USO DE NANOCORPO QUE INIBE IL-17A E / OU IL-17F, UM INIBIDOR DE IL-17A E / OU IL-17F, UM AGENTE QUE SE LIGA SELETIVAMENTE À IL-17A E / OU IL-17F, UM AGENTE CONFIGURADO PARA INIBIR IL-17F, MÉTODOS PARA MONITORAR A REMISSÃO DE UMA CONDIÇÃO DEPENDENTE DE IL-17, IDENTIFICAR UM INDIVÍDUO EM RISCO OU PORTADOR DE HIDRADENITE SUPURATIVA, DETECTAR HIDRADENITE SUPURATIVA E KITS PARA IDENTIFICAR UM INDIVÍDUO EM RISCO OU QUE NECESSITA DE TRATAMENTO E PARA TRATAR UMA CONDIÇÃO DEPENDENTE DE IL-17

Abstract

Biomarker-based treatment, monitoring, and diagnostic methods for IL-17 dependent conditions, including hidradenitis suppurativa, are disclosed. The biomarkers may be selected from IL6, PLA2G2A, IL19, PI3, CST7, IL17A, IL17F, GH1, MZB1, IL1B, IFNG, TNC, CXCL9, SLAMF7, VEGFA, IL17C, SLAMF1, SDC1, OSM, LBP, REG3A, CD79B, COL4A1, CLEC4D, VWF, IL5RA, CSF3, TGFA, IL2RA, ITIH3, FCAR, CCL23, NRCAM, RETN, SERPINA11, CLEC4G, CSF1, HGF, CRELD2, EFEMP1, LTBR, NME3, CKAP4, CD276, SPON2, GGH, TIMP1, LY9, MCFD2, TCN2, QPCT, HYOU1, TNSFSF13B, CCL2, CCL3, CCL4, CCL5, CCL7, CCL20, CXCL1, CXCL8, PDFGA, CXCR2, CCR6, CXCL13, PCDH1, BOC, MEPE, ADAM23, THOP1, IL1RL2, RCOR1, EDAR, and combinations thereof. Kits for measuring the biomarkers, diagnosing and treating IL-17-dependent conditions, and identifying super-responders are also disclosed.

Description

CROSS-REFERENCE TO RELATED PATENT APPLICATIONS

[001] This patent application claims the benefit of this patent, pursuant to section 119(e) of the United States Code, Title 35, to U.S. Provisional Patent Application No. 63 / 460 240, filed April 18, 2023, as well as to U.S. Provisional Patent Application No. 63 / 460 230, filed April 18, 2023, the contents of which are hereby expressly incorporated in their entirety by reference. DECLARATION OF INCORPORATION BY REFERENCE RELATED TO THE LISTING OF SEQUENCES

[002] This patent application contains a Listing of The sequence was submitted electronically in XML file format and is incorporated herein in its entirety by reference. Said XML copy, created on April 17, 2024, is named “P68859_SL.xml” and its size is 94,394 bytes. FUNDAMENTALS OF THE INVENTION

[003] Biomarkers have been described for several immune-mediated diseases. For example, WO 2019 / 143585 describes detecting the presence of IL-19 in a sample from a patient with an immune-related disease, such as psoriasis, atopic dermatitis, or neuropathy. Petition 870260065164, dated 02 / 07 / 2026, page 13 / 213 / 85 diabetic, and treat the patient with an antibody against IL-19 if IL-19 is detected to be above a reference value. As another example, WO 2014 / 100312 describes prospectively selecting patients with psoriasis who are likely to benefit from treatment with IL-23 antagonists based on the presence of one or more single nucleotide polymorphisms in the genome. WO 2012 / 093254 refers to the use of lipocalin 2 (LCN2) as a biomarker, as well as the use of an anti-IL-17A antibody to reduce LCN2 expression in an animal model of multiple sclerosis.However, there is still a need for more personalized treatment regimens, as well as for earlier and more accurate identification of patients with immune system-related diseases to assess the severity of these diseases, particularly IL-17-dependent conditions, in order to more effectively control disease progression and / or recurrence after treatment. There is also a need to identify specific patients and / or patient populations among those who meet standard diagnostic criteria and respond positively to treatment with any particular therapeutic agent.

[004] Historically, IL-17 was used to describe what was later revealed to be only one member of the IL-17 family of cytokines. Experts in the field therefore assumed that IL-17A was the primary and principal pro-inflammatory signal driving IL-17 pathway-related immune conditions such as psoriasis, psoriatic arthritis, and axial spondyloarthropathies. Non-communicable inflammatory skin diseases distinguished by exaggerated IL-17 activity have also been termed Type 3 diseases (Nakamura et al., Curr Rheumatol Rep. 23(5):31 (2021); Eyerich et al., J Eur Acad Dermatol Venereol. 32(5):692-703 (2018); Annunziato et al., 135(3):626-35 (2015)) and, over the years, several prevalent and complicated chronic conditions that follow this pattern have been identified, including the skin disease hidradenitis suppurativa (HS). Petition 870260065164, dated 02 / 07 / 2026, page 14 / 213 / 85 The first monoclonal antibody therapies developed to treat Type 3 disease were antibodies that specifically inhibited IL-17A, based on the traditional concept that this mediator exerts the main pro-inflammatory activity.

[005] The current concept behind IL-17-induced inflammation in human disease is based on the finding that two members of the IL17 cytokine family, IL-17A and IL-17F, form dimers that exert pro-inflammatory functions after binding to IL-17 receptors composed of two receptor chains, IL-17RA and IL-17RC. Traditionally, it has been believed that the inflammatory potential and affinity for the RA / RC receptor decreases from IL-17A / A to IL-17A / F to IL-17F / F, but the amount of dimers present in a given disease condition (e.g., more IL-17F / F than IL-17A / A) or the presence of different receptor types in relevant target cells (e.g., RC / RC receptors) that favor IL-17F biological activity point to an important independent pro-inflammatory role of IL-17F / F. In fact, cells that produce exclusively IL-17F have been identified that do not appear to be regulated by mechanisms that control IL-17A-producing cells, such as stimulation by IL-23.The IL-17F / F dimer is not inhibited by traditional monoclonal antibody therapies that block IL-17A.

[006] HS is a chronic inflammatory skin disease characterized by painful inflammatory lesions that, if not treated properly, can progress to irreversible tissue destruction, including tunneling and scarring (Sabat et al., Nat Rev Dis Primers 6, 18 (2020); Navrazhina et al., J Allergy Clin Immunol 147, 2213-2224 (2021)). The disease is accompanied by a significant impact on quality of life and work productivity (Merchant et al., Clin Exp Dermatol. 9:11a120 (2024)). Currently, there is a significant latency between the onset of the first signs of HS and the diagnosis and initiation of appropriate treatment. Petition 870260065164, dated 02 / 07 / 2026, page 15 / 213 / 85 (Saunte et al., Br J Dermatol 173, 1546-1549 (2015); Garg et al., J Am Acad Dermatol 82, 366-376 (2020); Tsentemeidou et al., Australas J Dermatol (2024)). Due to the long period of time between the first appearance of HS signs and the establishment of the diagnosis and the start of appropriate therapies, the window of opportunity for successful medical treatment is lost in many patients. In late-stage disease, when irreversible skin damage has already occurred, only surgical procedures remain as an option. These often involve extensive operations with wide excisions and removal of affected tissue, increasing morbidity and limitations for patients. It is therefore mandatory to identify patients with high HS inflammatory activity and initiate optimal anti-inflammatory treatment early to prevent irreversible tissue damage.

[007] The main inflammatory clinical phenotypes used to assess disease severity and determine appropriate treatments for HS are (i) nodules, which are more superficial inflammatory lesions originating from inflamed hair follicles, (ii) abscesses, correlated with deep dermal lesions that develop subsequent to hair follicle rupture and a more pronounced influx of inflammatory cells, and (iii) tunnels. These tunnels are deep dermal structures that can connect and originate from ruptured follicles, but can also reach the skin surface, appearing as openings. These tunnels typically undergo re-epithelialization and become the primary source of inflammation and the main cause of HS (Active tunnels fill with neutrophils and bacteria and often exude or “drain” foul-smelling pus onto the skin surface.The subsequent destruction of tissue into nodules, abscesses, and inflammation within and around the tunnels results in scar formation. When the stage of excessive scar and tunnel formation is reached, patients often require surgical intervention, which can further adversely affect morbidity and overall well-being. Petition 870260065164, dated 02 / 07 / 2026, p. 16 / 213 / 85

[008] Unlike other more superficial chronic inflammatory skin diseases, such as psoriasis or atopic dermatitis, the presence and severity of HS lesions can hardly be assessed solely by clinical inspection and investigation, especially in the presence of tunneling. This is a significant, currently unresolved problem concerning the timely diagnosis of HS, adequate assessment of the inflammatory activity of the disease, selection and initiation of appropriate therapy, and monitoring of the treatment response and long-term management of HS therapy. And, although IL-17A and IL-17F have been identified as key mediators inducing HS disease activity, in particular, the activation of keratinocytes and the release of chemoattractant cytokines responsible for the influx of neutrophils, T cells, and other immune cells that initiate, intensify, and perpetuate the inflammatory facet of HS (Lima et al., Br J Dermatol.174(3):514-21 (2016)), it remains necessary to identify biomarkers that allow for improved control and treatment of HS and other IL-17-dependent conditions. There is also a need for early diagnosis, prediction of treatment response in relation to existing therapies and / or analogues thereof, and long-term disease surveillance and control. There is also a need for more personalized and effective treatments for inflammatory skin conditions. In the case of diseases such as HS or psoriatic arthritis with difficult-to-reach inflammatory sites, providing a mechanism of action that inhibits IL-17F and / or IL-17A would benefit from the development of targeted therapies with enhanced tissue penetration. SUMMARY OF THE INVENTION

[009] Methods for treating an IL-17-dependent condition are described herein, comprising administering a drug, comprising a nanobody that inhibits IL-17A and / or IL-17F, to an individual, wherein the individual has been identified as having a level Petition 870260065164, dated 02 / 07 / 2026, page. 17 / 213 / 85 elevated of one or more biomarkers selected from IL6, PLA2G2A, IL19, PI3, CST7, IL17A, IL17F, GH1, MZB1, IL1B, IFNG, TNC, CXCL9, SLAMF7, VEGFA, IL17C, SLAMF1, SDC1, OSM, LBP, REG3A, CD79B, COL4A1, CLEC4D, VWF, IL5RA, CSF3, TGFA, IL2RA, ITIH3, FCAR, CCL23, NRCAM, RETN, SERPINA11, CLEC4G, CSF1, HGF, CRELD2, EFEMP1, LTBR, ​​NME3, CKAP4, CD276, SPON2, GGH, TIMP1, LY9, MCFD2, TCN2, QPCT, HYOU1, TNSFSF13B, CCL2, CCL3, CCL4, CCL5, CCL7, CCL20, CXCL1, CXCL8, PDFGA, CXCR2, CCR6 and CXCL13.

[0010] In addition, methods for treating hidradenitis suppurativa (HS) are described herein, comprising administering a drug comprising an IL-17A and / or IL-17F inhibitor to an individual, wherein the individual has been identified as having an elevated level of one or more biomarkers selected from among IL6, PLA2G2A, IL19, PI3, CST7, IL17A, IL17F, GH1, MZB1, IL1B, IFNG, TNC, CXCL9, SLAMF7, VEGFA, IL17C, SLAMF1, SDC1, OSM, LBP, REG3A, CD79B, COL4A1, CLEC4D, VWF, IL5RA, CSF3, TGFA, IL2RA, ITIH3, FCAR, CCL23, NRCAM, RETN, SERPINA11, CLEC4G, CSF1, HGF, CRELD2, EFEMP1, LTBR, ​​NME3, CKAP4, CD276, SPON2, GGH, TIMP1, LY9, MCFD2, TCN2, QPCT, HYOU1, TNSFSF13B, CCL2, CCL3, CCL4, CCL5, CCL7, CCL20, CXCL1, CXCL8, PDFGA, CXCR2, CCR6, and CXCL13. In embodiments, such a method is contemplated in which the IL-17A and / or IL-17F inhibitor comprises a nanobody.

[0011] Treatment methods such as those described above are also described, in which the nanobody is configured to bind specifically to IL-17A and IL-17F, preferably the nanobody is soneloquimab (SLK).

[0012] Treatment methods such as those described above are also described, in which the elevated level is compared to: (i) the level present in uninjured skin, preferably in perilesional skin, (ii) the level present in the peripheral blood of a healthy patient, or (iii) the level in the same individual before treatment. Petition 870260065164, dated 02 / 07 / 2026, page 18 / 213 / 85 initial.

[0013] Treatment methods are also described as above, wherein the elevated level is compared to a reference value, and the reference value is (i) the biomarker expression level of the corresponding body fluid or tissue sample obtained from a healthy individual; (ii) the average biomarker level expressed in the corresponding body fluid or tissue of a plurality of healthy individuals; or (iii) the average biomarker level expressed in healthy tissue, preferably healthy tissue from the same individual, more preferably perilesional skin from the same individual.

[0014] Treatment methods such as those described above are also included, comprising analyzing a sample of body tissue or fluid, preferably a skin or peripheral blood sample, from a patient who has or is at risk of having an IL-17-dependent condition for the level of one or more biomarkers prior to treatment.

[0015] Treatment methods are also described as above, wherein the elevated level of one or more of the biomarkers indicates that the patient has (i) an inflammatory skin disease, preferably an inflammatory skin disease affecting the epidermis and dermis, more preferably an inflammatory skin disease involving hair follicle structures, even more preferably an inflammatory skin disease involving acneiform lesions, most preferably hidradenitis suppurativa (HS), such as moderate to severe HS and / or (ii) a phenotype that includes one or more drainage tunnels in the skin.

[0016] Treatment methods are also described as above, in which the higher the level of one or more of the biomarkers, the greater the number of drainage tunnels present in the individual.

[0017] Treatment methods such as those described above are also described, in which the individual has been clinically diagnosed as having HS in Petition 870260065164, dated 02 / 07 / 2026, page 19 / 213 / 85 Hurley Stage I, II, or III.

[0018] Treatment methods such as those described above are also included, where the individual has been clinically diagnosed as having mild HS, moderate HS, moderate to severe HS, severe HS, or juvenile HS.

[0019] Treatment methods are also described as above, in which the individual does not have drainage tunnels or in which the individual has at least one drainage tunnel.

[0020] Treatment methods such as those described above are also described, in which the biomarkers comprise protein and / or mRNA biomarkers.

[0021] Treatment methods such as those described above are also described, in which one or more of the biomarkers are selected from among IL6, PLA2G2A, PI3, CST7, IL17A, IL17F, GH1, MZB1, IL1B, IFNG, TNC, CXCL9, SLAMF7, VEGFA, IL17C, SLAMF1, SDC1, OSM, LBP, REG3A, CD79B, COL4A1, CLEC4D, VWF, IL5RA, CSF3, TGFA, IL2RA, ITIH3, FCAR, CCL23, NRCAM, RETN, SERPINA11, CLEC4G, CSF1, HGF, CRELD2, EFEMP1, LTBR, ​​NME3, CKAP4, CD276, SPON2, GGH, TIMP1, LY9, MCFD2, TCN2, QPCT, HYOU1, TNSFSF13B, CCL2, CCL3, CCL4, CCL5, CCL7, CCL20, CXCL1, CXCL8, PDFGA, CXCR2, CCR6 and CXCL13.

[0022] Treatment methods such as those described above are also described, in which one or more of the biomarkers are selected from among IL6, PLA2G2A, IL19, PI3, CST7, GH1, MZB1, IL1B, IFNG, TNC, CXCL9, SLAMF7, VEGFA, IL17C, SLAMF1, SDC1, OSM, LBP, REG3A, CD79B, COL4A1, CLEC4D, VWF, IL5RA, CSF3, TGFA, IL2RA, ITIH3, FCAR, CCL23, NRCAM, RETN, SERPINA11, CLEC4G, CSF1, HGF, CRELD2, EFEMP1, LTBR, ​​NME3, CKAP4, CD276, SPON2, GGH, TIMP1, LY9, MCFD2, TCN2, QPCT, HYOU1, TNSFSF13B, CCL2, CCL3, CCL4, CCL5, CCL7, PDFGA, CXCR2, CCR6 and CXCL13.

[0023] Treatment methods such as those described above are also used, in which one or more biomarkers are selected from CSF3, CCL2, Petition 870260065164, dated 02 / 07 / 2026, page 20 / 213 / 85 CCL3, CCL4, CCL5, CCL7, CCL20, CXCL1, CXCL8 and PDFGA.

[0024] Treatment methods such as those described above are also included, in which one or more of the biomarkers are selected from CCL20, CXCL8, CXCL1, IL17A and IL17F.

[0025] Also described here is the use of an agent that selectively binds to IL-17A and / or IL-17F in an individual determined to have an elevated level of at least one of the following biomarkers: IL6, PLA2G2A, IL19, PI3, CST7, IL17A, IL17F, GH1, MZB1, IL1B, IFNG, TNC, CXCL9, SLAMF7, VEGFA, IL17C, SLAMF1, SDC1, OSM, LBP, REG3A, CD79B, COL4A1, CLEC4D, VWF, IL5RA, CSF3, TGFA, IL2RA, ITIH3, FCAR, CCL23, NRCAM, RETN, SERPINA11, CLEC4G, CSF1, HGF, CRELD2, EFEMP1, LTBR, ​​NME3, CKAP4, CD276, SPON2, GGH, TIMP1, LY9, MCFD2, TCN2, QPCT, HYOU1, TNSFSF13B, CCL2, CCL3, CCL4, CCL5, CCL7, CCL20, CXCL1, CXCL8, PDFGA, CXCR2, CCR6 and CXCL13, compared to a healthy control, preferably where the elevated level is present in the skin and / or blood, for use according to the present invention and any embodiment, any combination and / or any group of biomarkers described apply accordingly.

[0026] A use such as the above is also described, wherein the elevated level of at least one biomarker is the level present in a biological sample from the individual, and the level of at least one corresponding biomarker present in the healthy control is representative of the level present in a biological sample not affected by an IL17-dependent condition, preferably by an IL17-dependent inflammatory skin disease, more preferably by hidradenitis suppurativa (HS).

[0027] A use such as the above is also described, in which the biomarkers are associated with an inflammatory skin disease, preferably an inflammatory skin disease affecting the epidermis and dermis, more preferably an inflammatory skin disease involving Petition 870260065164, dated 02 / 07 / 2026, page 21 / 213 / 85 hair follicle structures, even more preferably an inflammatory skin disease involving acneiform lesions, most preferably hidradenitis suppurativa (HS).

[0028] Also described is a use such as above, which is distinguished by an elevated mRNA level or elevated protein level of at least one or more biomarkers selected from IL6, PLA2G2A, IL19, PI3, CST7, IL17A, IL17F, GH1, MZB1, IL1B, IFNG, TNC, CXCL9, SLAMF7, VEGFA, IL17C, SLAMF1, SDC1, OSM, LBP, REG3A, CD79B, COL4A1, CLEC4D, VWF, IL5RA, CSF3, TGFA, IL2RA, ITIH3, FCAR, CCL23, NRCAM, RETN, SERPINA11, CLEC4G, CSF1, HGF, CRELD2, EFEMP1, LTBR, ​​NME3, CKAP4, CD276, SPON2, GGH, TIMP1, LY9, MCFD2, TCN2, QPCT, HYOU1, TNSFSF13B, CCL2, CCL3, CCL4, CCL5, CCL7, CCL20, CXCL1, CXCL8, PDFGA, CXCR2, CCR6 and CXCL13 and, preferably, at least one or more biomarkers selected from CCL20, CXCL8, CXCL1, IL17A and IL17F.

[0029] A use such as the above is also described, which is distinguished by a high level of mRNA or a high level of protein in a skin sample with a lesion, compared to the respective mRNA or protein level of a skin sample without a lesion.

[0030] A use such as the above is also described, in which a ratio between lesional IL-17F mRNA or protein and non-lesional IL-17 is determined.

[0031] A use such as the above is also described, in which the individual has been identified as having an inflammatory skin disease, preferably an inflammatory skin disease affecting the epidermis and dermis, more preferably an inflammatory skin disease involving hair follicle structures, even more preferably an inflammatory skin disease involving acneiform lesions, most preferably hidradenitis suppurativa, exhibiting, respectively, an elevated level of one or more biomarkers. Petition 870260065164, dated 02 / 07 / 2026, page 22 / 213 / 85

[0032] A use such as above is also described, in which the individual has been clinically diagnosed as having HS in Hurley Stage I, II or III.

[0033] A use such as the above is also described, in which the release of IL-17A and / or IL-17F in Hurley Stage I, II and / or III of hidradenitis suppurativa is inhibited by the agent.

[0034] A use such as the above is also described, in which the agent is an IL-17A and / or IL-17F inhibitor.

[0035] A use such as the above is also described, in which inflammation and / or tissue destruction are inhibited.

[0036] A use such as the above is also described, in which the agent comprises an antibody, an antibody fragment or a nanobody. In embodiments of such use, the agent may comprise a nanobody, preferably the nanobody is soneloquimab or a derivative thereof.

[0037] Also described is a use such as the above, wherein the agent is a nanobody, preferably soneloquimab or a derivative thereof, and a biomarker panel comprises a) CCL20, CXCL1, CXCL8, CXL1, IL17A, IL17F, IL19, LT01, CSF3, OSM, PLA2G2A, CST7 and / or PI3, b) IL17A, IL17F, CCL20, CXCL1 and / or CXCL8, c) IL17A, IL17F, CCL20, and / or CXCL8, d) LT01, IL17A, CSF3, OSM, PLA2G2A and / or CST7 e) CCL20, CXCL8, IL19 and PI3; or f) PI3 and IL19.

[0038] In addition, methods for treating an IL-17 dependent condition are described herein, comprising administering a drug comprising an IL-17A and / or IL-17F inhibitor to an individual, wherein the individual has been identified as having a reduced level of one or more biomarkers selected from PCDH1, BOC, MEPE, ADAM23, THOP1, IL1RL2, RCOR1 and EDAR.

[0039] Methods are also described for treating individuals identified as having a reduced level of one or more biomarkers. Petition 870260065164, dated 02 / 07 / 2026, page 23 / 213 / 85 as above, in which the IL-17A and / or IL-17F inhibitor comprises a nanobody.

[0040] Methods are also described for treating individuals identified as having a reduced level of one or more biomarkers as above, wherein the nanobody is configured to bind specifically to IL-17A and IL-17F, preferably the nanobody is soneloquimab (SLK).

[0041] Methods are also described for treating individuals identified as having a reduced level of one or more biomarkers as above, wherein the reduced level is compared to: (i) the level present in uninjured skin, preferably in perilesional skin, (ii) the level present in the peripheral blood of a healthy patient, or (iii) the level in the same individual before initial treatment.

[0042] Methods are also described for treating individuals identified as having a reduced level of one or more biomarkers as above, wherein the reduced level is compared to a reference value, and the reference value is (i) the biomarker expression level of the corresponding body fluid or tissue sample obtained from a healthy individual; (ii) the average biomarker level expressed in the corresponding body fluid or tissue of a plurality of healthy individuals; or (iii) the average biomarker level expressed in healthy tissue, preferably healthy tissue from the same individual, more preferably perilesional skin from the same individual.

[0043] Methods are also described for treating individuals identified as having a reduced level of one or more biomarkers as above, comprising analyzing a tissue or body fluid sample, preferably a skin or peripheral blood sample, from a patient who has or is at risk of having an IL-17-dependent condition for the level of one or more of the biomarkers prior to treatment. Petition 870260065164, dated 02 / 07 / 2026, page 24 / 213 / 85

[0044] Methods are also described for treating individuals identified as having a reduced level of one or more biomarkers as above, wherein the reduced level of one or more biomarkers indicates that the patient has (i) an inflammatory skin disease, preferably an inflammatory skin disease affecting the epidermis and dermis, more preferably an inflammatory skin disease involving hair follicle structures, even more preferably an inflammatory skin disease involving acneiform lesions, most preferably hidradenitis suppurativa (HS), such as moderate to severe HS and / or (ii) a phenotype that includes one or more drainage tunnels in the skin.

[0045] Methods are also described for treating individuals identified as having a reduced level of one or more biomarkers as above, where the lower the level of one or more of the biomarkers, the greater the number of drainage tunnels that are present in the individual.

[0046] Methods are also described for treating individuals identified as having a reduced level of one or more biomarkers as above, where the individual has been clinically diagnosed as having HS in Hurley Stage I, II or III.

[0047] Methods are also described for treating individuals identified as having a reduced level of one or more biomarkers as above, where the individual has been clinically diagnosed as having mild HS, moderate HS, moderate to severe HS, severe HS or juvenile HS.

[0048] Methods are also described for treating individuals identified as having a reduced level of one or more biomarkers as above, where the individual does not have drainage tunnels or where the individual has at least one drainage tunnel.

[0049] Methods for treating individuals are also described. Petition 870260065164, dated 02 / 07 / 2026, p. 25 / 213 / 85 identified as having a reduced level of one or more biomarkers as above, where the biomarkers comprise protein and / or mRNA biomarkers.

[0050] Also described here is the use of an agent that selectively binds to IL-17A and / or IL-17F in an individual determined to have a reduced level of at least one of the following biomarkers: PCDH1, BOC, MEPE, ADAM23, THOP1, IL1RL2, RCOR1 and EDAR in the skin and / or blood compared to a healthy control, preferably where the reduced level is present in the skin and / or blood.

[0051] In addition, methods for monitoring the progress of treatment or remission of an IL-17-dependent condition are described herein, which methods comprise analyzing a biological sample from an individual previously treated for the IL-17-dependent condition, preferably hidradenitis suppurativa, for one or more biomarkers selected from IL6, PLA2G2A, IL19, PI3, CST7, IL17A, IL17F, GH1, MZB1, IL1B, IFNG, TNC, CXCL9, SLAMF7, VEGFA, IL17C, SLAMF1, SDC1, OSM, LBP, REG3A, CD79B, COL4A1, CLEC4D, VWF, IL5RA, CSF3, TGFA, IL2RA, ITIH3, FCAR, CCL23, NRCAM, RETN, SERPINA11, CLEC4G, CSF1, HGF, CRELD2, EFEMP1, LTBR, ​​NME3, CKAP4, CD276, SPON2, GGH, TIMP1, LY9, MCFD2, TCN2, QPCT, HYOU1, TNSFSF13B, CCL2, CCL3, CCL4, CCL5, CCL7, CCL20, CXCL1, CXCL8, PDFGA, CXCR2, CCR6, CXCL13, PCDH1, BOC, MEPE, ADAM23, THOP1, IL1RL2, RCOR1 and EDAR.

[0052] Monitoring methods such as those described above are also described, in which the biomarkers include PI3 and IL19.

[0053] Monitoring methods such as those described above are also described, where normalization of the level of one or more biomarkers to the level of a healthy control indicates (i) remission of inflammation; (ii) that any tunnels present in the individual remain present, but are not Petition 870260065164, dated 02 / 07 / 2026, page 26 / 213 / 85 more active; and / or (iii) that treatment should be suspended.

[0054] In addition, methods are described here for identifying an individual who is a carrier or at risk of being a carrier of hidradenitis suppurativa (HS), which includes determining the IL-17F / IL-17A protein or mRNA ratio present in a tissue sample from the individual.

[0055] In addition, methods for detecting hidradenitis suppurativa (HS) are described herein, comprising analyzing a sample from an individual who has or is at risk of having HS for elevated levels of one or more of the following: IL6, PLA2G2A, IL19, PI3, CST7, IL17A, IL17F, GH1, MZB1, IL1B, IFNG, TNC, CXCL9, SLAMF7, VEGFA, IL17C, SLAMF1, SDC1, OSM, LBP, REG3A, CD79B, COL4A1, CLEC4D, VWF, IL5RA, CSF3, TGFA, IL2RA, ITIH3, FCAR, CCL23, NRCAM, RETN, SERPINA11, CLEC4G, CSF1, HGF, CRELD2, EFEMP1, LTBR, ​​NME3, CKAP4, CD276, SPON2, GGH, TIMP1, LY9, MCFD2, TCN2, QPCT, HYOU1, TNSFSF13B, CCL2, CCL3, CCL4, CCL5, CCL7, CCL20, CXCL1, CXCL8, PDFGA, CXCR2, CCR6 and CXCL13; or reduced levels of one or more of PCDH1, BOC, MEPE, ADAM23, THOP1, IL1RL2, RCOR1 and EDAR.

[0056] Detection methods are also described as above, in which the respective elevated or reduced level is compared to: (i) the level present in uninjured skin, preferably in perilesional skin, (ii) the level present in the peripheral blood of a healthy patient, or (iii) the level in the same individual before initial treatment.

[0057] Detection methods are also described as above, wherein the respective elevated or reduced level is compared to a reference value, and the reference value is (i) the expression level of the biomarker in the corresponding body fluid or tissue sample obtained from a healthy individual; (ii) the average level of the biomarker expressed in the corresponding body fluid or tissue from a plurality of healthy individuals; Petition 870260065164, dated 02 / 07 / 2026, page 27 / 213 / 85 or (iii) the average level of the biomarker expressed in healthy tissue, preferably healthy tissue from the same individual, more preferably perilesional skin from the same individual.

[0058] Detection methods such as those described above are also included, comprising analyzing a sample of body tissue or fluid, preferably a skin or peripheral blood sample, from a patient who has or is at risk of having HS.

[0059] Also described here is a method for treating an individual with a lesional IL-17F / non-lesional IL-17F protein ratio result equal to or greater than 2, preferably equal to or greater than 10, more preferably equal to 2-50 and, most preferably, equal to 10-30, which comprises administering an effective amount of an agent configured to inhibit IL-17F present in the dermis of an inflammatory skin lesion of the individual.

[0060] Also described here is a method for treating an individual with a lesional IL-17F mRNA ratio of 5 or higher, preferably 10 or higher, more preferably 5-500 and most preferably 10-300, which comprises administering an effective amount of an agent configured to inhibit IL-17F present in the dermis of an inflammatory skin lesion of the individual.

[0061] Also described herein is a method for treating hidradenitis suppurativa, comprising administering a drug comprising an IL-17A and / or IL-17F inhibitor to an individual, wherein the individual has been identified as having elevated levels of one or more biomarkers selected from (a) LTO1, (b) CSF3, (c) OSM, (d) PLA2G2A or (e) a combination of IL17A and TNC.

[0062] A method for identifying a patient with hidradenitis suppurativa is also described here, where the patient is responsive to Petition 870260065164, dated 02 / 07 / 2026, page 28 / 213 / 85 treatment with a nanobody that inhibits IL-17A and / or IL-17F, comprising analyzing a biological sample from the patient for the presence of one or more biomarkers selected from (a) LTO1, (b) CSF3, (c) OSM, (d) PLA2G2A or (e) a combination of IL17A and TNC, wherein the presence of an elevated level of at least one, two, three or more of the biomarkers indicates that the patient is responsive to treatment with a nanobody that inhibits IL-17A and / or IL-17F.

[0063] This identification method may involve identifying a patient who is a super-responder.

[0064] A method of identification is also described herein, in which the identified patient receives treatment with a nanobody that inhibits IL-17A and / or IL-17F, preferably soneloquimab.

[0065] A method of identification is also described here, in which the nanobody comprises soneloquimab.

[0066] Also described herein is a kit for identifying an individual at risk of, or in need of treatment for, an IL-17-dependent condition, which kit comprises a reagent or reagents for measuring the level or expression of one or more of the following: IL6, PLA2G2A, IL19, PI3, CST7, IL17A, IL17F, GH1, MZB1, IL1B, IFNG, TNC, CXCL9, SLAMF7, VEGFA, IL17C, SLAMF1, SDC1, OSM, LBP, REG3A, CD79B, COL4A1, CLEC4D, VWF, IL5RA, CSF3, TGFA, IL2RA, ITIH3, FCAR, CCL23, NRCAM, RETN, SERPINA11, CLEC4G, CSF1, HGF, CRELD2, EFEMP1, LTBR, ​​NME3, CKAP4, CD276, SPON2, GGH, TIMP1, LY9, MCFD2, TCN2, QPCT, HYOU1, TNSFSF13B, CCL2, CCL3, CCL4, CCL5, CCL7, CCL20, CXCL1, CXCL8, PDFGA, CXCR2, CCR6, CXCL13, PCDH1, BOC, MEPE, ADAM23, THOP1, IL1RL2, RCOR1 and EDAR.

[0067] Such a kit as described above may additionally comprise packaged components for obtaining a biological sample from an individual, preferably for obtaining a skin sample or fluid sample. Petition 870260065164, dated 02 / 07 / 2026, page 29 / 213 / 85 bodily fluid, optionally where the bodily fluid sample is a blood sample.

[0068] Kits such as those above may comprise an adhesive strip for obtaining a skin sample or packaged components for obtaining a punch biopsy, microbiopsy, or surgical specimen.

[0069] Also described herein is a kit for treating an IL-17 dependent dermatological condition, wherein the kit comprises a pharmaceutical composition comprising an IL-17A and / or IL-17F inhibitor and a reagent for measuring the level or expression of IL-6, PLA2G2A, IL-19, PI-3, CST-7, IL-17A, IL-17F, GH-1, MZB-1, IL-1B, IFNG-1, TNC-1, CXCL-9, SLAMF-7, VEGFA-1, IL-17C, SLAMF-1, SDC-1, OSM-1, LBP-1, REG3A-1, CD79B-1, COL4A1-1, CLEC4D-1, VWF-1, IL5RA-1, CSF3-1, TGFA-1, IL2RA-1, ITIH3-1, FCAR-1, CCL23-1, NRCAM-1, RETN-1, SERPINA11-1, CLEC4G-1, CSF1-1, HGF-1, CRELD2-1, EFEMP1-1, LTBR-1, NME3-1, CKAP4, CD276, SPON2, GGH, TIMP1, LY9, MCFD2, TCN2, QPCT, HYOU1, TNSFSF13B, CCL2, CCL3, CCL4, CCL5, CCL7, CCL20, CXCL1, CXCL8, PDFGA, CXCR2, CCR6, CXCL13, PCDH1, BOC, MEPE, ADAM23, THOP1, IL1RL2, RCOR1 and / or EDAR, in a sample taken from an individual. BRIEF DESCRIPTION OF THE DRAWINGS

[0070] Figures 1A-1D. Onset and clinical location of hidradenitis suppurativa (HS).

[0071] Figure 1A. Sebaceous glands (top arrow in Figure 1A) release their secretion into hair follicles (also called follicle-pilosebaceous units or FPSUs). HS affects hair follicles that also contain apocrine glands (bottom arrow in Figure 1A). Both glands connect to the hair follicle in the microanatomical compartment called the infrainfundibulum.

[0072] Figure 1B. Location of the micro-anatomical compartment called the infrainfundibulum (area “B” in Figure 1B). Hyperkeratinization Petition 870260065164, dated 02 / 07 / 2026, page 30 / 213 / 85 in this area (marked with arrows in Figure 1B) is considered an initial event in the pathophysiology of HS, leading to obstruction and accumulation of glandular products in the affected follicle. Image in Figure 1B at https: / / plasticsurgerykey.com / the-folliculopilosebaceous-unit-the-normalfpsu / ; Accessed June 2017; von Laffert M et al. Br J Dermatol 164:367-71, 2011

[0073] Figure 1C. Follicle affected by HS. Consequently, HS primarily affects those areas of the body that contain apocrine glands.

[0074] Figure 1D. Areas of the body that contain apocrine glands.

[0075] Figure 2. Immune-mediated progression of HS. Follicular hyperkeratosis and obstruction (clinical correlate: acneiform lesions) lead to alterations in the local microbiome and bacterial superinfection along with initial activation of immune mechanisms (activation of antigen-presenting cells, such as dendritic cells and macrophages) and neutrophil influx (clinical correlate: folliculitis and perifolliculitis). Advanced folliculitis and hair follicle rupture are accompanied by intensification of inflammation (influx and activation of lymphocytes such as T cells and neutrophils) and lead to the formation of superficial nodules. A pathophysiological “vicious circle” arises in which products released by immune cells, such as IL-17A and IL-17F, activate keratinocytes to release chemoattractant mediators, such as CXCL1, CXCL8, and CCL20, which further intensify the influx and activation of immune cells; deep inflammatory lesions (clinical correlate: abscesses) develop.Inflammatory tissue and follicle destruction lead to dermal scarring and tunnel formation. These dermal tunnels can connect deep follicles, but they can also connect to the skin surface. Probably as a consequence of stem cell activation in the outer root sheath of the hair follicle protrusion region, these tunnels become epithelialized; the keratinocytes around the tunnels will respond to activation by IL-17A and IL-11. 17F, attracting neutrophils to the tunnel lumen (clinical correlate: drainage tunnels) and further increasing inflammation in the deep dermis. Hurley stages primarily describe the absence (Stage I) or presence of some (Stage II) or multiple tunnels and scars (Stage III). Hurley stages II and III are typically used in clinical development to define moderate to severe HS.

[0076] Figure 3. The “vicious circle” of HS pathophysiology: the main cellular participants and the central role of IL-17A and IL-17F in immune system-mediated progression of HS. The interaction between immune cells and keratinocytes plays a crucial role in the initiation and perpetuation of HS. IL-17A and IL-17F (released from various cellular sources, including CD4+ and CD8+ T cells, γδ T cells, group 3 innate lymphoid cells, mucosa-associated invariant T cells (MAITs)) are the main cytokines that activate keratinocytes in HS. Activated keratinocytes proliferate (upregulation of, for example, Ki-67 and lipocalin-2) and produce chemoattractant mediators (or chemokines) that stimulate the influx of immune cells into HS lesions.For example, chemokines that stimulate the influx of immune cells are CXCL1 and CXCL8, which attract neutrophils, one of the most prominent immune cells involved in HS, and CCL20, which intensifies the influx of more T cells capable of producing IL-17 (Th17 cells). The chemokine-mediated influx of antigen-presenting cells (such as CD11c+ dendritic cells), T cells, and neutrophils intensifies cutaneous inflammation, resulting in the secretion of more IL-17A and IL-17F.

[0077] Figure 4. Clinical phenotypes of the different stages of HS (which may present simultaneously in the same patient). Early HS is typically distinguished by acneiform lesions and folliculitis, while more advanced HS presents with larger, more superficial (nodules) or deep (abscesses) inflammatory lesions. Patients with chronic destructive HS Petition 870260065164, dated 02 / 07 / 2026, page 32 / 213 / 85 frequently shows varying degrees of scarring and tunneling. Active (draining) tunnels that connect to the skin secrete pus (neutrophils from the tunnel lumen) onto the skin surface – one of the most bothersome aspects of HS for affected patients.

[0078] Figures 5A-5B. Current concept of the main events in the pathophysiology of chronic HS.

[0079] Figure 5A. Immune cells are activated by antigen-presenting cells, such as Langerhans cells in the epidermis and dendritic cells in the dermis. The main mediators released by activated immune cells, such as T cells, are IL-17A and IL-17F. Both cytokines cooperatively activate keratinocytes to proliferate (upregulation of the proliferation marker Ki-67 and formation of psoriasis-like epidermal hyperplasia) and release chemoattractant mediators such as CXCL1 and CXCL8. IL-17A and IL-17F also activate other pro-inflammatory pathways in keratinocytes, including autocrine secretion that intensifies inflammation of IL-36 and IL-17C. CXCL1, CXCL8, and other chemokines induced in keratinocytes by IL-17A and IL-17F regulate the influx of inflammatory cells, such as neutrophils and T cells, into HS lesions.Keratinocytes surrounding deep neo-epithelialized dermal tunnels represent de novo targets of IL-17A and IL-17F, further intensifying inflammation in the dermis and the influx of neutrophils into the lumen of the tunnels (underlying “drainage” tunnels). Image adapted from Navrazhina K, et al. J Allergy Clin Immunol 2021;147:2213-24.

[0080] Figure 5B. Quantitative RT-PCR demonstrates higher levels of IL-17A and IL-17F mRNA in the dermis compared to the epidermal compartment in HS lesions, indicating maximum inflammatory activity around the dermal tunnels.

[0081] Figure 6. Experimental approach for the identification of IL-17i biomarkers relevant to HS and the distinction of properties of Petition 870260065164, dated 02 / 07 / 2026, page 33 / 213 / 85 specific molecular targets. Punch biopsies of specific HS phenotypes (perilesional tissue, nodule-containing tissue, tunnel-containing tissue) were obtained from larger surgical specimens of patients undergoing surgery for HS. The biopsies were first subjected to imaging visualization [H&E staining, for example, to identify nodules and tunnels, multichannel immunofluorescence (IF) to distinguish keratinocyte activation and immune cell infiltrate (see Workflow in (i))]. The biopsies were then subjected to protein lysate and mRNA extraction which were additionally analyzed by multiple cytokine array or ELISA and analyses by bulk RNA sequencing and quantitative RT-PCR (see Workflow in (ii) and (iii)).Finally, selected perilesional and tunnel-containing biopsies were used in air-liquid interface organ culture to test the penetration and specific anti-inflammatory effects of IL-17 inhibitory therapeutic molecules (IL17i) (see Workflow in (iv)). Keratinocytes were then exposed to different IL-17 dimers to test the specific pro-inflammatory effects of IL-17A and IL-17F (see Workflow in (v)). Different IL-17i therapeutic molecules were added to evaluate the specific inhibitory potential at different concentrations of these molecules (see Workflow in (vi)). Separately, peripheral blood was collected from HS patients before and after treatment with an IL-17 inhibitor (IL17i), along with peripheral blood collection from healthy controls. Proteomics (Olink®) was used to identify biomarkers for HS in more detail (see Workflow in (vii)).

[0082] Figure 7. Experimental procedure for evaluating biomarkers in peripheral blood. Blood samples were collected from individuals with HS participating in a clinical trial (n=234) and from healthy age- and sex-matched controls (n=50). Clinical trial samples were collected at baseline and after 12 weeks of IL treatment. Petition 870260065164, dated 02 / 07 / 2026, page 34 / 213 / 85 17i or placebo were analyzed using the Olink® proteomics platform, specifically the Explore 384 Inflammation and 384 Cardiometabolic panels. Over 700 peripheral blood proteins were investigated. NPX, Normalized Protein eXpression, is an arbitrary unit that uses a Log2 scale to identify variations in protein levels across different datasets.

[0083] Figure 8A-8F. Validation of biopsy material used for the identification of IL-17i biomarkers relevant to HS.

[0084] Figure 8A. Biopsies were investigated by hematoxylin and eosin (H&E) staining and multichannel immunofluorescence. Microscopic analysis confirmed the presence of HS-specific phenotypes (nodules and / or tunnels) in the biopsies obtained.

[0085] Figure 8B. Tunnel activation (drainage) was confirmed by H&E and the demonstration of MPO+ neutrophils in the tunnel lumen.

[0086] Figure 8C. The activation of keratinocytes, typical of HS (compare Figures 3 and 5A), was confirmed by upregulation of Ki-67 and lipocalin-2 expression in the epithelium above the HS nodule.

[0087] Figure 8D. Shows perilesional tissue documenting the typical influx of immune cells (e.g., CD3+ T cells, CD11c+ dendritic cells; compare Figures 3 and 5A).

[0088] Figure 8E. Shows an active nodule documenting the typical influx of immune cells (e.g., CD3+ T cells, CD11c+ dendritic cells; compare Figures 3 and 5A).

[0089] Figure 8F. Shows the presence of T cells containing IL-17A and / or IL-17F among the infiltrating immune cells.

[0090] Figures 9A-9V. Biomarkers in tissue and blood for HS disease tunneling activity. mRNA. Crude normalized mean ± SEM (seq. RNA) counts from patient biopsies (n=4-5) in the respective Petition 870260065164, dated 02 / 07 / 2026, page 35 / 213 / 85 skin compartments. Tissue protein: Mean ± SEM of cytokine protein levels in punch biopsy lysates from the perilesional region and HS lesion (n=7). Kruskal-Wallis test and uncorrected Dunn test p-values. Peripheral blood protein: Scatter plot of significant proteins associated with drainage tunnel count. Kruskal-Wallis test and uncorrected Dunn test p-values; ***P<0.001; **P<0.01; *P<0.05.

[0091] Figure 9A - Presents the biomarkers Interleukin-6 (IL6), Interleukin-19 (IL19) and Elafin (P13).

[0092] Figure 9B - Presents the biomarkers Cystatin-F (CST7), Marginal zone B and B cell-specific protein (MZB1) and Interleukin-1B (IL1B).

[0093] Figure 9C - Presents the biomarkers IFN-γ (IFNG), Tenascin C (TNC) and Chemokine Ligand 9 with CXC motif (CXCL9).

[0094] Figure 9D - Presents the biomarkers SLAM family member 7 (SLAMF7), Vascular endothelial growth factor A, long form (VEGFA) and Interleukin 17C (IL17C).

[0095] Figure 9E - Presents the biomarkers Lymphocyte activation signaling molecule (SLAMF1), Oncostatin-M (OSM) and Lipopolysaccharide binding protein (LBP).

[0096] Figure 9F. Presents the biomarkers B cell antigen receptor complex-associated protein beta chain (CD79B), Collagen (IV) alpha-1 chain (COL4A1) and Lectin type C domain family, 4 members D (CLEC4D).

[0097] Figure 9G. Presents the biomarkers von Willebrand factor (VWF), Interleukin 5 receptor alpha subunit (IL5RA), and Granulocyte colony-stimulating factor (CSF3).

[0098] Figure 9H. Presents the biomarkers Interleukin-2 receptor alpha subunit (IL2RA), Interleukin-2 inhibitor H3 heavy chain Petition 870260065164, dated 02 / 07 / 2026, page 36 / 213 / 85 alpha-trypsin (ITIH3) and Fc receptor for immunoglobulin alpha (FCAR).

[0099] Figure 9I. Presents the biomarkers Neuronal Cell Adhesion Molecule (NRCAM), Resistin (RETN) and Hepatocyte Growth Factor (HGF).

[00100] Figure 9J. Presents the biomarkers Creld2 disulfide isomerase protein (CRELD2), CD276 antigen (CD276) and metalloproteinase inhibitor 1 (TIMP1).

[00101] Figure 9K. Presents the biomarkers T lymphocyte surface Ly-9 antigen (LY9), Transcobalamin-2 (TCN2) and Hypoxia-regulated upregulated protein 1 (HYOU1).

[00102] Figure 9L. Shows the biomarker Interleukin-17A (IL17A).

[00103] Figure 9M. Shows the biomarker Interleukin-17F (IL17F).

[00104] Figure 9N. Presents the biomarkers Somatotropin (GH1), Syndecan 1 (SDC1) and Transforming Growth Factor alpha (TGFA).

[00105] Figure 9O. Presents the biomarkers C-type lectin domain family, 4 G members (CLEC4G), Macrophage colony-stimulating factor 1 (CSF1) and Regenerating islet-derived protein 3-alpha (REG3A).

[00106] Figure 9P. Shows the biomarkers Cytoskeletal-associated protein 4 (CKAP4), Spondin-2 (SPON2) and Gamma-glutamyl hydrolase (GGH).

[00107] Figure 9Q. Presents the biomarkers Protocadherin-1 (PCDH1), CDO Brother (BOC) and Extracellular Matrix Phosphoglycoprotein (MEPE).

[00108] Figure 9R. Presents the biomarkers REST co-repressor 1 (RCOR1) and EDAR Member of the tumor necrosis factor receptor (EDAR) superfamily. Petition 870260065164, dated 02 / 07 / 2026, page 37 / 213 / 85

[00109] Figure 9S - Presents the biomarkers Chemokine containing CC motif 4 (CCL4), Chemokine ligand containing CC motif 5 (CCL5) and Chemokine 20 containing CC motif (CCL20).

[00110] Figure 9T - Presents the biomarkers Growth-regulated protein alpha (CXCL1), Chemokine 8 containing CXC motif (CXCL8) and Platelet-derived growth factor subunit A (PDGA).

[00111] Figure 9U - Shows the biomarkers Chemokine 2 containing CC motif (CCL2) and Chemokine 3 containing CC motif (CCL3).

[00112] Figure 9V - Shows the biomarkers Chemokine Ligand 7 with CC motif (CCL7) and Chemokine 13 containing C-XC motif (CXCL13).

[00113] Figure 10. Biomarkers in tissue and blood for HS disease and tunneling activity. Upregulation of biomarkers in lesioned tissue is not limited to the chemokines CCL20 and CXCL8, but also extends to their receptors. mRNA: Mean ± SEM normalized crude counts (seq. RNA) of patient biopsies used for array of proteins that qualify for Seq. RNA (4-5 / 7) in the respective skin compartments. Protein: Mean ± SEM of cytokine protein levels in punch biopsy lysates in the perilesional region and in HS lesions (n=7). Kruskal-Wallis test and Dunn's test p-values ​​uncorrected, ***P<0.001. ** P <0.01. * P <0.05.

[00114] Figure 11. The soneloquinumab (SLK) nanobody exhibits high affinity for IL-17A / A and an equally high affinity for IL-17F / F, unlike the bimekizumab antibody which shows a higher affinity for IL-17A / A but a lower affinity for IL-17F / F. The surface plasmon resonance (SPR) assay compares the equilibrium dissociation constant (KD) between the secukinumab antibody that inhibits IL-17A, the bimekizumab antibody that inhibits IL-17A and IL-17F, and the soneloquinumab nanobody that inhibits IL-17A and IL-17F. KD describes the concentration at Petition 870260065164, dated 02 / 07 / 2026, page 38 / 213 / 85 where half of all binding sites are occupied (under equilibrium conditions, i.e., when the association and dissociation rate constants are equal). When comparing the Kds of two molecules, a smaller Kd indicates a higher affinity.

[00115] Figure 12. Tetrameric modeling of soneloquimab. The modeling indicates simultaneous binding of two IL-17 dimers and human serum albumin with preferential binding of IL-17F-containing dimers.

[00116] Figure 13. Sonelokinumab inhibits interactions of IL-17 dimers with their respective high-potency receptors. Protein-protein interaction assay of IL-17 dimers with IL-17 receptor chains. IC50 analyses demonstrate high inhibitory potency of sonelokinumab with a 100-fold difference in IC50 between sonelokinumab and the IL-17A inhibitor antibody secukinumab.

[00117] Figure 14. Treatment with soneloquimab leads to greater IL-17 target binding capacity in synovial fluid than an IL-17A and IL-17F binding antibody in a primate “human PsA” model. Arthritis was induced in n~50 female Cynomolgus monkeys, and the treatment arms included the IL-17A and IL-17F inhibitor soneloquimab nanobody and an IL-17A and IL-17F inhibitor mAb. IL-17A (left bar graph) and IL-17F (right bar graph) binding capacity were determined in the synovial fluid of affected animals 8 weeks after immunization (collagen-induced arthritis). Treatment doses with the nanobody and antibody were corrected for the different molecule size (soneloquimab 2.8 mg / kg, anti-IL-17A / F mAb 10 mg / kg). The binding capacity of IL-17A and IL-17F in synovial fluid was much greater in animals treated with the nanobody, indicating preferential accumulation in inflamed joints compared to the antibody.This difference was associated with a better clinical response (upper right panel). Joints. Petition 870260065164, dated 02 / 07 / 2026, page 39 / 213 / 85 evaluated for the determination of the Arthritis Score. Joints with scores are indicated (circles) for the large joints (upper panel), for limb joints (middle panel) and hind leg joints (lower panel). DIP, distal interphalangeal joint; PIP, proximal interphalangeal joint; MCP, metacarpophalangeal joint; MTP, metatarsophalangeal joint; 2 mAb Exp IL-17A and IL-17F (Novimmune); SLK=soneloquimab.

[00118] Figures 15A-15B. Direct evidence of disease modification with IL-17i.

[00119] Figure 15A. Following a 2-week SLK regimen, a significant number of patients achieved complete resolution of drainage tunnels (DT100), in contrast to those who received placebo. The percentage of patients who achieved complete resolution of drainage tunnels reached 49% after 24 weeks of treatment.

[00120] Figure 15B. Ultrasound images showed a substantial change in the size and shape of the drainage tunnels (indicated by dashed straight lines) in a patient undergoing IL-17i treatment. The dotted circles highlight the increased blood flow due to inflammation, a defining characteristic of the tissue surrounding HS tunnels. After a 24-week course of IL-17i treatment, there was a notable decrease in inflammation around the drainage tunnels, as evidenced by the reduced size of the dotted circles.

[00121] Figure 16. IL-17F is highly upregulated in HS lesions compared to perilesional tissue and is more abundant than IL-17A. IL-17A and IL-17F levels were measured by multiple cytokine array in biopsies from the perilesional region of HS and in defined HS lesions (nodules, tunnels). Compared to psoriasis (protein levels measured with a different technique in interstitial fluid in the dermis; ref. 1), IL-17F Petition 870260065164, dated 02 / 07 / 2026, page 40 / 213 / 85 showed more upregulation in the region with HS lesion versus the perilesional region of HS than in the region with lesion versus the region without psoriasis lesion. In HS lesions (nodules and tunnels), IL-17F was more abundant than IL-17A with observed protein ratios of approximately 1.5 to 2.2. Mean ± SEM of cytokine expression levels in punch biopsy lysates in the perilesional (PL) region and HS lesion (n=7 independent patients with two replicated technical measurements). Differences in IL-17F protein levels were significantly different between the perilesional region and nodules and tunnels, respectively (Kruskal-Wallis test and uncorrected Dunn test, p<0.05). Ref. 1 = Data from Kolbinger et al. J Allergy Clin Immunol 2017;139:923-932; the differences between lesioned and non-lesioned (NL) regions of PsO were not significant (p>0.05).

[00122] Figure 17. IL-17F potentially activates human keratinocytes, independently of IL-17A, to release inflammatory mediators that are upregulated in HS. IL-17F stimulates the production of CCL20, an important chemoattractant for Th17 cells, and CXCL8, a chemokine essential for neutrophils, in keratinocytes. mRNA data are shown as mean ± SEM of n=3 independent experiments after stimulation for 6 hours. Gene expression of CCL20 and CXCL8 is provided in fold change versus TNF (defined as “1”) after normalization with GAPDH.

[00123] Figure 18. SLK exerts an enhanced inhibitory effect on keratinocytes activated by IL-17 dimers. Percentage of inhibition on mean ± SEM of CCL20 and CXCL8 gene expression induced by IL-17 dimer and TNF stimulation. n=3 independent experiments; normal human primary keratinocytes were treated in vitro for 6 hours with selected combinations of TNF plus IL-17A / A, IL-17A / F or IL-17F / F dimers in combination with varying concentrations of an IL-17i. qRT PCR conducted with GAPDH as the housekeeping (constitutive) gene of Petition 870260065164, dated 02 / 07 / 2026, page 41 / 213 / 85 reference. Average of n=3 independent experiments. SLK, soneloquimab.

[00124] Figure 19. Experimental approach to investigate specific inhibitory effects of an IL-17i on the expression of relevant IL-17 biomarkers in HS organ cultures. To further investigate the inhibitory effects observed with soneloquimab on the expression of IL-17-induced chemokines in human keratinocytes, biopsies from the perilesional region (control) and biopsies from defined HS phenotypes (nodules, tunnels) were cultured for 24 hours under air-liquid interface conditions in the presence or absence of soneloquimab. Material was obtained for quantitative analysis of mRNA and protein expression levels of chemokines in tissue culture supernatant.

[00125] Figure 20. Evidence that an IL17 inhibitor nanobody inhibits the release of relevant IL-17i biomarkers in organ cultures from HS lesion regions. The figure illustrates the mRNA expression levels of CCL20 (left panel) and CXCL8 (right panel) in the perilesional skin sample. Furthermore, it highlights the increased expression of CCL20 and CXCL8 in HS lesions containing tunnels, and how the expression of both is reduced to levels comparable to those observed in perilesional HS samples when treated with IL-17i soneloquimab. The relative mRNA expression levels of CCL20 and CXCL8 (mean ± SEM) were measured by qRT-PCR in air-liquid interface cultures of perilesional and tunnel biopsies from n=4 independent donors after 24-hour ex vivo treatment with SLK 10 pg / mL or vehicle buffer (VEH).The average expression of the HECT, UBA, and WWE domains containing the E3 Ubiquitin Ligase 1 (HUWEI1) protein, and Microtubule-actin crosslinking factor 1 (MACF1) was used as the internal housekeeping reference.

[00126] Figure 21. Pharmacodynamic biomarkers: After treatment with an IL-17i, the levels of circulating biomarkers Petition 870260065164, dated 02 / 07 / 2026, page 42 / 213 / 85 related to HS activity were normalized to those verified in a healthy control population, indicating molecular cure (n = 50). Significant downregulation of Elafin (left) and IL-19 (right), from Baseline to Week 12 after treatment with soneloquimab. HC, healthy controls; SLK, soneloquimab; ADA, adalimumab. Paired t-test, *** P <0.001. ** P <0.01. * P <0.05.

[00127] Figure 22. Biomarkers to identify super-responders with HS to IL-17i: LOT1, IL-17A+TNC, G-CSF, OSM, PLA2G2A. Subgroup Identification based on Differential Effect Search (SIDES) was employed as a partitioning method to determine treatment responses within specific patient groups. Subgroups of patients with higher biomarker levels demonstrated improved clinical outcome, as evidenced by the delta relative to placebo in response to HiSCR75 when compared to unselected patients. Applied threshold (NPX): LOT1 > -0.4123; IL-17A > -0.8321; TNC > -0.0153; CSF3 > -0.2455; OSM > -0.4974; PLA2G2A > 0.6373; CST7 > -0.628. DETAILED DESCRIPTION OF THE INVENTION

[00128] The details shown in this descriptive report are by way of example and only for the purpose of illustrating the various modalities and are presented in the interest of what is believed to be the most useful and quickly understood description of the principles and conceptual aspects of the methods and compositions described herein. In this respect, no attempt is made to show more detail than is necessary for a fundamental understanding, the description making it clear to those skilled in the art how the various forms can be incorporated into practice.

[00129] The present invention will now be described by reference to more detailed embodiments. This invention may, however, be incorporated Petition 870260065164, dated 02 / 07 / 2026, page 43 / 213 / 85 in different forms and should not be interpreted as limited to the modalities presented here. Instead, these modalities are provided so that this description may be thorough and complete, and will express the scope for those skilled in the art.

[00130] Unless defined otherwise, all technical and scientific terms in this descriptive report have the same meaning as commonly understood by any person skilled in the art to which this invention pertains. The terminology used in this description is only for the purpose of describing specific embodiments and is not intended to be limiting. In this descriptive report and the appended claims, the singular forms “a”, “an”, “the” and “the” are intended to include the plural forms as well, unless the context clearly indicates otherwise. All publications, patent applications, patents and other references mentioned herein are expressly incorporated, in their entirety, by reference.

[00131] Unless otherwise indicated, the numerical parameters set forth in the following descriptive report and appended claims are approximations that may vary depending on the desired properties sought to be obtained and, therefore, may be modified by the term “around”. At a minimum, and not as an attempt to limit the application of the doctrine of equivalents to the scope of the claims, each numerical parameter should be interpreted in light of the number of significant digits and common rounding approaches.

[00132] Although the ranges and numerical parameters establishing the extended scope are approximations, the numerical values ​​established in the specific examples are reported as accurately as possible. Any numerical value, however, inherently contains certain errors necessarily resulting from the standard deviation verified in its respective test measurements. Each numerical range provided throughout this descriptive report will include every narrower numerical range that falls within it. Petition 870260065164, dated 02 / 07 / 2026, page 44 / 213 / 85 of such a wider numerical range, as if such narrower numerical ranges had been expressly written in this descriptive report. The Petitioner also contemplates ranges derived from data points and ranges expressly described herein. DEFINITIONS

[00133] In this descriptive report, “treatment” and / or “treat” and / or “treats” refers to all methods or schemes in which there may be a slowing, interruption, halting, prevention, or reversal of the progression of the disorders described herein. However, these terms do not necessarily indicate a total elimination of all symptoms of the disorder subject to treatment. Treatment includes the administration of medication for the treatment of a disease or condition in an individual who would benefit, for example, from a reduction in the activity of an elevated biomarker. In this way, treatment may include inhibiting further disease progression, i.e., halting its development, and / or attenuating the disease, i.e., causing regression of the disease or disorder or alleviating symptoms or complications thereof.

[00134] In this descriptive report, an “IL17-dependent condition” refers to diseases, disorders, or conditions that are mediated by IL-17 and may include autoimmune, inflammatory, or neurological diseases. IL-17-dependent conditions, as contemplated herein, preferentially include, but are not limited to, skin diseases, and include, for example, psoriasis, psoriatic arthritis, rheumatoid arthritis, and inflammatory skin diseases, including non-reportable Type III inflammatory skin diseases. Type III diseases are defined by Th17 immunity and the presence of neutrophils in the skin and include psoriasis, including pustular psoriasis, guttate psoriasis, pityriasis rubra pilaris, acne and acneic syndromes, hidradenitis suppurativa, and folliculitis decalvans.

[00135] In this descriptive report, “drainage tunnel” or “tunnel Petition 870260065164, dated 02 / 07 / 2026, page 45 / 213 / 85 active” refers to a symptom of moderate to severe HS in which epithelialized tissue forms one or more tunnel-like openings in the dermis, optionally connecting with the skin surface, and in which the opening is actively draining, i.e., containing pus that may be discharged onto the skin surface.

[00136] A “healthy control,” in this descriptive report, may refer to the determined level of one or more biomarkers in an unaffected biological sample comprising one or more of the biomarkers. The biological sample may be isolated from the same individual suffering from the disease within the meaning of the present invention, but from a part of the body without any signs or symptoms associated with the disease. Alternatively, the biological sample may be taken from another healthy individual from a corresponding part of the body where the patient suffering from the disease exhibits the distinguished symptoms. The method for collecting tissue, blood samples, RNA extraction, and protein isolation are well known to those skilled in the art. Examples of suitable methods are shown in this descriptive report.

[00137] A “derivative” of a polypeptide (e.g., nanobody), as described herein, may include one or more amino acid substitutions, additions, insertions, or deletions compared to the reference polypeptide, for example, 1, 2, 3, 4, 5, 6-20 or 21-50 amino acid substitutions, additions, insertions, or deletions. Alternatively, the “derivative” may have a certain percentage of sequence identity with the reference polypeptide and / or include amino acid substitutions, additions, insertions, or deletions as described elsewhere in this document.

[00138] Biomarkers, biomarker combinations and corresponding methods

[00139] In this document, we describe the identification of Petition 870260065164, dated 02 / 07 / 2026, p. 46 / 213 / 85 biomarkers with abnormal expression in peripheral blood and / or in HS lesions that allow the evaluation of the immunological activity of the disease and, especially, of HS and active tunnels in patients with HS. We also describe how the biomarkers can be used to monitor the molecular immune response to drugs that inhibit IL-17 and to identify patients with preferential responses (so-called super-responders) to drugs that inhibit IL-17 such as soneloquimab. The biomarkers, as contemplated herein, include “analytes” determined by the methods as described herein and by methods of the invention. A biomarker as contemplated and described herein may, however, be used as such, i.e., as a functional biomarker for the diseases and / or conditions described herein.

[00140] Whether one or more biomarkers or a panel / combination of biomarkers is most appropriate within the meaning of the invention may depend on the individual, the stage of the disease and the individual phenotype. Suitable biomarkers within the meaning of the invention are provided herein, from which any combination of one, two, three, four, five, six, seven, eight, nine, ten or more biomarkers may be used.

[00141] Notably, the expression of the following biomarkers was observed to be elevated in HS: IL6, PLA2G2A, IL19, PI3, CST7, IL17A, IL17F, GH1, MZB1, IL1B, IFNG, TNC, CXCL9, SLAMF7, VEGFA, IL17C, SLAMF1, SDC1, OSM, LBP, REG3A, CD79B, COL4A1, CLEC4D, VWF, IL5RA, CSF3, TGFA, IL2RA, ITIH3, FCAR, CCL23, NRCAM, RETN, SERPINA11, CLEC4G, CSF1, HGF, CRELD2, EFEMP1, LTBR, ​​​​NME3, CKAP4, CD276, SPON2, GGH, TIMP1, LY9, MCFD2, TCN2, QPCT, HYOU1, TNSFSF13B, CCL2, CCL3, CCL4, CCL5, CCL7, CCL20, CXCL1, CXCL8, PDFGA, CXCR2, CCR6 and CXCL13.

[00142] In contrast, the expression of the following biomarkers was observed to be reduced in HS: PCDH1, BOC, MEPE, ADAM23, THOP1, Petition 870260065164, dated 02 / 07 / 2026, page 47 / 213 / 85 IL1RL2, RCOR1 and EDAR.

[00143] Biomarkers for use herein may include any selected from Table 1 or wild-type proteins homologous to those described in Table 1. Isoforms and variants thereof are also contemplated. For example, a sequence homologous to the amino acid sequence represented by SEQ ID NO: 1 may function as a biomarker for an IL-17-dependent condition as described herein, and may be a protein that has the same amino acid sequence as the amino acid sequence represented by SEQ ID NO: 1 except that one or more amino acids are deleted, substituted, inserted and / or added. In the case of substitution, insertion or addition, conservative mutations resulting from the conservative substitution, insertion or addition of one or more amino acids are possible. “One or more amino acids” herein means 1 to 50, preferably 1 to 20, more preferably 1 to 10, even more preferably 1 to 5 or 1 to 3 amino acids.

[00144] Furthermore, by way of example, a protein with an amino acid sequence homologous to the sequence represented by SEQ ID NO: 1 includes a protein that has an amino acid sequence with an identity of not less than 60% with the amino acid sequence represented by SEQ ID NO: 1, in its complete form. The protein includes a protein that has an amino acid sequence with an identity of not less than 70%, preferably not less than 80%, more preferably not less than 90%, and even more preferably not less than 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% with the amino acid sequence described above in its complete form. The same applies to the other SEQ ID NOs: 2-73, to other biomarkers, as contemplated herein, and to nucleic acid sequences that encode such biomarkers or sequences.

[00145] “Sequence identity” can refer, in nucleotide sequences or amino acid sequences, to the percentage of nucleotides Petition 870260065164, dated 02 / 07 / 2026, p. 48 / 213 / 85 or identical amino acids shared between two sequences, the percentage of which is determined by aligning those two sequences in an optimal pairwise alignment, optionally using a conventional or commercially available algorithm.

[00146] Methods for treating an IL-17-dependent condition are described herein, comprising administering a drug, comprising a nanobody that inhibits IL-17A and / or IL-17F, to an individual, wherein the individual has been identified as having an elevated level of one or more biomarkers selected from among IL6, PLA2G2A, IL19, PI3, CST7, IL17A, IL17F, GH1, MZB1, IL1B, IFNG, TNC, CXCL9, SLAMF7, VEGFA, IL17C, SLAMF1, SDC1, OSM, LBP, REG3A, CD79B, COL4A1, CLEC4D, VWF, IL5RA, CSF3, TGFA, IL2RA, ITIH3, FCAR, CCL23, NRCAM, RETN, SERPINA11, CLEC4G, CSF1, HGF, CRELD2, EFEMP1, LTBR, ​​NME3, CKAP4, CD276, SPON2, GGH, TIMP1, LY9, MCFD2, TCN2, QPCT, HYOU1, TNSFSF13B, CCL2, CCL3, CCL4, CCL5, CCL7, CCL20, CXCL1, CXCL8, PDFGA, CXCR2, CCR6 and CXCL13.

[00147] In addition, methods for treating hidradenitis suppurativa (HS) are described herein, comprising administering a drug comprising an IL-17A and / or IL-17F inhibitor to an individual, wherein the individual has been identified as having an elevated level of one or more biomarkers selected from IL6, PLA2G2A, IL19, PI3, CST7, IL17A, IL17F, GH1, MZB1, IL1B, IFNG, TNC, CXCL9, SLAMF7, VEGFA, IL17C, SLAMF1, SDC1, OSM, LBP, REG3A, CD79B, COL4A1, CLEC4D, VWF, IL5RA, CSF3, TGFA, IL2RA, ITIH3, FCAR, CCL23, NRCAM, RETN, SERPINA11, CLEC4G, CSF1, HGF, CRELD2, EFEMP1, LTBR, ​​NME3, CKAP4, CD276, SPON2, GGH, TIMP1, LY9, MCFD2, TCN2, QPCT, HYOU1, TNSFSF13B, CCL2, CCL3, CCL4, CCL5, CCL7, CCL20, CXCL1, CXCL8, PDFGA, CXCR2, CCR6 and CXCL13.

[00148] The use of an agent that connects is also contemplated here. Petition 870260065164, dated 02 / 07 / 2026, p. 49 / 213 / 85 selectively to IL-17A and / or IL-17F in an individual determined to have an elevated level of at least one of the following biomarkers: IL6, PLA2G2A, IL19, PI3, CST7, IL17A, IL17F, GH1, MZB1, IL1B, IFNG, TNC, CXCL9, SLAMF7, VEGFA, IL17C, SLAMF1, SDC1, OSM, LBP, REG3A, CD79B, COL4A1, CLEC4D, VWF, IL5RA, CSF3, TGFA, IL2RA, ITIH3, FCAR, CCL23, NRCAM, RETN, SERPINA11, CLEC4G, CSF1, HGF, CRELD2, EFEMP1, LTBR, ​​NME3, CKAP4, CD276, SPON2, GGH, TIMP1, LY9, MCFD2, TCN2, QPCT, HYOU1, TNSFSF13B, CCL2, CCL3, CCL4, CCL5, CCL7, CCL20, CXCL1, CXCL8, PDFGA, CXCR2, CCR6 and CXCL13, compared to a healthy control, preferably where the elevated level is present in the skin and / or blood.

[00149] Such methods and / or uses may include analyzing a tissue or body fluid sample, preferably a skin or peripheral blood sample, from a patient who has or is at risk of having an IL-17-dependent condition for the level of one or more biomarkers prior to treatment.

[00150] Methods and / or uses such as those described above are contemplated, wherein an elevated level of one or more of the biomarkers indicates that the patient has (i) an inflammatory skin disease, preferably an inflammatory skin disease affecting the epidermis and dermis, more preferably an inflammatory skin disease involving hair follicle structures, even more preferably an inflammatory skin disease involving acneiform lesions, most preferably hidradenitis suppurativa (HS), such as moderate to severe HS and / or (ii) a phenotype that includes one or more drainage tunnels in the skin.

[00151] In modalities, the higher the level of one or more biomarkers, the greater the number of drainage tunnels present in the individual.

[00152] In modalities, the individual may have been clinically Petition 870260065164, dated 02 / 07 / 2026, page 50 / 213 / 85 diagnosed as having HS in Hurley Stage I, II or III.

[00153] In modalities, the individual may have been clinically diagnosed as having mild HS, moderate HS, moderate to severe HS, severe HS, or juvenile HS.

[00154] In one form, the individual may not have drainage tunnels or, alternatively, may have at least one drainage tunnel.

[00155] The biomarkers as described herein may consist of or comprise protein. Alternatively, the biomarkers may consist of or comprise mRNA. Both protein-based and mRNA-based biomarkers are contemplated.

[00156] As contemplated herein, the elevated level of at least one biomarker may be the level present in a biological sample from the individual, and the level of at least one corresponding biomarker present in the healthy control may be representative of the level present in a biological sample not affected by an IL-17-dependent condition, preferably by an IL-17-dependent inflammatory skin disease, more preferably by HS.

[00157] As contemplated herein, biomarkers may be associated with an inflammatory skin disease, preferably an inflammatory skin disease affecting the epidermis and dermis, more preferably an inflammatory skin disease involving hair follicle structures, even more preferably an inflammatory skin disease involving acneiform lesions, most preferably hidradenitis suppurativa (HS).

[00158] In a preferred embodiment, one or more of the biomarkers may be selected from the following biomarker combination: IL6, PLA2G2A, PI3, CST7, IL17A, IL17F, GH1, MZB1, IL1B, IFNG, TNC, CXCL9, SLAMF7, VEGFA, IL17C, SLAMF1, SDC1, OSM, LBP, REG3A, Petition 870260065164, dated 02 / 07 / 2026, p. 51 / 213 / 85 CD79B, COL4A1, CLEC4D, VWF, IL5RA, CSF3, TGFA, IL2RA, ITIH3, FCAR, CCL23, NRCAM, RETN, SERPINA11, CLEC4G, CSF1, HGF, CRELD2, EFEMP1, LTBR, ​​NME3, CKAP4, CD276, SPON2, GGH, TIMP1, LY9, MCFD2, TCN2, QPCT, HYOU1, TNSFSF13B, CCL2, CCL3, CCL4, CCL5, CCL7, CCL20, CXCL1, CXCL8, PDFGA, CXCR2, CCR6 and CXCL13.

[00159] In another preferred embodiment, one or more of the biomarkers may be selected from the following biomarker combination: IL6, PLA2G2A, IL19, PI3, CST7, GH1, MZB1, IL1B, IFNG, TNC, CXCL9, SLAMF7, VEGFA, IL17C, SLAMF1, SDC1, OSM, LBP, REG3A, CD79B, COL4A1, CLEC4D, VWF, IL5RA, CSF3, TGFA, IL2RA, ITIH3, FCAR, CCL23, NRCAM, RETN, SERPINA11, CLEC4G, CSF1, HGF, CRELD2, EFEMP1, LTBR, ​​NME3, CKAP4, CD276, SPON2, GGH, TIMP1, LY9, MCFD2, TCN2, QPCT, HYOU1, TNSFSF13B, CCL2, CCL3, CCL4, CCL5, CCL7, PDFGA, CXCR2, CCR6 and CXCL13.

[00160] In another preferred embodiment, one or more of the biomarkers may be selected from the following combination of biomarkers: CSF3, CCL2, CCL3, CCL4, CCL5, CCL7, CCL20, CXCL1, CXCL8 and PDFGA.

[00161] Methods and uses as above may also be distinguished by an elevated mRNA level or elevated protein level of at least one or more biomarkers selected from the following biomarker combination: CCL20, CXCL8, CXCL1, IL17A and IL17F.

[00162] In embodiments, combinations or panels of biomarkers may be formed based on the physiological function of the biomarker, for example, as described in Table 1. In an exemplary embodiment, the person skilled in the art may determine that a panel of biomarkers associated with neutrophil activation or T cell activation may be advantageous. Replacing one neutrophil-activating biomarker in Table 1 with another Petition 870260065164, dated 02 / 07 / 2026, p. 52 / 213 / 85 of Table 1 in any given combination is also contemplated.

[00163] Methods and uses as described above can be distinguished by an elevated mRNA level or elevated protein level in a skin sample with a lesion, compared to the respective mRNA or protein level in a skin sample without a lesion.

[00164] Methods and uses such as those described above are also contemplated where the individual has been identified as having an inflammatory skin disease, preferably hidradenitis suppurativa, exhibiting an elevated level of one or more biomarkers.

[00165] Methods and uses such as those above are also contemplated, wherein the release of IL-17A and / or IL-17F in Hurley Stage I, II and / or III of hidradenitis suppurativa is inhibited by the agent.

[00166] Methods and uses such as those described above are also contemplated, where the agent is an IL-17A and / or IL-17F inhibitor.

[00167] Methods and uses such as those above are also contemplated, wherein the agent comprises an antibody, an antibody fragment or a nanobody.

[00168] In a preferred embodiment, methods and / or uses such as those above are contemplated wherein the agent is a nanobody, preferably soneloquimab or a derivative thereof, and a biomarker panel comprises a) CCL20, CXCL1, CXCL8, CXL1, IL17A, IL17F, IL19, LT01, CSF3, OSM, PLA2G2A, CST7 and / or PI3, b) IL17A, IL17F, CCL20, CXCL1, and / or CXCL8, c) IL17A, IL17F, CCL20 and / or CXCL8, d) LT01, IL17A + TNC, CSF3, OSM, PLA2G2A and / or CST7, e) CCL20, CXCL8, IL19 and PI3; or f) PI3 and IL19.

[00169] In one embodiment, such methods and / or uses may further comprise comparing the expression level of at least one biomarker in a skin sample with lesions from the individual with the expression level of at least one biomarker in a healthy skin sample from the Petition 870260065164, dated 02 / 07 / 2026, page 53 / 213 / 85 individual and determine that the individual is a carrier or at risk of being a carrier of HS if one or more of the biomarkers are elevated in the skin sample with lesion compared to the healthy skin sample.

[00170] In addition, methods for treating an IL-17 dependent condition are described herein, comprising administering a drug comprising an IL-17A and / or IL-17F inhibitor to an individual, wherein the individual has been identified as having a reduced level of one or more biomarkers selected from PCDH1, BOC, MEPE, ADAM23, THOP1, IL1RL2, RCOR1 and EDAR.

[00171] Also contemplated here is the use of an agent that selectively binds to IL-17A and / or IL-17F in an individual determined to have a reduced level of at least one of the following biomarkers: PCDH1, BOC, MEPE, ADAM23, THOP1, IL1RL2, RCOR1 and EDAR in the skin and / or blood compared to a healthy control, preferably where the reduced level is present in the skin and / or blood.

[00172] As described above, the IL-17A and / or IL-17F inhibitor may comprise an antibody, antibody fragment, or a nanobody. In embodiments, the nanobody may be configured to bind specifically to IL-17A and IL-17F, preferably the nanobody is SLK.

[00173] As explained above, the reduced level in the individual can be compared to: (i) the level present in uninjured skin, preferably in perilesional skin, (ii) the level present in the peripheral blood of a healthy patient, or (iii) the level in the same individual before initial treatment.

[00174] Alternatively, the reduced level may be compared to a reference value, and the reference value may be (i) the biomarker expression level of the corresponding body fluid or tissue sample obtained from a healthy individual; (ii) the average biomarker level expressed in the corresponding body fluid or tissue of a plurality of healthy individuals; or (iii) the average biomarker level Petition 870260065164, dated 02 / 07 / 2026, p. 54 / 213 / 85 expressed in healthy tissue, preferably healthy tissue from the same individual, more preferably perilesional skin from the same individual.

[00175] In modalities, methods such as the above that involve the use of biomarkers with reduced expression may comprise analyzing a tissue or body fluid sample, preferably a skin or peripheral blood sample, from a patient who has or is at risk of having an IL-17-dependent condition for the level of one or more biomarkers prior to treatment.

[00176] In modalities, a reduced level of one or more of the biomarkers may indicate that the individual has (i) an inflammatory skin disease, preferably an inflammatory skin disease affecting the epidermis and dermis, more preferably an inflammatory skin disease involving hair follicle structures, even more preferably an inflammatory skin disease involving acneiform lesions, most preferably hidradenitis suppurativa (HS), such as moderate to severe HS and / or (ii) a phenotype that includes one or more drainage tunnels in the skin.

[00177] In modalities, the lower the level of one or more biomarkers, the greater the number of drainage tunnels that may be present in the individual.

[00178] Methods such as those described above involving the use of biomarkers with reduced expression are also contemplated, where (i) the individual has been clinically diagnosed as having HS in Hurley Stage I, II or III; (ii) where the individual has been clinically diagnosed as having mild HS, moderate HS, moderate to severe HS, severe HS or juvenile HS; (iii) where the individual does not have drainage tunnels; and / or (iv) where the individual has at least one drainage tunnel.

[00179] As explained above, methods and uses are contemplated in which biomarkers include protein and / or mRNA biomarkers. Petition 870260065164, dated 02 / 07 / 2026, page 55 / 213 / 85

[00180] Treatment methods as contemplated herein may also include methods comprising treating an individual with a lesional IL-17F / non-lesional IL-17F mRNA ratio result equal to or greater than 5, preferably equal to or greater than 10, more preferably equal to 5-500 and, most preferably, equal to 10-300. Here, such methods may comprise administering to the individual an effective amount of an agent configured to inhibit IL-17F present in the dermis of an inflammatory skin lesion of the individual.

[00181] Also contemplated herein is a method for treating hidradenitis suppurativa, comprising administering a medicament comprising an IL-17A and / or IL-17F inhibitor to an individual, wherein the individual has been identified as having elevated levels of one or more biomarkers selected from (a) LTO1, (b) CSF3, (c) OSM, (d) PLA2G2A, or (e) a combination of IL17A and TNC. Diagnostic methods

[00182] Diagnostic methods and methods for, for example, detecting hidradenitis suppurativa (HS) are also contemplated here, which include analyzing a sample from an individual who has or is at risk of having HS for elevated levels of one or more of the following: IL6, PLA2G2A, IL19, PI3, CST7, IL17A, IL17F, GH1, MZB1, IL1B, IFNG, TNC, CXCL9, SLAMF7, VEGFA, IL17C, SLAMF1, SDC1, OSM, LBP, REG3A, CD79B, COL4A1, CLEC4D, VWF, IL5RA, CSF3, TGFA, IL2RA, ITIH3, FCAR, CCL23, NRCAM, RETN, SERPINA11, CLEC4G, CSF1, HGF, CRELD2, EFEMP1, LTBR, ​​NME3, CKAP4, CD276, SPON2, GGH, TIMP1, LY9, MCFD2, TCN2, QPCT, HYOU1, TNSFSF13B, CCL2, CCL3, CCL4, CCL5, CCL7, CCL20, CXCL1, CXCL8, PDFGA, CXCR2, CCR6 and CXCL13; or reduced levels of one or more of PCDH1, BOC, MEPE, ADAM23, THOP1, IL1RL2, RCOR1 and EDAR.

[00183] In modalities, the respective high or low level may Petition 870260065164, dated 02 / 07 / 2026, p. 56 / 213 / 85 to be compared to: (i) the level present in uninjured skin, preferably in perilesional skin, (ii) the level present in the peripheral blood of a healthy patient, or (iii) the level in the same individual before initial treatment.

[00184] In alternative embodiments, the respective elevated or reduced level may be compared to a reference value wherein the reference value is (i) the biomarker expression level of the corresponding body fluid or tissue sample obtained from a healthy individual; (ii) the average biomarker level expressed in the corresponding body fluid or tissue of a plurality of healthy individuals; or (iii) the average biomarker level expressed in healthy tissue, preferably healthy tissue from the same individual, more preferably perilesional skin from the same individual.

[00185] Diagnostic methods as described above may include analyzing a sample of body tissue or fluid, preferably a skin or peripheral blood sample, from a patient who has or is at risk of having HS.

[00186] In modalities, diagnostic methods such as the above may involve identifying an individual who is a carrier or at risk of being a carrier of hidradenitis suppurativa (HS) by determining the IL-17F / IL-17A protein or mRNA ratio present in a tissue sample from the individual.

[00187] Methods are also contemplated here where a ratio of lesional IL-17F protein to non-lesional IL-17F equal to or greater than 2, preferably equal to or greater than 10, more preferably equal to 2-50 and, most preferably, equal to 10-30 indicates that the individual is a carrier or at risk of being a carrier of HS.

[00188] Diagnostic methods are also considered here, where an IL-17F / IL-17A protein ratio equal to or greater than 1.5, preferably a ratio of 1.5-3.0 and, most preferably, a ratio of 1.5-2.2 indicates that the individual is a carrier or is at risk of being a carrier. Petition 870260065164, dated 02 / 07 / 2026, p. 57 / 213 / 85 carrier of HS. In one embodiment, such a method may comprise obtaining a tissue sample from the individual and then measuring the ratio of IL-17F / IL-17A mRNA in the tissue sample obtained.

[00189] Methods for identifying a treatment-responsive individual are also described herein. For example, a method is contemplated for identifying a patient with hidradenitis suppurativa who is responsive to treatment with a nanobody that inhibits IL-17A and / or IL-17F, the method comprising analyzing a biological sample from the patient for the presence of one or more biomarkers selected from (a) LTO1, (b) CSF3, (c) OSM, (d) PLA2G2A, or (e) a combination of IL17A and TNC. The presence of an elevated level of at least one, two, three, or more of the biomarkers indicates that the patient is highly responsive to treatment with a nanobody that inhibits IL-17A and / or IL-17F (so-called superresponders).

[00190] In one embodiment of the above methods for identification, the nanobody may comprise SLK.

[00191] In addition, methods are described here for identifying an individual who has or is at risk of having hidradenitis suppurativa (HS), which include analyzing the expression level of at least one biomarker selected from CCL2, CCL3, CCL4, CCL5, CCL7, CCL20, CXCL1, CXCL8, PDFGAA and CSF3 in a tissue sample from the individual.

[00192] In one embodiment, such methods may comprise analyzing the expression level of at least one biomarker selected from CCL20, CXCL1, and / or CXCL8 in a tissue sample from the individual.

[00193] In another aspect, the biomarkers CCL20, CXCL8, CXCL1, IL17A, and / or IL17F may be sufficient and effective to identify a patient with HS or highly responsive to an agent for the treatment of HS. The person skilled in the art may consider using a biomarker panel comprising IL19, PI3, IL17A, IL17F, CCL7, and / or CCL3. Petition 870260065164, dated 02 / 07 / 2026, page 58 / 213 / 85 a panel of biomarkers comprising LT01, IL17A, CSF3, OSM, PLA2G2A and / or CST7 or any combination of the groups or a different combination of biomarkers from the groups mentioned above for this purpose. In another embodiment, the combination of IL19 and PI3 may be sufficient. The person skilled in the art is free to combine any combination of biomarkers from Table 1 within the meaning of the invention.

[00194] In another embodiment, it is appropriate and advantageous to use a biomarker panel with at least CCL20, CXCL8, CXL1, IL17A and / or IL17F for diagnosis and another biomarker panel for monitoring treatment over time. For those skilled in the art, it is evident that biomarkers representative of the evolution of pathogenesis are not necessarily the same as those used to diagnose an individual at risk of being a carrier of HS or to identify a super-responder.

[00195] In one modality, the expression level of at least CCL20 and CXCL8 can be evaluated for the diagnosis of HS. In another modality, a combination of CCL20, CXCL8, and PI3 can be used for this purpose.

[00196] Also described here is a method for predicting the efficacy of a drug in an individual with an IL-17-dependent dermatological condition, which method comprises: determining the level or protein expression of IL-17F in a skin sample with lesion from the individual and the level or protein expression of IL-17F in a skin sample without lesion from the individual, wherein the drug comprises an agent that inhibits IL-17F; wherein a ratio of lesional IL-17F protein to non-lesional IL-17F equal to or greater than 2, preferably equal to or greater than 10, more preferably equal to 2-50 and, most preferably, equal to 10-30, indicates that the drug will be effective in inhibiting or treating the IL-17-dependent dermatological condition in the individual; and wherein the individual is a human or a non-human animal. Petition 870260065164, dated 02 / 07 / 2026, page 59 / 213 / 85

[00197] Also described herein is a method for predicting the efficacy of a drug in an individual with an IL-17-dependent dermatological condition, which method comprises determining the level or expression of IL-17F mRNA in a skin sample with lesion from the individual and the level or expression of IL-17F mRNA in a skin sample without lesion from the individual, wherein the drug comprises an agent that inhibits IL-17F; wherein a ratio of lesional IL-17F / non-lesional IL-17 mRNA equal to or greater than 5, preferably equal to or greater than 10, more preferably equal to 5-500 and, most preferably, equal to 10-300, indicates that the drug will be effective in inhibiting or treating the IL-17-dependent dermatological condition in the individual; and wherein the individual is a human or a non-human animal.

[00198] In one embodiment, such a method is contemplated here where the IL-17-dependent dermatological condition is hidradenitis suppurativa.

[00199] In one embodiment, the method may additionally comprise administering the medication to the individual.

[00200] Also described herein is a method for predicting the efficacy of a drug in an individual with an IL-17-dependent dermatological condition, which method comprises determining the level or expression of IL-17F and IL-17A present in a tissue sample from the individual before an initial treatment period with the drug; wherein the drug comprises an agent that inhibits IL-17F; wherein an IL-17F / IL-17A ratio equal to or greater than 1.5, preferably a ratio equal to 1.5-3 and, most preferably, a ratio equal to 1.5-2.2 in the tissue sample indicates that the drug will be effective in inhibiting or treating the IL-17-dependent dermatological condition in the individual, and wherein the individual is a human or a non-human animal.

[00201] In one embodiment, the IL-17-dependent dermatological condition may be hidradenitis suppurativa. Petition 870260065164, dated 02 / 07 / 2026, page 60 / 213 / 85

[00202] In one embodiment, such a method may additionally comprise administering the medication to the individual.

[00203] In one embodiment, such a method is contemplated here in which the initial treatment period is at least one week, at least two weeks, at least four weeks, at least eight weeks, at least twelve weeks, at least eighteen weeks, or at least twenty-four weeks.

[00204] Monitoring the evolution, remission and therapeutic need of an IL-17 dependent condition

[00205] Methods for monitoring the progress of treatment or remission of an IL-17-dependent condition are also contemplated here, comprising analyzing a biological sample from an individual previously treated for the IL-17-dependent condition, preferably hidradenitis suppurativa, for one or more biomarkers selected from IL6, PLA2G2A, IL19, PI3, CST7, IL17A, IL17F, GH1, MZB1, IL1B, IFNG, TNC, CXCL9, SLAMF7, VEGFA, IL17C, SLAMF1, SDC1, OSM, LBP, REG3A, CD79B, COL4A1, CLEC4D, VWF, IL5RA, CSF3, TGFA, IL2RA, ITIH3, FCAR, CCL23, NRCAM, RETN, SERPINA11, CLEC4G, CSF1, HGF, CRELD2, EFEMP1, LTBR, ​​NME3, CKAP4, CD276, SPON2, GGH, TIMP1, LY9, MCFD2, TCN2, QPCT, HYOU1, TNSFSF13B, CCL2, CCL3, CCL4, CCL5, CCL7, CCL20, CXCL1, CXCL8, PDFGA, CXCR2, CCR6, CXCL13, PCDH1, BOC, MEPE, ADAM23, THOP1, IL1RL2, RCOR1 and EDAR.

[00206] In one embodiment, the biomarkers may include PI3 and IL19.

[00207] Methods for monitoring treatment progress or remission are also contemplated as above, where normalization of the level of one or more biomarkers to the level of a healthy control indicates (i) remission of inflammation; (ii) any tunnels present in the individual. Petition 870260065164, dated 02 / 07 / 2026, page 61 / 213 / 85 remain present, but are no longer active; and / or (iii) treatment should be suspended.

[00208] As described herein, such methods may preferably comprise monitoring the progress of treatment or remission of an inflammatory skin disease, preferably an inflammatory skin disease affecting the epidermis and dermis, more preferably an inflammatory skin disease involving hair follicle structures, even more preferably an inflammatory skin disease involving acneiform lesions, most preferably hidradenitis suppurativa.

[00209] Also as described herein, such methods may comprise steps such as determining, prior to analyzing a biological sample from an individual previously treated for the IL-17-dependent condition, whether an mRNA and / or protein level of one or more biomarkers is elevated in a biological sample from an individual suffering from the IL-17-dependent condition, compared to a healthy mRNA and / or protein level of the same or more biomarkers in a healthy or unaffected biological sample. Such methods may further or alternatively comprise determining the mRNA and / or protein level of one or more biomarkers in at least one other biological sample from the individual suffering from the IL-17-dependent condition, wherein at least one other biological sample was obtained at a time after treatment has begun.

[00210] In modalities, an individual previously treated for the IL-17-dependent condition was treated with a nanobody that inhibits IL-17A and / or IL-17F, preferably soneloquimab or a derivative thereof is used.

[00211] In modalities, methods such as those above are contemplated in which the mRNA and / or protein level of one or more biomarkers in at least one other biological sample is determined after one day, two Petition 870260065164, dated 02 / 07 / 2026, page 62 / 213 / 85 days, three days or more days, one week, two weeks or more weeks, after 12 weeks, respectively, after the initial treatment.

[00212] Methods are also contemplated here that comprise: administering an IL-17 inhibitor for a total of at least 4 weeks and preferably for a total of no more than 24 weeks to an individual identified by one or more of the biomarkers described herein, interrupting treatment for a period exceeding two weeks, and then restarting treatment if one or more symptoms of the IL-17-dependent condition recur or if the expression of one or more of the biomarkers becomes abnormal again. In one embodiment, administration may be restarted when the individual presents a Hidradenitis Suppurativa Clinical Response Score (HiSCR) below a certain threshold. Alternatively, administration may be restarted when the individual presents an International Hidradenitis Suppurativa Severity Scoring System (IHS4) below a certain threshold.In one modality, restarting treatment may involve administering an effective amount of the inhibitor with a new induction dosing regimen or restarting the maintenance dosing regimen.

[00213] In one modality, the treatment-responsive individual may have a HiSCR score of 75 to 90, preferably a HiSCR score of 90 or higher (e.g., 90-100 or 91-100). Alternatively, in one modality, the treatment-responsive individual may have an IHS4 score of 75 to 90, preferably an IHS4 score of 90 or higher (e.g., 90-100 or 91-100). This score can be achieved after a treatment period of 4 weeks or more, after a treatment period of 8 weeks or more, after a treatment period of 10 weeks or more, after a treatment period of 12 weeks or more, after a treatment period of 14 weeks or more, after a treatment period of 16 weeks or more, after a treatment period of 18 weeks or more, after a treatment period of 20 weeks or more, or after a treatment period of 24 weeks or more. Petition 870260065164, dated 02 / 07 / 2026, page 63 / 213 / 85 weeks of treatment. In this modality, the treatment-responsive individual has or is at risk of having hidradenitis suppurativa and may have withdrawn from previous treatment with an IL-17 inhibitor after a period of 4 weeks or more, after a period of 8 weeks or more, after a period of 10 weeks or more, after a period of 12 weeks or more, after a period of 14 weeks or more, after a period of 16 weeks or more, after a period of 18 weeks or more, after a period of 20 weeks or more, or after a period of 24 weeks.

[00214] Assessment and / or measurement of high or low levels of Biomarkers

[00215] The manner in which the biomarkers described herein may be measured or assessed is not particularly limited, and may include one or more of the following: (i) measurement of protein levels in peripheral blood, (ii) measurement of mRNA from peripheral blood cells or circulating DNA, (iii) analysis of surface markers (e.g., in the case of cytokine receptors or receptors for other receptors) in peripheral cells, (iv) analysis of intracellular markers in peripheral cells by in situ techniques (e.g., flow cytometry), (v) all the measurements described in (i) to (iv) in other body fluids, including, but not limited to, cerebrospinal fluid, breast milk, amniotic fluid, urine, saliva, serous fluid, (vi) measurement of protein levels in tissue or tissue-derived cells (vii) including tissue or cells collected by patches applied to the skin surface, (viii) measurement of RNA in tissue (e.g.,quantitative RT-PCR or bulk RNA sequencing) or in tissue-derived cells (e.g., single-cell RNA sequencing) (ix) including measurement of RNA in tissue or cells collected by patches applied to the skin surface, (x) measurement of changes in biomarker quantity or function induced by genetic variations including, but not limited to, single nucleotide polymorphisms, insertions, Petition 870260065164, dated 02 / 07 / 2026, page 64 / 213 / 85 deletions, copy number variations, translocations and inversions and / or (xi) epigenetic modifications including, among others, histone alterations, DNA methylation and / or non-coding RNAs.

[00216] The level or amount of expression of one or more biomarkers can be determined in vitro, for example, from an in vitro sample or from an ex vivo sample. The in vitro determination can then be followed by the administration of an IL-17 inhibitor as contemplated here to the individual in vivo.

[00217] In methods and uses such as contemplated herein, the elevated level may be compared to: (i) the level present in uninjured skin, preferably in perilesional skin, (ii) the level present in the peripheral blood of a healthy patient, or (iii) the level in the same individual before initial treatment.

[00218] In methods and uses such as contemplated herein, the elevated level may be as compared to a reference value where the reference value is (i) the biomarker expression level of the corresponding body fluid or tissue sample obtained from a healthy individual; (ii) the average biomarker level expressed in the corresponding body fluid or tissue of a plurality of healthy individuals; or (iii) the average biomarker level expressed in healthy tissue, preferably healthy tissue from the same individual, more preferably perilesional skin from the same individual.

[00219] In a preferred embodiment, the elevated level of an mRNA-based biomarker, determined in an affected biological sample, can be compared with the mRNA level of the same biomarker determined in an unaffected biological sample (=healthy level). The biological samples may be from the same individual suffering from the disease according to the present invention, but from different body regions – healthy region and diseased region – or the healthy control may be obtained from a sample Petition 870260065164, dated 02 / 07 / 2026, page 65 / 213 / 85 biological sample from another individual who does not suffer from the disease according to the present invention. The affected biological sample can be obtained from the skin with lesion or from the blood and the unaffected biological sample from the skin without lesion or from the blood, preferably from the perilesional skin, of the same individual or from another individual.

[00220] In the present description, the term “elevated” may refer to an increase, for example, in the level of a given biomarker, compared to a reference value (e.g., healthy control). The degree of increase may be, for example, at least 5%, at least 6%, at least 7%, at least 8%, at least 9%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, or at least 50%, or at least 100% or multiples of at least 100%.

[00221] In the present description, the term “reduced” may refer to a decrease, for example, in the level of a given biomarker, compared to a reference value (e.g., healthy control). The degree of decrease may be, for example, at least 5%, at least 6%, at least 7%, at least 8%, at least 9%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, or at least 50%, or at least 100% or multiples of at least 100%.

[00222] “Elevated” or “reduced” levels of one or more biomarkers as contemplated herein may also be assessed based on the magnitude of differences (fold differences) in the level present in a biological sample compared to a healthy control (e.g., reference value or level present in healthy tissue or blood from the same / different individual). For example, a “high” level of a biomarker as contemplated herein may exhibit a magnitude increase of 1.1; 1.2; 1.3; 1.4; 1.5; 1.6; 1.7; 1.8; 1.9; 2.0; 2.5; 3.0; 3.5; 4.5; 5.0; 5.5; 6.0; 6.5; 7.0; 7.5; 8.0; 8.5; Petition 870260065164, dated 02 / 07 / 2026, p. 66 / 213 / 85 9.0; 9.5; 10; 20; 30; 40; 50 or at least 50 times or at least 100 times or multiples thereof compared to a healthy control. As another example, a “reduced” level of a biomarker as contemplated may exhibit a magnitude of decrease of 1.1; 1.2; 1.3; 1.4; 1.5; 1.6; 1.7; 1.8; 1.9; 2.0; 2.5; 3.0; 3.5; 4.5; 5.0; 5.5; 6.0; 6.5; 7.0; 7.5; 8.0; 8.5; 9.0; 9.5; 10; 20; 30; 40; 50 or at least 50 times or at least 100 times or multiples thereof compared to a healthy control.

[00223] The mRNA and / or protein level can be determined for a biopsy sample, a tissue sample, or a peripheral blood sample. The mRNA or protein level can be based on the overall mRNA or protein level of multiple samples. Alternatively, the mRNA or protein level can be based on a specific category of samples (e.g., peripheral blood, HS lesions or nodules) or an individual sample. There may be advantages in monitoring both protein and mRNA levels, since some biomarkers can be regulated at the transcriptional and / or translational level. Individuals

[00224] In the present description, the term “individual,” or similar terms such as “patient” or “person,” may refer to the recipient of the medication or may refer to the individual from whom a biological sample was obtained for biomarker evaluation. This individual may be, for example, a mammal, preferably a human. The human is not limited and may be of any disease state, weight, age, or sex. For example, the individual may be a human adolescent, i.e., a person aged 12–17, or a young person, or a child aged 1–11, 2–10, 3–9, or 6–12 years of age, or an infant (e.g., an infant at least six months old). The individual may be one who has or is at risk of developing a disease, disorder, or condition that would benefit from the Petition 870260065164, dated 02 / 07 / 2026, page 67 / 213 / 85 measurement of the biomarker and / or treatment as described herein. Furthermore, the individual may be an animal, including, without limitation, a non-human animal including, for example, farm animals (such as cattle, sheep, pigs, goats, horses, donkeys, mules, buffalo, oxen, llamas, alpacas or camels) or domesticated animals (such as dogs or cats).

[00225] The present description identifies individuals with one or more of the biomarkers in Table 1, or any combination or combinations thereof, or with at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20 or more thereof, as constituting a new group of patients who may, for example, be treated with an IL-17 inhibitor and / or be particularly responsive to treatment with an IL-17 inhibitor and / or whose disease progresses or whose remission can be monitored based on the expression levels of the biomarker(s) present in a biological sample (e.g., versus a healthy control or an appropriate reference value).

[00226] The individual may have any of the IL-17-dependent conditions described herein or be at risk of having any of these conditions.

[00227] In modalities, the individual may have been clinically diagnosed as having HS in Hurley Stage I, II or III.

[00228] In modalities, the individual may have been clinically diagnosed as having mild HS, moderate HS, moderate to severe HS, severe HS, or juvenile HS. Biological sample

[00229] A “sample” or “biological sample,” in this descriptive report, refers to a sample derived from an individual. Non-limiting sources of a sample include blood, plasma, serum, cerebrospinal fluid, lymph, biopsy aspirates, ascites, fluid extracts, solid or soft tissue, external sections of the skin, respiratory, intestinal and genitourinary tracts, tears, saliva, milk, tumors, organs, cell cultures and / or Petition 870260065164, dated 02 / 07 / 2026, page 68 / 213 / 85 constituents of cell culture. The sample can be obtained by any means, such as a syringe, adhesive strip, punch biopsy, microbiopsy, surgical removal or similar.

[00230] In one embodiment, the biological sample comprises a biopsy sample, tissue, and peripheral blood. In one embodiment, the tissue sample may be a sample of skin cells, obtained by means of a biopsy, a microbiopsy, or an adhesive strip that is configured for the acquisition of skin cells from the individual.

[00231] Biological samples are considered from the axilla, buttocks, perianal and gluteal regions, groin, and breast, including skin samples from these locations. The sample may be from a lesioned tissue (e.g., abscess, nodule, or tunnel from an individual who is a carrier or suspected of being a carrier of HS) or it may be from healthy tissue or tissue with a healthy phenotype.

[00232] IL-17F as a target in IL-17-dependent conditions

[00233] IL-17F is a unique target in hidradenitis suppurativa (HS) and psoriasis (PsO) and other inflammatory skin diseases. For example, IL-17F is specifically upregulated in skin and joint inflammation. In fact, IL-17F is more upregulated in HS than in PsO and is more abundant than IL-17A in HS lesions. IL-17F is also capable of activating keratinocytes independently of IL-17A. In view of this, IL-17F inhibitors and / or inhibitors that block IL-17F at least as effectively as IL-17A will be more effective for the treatment of HS and PsO and other inflammatory skin diseases. IL-17 inhibitors

[00234] IL-17 inhibitors as contemplated herein are not particularly limited and may comprise an antibody, antibody fragment or a nanobody. IL-17 inhibitors may be able to modulate, for example, block, inhibit, reduce, antagonize, neutralize or, Petition 870260065164, dated 02 / 07 / 2026, p. 69 / 213 / 85 otherwise, interfere with IL-17, that is, with the production of pro-inflammatory cytokines and / or chemokines mediated by IL-17A and / or IL-17F.

[00235] IL-17 inhibitors as discussed herein may bind specifically to IL-17F, an IL-17F homodimer, IL-17A, an IL-17A homodimer, and / or an IL-17A / IL-17F heterodimeric complex.

[00236] In this descriptive report, the term “antibody” may refer to immunoglobulin molecules and immunologically active portions of immunoglobulin (Ig) molecules, i.e., molecules containing an antigen-binding site that specifically binds (immunoreacts with) an antigen. For example, an antibody may be considered to react with one or more antigenic determinants of the desired antigen and not react with other polypeptides or to bind with much lower affinity.

[00237] Antibodies include polyclonal, monoclonal, chimeric, dAb (domain antibody), single-chain fragments, Fab, Fab' and F(ab')2, and scFvs. Antibody fragments and antibodies that combine structures or characteristics of one or more of the above antibody types are also contemplated.

[00238] The basic structural unit of an antibody is known to those skilled in the art. Each antibody comprises a tetramer composed of two “light” chains (approximately 25 kDa each) and two “heavy” chains (approximately 50–70 kDa each). The amino-terminal portion of each chain includes a variable region of approximately 100 to 110 or more amino acids, primarily responsible for antigen recognition. The carboxy-terminal portion of each chain defines a constant region. Human antibody molecules can be related to any of the IgG, IgM, IgA, IgE, and IgD classes, which differ from one another by the nature of the heavy chain present in the molecule. In humans, the light chain can be a kappa chain or a lambda chain.

[00239] The term “monoclonal antibody” (mAb) in this report Petition 870260065164, dated 02 / 07 / 2026, page 70 / 213 / 85 descriptive, may refer to a single antibody species or molecule or to a population of antibody molecules containing only one molecular species of the antibody molecule, each consisting of a unique light chain gene product and a unique heavy chain gene product. The complementarity-determining regions (CDRs) of the monoclonal antibody are identical in all molecules of the population.

[00240] “Nanobody” or “VHH single-domain antibody”, in this descriptive report, are synonymous and may be used interchangeably. A VHH single-domain antibody comprises a single immunoglobulin variable domain (“ISV”). A single immunoglobulin variable domain is an amino acid sequence that: (i) comprises an immunoglobulin fold or that, under suitable conditions (such as physiological conditions), is capable of forming an immunoglobulin fold (i.e., by folding), i.e., so as to form an immunoglobulin variable domain (such as, for example, a VH, VL, or VHH domain); and that (ii) forms (or under suitable conditions is capable of forming) an immunoglobulin variable domain comprising functional antigen-binding activity (in the sense that it does not require an interaction with another immunoglobulin variable domain (such as a VH-VL interaction) to form a functional antigen-binding site).Preferred examples of single immunoglobulin variable domain nanobodies or domains suitable for use in the invention include VHHs, such as humanized VHH or camelized VH, such as camelized human VH, dAbs, and single-domain antibodies. As contemplated herein, a nanobody may comprise or consist of a single ISV or VHH domain; as contemplated herein, a nanobody may also comprise or consist of multiple ISV or VHH domains, and thus a nanobody includes embodiments such as a multi-domain VHH antibody. Antibodies and antibody fragments combined with ISVs, VHH structures, or nanobodies are also included. Petition 870260065164, dated 02 / 07 / 2026, page 71 / 213 / 85 contemplated.

[00241] In preferred embodiments, the IL-17 inhibitor may be selected from bimekizumab, secukinumab, ixekizumab, brodalumab, netakimab, or izokib.

[00242] In a preferred embodiment, the IL-17 inhibitor may be an IL-17A and / or IL-17F inhibitor and may comprise a Fab, a VHH single-domain antibody, or a scFV (single-chain Fv fragment) with an ISV.

[00243] In one embodiment, the nanobody can have a mass of 3545 kDa. The small size of nanobody-type inhibitors allows for a tissue / serum ratio 10x higher than conventional mAb.

[00244] In one embodiment, the nanobody can be configured to bind specifically to IL-17A and IL-17F.

[00245] The nanobody may comprise a region that specifically binds to IL-17F, a region that specifically binds to human serum albumin, and a region that specifically binds to IL-17A / F.

[00246] In embodiments, the nanobody can bind to IL17F / F dimers at least as well as it binds to IL-17A / A dimers.

[00247] In embodiments, the nanobody exhibits an affinity for IL-17A / A, IL-17A / F and / or IL-17F / F dimers of 0.037 nM or less, preferably 0.004 nM or less, as measured by surface plasmon resonance.

[00248] In modalities, the nanobody is soneloquimab (SLK) or a derivative thereof. Soneloquimab is a nanobody that inhibits IL-17A and IL-17F with enhanced potential to penetrate and accumulate at sites of inflammation in deep, hard-to-reach tissue structures, such as inflammatory and fibrotic dermal lesions of HS.

[00249] Molecular PK and PD modeling of soneloquimab resulting from subcutaneous administration for tissue penetration shows Petition 870260065164, dated 02 / 07 / 2026, page 72 / 213 / 85 unique advantages of nanobodies that derive from their small size, enhanced absorption after SC administration, and ability to penetrate tissue. It is anticipated that this will allow for control of the disease at lower minimum levels due to smaller doses or longer intervals between injections, with an improved risk-benefit ratio compared to mAb. Administration modes

[00250] In the present description, the term “administer” refers to providing a medication to an individual. The method or route of administration is not particularly limited and may be, for example, subcutaneous, intravenous, intraperitoneal, intramuscular, or transdermal. In a preferred embodiment, administration is systemic (e.g., via injection). Subcutaneous injection is also contemplated. Subcutaneous injection may include injections via pre-filled syringe, autoinjector, or SC injection of reconstituted lyophilized powder.

[00251] An “effective” or “therapeutically effective” amount of the drug is typically administered. An effective amount refers to the quantity needed (in doses and over periods of time and by means of administration) to achieve the desired therapeutic result. An effective amount of the drug may vary depending on factors such as the disease state, the individual’s age, sex, and weight, and the drug’s ability to elicit a desired response in the individual. An effective amount is also one in which any toxic or harmful effects of the drug are offset by the therapeutically beneficial effects.

[00252] Also described here is a method for treating an individual who has or is at risk of having hidradenitis suppurativa, which comprises administering an effective amount of an agent configured to inhibit IL-17F present in the dermis of an inflammatory skin lesion of the individual, wherein the effective amount is the same dose required to treat Petition 870260065164, dated 02 / 07 / 2026, page 73 / 213 / 85 effectively treats psoriasis with the same agent.

[00253] In one embodiment, such a method may comprise administering the effective amount to an individual with a protein analysis result of the lesional IL-17F / non-lesional IL-17F ratio equal to or greater than 2, preferably equal to or greater than 10, more preferably equal to 2-50 and, most preferably, equal to 10-30.

[00254] In one embodiment, such a method may comprise administering the effective amount to an individual with an mRNA ratio analysis result between lesional IL-17F / non-lesional IL-17F equal to or greater than 5, preferably equal to or greater than 10, more preferably equal to 5-500 and, most preferably, equal to 10-300.

[00255] In one embodiment, the agent configured to inhibit IL-17F may comprise an antibody, an antibody fragment, or a nanobody. In one embodiment, the agent may comprise a nanobody and the nanobody may have a mass of 35-45 kDa. Kits

[00256] Kits for diagnosing IL-17-dependent conditions, identifying super-responders and / or simply measuring biomarkers are contemplated.

[00257] For example, a kit is contemplated here for identifying an individual at risk of, or in need of treatment for, an IL-17-dependent condition, which kit comprises a reagent or reagents for measuring the level or expression of one or more of the following: IL6, PLA2G2A, IL19, PI3, CST7, IL17A, IL17F, GH1, MZB1, IL1B, IFNG, TNC, CXCL9, SLAMF7, VEGFA, IL17C, SLAMF1, SDC1, OSM, LBP, REG3A, CD79B, COL4A1, CLEC4D, VWF, IL5RA, CSF3, TGFA, IL2RA, ITIH3, FCAR, CCL23, NRCAM, RETN, SERPINA11, CLEC4G, CSF1, HGF, CRELD2, EFEMP1, LTBR, ​​NME3, CKAP4, CD276, SPON2, GGH, TIMP1, LY9, MCFD2, TCN2, QPCT, HYOU1, TNSFSF13B, CCL2, CCL3, CCL4, CCL5, CCL7, Petition 870260065164, dated 02 / 07 / 2026, page 74 / 213 / 85 CCL20, CXCL1, CXCL8, PDFGA, CXCR2, CCR6, CXCL13, PCDH1, BOC, MEPE, ADAM23, THOP1, IL1RL2, RCOR1 and EDAR.

[00258] In one embodiment, the kit may additionally comprise packaged components for obtaining a biological sample from an individual, preferably for obtaining a skin sample, a blood sample, or another body fluid sample. In certain embodiments, such a kit may comprise an adhesive strip for obtaining a skin sample or packaged components for obtaining a punch biopsy, microbiopsy, or surgical specimen.

[00259] A kit for treating an IL-17 dependent dermatological condition is also contemplated herein, wherein the kit may comprise a pharmaceutical composition comprising an IL-17A and / or IL-17F inhibitor, and a reagent or reagents for measuring the level or expression of one or more of the following: IL6, PLA2G2A, IL19, PI3, CST7, IL17A, IL17F, GH1, MZB1, IL1B, IFNG, TNC, CXCL9, SLAMF7, VEGFA, IL17C, SLAMF1, SDC1, OSM, LBP, REG3A, CD79B, COL4A1, CLEC4D, VWF, IL5RA, CSF3, TGFA, IL2RA, ITIH3, FCAR, CCL23, NRCAM, RETN, SERPINA11, CLEC4G, CSF1, HGF, CRELD2, EFEMP1, LTBR, ​​NME3, CKAP4, CD276, SPON2, GGH, TIMP1, LY9, MCFD2, TCN2, QPCT, HYOU1, TNSFSF13B, CCL2, CCL3, CCL4, CCL5, CCL7, CCL20, CXCL1, CXCL8, PDFGA, CXCR2, CCR6, CXCL13, PCDH1, BOC, MEPE, ADAM23, THOP1, IL1RL2, RCOR1 and / or EDAR, in a sample taken from an individual.

[00260] In the present description, a “kit” may refer to those materials necessary to perform an assessment, including collecting and safely disposing of a sample. For example, a kit may include an adhesive strip used to obtain a skin sample. Alternatively, a kit may include materials for collecting bodily fluids, such as blood, and, if necessary, separating the blood into component parts such as plasma and red blood cells. Such materials could include, for example, a syringe or a Petition 870260065164, dated 02 / 07 / 2026, page 75 / 213 / 85 sponge. The kit may also include materials such as reagents (buffers, blocking agents, etc.), test cartridges and the like. A kit may also include written instructions for sample collection and testing.

[00261] Alternatively, a kit may include the materials needed to administer a medication. Such a kit may include the medication in the form of, for example, pills, tablets, creams, medication-containing foods or drinks, and injectable liquid medication. The kit may also include administration devices such as syringes or pens pre-filled with the medication. The kit may also include materials for safely disposing of the administration devices and written instructions for use.

[00262] Also described here is a kit for identifying an individual at risk or in need of treatment with an IL-17F inhibitor, which kit comprises an adhesive strip configured to obtain a skin sample for testing; a reagent for measuring the level or expression of IL17F and, optionally, a reagent for measuring the level or expression of IL17A.

[00263] Also described herein is a kit for treating an IL-17 dependent dermatological condition, wherein the kit comprises a pharmaceutical composition, a reagent for measuring the level or expression of IL17F in a sample taken from an individual and, optionally, a reagent for measuring the level or expression of IL17A in a sample taken from an individual, wherein the pharmaceutical composition comprises an IL-17F inhibitor.

[00264] In one embodiment, such a kit is contemplated herein, in which the sample taken from the individual to measure the IL-17F level is a sample of skin cells and the kit additionally comprises an adhesive strip configured to acquire the skin cell sample from the individual.

[00265] In one embodiment, such a kit is contemplated here where the IL-17-dependent dermatological condition is hidradenitis suppurativa. Petition 870260065164, dated 02 / 07 / 2026, page 76 / 213 / 85

[00266] Also described herein is a kit for identifying an individual at risk of having HS or requiring treatment with an IL-17A and / or IL-17F inhibitor, the kit comprising: an adhesive strip configured to obtain a skin sample for testing; and at least one reagent for measuring the level or expression of at least one biomarker in a sample taken from the individual, wherein the biomarker comprises one or more of CCL20, CXCL1, CXCL8, CCL2, CCL3, CCL4, CCL5, CCL7, PDFGAA or CSF3.

[00267] Also described herein is a kit for treating an IL-17 dependent dermatological condition, wherein the kit comprises a pharmaceutical composition and reagents for measuring the level or expression of at least one biomarker in a sample taken from an individual, wherein the pharmaceutical composition comprises an IL-17A and / or IL-17F inhibitor, and the biomarker comprises one or more of CCL20, CXCL1, CXCL8, CCL2, CCL3, CCL4, CCL5, CCL7, PDFGAA or CSF3.

[00268] In one embodiment, a kit such as the above is contemplated, wherein the sample taken from the individual is a sample of skin cells and the kit may additionally comprise an adhesive strip configured to acquire the skin cell sample from the individual.

[00269] In one embodiment, a kit such as the above is contemplated, in which the IL-17-dependent dermatological condition is hidradenitis suppurativa. Examples Example 1

[00270] Inflammatory activity based on IL-17A and IL-17F expression observed with maximum occurrence around dermal tunnels in HS

[00271] Quantitative RT-PCR was performed on HS samples from the dermis and epidermis as well as in healthy controls. Higher levels of IL-17A and IL-17F mRNA were observed in the dermal compartment compared to the epidermal compartment in HS lesions. The results indicate that maximum inflammatory activity occurs around the dermal tunnels. See a Petition 870260065164, dated 02 / 07 / 2026, page 77 / 213 / 85 Figure 5B. Example 2

[00272] Identification of IL-17i biomarkers relevant to HS and distinction of specific properties of target molecules

[00273] Punch biopsies of specific HS phenotypes (perilesional tissue, nodule-containing tissue, tunnel-containing tissue) were obtained from a larger surgical specimen of patients with a diagnosis of HS (Hurley disease severity II-III) undergoing surgery for HS. The biopsies were first subjected to imaging visualization [e.g., H&E staining to identify nodules and tunnels, multichannel immunofluorescence (IF) to distinguish keratinocyte activation and immune cell infiltrate (Figure 6 -- Workflow in (i)); see also Figures 8A-8F). The biopsies were then subjected to protein lysate and mRNA extraction, which were further analyzed by multiple cytokine array or ELISA and bulk RNA sequencing and quantitative RT-PCR analysis (Figure 6 - Workflow in (ii) and (iii); see also Table 1).

[00274] Selected biopsies from the perilesional region and containing tunnels were used for air-liquid interface organ culture to test the penetration and specific anti-inflammatory effects of IL-17 inhibitory therapeutic molecules (IL-17i) (Figure 6 -- Workflow in (iv); see also Figure 19 and Figure 20).

[00275] Keratinocytes were then exposed to different IL-17 dimers to test the specific pro-inflammatory effects of IL-17A and IL-17F (Figure 6 -- Workflow in (v)). Different IL-17i therapeutic molecules were added to assess the specific inhibitory potential at different concentrations of these molecules (Figure 6 -- Workflow in (vi); see also Figures 17 and 18).

[00276] Finally, the peripheral blood of patients with HS was Petition 870260065164, dated 02 / 07 / 2026, page 78 / 213 / 85 collected before and after treatment with an IL-17 inhibitor (IL17i), along with peripheral blood samples from healthy controls. Proteomics (Olink®) was used to identify biomarkers for HS in more detail (Figure 6 -- Workflow in (vii); see also Figures 7, 21, 22; and Table 1). In particular, a total of 502 serum samples from 233 individuals with HS were analyzed using the Olink® Explore platform, i.e., the Olink® Explore 384 Cardiometabolic and Olink® Explore 384 Inflammation panels, which together comprise >700 proteins linked to inflammation and / or metabolic disease. The Olink® Explore platform utilizes Proximity Extension Assay (PEA) technology coupled with a reading methodology based on Next Generation Sequencing (NGS).PEA technology is a dual recognition immunoassay in which pairs of matching antibodies carrying unique DNA labels (PEA probes) bind to a target protein. Upon binding to the target, the bound oligonucleotides are brought closer together and hybridize. The newly generated oligonucleotide sequence is then amplified by PCR and measured by NGS. Quality control (QC) and data normalization were performed using internal and external controls.

[00277] Notably, the expression of the following biomarkers was observed to be elevated in HS: IL6, PLA2G2A, IL19, PI3, CST7, IL17A, IL17F, GH1, MZB1, IL1B, IFNG, TNC, CXCL9, SLAMF7, VEGFA, IL17C, SLAMF1, SDC1, OSM, LBP, REG3A, CD79B, COL4A1, CLEC4D, VWF, IL5RA, CSF3, TGFA, IL2RA, ITIH3, FCAR, CCL23, NRCAM, RETN, SERPINA11, CLEC4G, CSF1, HGF, CRELD2, EFEMP1, LTBR, ​​NME3, CKAP4, CD276, SPON2, GGH, TIMP1, LY9, MCFD2, TCN2, QPCT, HYOU1, TNSFSF13B, CCL2, CCL3, CCL4, CCL5, CCL7, CCL20, CXCL1, CXCL8, PDFGA, CXCR2, CCR6, and CXCL13; in addition, the expression of the following biomarkers was observed to be reduced in HS: Petition 870260065164, dated 02 / 07 / 2026, page 79 / 213 / 85 PCDH1, BOC, MEPE, ADAM23, THOP1, IL1RL2, RCOR1, and EDAR. The identified biomarkers and relevant information related to each are summarized in Table 1. Petition 870260065164, dated 02 / 07 / 2026, page 80 / 213 / 85 Table 1. Biomarkers of HS Biomarker Protein symbol UniProt code / exemplary amino acid sequence Gene symbol Pseudonymous symbols Known functions include Aspects and characteristics of the invention Abnormal expression compartment Example methods for sample collection Technical data / effect Interleukin 6 (IL6) IL-6 P05231 / SEQ ID NO: 1 IL6 BSF2, HGF, HSF B cell activation; T / Th17 cell activation; angiogenesis Peripheral blood Blood test Protein (proteomics in blood): Elevated vs. healthy controls (FDR <0.05); Correlation with dT count (Slope: 0.13; Adjusted P: 6.92E-07) Figure 9A Membrane-associated phospholipase A2 (PLA2G2A) PLA2G2 A P14555 / SEQ ID NO: 2 PLA2G2 A PLA2B, PLA2L, RASF-A Epithelial regeneration; Antimicrobial defense Peripheral blood Blood test Protein (proteomics in blood): Elevated vs.Healthy controls (FDR <0.05); Correlation with dT count (Slope: 0.12; Adjusted P: 8.30E-06) Figure 9N Interleukin-19 (IL19) IL-19 Q9UHD0 / SEQ ID NO: 3 IL19 IL-19, MDA1, ZMDA1, IL10C, NG.1 Angiogenesis; neutrophil activation; epithelial regeneration; angiogenesis Peripheral blood Blood test Protein (blood proteomics): Elevated vs. healthy controls (FDR <0.05); Correlation with dT count (Slope: 0.11; Adjusted P: 5.49E-07) Figure 9A Elafin (PI3) Elafin P19957 / SEQ ID NO: 4 PI3 ESI, SKALP, ELAFIN, WAP3, WFDC14, cementoin Neutrophil activation / degradation; antimicrobial activity Peripheral blood Blood test Protein (proteomics in blood): Elevated vs.Healthy controls (FDR <0.05); Correlation with dT count (Slope: 0.10; Adjusted P: 6.28E-09) Figure 9A Cystatin-F (CST7) CST7 O76096 / SEQ ID NO: 5 CST7 Leukocystatin Cystatin-7, CMAP NK cell activation; granulocyte regulation Skin sample with lesion and peripheral blood Blood test, tape swab, punch biopsies, microbiopsy and any type of surgical specimen Protein (proteomics in blood): Elevated vs. healthy controls (FDR <0.05); Correlation with dT count (Slope: 0.10; Adjusted P: 9.91E-04) mRNA (seq. RNA): lesional vs. perilesional (P < 0.05) Figure 9B. Petition 870260065164, dated 02 / 07 / 2026, page 81 / 213 / 85 Interleukin 17A (IL17A) IL-17A Q16552 / SEQ ID NO: 6 IL17A IL-17 T / Th17 cell activation; neutrophil activation Skin sample with lesion and peripheral blood Blood test, tape test, punch biopsies, microbiopsy and any type of surgical specimen Protein (proteomics in blood): Elevated vs. healthy controls (FDR <0.05); Correlation with dT count (Slope: 0.09; Adjusted P: 3.91E-04) mRNA (seq. RNA): lesional vs. perilesional (P < 0.05) Protein: lesional vs. perilesional (P < 0.05) Figure 9L Interleukin 17F (IL17F) IL-17F Q96PD4 / SEQ ID NO: 7 IL17F ML-1, ML1 T / Th17 cell activation; neutrophil activation Skin sample with lesion and peripheral blood Blood test, tape test, punch biopsies, microbiopsy and any type of surgical specimen Protein (proteomics in blood): Correlation with dT count (Slope: 0.07; adjusted P: 3.35E-03) Protein: lesional vs.perilesional (P < 0.05) Figure 9M Somatotropin a (GH1) GH P01241 / SEQ ID NO: 8 GH1 GH-N, GHN, GH, hGH-N Hormonal response Peripheral blood Blood test Protein (blood proteomics): Elevated vs. healthy controls (FDR <0.05); Correlation with dT count (Slope: 0.09; Adjusted P: 3.30E-02) Figure 9N B-cell and B1-specific marginal zone protein (MZB1) MZB1 Q8WU39 / SEQ ID NO: 9 MZB1 PACAP, MGC29506, HSPC190, pERp1, MEDA-7 B-cell activation Skin sample with lesion and peripheral blood Blood test, tape swab, punch biopsies, microbiopsy and any type of surgical specimen Protein (proteomics in blood): Elevated vs. healthy controls (FDR <0.05); Correlation with dT count (Slope: 0.08; Adjusted P: 2.14E-06) mRNA (seq. RNA): lesional vs.perilesional (P < 0.05) Figure 9B Interleukin 1 beta (IL1B) IL-1P P01584 / SEQ ID NO: 10 IL1B IL1F2, IL-1B, IL1-BETA T / Th17 cell activation; B cell activation; epithelial regeneration Peripheral blood Blood test Protein (proteomics in blood): Correlation with dT count (Slope: 0.08; Adjusted P: 1.82E-04) Figure 9B. Petition 870260065164, dated 02 / 07 / 2026, page 82 / 213 / 85 IFN-γ (IFNG) IFN-γ P01579 / SEQ ID NO: 11 IFNG - Innate immunity; B cell activation; T cell activation; immune cell extravasation; NK cell activation, CD8+ Peripheral blood Blood test Protein (blood proteomics): Elevated vs. healthy controls (FDR <0.05); Correlation with dT count (Slope: 0.08; Adjusted P: 2.03E-02) Figure 9C Tenascin C (TNC) TNC P24821 / SEQ ID NO: 12 TNC TN, MGC167029 Neurogenesis Skin sample with lesion and peripheral blood Blood test, tape swab, punch biopsies, microbiopsy and any type of surgical specimen Protein (blood proteomics): Elevated vs. healthy controls (FDR <0.05); Correlation with dT count (Slope: 0.07; Adjusted P: 5.49E-07) mRNA (seq. RNA): lesional vs.perilesional (P < 0.05) Figure 9C Chemokine ligand 9 with CXC motif (CXCL9) CXCL9 Q07325 / SEQ ID NO: 13 CXCL9 SCYB9, Humig, crg10 Immune cell extravasation; T cell activation Peripheral blood Blood test Protein (blood proteomics): Elevated vs. healthy controls (FDR <0.05); Correlation with dT count (Slope: 0.07; Adjusted P: 1.04E-03) Figure 9C SLAM family member 7 (SLAMF7) SLAMF7 Q9NQ25 / SEQ ID NO: 14 SLAMF7 CRACC, 19A, CS1, CD319 NK cell activation; T cell activation Skin sample with lesion and peripheral blood Blood test, tape, punch biopsies, microbiopsy and any type of surgical specimen Protein (proteomics in blood): Elevated vs. healthy controls (FDR <0.05); Correlation with dT count (Slope: 0.07; Adjusted P: 1.78E-03) mRNA (seq. RNA): lesional vs.perilesional (P < 0.05) Figure 9D Vascular endothelial growth factor A, long form (VEGFA) VEGFA P15692 / SEQ ID NO: 15 VEGFA VEGF Angiogenesis; regulation of endothelial cell growth Peripheral blood Blood test Protein (proteomics in blood): Elevated vs. healthy controls (FDR <0.05); Correlation with dT count (Slope: 0.06; Adjusted P: 2.91E-03) Figure 9D Interleukin 17C (IL17C) IL-17C Q9P0M4 / SEQ ID NO: 16 IL17C IL-17C, CX2, IL-21, MGC126884, MGC138401 Immune regulation of epithelial cells Peripheral blood Blood test Protein (proteomics in blood): Correlation with dT count (Slope: 0.06; Adjusted P: 1.36E-02) Figure 9D. Petition 870260065164, dated 02 / 07 / 2026, page 83 / 213 / 85 Lymphocytic activation signaling molecule (SLAMF1) SLAMF1 Q13291 / SEQ ID NO: 17 SLAMF1 CD150 T cell activation Skin sample with lesion and peripheral blood Blood test, tape test, punch biopsies, microbiopsy and any type of surgical specimen Protein (proteomics in blood): Elevated vs. healthy controls (FDR <0.05); Correlation with dT count (Slope: 0.06; Adjusted P: 8.27E-03) mRNA (seq. RNA): lesional vs. perilesional (P < 0.05) Figure 9E Syndecan 1 (SDC1) SYND1 P18827 / SEQ ID NO: 18 SDC1 CD138, Syndecan, SYND1 Angiogenesis; epithelial regeneration Peripheral blood Blood test Protein (proteomics in blood): Elevated vs.Healthy controls (FDR <0.05); Correlation with dT count (Slope: 0.06; Adjusted P: 1.69E-03) Figure 9N OncostatinM (OSM) OSM P13725 / SEQ ID NO: 19 OSM MGC20461 Immune regulation of epithelial cells; epithelial regeneration Peripheral blood Blood test Protein (blood proteomics): Correlation with dT count (Slope: 0.06; Adjusted P: 7.07E-03) Figure 9E Lipopolysaccharide-binding protein (LBP) LBP P18428 / SEQ ID NO: 20 LBP BPIFD2 Innate immunity Peripheral blood Blood test Protein (blood proteomics): Elevated vs.healthy controls (FDR <0.05); Correlation with dT count (Slope: 0.05; Adjusted P: 1.39E-02) Figure 9E Regenerating islet-derived protein 3-alpha (REG3A) REG3A Q06141 / SEQ ID NO: 21 REG3A HIP, REG-III, REG3, PBCGF, PAP1 Regulation of keratinocyte proliferation Peripheral blood Blood test Protein (proteomics in blood): Correlation with dT count (Slope: 0.05; Adjusted P: 3.41E-02) Figure 9O Beta chain of B-cell antigen receptor complex-associated protein (CD79B) CD79B P40259 / SEQ ID NO: 22 CD79B B29, Ig-beta, Ig-beta B-cell activation Skin sample with lesion and peripheral blood Blood test, tape swab, punch biopsies, Microbiopsy and any type of surgical specimen Protein (proteomics in blood): Elevated vs. healthy controls (FDR <0.05); Correlation with dT count (Slope: 0.05; Adjusted P: 1.29E-02) mRNA (seq. RNA): lesional vs. perilesional (P < 0.01) Figure 9F. Petition 870260065164, dated 02 / 07 / 2026, p. 84 / 213 / 85 Alpha-1 chain collagen (IV) (COL4A1) COL4A1 P02462 / SEQ ID NO: 23 COL4A1 NA Angiogenesis; regulation of endothelial cell growth Skin sample with lesion and peripheral blood Blood test, tape, punch biopsies, microbiopsy and any type of surgical specimen Protein (proteomics in blood): Correlation with dT count (Slope: 0.05; adjusted P: 2.54E-02) mRNA (seq. RNA): lesional vs. perilesional (P < 0.01) Figure 9F C-domain family of lectins, 4 D members (CLEC4D) CLEC4D Q8WXI8 / SEQ ID NO: 24 CLEC4D Mpcl, CD368, MCL, Dectin-3 T / Th17 cell activation Peripheral blood Blood test Protein (blood proteomics): Elevated vs.healthy controls (FDR <0.05); Correlation with dT count (Slope: 0.05; Adjusted P: 3.41E-02) Figure 9F Von Willebrand factor (VWF) vWF P04275 / SEQ ID NO: 25 VWF NA Extracellular matrix structure Peripheral blood Blood test Protein (proteomics in blood): Correlation with dT count (Slope: 0.05; Adjusted P: 7.46E-03) Figure 9G Interleukin 5 receptor alpha subunit (IL5RA) IL-5RA Q01344 / SEQ ID NO: 26 IL5RA CDw125, CD125 Eosinophil regulation Peripheral blood Blood test Protein (proteomics in blood): Correlation with dT count (Slope: 0.05; Adjusted P: 3.14E-02) Figure 9G Granulocyte colony-stimulating factor (CSF3) G-CSF P09919 / SEQ ID NO: 27 CSF3 C17orf33, GCSF Granulocyte and macrophage activation (in the case of granulocytes, it stimulates survival, proliferation, differentiation and function); binds to G-CSF-FR; is produced by macrophages, keratinocytes Peripheral blood Blood test Protein (proteomics in blood): Elevated vs.Healthy controls (FDR <0.05); Correlation with dT count (Slope: 0.04; Adjusted P: 1.50E-03) Figure 9G Transforming growth factor alpha (TGFA) TGF-alpha P01135 / SEQ ID NO: 28 TGFA NA Epithelial regeneration; neurogenesis Peripheral blood Blood test Protein (proteomics in blood): Elevated vs. healthy controls (FDR <0.05); Correlation with dT count (Slope: 0.04; Adjusted P: 3.80E-02) Figure 9N. Petition 870260065164, dated 02 / 07 / 2026, page 85 / 213 / 85 Interleukin-2 receptor alpha subunit (IL2RA) IL-2RA P01589 / SEQ ID NO: 29 IL2RA CD25 T cell activation Skin sample with lesion and peripheral blood Blood test, tape test, punch biopsies, microbiopsy and any type of surgical specimen Protein (proteomics in blood): Elevated vs. healthy controls (FDR <0.05); Correlation with dT count (Slope: 0.04; Adjusted P: 6.75E-04) mRNA (seq. RNA): lesional vs. perilesional (P < 0.05) Figure 9H Inter-alphatrypsin inhibitor H3 heavy chain (ITIH3) ITI-HC3 Q06033 / SEQ ID NO: 30 ITIH3 H3P Hyaluronan transport Peripheral blood Blood test Protein (proteomics in blood): Elevated vs.Healthy controls (FDR <0.05); Correlation with dT count (Slope: 0.04; Adjusted P: 7.93E-04) Figure 9H Immunoglobulin alpha Fc receptor (FCAR) IgA Fc receptor P24071 / SEQ ID NO: 31 FCAR CD89 Antibody-dependent cell-mediated cytotoxicity Peripheral blood Blood test Protein (blood proteomics): Elevated vs. healthy controls (FDR <0.05); Correlation with dT count (Slope: 0.04; Adjusted P: 2.54E-02) Figure 9H Chemokine 23 containing CC motif (CCL23) CCL23 P55773 / SEQ ID NO: 32 CCL23 MIP3, MPIF1, SCYA23 Activation of T cells, neutrophils and monocytes Peripheral blood Blood test Protein (proteomics in blood): Elevated vs.Healthy controls (FDR <0.05); Correlation with dT count (Slope: 0.04; Adjusted P: 2.35E-02) Figure 9N Neuronal cell adhesion molecule (NRCAM) Nr-CAM Q92823 / SEQ ID NO: 33 NRCAM KIAA0343 Neurogenesis Skin sample with lesion and peripheral blood Blood test, tape, punch biopsies, microbiopsy and any type of surgical specimen Protein (proteomics in blood): Elevated vs. healthy controls (FDR <0.05); Correlation with dT count (Slope: 0.04; Adjusted P: 1.88E-02) mRNA (seq. RNA): lesional vs. perilesional (P < 0.05) Figure 9I. Petition 870260065164, dated 02 / 07 / 2026, page 86 / 213 / 85 Resistin (RETN) RETN Q9HD89 / SEQ ID NO: 34 RETN FIZZ3, ADSF, RETN1 Chemotaxis of myeloid cells; hormonal response Peripheral blood Blood test Protein (blood proteomics): Elevated vs. healthy controls (FDR <0.05); Correlation with dT count (Slope: 0.04; Adjusted P: 9.02E-03) Figure 9I Serpin A11 (SERPIN1 1) SERPIN A11 Q86U17 / SEQ ID NO: 35 SERPIN A11 NA Endopeptidase inhibitory activity Peripheral blood Blood test Protein (blood proteomics): Elevated vs. healthy controls (FDR <0.05); Correlation with dT count (Slope: 0.04; Adjusted P: 7.78E-03) Figure 9N C-type lectin domain family, 4 G members (CLEC4G) CLEC4G Q6UXB4 / SEQ ID NO: 36 CLEC4G UNQ431, LSECTIN Cell adhesion Peripheral blood Blood test Protein (proteomics in blood): Elevated vs.Healthy controls (FDR <0.05); Correlation with dT count (Slope: 0.04; Adjusted P: 9.24E-04) Figure 9 Macrophage colony-stimulating factor 1 (CSF1) CSF-1 P09603 / SEQ ID NO: 37 CSF1 M-CSF, MCSF, MGC31930 Regulation of hematopoietic precursor cells Peripheral blood Blood test Protein (proteomics in blood): Elevated vs. healthy controls (FDR <0.05); Correlation with dT count (Slope: 0.03; Adjusted P: 1.69E-03) Figure 9O Hepatocyte growth factor (HGF) HGF P14210 / SEQ ID NO: 38 HGF HPTA Growth factor Skin sample with lesion and peripheral blood Blood test, tape, punch biopsies, microbiopsy and any type of surgical specimen Protein (proteomics in blood): Elevated vs. healthy controls (FDR <0.05); Correlation with dT count (Slope: 0.03; Adjusted P: 4.14E-02) mRNA (seq. RNA): lesional vs. perilesional (P < 0.05) Figure 9I. Petition 870260065164, dated 02 / 07 / 2026, page 87 / 213 / 85 Protein disulfide isomerase CRELD2 (CRELD2) CRELD2 Q6UXH1 / SEQ ID NO: 39 CRELD2 MGC11256 Isomerase Skin sample with lesion and peripheral blood Blood test, tape, punch biopsies, microbiopsy and any type of surgical specimen Protein (proteomics in blood): Elevated vs. healthy controls (FDR <0.05); Correlation with dT count (Slope: 0.03; Adjusted P: 4.39E-02) mRNA (seq. RNA): lesional vs. perilesional (P < 0.05) Figure 9J EGF-containing fibulin-like extracellular matrix protein 1 (EFEMP1) EFEMP1 Q12805 / SEQ ID NO: 40 EFEMP1 S1-5, FBLN3, MTLV Growth factor; cell adhesion; Neurogenesis Peripheral blood Blood test Protein (proteomics in blood): Elevated vs. Figure 9Healthy controls (FDR <0.05); Correlation with dT count (Slope: 0.03; Adjusted P: 2.04E-02) Member 3 of the tumor necrosis factor receptor (LTBR) superfamily TNF-RIII P36941 / SEQ ID NO: 41 LTBR D12S370, TNFCR, TNFR3, TNFRSF3 Lipid metabolism; immune response; cell death Peripheral blood Blood test Protein (blood proteomics): Elevated vs. healthy controls (FDR <0.05); Correlation with dT count (Slope: 0.03; Adjusted P: 4.21E-03) Figure 9 Nucleoside diphosphate kinase 3 (NME3) NDK 3 Q13232 / SEQ ID NO: 42 NME3 DR-nm23, NM23-H3, NDPKC Granulocyte regulation; nucleotide metabolism Peripheral blood Blood test Protein (proteomics in blood): Elevated vs.Healthy controls (FDR <0.05); Correlation with dT count (Slope: 0.03; Adjusted P: 4.08E-03) Figure 9O Cytoskeleton-associated protein 4 (CKAP4) CKAP4 Q07065 / SEQ ID NO: 43 CKAP4 P63, CLIMP63, CLIMP63, ERGIC-63 Mediates cell proliferation Peripheral blood Blood test Protein (proteomics in blood): Elevated vs. healthy controls (FDR <0.05); Correlation with dT count (Slope: 0.03; Adjusted P: 4.07E-02) Figure 9P. Petition 870260065164, dated 02 / 07 / 2026, page 88 / 213 / 85 CD276 Antigen (CD276) CD276 Q5ZPR3 / SEQ ID NO: 44 CD276 B7H3 T / Th17 cell activation; NK cell regulation Skin sample with lesion and peripheral blood Blood test, tape test, punch biopsies, microbiopsy and any type of surgical specimen Protein (proteomics in blood): Elevated vs. healthy controls (FDR <0.05); Correlation with dT count (Slope: 0.03; Adjusted P: 2.54E-02) mRNA (seq. RNA): lesional vs. perilesional (P < 0.05) Figure 9J Spondin-2 (SPON2) SPON2 Q9BUD6 / SEQ ID NO: 45 SPON2 DIL1 Cell adhesion; Innate immunity Peripheral blood Blood test Protein (proteomics in blood): Elevated vs. healthy controls (FDR <0.05); Correlation with dT count (Slope: 0.03; Adjusted P: 2.23E-02) Figure 9P Gamma-glutamyl hydrolase (GGH) GGH Q92820 / SEQ ID NO: 46 GGH GATD10 Hydrolase; neutrophil degranulation Peripheral blood Blood test Protein (blood proteomics): Elevated vs.Healthy controls (FDR <0.05); Correlation with dT count (Slope: 0.03; Adjusted P: 2.54E-02) Figure 9P Metalloproteinase inhibitor 1 (TIMP1) TIMP-1 P01033 / SEQ ID NO: 47 TIMP1 CLGI, TIMP Growth factor; proteinase inhibitor Peripheral blood Blood test Protein (blood proteomics): Elevated vs. healthy controls (FDR <0.05); Correlation with dT count (Slope: 0.03; Adjusted P: 4.45E-02) Figure 9J T-cell surface Ly9 antigen (LY9) Ly-9 Q9HBG7 / SEQ ID NO: 48 LY9 CD229, mLY9, SLAMF3, hly9 Cell adhesion Skin sample with lesion and peripheral blood Blood test, tape swab, punch biopsies, microbiopsy and any type of surgical specimen Protein (proteomics in blood): Elevated vs. healthy controls (FDR <0.05); Correlation with dT count (Slope: 0.03; Adjusted P: 4.93E-02) mRNA (seq. RNA): lesional vs.perilesional (P < 0.05) Figure 9K Multiple coagulation factor deficiency protein 2 (MCFD2) MCFD2 Q8NI22 / SEQ ID NO: 49 MCFD2 F5F8D, LMAN1IP, SDNSF Protein transport; coagulation factor secretion Peripheral blood Blood test Protein (proteomics in blood): Correlation with dT count (Slope: 0.03; adjusted P: 1.61E-02) Figure 9P. Petition 870260065164, dated 02 / 07 / 2026, page 89 / 213 / 85 Transcobalamin-2 (TCN2) TC-2 P20062 / SEQ ID NO: 50 TCN2 D22S676, D22S750, TC2 Vitamin B12 binding and transport protein Peripheral blood Blood test Protein (blood proteomics): Elevated vs. healthy controls (FDR <0.05); Correlation with dT count (Slope: 0.02; Adjusted P: 3.83E-02) Figure 9K Glutaminylpeptide cyclotransferase (QPCT) QPCT Q16769 / SEQ ID NO: 51 QPCT QC, GCT Peptide biosynthesis Peripheral blood Blood test Protein (blood proteomics): Elevated vs. healthy controls (FDR <0.05); Correlation with dT count (Slope: 0.02; Adjusted P: 3.24E-02) Figure 9P Hypoxia-positively regulated protein 1 (HYOU1) HYOU1 Q9Y4L1 / SEQ ID NO: 52 HYOU1 ORP150, HSP12A, Grp170 Molecular chaperone: cytoprotective in cellular oxygen deprivation Skin sample with lesion and peripheral blood Blood test, tape, punch biopsies, microbiopsy and any type of surgical specimen Protein (proteomics in blood): Elevated vs.Healthy controls (FDR <0.05); Correlation with dT count (Slope: 0.02; Adjusted P: 8.79E-03) mRNA (seq. RNA): lesional vs. perilesional (P < 0.05) Figure 9K Member 13B of the tumor necrosis factor ligand superfamily (TNFSF13B) BAFF Q9Y275 / SEQ ID NO: 53 TNFSF13 B AFF, BLYS, TALL1, TNFSF20, ZTNF4 B cell activation; T / Th17 cell activation Peripheral blood Blood test Protein (blood proteomics): Elevated vs.Healthy controls (FDR <0.05); Correlation with dT count (Slope: 0.02; Adjusted P: 4.25E-02) Figure 9P CC motif chemokine ligand 7 (CCL7) CCL7 P80098 / SEQ ID NO: 54 CCL7 MCP-3, NC28, FIC, MARC, MCP3 Chemoattractant; neutrophil activation / degradation; NK cell activation; acts on monocytes, dendritic cells, neutrophils, NK cells and activated T cells; binds to CCR2; is produced by leukocytes, keratinocytes Skin sample with lesion Adhesive tape, punch biopsies, microbiopsy and any type of surgical specimen mRNA (RNA seq.): lesional vs. perilesional (3 times) Figure 9V. Petition 870260065164, dated 02 / 07 / 2026, page 90 / 213 / 85 Chemokine 13 containing C-XC motif (CXCL13) CXC13 O43927 / SEQ ID NO: 55 CXCL13 BLC, BCA-1, BLR1L, ANGIE, ANGIE2 B-cell chemoattractant Skin sample with lesion Adhesive tape, punch biopsies, microbiopsies and any type of surgical specimen mRNA (RNA seq): lesional vs.perilesional (P < 0.01) Figure 9V Protocadherin α-1 (PCDH1) PCDH1 Q08174 / SEQ ID NO: 56 PCDH1 pc42 Cell-cell interaction and adhesion Peripheral blood Blood test Protein (proteomics in blood): Correlation with dT count (Slope: 0.01; adjusted P: 6.75E-04) (decreased protein level associated with higher tunnel counts) Figure 9Q Bovine duct coccidiosis (BDC) BDC Q9BWV1 / SEQ ID NO: 57 BDC CDON2, Bovine Cell adhesion Skin sample with lesion and peripheral blood Blood test, tape, punch biopsies, microbiopsy and any type of surgical specimen Protein (proteomics in blood): Correlation with dT count (Slope: 0.02; adjusted P: 3.00E-02) (decreased protein level associated with higher tunnel counts) mRNA (seq. RNA): lesional vs.perilesional (P < 0.05) Figure 9Q Extracellular matrix phosphoglycoprotein (MEPE) MEPE Q9NQ76 / SEQ ID NO: 58 MEPE NA Bone mineralization; Cell proliferation and differentiation Blood test Protein (blood proteomics): Correlation with dT count (Slope: 0.03; Adjusted P: 1.79E-02) (decreased protein level associated with higher tunnel counts) Figure 9Q Disintegrin and protein 23 containing metalloproteinase domain (ADAM23) ADAM 23 O75077 / SEQ ID NO: 59 ADAM23 MDC3 Cell-cell interaction and adhesion Peripheral blood Blood test Protein (blood proteomics): Correlation with dT count (Slope: 0.03; Adjusted P: 4.16E-02) (decreased protein level associated with higher tunnel counts) Figure 9Q. Petition 870260065164, dated 02 / 07 / 2026, page 91 / 213 / 85 Thimet oligopeptides and (THOP1) THOP1 P52888 / SEQ ID NO: 60 THOP1 NA Neuropeptide metabolism Peripheral blood Blood test Protein (blood proteomics): Correlation with dT count (Slope: 0.03; Adjusted P: 7.17E-03) (decreased protein level associated with higher tunnel counts) Figure 9Q Interleukin-1 receptor-like 2 (IL1RL2) IL-1RL2 Q9HB29 / SEQ ID NO: 61 IL1RL2 IL1R-rp2, IL1RRP2, IL36R T cell activation Peripheral blood Blood test Protein (blood proteomics): Correlation with dT count (Slope: 0.03; Adjusted P: 4.39E-02) (decreased protein level associated with higher tunnel counts) Figure 9Q REST corepressor 1 (RCOR1) RCOR1 Q9UKL0 / SEQ ID NO: 62 RCOR1 COREST, KIAA0071 Regulation of transcription Peripheral blood Blood test Protein (proteomics in blood): Correlation with dT count (Slope: 0.03;Adjusted P: 4.93E-02) (decreased protein level associated with higher tunnel counts) Figure 9R Member of the tumor necrosis factor receptor (EDAR) superfamily EDAR Q9UNE0 / SEQ ID NO: 63 EDAR ED5, EDA3, ED1R, EDA1R Mediates NFkappa-B activation Peripheral blood Blood test Protein (blood proteomics): Correlation with dT count (Slope: 0.07; Adjusted P: 1.43E-02) (decreased protein level associated with higher tunnel counts) Figure 9R; Petition 870260065164, dated 02 / 07 / 2026, page 92 / 213 / 85 Chemokine 2 containing CC motif (CCL2) CCL2 P13500 / SEQ ID NO: 64 CCL2 MCP1, MCP1, MCAF, SMC-CF, GDCF-2, HC11, MGC9434 Chemoattractant; acts on monocytes, memory T cells, dendritic cells; binds to CCR2 and CCR4; T cell activation; immune cell extravasation; produced by monocytes, macrophages, dendritic cells, keratinocytes Skin sample with lesion Adhesive tape, punch biopsies, microbiopsy and any type of surgical specimen mRNA (seq. RNA): lesional vs. perilesional (P < 0.05) Protein: lesional vs. perilesional (P < 0.05) Figure 9U Chemokine 3 containing CC motif (CCL3) CCL3 P10147 / SEQ ID NO: 65 CCL3 G0S19-1, LD78ALFA, MIP-1-alpha, LD78, SCI Chemoattractant; neutrophil activation; ligase to CCR1, 4, 5; produced by leukocytes Skin sample with lesion Adhesive tape, punch biopsies, microbiopsy and any type of surgical specimen mRNA (seq. RNA): lesional vs.perilesional (P < 0.05) Figure 9U Chemokine containing CC4 motif (CCL4) CCL4 P13236 / SEQ ID NO: 66 CCL4 MIP-1-beta, Act-2. AT744.1 Chemoattractant; NK cell activation; immune cell extravasation: angiogenesis; acts on NK cells, monocytes, other leukocytes; binds to CCR5, 8; is produced by monocytes, T cells, dendritic cells, neutrophils, NK cells Skin sample with lesion Adhesive tape, punch biopsies, microbiopsy and any type of surgical specimen mRNA (seq. RNA): lesional vs. perilesional (P < 0.05) Protein: lesional vs. perilesional (P < 0.01) Figure 9S CC motif-containing chemokine ligand 5 (CCL5) CCL5 P13501 / SEQ ID NO: 67 CCL5 RANTES, SISd, TCP228, MGC17164 Chemoattractant; T cell activation; NK cell activation; immune cell extravasation; binds to CCR5; is produced by T cells, monocytes, keratinocytes Skin sample with lesion Adhesive tape, punch biopsies, microbiopsies and any type of surgical specimen mRNA (seq.RNA): lesional vs. perilesional (P < 0.05) Protein: lesional vs. perilesional (P < 0.05); Figure 9S. Petition 870260065164, dated 02 / 07 / 2026, page 93 / 213 / 85 Chemokine 20 containing CC motif (CCL20) CCL20 P78556 / SEQ ID NO: 68 CCL20 LARC, MIP3a, exodus-1, ST38, CKb4 Chemoattractant; T / Th17 cell activation; acts on B cells and DCs; binds to CCR6; is produced by neutrophils, NK cells, Th17 cells, B cells, DCs, LCs, macrophages, and keratinocytes Skin sample with lesion and peripheral blood Blood test, tape swab, punch biopsies, microbiopsy, and any type of surgical specimen Protein (proteomics in blood): Elevated vs. healthy controls (FDR <0.05); Protein: lesional vs. perilesional (P < 0.001) Figure 9S Growth-regulated protein alpha (CXCL1) CXCL1 P09341 / SEQ ID NO: 69 CXCL1 SCYB1, GROa, MGSA-a, NAP-3 Chemoattractant; neutrophil activation / degradation; ligase to CXCR2; produced by macrophages, neutrophils, Th17 cells, and keratinocytes Skin sample with lesion Adhesive tape, punch biopsies, microbiopsies, and any type of surgical specimen mRNA (RNA sequence): lesional vs.perilesional (P < 0.05); Protein: lesional vs. perilesional (P < 0.01) Figure 9T Chemokine 8 containing C-XC motif (CXCL8) CXCL8 P10145 / SEQ ID NO: 70 CXCL8 SCYB8, LUCT, LECT, MDNCF, TSG-1, IL-8, MONAP, K60, GCP1, NAP1 Chemoattractant; neutrophil activation / degradation; ligase to CXCR1>CXCR2; produced by macrophages, keratinocytes Skin sample with lesion Adhesive tape, punch biopsies, microbiopsy and any type of surgical specimen mRNA (seq. RNA): lesional vs. perilesional (P < 0.01); Protein: lesional vs. perilesional (P < 0.01) Figure 9T Platelet-derived growth factor (PDGF-A) subunit A PDGFAA P04085 / SEQ ID NO: 71 PDGFA PDGF1, PDGF-A Growth factor; Cell proliferation, migration and chemotaxis; acts on fibroblasts; binds to PDGF-Ra and b; is produced, for example, by macrophages Skin sample with lesion Adhesive tape, punch biopsies, microbiopsy and any type of surgical specimen Protein: lesional vs.perilesional (P < 0.05) Figure 9T CXC chemokine receptor type 2 (CXCR2) CXCR2 P25025 / SEQ ID NO: 72 CXCR2 CMKAR2, CD182 Receptor for GRO-alpha and CXCL8 Skin sample with lesion Adhesive tape, punch biopsies, microbiopsy and any type of surgical specimen mRNA (seq. RNA): lesional vs. perilesional (2 times) Figure 10 Chemokine receptor type 6 CC (CCR6) CCR6 P51684 / SEQ ID NO: 73 CCR6 CKR-L3, GPR-CY4, CMKBR6, GPR29, DRY-6, DCR2, BN-1, CD196 Receptor for CCL20 Skin sample with lesion Adhesive tape, punch biopsies, microbiopsy and any type of surgical specimen mRNA (seq. RNA): lesional vs. perilesional (3 times) Figure 10.

[00278] As additionally shown in Table 1, the research and Petition 870260065164, dated 02 / 07 / 2026, page 94 / 213 / 85. The above tests resulted in the identification of a significant elevation in biomarker levels in the peripheral blood of patients with HS compared to healthy controls (HCs). This number and variety of biomarkers reflect the remarkable inflammatory activity and complexity of HS. Here, a paired t-test was employed, defining the cutoff for significance at FDR<0.05.

[00279] Regression analysis was also conducted to establish a correlation between biomarker levels and the number of drainage tunnels. The slope value in Table 1 corresponds to the coefficient value; the higher the absolute value, the stronger the correlation. Notably, high drainage tunnel counts were linked with high levels of 58 biomarkers. High drainage tunnel counts also correlated with decreasing levels of 8 other biomarkers: PCDH1, BOC, MEPE, ADAM23, THOP1, IL1RL2, RCOR1, and EDAR. These findings underscore the active role of drainage tunnels in the pathophysiology of HS, positioning them as key contributors to HS pathology.

[00280] The molecular signature of drainage tunnel biomarkers in peripheral blood, along with the signature of additional mediating biomarkers, pathway and receptors of HS, were also explored in the tissue of HS drainage tunnels and compared to the signatures in perilesional tissue and inflammatory nodules at the mRNA and / or protein level with RNA sequencing and / or cytokine array or ELISA. In skin tissue with HS, higher expression of biomarkers was observed in the drainage tunnels compared to perilesional skin or inflammatory nodules.

[00281] The identification of such a panel of biomarkers with functional relevance not only for the timely diagnosis of HS, but also (i) assessment of the inflammatory activity of the disease as a correlation with the Petition 870260065164, dated 02 / 07 / 2026, page 95 / 213 / 85 tunnel counting, (ii) selection and initiation of appropriate therapy and (iii) monitoring of treatment response and management of therapy for long-term HS was unexpected. Example 3 Levels of elafin and IL-19 (circulating biomarkers) normalized after treatment compared to those observed in a healthy control population.

[00282] After 12 weeks of treatment with the IL-17 inhibitor SLK, the levels of two circulating biomarkers related to HS activity were normalized to those observed in a healthy control population (n = 50). The results indicate molecular cure of patients with HS and confirm the value of these biomarkers in the diagnosis and monitoring of HS. See Figure 21 and Table 2. Table 2. Biomarkers for monitoring the molecular response to treatment with IL-17 inhibitors. Biomarkers Data / Technical Effect Elafin (PI3) Figure 21 Interleukin-19 (IL19) Example 4 Biomarkers identifying super-responders with HS

[00283] The analysis “Subgroup Identification based on Differential Effect The “Search” (SIDES) (Lipkovich et al., Stat Med. 30(21):2601-21 (2011)) was employed as a partitioning method to determine treatment responses within specific patient groups. Subgroups of patients with higher biomarker expression levels demonstrated improved clinical outcomes in response to 120 mg of soneloquimab, as evidenced by the delta for placebo in response to HiSCR75 when compared to unselected patients. Applied threshold (NPX): LTO1 > -0.4123; IL-17A > -0.8321; TNC > -0.0153; CSF3 > -0.2455; OSM > -0.4974; PLA2G2A > 0.6373; CST7 > -0.628. Thus, each of a) LOT1, b) a combination of IL17A and TNC, c) G-CSF, d) OSM ee) Petition 870260065164, dated 02 / 07 / 2026, page 96 / 213 / 85 PLA2G2A surprisingly proved capable of identifying HS superresponders to an IL-17 inhibitor. See Figure 22 and Table 3.

[00284] Many of the biomarkers described in Table 1 reflect pathways involved in the pathophysiology of HS, such as neutrophil activation and degradation, angiogenesis and neurogenesis, innate immunity, T cell activation and especially Th17 cell activation, B cell activation, epithelial regeneration, extracellular matrix organization, keratinocyte activation, immune cell extravasation, and NK and CD8+ cell activation. However, other biomarkers have not been implicated in inflammatory conditions including HS. For example, LOT1 (also called PLAGL1 or ZAC1; see also Table 3) is a zinc finger nuclear transcription factor known to play a role in regulating cell growth. Associated diseases include growth retardation, neonatal diabetes mellitus, and various types of cancer (Abdollahi, J Cell Physiol. 2007 Jan; 210(1):16-25), but a role for this biomarker in inflammatory diseases, including HS, had not been previously described.Furthermore, a role for CST7, COL4A1, NRCAM, HYOU1, and SDC1 in HS had not yet been described. Table 3. Biomarkers indicative of Super-responders (Patient population highly responsive to treatment) with a specific nanobody against IL-17A+F___________________________________________________ Biomarkers Data / Technical Effect LTO1 protein homolog (LTO1) Figure 22 Interleukin-17A (IL17A) + Tenascin C (TNC) Granulocyte colony-stimulating factor (CSF3) Oncostatin-M (OSM) Membrane-associated phospholipase A2 (PLA2G2A) Cystatin-F (CST7)

Claims

1. Use of a nanobody that inhibits IL-17A and / or IL-17F, characterized by being in the preparation of a drug to treat an interleukin 17 (IL-17)-dependent condition, in which the individual has been identified as having an elevated level of one or more biomarkers selected from among IL6, PLA2G2A, IL19, PI3, CST7, IL17A, IL17F, GH1, MZB1, IL1B, IFNG, TNC, CXCL9, SLAMF7, VEGFA, IL17C, SLAMF1, SDC1, OSM, LBP, REG3A, CD79B, COL4A1, CLEC4D, VWF, IL5RA, CSF3, TGFA, IL2RA, ITIH3, FCAR, CCL23, NRCAM, RETN, SERPINA11, CLEC4G, CSF1, HGF, CRELD2, EFEMP1, LTBR, ​​NME3, CKAP4, CD276, SPON2, GGH, TIMP1, LY9, MCFD2, TCN2, QPCT, HYOU1, TNSFSF13B, CCL2, CCL3, CCL4, CCL5, CCL7, CCL20, CXCL1, CXCL8, PDFGA, CXCR2, CCR6 and CXCL13.

2. Use of an IL-17A and / or IL-17F inhibitor, characterized by being in the manufacture of a drug to treat hidradenitis suppurativa (HS), in which the individual was identified as having an elevated level of one or more biomarkers selected from among IL6, PLA2G2A, IL19, PI3, CST7, IL17A, IL17F, GH1, MZB1, IL1B, IFNG, TNC, CXCL9, SLAMF7, VEGFA, IL17C, SLAMF1, SDC1, OSM, LBP, REG3A, CD79B, COL4A1, CLEC4D, VWF, IL5RA, CSF3, TGFA, IL2RA, ITIH3, FCAR, CCL23, NRCAM, RETN, SERPINA11, CLEC4G, CSF1, HGF, CRELD2, EFEMP1, LTBR, ​​NME3, CKAP4, CD276, SPON2, GGH, TIMP1, LY9, MCFD2, TCN2, QPCT, HYOU1, TNSFSF13B, CCL2, CCL3, CCL4, CCL5, CCL7, CCL20, CXCL1, CXCL8, PDFGA, CXCR2, CCR6 and CXCL13.

3. Use according to claim 2, characterized in that the IL-17A and / or IL-17F inhibitor comprises a nanobody.

4. Use according to claim 1 or 3, characterized in that the nanobody is configured to bind specifically to IL-17A and IL-17F, preferably the nanobody is soneloquimab (SLK). Petition 870260065164, dated 02 / 07 / 2026, p. 98 / 213 2 / 13 5. Use in accordance with any one of claims 1 to 4, characterized in that the elevated level is compared to: (i) the level present in uninjured skin, preferably in perilesional skin, (ii) the level present in the peripheral blood of a healthy patient, or (iii) the level in the same individual before initial treatment.

6. Use in accordance with any one of claims 1 to 4, characterized in that the elevated level is compared to a reference value, and the reference value is (i) the biomarker expression level of the corresponding body fluid or tissue sample obtained from a healthy individual; (ii) the average biomarker level expressed in the corresponding body fluid or tissue of a plurality of healthy individuals; or (iii) the average biomarker level expressed in healthy tissue, preferably healthy tissue from the same individual, more preferably perilesional skin from the same individual.

7. Use in accordance with any of claims 1 to 6, characterized in that it comprises analyzing a tissue or body fluid sample, preferably a skin or peripheral blood sample, from a patient who has or is at risk of having an IL-17-dependent condition for the level of one or more biomarkers prior to treatment.

8. Use in accordance with any of claims 1 to 7, characterized in that an elevated level of one or more of the biomarkers indicates that the patient has (i) an inflammatory skin disease, preferably an inflammatory skin disease affecting the epidermis and dermis, more preferably an inflammatory skin disease involving hair follicle structures, even more preferably an inflammatory skin disease involving acneiform lesions, most preferably hidradenitis suppurativa (HS), such as moderate to severe HS, and / or (ii) a phenotype that includes one or more drainage tunnels in the skin. Petition 870260065164, dated 02 / 07 / 2026, p. 99 / 213 3 / 13 9. Use in accordance with any of claims 1 to 8, characterized in that the higher the level of one or more of the biomarkers, the greater the number of drainage tunnels present in the individual.

10. Use in accordance with any of claims 1 to 6, characterized in that the individual has been clinically diagnosed as having HS in Hurley Stage I, II or III.

11. Use in accordance with any of claims 1 to 6, characterized in that the individual has been clinically diagnosed as having mild HS, moderate HS, moderate to severe HS, severe HS, or juvenile HS.

12. Use in accordance with any of claims 1 to 6, characterized in that the individual does not have drainage tunnels.

13. Use in accordance with any one of claims 1 to 6, characterized in that the individual has at least one drainage tunnel.

14. Use in accordance with any one of claims 1 to 12, characterized in that the biomarkers comprise protein and / or mRNA biomarkers.

15. Use according to any of claims 1 to 14, characterized in that one or more of the biomarkers are selected from IL6, PLA2G2A, PI3, CST7, IL17A, IL17F, GH1, MZB1, IL1B, IFNG, TNC, CXCL9, SLAMF7, VEGFA, IL17C, SLAMF1, SDC1, OSM, LBP, REG3A, CD79B, COL4A1, CLEC4D, VWF, IL5RA, CSF3, TGFA, IL2RA, ITIH3, FCAR, CCL23, NRCAM, RETN, SERPINA11, CLEC4G, CSF1, HGF, CRELD2, EFEMP1, LTBR, ​​NME3, CKAP4, CD276, SPON2, GGH, TIMP1, LY9, MCFD2, TCN2, QPCT, HYOU1, TNSFSF13B, CCL2, CCL3, CCL4, CCL5, CCL7, CCL20, CXCL1, CXCL8, PDFGA, CXCR2, CCR6 and CXCL13. Petition 870260065164, dated 02 / 07 / 2026, page 100 / 213 4 / 13 16. Use according to any of claims 1 to 14, characterized in that one or more of the biomarkers are selected from IL6, PLA2G2A, IL19, PI3, CST7, GH1, MZB1, IL1B, IFNG, TNC, CXCL9, SLAMF7, VEGFA, IL17C, SLAMF1, SDC1, OSM, LBP, REG3A, CD79B, COL4A1, CLEC4D, VWF, IL5RA, CSF3, TGFA, IL2RA, ITIH3, FCAR, CCL23, NRCAM, RETN, SERPINA11, CLEC4G, CSF1, HGF, CRELD2, EFEMP1, LTBR, ​​NME3, CKAP4, CD276, SPON2, GGH, TIMP1, LY9, MCFD2, TCN2, QPCT, HYOU1, TNSFSF13B, CCL2, CCL3, CCL4, CCL5, CCL7, PDFGA, CXCR2, CCR6 and CXCL13.

17. Use in accordance with any of claims 1 to 14, characterized in that one or more of the biomarkers are selected from CSF3, CCL2, CCL3, CCL4, CCL5, CCL7, CCL20, CXCL1, CXCL8 and PDFGA.

18. Use in accordance with any one of claims 1 to 14, characterized in that one or more of the biomarkers are selected from CCL20, CXCL8, CXCL1, IL17A and IL17F.

19. Use of an agent that selectively binds to interleukin 17A (IL-17A) and / or interleukin 17F (IL-17F), characterized by the fact that it is used in the manufacture of a medicament to treat a condition in an individual determined to have an elevated level of at least one of the following biomarkers: IL6, PLA2G2A, IL19, PI3, CST7, IL17A, IL17F, GH1, MZB1, IL1B, IFNG, TNC, CXCL9, SLAMF7, VEGFA, IL17C, SLAMF1, SDC1, OSM, LBP, REG3A, CD79B, COL4A1, CLEC4D, VWF, IL5RA, CSF3, TGFA, IL2RA, ITIH3, FCAR, CCL23, NRCAM, RETN, SERPINA11, CLEC4G, CSF1, HGF, CRELD2, EFEMP1, LTBR, ​​​​NME3, CKAP4, CD276, SPON2, GGH, TIMP1, LY9, MCFD2, TCN2, QPCT, HYOU1, TNSFSF13B, CCL2, CCL3, CCL4, CCL5, CCL7, CCL20, CXCL1, CXCL8, PDFGA, CXCR2, CCR6 and CXCL13, compared to a healthy control, preferably where the elevated level is present in the skin and / or blood. Petition 870260065164, dated 02 / 07 / 2026, page 101 / 213 5 / 13 20. Use according to claim 19, characterized in that the elevated level of at least one biomarker is the level present in a biological sample from the individual, and the level of at least one corresponding biomarker present in the healthy control is representative of the level present in a biological sample not affected by an IL-17-dependent condition, preferably by an IL-17-dependent inflammatory skin disease, more preferably by hidradenitis suppurativa (HS).

21. Use according to claim 19, characterized in that the biomarkers are associated with an inflammatory skin disease, preferably an inflammatory skin disease affecting the epidermis and dermis, more preferably an inflammatory skin disease involving hair follicle structures, even more preferably an inflammatory skin disease involving acneiform lesions, most preferably hidradenitis suppurativa (HS).

22. Use in accordance with any of claims 19 to 21, characterized in that an elevated mRNA level or an elevated protein level is of at least one or more biomarkers selected from CCL20, CXCL8, CXCL1, IL17A and IL17F.

23. Use in accordance with any of claims 19 to 22, characterized in that an elevated level of mRNA or an elevated level of protein is present in a skin sample with a lesion compared to the respective mRNA or protein level in a skin sample without a lesion.

24. Use in accordance with any of claims 19 to 23, characterized in that a lesional IL-17F mRNA / non-lesional IL-17F ratio or protein ratio is determined.

25. Use in accordance with any of claims 19 to 24, characterized in that the individual has been identified as having an inflammatory skin disease, preferably an inflammatory skin disease affecting the epidermis and dermis, more preferably an inflammatory skin disease involving hair follicle structures, even more preferably an inflammatory skin disease involving acneiform lesions, most preferably hidradenitis suppurativa, exhibiting an elevated level of one or more biomarkers.

26. Use in accordance with any of claims 19 to 25, characterized in that the individual has been clinically diagnosed as having HS in Hurley Stage I, II or III.

27. Use in accordance with any of claims 19 to 26, characterized in that the release of IL-17A and / or IL-17F in Hurley Stage I, II and / or III of hidradenitis suppurativa is inhibited by the agent.

28. Use in accordance with any of claims 19 to 27, characterized in that the agent is an inhibitor of IL-17A and / or IL-17F.

29. Use in accordance with any of claims 19 to 28, characterized in that inflammation and / or tissue destruction are inhibited.

30. Use in accordance with any one of claims 19 to 29, characterized in that the agent comprises an antibody, an antibody fragment or a nanobody.

31. Use according to claim 30, characterized in that the agent comprises a nanobody.

32. Use according to any one of claims 19 to 21, characterized in that the agent is a nanobody, preferably soneloquimab or a derivative thereof, and a biomarker panel comprises a) CCL20, CXCL1, CXCL8, CXL1, IL17A, IL17F, IL19, LT01, CSF3, OSM, PLA2G2A, CST7 and / or PI3, b) IL17A, IL17F, CCL20, CXCL1, and / or CXCL8, c) IL17A, IL17F, CCL20, and / or CXCL8, d) LT01, IL17A, CSF3, OSM, PLA2G2A and / or CST7, e) CCL20, CXCL8, IL19 and PI3; or f) PI3 Petition 870260065164, dated 02 / 07 / 2026, page 103 / 213 7 / 13 and IL19.

33. Use of an IL-17A and / or IL-17F inhibitor, characterized by being in the manufacture of a drug to treat an interleukin 17 (IL-17)-dependent condition, in which the individual has been identified as having a reduced level of one or more biomarkers selected from PCDH1, BOC, MEPE, ADAM23, THOP1, IL1RL2, RCOR1 and EDAR.

34. Use according to claim 33, characterized in that the IL-17A and / or IL-17F inhibitor comprises a nanobody.

35. Use according to claim 33 or 34, characterized in that the nanobody is configured to bind specifically to IL-17A and IL-17F, preferably the nanobody is soneloquimab (SLK).

36. Use in accordance with any of claims 33 to 35, characterized in that the reduced level is compared to: (i) the level present in uninjured skin, preferably in perilesional skin, (ii) the level present in the peripheral blood of a healthy patient, or (iii) the level in the same individual before initial treatment.

37. Use in accordance with any one of claims 33 to 35, characterized in that the reduced level is compared to a reference value, and the reference value is (i) the biomarker expression level of the corresponding body fluid or tissue sample obtained from a healthy individual; (ii) the average biomarker level expressed in the corresponding body fluid or tissue of a plurality of healthy individuals; or (iii) the average biomarker level expressed in healthy tissue, preferably healthy tissue from the same individual, more preferably perilesional skin from the same individual.

38. Use in accordance with any of claims 33 to 37, characterized in that it comprises analyzing a sample of body tissue or fluid, preferably a skin or peripheral blood sample, from a patient who has or is at risk of having an IL-17 dependent condition for the level of one or more biomarkers prior to treatment.

39. Use in accordance with any of claims 33 to 38, characterized in that the reduced level of one or more of the biomarkers indicates that the patient has (i) an inflammatory skin disease, preferably an inflammatory skin disease affecting the epidermis and dermis, more preferably an inflammatory skin disease involving hair follicle structures, even more preferably an inflammatory skin disease involving acneiform lesions, most preferably hidradenitis suppurativa (HS), such as moderate to severe HS and / or (ii) a phenotype that includes one or more drainage tunnels in the skin.

40. Use in accordance with any of claims 33 to 39, characterized in that the lower the level of one or more of the biomarkers, the greater the number of drainage tunnels present in the individual.

41. Use in accordance with any of claims 33 to 40, characterized in that the individual has been clinically diagnosed as having HS in Hurley Stage I, II or III.

42. Use in accordance with any of claims 33 to 41, characterized in that the individual has been clinically diagnosed as having mild HS, moderate HS, moderate to severe HS, severe HS, or juvenile HS.

43. Use in accordance with any of claims 33 to 42, characterized in that the individual does not have drainage tunnels.

44. Use in accordance with any of claims 33 to 43, characterized in that the individual has at least one drainage tunnel.

45. Use in accordance with any of claims 33 to 44, characterized in that the biomarkers comprise Petition 870260065164, dated 02 / 07 / 2026, page 105 / 213 9 / 13 protein and / or mRNA biomarkers.

46. ​​Use of an agent that selectively binds to interleukin 17A (IL-17A) and / or interleukin 17F (IL-17F), characterized by being in the manufacture of a medicament to treat a condition in a determined individual to have a reduced level of at least one of the following biomarkers: PCDH1, BOC, MEPE, ADAM23, THOP1, IL1RL2, RCOR1 and EDAR in the skin and / or blood compared to a healthy control, preferably where the reduced level is present in the skin and / or blood.

47. A method for monitoring the progress of treatment or remission of an interleukin 17 (IL-17)-dependent condition, characterized in that it comprises analyzing a biological sample from an individual previously treated for the IL-17-dependent condition, preferably hidradenitis suppurativa, for one or more biomarkers selected from IL6, PLA2G2A, IL19, PI3, CST7, IL17A, IL17F, GH1, MZB1, IL1B, IFNG, TNC, CXCL9, SLAMF7, VEGFA, IL17C, SLAMF1, SDC1, OSM, LBP, REG3A, CD79B, COL4A1, CLEC4D, VWF, IL5RA, CSF3, TGFA, IL2RA, ITIH3, FCAR, CCL23, NRCAM, RETN, SERPINA11, CLEC4G, CSF1, HGF, CRELD2, EFEMP1, LTBR, ​​NME3, CKAP4, CD276, SPON2, GGH, TIMP1, LY9, MCFD2, TCN2, QPCT, HYOU1, TNSFSF13B, CCL2, CCL3, CCL4, CCL5, CCL7, CCL20, CXCL1, CXCL8, PDFGA, CXCR2, CCR6, CXCL13, PCDH1, BOC, MEPE, ADAM23, THOP1, IL1RL2, RCOR1 and EDAR.

48. Method according to claim 47, characterized in that the biomarkers comprise PI3 and IL19.

49. Method according to claim 47 or 48, characterized in that normalization of the level of one or more biomarkers to the level of a healthy control indicates (i) remission of inflammation; (ii) any tunnels present in the individual remain present but are no longer active; and / or (iii) treatment should be discontinued. Petition 870260065164, dated 02 / 07 / 2026, pp. 106 / 213 10 / 13 50. A method for identifying an individual who has or is at risk of having hidradenitis suppurativa (HS), characterized in that it comprises determining the IL-17F / IL-17A protein or mRNA ratio present in a tissue sample from the individual.

51. Method for detecting hidradenitis suppurativa (HS), characterized in that it comprises analyzing a sample from an individual who has or is at risk of having HS for elevated levels of one or more of the following: IL6, PLA2G2A, IL19, PI3, CST7, IL17A, IL17F, GH1, MZB1, IL1B, IFNG, TNC, CXCL9, SLAMF7, VEGFA, IL17C, SLAMF1, SDC1, OSM, LBP, REG3A, CD79B, COL4A1, CLEC4D, VWF, IL5RA, CSF3, TGFA, IL2RA, ITIH3, FCAR, CCL23, NRCAM, RETN, SERPINA11, CLEC4G, CSF1, HGF, CRELD2, EFEMP1, LTBR, ​​NME3, CKAP4, CD276, SPON2, GGH, TIMP1, LY9, MCFD2, TCN2, QPCT, HYOU1, TNSFSF13B, CCL2, CCL3, CCL4, CCL5, CCL7, CCL20, CXCL1, CXCL8, PDFGA, CXCR2, CCR6 and CXCL13; or reduced levels of one or more of PCDH1, BOC, MEPE, ADAM23, THOP1, IL1RL2, RCOR1 and EDAR.

52. Method according to claim 51, characterized in that the respective elevated or reduced level is compared to: (i) the level present in uninjured skin, preferably in perilesional skin, (ii) the level present in the peripheral blood of a healthy patient, or (iii) the level in the same individual before initial treatment.

53. Method according to claim 51, characterized in that the respective elevated or reduced level is compared to a reference value, and the reference value is (i) the expression level of the biomarker in the corresponding body fluid or tissue sample obtained from a healthy individual; (ii) the average level of the biomarker expressed in the corresponding body fluid or tissue of a plurality of healthy individuals; or (iii) the average level of the biomarker expressed in healthy tissue, preferably healthy tissue from the same individual, more preferably perilesional skin from the same individual.

54. A method according to any one of claims 51 to 53, characterized in that it comprises analyzing a sample of body tissue or fluid, preferably a skin or peripheral blood sample, from a patient who has or is at risk of having HS.

55. Use of an agent configured to inhibit IL-17F, characterized by being used in the manufacture of a medicament to treat an individual with an analyzed lesional / non-lesional interleukin 17F (IL-17F) protein ratio of 2 or more, preferably 10 or more, more preferably 2 to 50 and, most preferably, 10 to 30, where IL-17F is present in the dermis of an inflammatory skin lesion of the individual.

56. Use of an agent configured to inhibit IL-17F, characterized by being in the manufacture of a medicament to treat an individual with an analyzed messenger ribonucleic acid (mRNA) ratio of lesional interleukin 17F (IL-17F) to non-lesional interleukin 17F (IL-17F) of 5 or more, preferably 10 or more, more preferably 5 to 500 and, most preferably, 10 to 300, where IL-17F is present in the dermis of an inflammatory skin lesion of the individual.

57. Use of an IL-17A and / or IL-17F inhibitor, characterized by being in the manufacture of a drug to treat hidradenitis suppurativa, wherein the individual has been identified as having elevated levels of one or more biomarkers selected from (a) LTO1, (b) CSF3, (c) OSM, (d) PLA2G2A, or (e) a combination of IL17A and TNC.

58. Method for identifying a patient with hidradenitis suppurativa who responds to treatment with a nanobody that inhibits interleukin 17A (IL-17A) and / or interleukin 17F (IL-17F), characterized in that it comprises analyzing a biological sample from the patient Petition 870260065164, dated 02 / 07 / 2026, page 108 / 213 12 / 13 for the presence of one or more biomarkers selected from (a) LTO1, (b) CSF3, (c) OSM, (d) PLA2G2A or (e) a combination of IL17A and TNC, wherein the presence of an elevated level of at least one, two, three or more of the biomarkers indicates that the patient responds to treatment with a nanobody that inhibits IL-17A and / or IL-17F.

59. Method according to claim 58, characterized in that it comprises identifying a patient who is a superresponder.

60. Method according to claim 58 or 59, characterized in that the identified patient receives treatment with a nanobody that inhibits IL-17A and / or IL-17F, preferably soneloquimab.

61. Method according to any one of claims 58 to 60, characterized in that the nanobody comprises soneloquimab.

62. Kit for identifying an individual at risk or in need of treatment for an interleukin 17 (IL-17)-dependent condition, characterized in that the kit comprises a reagent or reagents for measuring the level or expression of one or more of the following: IL6, PLA2G2A, IL19, PI3, CST7, IL17A, IL17F, GH1, MZB1, IL1B, IFNG, TNC, CXCL9, SLAMF7, VEGFA, IL17C, SLAMF1, SDC1, OSM, LBP, REG3A, CD79B, COL4A1, CLEC4D, VWF, IL5RA, CSF3, TGFA, IL2RA, ITIH3, FCAR, CCL23, NRCAM, RETN, SERPINA11, CLEC4G, CSF1, HGF, CRELD2, EFEMP1, LTBR, ​​NME3, CKAP4, CD276, SPON2, GGH, TIMP1, LY9, MCFD2, TCN2, QPCT, HYOU1, TNSFSF13B, CCL2, CCL3, CCL4, CCL5, CCL7, CCL20, CXCL1, CXCL8, PDFGA, CXCR2, CCR6, CXCL13, PCDH1, BOC, MEPE, ADAM23, THOP1, IL1RL2, RCOR1 and EDAR.

63. Kit according to claim 62, characterized in that it further comprises packaged components for obtaining a biological sample from an individual, preferably for obtaining a skin sample or a body fluid sample, optionally wherein the body fluid sample is a blood sample.

64. Kit according to claim 62 or 63, characterized in that it comprises an adhesive strip for obtaining a skin sample or packaged components for obtaining a punch biopsy, microbiopsy or surgical specimen.

65. Kit for treating a dermatological condition dependent on interleukin 17 (IL-17), characterized in that the kit comprises a pharmaceutical composition comprising an IL-17A and / or IL-17F inhibitor, and a reagent for measuring the level or expression of IL-6, PLA2G2A, IL-19, PI-3, CST-7, IL-17A, IL-17F, GH-1, MZB-1, IL-1B, IFNG-1, TNC-1, CXCL-9, SLAMF-7, VEGFA-1, IL-17C, SLAMF-1, SDC-1, OSM-1, LBP-1, REG3A-1, CD79B-1, COL4A1-1, CLEC4D-1, VWF-1, IL5RA-1, CSF3-1, TGFA-1, IL2RA-1, ITIH3-1, FCAR-1, CCL23-1, NRCAM-1, RETN-1, SERPINA11-1, CLEC4G-1, CSF1-1, HGF-1, CRELD2-1, EFEMP1-1, LTBR-1, NME3, CKAP4, CD276, SPON2, GGH, TIMP1, LY9, MCFD2, TCN2, QPCT, HYOU1, TNSFSF13B, CCL2, CCL3, CCL4, CCL5, CCL7, CCL20, CXCL1, CXCL8, PDFGA, CXCR2, CCR6, CXCL13, PCDH1, BOC, MEPE, ADAM23, THOP1, IL1RL2, RCOR1 and / or EDAR, in a sample taken from an individual.

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