beneficial microorganisms, such as at least 30 beneficial microorganisms, such as at least 40 beneficial microorganisms, such as at least 50 beneficial microorganisms, such as at least 100 beneficial microorganisms.

[00148] In some embodiments, the ratio is calculated based on between 1 and 500 beneficial microorganisms, such as between 1 and 300 beneficial microorganisms, such as between 1 and 50 beneficial microorganisms, such as between 1 and 10 beneficial microorganisms, such as between 5 and 100 beneficial microorganisms, such as between 5 and 50 beneficial microorganisms, such as between 2 and 20 beneficial microorganisms, such as between 1 and 5 beneficial microorganisms, such as between 2 and 4 harmful microorganisms.

[00149] In some embodiments, the ratio is calculated based on at least one harmful microorganism, such as at least two harmful microorganisms, such as at least three harmful microorganisms, such as at least four harmful microorganisms, such as at least five harmful microorganisms, such as at least six harmful microorganisms, such as at least seven harmful microorganisms, such as at least eight harmful microorganisms, such as at least nine harmful microorganisms, such as at least ten harmful microorganisms, such as at least 15 harmful microorganisms, such as at least 20 harmful microorganisms, such as at least 25 harmful microorganisms, such as at least 30 harmful microorganisms, such as at least 40 harmful microorganisms, such as at least 50 harmful microorganisms, such as Petition 870260058481, dated 06 / 16 / 2026, page 51 / 140 / 131, at least 100 harmful microorganisms.

[00150] In some embodiments, the ratio is calculated based on between 1 and 500 harmful microorganisms, such as between 1 and 300 harmful microorganisms, such as between 1 and 50 harmful microorganisms, such as between 1 and 10 harmful microorganisms, such as between 5 and 100 harmful microorganisms, such as between 5 and 50 harmful microorganisms, such as between 2 and 20 harmful microorganisms, such as between 1 and 5 harmful microorganisms, such as between 2 and 4 harmful microorganisms.

[00151] Harmful microorganisms, i.e., pathogenic microorganisms, may be any microorganisms known in the art to be pathogenic and / or harmful at high levels. Beneficial microorganisms, i.e., non-pathogenic microorganisms, may be any microorganisms known in the art to be non-pathogenic. Thus, this ratio can be calculated based on any microorganisms known in the art to be pathogenic or non-pathogenic.

[00152] In some embodiments, the harmful microorganism is a gram-negative bacterium. In some embodiments, the harmful microorganism is selected from the group consisting of Staphylococcus aureus, Bacillus licheniformis, Bacillus cereus complex, Rothia amarae, Staphylococcus spp., Streptococcus spp., group A Streptococcus, such as Streptococcus pyogenes, and gram-negative bacteria, such as Pseudomonas aeruginosa, Proteobacteria spp., and Proteus spp.

[00153] In some embodiments, the harmful microorganism is at least one microorganism, such as at least two microorganisms, such as at least three microorganisms, such as at least four microorganisms, such as at least five microorganisms, such as at least six microorganisms, such as at least seven microorganisms, such as at least eight microorganisms, such as at least nine Petition 870260058481, dated 06 / 16 / 2026, p. 52 / 140 / 131 microorganisms, such as at least ten microorganisms, such as at least eleven microorganisms, such as at least twelve microorganisms, such as at least 13 microorganisms, such as at least 14 microorganisms, such as at least 15 microorganisms, such as at least 25 microorganisms, such as all microorganisms selected from the group consisting of Staphylococcus aureus, Bacillus licheniformis, Bacillus cereus complex, Rothia amarae, Staphylococcus spp., Streptococcus spp., Group A Streptococcus, such as Streptococcus pyogenes, and Gram-negative bacteria, such as Pseudomonas aeruginosa, Proteobacteria spp., and Proteus spp.

[00154] In some embodiments, the beneficial microorganism is selected from the group consisting of Staphylococcus xylosus, Staphylococcus hominis, Staphylococcus nepalensis, Staphylococcus warneri, Staphylococcus borealis, Staphylococcus petrasii, Staphylococcus epidermidis, Staphylococcus lugdunensis, Staphylococcus caprae, Staphylococcus saprophyticus, Staphylococcus capitis, Staphylococcus haemolyticus, Staphylococcus condiment, Micrococcus spp. and Corynebacterium spp.

[00155] In some embodiments, the beneficial microorganism is at least one microorganism, such as at least two microorganisms, such as at least three microorganisms, such as at least four microorganisms, such as at least five microorganisms, such as at least six microorganisms, such as at least seven microorganisms, such as at least eight microorganisms, such as at least nine microorganisms, such as at least ten microorganisms, such as at least eleven microorganisms, such as at least twelve microorganisms, such as at least 13 microorganisms, such as at least 14 microorganisms, such as at least 15 microorganisms, such as at least 25 microorganisms, such as all microorganisms selected from Petition 870260058481, of 06 / 16 / 2026, p. 53 / 140 / 131 from the group consisting of Staphylococcus xylosus, Staphylococcus hominis, Staphylococcus nepalensis, Staphylococcus warneri, Staphylococcus borealis, Staphylococcus petrasii, Staphylococcus epidermidis, Staphylococcus lugdunensis, Staphylococcus caprae, Staphylococcus saprophyticus, Staphylococcus capitis, Staphylococcus haemolyticus, Staphylococcus condiment, Micrococcus spp. and Corynebacterium spp.. Scars

[00156] A scar or scar tissue is an area of ​​fibrous tissue that replaces normal skin after an injury, such as after a wound. Many wounds, particularly wounds where the dermis is damaged, result in scarring. Generally, improving wound healing can decrease scar formation or prevent scarring from occurring.

[00157] Scars can be treated in any individual who needs it using the peptides described herein, as well as in any individual suffering from a disease or condition distinguished by scar formation. The individual may, for example, suffer from a disease or condition distinguished by blister formation, as described herein in the section “Disease or condition distinguished by blister formation”.

[00158] In some embodiments, however, the individual suffers from a skin disease or skin condition selected from the group consisting of burn wounds, chronic skin ulcers, acute infected wounds, pressure ulcers, and chronic wounds such as venous ulcers, for example, venous leg ulcers, or diabetic leg ulcers, wherein said wounds are distinguished by scar formation. In some embodiments, the individual suffers from an infected wound, such as a wound infected by pathogenic bacteria, for example, S. aureus.

[00159] In some modalities, the treatment is preventive.

[00160] In some modalities, the treatment reduces scar formation. Petition 870260058481, dated 06 / 16 / 2026, page 54 / 140 / 131

[00161] In some modalities, the treatment reduces the size of an existing scar.

[00162] In some modalities, the scar is a fibrotic scar.

[00163] In some modalities, the treatment reduces the size of the scar by at least 10%, such as at least 20%, such as at least 30%, such as at least 35%, such as at least 40%, such as at least 45%, such as at least 50%, such as at least 60%, such as at least 70%, such as at least 80%, such as at least 90%, such as when the treatment reduces scar formation by at least 95%.

[00164] In some modalities, the said reduction is compared to the size of a scar formed from a wound of similar size and characteristics that was not treated.

[00165] In some modalities, the treatment reduces the size of the scar by between 10% and 95%, as well as between 10% and 90%, as well as between 15% and 80%, as well as between 10% and 40%, as well as between 30% and 80%, as well as between 50% and 90%, as well as between 20% and 50%, as well as between 40% and 60%, as well as between 10% and 25%, as well as between 30% and 70%, as well as between 80% and 90%, as well as between 70% and 80%, as well as between 50% and 70%, as well as between 20% and 70%. Peptides

[00166] The invention relates to compounds comprising peptides for use in methods of treating wounds and blisters in patients suffering from a skin disease or skin condition selected from the group consisting of blistering disease, a disease or condition distinguished by excessive wound exudate, a disease or condition distinguished by a dysregulated skin microbiome, and scarring.

[00167] The invention further relates to compounds comprising peptides for use in methods of treating a skin disease or skin condition in an individual who needs such treatment, wherein the skin disease or skin condition is a disease with blistering or Petition 870260058481, dated 06 / 16 / 2026, p. 55 / 140 / 131 a wound, and in which the treatment reduces the amount of fluid that oozes from one or more blisters or wounds.

[00168] The invention further relates to compounds comprising peptides for use in methods to promote a healthy skin microbiome in an individual who needs it.

[00169] The compound may thus comprise a peptide consisting of any of the amino acids mentioned below, wherein the peptide has been further derivatized or conjugated into one or more additional moieties. Those skilled in the art will recognize that, in a compound comprising a peptide consisting of any of the amino acids mentioned below, one or more hydrogen moieties of said peptide may be replaced by a conjugated moiety.

[00170] Peptides can be thrombin-derived C-terminal peptides (TCPs).

[00171] In some embodiments, the compound comprises a peptide comprising or consisting of the amino acid sequence X1-X2-X3-X4-X5-X6-W-X8-X9-X10, where X4, 6, 9 is any standard amino acid. X1 is I, L, or V. X2 is any standard amino acid except C. X3 is A, E, Q, R, or Y. X5 is any standard amino acid except R. X8 is I or L, X10 is any standard amino acid, except H, in which the peptide has a length of 10 to 100 amino acid residues.

[00172] In some embodiments, the peptide comprises or consists of the amino acid sequence X1-X2-X3-X4-X5-X6-W-X8-X9-X10-X11-X12-X13, where Petition 870260058481, dated 06 / 16 / 2026, page 56 / 140 / 131 X4, 6, 9, 11 is any standard amino acid. X1, is it I, L or V X2 is any standard amino acid except C. X3 is A, E, Q, R, or Y. X5 is any standard amino acid except R. X8 is I or L X10 is any standard amino acid except H. X12 is I, M, or T X13 is D, K, Q, or R, and the peptide in question has a length of 20 to 100 amino acid residues.

[00173] In some embodiments, the peptide comprises or consists of the amino acid sequence X1-X2-X3-X4-X5-X6-W-X8-X9-X10-X11-X12-X13-X14X15-X16-X17, where X4, 6, 9, 11, 14, 15 are any standard amino acids. X1 is I, L, or V X2 is any standard amino acid except C. X3 is A, E, Q, R, or Y. X5 is any standard amino acid except R. X8 is I or L X10 is any standard amino acid except H. X12 is I, M, or T X13 is D, K, Q, or R X16éGou D X17 is E, L, G, R, or K, and the peptide in question has a length of 20 to 100 amino acid residues.

[00174] In some embodiments, the peptide presents a Petition 870260058481, dated 06 / 16 / 2026, page 57 / 140 / 131 length of at least 10 amino acids, such as at least 12 amino acids, such as at least 14 amino acids, such as at least 16 amino acids, such as at least 18 amino acids, such as at least 20 amino acids, such as at least 25 amino acids, such as at least 30 amino acids, such as at least 40 amino acids, such as at least 50 amino acids, such as at least 60 amino acids, such as at least 70 amino acids, such as at least 80 amino acids, such as when the peptide has a length of at least 90 amino acids.

[00175] In some embodiments, the peptide has a length of between 10 and 50 amino acids, as well as between 10 and 40 amino acids, as well as between 10 and 30 amino acids, as well as between 10 and 25 amino acids, as well as between 12 and 25 amino acids, as well as between 15 and 25 amino acids, as well as between 20 and 40 amino acids, as well as between 20 and 30 amino acids, as well as between 10 and 35 amino acids, as well as between 10 and 25 amino acids, as well as between 13 and 23 amino acids, as well as between 18 and 25 amino acids.

[00176] In some embodiments, the peptide comprises or consists of any of the following amino acid sequences: GKYGFYTHVFRLKKWIQKVIDQFGE (SEQ ID NO: 1), FYTHVFRLKKWIQKVIDQFGE (SEQ ID NO: 2), GKYGFYTHVFRLKKWIQKVI (SEQ ID NO: 3), HVFRLKKWIQKVIDQFGE (SEQ ID NO: 4), KYGFYTHVFRLKKWIQKVIDQFGE (SEQ ID NO: 5), GKYGFYTHVFRLKKWIQKVIDQF (SEQ ID NO: 6), GKYGFYTHVFRLKKWIQKV (SEQ ID NO: 7), or KKWIQKVIDQFGE (SEQ ID NO: 8); in which up to 2 amino acids from said sequences can be replaced by another amino acid.

[00177] In some embodiments, the peptide comprises or consists Petition 870260058481, of 06 / 16 / 2026, p. 58 / 140 / 131 in any of the amino acid sequences: GKYGFYTHVFRLKKWIQKVIDQFGE (SEQ ID NO: 1), FYTHVFRLKKWIQKVIDQFGE (SEQ ID NO: 2), GKYGFYTHVFRLKKWIQKVI (SEQ ID NO: 3), HVFRLKKWIQKVIDQFGE (SEQ ID NO: 4), KYGFYTHVFRLKKWIQKVIDQFGE (SEQ ID NO: 5), GKYGFYTHVFRLKKWIQKVIDQF (SEQ ID NO: 6), GKYGFYTHVFRLKKWIQKV (SEQ ID NO: 7), or KKWIQKVIDQFGE (SEQ ID NO: 8).

[00178] In some embodiments, the peptide comprises or consists of any of the following amino acid sequences: GKYGFYTHVFRLKKWIQKVIDQFGE (SEQ ID NO: 1), or GKYGFYTHVFRLKKWIQKVI (SEQ ID NO: 3)

[00179] In some embodiments, the peptide exhibits at least 80% sequence identity, such as at least 85% sequence identity, such as at least 90% sequence identity, such as at least 95% sequence identity, such as at least 99% sequence identity with the amino acid sequence: GKYGFYTHVFRLKKWIQKVIDQFGE (SEQ ID NO: 1) (SEQ ID NO: 5), GKYGFYTHVFRLKKWIQKVIDQF (SEQ ID NO: 6), GKYGFYTHVFRLKKWIQKV (SEQ ID NO: 7), or KKWIQKVIDQFGE (SEQ ID NO: 8).

[00180] In some embodiments, the peptide consists of the following amino acid sequence: GKYGFYTHVFRLKKWIQKVIDQFGE (SEQ ID NO: 1). Petition 870260058481, dated 06 / 16 / 2026, p. 59 / 140 / 131

[00181] In some embodiments, the peptide comprises or consists of one of the amino acid sequences selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6 and SEQ ID NO: 7, wherein any of said sequences comprises an amino acid substitution, such as two amino acid substitutions, such as three amino acid substitutions, such as four amino acid substitutions, such as five amino acid substitutions.

[00182] In some forms, amino acid substitution is a conservative substitution.

[00183] In some embodiments, the compound described herein may consist of the peptides described above. However, in other embodiments, the compound may comprise a peptide conjugated to one or more additional moieties. Thus, the peptide of the present invention may be modified or derivatized in any suitable manner. In other words, any of the amino acids comprised in the peptides may be modified or derivatized. In some embodiments, one or more of the amino acids comprised in the peptide are PEGylated, esterified, amidated, acylated, acetylated, alkenylated and / or alkylated.

[00184] Additionally, the peptide can be modified or derivatized in the manner described in international patent application WO2011 / 036442, from p. 11, 1.1 to p. 15, 1.14.

[00185] Thus, in some embodiments, one or more amino acids of the peptide are PEGylated, amidated, acylated, acetylated, alkenylated and / or alkylated. Thus, the peptide may consist of the sequence X1-X2-X3-X4-X5X6-W-X8-X9-X10, where each X is as defined above, except that one or more amino acids may be PEGylated, amidated, acylated, acetylated, alkenylated and / or alkylated.

[00186] The compound may also be an acid addition salt or Petition 870260058481, dated 06 / 16 / 2026, page 60 / 140 / 131 pharmaceutically acceptable basis of the peptide. The acids used to prepare pharmaceutically acceptable acid addition salts of peptides are those that form non-toxic acid addition salts, i.e., salts containing pharmacologically acceptable anions, such as hydrochloride, hydrobromide, iodide, nitrate, sulfate, bisulfate, acid, acetate, lactate, citrate, acid citrate, tartrate, bitartrate, succinate, maleate, fumarate, gluconate, saccharate, benzoate, methanesulfonate, ethanesulfonate, benzenesulfonate, ptoluenesulfonate and pamoate salts [i.e., 1,1'-methylene-bis-(2-hydroxy-3-naphthoate)], among others. Individual

[00187] The present invention relates to a compound for use in methods of treating a skin disease or skin condition selected from the group consisting of a disease or condition distinguished by blistering, a disease or condition distinguished by excessive wound exudate, a disease or condition distinguished by a dysregulated skin microbiome and scarring, in an individual who needs this.

[00188] The present invention further refers to a compound for use in a method of treating a skin disease or skin condition in an individual who needs it, wherein the skin disease or skin condition is a wound or a disease or condition distinguished by blistering, and wherein the treatment reduces the amount of fluid exuding from one or more wounds or blisters.

[00189] The present invention also relates to a compound for use in a method for promoting a healthy skin microbiome in an individual who needs it.

[00190] Preferably, the individual is a human being.

[00191] In some forms, the individual is a child, such as a human being no older than 18 years of age. Petition 870260058481, dated 06 / 16 / 2026, p. 61 / 140 / 131

[00192] As described herein, the individual may suffer from one or more skin conditions or skin diseases selected from the group consisting of a disease or condition distinguished by blistering, a disease or condition distinguished by excessive wound exudate, a disease or condition distinguished by a dysregulated skin microbiome, and scarring.

[00193] In one form, the individual suffers from a disease or condition distinguished by blister formation. Commonly, diseases with blister formation result in blisters that evolve into wounds.

[00194] In one embodiment, the disease or condition distinguished by blister formation is selected from the group consisting of: Epidermolysis bullosa (EB), burn-induced blisters, chilblains, cryotherapy-induced blisters, virus-induced blisters such as chickenpox, herpes zoster, herpes simplex, atypical enterovirus infection, hand-foot-and-mouth disease, herpetic eczema, bullous impetigo and staphylococcal scalded skin syndrome, pemphigus such as pemphigus foliaceus, pemphigus vulgaris, paraneoplastic pemphigus, pemphigus erythematosus or pemphigus vegetans, pemphigoid such as bullous pemphigoid, cicatricial pemphigoid, pemphigoid 200k or mucous membrane pemphigoid, linear IA bullous dermatosis, dermatitis herpetiformis, porphyria cutanea tarda, bullous lupus erythematosus, Hailey-Hailey disease and Stevens-Johnson syndrome (toxic epidermal necrolysis).

[00195] In one form, the individual suffers from EB. In some Petition 870260058481, dated 06 / 16 / 2026, page 62 / 140 / 131 modalities, the individual suffers from hereditary EB or bullous EB. In some modalities, the individual suffers from simple epidermolysis bullosa, junctional epidermolysis bullosa, dystrophic epidermolysis bullosa, dominant dystrophic epidermolysis bullosa, recessive dystrophic epidermolysis bullosa, Kindler syndrome, or acquired epidermolysis bullosa.

[00196] In one form, the individual suffers from blisters induced by burns.

[00197] In one embodiment, the individual suffers from a disease or condition distinguished by excessive wound exudate.

[00198] In some embodiments, the said disease or condition distinguished by excessive wound exudate is selected from the group consisting of burn wounds, chronic skin ulcers, acute infected wounds, pressure ulcers and chronic wounds such as venous ulcers, for example, venous leg ulcers, or diabetic leg ulcers.

[00199] In some modalities, the disease or condition distinguished by excessive wound exudate is a disease or condition distinguished by blistering. For example, the disease or condition distinguished by excessive wound exudate may be EB and / or burn-induced blisters as defined herein above.

[00200] In some modalities, the individual suffers from a disease or condition distinguished by a dysregulated skin microbiome.

[00201] In some modalities, the said disease or condition distinguished by dysregulated skin microbiome is selected from the group consisting of burn wounds, chronic skin ulcers, acute infected wounds, pressure ulcers and chronic wounds such as venous ulcers, for example, venous leg ulcers, or diabetic leg ulcers.

[00202] In some modalities, the disease or condition distinguished Petition 870260058481, dated 06 / 16 / 2026, p. 63 / 140 / 131, states that a dysregulated skin microbiome is a disease or condition distinguished by blistering. For example, a disease or condition distinguished by a dysregulated skin microbiome could be EB.

[00203] In some modalities, the individual suffers from scarring or a disease or condition distinguished by or resulting in scarring of the skin.

[00204] In some embodiments, the said disease or condition distinguished by or resulting in skin scarring is selected from the group consisting of burn wounds, chronic skin ulcers, acute infected wounds, pressure ulcers and chronic wounds such as venous ulcers, for example, venous leg ulcers, or diabetic leg ulcers.

[00205] In some modalities, the disease or condition distinguished by or resulting in skin scarring is a disease or condition distinguished by blistering. For example, the disease or condition distinguished by or resulting in skin scarring may be EB. Administration

[00206] The invention provides compounds comprising peptides for use in treatment methods. The treatment may be preventive, curative and / or aphrodisiac, preferably curative and / or aphrodisiac.

[00207] Compounds comprising peptides may be administered to the individual who needs them by any suitable route of administration. For example, the compound may be administered systemically or by local administration directly to the area affected by the disorder or condition.

[00208] Preferably, the compound is administered topically. For example, the compound is applied to one or more areas of the individual affected by the skin condition or disorder.

[00209] In some embodiments, the compound is contained in a Petition 870260058481, dated 06 / 16 / 2026, page 64 / 140 / 131 product. For example, the compound may be contained in an adhesive, a dry adhesive, a plaster, a bandage, a film, or a dressing.

[00210] The compound can be formulated in any manner suitable for the route of administration. In some embodiments, the compound is formulated as an ointment, cream, emulsion, lotion, powder, spray, solution, viscous solution, or gel, such as a hydrogel. Preferably, the compound is formulated as a hydrogel. In some embodiments, the formulated compound is contained in an adhesive, a dry adhesive, a plaster, a bandage, a film, or a dressing.

[00211] Those skilled in the art will be able to formulate the compounds of the invention in a manner suitable for the chosen route of administration. For a brief review of current methods useful for drug administration, see Langer, Science 249:1527-1533 (1990). Methods for the preparation of administrable compounds are known or evident to those skilled in the art and are described in more detail, for example, in Remington's Pharmaceutical Science, 17th edition, Mack Publishing Company, Easton, Pennsylvania (1985), which is hereafter referred to as "Remington".

[00212] In one embodiment, the compound is formulated in the manner described in international patent application WO 2021 / 121843.

[00213] Preferably, the compound is administered in a therapeutically effective amount. Even more preferably, the compound is administered in an effective dose, that is, a therapeutically effective amount, periodically, at an interval of administration such that at least one symptom or feature of the skin disorder or skin condition is reduced in intensity, severity, duration, or frequency. Composition

[00214] The compound may be formulated in any suitable form, such as in any composition suitable for the treatment of the individual who needs it. Thus, in some modalities, the compound is formulated Petition 870260058481, dated 06 / 16 / 2026, pp. 65 / 140 / 131 in a composition. In some embodiments, the composition additionally comprises one or more pharmaceutically acceptable carriers.

[00215] In some embodiments, the composition is contained within a product. For example, the compound may be contained in an adhesive, a dry adhesive, a dressing, a bandage, a film, or a dressing.

[00216] In some embodiments, the concentration of the compound in the composition is between 0.5 and 50 mg / mL, as well as between 0.8 and 10 mg / mL, as well as between 0.8 and 3 mg / mL, as well as between 2.5 and 9 mg / mL, as well as between 0.86 and 8.6 mg / mL, as well as between 2.9 and 8.6 mg / mL.

[00217] In some embodiments, the concentration of the peptide or compound in the composition is 0.86 mg / mL, 2.9 mg / mL or 8.6 mg / mL.

[00218] In some embodiments, the concentration of the compound in the composition is between 0.05% by weight and 5% by weight, such as between 0.08% by weight and 1% by weight, such as between 0.08% by weight and 0.3% by weight, such as between 0.25% by weight and 0.9% by weight, such as between 0.086% by weight and 0.86% by weight, such as between 0.29% by weight and 0.86% by weight.

[00219] In some embodiments, the concentration of the peptide or compound in the composition is 0.086% by weight, 0.29% by weight, or 0.86% by weight.

[00220] Preferably, the composition is administered in a therapeutically effective amount.

[00221] In some embodiments, between 0.075 mg / cm2 and 600 mg / cm2 of the compound is administered to the individual affected by the skin condition or skin disorder, such as between 0.1 mg / cm2 and 1.5 mg / cm2.

[00222] In some embodiments, 0.145 mg / cm2, 0.29 mg / cm2, 0.43 mg / cm2 or 0.86 mg / cm2 of the peptide or compound is administered to the individual affected by the skin condition or skin disorder.

[00223] In some modalities, the composition, compound or peptide is administered for at least one week, such as at least Petition 870260058481, dated 06 / 16 / 2026, page 66 / 140 / 131 two weeks, such as at least three weeks, such as at least four weeks, such as at least five weeks, such as at least six weeks, such as at least seven weeks, such as at least eight weeks, such as at least ten weeks, such as at least twelve weeks, or more.

[00224] In some modalities, the composition, compound or peptide is administered between one week and twelve weeks, such as between two weeks and eight weeks.

[00225] In some embodiments, the composition, compound or peptide is administered for at least one month, such as at least two months, such as at least three months, such as at least four months, such as at least five months, such as at least six months, such as at least seven months, such as at least eight months, such as at least ten months, such as at least one year, such as at least two years.

[00226] In some embodiments, the composition, compound or peptide is administered between one month and two years, such as between one month and one year, such as between one month and six months, such as between one month and two months.

[00227] In some embodiments, the peptide or compound is administered for two weeks at a concentration of between 2.5 and 3.5 mg / mL, such as 2.9 mg / mL, followed by administration for two weeks at a concentration of between 8 and 9 mg / mL, such as 8.6 mg / mL.

[00228] In some modalities, the composition, compound or peptide is administered three times a week, such as every second or third day for at least four weeks.

[00229] In some embodiments, the peptide or compound is administered at an increasing dose or concentration over time, such as for two, three, four or more periods in which the dose or concentration of peptide or compound is increased for each period. Petition 870260058481, dated 06 / 16 / 2026, page 67 / 140 / 131

[00230] In some modalities: a. between 0.025 and 0.075 mL / cm2, such as 0.05 mL / cm2, of the peptide or compound is administered to the individual affected by the skin condition or skin disorder during the first treatment period, where the concentration of said peptide or compound is between 2.5 and 3.5 mg / mL, such as 2.9 mg / mL; b. between 0.05 and 0.15 mL / cm2, such as 0.1 mL / cm2, of the peptide or compound is administered to the individual affected by the skin condition during the second treatment period, in which the concentration of said peptide or compound is between 2.5 and 3.5 mg / mL, such as 2.9 mg / mL; c. between 0.025 and 0.075 mL / cm2, such as 0.05 mL / cm2, of the peptide or compound is administered to the individual affected by the skin condition during the third treatment period, where the concentration of said peptide or compound is between 8 and 9 mg / mL, such as 8.6 mg / mL; and d. between 0.05 and 0.15 L / cm2, such as 0.1 mL / cm2, of the peptide or compound is administered to the individual affected by the skin condition during the fourth treatment period, in which the concentration of said peptide or compound is between 8 and 9 mg / mL, such as 8.6 mg / mL; optionally, each treatment period is approximately one week, or optionally, the compound or peptide is administered three times a week, such as every second or third day.

[00231] In some modalities: a. between 0.1 and 0.2 mg / cm2, such as 0.14 mg / cm2, of the peptide or compound is administered to the individual affected by the skin condition or skin disorder during the initial treatment period; b. between 0.25 and 0.35 mg / cm2, such as 0.29 mg / cm2, of the peptide or compound is administered to the individual affected by the skin condition during the second treatment period; Petition 870260058481, dated 06 / 16 / 2026, page 68 / 140 / 131 c. between 0.4 and 0.5 mg / cm2, such as 0.43 mg / cm2, of the peptide or compound is administered to the individual affected by the skin condition or skin lesion during the third treatment period; and d. between 0.8 and 0.9 mg / cm2, such as 0.86 mg / cm2, of the peptide or compound is administered to the individual affected by the skin condition or skin lesion during the fourth treatment period; optionally, each treatment period is approximately one week, or optionally, the compound or peptide is administered three times a week, such as every second or third day.

[00232] In some modalities, the first, second, third and fourth treatment periods are between 2 days and 2 months, such as between 4 days and 1 month, such as between 6 days and 3 weeks, such as between one week and two weeks.

[00233] The composition may additionally include any suitable components.

[00234] In one embodiment, the composition is a hydrogel comprising EDTA.

[00235] In some forms, the composition additionally includes: a. EDTA, and b. an aqueous buffer, in which i. the composition has a pH of no more than 8 and / or ii. the concentration of the compound in the composition is at least 0.08% by weight.

[00236] In other forms, the composition additionally includes: a. a polymer capable of forming a hydrogel when Petition 870260058481, dated 06 / 16 / 2026, pages 69 / 140 / 131 mixed with an aqueous solution, and b. an aqueous solution in which i. the concentration of the compound in the composition is at least 0.08% by weight and / or ii. the polymer is present in said composition at a concentration of at least 0.05% by weight. Items

[00237] 1. A compound for use in a method for treating a skin disease or skin condition in an individual who needs it, wherein said skin disease or skin condition is selected from the group consisting of a disease or condition distinguished by blistering, a disease or condition distinguished by excessive wound exudate, a disease or condition distinguished by a dysregulated skin microbiome and scarring, wherein the compound comprises a peptide comprising or consisting of the amino acid sequence X1-X2-X3-X4-X5-X6-W-X8-X9-X10, where X4, 6, 9 is any standard amino acid. X1 is I, L, or V. X2 is any standard amino acid except C. X3 is A, E, Q, R, or Y. X5 is any standard amino acid except R. X8 is I or L, X10 is any standard amino acid except H, wherein the peptide has a length of 10 to 100 amino acid residues.

[00238] 2. A method for treating a skin disease or skin condition in an individual who needs it, wherein the said disease of Petition 870260058481, dated 06 / 16 / 2026, p. 70 / 140 / 131 skin or skin condition is selected from the group consisting of a disease or condition distinguished by blistering, a disease or condition distinguished by excessive wound exudate, a disease or condition distinguished by a dysregulated skin microbiome and scarring, said method comprising administering a compound comprising a peptide comprising or consisting of the amino acid sequence X1-X2-X3-X4-X5-X6-W-X8-X9-X10, where X4, 6, 9 is any standard amino acid. X1 is I, L, or V. X2 is any standard amino acid except C. X3 is A, E, Q, R, or Y. X5 is any standard amino acid except R. X8 is I or L, X10 is any standard amino acid except H, wherein the peptide has a length of 10 to 100 amino acid residues.

[00239] 3. A pharmaceutical composition for use in the treatment of a skin disease or skin condition in an individual who needs it, wherein said skin disease or skin condition is selected from the group consisting of a disease or condition distinguished by blistering, a disease or condition distinguished by excessive wound exudate, a disease or condition distinguished by a dysregulated skin microbiome and scarring, wherein the composition comprises a compound comprising a peptide comprising or consisting of the amino acid sequence X1-X2-X3-X4-X5-X6-W-X8-X9-X10, where X4, 6, 9 is any standard amino acid. Petition 870260058481, dated 06 / 16 / 2026, p. 71 / 140 / 131 Xi is I, L, or V. X2 is any standard amino acid except C. X3 is A, E, Q, R, or Y. X5 is any standard amino acid except R. X8 is I or L, X10 is any standard amino acid except H, wherein the peptide has a length of 10 to 100 amino acid residues.

[00240] 4. Use of a compound in the manufacture of a medicament for the treatment of a skin disease or skin condition in an individual who needs it, wherein said skin disease or skin condition is selected from the group consisting of a disease or condition distinguished by blistering, a disease or condition distinguished by excessive wound exudate, a disease or condition distinguished by a dysregulated skin microbiome and scarring, wherein the compound comprises a peptide comprising or consisting of the amino acid sequence X1-X2-X3-X4-Xs-X6-W-X8-X9-X10, where X4, 6, 9 is any standard amino acid. X1 is I, L, or V. X2 is any standard amino acid except C. X3 is A, E, Q, R, or Y. X5 is any standard amino acid except R. X8 is I or L, X10 is any standard amino acid except H, wherein the peptide has a length of 10 to 100 amino acid residues.

[00241] 5. A compound for use in a method for reducing the amount of fluid exuding from one or more wounds or blisters in a Petition 870260058481, dated 06 / 16 / 2026, p. 72 / 140 / 131 individual who needs this, where the compound comprises a peptide comprising or consisting of the amino acid sequence X1-X2-X3-X4-X5-X6-W-X8-X9-X10, where X4, 6, 9 is any standard amino acid. X1 is I, L, or V. X2 is any standard amino acid except C. X3 is A, E, Q, R, or Y. X5 is any standard amino acid except R. X8 is I or L, X10 is any standard amino acid, except H, in which the peptide has a length of 10 to 100 amino acid residues.

[00242] 6. A method for reducing the amount of fluid exuding from one or more wounds or blisters in an individual who needs it, said method comprising administering a compound comprising a peptide comprising or consisting of the amino acid sequence X1-X2-X3-X4-X5-X6-W-X8-X9-X10, where X4, 6, 9 is any standard amino acid. X1 is I, L, or V. X2 is any standard amino acid except C. X3 is A, E, Q, R, or Y. X5 is any standard amino acid except R. X8 is I or L, X10 is any standard amino acid, except H, in which the peptide has a length of 10 to 100 amino acid residues.

[00243] 7. A compound for use in a treatment method of Petition 870260058481, dated 06 / 16 / 2026, p. 73 / 140 / 131 a skin disease or skin condition in an individual who needs it, wherein the skin disease or skin condition is a wound or a disease or condition distinguished by blistering, and wherein the treatment reduces the amount of fluid exuding from one or more wounds or blisters, and wherein the compound comprises a peptide comprising or consisting of the amino acid sequence X1-X2-X3-X4-X5-X6-W-X8-X9-X10, where X4, 6, 9 is any standard amino acid. X1 is I, L, or V. X2 is any standard amino acid except C. X3 is A, E, Q, R, or Y. X5 is any standard amino acid except R. X8 is I or L, X10 is any standard amino acid except H, wherein the peptide has a length of 10 to 100 amino acid residues.

[00244] 8. A method of treating a skin disease or skin condition in an individual who needs it, wherein the skin disease or skin condition is a wound or a disease or condition distinguished by blistering, and wherein the treatment reduces the amount of fluid exuding from one or more wounds or blisters, said method comprising administering a compound comprising a peptide comprising or consisting of the amino acid sequence X1-X2-X3-X4-X5-X6-W-X8-X9-X10, where X4, 6, 9 is any standard amino acid. X1 is I, L, or V. X2 is any standard amino acid except C. X3 is A, E, Q, R, or Y. Petition 870260058481, dated 06 / 16 / 2026, p. 74 / 140 / 131 X5 is any standard amino acid except R. X8 is I or L, X10 is any standard amino acid except H, wherein the peptide has a length of 10 to 100 amino acid residues.

[00245] 9. A compound to promote a healthy skin microbiome in an individual who needs it, wherein the compound comprises a peptide comprising or consisting of the amino acid sequence X1-X2-X3-X4-X5-X6-W-X8-X9-X10, where X4, 6, 9 is any standard amino acid. X1 is I, L, or V. X2 is any standard amino acid except C. X3 is A, E, Q, R, or Y. X5 is any standard amino acid except R. X8 is I or L, X10 is any standard amino acid, except H, in which the peptide has a length of 10 to 100 amino acid residues.

[00246] 10. A method for promoting a healthy skin microbiome in an individual who needs it, said method comprising administering a compound comprising a peptide comprising or consisting of the amino acid sequence X1-X2-X3-X4-X5-X6-W-X8-X9-X10, where X4, 6, 9 is any standard amino acid. X1 is I, L, or V. X2 is any standard amino acid except C. X3 is A, E, Q, R, or Y. Petition 870260058481, dated 06 / 16 / 2026, p. 75 / 140 / 131 X5 is any standard amino acid except R. X8 is I or L, X10 is any standard amino acid except H, wherein the peptide has a length of 10 to 100 amino acid residues.

[00247] 11. The compound for use, the method, the pharmaceutical composition or the use in accordance with any of the preceding items, in which the individual suffers from a skin disease or skin condition selected from the group consisting of a disease or condition distinguished by blistering, a disease or condition distinguished by excessive wound exudate, a disease or condition distinguished by a dysregulated skin microbiome and scarring.

[00248] 12. The compound for use, the method, the pharmaceutical composition or the use according to any of the preceding items, in which the individual suffers from a skin disease or skin condition selected from the group consisting of burn wounds, chronic skin ulcers, acute infected wounds, pressure ulcers and chronic wounds such as venous ulcers, for example, venous leg ulcers, and diabetic leg ulcers.

[00249] 13. The compound for use, the method, the pharmaceutical composition or the use in accordance with any of the preceding items, in which the individual suffers from eczema, such as atopic dermatitis.

[00250] 14. The compound for use, the method, the pharmaceutical composition or the use according to any of the preceding items, in which the disease or condition distinguished by blister formation is selected from the group consisting of: epidermolysis bullosa (EB), burn-induced blisters, chilblains, Petition 870260058481, dated 06 / 16 / 2026, p. 76 / 140 / 131 cryotherapy-induced blisters, virus-induced blisters, such as chickenpox, herpes zoster, herpes simplex, atypical enterovirus infection, hand-foot-and-mouth disease, herpetic eczema, bullous impetigo and staphylococcal scalded skin syndrome, pemphigus, such as pemphigus foliaceus, pemphigus vulgaris, paraneoplastic pemphigus, pemphigus erythematosus or pemphigus vegetans, pemphigoid, such as bullous pemphigoid, cicatricial pemphigoid, pemphigoid 200k or mucous membrane pemphigoid, linear IA bullous dermatosis, dermatitis herpetiformis, porphyria cutanea tarda, bullous lupus erythematosus, Hailey-Hailey disease and Steven Johnson syndrome (toxic epidermal necrolysis).

[00251] 15. The compound for use, the method, the pharmaceutical composition or use according to any of the preceding items, in which the disease or condition distinguished by blister formation is epidermolysis bullosa (EB).

[00252] 16. The compound for use, the method, the pharmaceutical composition or the use according to any of the preceding items, wherein the disease or condition distinguished by blistering is EB, and wherein EB is inherited epidermolysis bullosa or acquired epidermolysis bullosa.

[00253] 17. The compound for use, the method, the pharmaceutical composition or the use in accordance with any of the preceding items, wherein the disease or condition distinguished by blistering is EB, wherein EB is simple epidermolysis bullosa, junctional epidermolysis bullosa, dystrophic epidermolysis bullosa, such as dominant dystrophic epidermolysis bullosa or recessive dystrophic epidermolysis bullosa, Kindler syndrome or acquired epidermolysis bullosa. Petition 870260058481, dated 06 / 16 / 2026, p. 77 / 140 / 131

[00254] 18. The compound for use, the method, the pharmaceutical composition or the use in accordance with any of the preceding items, wherein said treatment reduces the size of one or more blisters or wounds.

[00255] 19. The compound for use, the method, the pharmaceutical composition or the use in accordance with any of the preceding items, wherein treatment reduces the size of one or more blisters or wounds by at least 10%, such as at least 20%, such as at least 30%, such as at least 35%, such as at least 40%, such as at least 45%, such as at least 50%, such as at least 60%, such as at least 70%, such as at least 80%, such as at least 90%, such as when treatment reduces the size of one or more blisters or wounds by at least 95%, compared to the size of one or more blisters or wounds before treatment, or compared to the size of a blister or wound that was not treated with the compound comprising the peptide, and which before treatment was of similar size and characteristics to one or more treated blisters or wounds.

[00256] 20. The compound for use, the method, the pharmaceutical composition or the use in accordance with any of the preceding items, wherein treatment reduces the size of one or more blisters or wounds by 100%, so that the treatment results in the complete healing of one or more blisters or wounds.

[00257] 21. The compound for use, the method, the pharmaceutical composition or the use according to any of the preceding items, in which the size of one or more blisters or wounds is reduced after treatment for at least two days, such as at least five days, such as at least one week, such as at least two weeks, such as at least three weeks, such as at least four weeks, such as at least one month, such as at least two months, such as at least five months, such Petition 870260058481, dated 16 / 06 / 2026, p. 78 / 140 / 131, such as at least six months, such as at least seven months, such as at least eight months, such as at least nine months, such as at least ten months, such as at least eleven months, such as when the size of one or more blisters or wounds is reduced after one year of treatment.

[00258] 22. The compound for use, the method, the pharmaceutical composition or the use in accordance with any of the preceding items, wherein the wound or blister remains healed and does not reopen for at least two days, such as at least five days, such as at least one week, such as at least two weeks, such as at least three weeks, such as at least four weeks, such as at least one month, such as at least two months, such as at least five months, such as at least six months, such as at least seven months, such as at least eight months, such as at least nine months, such as at least ten months, such as at least eleven months, such as at least one year, such as at least two years, such as at least three years, such as at least four years, such as at least five years after the treatment is completed, such as when the wound or blister remains healed and does not reopen in any way after the treatment is completed.

[00259] 23. The compound for use, the method, the pharmaceutical composition or the use in accordance with any of the preceding items, wherein said treatment reduces the pain felt by the individual, such as wherein said treatment reduces the pain of one or more wounds or blisters, optionally wherein the pain is measured using a pain scale selected from the group consisting of Neonatal / Infant Pain Scale (NIPS), Children's Hospital of Eastern Ontario Pain Scale (CHEOPS), Face, Legs, Activity, Cry, Consolability Scale (FLACC), Faces Pain Scale (Wong-Baker Faces Pain Rating Scale), Color Analog Scale, Visual Analog Scale, Verbal Numerical Rating Scale and Wharton Disability and Pain Scale. Petition 870260058481, dated 06 / 16 / 2026, pp. 79 / 140 / 131

[00260] 24. The compound for use, the method, the pharmaceutical composition or the use in accordance with any of the preceding items, wherein pain is reduced by at least one step or score on a pain scale, such as at least two steps or scores, such as at least three steps or scores, such as at least four steps or scores, such as at least five steps or scores, such as at least six steps or scores, such as at least seven steps or scores, such as at least eight steps or scores, such as at least nine steps or scores, such as when pain is reduced by ten steps or scores on a pain scale, optionally wherein pain is measured using a pain scale selected from the group consisting of Neonatal / Infant Pain Scale (NIPS), Children's Hospital of Eastern Ontario Pain Scale (CHEOPS), Face, Legs, Activity, Cry, Consolability Scale (FLACC), Faces Pain Scale (Faces Pain Rating Scale) by Wong-Baker),Color Analog Scale, Visual Analog Scale, Verbal Numerical Rating Scale, and Wharton Pain and Disability Scale.

[00261] 25. The compound for use, the method, the pharmaceutical composition or the use in accordance with any of the foregoing items, wherein said treatment reduces itching felt by the individual, such as itching from one or more wounds or blisters, optionally wherein itching is assessed by means of subjective report by the patient or by objective measurement of scratching activity or skin changes induced by itching, optionally wherein itching is measured using the Leuven Itch Scale, optionally wherein itching is measured using the 5-D Itch Scale.

[00262] 26. The compound for use, the method, the pharmaceutical composition or the use in accordance with any of the preceding items, in Petition 870260058481, dated 06 / 16 / 2026, p. 80 / 140 / 131, which states that treatment reduces the amount of fluid exuding from one or more blisters or wounds, just as when treatment reduces the amount of wound exudate.

[00263] 27. The compound for use, treatment method, pharmaceutical composition or use according to any of the preceding items, wherein treatment reduces the amount of fluid exuding from a wound or blister by at least 10%, such as at least 20%, such as at least 30%, such as at least 35%, such as at least 40%, such as at least 45%, such as at least 50%, such as at least 60%, such as at least 70%, such as at least 80%, such as at least 90%, such as when the amount of wound exudate is reduced by at least 95%, optionally wherein the amount of wound exudate is estimated by visual inspection of the wound dressing, optionally wherein the amount of wound exudate is measured by imaging the wound dressing, optionally wherein the amount of wound exudate is measured by weighing the wound dressing,optionally where the amount of wound exudate is measured by measuring the protein content in the wound dressing, such as the total protein content in the wound dressing, optionally where the protein content is measured using the Bradford protein assay, optionally where the decrease is compared to before the start of treatment of the wound or blister, optionally where the decrease is compared to a wound or blister of similar size and characteristics that was not treated with the compound comprising the peptide and that before treatment had a similar amount of wound exudate as the treated wound or blister.

[00264] 28. The compound for use, treatment method, composition Petition 870260058481, dated 06 / 16 / 2026, page 81 / 140 / 131 pharmaceutical or use in accordance with any of the preceding items, wherein treatment decreases the amount of fluid exuding from the wound or blister by at least one step or score on an exudate scale, such as at least two steps or scores, such as at least three steps or scores, such as at least four steps or scores, such as at least five steps or scores on a wound exudate scale, optionally wherein the exudate score or scale is performed by visual inspection of the wound dressing, optionally wherein the leakage score or scale is performed using a visual scoring scale of 0-5, wherein 0 represents “No exudation in the wound area” and 5 represents “Exudation soaking the dressing in an area that exceeds the wound area”.

[00265] 29. The compound for use, method of treatment, pharmaceutical composition or use according to any of the preceding items, wherein treatment reduces the amount of heparin-binding protein in wound exudate, optionally wherein the amount of HBP is decreased by at least 20%, such as at least 30%, such as at least 40%, such as at least 50%, such as at least 60%, such as at least 70%, such as at least 80%, such as at least 90%, optionally wherein the decrease is compared to before the start of treatment of the wound or blister, optionally wherein the decrease is compared to a wound or blister of similar size and characteristics that was not treated with the compound comprising the peptide and that before treatment had a similar amount of wound exudate as the treated wound or blister.

[00266] 30. The compound for use, method of treatment, pharmaceutical composition or use according to any of the preceding items, in which treatment reduces the total protein content exuding from a wound or Petition 870260058481, dated 06 / 16 / 2026, page 82 / 140 / 131 bubble.

[00267] 31. The compound for use, method of treatment, pharmaceutical composition or use according to any of the foregoing items, wherein the treatment reduces the number of times dressings need to be changed in a defined period of time, such as when the treatment increases the number of days elapsed before dressings need to be changed, such as when the treatment results in dressings that do not need to be changed as frequently compared to the start of treatment, optionally wherein the timing for dressing change is determined based on the amount of exudate present in the dressing, optionally wherein the timing for dressing change is determined to reduce the risk of inflammation and / or infection.

[00268] 32. The compound for use, treatment method, pharmaceutical composition or use according to any of the preceding items, wherein the treatment increases the number of days elapsed between dressing changes by half a day, such as by one day, such as by 1.5 days, such as by 2 days, such as by 2.5 days, such as by 3 days, such as by 3.5 days, such as by 4 days, such as by 4.5 days, such as by 5 days, such as when treatment increases the number of days elapsed between dressing changes for wounds by 6 days, optionally wherein the treatment results in the dressing needing to be changed only every three days, such as every four days, such as every five days, such as every six days, such as wherein the treatment results in the dressing needing to be changed only once a week.

[00269] 33. The compound for use, the method, the pharmaceutical composition or the use in accordance with any of the preceding items, in which treatment reduces the total quantity of microorganisms present in one or more wounds or blisters, such as the total quantity of bacteria present in one or more wounds or blisters. Petition 870260058481, dated 06 / 16 / 2026, p. 83 / 140 / 131

[00270] 34. The compound for use, the method, the pharmaceutical composition or the use in accordance with any of the preceding items, wherein treatment reduces the total quantity of microorganisms present in one or more wounds or blisters by at least 10%, such as at least 20%, such as at least 30%, such as at least 35%, such as at least 40%, such as at least 45%, such as at least 50%, such as at least 60%, such as at least 70%, such as at least 80%, such as at least 90%, such as when the total quantity of microorganisms present in one or more wounds or blisters is reduced by at least 95% compared to the quantity of bacteria present before treatment, optionally wherein the quantity of microorganisms is measured by measuring the quantity of colony-forming units (CFU) present in a wound dressing and / or in a wound or blister on the skin, wherein said measurement occurs before, during and / or after treatment.

[00271] 35. The compound for use, the method, the pharmaceutical composition or the use according to any of the preceding items, wherein the dysregulated skin microbiome is distinguished by a decreased ratio of beneficial:harmful microorganisms compared to the ratio of beneficial:harmful microorganisms in an individual not suffering from a dysregulated microbiome, such that harmful microorganisms comprise a larger part of the total skin microbiome in the dysregulated skin microbiome, compared to the skin microbiome of an individual suffering from a dysregulated skin microbiome.

[00272] 36. The compound for use, the method, the pharmaceutical composition or the use according to any of the preceding items, wherein the beneficial microorganisms are non-pathogenic microorganisms, such as non-pathogenic bacteria, and wherein the harmful microorganisms are pathogenic microorganisms, such as pathogenic bacteria.

[00273] 37. The compound for use, the method, the composition Petition 870260058481, dated 06 / 16 / 2026, page 84 / 140 / 131 pharmaceutical or use in accordance with any of the preceding items, wherein treatment promotes a healthy skin microbiome.

[00274] 38. The compound for use, the method, the pharmaceutical composition or the use in accordance with any of the preceding items, wherein treatment reduces the total amount of commensal skin microorganisms in the skin microbiome, such as wherein treatment reduces the load of excessive bacteria, for example, wherein treatment reduces the overall bacterial load in a wound or blister.

[00275] 39. The compound for use, the method, the pharmaceutical composition or the use in accordance with any of the preceding items, wherein treatment preserves the composition of the skin microbiome, such as when treatment preserves the microbial diversity of the skin microbiome.

[00276] 40. The compound for use, the method, the pharmaceutical composition or the use in accordance with any of the preceding items, in which treatment preserves the ratio between different microbial species and / or strains in the skin microbiome, such as when the ratio between different microbial species and / or strains in the skin microbiome is the same or similar before, during and / or after treatment.

[00277] 41. The compound for use, the method, the pharmaceutical composition or the use in accordance with any of the preceding items, wherein the treatment maintains the ratio of beneficial to harmful microorganisms in the skin microbiome, such as when the ratio of beneficial to harmful microorganisms in the skin microbiome is the same or similar before, during and / or after treatment, optionally wherein the treatment increases the ratio of beneficial to harmful microorganisms in the skin microbiome, for example, wherein the treatment doubles, triples or quadruples the ratio of beneficial to harmful microorganisms in the skin microbiome, in such a way that the Petition 870260058481, dated 06 / 16 / 2026, page 85 / 140 / 131 beneficial microorganisms during and / or after treatment constitute a larger part of the total skin microbiome compared to harmful microorganisms.

[00278] 42. The compound for use, treatment method, pharmaceutical composition or use according to any of the preceding items, wherein the harmful microorganism is selected from the group consisting of Staphylococcus aureus, Bacillus licheniformis, Bacillus cereus complex, Rothia amarae, Staphylococcus spp., Streptococcus spp., Group A Streptococcus, such as Streptococcus pyogenes, and Gram-negative bacteria, such as Pseudomonas aeruginosa, Proteobacteria spp. and Proteus spp..

[00279] 43. The compound for use, the method, the pharmaceutical composition or the use according to any of the preceding items, wherein the beneficial microorganism is selected from the group consisting of Staphylococcus xylosus, Staphylococcus hominis, Staphylococcus nepalensis, Staphylococcus warneri, Staphylococcus borealis, Staphylococcus petrasii, Staphylococcus epidermidis, Staphylococcus lugdunensis, Staphylococcus caprae, Staphylococcus saprophyticus, Staphylococcus capitis, Staphylococcus haemolyticus, Staphylococcus condiment, Corynebacterium spp. and Micrococcus spp.

[00280] 44. The compound for use, the method, the pharmaceutical composition or the use in accordance with any of the preceding items, in which treatment reduces the size of the scar.

[00281] 45. The compound for use, the method, the pharmaceutical composition or use according to any of the preceding items, in which treatment reduces scar formation.

[00282] 46. The compound for use, the method, the pharmaceutical composition or the use in accordance with any of the preceding items, in which treatment reduces the size of the scar by at least 10%, such as at least 20%, such as at least 30%, such as at least 35%, such Petition 870260058481, dated 16 / 06 / 2026, p. 86 / 140 / 131 as at least 40%, such as at least 45%, such as at least 50%, such as at least 60%, such as at least 70%, such as at least 80%, such as at least 90%, such as when treatment reduces scar formation by at least 95% compared to the size of a scar formed by a wound of similar size and characteristics that was not treated.

[00283] 47. The compound for use, the method, the pharmaceutical composition or the use according to any of the preceding items, wherein the compound is administered topically in a therapeutically effective amount.

[00284] 48. The compound for use, the method, the pharmaceutical composition or the use in accordance with any of the preceding items, wherein the compound is administered to one or more areas of the individual affected by the skin condition or skin disorder.

[00285] 49. The compound for use, the method, the pharmaceutical composition or the use in accordance with any of the preceding items, wherein treatment is preventive, curative or improvement treatment.

[00286] 50. The compound for use, the method, the pharmaceutical composition or the use according to any of the preceding items, wherein the compound is contained in an adhesive, a dry adhesive, a plaster, a bandage, a film or a dressing.

[00287] 51. The compound for use, the method, the pharmaceutical composition or the use according to any of the preceding items, wherein the compound is formulated in an ointment, cream, emulsion, lotion, powder, spray, solution, viscous solution or gel, such as a hydrogel, preferably wherein the compound is formulated in a hydrogel.

[00288] 52. The compound for use, the method, the pharmaceutical composition or the use according to any of the preceding items, wherein the compound is administered in an effective dose periodically in a Petition 870260058481, dated 06 / 16 / 2026, page 87 / 140 / 131 administration interval such that at least one symptom or characteristic of the skin disorder or skin condition is reduced in intensity, severity, duration, or frequency.

[00289] 53. The compound for use, the method, the pharmaceutical composition or the use according to any of the preceding items, wherein the individual is a human being.

[00290] 54. The compound for use, the method, the pharmaceutical composition or the use in accordance with any of the preceding items, wherein a. The peptide comprises or consists of the sequence of amino acids X1-X2-X3-X4-X5-X6-W-X8-X9-X10-X11-X12-X13, where X4, 6, 9, 11 are any standard amino acids, and X1 is I, L, or V. X2 is any standard amino acid except C. X3 is A, E, Q, R, or Y. X5 is any standard amino acid except R. X8 is I or L X10 is any standard amino acid except H. X12 is I, M, or T X13 is D, K, Q, or R, wherein said peptide has a length of 20 to 100 amino acid residues; or b. the peptide comprises or consists of the amino acid sequence X1-X2-X3-X4-X5-X6-W-X8-X9-X10-X11-X12-X13-X14X15-X16-X17, where X4, 6, 9, 11, 14, 15 are any standard amino acids. X1 is I, L, or V Petition 870260058481, dated 06 / 16 / 2026, p. 88 / 140 / 131 X2 is any standard amino acid except C. X3 is A, E, Q, R, or Y. X5 is any standard amino acid except R. X8 is I or L X10 is any standard amino acid except H. X12 is I, M, or T X13 is D, K, Q, or R X16éGou D X17 is E, L, G, R, or K, and the peptide in question has a length of 20 to 100 amino acid residues.

[00291] 55. The compound for use, the method, the pharmaceutical composition or the use according to any of the preceding items, wherein the peptide has a length of 10 to 35 amino acids, such as 10 to 25 amino acids, such as 12 to 25 amino acids, such as 13 to 23 amino acids, such as 20 to 30 amino acids, preferably 15 to 25 amino acids.

[00292] 56. The compound for use, the method, the pharmaceutical composition or the use according to any of the preceding items, wherein the peptide comprises or consists of any of the following amino acid sequences: GKYGFYTHVFRLKKWIQKVIDQFGE (SEQ ID NO: 1), FYTHVFRLKKWIQKVIDQFGE (SEQ ID NO: 2), GKYGFYTHVFRLKKWIQKVI (SEQ ID NO: 3), HVFRLKKWIQKVIDQFGE (SEQ ID NO: 4), KYGFYTHVFRLKKWIQKVIDQFGE (SEQ ID NO: 5), GKYGFYTHVFRLKKWIQKVIDQF (SEQ ID NO: 6), GKYGFYTHVFRLKKWIQKV (SEQ ID NO: 7), or KKWIQKVIDQFGE (SEQ ID NO: 8); Petition 870260058481, dated 06 / 16 / 2026, pp. 89 / 140 / 131, preferably wherein the peptide comprises or consists of any of the following amino acid sequences: GKYGFYTHVFRLKKWIQKVIDQFGE (SEQ ID NO: 1), or GKYGFYTHVFRLKKWIQKVI (SEQ ID NO: 3); or wherein the peptide exhibits at least 80% sequence identity, such as at least 85% sequence identity, such as at least 90% sequence identity, such as at least 95% sequence identity with any of the amino acid sequences: GKYGFYTHVFRLKKWIQKVIDQFGE (SEQ ID NO: 1) (SEQ ID NO: 5), GKYGFYTHVFRLKKWIQKVIDQF (SEQ ID NO: 6), GKYGFYTHVFRLKKWIQKV (SEQ ID NO: 7), or KKWIQKVIDQFGE (SEQ ID NO: 8); preferably where the peptide consists of the following amino acid sequence: GKYGFYTHVFRLKKWIQKVIDQFGE (SEQ ID NO: 1).

[00293] 57. The compound for use, the method, the pharmaceutical composition or the use according to any of the preceding items, wherein one or more of the standard amino acids comprised in the peptide are modified or derivatized, optionally wherein one or more of the standard amino acids comprised in the peptide are PEGylated, amidated, acylated, acetylated, alkenylated and / or alkylated.

[00294] 58. The compound for use, the method, the pharmaceutical composition or the use according to any of the preceding items, in which the compound is formulated into a composition.

[00295] 59. The compound for use, the method, the composition Petition 870260058481, dated 06 / 16 / 2026, pp. 90 / 140 / 131 pharmaceutical or use in accordance with any of the preceding claims, wherein the composition is formulated as an ointment, cream, emulsion, lotion, powder, spray, solution, viscous solution or gel, such as a hydrogel, preferably wherein the compound is formulated in a hydrogel.

[00296] 60. The compound for use, the method, the pharmaceutical composition or the use according to any of the preceding items, wherein the composition additionally comprises one or more pharmaceutically acceptable carriers.

[00297] 61. The compound for use, the method, the pharmaceutical composition or the use according to any of the preceding items, wherein the composition is contained in an adhesive, a dry adhesive, a plaster, a bandage, a film or a dressing.

[00298] 62. The compound for use, the method, the pharmaceutical composition or the use in accordance with any of the preceding items, in which the composition, compound or peptide is administered for at least one week, such as at least two weeks, such as at least three weeks, such as at least four weeks, such as at least five weeks, such as at least six weeks, such as at least seven weeks, such as at least eight weeks, such as at least ten weeks, such as at least twelve weeks, or more.

[00299] 63. The compound for use, the method, the pharmaceutical composition or the use according to any of the preceding items, wherein the composition, compound or peptide is administered between one week and twelve weeks, such as between two weeks and eight weeks.

[00300] 64. The compound for use, the method, the pharmaceutical composition or the use in accordance with any of the preceding items, in which the composition, compound or peptide is administered for at least one month, such as at least two months, such as at least three months, such as at least four months, such as Petition 870260058481, dated 06 / 16 / 2026, p. 91 / 140 / 131 at least five months, as well as at least six months, as well as at least seven months, as well as at least eight months, as well as at least ten months, as well as at least one year, as well as at least two years.

[00301] 65. The compound for use, the method, the pharmaceutical composition or the use in accordance with any of the preceding items, in which the composition, compound or peptide is administered between one month and two years, such as between one month and one year, such as between one month and six months, such as between one month and two months.

[00302] 66. The compound for use, the method, the pharmaceutical composition or the use according to any of the preceding items, wherein the concentration of the peptide or compound in said composition is between 0.5 and 50 mg / mL, such as between 0.8 and 10 mg / mL, such as between 0.8 and 3 mg / mL, such as between 2.5 and 9 mg / mL.

[00303] 67. The compound for use, the method, the pharmaceutical composition or the use according to any of the preceding items, wherein the concentration of the peptide or compound in said composition is 0.86 mg / mL, 2.9 mg / mL or 8.6 mg / mL.

[00304] 68. The compound for use, the method, the pharmaceutical composition or the use according to any of the preceding items, wherein the composition, compound or peptide is administered three times a week, such as every second or third day, optionally for at least four weeks.

[00305] 69. The compound for use, the method, the pharmaceutical composition or the use according to any of the preceding items, wherein between 0.075 mg / cm2 and 600 mg / cm2 of the peptide or compound is administered to the individual affected by the skin condition or skin disorder, such as between 0.1 mg / cm2 and 1.5 mg / cm2.

[00306] 70. The compound for use, the method, the pharmaceutical composition or the use according to any of the preceding items, in Petition 870260058481, dated 06 / 16 / 2026, page 92 / 140 / 131, states that the peptide or compound is administered in an increasing dose or concentration over time, such as for two, three, four or more periods in which the dose or concentration of peptide or compound is increased for each period.

[00307] 71. The compound for use, the method, the pharmaceutical composition or the use according to any of the preceding items, wherein the first, second, third and fourth treatment period is between 2 days and 2 months, such as between 4 days and 1 month, such as between 6 days and 3 weeks, such as between one week and two weeks.

[00308] 72. The compound for use, the method, the pharmaceutical composition or the use according to any of the preceding items, wherein the peptide or compound is administered for two weeks at a concentration of between 2.5 and 3.5 mg / mL, such as 2.9 mg / mL, followed by administration for two weeks at a concentration of between 8 and 9 mg / mL, such as 8.6 mg / mL.

[00309] 73. The compound for use, the method, the pharmaceutical composition or the use according to any of the preceding items, wherein: a. between 0.025 and 0.075 mL / cm2, such as 0.05 mL / cm2, of the peptide or compound is administered to the individual affected by the skin condition or skin disorder during the first treatment period, where the concentration of said peptide or compound is between 2.5 and 3.5 mg / mL, such as 2.9 mg / mL; b. between 0.05 and 0.15 mL / cm2, such as 0.1 mL / cm2, of the peptide or compound is administered to the individual affected by the skin condition during the second treatment period, in which the concentration of said peptide or compound is between 2.5 and 3.5 mg / mL, such as 2.9 mg / mL; c. between 0.025 and 0.075 mL / cm2, such as 0.05 mL / cm2, of Petition 870260058481, dated 06 / 16 / 2026, page 93 / 140 / 131 peptide or compound is administered to the individual affected by the skin or fur condition during the third treatment period, in which the concentration of said peptide or compound is between 8 and 9 mg / mL, such as 8.6 mg / mL; and d. between 0.05 and 0.15 mL / cm2, such as 0.1 mL / cm2, of the peptide or compound is administered to the individual affected by the skin or fur condition during the fourth treatment period, in which the concentration of said peptide or compound is between 8 and 9 mg / mL, such as 8.6 mg / mL; optionally, each treatment period is approximately one week, or optionally, the compound or peptide is administered three times a week, such as every second or third day.

[00310] 74. The compound for use, the method, the pharmaceutical composition or the use according to any of the preceding items, wherein: a. between 0.1 and 0.2 mg / cm2, such as 0.14 mg / cm2, of the peptide or compound is administered to the individual affected by the skin condition or skin disorder during the initial treatment period; b. between 0.25 and 0.35 mg / cm2, such as 0.29 mg / cm2, of the peptide or compound is administered to the individual affected by the skin condition during the second treatment period; c. between 0.4 and 0.5 mg / cm2, such as 0.43 mg / cm2, of the peptide or compound is administered to the individual affected by the skin condition or skin lesion during the third treatment period; and d. between 0.8 and 0.9 mg / cm2, such as 0.86 mg / cm2, of the peptide or compound is administered to the individual affected by the skin condition or skin lesion during the fourth treatment period; optionally in which each treatment period is approximately one week, optionally in which the compound or peptide is administered Petition 870260058481, dated 06 / 16 / 2026, pp. 94 / 140 / 131 three times a week, as well as every second or third day.

[00311] 75. The compound for use, the method, the pharmaceutical composition or the use according to any of the preceding items, wherein the concentration of the peptide or compound in said composition is between 0.05% by weight and 5% by weight, such as between 0.08% by weight and 1% by weight, such as between 0.8% by weight and 3% by weight, such as between 2.5% by weight and 9% by weight.

[00312] 76. The compound for use, the method, the pharmaceutical composition or the use according to any of the preceding items, wherein the concentration of the peptide or compound in said composition is between 0.05% by weight and 5% by weight, such as between 0.08% by weight and 1% by weight, such as between 0.08% by weight and 0.3% by weight, such as between 0.25% by weight and 0.9% by weight.

[00313] 77. The compound for use, the method, the pharmaceutical composition or the use according to any of the preceding items, wherein the concentration of the peptide or compound in said composition is 0.086% by weight, 0.29% by weight or 0.86% by weight.

[00314] 78. The compound for use, the method, the pharmaceutical composition or the use according to any of the preceding items, wherein the composition further comprises: a. EDTA, and b. an aqueous buffer, in which i. the composition has a pH of no more than 8 and / or ii. the concentration of the compound in the composition is at least 0.08% by weight.

[00315] 79. The compound for use, the method, the pharmaceutical composition or the use according to any of the preceding items, wherein the composition further comprises: Petition 870260058481, dated 06 / 16 / 2026, pp. 95 / 140 / 131 a. a polymer capable of forming a hydrogel when mixed with an aqueous solution, and b. an aqueous solution in which i. the concentration of the compound in the composition is at least 0.08% by weight and / or ii. the polymer is present in said composition at a concentration of at least 0.05% by weight. EXAMPLES Introduction

[00316] To heal wounds effectively, it is essential not only to prevent and treat infections, but also to treat the excessive and harmful inflammation, for which there is currently no commercially available treatment. Local and systemic antibiotics and topical wound treatments based on dressings with anti-infective components, such as silver, do not treat the excessive and harmful inflammation associated with wounds. Furthermore, despite the widespread use of antiseptics for various wound indications, such as EB, there is little clinical evidence demonstrating that such treatments improve wound healing or prevent infections. In addition, infection management is complicated by the decreased effectiveness of antibiotics and antimicrobial agents due to antimicrobial resistance (AMR).

[00317] Initially found in wounds, approximately 2 kDa thrombin-derived C-terminal peptides (TCPs), such as FYT21 (FYTHVFRLKKWIQKVIDQFGE) and HVF18 (HVFRLKKWIQKVIDQFGE), have been shown to exert anti-endotoxic functions in vitro and in vivo (Saravanan et al., 2018; van der Plas et al., 2016; Kalle et al., 2012). TCP-25 (GKYGFYTHVFRLKKWIQKVIDQFGE), including sequences of natural TCPs previously identified in human wounds, has demonstrated Petition 870260058481, dated 06 / 16 / 2026, page 96 / 140 / 131 to neutralize LPS in vitro and protect against Pseudomonas aeruginosa sepsis and LPS-mediated shock in experimental animal models, mainly by reducing systemic cytokine responses (Saravanan et al., 2018; Kalle et al., 2012). A hydrogel containing TCP-25 treated both infection and inflammation in murine and porcine wound infection models with excellent results (Puthia et al., 2020). Bioactive cleavage fragments of the peptide were similar to those found in human wound fluid. The mode of action is well-defined and involves interactions in the μM range with LPS, other bacterial products, and the cellular receptor CD14, allowing for negative modulation of inflammation while exerting direct antimicrobial effects. It is important to highlight that TCP-25 acts on multiple multidrug-resistant bacterial isolates in these models (Puthia et al., 2020).

[00318] The safety and tolerability of three dose levels of TCP25 were tested in experimental wounds generated by the suction blister technique. Suction blister wounds are standardized in terms of wound depth (the entire epidermal layer is ablated and the dermis is exposed), size, and closure time. Mechanical abrasion without bleeding triggers an innate immune response accompanied by increased blood flow and infiltration of the underlying dermis with inflammatory cells. Epidermal regeneration occurs from the edges and appendages (Ahlstrom et al., 2018).Interestingly, the inventors discovered that suction blister wounds can be useful as a model for studying EB, although suction blister wounds do not exhibit the genetic history of EB and do not evolve into non-healing, dysbiotic wounds, which are typically colonized and chronically infected by bacteria such as Staphylococcus aureus, a major pathogen causing wound infections (Bar et al., 2021). However, the inventors realized that suction blister wounds are similar to EB. Petition 870260058481, dated 06 / 16 / 2026, p. 97 / 140 / 131 in other aspects, for example, due to not having the epidermal component and presenting the same wound depth as the EB types. Therefore, the combination of TCP-25 application in suction blister wounds captures relevant actions of TCP-25 in wounds relevant for BE indications. Example 1

[00319] The effects of a hydrogel containing the host defense immunomodulator peptide TCP-25 (GKYGFYTHVFRLKKWIQKVIDQFGE) on bacteria and wound inflammation were studied in healthy subjects included in the trial after informed consent. Blistering wounds were formed on the medial aspect of the thigh, two blisters on each leg, defined as day 1. Each wound was treated with 0.15 mL of a sterile gel containing TCP-25 (0.86, 2.9 or 8.6 mg / mL, depending on the dose group) or placebo (0 mg / mL TCP-25), applied topically on day 1. The gel composition is shown below.

[00320] Low concentration: 0.86 mg / mL TCP-25, 1.35% Natrosol 250 HX, 2% glycerol, in 10 mM Tris pH 7.

[00321] Average concentration: 2.9 mg / mL TCP-25, 1.2% Natrosol 250 HX, 2% glycerol, in 10 mM Tris pH 7.

[00322] High concentration: 8.6 mg / mL TCP-25, 1% Natrosol 250 HX, 2% glycerol, in 10 mM Tris pH 7.

[00323] After gel application, each wound was treated with a 2 x 2 cm Mepilex transfer dressing (Molnlycke health care) as the primary dressing and covered with a secondary dressing (Tegaderm, 3M™). A secondary protective layer was applied, consisting of overlapping gauze compresses covered with a Tegaderm secondary dressing. Assessments were performed on days 2, 3, 5, and 8, when a new gel was applied. Previous dressings were collected. Wound photographs were taken, and samples of wound material were collected with swabs and tissue paper. Petition 870260058481, dated 06 / 16 / 2026, page 98 / 140 / 131 sterile filter. A new gel was applied, followed by dressing each wound. On day 11, photos of the wound area were taken, swab and filter paper samples were collected, and the previous dressing was collected. On day 11, all wounds were healed (Figure 1). Results Quantification of bacteria

[00324] Bacteria were quantified from the wound surface and dressing. The results showed that TCP-25 gel significantly reduced the increase in microbial load during wound healing, both on the dressing and on the wound surface (Figures 2 and 3). Notably, bacterial reduction was observed at all three doses of 0.86, 2.9, and 8.6 mg / mL. Data analysis showed that TCP-25 gel was able to control bacteria, particularly on the wound surface (Figures 2 and 3).

[00325] In order to analyze the relative reduction in each leg, the level of bacteria in the controls was normalized and the bacterial level after treatment with TCP-25 was expressed relative to the control. The results showed that TCP-25 reduced the bacterial load relative to the adjacent control (Figure 4).

[00326] Analysis using a replication method (Figure 5) provides spatial data of bacteria in wounds. Figure 6 AC shows that TCP-25 gel reduced bacterial levels in the wound and perilesional areas. Bacteria on the skin adjacent to the dressing remained unchanged. Identification of bacterial types

[00327] Bacteria were identified on the wound surface and dressing on days 3 and 8. The results showed the development of a microbiome with generally 1 to 3 types present. Commensal bacteria predominated, and a correspondence was observed between the types found on the wound surface and dressing. It is important to note that treatment with TCP-25 did not alter the overall composition of the commensal microbiome (Figure Petition 870260058481, dated 06 / 16 / 2026, pp. 99 / 140 / 131 7).

[00328] S. aureus can colonize and infect epidermal wounds. The bacterium was detected in several wounds. It is important to note that treatment with TCP-25 was able to reduce bacterial levels, particularly on the wound surface, thus demonstrating that the treatment controlled excessive levels of S. aureus (Figure 8). A similar observation was made for wounds colonized by the Bacillus species (Figure 8). Analysis of wound exudate

[00329] Wound exudation was determined by analyzing the total protein content in the dressing fluid. The results showed that commensal bacteria did not significantly influence exudation during the study. Therefore, no correlation was detected between bacterial levels and protein leakage on different days (Figure 9). Treatment with TCP-25 reduced exudation, particularly on days 5 and 8, in a dose-dependent manner (Figure 10). The difference in exudation levels was calculated relative to the adjacent control wound. 2.6 and 8.6 mg / mL of TCP25 reduced protein content, and notably, 8.6 mg / mL of TCP-25 showed significant reductions, with only 20-30% less exudation compared to the control (Figure 11). Figure 12 illustrates the reduction in protein leakage in the dressing by TCP-25. Analysis of neutrophil proteins in wounds

[00330] Next, the levels of several neutrophil-derived proteins were measured by ELISA in fluid samples from the dressing. Overall, MPO levels were lower at most time points for all 3 doses of TCP-25 compared to placebo, with the greatest reductions occurring on Day 5 (Figure 19A, top panels). Similarly, all 3 doses of TCP-25 reduced NE, primarily on Days 5 and 8, compared to the control (Figure 19A, middle panels). Finally, Petition 870260058481, dated 06 / 16 / 2026, pp. 100 / 140 / 131, TCP-25 reduced HBP levels at all times and at all doses, extinguishing HBP expression to near-zero levels (Figure 19A, lower panels).

[00331] Notably, although not a neutrophil protein per se in the early inflammatory phase of wound healing, the content of chemotaxis-inducing IL-8 in wounds decreased with all 3 doses of TCP-25 on Days 5 and 8 (Figure 19B).

[00332] HBP is an important factor known to cause vascular leakage and is also consistently elevated in chronic non-healing wounds, distinguished by persistent inflammation and wound leakage. The significant dose-dependent reduction in HBP levels could therefore underlie the observed reduction in wound exudation in this study.

[00333] Significantly reduced leakage was also observed in patients with venous leg ulcers. When treated with a TCP-25 formulation, as described in Example 1, a significant reduction in leakage from the treated venous leg ulcers was observed. Healing analysis

[00334] In a separate experiment, conducted as described above, wound healing and pigmentation were analyzed. The results showed that TCP-25 reduced pigmentation on day 11 (Figure 13). To better study the effects of TCP-25 on wound healing, a mouse model was used. A suture was contaminated with S. aureus, implanted subcutaneously, and then subjected to either a tampon or TCP-25. TCP-25 significantly reduced wound healing (Figure 14). Conclusions

[00335] The results showed that TCP-25 reduced excess bacteria even at the lowest dose, while maintaining the spectrum of microbes (i.e., the skin's natural microbiome). It also controlled excessive levels of S. Petition 870260058481, dated 06 / 16 / 2026, p. 101 / 140 / 131 aureus. Furthermore, we demonstrated that TCP-25 reduces wound leakage in a dose-dependent manner. However, TCP-25 reduced bacteria to a similar extent at all three doses. Therefore, leakage reduction was not observed at the lowest dose that showed bacterial reduction, demonstrating that the effect of TCP-25 on exudation and its effect on bacterial reduction are two distinct aspects of its action.

[00336] Patients with BE suffer from microbiome dysbiosis and wound leakage, and more importantly, wound leakage and associated skin maceration can lead to increased blister size and risk of infection. It can be concluded that TCP-25 can be used to regulate skin microbiome dysbiosis and wound leakage to improve wound healing and decrease blister / wound size and infection.

[00337] The results also showed that TCP-25 can reduce pigmentation and scar formation. Methods Formation of blistering wounds due to suction.

[00338] Blistering wounds were formed on the medial aspect of the thigh, two blisters on each leg, 6 cm apart. Before wounding, the hair at the wound sites was shaved. Each wound site was cleaned with gauze soaked in ethanol. The exact wound locations were marked with a skin marker.

[00339] The bubbles were formed using the Model NP-4 suction device (Electronic Diversities, Finksburg, MD) (11), operating in the negative pressure range of 8 to 16 inches of mercury (20 to 40 cmHg), with heating for optimal bubble formation. The bubble wound diameter was 10 mm. The device was kept running until all bubbles were formed, which takes approximately 60 to 70 minutes. The blister roof was excised with sterile forceps and scissors. Interventions Petition 870260058481, dated 06 / 16 / 2026, pp. 102 / 140 / 131

[00340] Treatment: Each wound received 0.15 mL of a sterile gel containing TCP-25 (0.86, 2.9 or 8.6 mg / mL, according to the dose group) or placebo (0 mg / mL of TCP-25), applied topically.

[00341] Dressing: After gel application, each wound was treated with a 2 x 2 cm Mepilex transfer dressing (Molnlycke health care) as a primary dressing and covered with a secondary dressing (Tegaderm, 3M™). A secondary protective layer was applied, consisting of overlapping gauze swabs covered with a Tegaderm secondary dressing. Allocation

[00342] Each individual received four suction blister wounds, two on each thigh. The wounds were identified as R1 (right thigh, distal), R2 (right thigh, proximal), L1 (left thigh, distal), and L2 (left thigh, proximal). (Figure 1)

[00343] A computer-generated randomization list was created using SAS Proc Plan, SAS Version 9.4. The randomization list contained the individual's number, wound location, thigh (left / right), and treatment, and was kept by the randomizer in a sealed envelope until the database was closed. On Day 1, individuals in each dose group (n=8) were randomized to treatment allocation for each wound. Two wounds per patient received TCP-25 and the other two received placebo. The proximal wound (R1 or L1) of one thigh and the distal wound of the other thigh (L2 or R2) received the same treatment, according to the assigned treatment allocation. Two syringes per patient were prepared by a non-blinded nurse in a nearby medical room, one with TCP-25 and the other with placebo, labeled with the patient's randomization number and the identification of two wounds (R1 + L2 or R2 + L1) according to the assigned treatment allocation. Blindness Petition 870260058481, dated 06 / 16 / 2026, pages 103 / 140 / 131

[00344] This was a double-blind study and the allocation of treatments was not described until the clean file was declared and the database locked. Bacterial quantification Swab Procedure

[00345] The swab was pre-moistened with phosphate-buffered saline. Using a twisting motion, the swab was rotated 10 times, covering the entire wound with light pressure, and then placed in a microtube containing 0.5 mL of sterile phosphate-buffered saline (PBS) and kept on ice. The tube was vortexed to remove bacteria from the swab. The amount of bacteria was quantified as described below. Dressing removal procedure

[00346] The Mepilex dressing was removed from the wound and then placed in an empty conical tube and kept on ice. Each tube containing the dressing was dried and weighed, and the dressing was then removed and placed in a 5 mL syringe secured with a stopper. Cold sterile Tris buffer (2 mL) was added to the syringe and the syringe was vortexed for 5 minutes. The fluid was then extracted from the dressing by pressing the plunger down to squeeze the fluid into the original dressing collection tube. The extracted fluid was kept on ice. The amount of bacteria, protein content, neutrophil proteins, and cytokines were quantified as described below. Quantitative bacterial counts

[00347] The swab and dressing fluid, collected as described above, were diluted with sterile PBS to form seven serial 10-fold dilutions (10x, 100x, 1,000x, 10,000x, 100,000x, 1,000,000x, 10,000,000x). From the undiluted sample and each of the dilutions, six 10 μL drops were seeded onto an agar plate. The Petition 870260058481, dated 06 / 16 / 2026, page 104 / 140 / 131 plates were incubated at 37°C in 5% CO2 overnight. The following morning, the number of colonies was counted and recorded. replication procedure

[00348] A sterile (autoclaved) 12.5 cm filter paper (Whatman) was pre-moistened with 3 mL of sterile PBS before being transferred to the wound. The filter paper was positioned to cover both wounds on the leg and, using the lid of the Petri dish, was gently pressed onto the wounds for 1 minute with a rocking motion to ensure uniform contact of the wounds with the filter paper. The filter paper was then placed face down on a 15 cm agar plate and incubated at room temperature for at least 1 hour. The filter paper was then discarded from the plate and the plate was incubated at 37°C in 5% CO2 overnight. Image formation and image processing

[00349] The following day, the filter paper was imaged using the ChemiDoc MP Imaging System (Bio-Rad), using the Stain Free Blot imaging method and an exposure time of 0.386 s, producing grayscale images of all replicas. The images were then trimmed to remove excess background. Using ImageJ Fiji, an individual threshold value for each grayscale replica image was chosen to acquire a binary image. The threshold was manually selected so that the bright edges of each replica agar plate had comparable apparent intensity and that nothing, except microbial colonies, would light up in the wound area. Manual scoring

[00350] Four people independently rated the number of microbial colonies in all control wounds on a 5-point scale, ranging from 0 to 4, with 0 being the lowest number of bacteria and 4 the highest. The raters assigned a separate rating to the central area. Petition 870260058481, dated 06 / 16 / 2026, pp. 105 / 140 / 131, where the wound was located, the dressing area, and the surrounding area. Identification of bacteria.

[00351] The swab and dressing fluid, extracted as described above, were seeded onto a blood agar plate and incubated at 37°C overnight. Bacterial samples were analyzed with MALDI-TOF MS on a M@ldi LR (Waters / Micromass, Milford, MA, USA) in linear mode. For MALDI-TOF MS analysis, a spectrum of 100 summed laser shots was acquired for each sample point. MassLynx 4.1 was used to control the Waters instrument. Bacterial identification experiments were performed on an ultrafleXtreme MALDI-TOF / TOF (Bruker Daltronik GmbH, Germany) in linear mode, in a mass range of 2 to 20 kDa, and were analyzed using FlexControl and MALDI Biotyper 3.1 software (Bruker Daltronik GmbH, Germany). The identification results were evaluated according to the manufacturer's instructions.Values ​​above 2 suggested probable identification at the species level; values ​​between 1.7 and 2 indicated genus identification, and values ​​of 1.7 and below were considered unreliable. Wound exudate analysis

[00352] The wound fluid was analyzed for protein content using the bicinchoninic acid (BCA) assay (Thermo Fisher), according to the manufacturer's instructions, using bovine serum albumin as the standard. Quantification of neutrophil proteins

[00353] Human neutrophil elastase (NE) and human myeloperoxidase (MPO) were measured using ELISA kits from R&D Systems (Minneapolis, MN, USA); heparin-binding protein (HBP) was determined using an ELISA kit from Aviva Systems Biology (San Diego, CA, USA). Samples were collected in duplicate, according to Petition 870260058481, dated 06 / 16 / 2026, pp. 106 / 140 / 131 with the manufacturer's instructions. ELISA signals were read at 450 nm on a microplate reader (BioRad). A standard curve was established with reference standards in GraphPad Prism 9 to calculate the concentration in each sample.

[00354] IL-8 was measured using the V-PLEX Proinflammatory Panel 1 (human) kit (Meso Scale Diagnostics, art.no: K15049D), according to the manufacturer's instructions, at a 5° dilution. Samples with IL-8 above the upper limit of detection were re-analyzed using the U-PLEX Biomarker Group 1 (human) kit (Meso Scale Diagnostics, art.no: K151TYK-2) at a higher dilution. IL-8 concentration was calculated using MSD Discovery Workbench analysis software. Samples with concentrations below the limit of detection were not quantified by the analysis software and received a value of zero for all analyses.

[00355] For all neutrophil protein and IL-8 measurements, the assessor was not blinded to the identity of the assigned intervention. Wound image

[00356] A ruler with a centimeter scale was attached to the skin near the wounds. A Canfield camera was used with the magnification scale, positioned so that both wounds on the same leg were visible. Two images were obtained of each set of wounds on each leg. Example 2 Methods Mouse model of EB

[00357] Two murine EB models will be used in this study. 1. B6. 129X1-Lamc2jeb / DcrJ, stock number 025467

[00358] This Lamc2jebé mutant murine strain is useful in BE studies and is a model for Non-Herlitz Junctional Epidermolysis Bullosa. The gene Petition 870260058481, dated 06 / 16 / 2026, pp. 107 / 140 / 131 Lamc2 encodes the gamma-2 subunit of laminin 5, which is an extracellular matrix glycoprotein found in the basement membranes of skin. These mice carry a spontaneous Lamc2 mutation that arose in background 129X1 and is a single retroviral insertion (long terminal repeat of murine leukemia virus) in intron 18. 2. C57BL / 6J-Col17a1em8Dcr / J, stock number 033908

[00359] These TALEN-derived mice carry a 10 bp deletion in exon 50 of Col17a1 (collagen, type XVII, alpha 1). Col17a1 (collagen, type XVII, alpha 1) encodes the alpha chain of collagen type XVII. Collagen XVII is a transmembrane protein involved in keratinocyte adhesion to the basement membrane. Mutations in Col17a1 are associated with human junctional epidermolysis bullosa (EBJ), a genetic condition that causes skin fragility and blistering. This TALEN-derived allele has a 10 bp deletion in exon 50. Experimental approach and treatment Group 1 (No infection)

[00360] 1. TCP-25 gel will be applied once a day to a defined area of ​​the tail and ears.

[00361] 2. The area will be covered with a secondary dressing and a final adhesive dressing will be applied.

[00362] 3. In the control animals, the gel without TCP-25 will be applied.

[00363] 4. The treatment will end on day 3, day 7 or day 14. Group 2 (addition of infection)

[00364] 1. A solution containing S. aureus or P. aeruginosa will be applied to the defined area and treatment will begin 30 minutes later.

[00365] 2. The TCP-25 gel will be applied once a day.

[00366] 3. The area will be covered with a secondary dressing and a final adhesive dressing will be applied.

[00367] 4. In the control animals, the gel without TCP-25 will be applied. Petition 870260058481, dated 06 / 16 / 2026, pp. 108 / 140 100 / 131

[00368] 5. The treatment will end on day 2, day 7 or day 14. Group 3 (recurrence)

[00369] The goal of this group is to study whether the treatment has any lasting benefit on the microbiome or histology of the skin.

[00370] 1. As in group 1, the mice will be treated for days.

[00371] 2. After 7 days without treatment, on day 14, all readings will be taken to assess effectiveness. Readings:

[00372] 1. Clinical observation (at each dressing change).

[00373] 2. Photograph (at each dressing change).

[00374] 3. Swab for UFC (Days 1, 2, 4, 7, 10, 14).

[00375] 4. Swab for microbiome analysis (Days 7 and 14).

[00376] 5. Histology (day 2, day 7 or day 14). The score will be determined.

[00377] 6. Immunohistochemistry (day 2, day 7 or day 14).

[00378] 7. IVIS image in group 2 (during dressing change).

[00379] 8. Tissue collection (at the termination) for DNA or transcriptomics. Expected results Microbiome control

[00380] As in the study with human epidermal wounds, TCP-25 achieves a significant reduction in excessive bacterial levels. In non-infected wounds, TCP-25 controls excessive colonization by pathogenic S. aureus. In S. aureus and P. aeruginosa infection models, TCP-25 is able to reduce bacterial levels and blister formation. Microbiome Identities

[00381] Analysis using MALDI TOF and also 16S DNA analysis shows that TCP-25 prevents excessive dysbiosis. Damage to the barrier Petition 870260058481, dated 06 / 16 / 2026, pp. 109 / 140 101 / 131

[00382] Because exudation is difficult to assess in the mouse model, a histological evaluation was performed. The results showed that TCP-25 normalized the skin barrier. Example 3 - Mouse model of epidermolysis bullosa

[00383] The B6.129X1-Lamcjeb / DcrJ mouse model of EB was studied based on the description in Example 2. However, further studies were conducted and modifications were made as described in detail in this example. Materials and methods Mouse model of epidermolysis bullosa

[00384] B6.129X1-Lamc2jeb / DcrJ (Strain number: 025467). This Lamc2jeb mutant murine strain is useful in studies of epidermolysis bullosa and is a model for non-Herlitz type junctional epidermolysis bullosa (Bubier et al., 2010; Sproule et al., 2014; JAX stock number 025467). In homozygous mice, skin blistering occurs at approximately 13 weeks. Mice were housed under standard conditions in a disposable VCI cage system (Inovive). Mouse model of epidermolysis bullosa - without induction of wounds or infection.

[00385] A mouse model (Lamc2jeb mice) of human EB (15-16 weeks old) was used. The procedures were performed under isoflurane anesthesia (4% induction, 2% maintenance). Using a trimmer, the fur on the mouse's back was trimmed and the skin was cleaned with sterile gauze. The left side of the mice was treated with 200 g / L of TCP-25 gel (8.6 mg / mL) and the right side was treated with control gel. A 1.5 x 1.8 cm polyurethane primary dressing (Mepilex Transfer) was applied to each side of the skin, followed by a secondary dressing (Tegaderm). Finally, an adhesive dressing was applied. Petition 870260058481, dated 06 / 16 / 2026, pp. 110 / 140 102 / 131 (Vet tape) was applied to secure the dressings underneath. Mice were treated on days 0, 2, 5, 8, and 11. Swab and dressing samples were collected at each dressing change and analyzed for CFU and cytokines. For CFU analysis, 500 pL of PBS was added to the swab or dressing samples, and serial dilutions were seeded onto THA (Todd-Hewitt Agar) plates and incubated overnight at 37°C. Wound fluid extracts from the dressings were analyzed for cytokines using the V-PLEX Cytokine Panel 1 Mouse Kit (MSD), following the manufacturer's protocol. One day after the last treatment, the experiment was terminated, and skin biopsies were collected. The biopsies were fixed overnight in 10% neutral buffered formalin. Using standard procedures, the fixed tissues were embedded in paraffin, sectioned, and stained for H&E. Mouse model of epidermolysis bullosa - by wound puncture

[00386] A mouse model (Lamc2jeb mice) of human EB (15-16 weeks old) was used. The procedures were performed under isoflurane anesthesia (4% induction, 2% maintenance). Using a trimmer, the fur on the mouse's back was trimmed and the skin was cleaned with sterile gauze. Using a 4 mm biopsy puncture, two full-thickness wounds were made on the left and right sides (4 mm in diameter). The left wound was treated with 200 pL of TCP-25 gel (2.9 or 8.6 mg / mL) and the right side was treated with control gel. A 1.5 x 1.8 cm polyurethane primary dressing (Mepilex Transfer) was applied to each wound, followed by a secondary dressing (Tegaderm). Finally, an adhesive dressing (Vet tape) was applied to secure the dressings underneath. The mice were treated on days 0, 1, 2, 4, 6, and 8.Swab and dressing samples were collected at each dressing change and analyzed for CFU and cytokines. For CFU analysis, 500 pL of PBS were added to the swab or dressing samples and serial dilutions were plated on. Petition 870260058481, dated 06 / 16 / 2026, pp. 111 / 140 103 / 131 THA (Todd-Hewitt Agar) plates were incubated overnight at 37°C. Wound fluid extracts from the dressings were analyzed for cytokines using the V-PLEX Cytokine Panel 1 Mouse Kit (MSD) following the manufacturer's protocol. One day after the last treatment, the experiment was terminated and skin biopsies were collected. The biopsies were fixed overnight in 10% neutral buffered formalin. Using standard procedures, the fixed tissues were paraffin-embedded, sectioned, and stained for H&E. Mouse model of epidermolysis bullosa - puncture wound infected by Staphylococcus aureus

[00387] A mouse model (Lamc2jeb mice) of human EB (15-16 weeks old) was used. The procedures were performed under isoflurane anesthesia (4% induction, 2% maintenance). Using a trimmer, the fur on the mouse's back was trimmed and the skin was cleaned with sterile gauze. Using a 4 mm punch biopsy, two full-thickness wounds were made on the left and right sides (4 mm in diameter). The wounds were infected with bioluminescent S. aureus (SAP229). The left wound was treated with 200 pL of TCP-25 gel (8.6 mg / mL) and the right wound was treated with control gel. A 1.5 x 1.8 cm polyurethane primary dressing (Mepilex Transfer) was applied to each wound, followed by a secondary dressing (Tegaderm). Finally, an adhesive dressing (Vet adhesive tape) was applied to secure the underlying dressings. The mice were treated on days 0, 1, 2, 3, and 6.Swab and dressing samples were collected at each dressing change and analyzed for CFU and cytokines. On the indicated days, during dressing changes, in vivo bioimaging of the infection was performed using the IVIS imaging system in luminescent imaging mode. Bioluminescent signals from mice were acquired and quantified using Living Image 4.0 software (PerkinElmer). For CFU analysis, 500 pL of PBS was used. Petition 870260058481, dated 06 / 16 / 2026, pp. 112 / 140 104 / 131 added to swab or dressing samples and serial dilutions were seeded onto THA (Todd-Hewitt Agar) plates and incubated overnight at 37°C. Wound fluid extracts from the dressings were analyzed for cytokines using the V-PLEX Cytokine Panel 1 Mouse kit (MSD) following the manufacturer's protocol. One day after the last treatment, the experiment was terminated and skin biopsies were collected. Biopsies were fixed overnight in 10% neutral buffered formalin. Using standard procedures, the fixed tissues were paraffin-embedded, sectioned, and stained for H&E. Preparation of TCP-25 gel and control gel

[00388] Control gel: Natrosol™ 250HX (Ashland Inc., UK) (1.6% w / v) was dissolved in 1.21 g / L of Tris-HCl at pH 7 containing 25 g / L of glycerol and then sterilized in an autoclave (Phase A).

[00389] 2.9 mg / mL Gel: Natrosol™ 250HX (Ashland Inc., UK) (1.6% w / v) was dissolved in 1.21 g / L of Tris-HCl at pH 7 containing 25 g / L of glycerol and then sterilized in an autoclave (Phase A). TCP-25 was dissolved in water containing 25 g / L of glycerol to a final concentration of 20.0 mg / mL. The TCP-25 solution was filtered with a 0.2 µm filter (Pall KA02ECVP8G Mini Kleenpak Filter Capsule, Life Sciences, NY, USA) and then corrected for Tris content and pH. The final composition of the TCP-25 solution (designated Phase B) contained 11.4 g / L of TCP-25, 25 g / L of glycerol in 1.21 g / L of Tris-HCl at pH 7. Phase B was mixed with Phase A in a 1:3 ratio. The final gel contained 2.9 mg / mL of TCP-25, 1.37% of Natrosol™ 250HX, 1.21 g / L of Tris-HCl, and 25 g / L of glycerol at pH 7.

[00390] 8.6 mg / mL Gel: Natrosol™ 250HX (Ashland Inc., UK) (1.33% w / v) was dissolved in 1.21 g / L of Tris-HCl at pH 7 containing 25 g / L of glycerol and then sterilized in an autoclave (Phase A). TCP25 was dissolved in water containing 25 g / L of glycerol to a final concentration of 60.0 mg / mL. The TCP-25 solution was filtered with a 0.2 µm (Pall) filter. Petition 870260058481, dated 06 / 16 / 2026, pp. 113 / 140 105 / 131 KA02ECVP8G Mini Kleenpak Filter Capsule, Life Sciences, NY, United States) and then corrected for Tris content and pH. The final composition of the TCP-25 solution (designated Phase B) contained 34.4 g / L of TCP-25, 25 g / L of glycerol in 1.21 g / L of Tris-HCl at pH 7. Phase B was mixed with Phase A in a 1:3 ratio. The final gel contained 8.6 mg / mL of TCP-25, 1.37% Natrosol™ 250HX, 1.21 g / L of Tris-HCl and 25 g / L of glycerol at pH 7. Primary and secondary dressing

[00391] A 1.5 x 1.8 cm polyurethane primary dressing (Mepilex Transfer) was applied to each wound, followed by a secondary dressing (Tegaderm). Finally, an adhesive dressing (Vet adhesive tape) was applied to secure the underlying dressings. Analysis of CFU and cytokines in swabs and dressings.

[00392] For CFU analysis, 500 pL of PBS were added to swab or dressing samples and serial dilutions were seeded onto THA (Todd-Hewitt Agar) plates and incubated overnight at 37°C. Wound fluid extracts from dressings were analyzed for cytokines using the V-PLEX Cytokine Panel 1 Mouse Kit (MSD), following the manufacturer's protocol. Skin biopsy

[00393] The wound area, including the surrounding skin, was harvested with scissors. The harvested skin was placed on absorbent paper to prevent rippling, which was fixed overnight in 10% neutral buffered formalin. Hematoxylin and eosin (H&E) staining and microscopy

[00394] After serial dehydration, the tissue was embedded in paraffin blocks, sectioned at 5 µm, and stained with hematoxylin and eosin (H&E). Samples were obtained using bright-field microscopy (Axioplan2, Zeiss, Germany) at 100x and 200x magnifications. Histology score Petition 870260058481, dated 06 / 16 / 2026, pp. 114 / 140 106 / 131

[00395] For mouse tissue, four random microscopic sections (100x) of each H&E-stained cutaneous tissue section were scored. The histological score was based on epithelialization, inflammatory cells, abscesses, and tissue architecture. The score was based on a scale of 0 to 5. For each wound tissue section, 4 to 5 areas were examined under 100x magnification. Needle biopsy

[00396] The procedures were performed under isoflurane anesthesia (4% induction, 2% maintenance). Using a trimmer, the mouse's back hair was trimmed and the skin was cleaned with sterile gauze. Using a 4 mm punch biopsy, two full-thickness wounds were made on the left and right sides (4 mm in diameter). In vivo bioimaging

[00397] The procedures were performed under isoflurane anesthesia (4% induction, 2% maintenance). On the indicated days, during dressing changes, in vivo bioimaging of the infection was performed using the IVIS imaging system in luminescence imaging mode. Bioluminescent signals from the mice were acquired and quantified using Living Image 4.0 software (PerkinElmer). Wound healing rate

[00398] The wound healing rate (WHR) was calculated using the equation: [(Ai - Af) / Ai], where Ai represents the initial wound area and Af represents the final area / measurement (Reference: Masson-Meyers DS, Andrade TAM, Caetano GF, Guimarães FR, Leite MN, Leite SN, Frade MAC. Experimental models and methods for evaluating cutaneous wound healing. Int J Exp Pathol. 2020 Feb;101(1-2):21-37. The wound area was measured using ImageJ software. Results Petition 870260058481, dated 06 / 16 / 2026, pp. 115 / 140 107 / 131 Mouse model of epidermolysis bullosa - without lesion or infection induced

[00399] The mouse model (Lamc2jeb mice) of human EB, as described in the previous materials and methods, was used for the experiment. Briefly, the fur on the mouse's back was trimmed and the skin was cleaned with sterile gauze. The left side of the mice was treated with TCP-25 gel (8.6 mg / mL) and the right side was treated with control gel. Swab and dressing samples were collected at each dressing change. After ten days of treatment, skin biopsies were collected.

[00400] A reduction in CFUs was observed in swab and dressing samples from mice treated with TCP-25 gel compared to mice treated with the control gel (Figure 15A and Figure 15B).

[00401] As can be seen in the figure, no CFUs were detected in swab and dressing samples on days 2 and 5 of mice treated with TCP-25 gel.

[00402] Representative photographs of the epidermis and dermis of mice treated with TCP-25 gel and treated with control gel, stained with H&E, revealed immature epidermis and dermis with deficient architecture in the area treated with control gel, while the skin treated with TCP-25 gel presented comparatively mature epidermis with improved dermal architecture (Figure 15C). Furthermore, an improved histological skin score was observed in the skin of mice treated with TCP-25 gel compared to control mice (Figure 15D). Mouse model of epidermolysis bullosa - by wound puncture

[00403] The mouse model (Lamc2jeb mice) of human EB, as described in the previous materials and methods, was used for the experiment. Briefly, the hairs on the mouse's back Petition 870260058481, dated 06 / 16 / 2026, pp. 116 / 140 108 / 131 mice were trimmed and the skin was cleaned with sterile gauze. Under anesthesia, two full-thickness puncture biopsy wounds were made on the left and right sides. The left wound of the mice was treated with TCP-25 gel (2.9 or 8.6 mg / mL) and the right wound was treated with control gel. After 7 days of treatment, biopsies of the wound were collected. Swab and dressing samples were collected at each dressing change.

[00404] A reduction in CFUs was observed in swab and dressing samples from mice treated with TCP-25 gel compared to mice treated with the control gel (Figure 16A). In addition, a reduction in pro-inflammatory cytokines in the wound fluid was observed in mice treated with TCP-25 gel compared to mice treated with the control gel (Figure 16B).

[00405] Representative photographs of the epidermis and dermis of mice treated with TCP-25 gel and treated with control gel, stained with H&E, revealed immature epidermis and dermis with deficient architecture in the area treated with control gel, while the skin treated with TCP-25 gel presented comparatively mature epidermis with improved dermal architecture (Figure 16C). Furthermore, an improvement in the histological wound score was observed in mice treated with TCP-25 gel compared to control mice (Figure 16D). Mouse model of epidermolysis bullosa - puncture wound infected by Staphylococcus aureus

[00406] The mouse model (Lamc2jeb mice) of human EB, as described in the previous materials and methods, was used for the experiment. Briefly, the fur on the mouse's back was trimmed and the skin was cleaned with sterile gauze. Under anesthesia, two full-thickness punch biopsies were performed on the left and right sides. The wounds were infected with bioluminescent S. aureus (SAP229). The left wound of the mice was treated with TCP-25 gel (8.6 mg / mL). Petition 870260058481, dated 06 / 16 / 2026, pp. 117 / 140 109 / 131 and the right wound was treated with control gel. In vivo bioimaging of the infection was performed using the IVIS imaging system. After 5 days of treatment, wound biopsies were collected. Swab and dressing samples were collected at each dressing change.

[00407] A reduction in CFUs was observed in swab and dressing samples from mice treated with TCP-25 gel compared to mice treated with the control gel (Figure 17A). Furthermore, a reduction in bacterial bioluminescence was observed after treatment with TCP-25 gel compared to treatment with the control gel (Figure 17B). The wound healing rate was significantly improved in mice treated with TCP-25 gel compared to mice treated with the control gel (Figure 17C). In other words, treatment with TCP-25 gel resulted in better wound healing. This indicates that treatment with TCP-25 reduces the wound area over time. Example 4 - Clinical study protocol Table 1 Summary EudraCT Number: 2021-004728-14 Sponsor Protocol Code Number: TCP25-001 National Competent Authority: Sweden - MPA Clinical Trial Type: EEA CTA Trial Status: Ongoing Table 2 Index A. PROTOCOL INFORMATION B. SPONSOR INFORMATION C. APPLICANT IDENTIFICATION D. IDENTIFICATION OF IMPORTS D.8 INFORMATION ABOUT THE PLACEBO E. GENERAL INFORMATION ABOUT THE STUDY F. STUDY SUBJECT POPULATION G. NETWORKS OF RESEARCHERS TO BE INVOLVED IN THE STUDY Petition 870260058481, dated 06 / 16 / 2026, pp. 118 / 140 110 / 131 N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE OF THE COUNTRY IN QUESTION P. END OF TEST Table 3 A. Protocol Information A.1 Member State Involved Sweden - MPA A.2 EudraCT Number 2021-004728-14 A.3 Full Trial Title A three-part Phase I study to evaluate the safety, tolerability and pharmacokinetics (PC) of topical doses of TCP-25 in healthy male and female volunteers with epidermal suction blister wounds and in patients with non-healing leg ulcers and patients with dystrophic epidermolysis bullosa (EB) A.3.1 Trial title for laypersons, in easily understandable language, i.e., non-technical language. A three-part Phase I study to evaluate the safety, tolerability, and pharmacokinetics (PK) of topical doses of TCP-25 in healthy male and female volunteers with epidermal suction blister wounds and in patients with non-healing leg ulcers and patients with Dystrophic Epidermolysis Bullosa (DEM) A.4.1 Sponsor protocol code TCP25-001 A.7 Trial is part of a Pediatric Research Plan No. A.8 EMA Decision Number of the Pediatric Research Plan. Table 4 B. Sponsor Information B. Sponsor: 1 B.1.1 Sponsor Name: Xinnate AB B.1.3.4 Country: Sweden B.3.1 and B.3.2 Sponsor Position: Commercial B.4 Source(s) of Monetary or Material Support for the Clinical Trial: B.4.1 Name of the organization providing support: Xinnate AB B.4.2 Country: Sweden B.5 Contact point designated by the sponsor for obtaining additional information about the trial Petition 870260058481, dated 06 / 16 / 2026, pp. 119 / 140 111 / 131 B.5.1 Organization Name: CTC Clinical Trial Consultants AB B.5.2 CRM Contact Point Functional Name B.5.3 Address: B.5.3.1 Dag Hammarskjoldsvâg Street 10 B B.5.3.2 City: Uppsala B.5.3.3 Postcode: 75237 B.5.3.4 Country: Sweden B.5.6 Email: caroline.hammarstrom@ctc-ab.se Table 5 D. Identification IMP D.IMP: 1 D.1.2 and D.1.3 IMP Test Role D.2 Position of the IMP to be used in the clinical trial D.2.1 The IMP to be used in the trial does not have marketing authorization. No D.2.5 The IMP has not been designated in this indication as an orphan drug in the Community. D.2.5.1 Orphan drug designation number D.3 Description of IMP D.3.1 Product name TCP-25 D.3.2 Product code TCP-25 D.3.4 Pharmaceutical form Transdermal gel D.3.4.1 Specific pediatric formulation No D.3.7 Routes of administration for this IMP Topical D.3.8 to D.3.10 IMP Identification Details (Active Substances) D.3.8 INN - Proposed INN TCP-25 D.3.9.2 Current sponsor code TCP-25 D.3.9.3 Other descriptive name H-Gly-Lys-Tyr-Gly-Phe-TyrThr-His-Val-Phe-Arg-LeuLys-Lys-Trp-Ile-Gln-Lys-ValIle-Asp-Gln-Phe-Gly-Glu-OH D.3.9.4 Substance Code EV SUB245389 D.3.10 Strength D.3.10.1 Concentration Unit mg / mL milligram(s) / milliliter D.3.10.2 Concentration Type Range D.3.10.3 Concentration Number 0.86 to 8.6. Petition 870260058481, dated 06 / 16 / 2026, pp. 120 / 140 112 / 131 D.3.11 The IMP contains a: D.3.11.1 Active substance of chemical origin Yes D.3.11.2 Active substance of biological / biotechnological origin (other than an Advanced Therapy IMP (ATIMP)) No The IMP is a: D.3.11.3 Advanced Therapy IMP (ATIMP) No D.3.11.3.1 Somatic cell therapy drug No D.3.11.3.2 Gene therapy medical device No D.3.11.3.3 Tissue engineered product No D.3.11.3.4 Combination ATIMP (i.e., involving a medical device) No D.3.11.3.5 The Committee on Advanced Therapies (CAT) has issued a classification for this product No D.3.11.4 Combination product that includes a device but does not involve an Advanced Therapy No D.3.11.5 Radiopharmaceutical drug No D.3.11.6 Immunological drug (such as vaccine, allergen, immune serum) No D.3.11.7 Plasma-derived drug No D.3.11.8 Extracted drug No D.3.11.9 Recombinant drug No D.3.11.10 Drug containing genetically modified organisms No D.3.11.11 Herbal medicine No D.3.11.12 Homeopathic medicine No D.3.11.13 Other type of medicine No. Table 6 D.8 Placebo Information D.8 Placebo: 1 D.8.1 Was a placebo used in this study? Yes D.8.3 Pharmaceutical form of the placebo Transdermal gel D.8.4 Route of administration of the placebo Topical Table 7 E. General Information in the Trial E. 1 Medical condition or disease under investigation E. 1.1 Medical condition(s) being treated The TCP-25 gel acts on both bacteria and inflammation, aspects common to many wounds, and is being developed for a range of wound healing indications, including prevention and treatment. Petition 870260058481, dated 06 / 16 / 2026, pp. 121 / 140 113 / 131 Infection and inflammation in epidermolysis bullosa wounds and other acute or non-healing wounds. E.1.1.1 Medical condition in easily understandable language. Treatment should be administered to patients with Epidermolysis Bullosa to promote wound healing. E.1.1.2 Therapeutic Area Diseases [C] - Bacterial and Mycotic Infections [C01] MedDRA Classification E.1.2 Medical condition or disease under investigation E.1.2 Version 20.0 E.1.2 Level PT E.1.2 Classification code 10014989 E.1.2 Term Epidermolysis bullosa E.1.2 System Organ Class 10010331 - Congenital, familial and genetic disorders E.1.3 Condition being studied is a rare disease Yes E.2 Trial objective E.2.1 Primary objective of the trial Part 1: The primary objective is to evaluate the safety and tolerability of three dose levels of TCP-25 gel (0.86 mg / mL, 2.9 mg / mL and 8.6 mg / mL) applied topically to suction epidermal blister wounds.Part 2: The primary objective is to evaluate the safety and tolerability of two doses of TCP-25 gel (2.9 mg / mL and 8.6 mg / mL) after topical application to non-healing leg ulcers. Part 3: The primary objective is to evaluate the safety and tolerability of up to four dose levels of TCP-25 applied topically with two concentrations of TCP-25 gel (2.9 mg / mL and 8.6 mg / mL, respectively) in patients with EBD. E.2.2 Secondary objectives of the trial Part 1: The secondary objective is to evaluate systemic exposure to TCP-25 after topical application to wounds with epidermal suction blisters. Part 2: The secondary objective is to evaluate systemic exposure to TCP-25 after topical application to non-healing leg ulcers. Part 3: The secondary objective is to evaluate the systemic exposure of TCP-25 when applied topically at up to four dose levels, using two concentrations of TCP-25 gel (2.9 mg / mL and 8.6 mg / mL) topically in patients with DEB. Petition 870260058481, dated 06 / 16 / 2026, pp. 122 / 140 114 / 131 E.2.3 Trial substudy contains a No E.3 Main inclusion criteria Part 1 1. Willingness and ability to provide written informed consent to participate in the study 2. Healthy male or female individual aged between 18 and 60 years (inclusive) at the time of signing the informed consent. 3. Body Mass Index (BMI) > 18.0 and < 30.0 kg / m2 4. Healthy and intact skin at the site where suction blisters will be induced 5. Women of childbearing potential (WOCBP) must present a documented negative pregnancy test at the screening visit, within 4 weeks before suction blister formation and the start of study treatment. WOCBP women must abstain from at least 4 weeks before the dose until 4 weeks after the last dose. Women must refrain from donating eggs from the date of administration until 3 months after IMP administration.The male partner must agree to use a condom during the same period if he has not undergone a vasectomy. Male individuals must be willing to use a condom, undergo a vasectomy, or practice sexual abstinence to avoid pregnancy and exposure of their partner to medication, and refrain from donating sperm from the date of the last dose until 3 months after the last dose with the IMP. Their partner with the potential to become pregnant must use contraceptive methods with a failure rate < 1% to avoid pregnancy. 6. Clinically relevant medical history, physical findings, vital signs, ECG, and laboratory values ​​at the time of screening, as assessed by the Researcher. Part 2: 1. Willingness and ability to give written informed consent to participate in the study. 2. Male patient, or female patient without the potential to become pregnant, > 40 years of age at the time of signing the informed consent. 3.Male subjects must be willing to use condoms, undergo vasectomy, or practice sexual abstinence to prevent pregnancy and exposure of their partner to medication, and refrain from donating sperm from the date of their last dose until 3 months after their last dose with the IMP. Their partner with the potential to become pregnant must use contraceptive methods with a failure rate < 1% to prevent pregnancy. 4. Clinically relevant medical history, vital signs, ECG, and laboratory values ​​at the time of screening, as assessed by the Investigator. 5. Patients diagnosed with venous insufficiency by relevant physiological examinations, including Doppler or venous plethysmography. Petition 870260058481, dated 06 / 16 / 2026, pp. 123 / 140 115 / 131 or diagnosed by relevant clinical assessments. 6. Systolic index > 0.6 (Data from medical records from the last 2 years, or the assessment must be repeated at the screening visit) 7. Ulcer duration > 6 weeks 8. Total area of ​​the target ulcer applicable to treatment: > 40 and < 120 cm2 (as measured with the Silhouette imaging equipment at the screening visit). (The target ulcer area cannot consist of > 2 separate ulcers) 9. Ability to tolerate compressive dressings 10. Willingness to participate in study site visits Part 3 1. Willingness and ability to provide written informed consent to participate in the study. For young people aged 15 to 17 years: Separate consent is required from both (if applicable) of the patient's parents / legal guardians. 2. Male or female patient, not of childbearing potential, with a documented diagnosis of hereditary BDD, > 15 years of age at the time of signing the informed consent. 3.Male subjects must be willing to use condoms, undergo vasectomy, or practice sexual abstinence to prevent pregnancy and exposure of their partner to drugs, and refrain from donating sperm from the date of their last dose until 3 months after their last dose with the IMP. Their partner with the potential to become pregnant must use contraceptive methods with a failure rate < 1% to prevent pregnancy. 4. Clinically relevant medical history at the time of screening, as assessed by the investigator. 5. Presence of two 50 cm2 target areas. The primary wound area should not be located in anatomical locations with a high probability of accidental trauma (e.g., knee, elbow). The secondary wound area may be located in anatomical locations with a high probability of accidental trauma or be in the older age range. Both wound areas must meet all of the following characteristics: a.Including open wound with a surface area < 30 cm2 (measured with Silhouette imaging equipment at the screening visit). b. At Visit 2 (first IMP treatment), each target wound should not show a surface area reduction > 30% compared to the screening visit. c. Wound age > 3 weeks to < 9 months at the screening visit. 6. Presence of a reference wound area of ​​50 cm2 being treated only with standard treatment and included in the exploratory assessment. The wound area should correspond to the primary wound area in the following characteristics: a. Including open wound with a surface area < 30 cm2 (measured with Silhouette imaging equipment at the screening visit). Petition 870260058481, dated 06 / 16 / 2026, pp. 124 / 140 116 / 131 (screening consultation). b. At Visit 2 (first treatment with IMP), the wound should not show a surface area reduction > 30% compared to the screening visit. c. Wound age > 3 weeks to < 9 months at the screening visit. d. Not located in anatomical sites with a high probability of accidental trauma (e.g., knee, elbow). 7. Willingness to participate in visits to the study site. E.4 Main exclusion criteria Part 1: 1. History of any clinically significant disease or disorder that, in the researcher's opinion, may put the subject at risk due to participation in the study or influence the results or the subject's ability to participate in the study. 2.Diseases that may interfere with wound healing, for example, type I / II diabetes, arterial, renal, hepatic or cardiac insufficiency, chronic obstructive pulmonary disease, cancer, autoimmune disease, edema at the study site, severe obesity, or known pre-existing wound healing problems, at the investigator's discretion. 3. Active skin disease, for example, dermatitis, psoriasis, and wounds and / or tattoos in the areas where suction blisters will be induced, at the investigator's discretion. 4. Any major surgery planned during the study period. 5. After 10 minutes of rest in the supine position at the time of screening, any vital sign values ​​outside the following ranges: • Systolic blood pressure <90 or >160 mmHg, or • Diastolic blood pressure <50 or >100 mmHg, or • Pulse <40 or >90 beats per minute (bpm) 6. Any clinically significant abnormalities on the resting ECG at the time of screening, as assessed by the investigator. 7.Current smokers or users of nicotine products. Irregular nicotine use (e.g., smoking, inhaling, chewing tobacco) less than three times per week is permitted prior to the screening appointment. 8. Pregnant women, breastfeeding women, or women planning to become pregnant. 9. Systemic immunosuppressive treatment. 10. Individuals who are receiving or have received the following treatments in the 2 weeks prior to screening are excluded from the study: - systemic corticosteroids or immunosuppressive agents; or - antibiotics by any route. 11. Regular use of anticoagulants (i.e., heparin, warfarin, coumarins, and other anticoagulants, at the investigator's discretion) or nonsteroidal anti-inflammatory drugs (NSAIDs) in the 2 weeks prior to screening. Petition 870260058481, dated 06 / 16 / 2026, pp. 125 / 140 117 / 131 weeks prior to (first) IMP administration, at the investigator's discretion. 12. History of severe allergy / hypersensitivity or ongoing allergy / hypersensitivity, at the investigator's discretion, or history of hypersensitivity to drugs with a chemical structure or class similar to TCP-25 or to any excipients of the hydrogel. 14. History of alcohol abuse or excessive intake, at the investigator's discretion. 15. Presence or history of drug abuse, as assessed by the Investigator. Part 2: 1. Presence or history of documented disease that, in the Investigator's opinion, may negatively affect wound healing or interfere with the conduct of the study. 2. Target wound present for more than 5 years. 3. Clinical signs of infection in or around the wound, requiring antibiotic treatment. 4. Albumin < 25 g / L or capillary Hb < 90 g / L, or HbA1c > 70 mmol / mol at the time of the screening visit. 5.Any major surgery planned during the study period. 6. Patients who are receiving or have received the following treatments in the 2 weeks prior to screening are excluded from the study: - systemic corticosteroids above 5 mg of prednisolone or equivalent, or - immunosuppressive agents; or - antibiotics by any route. 7. Regular use of anticoagulants (i.e., heparin, warfarin, coumarins, other anticoagulants affecting aPTT and / or pharmacokinetics / INR, at the investigator's discretion) in the 2 weeks prior to (first) IMP administration, at the investigator's discretion. 8. History of severe allergy / hypersensitivity or ongoing allergy / hypersensitivity, at the investigator's discretion, or history of hypersensitivity to drugs with a chemical structure or class similar to TCP-25 or to any excipients of the hydrogel. Part 3 1. Any EB subtype other than DEB. 2.Wounds with an EB index that present with infection and require systemic antibiotic treatment. 3. Presence of a documented disease that, in the investigator's opinion, may negatively affect wound healing or interfere with the conduct of the study. 4. The individual presents evidence of systemic infection or has used systemic antibiotics for EB-related infections in the 7 days prior to the screening visit (Visit 1). 5. Administration of systemic corticosteroids in the previous 30 days (> 10 mg daily of prednisolone or equivalent) or topical corticosteroids to the target wound areas (primary, secondary, and reference wound areas) in the 14 days prior to the screening visit. Petition 870260058481, dated 06 / 16 / 2026, pp. 126 / 140 118 / 131 (Consultation 1). Corticosteroids for inhalation, ophthalmic, or intranasal use are permitted. 6. The individual has undergone stem cell transplantation or gene therapy for the treatment of EB affecting the target wounds. 7. History of malignancy, including basal cell carcinoma or squamous cell carcinoma in the wound areas to be included in the study. 8. History of severe allergy / hypersensitivity or ongoing allergy / hypersensitivity, at the Investigator's discretion, or history of hypersensitivity to drugs with a chemical structure or class similar to TCP-25 or to any excipients of the hydrogel. 9. Planned treatment or treatment with another investigational drug within 3 months prior to Day -1. E.5 Outcomes E.5.1 Primary outcome(s) Part 1 and 2: •Frequency, intensity, and severity of adverse events (AEs).• Local Tolerability: Incidence of abnormal local reactions compared to the expected outcome of wound healing, as directly assessed by the Investigator: - Skin and wound erythema (abnormal reaction observed). - Skin and wound edema and swelling (abnormal reaction observed). - Necrosis, crusting, and wound hemorrhage (abnormal reactions observed). - Purulent wound discharge as a sign of excessive bacterial colonization and / or infection. • Clinically significant changes from baseline in electrocardiogram (ECG), vital signs (systolic / diastolic blood pressure, pulse rate), safety laboratory parameters (hematology, clinical biochemistry, and coagulation), and physical examinations. Part 3 • Frequency, intensity, and severity of adverse events (AEs).• Local tolerability: Incidence of abnormal local reactions compared to baseline, as directly assessed by the investigator: - Peri-wound erythema and open wound in the treated area (abnormal reaction observed) - Peri-wound edema and swelling and open wound in the treated area (abnormal reaction observed) - Peri-wound desquamation and open wound in the treated area (abnormal reaction observed) - Peri-wound burning / stinging and open wound in the treated area (abnormal reaction observed) E.5.1.1 Time(s) of assessment of this outcome Throughout the study period E.5.2 Secondary outcome(s) Part 1: Plasma concentrations of TCP-25 measured on Day 1, Day 2, Day 3 and Day 5. Part 2: Petition 870260058481, dated 06 / 16 / 2026, pp. 127 / 140 119 / 131 Plasma concentrations of TCP-25 measured on Days 8, 12, 15, 19, 22, 26, 29 (optional) and 33 (optional). Part 3: Plasma concentrations of TCP-25 measured on Day 22 E.5.2.1 Time(s) of assessment of this outcome Throughout the study period E.6 and E.7 Trial scope E.6 Trial scope E.6.1 Diagnosis No E.6.2 Prophylaxis No E.6.3 Therapy No E.6.4 Safety Yes E.6.5 Efficacy No E.6.6 Pharmacokinetics Yes E.6.7 Pharmacodynamics No E.6.8 Bioequivalence No E.6.9 Dose-response No E.6.10 Pharmacogenetics No E.6.11 Pharmacogenomics No E.6.12 Pharmacoeconomics No E.6.13 Other No E.7 Trial type and phase E.7.1 Human pharmacology (Phase I) Yes E.7.1.1 First administration to humans Yes E.7.1.2 Bioequivalence study No E.7.1.3 Other No E.7.1.3.1 Description of another type of trial E.7.2 Exploratory therapeutic trial (Phase II) No E.7.3 Confirmatory therapeutic trial (Phase III) No E.7.4 Therapeutic use trial (Phase IV) No E.8 Trial design E.8.1 Controlled Yes E.8.1.1. Randomized Yes. Petition 870260058481, dated 06 / 16 / 2026, pp. 128 / 140 120 / 131 E.8.1.2 Open Yes E.8.1.3 Single-blind No E.8.1.4 Double-blind Yes E.8.1.5 Parallel group No E.8.1.6 Crossover No E.8.1.7 Other Yes E.8.1.7.1 Other description of the trial design Part 1 = controlled, randomized, and double-blind. Part 2 and 3 = open E.8.2 Controlled trial comparator E.8.2.1 Other drug(s) No E.8.2.2 Placebo Yes E.8.2.3 Other No E.8.2.4 Number of treatment arms in the trial 5 E.8.3 The trial involves a single center in the Member State in question Yes E.8.4 The trial involves multiple centers in the Member State in question No E.8.5 The trial involves multiple Member States No E.8.6 Trial involving sites outside the EEA E.8.6.1 Trial being conducted both inside and outside the EEA No E.8.6.2 Trial being conducted entirely outside the EEA No E.8.7 The trial has a data monitoring committee No E.8.8 Definition of the end of the trial and justification when it is not the last visit of the last subject submitted to the trial. The end of the study is defined as the date of the last visit of the last subject in the study. E.8.9 Initial estimate of the duration of the trial E.8.9.1 In the Member State in question, years E.8.9.1 In the Member State in question, months E.8.9.1 In the Member State in question, days. Petition 870260058481, dated 06 / 16 / 2026, pp. 129 / 140 121 / 131 Table 8 F. Study Subject Population F.1 Age Range F.1.1 The study included participants under 18 years of age Yes F.1.1 Number of participants for this age range: 5 F.1.1.1 In utero No F.1.1.2 Premature newborns (up to gestational age < 37 weeks) No F.1.1.3 Newborns (0-27 days) No F.1.1.4 Infants and toddlers (28 days-23 months) No F.1.1.5 Children (2-11 years) No F.1.1.6 Adolescents (12-17 years) Yes F.1.1.6.1 Number of individuals for this age range: 5 F.1.2 Adults (18-64 years) Yes F.1.2.1 Number of individuals for this age range: 30 F.1.3 Elderly (>=65 years) No F.2 Gender F.2.1 Female Yes F.2.2 Male Yes F.3 Trial participant group F.3.1 Healthy volunteers Yes F.3.2 Patients Yes F.3.3 Specific vulnerable populations Yes F.3.3.1 Women of childbearing age not using contraception No F.3.3.2 Women of childbearing age using contraception Yes F.3.3.3 Pregnant No F.3.3.4 Breastfeeding No F.3.3.5 Emergency situation No F.3.3.6 Subjects unable to give consent in person No F.3.3.7 Other No F.4 Planned number of subjects to be included F.4.1 In the member state 35 F.5 Treatment or care plans after the subject's participation in the study ends (if different from the normal expected treatment for this condition) None. Petition 870260058481, dated 06 / 16 / 2026, pages 130 / 140 122 / 131 Table 9 G. Networks of Investigators to be involved in the Trial Table 10 N. Review by the Competent Authority or Ethics Committee of the country in question N. Decision of the Competent Authority Authorized N. Opinion of the Ethics Committee on the trial application Favorable N. Opinion of the Ethics Committee: Reason(s) for the unfavorable opinion Table 11 P. End of Test P. Position at the End of Test In Progress

[00408] TCP-25 gel acts on both bacteria and inflammation, aspects common to many wounds, and is being developed for a range of wound healing indications, including prevention and treatment of infection and inflammation in Epidermolysis Bullosa wounds and other acute or non-healing wounds.

[00409] Treatment should be administered to patients with Epidermolysis Bullosa to promote wound healing. Exploratory objectives

[00410] Assess signs of healing and wound quality by independent assessors, based on photographs.

[00411] Collect and store samples of dressings and wound surface for future exploratory research on changes in microbiological, molecular, and biochemical markers that reflect inflammation and / or infection. Example 5 - Clinical study of patients with EBD Materials and methods Clinical study

[00412] A clinical study was conducted in patients aged 15 or Petition 870260058481, dated 06 / 16 / 2026, pages 131 / 140 123 / 131 more with confirmed Dystrophic Epidermolysis Bullosa (DEB), as described in Example 4. In each patient, according to the selection criteria of Example 4, a pair of corresponding chronic wounds (primary wound and reference wound) and a more severe secondary wound, located in anatomical sites with a high probability of accidental trauma or within the highest age range, were identified. The wound areas were assessed from baseline (Day 1) to Day 29. The study included four participants who completed the study. Treatment of wound areas (Primary wound, Secondary wound and Reference wound)

[00413] The three wound areas, each measuring 50 cm2, were handled and cleaned according to standard care. A sterile, non-adhesive dressing, limited to a polyurethane dressing (such as Mepilex Lite), was used to cover the open wound and the adjacent skin area. After dressing removal, the wound areas were carefully cleaned according to established routines for EB wounds. Solutions such as potassium permanganate or other locally applied antiseptics should be avoided during the study weeks in the wound areas. However, hypochlorite or potassium permanganate baths were permitted if they were part of the regular cleaning routine.

[00414] Primary and secondary wound areas: TCP-25 gel was applied at each dressing change, every 2nd to 3rd day. The sequential treatment periods consisted of two weeks with 2.9 mg / mL TCP-25 (0.05 mL / cm² of TCP-25 gel per treatment application during week 1, 0.1 mL / cm² of TCP-25 gel per application during week 2), followed by two weeks with 8.6 mg / mL TCP-25 (0.05 mL / cm² of TCP-25 gel per application during week 1, 0.1 mL / cm² of TCP-25 gel per application during week 2). In total, each patient received 12 dose applications (6 applications of TCP-25 2.9 mg / mL + 6 applications of TCP-25 8.6 mg / mL). Petition 870260058481, dated 06 / 16 / 2026, pp. 132 / 140 124 / 131 mg / mL) during the study (Days 1, 3, 6, 8, 10, 13, 15, 17, 20, 22, 24, and 27). The gel was applied from vials using a plastic syringe or spatula. For a dose volume of 0.05 mL / cm², the contents of one vial correspond to a treatment area of ​​50 cm². For a dose volume of 0.1 mL / cm², the contents of two vials correspond to a treatment area of ​​50 cm².

[00415] The reference wounds were treated with the standard of care.

[00416] The primary wound is also referred to here as a “simple wound”. The secondary wound is also referred to here as a “complex wound”. For biomarker assessment purposes, additional larger reference wounds (not treated with TCP) were identified in 2 patients to correspond to the larger secondary wounds. TCP-25 Gels

[00417] The gel composition is as follows.

[00418] Average concentration: 2.9 mg / mL of TCP-25, 1.2% of Natrosol 250 HX, 2% Glycerol, in 10 mM Tris pH 7.

[00419] High concentration: 8.6 mg / mL TCP-25, 1% Natrosol 250 HX, 2% Glycerol, in 10 mM Tris pH 7. Measuring the wound area and calculating wound healing.

[00420] Photos for evaluating signs of healing and wound quality, specifically the open wound area, were measured using the Silhouette wound camera system. Measurement of wound leakage, BPH, and cytokines.

[00421] Leakage score on dressings was performed using a visual scale from 0 to 5, where 0 represented “No exudate in the wound area” and 5 represented “Exudate soaking the dressing in an area that exceeds the wound area”.

[00422] Samples of the dressings were collected from each of the Petition 870260058481, dated 06 / 16 / 2026, pages 133 / 140 125 / 131 wounds to determine the amount of heparin-binding protein (HBP) and cytokines, according to the following procedure:

[00423] At each dressing change, the dressing was removed from the wound, placed in an empty sterile Petri dish, and kept on ice. The dressing and 50 milliliters of sterile, cold, pH 7.4 10 mM Tris buffer were added to a 60 mL syringe and then vortexed. The fluid was then extracted from the dressing by squeezing it into the syringe. The extracted fluid was kept on ice. We added 100x Halt Protease Inhibitory Cocktail (Thermo Fisher Scientific, USA) to half of the dressing fluid, according to the manufacturer's instructions, to a final concentration of 1x, and the samples were then aliquoted and frozen at -80°C.

[00424] Cytokines in the dressing fluid were quantified in stored samples containing protease inhibitor. Cytokines were measured using a V-PLEX Proinflammatory Panel (human) kit (Meso Scale Diagnostics, Rockville, MD, USA, art. no: K15049D) according to the manufacturer's instructions. The concentration of each cytokine was calculated using MSD Discovery Workbench analysis software. Cytokine levels were expressed as concentration per cm2 of wound area.

[00425] The amount of heparin-binding protein (HBP) was determined using an ELISA kit from Aviva Systems Biology (San Diego, CA, United States). Samples were analyzed in duplicate according to the manufacturer's instructions. ELISA signals were read at 450 nm on a microplate reader (BioRad, Hercules, CA, United States). A standard curve was established with reference standards to calculate the concentration in each sample. Results Wound area

[00426] The study results show a significant reduction in Petition 870260058481, dated 06 / 16 / 2026, pp. 134 / 140 126 / 131 Wound size in patients with EBD over a 29-day treatment period (Figure 18, Figure 21 and the following table), for both primary and secondary wounds. The latter was located in anatomically more challenging locations, assessed as more difficult to heal and treat. The application of TCP-25, at different concentrations, to these non-healing chronic EBD wounds in four patients produced notable effects, observed and quantified by measuring the wound area, demonstrating the effectiveness of TCP treatment and the healing process for patients with EBD.

[00427] It is important to highlight that the healing rate was significantly higher than that reported for chronic DEB wounds of the included type. Table 12 Primary wound TCP-25 Reference wound, standard of care Secondary wound, TCP25 Reference value (cm2) 4.0 3.1 12.7 Day 29 (cm2) 0.9 1.5 5.0 Reduction in open area relative to reference value (cm2) 3.1 1.6 7.7 Wound leakage, BPH, and cytokines

[00428] Treatment with TCP-25 reduced wound leakage (i.e., wound exudation) in DEB wounds. Leakage was reduced after TCP-25 gel treatment on day 29 compared to day 8. Leakage after 4 weeks of treatment (day 29) was less than that observed for wounds not treated with TCP-25. Figure 20A shows the mean wound leakage of all primary (i.e., “simple”) wounds treated with TCP25 (n = 3) on days 8 and 29 and for reference SOC wounds (n = 3). It also shows the mean wound leakage of secondary (i.e., “complex”) wounds treated with TCP-25 (n = 3) on days 8 and 29, compared to additional untreated TCP wounds of similar size (n = 2). Figure 20B illustrates wound leakage from primary, secondary, and complex wounds. Petition 870260058481, dated 06 / 16 / 2026, pp. 135 / 140 127 / 131 Reference SOC for one of the treated patients.

[00429] Wound fluid from wounds treated with TCP-25 for 29 days showed a reduction in HBP levels compared to reference wounds not treated with TCP-25. The amount of heparin-binding protein (HBP) in the complex wound fluid from two patients is shown in the following table. Table 13 After 29 days of treatment: Secondary wound treated with TCP Wound not treated with TCP (SOC) Pair of wounds 1 582 ng / mL 2,005 ng / mL Pair of wounds 2 421 ng / mL 2,154 ng / mL

[00430] A reduction in K-1β, TNF-α and IL-6 levels was observed in wounds treated with secondary TCP after 15 and 29 days of treatment, compared with wounds not treated with TCP25 of similar size, larger than 5 cm2 (Figure 22). Table 14. Mean and standard deviation (SD) of cytokine concentrations (pg / mL) / Wound area (cm2). IL-6 IL-1b TNF-a Day 15 Secondary wound (2.9 mg / mL) 7.882, SD 0.9997 27.02, SD 21.90 0.4212, SD 0.3187 Day 29 Secondary wound (8.6 mg / mL) 3.610, SD 4.152 23.33, SD 16.59 0.2313, SD 0.07046 Wounds not treated with TCP-25 (SOC) 33.22, SD 36.94 112.6, SD 80.07 1.029, SD 0.5799

[00431] In patients with recessive DEB, in particular, the continuous formation of blisters, inflammation, recurrent infections, and impaired regeneration lead to painful, chronically inflamed, and often non-healing wounds. Furthermore, mild and repeated mechanical stress before the wound healing process is complete limits the potential for skin regeneration. Consequently, over time, these chronic wounds are accompanied by fibrosis, scarring, glove deformities, and frequently a deadly aggressive form of metastatic squamous cell carcinoma. Petition 870260058481, dated 06 / 16 / 2026, pages 136 / 140 128 / 131

[00432] Recently, several investigations have focused on the immunological aspects of EB, and accumulated studies now support the idea that immunological mechanisms promote wound development. In line with this, studies have also provided evidence of an intrinsic pro-inflammatory state in EB patients. For example, high levels of cytokines, such as interleukin (IL)-1e and IL-6, have been observed. This high pro-inflammatory state not only hinders healing but also drives the development of fibrosis and skin carcinoma. Therefore, these results indicate that TCP-25-mediated cytokine reduction may improve wound healing and reduce the risk of fibrosis and cancer development. Table 15. Sequence overview SEQ ID NO Sequência 1 GKYGFYTHVFRLKKWIQKVIDQFGE 2 FYTHVFRLKKWIQKVIDQFGE 3 GKYGFYTHVFRLKKWIQKVI 4 HVFRLKKWIQKVIDQFGE 5 KYGFYTHVFRLKKWIQKVIDQFGE 6 GKYGFYTHVFRLKKWIQKVIDQFGE 7 GKYGFYTHVFRLKKWIQKVIDQFGE 8 KKWIQKVIDQFGE REFERENCES

[00433] Papanikolaou, M., A. Onoufriadis, JE Mellerio, LA Nattkemper, G. Yosipovitch, M. Steinhoff, and JA McGrath. 2021. 'Prevalence, pathophysiology and management of itch in epidermolysis bullosa', Br J Dermatol, 184: 816-25.

[00434] Bernasconi, R., K. Thriene, E. Romero-Fernandez, C. Gretzmeier, T. Kuhl, M. Maler, P. Nauroy, S. Kleiser, A. C. Ruhl-Muth, M. Stumpe, D. Kiritsi, S. F. Martin, B. Hinz, L. Bruckner-Tuderman, J. Dengjel, and A. Nystrom. 2021. 'Pro-inflammatory immunity supports fibrosis advancement in epidermolysis bullosa: intervention with Ang-(1-7)', EMBO Mol Med, 13: e14392. Petition 870260058481, dated 16 / 06 / 2026, p. 137 / 140 129 / 131

[00435] van der Kooi-Pol, MM, YK Veenstra-Kyuchukova, JC Duipmans, GN Pluister, LM Schouls, AJ de Neeling, H. Grundmann, MF Jonkman, and JM van Dijl. 2012. 'High genetic diversity of Staphylococcus aureus strains colonizing patients with epidermolysis bullosa', Exp Dermatol, 21: 463-6.

[00436] Hoste, E., EN Arwert, R. Lal, AP South, JC SalasAlanis, DF Murrell, G. Donati, and FM Watt. 2015. 'Innate sensing of microbial products promotes wound-induced skin cancer', Nat Commun, 6: 5932.

[00437] Robertson, SJ, E. Orrin, MK Lakhan, G. O'Sullivan, J. Felton, A. Robson, DT Greenblatt, C. Bernardis, JA McGrath, AE Martinez, and JE Mellerio. 2021. 'Cutaneous squamous cell carcinoma in epidermolysis bullosa: a 28-year retrospective study', Acta Derm Venereol, 101:adv00523.

[00438] Tang, JY, MP Marinkovich, E. Lucas, E. Gorell, A. Chiou, Y. Lu, J. Gillon, D. Patel, and D. Rudin. 2021. 'A systematic literature review of the disease burden in patients with recessive dystrophic epidermolysis bullosa', Orphanet J Rare Dis, 16: 175.

[00439] Cutting, Br J Comm Nurse, 2003

[00440] Adderley, Wound essentials, vol 3, 2008

[00441] Pillay and Clapham, 2018, Wounds international, vol 9, 4

[00442] Pope et al., Am Acad Dermatol. 2012 November

[00443] Prodinger, C., J. Reichelt, J. W. Bauer, and M. Laimer. 2019. 'Epidermolysis bullosa: Advances in research and treatment', Exp Dermatol, 28: 1176-89.

[00444] Levin et al. 2021. 'Characterization of wound microbes in epidermolysis bullosa: Results from the epidermolysis bullosa clinical characterization and outcomes database', Pediatric Dermatology, 38: 119-125.

[00445] Saravanan, R., DA Holdbrook, J. Petrlova, S. Singh, NA Petição 870260058481, de 16 / 06 / 2026, pág. 138 / 140 130 / 131 Berglund, Y. K. Choong, S. Kjellstrom, P. J. Bond, M. Malmsten, and A. Schmidtchen. 2018. 'Structural basis for endotoxin neutralisation and antiinflammatory activity of thrombin-derived C-terminal peptides', Nat Commun, 9: 2762

[00446] van der Plas, M. J., R. K. Bhongir, S. Kjellstrom, H. Siller, G. Kasetty, M. Morgelin, and A. Schmidtchen. 2016. 'Pseudomonas aeruginosa elastase cleaves a C-terminal peptide from human thrombin that inhibits host inflammatory responses', Nat Commun, 7: 11567.

[00447] Kalle, M., P. Papareddy, G. Kasetty, M. Morgelin, M. J. van der Plas, V. Rydengard, M. Malmsten, B. Albiger, and A. Schmidtchen. 2012. 'Host defense peptides of thrombin modulate inflammation and coagulation in endotoxin-mediated shock and Pseudomonas aeruginosa sepsis', PLoS One, 7: e51313.

[00448] Puthia, M., M. Butrym, J. Petrlova, A. C. Stromdahl, M. A. Andersson, S. Kjellstrom, and A. Schmidtchen. 2020. 'A dual-action peptidecontaining hydrogel targets wound infection and inflammation', Sci Transl Med, 12.

[00449] Ahlstrom, M. G., L. M. R. Gjerdrum, H. F. Larsen, C. Fuchs, A. L. Sorensen, J. L. Forman, M. S. Agren, and M. Mogensen. 2018. 'Suction blister lesions and epithelialization monitored by optical coherence tomography', Skin Res Technol, 24: 65-72.

[00450] Bar et al., Clinical and Experimental Dermatology (2021) 46, pp1223-1229

[00451] Byrd, Nature Reviews Microbiology, 2018, 16, 143

[00452] Bubier JA, et al. (2010) A Mouse Model of Generalized NonHerlitz Junctional Epidermolysis Bullosa. J Invest Dermatol 130(7):1819-28

[00453] Sproule et al. (2014) Molecular identification of collagen 17a1 as a major genetic modifier of laminin gamma 2 mutation-induced junctional epidermolysis bullosa in mice. PLoS Genet 10(2):e1004068 Petition 870260058481, 16 / 06 / 2026, pág. 139 / 140 131 / 131

[00454] Masson-Meyers DS, Andrade TAM, Caetano GF, Guimaraes FR, Leite MN, Leite SN, Frade MAC. Experimental models and methods for cutaneous wound healing assessment. Int J Exp Pathol. 2020 Feb;101(12):21-37. Petition 870260058481, 16 / 06 / 2026, pág. 140 / 140

Claims

1 / 7 CLAIMS 1. A compound for use in the treatment of a skin disease or skin condition in an individual who needs it, wherein said skin disease or skin condition is selected from the group consisting of a disease or condition distinguished by blistering, a disease or condition distinguished by excessive wound exudate, a disease or condition distinguished by a dysregulated skin microbiome and scarring, characterized in that the compound comprises a peptide comprising or consisting of the amino acid sequence X1-X2-X3-X4-X5-X6-X8-X9-X10, wherein X4, 6, 9 is any standard amino acid, X1 is I, L or V, X2 is any standard amino acid except C, X3 is A, E, Q, R or Y, X5 is any standard amino acid except R, X8 is I or L, X10 is any standard amino acid except H, wherein said peptide has a length of 10 to 100 amino acid residues.

2. Compound for use in reducing the amount of fluid exuding from one or more wounds or blisters in an individual who needs it, characterized in that the compound comprises a peptide comprising or consisting of the amino acid sequence X1-X2-X3-X4-X5-X6-W-X8-X9-X10, wherein X4, 6, 9 is any standard amino acid, X1 is I, L or V, X2 is any standard amino acid except C, X3 is A, E, Q, R or Y, X5 is any standard amino acid except R, Petition 870250065684, dated 07 / 29 / 2025, p. 144 / 314 2 / 7 Xs is I or L, Χίο is any standard amino acid except H, wherein said peptide has a length of 10 to 100 amino acid residues, in which the individual suffers from a disease or condition distinguished by excessive wound exudate.

3. A compound for use in promoting a healthy skin microbiome in an individual in need thereof, characterized in that the compound comprises a peptide comprising or consisting of the amino acid sequence X1-X2-X3-X4-X5-X6-X8-X9-X10, wherein X4, 6, 9 are any standard amino acid, X1 is I, L or V, X2 is any standard amino acid except C, X3 is A, E, Q, R or Y, X5 is any standard amino acid except R, X8 is I or L, X10 is any standard amino acid except H, wherein said peptide has a length of 10 to 100 amino acid residues, in which the individual suffers from a disease or condition distinguished by a dysregulated skin microbiome.

4. Compound for use in reducing scarring in an individual who needs it, characterized in that the compound comprises a peptide comprising or consisting of the amino acid sequence X1-X2-X3-X4-X5-X6-X8-X9-X10, wherein X4, 6, 9 is any standard amino acid, X1 is I, L or V, Petition 870250065684, dated 29 / 07 / 2025, p. 145 / 314 3 / 7 X2 is any standard amino acid except C, X3 is A, E, Q, R or Y, X5 is any standard amino acid except R, X8 is I or L, X10 is any standard amino acid except H, wherein said peptide has a length of 10 to 100 amino acid residues, in which the individual suffers from a disease or condition distinguished by scarring.

5. Compound for use according to any of the preceding claims, characterized in that said skin disease or skin disorder, or said disease or condition, is selected from the group consisting of: epidermolysis bullosa (EB), burn-induced blisters, chilblains, cryotherapy-induced blisters, virus-induced blisters, chickenpox, herpes zoster, herpes simplex, atypical enterovirus infection, hand-foot-and-mouth disease, herpetic eczema, bullous impetigo and staphylococcal scalded skin syndrome, pemphigus, pemphigus foliaceus, pemphigus vulgaris, paraneoplastic pemphigus, pemphigus erythematosus, pemphigus vegetans, pemphigoid, bullous pemphigoid, cicatricial pemphigoid, pemphigoid 200k, mucous membrane pemphigoid, linear IA bullous dermatosis, dermatitis herpetiformis, cutaneous porphyria Late-onset lupus erythematosus, bullous lupus erythematosus, Hailey-Hailey disease, Stevens-Johnson syndrome (toxic epidermal necrolysis).

6. Compound for use in accordance with any of the preceding claims, characterized in that said skin disease or skin disorder, or said disease or condition, is EB.

7. Compound for use in accordance with any of the preceding claims, characterized in that the skin disease or skin disorder, or said disease or condition, is EB, where EB is Petition 870250065684, dated 07 / 29 / 2025, page 146 / 314 4 / 7 simple epidermolysis bullosa, junctional epidermolysis bullosa, dystrophic epidermolysis bullosa, dominant dystrophic epidermolysis bullosa, recessive dystrophic epidermolysis bullosa, Kindler syndrome or acquired epidermolysis bullosa.

8. A compound for use in accordance with any of the preceding claims, characterized in that said disease or condition is selected from the group consisting of burn wounds, chronic skin ulcers, acute infected wounds, pressure ulcers, chronic wounds, venous ulcers, venous leg ulcers, diabetic leg ulcers, eczema and atopic dermatitis, in which said disease or condition is distinguished by blister formation, excessive wound exudate, a dysregulated skin microbiome or scarring.

9. A compound for use according to any of the preceding claims, characterized in that the compound is administered topically in a therapeutically effective amount.

10. Compound for use according to any of the preceding claims, characterized in that the compound is administered to one or more areas of the individual affected by the skin condition or skin disorder.

11. Compound for use according to any of the preceding claims, characterized in that the treatment: a. reduces the size of one or more blisters or wounds, b. reduces the amount of fluid oozing from one or more blisters or wounds, c. reduces the size of the scar or reduces scar formation, d. promotes a healthy skin microbiome, and / or e. reduces the total amount of microorganisms present in one or more wounds or blisters. Petition 870250065684, dated 07 / 29 / 2025, p. 147 / 314 5 / 7 12. Compound for use according to any of the preceding claims, characterized in that: a. the peptide comprises or consists of the amino acid sequence: X1-X2-X3-X4-X5-X6-W-X8-X9-X10-X11-X12-X13, wherein X4, 6, 9, 11 is any standard amino acid, X1 is I, L or V, X2 is any standard amino acid except C, X3 is A, E, Q, R or Y, X5 is any standard amino acid except R, X8 is I or L, X10 is any standard amino acid except H, X12 is I, M or T, X13 is D, K, Q or R, and wherein said peptide has a length of 20 to 100 amino acid residues; or b. The peptide comprises or consists of the amino acid sequence: X1-X2-X3-X4-X5-X6-W-X8-X9-X10-X11-X12-X13-X14-X15-X16-X17, wherein X4, 6, 9, 11, 14, 15 is any standard amino acid; X1 is I, L, or V; X2 is any standard amino acid except C; X3 is A, E, Q, R, or Y; X5 is any standard amino acid except R; X8 is I or L; X10 is any standard amino acid except H; X12 is I, M, or T. Petition 870250065684, dated 07 / 29 / 2025, page 1.148 / 314 6 / 7 X13 is D, K, Q or R X16 is G or D X17 is E, L, G, R or K and wherein said peptide has a length of 20 to 100 amino acid residues.

13. Compound for use according to any of the preceding claims, characterized in that the peptide exhibits at least 80% sequence identity, such as at least 85% sequence identity, such as at least 90% sequence identity, such as at least 95% sequence identity with any of the amino acid sequences: GKYGFYTHVFRLKKWIQKVIDQFGE (SEQ ID NO: 1), FYTHVFRLKKWIQKVIDQFGE (SEQ ID NO: 2), GKYGFYTHVFRLKKWIQKVI (SEQ ID NO: 3), HVFRLKKWIQKVIDQFGE (SEQ ID NO: 4), KYGFYTHVFRLKKWIQKVIDQFGE (SEQ ID NO: 5), GKYGFYTHVFRLKKWIQKVIDQF (SEQ ID NO: 6), GKYGFYTHVFRLKKWIQKV (SEQ ID NO: 7), or KKWIQKVIDQFGE (SEQ ID NO: 8);or wherein the peptide comprises or consists of any of the following amino acid sequences: GKYGFYTHVFRLKKWIQKVIDQFGE (SEQ ID NO: 1), FYTHVFRLKKWIQKVIDQFGE (SEQ ID NO: 2), GKYGFYTHVFRLKKWIQKVI (SEQ ID NO: 3), HVFRLKKWIQKVIDQFGE (SEQ ID NO: 4), KYGFYTHVFRLKKWIQKVIDQFGE (SEQ ID NO: 5), GKYGFYTHVFRLKKWIQKVIDQF (SEQ ID NO: 6), GKYGFYTHVFRLKKWIQKV (SEQ ID NO: 7), or Petition 870250065684, dated 29 / 07 / 2025, p. 149 / 314 7 / 7 KKWIQKVIDQFGE (SEQ ID NO: 8); or wherein the peptide consists of the amino acid sequence: GKYGFYTHVFRLKKWIQKVIDQFGE (SEQ ID NO: 1).

14. A compound for use according to any of the preceding claims, characterized in that one or more of the standard amino acids comprised in the peptide are modified or derivatized.

15. Compound for use according to any of the preceding claims, characterized in that one or more of the standard amino acids comprised in the peptide are PEGylated, amidated, acylated, acetylated, alkenylated and / or alkylated.

16. Composition, characterized in that it comprises the compound for use as defined in any of the preceding claims.

17. Composition according to claim 16, characterized in that the composition is an ointment, a cream, an emulsion, a lotion, a powder, a spray, a solution, a viscous solution, a gel or a hydrogel.

18. Composition according to claim 16 or 17, characterized in that the composition comprises an adhesive, a dry adhesive, a plaster, a bandage, a film or a dressing.

19. Composition according to any one of claims 16 to 18, characterized in that the concentration of the peptide or compound in said composition is between 0.5 and 50 mg / mL, such as between 0.8 and 10 mg / mL, such as between 0.8 and 3 mg / mL, such as between 2.5 and 9 mg / mL, such as between 0.86 and 8.6 mg / mL, such as between 2.9 and 8.6 mg / mL. Petition 870250065684, dated 29 / 07 / 2025, p. 150 / 314

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