Methods and compositions for treating genital psoriasis

Abstract

The disclosure relates to methods of treating genital psoriasis comprising administering an anti-IL-23p19 antibody hum13B8-b to a patient in need thereof. The disclosure also relates to pharmaceutical compositions of an anti-IL-23p19 antibody hum13B8-b or antigen binding fragment thereof for the treatment of genital psoriasis in a patient. The disclosure further relates to the use of an anti-IL-23p19 antibody hum13B8-b or antigen binding fragment thereof for the manufacture of a medicament for treating genital psoriasis in a patient.

Description

MBHB Ref. 24-0818-WOMETHODS AND COMPOSITIONS FOR TREATING GENITAL PSORIASISCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of priority of Indian Provisional Application No. 202421071226, filed September 20, 2024, and Indian Provisional Application No. 202521068869, filed July 18, 2025, each of which is incorporated herein by reference in its entirety.REFERENCE TO AN ELECTRONIC SEQUENCE LISTING

[0002] This application is being filed electronically and includes an electronically submitted sequence listing. The sequence listing is entitled "24-0818-WO-Sequence- Listing.xml" and was created on September 17, 2025, and has a size of 8,465 bytes. The sequence listing contained in this xml file is part of the specification and is herein incorporated by reference in its entirety.FIELD OF THE DISCLOSURE

[0003] The disclosure relates to methods of treating genital psoriasis comprising administering an anti-IL-23pl9 antibody huml3B8-b to a patient in need thereof. The disclosure also relates to pharmaceutical compositions of an anti-IL-23pl9 antibody huml3B8-b or antigen binding fragment thereof for the treatment of genital psoriasis in a patient. The disclosure further relates to the use of an anti-IL-23pl9 antibody huml3B8-b or antigen binding fragment thereof for the manufacture of a medicament for treating genital psoriasis in a patient.BACKGROUND

[0004] Psoriasis is an immune-mediated chronic inflammatory skin disease characterized by recurrent episodes of sharply demarcated, erythematous, scaly plaques of variable size and confluence that affects ~2% of the global population. Psoriasis can present with a variety of different morphologies in the form of plaque, guttate, rupioid, erythrodermic, pustular, inverse, elephantine, and psoriatic arthritis. Site variation is associated with psoriasis and can involve the scalp, palmoplantar region, genitals, and nails.

[0005] Recent studies involving a physical examination of patients with psoriasis indicate that 38% have current genital involvement and 63% develop genital psoriasis at least once over the course of their disease. Genital region friction, moisture, and maceration contribute to genital psoriasis which is characterized by thin, symmetrical, and bright red plaques with well-defined edges, generally lacking the characteristic scale and thickness observed on other body areas. Genital psoriasis is further characterized by well-demarcated, erythematous thinMBHB Ref. 24-0818-WO plaques, with variable degrees of scale, which is often associated with intense itch, burning sensation, and dyspareunia. Genital psoriasis has a huge negative impact on quality of life, affecting daily activities social interaction, and sexual health.

[0006] Treatment of genital skin is a challenge due to the unique microenvironment of the genital skin, and the results of studies investigating treatments of classic psoriasis often do not transfer directly to genital psoriasis. Evidence-based recommendations for genital psoriasis indicate the use of short-term topical low-to-medium power corticoids as a first-line treatment option, which can be combined with vitamin D analogs or mild tar preparations. However, coal-tar preparations have been associated with irritation or folliculitis. Topical immunomodulator agents are also sometimes used but require close monitoring of patients for complications. Alternative common treatment modalities can also be used but are limited in utility and associated with a range of side effects.

[0007] Biologicals and traditional systemic medications are an option for patients with moderate-to-severe psoriasis. Currently approved biological treatments include tumor necrosis factor antagonist agents such as etanercept, infliximab, and adalimumab, and p40 (IL-12 and IL-23) antagonists such as ustekinumab, guselkumab, and risankizumab, and IL- 17 antagonists such as secukinumab, ixekizumab, and brodalumab (Sbidian et al.. Cochrane Database Syst. Rev. 12(12): CD011535 (2017); Ellis et al., Br. J. Dermatol. 180(2): 282-88 (2019)).

[0008] IL-23 is a heterodimeric cytokine consisting of a unique pl9 sub-unit and a common p40 sub-unit shared with IL- 12. It is mainly produced by activated myeloid cells, and signals through a heterodimeric IL-23 receptor complex consisting of a unique IL-23 receptor (IL23R) paired with IL-12Rpi. Soon after its discovery, IL-23 was recognized as a key driver of autoimmunity in mouse models and human diseases. This has been commonly attributed to the ability of IL-23 to polarize and activate Th 17 cells, a subset of T cells that has been identified as having a central role in autoimmunity. In recent years, accumulating data has implicated the IL-23 / Thl7 pathway in psoriasis pathogenesis. Recent genome-wide association studies have identified psoriasis risk alleles around gene regions that encode IL- 23 (IL23A, IL12B) and the IL-23 receptor (IL-23R). Indeed, both pl9 and p40 sub-units of IL-23 are over-expressed in psoriatic skin lesions, while the unique p35 sub-unit of IL-12 is not.

[0009] Tildrakizumab (SCH 900222 / MK-3222), hereafter referred to as tildrakizumab (MK-3222), is a high-affinity (297 pM), humanized IgGl / K antibody that specifically binds to IL-23pl9 (SN 08197) but does not bind human IL-12 (IL-12p40 and p35 heterodimer) orMBHB Ref. 24-0818-WO human p40. Efficacy and safety of tildrakizumab in the treatment of patients with moderate- to-severe plaque psoriasis was demonstrated in 2 pivotal Phase 3 studies (P010 and P011) (Beck etal., Psoriasis (Auckl.) 8: 49-58 (2018); Reich et al., Lancet 390(10091): 276-88 (2017)). Additionally, results from a Phase 2 dose-ranging study demonstrated that treatment with tildrakizumab demonstrated positive change in proportions of subjects with a PASI 75, or PASI 90 and increases in the proportion of subjects with a PGA score of "clear" or "minimal". Tildrakizumab was demonstrated to maintain efficacy over more than four years of treatment in plaque psoriasis. When combined with the results from the Phase 2 and Phase 3 studies tildrakizumab is generally well tolerated with a low incidence of drug-related AEs and AEs leading to discontinuation of the study medication.

[0010] Despite these results related to plaque psoriasis, there remains a need for therapeutic options for genital psoriasis that are effective and can be safely administered over the long-term.SUMMARY

[0011] Provided herein is a method of treating genital psoriasis comprising administering an anti-IL-23pl9 antibody huml3B8-b to a patient in need thereof. Also provided herein is a pharmaceutical composition of an anti-IL-23pl9 antibody huml3B8-b or antigen binding fragment thereof for the treatment of genital psoriasis in a patient. Further provided herein is the use of an anti-IL-23pl9 antibody huml3B8-b or antigen binding fragment thereof for the manufacture of a medicament for treating genital psoriasis in a patient. In some embodiments, provided herein are methods, pharmaceutical compositions, and medicaments for treating genital psoriasis wherein treatment results in the patient achieving a modified Static Physician's Global Assessment of Genitalia (sPGA-G) score of "clear" (0) or "minimal" (1) with at least a 2-point reduction from Baseline.

[0012] Further provided herein are methods, pharmaceutical compositions, and medicaments for treating genital psoriasis, wherein treatment results in the patient with a baseline Genital Psoriasis Itch Numerical Rating Scale (GPI-NRS) of >4, achieving at-least a 4-point improvement in weekly average of GPI-NRS.

[0013] Further provided herein are methods, pharmaceutical compositions, and medicaments for treating genital psoriasis, wherein treatment results in the patient exhibiting a change, from baseline, in the affected BSA.

[0014] Further provided herein are methods, pharmaceutical compositions, and medicaments for treating genital psoriasis, wherein treatment results in the patient having aMBHB Ref. 24-0818-WO means change, from baseline, in the Genital Psoriasis Symptoms Scale (GPSS) total score and individual items score.

[0015] Further provided herein are methods, pharmaceutical compositions, and medicaments for treating genital psoriasis wherein treatment improves plaque psoriasis as measured by body surface area (BSA) affected by plaque psoriasis or results in the patient maintaining at least a 75% reduction in the Psoriasis Area and Severity Index (PASI 75), or results in the patient maintaining at least a 90% reduction in the Psoriasis Area and Severity Index (PASI 90), or results in the patient maintaining a 100% reduction in the Psoriasis Area and Severity Index (PASI 100) compared to the baseline.

[0016] Further provided herein are methods, pharmaceutical compositions, and medicaments for treating genital psoriasis wherein treatment in patients with a baseline Static Physician's Global Assessment (sPGA) score of >3, who achieve an overall modified sPGA score of clear (0) or almost clear (1) with at-least a 2-point reduction from baseline.

[0017] Further provided herein are methods, pharmaceutical compositions, and medicaments for treating genital psoriasis wherein treatment improves plaque psoriasis, as measured by body surface area (BSA) affected by plaque psoriasis; or results in the patient maintaining at least a 75% reduction in the Psoriasis Area and Severity Index (PASI 75), or results in the patient maintaining at least a 90% reduction in the Psoriasis Area and Severity Index (PASI 90), or results in the patient maintaining a 100% reduction in the Psoriasis Area and Severity Index (PASI 100) compared to the baseline in subjects with BSA >_1%.

[0018] Further provided herein are methods, pharmaceutical compositions, and medicaments for treating genital psoriasis, wherein treatment results in the patient achieving an absolute PASI score of <2, or a PASI score of <1 at Week 16, Week 28, Week 40, and Week 52.

[0019] Further provided herein are methods, pharmaceutical compositions, and medicaments for treating genital psoriasis, wherein treatment improves genital psoriasis itch numerical rating scale (GPI-NRS) in the patient, as indicated by at least a 4-point improvement in GPI-NPRS within the score as measured by the genital psoriasis symptoms scale (GPSS).

[0020] Further provided herein are methods, pharmaceutical compositions, and medicaments for treating genital itch wherein treatment improves the health-related quality of life measured by dermatology life quality index (DLQI), and genital psoriasis symptoms as measured by GPSS.MBHB Ref. 24-0818-WO

[0021] Further provided herein are methods, pharmaceutical compositions, and medicaments for treating genital psoriasis wherein treatment results in the patient experiencing no increase in adverse events (AEs), drug-related AEs, severe adverse events (SAEs), Tier 1 AEs, or Tier 2 AEs for at least up to about 20 weeks after the last dose of an anti-IL-23pl9 antibody huml3B8-b.

[0022] Further provided herein is a method of treating genital psoriasis comprising administering an anti-IL-23pl9 antibody huml3B8-b to a patient in need thereof, wherein huml3B8-b comprises: (i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO: 1, and (ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO: 2; and wherein huml3B8-b is administered to the patient for at least up to about 52 weeks.

[0023] Further provided herein is a method of improving a modified_Static Physician Global Assessment of Genitalia (sPGA-G) score in genital psoriasis, comprising administering an anti-IL-23pl9 antibody huml3B8-b to a patient in need thereof, wherein huml3B8-b comprises: (i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO: 1, and (ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO: 2; and wherein huml3B8-b is administered to the patient for at least up to about 52 weeks.BRIEF DESCRIPTIONS OF THE DRAWINGS

[0024] The following detailed description of the embodiments of the present disclosure can be best understood when read in conjunction with the following drawings.

[0025] FIG. 1 is a schematic showing the study design for treating moderate to severe genital psoriasis, comprising a 16-week placebo-controlled period, a 36-week active treatment period, and a 20-week follow-up period. The Part 2 drug is tildrakizumab administered at 100 mg, subcutaneously. To maintain blinding, all subjects received corresponding placebo in Part 2 of the study.DETAILED DESCRIPTION

[0026] The present disclosure relates to methods and compositions of treating genital psoriasis comprising administering an anti-IL-23pl9 antibody huml3B8-b to a patient in need thereof. The present disclosure also relates to pharmaceutical compositions of an anti- IL-23pl9 antibody huml3B8-b or antigen binding fragment thereof for the treatment genital psoriasis in a patient. The present disclosure further relates to the use of an anti-IL-23pl9MBHB Ref. 24-0818-WO antibody huml3B8-b or antigen binding fragment thereof for the manufacture of a medicament for treating genital psoriasis in a patient.

[0027] In some embodiments, the disclosure relates to methods, pharmaceutical compositions, and medicaments for treating genital psoriasis wherein treatment results in the patient achieving a modified Static Physician's Global Assessment of Genitalia (s-PGA-G) score of "clear" (0) or "almost clear" (1) with at least a 2-point reduction from Baseline. In some embodiments, the disclosure relates to methods, pharmaceutical compositions, and medicaments for treating genital psoriasis wherein treatment improves plaque psoriasis as measured by body surface area (BSA) affected by plaque psoriasis; or results in the patient maintaining at least a 75% reduction in the Psoriasis Area and Severity Index (PASI 75), or results in the patient maintaining at least a 90% reduction in the Psoriasis Area and Severity Index (PASI 90), or results in the patient maintaining a 100% reduction in the Psoriasis Area and Severity Index (PASI 100) compared to the baseline. In some embodiments, the disclosure relates to methods, pharmaceutical compositions, and medicaments for treating genital psoriasis wherein treatment improves genital psoriasis itch numerical rating scale (GPI-NRS) as indicated by at least a 4-point improvement in GPI-NPRS within the score as measured by the genital psoriasis symptoms scale (GPSS). In some embodiments, the disclosure relates to methods, pharmaceutical compositions, and medicaments for treating genital itch wherein treatment improves the health related quality of life measured by dermatology life quality index (DLQI), and genital psoriasis symptoms as measured by GPSS. In some embodiments, the disclosure relates to methods, pharmaceutical compositions, and medicaments for treating genital psoriasis wherein treatment results in the patient experiencing no increase in adverse events (AEs), drug-related AEs, severe adverse events (SAEs), Tier 1 AEs, or Tier 2 AEs for at least up to about 20 weeks after the last dose of an anti-IL-23pl9 antibody huml3B8-b.

[0028] Before describing the present disclosure in detail, a number of terms will be defined. Unless otherwise required by context, singular terms shall include pluralities, and plural terms shall include the singular. For example, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise. It should be understood that the terms "a" and "an" as used herein refer to "one or more" of the enumerated components unless otherwise indicated or dictated by its context. The use of the alternative (e.g., "or") should be understood to mean either one, both, or any combination thereof of the alternatives unless otherwise indicated.MBHB Ref. 24-0818-WO

[0029] In the present disclosure, any concentration range, percentage range, ratio range, or integer range is to be understood to include the value of any integer within the recited range and, when appropriate, fractions thereof (such as one tenth and one hundredth of an integer), unless otherwise indicated.

[0030] The term "about" or "approximately" means within an acceptable error range for the particular value as determined by one of ordinary skill in the art, which will depend in part on how the value is measured or determined, z.e., the limitations of the measurement system. For example, "about" can mean within 3 or more than 3 standard deviations, per the practice in the art. Alternatively, "about" can mean a range of up to 20%, preferably up to 10%, more preferably up to 5%, and more preferably still up to 1% of a given value.Alternatively, particularly with respect to biological systems or processes, the term can mean within an order of magnitude, preferably within 5 -fold, and more preferably within 2-fold, of a value. With regard to the administration of the anti-IL-23pl9 antibody huml3B8-b or an antigen-binding fragment thereof as described herein, the term "about" when used with respect to a number of weeks means the number of weeks + / - 7 days.

[0031] It is noted that terms like "preferably," "commonly," and "typically" are not used herein to limit the scope of the claimed subject matter or to imply that certain features are critical, essential, or even important to the structure or function of the claimed subject matter. Rather, these terms are merely intended to highlight alternative or additional features that can or cannot be used in a particular embodiment of the present disclosure.

[0032] For the purposes of describing and defining the present disclosure it is noted that the term "substantially" is used herein to represent the inherent degree of uncertainty that can be attributed to any quantitative comparison, value, measurement, or other representation. The term "substantially" is also used herein to represent the degree by which a quantitative representation can vary from a stated reference without resulting in a change in the basic function of the subject matter at issue.

[0033] Unless expressly specified otherwise, the term "comprising" is used in the context of the present disclosure to indicate that further members may optionally be present in addition to the members of the list introduced by "comprising". It is, however, contemplated as a specific embodiment of the present disclosure that the term "comprising" encompasses the possibility of no further members being present.

[0034] As used in accordance with the present disclosure, unless otherwise indicated, all technical and scientific terms shall be understood to have the same meaning as commonly understood by one of ordinary skill in the art.MBHB Ref. 24-0818-WO

[0035] The present disclosure relates to relates to methods of treating genital psoriasis comprising administering an anti-IL-23pl9 antibody huml3B8-b to a patient in need thereof. The disclosure also relates to pharmaceutical compositions of an anti-IL-23pl9 antibody huml3B8-b or antigen binding fragment thereof for the treatment genital psoriasis in a patient. The disclosure further relates to the use of an anti-IL-23pl9 antibody huml3B8-b or antigen binding fragment thereof for the manufacture of a medicament for treating genital psoriasis in a patient.

[0036] In one embodiment, provided herein is a method of treating genital psoriasis comprising administering an anti-IL-23pl9 antibody huml3B8-b to a patient in need thereof, wherein huml3B8-b comprises: (i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO: 1, and (ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO: 2; and wherein huml3B8-b is administered to the patient for up to about at least 52 weeks.

[0037] In another embodiment, provided herein is a method for maintaining a modified Static Physician's Global Assessment of Genitalia (sPGA-G) score of "clear" or "minimal" with at least a 2-point reduction from Baseline in a patient with genital psoriasis comprising administering an anti-IL-23pl9 antibody huml3B8-b to a patient in need thereof, wherein huml3B8-b comprises: (i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO: 1, and (ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO: 2; and wherein huml3B8-b is administered to the patient for up to about at least 52 weeks.

[0038] In another embodiment, provided herein is a method for maintaining at least a 75% reduction in the Psoriasis Area and Severity Index (PASI 75) in a patient with plaque psoriasis comprising administering an anti-IL-23pl9 antibody huml3B8-b to a patient in need thereof, wherein huml3B8-b comprises: (i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO: 1, and (ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO: 2; and wherein huml3B8-b is administered to the patient for up to about at least 52 weeks.

[0039] In another embodiment, provided herein is a method for maintaining at least a 90% reduction in the Psoriasis Area and Severity Index (PASI 90) in a patient with plaque psoriasis comprising administering an anti-IL-23pl9 antibody huml3B8-b to a patient in need thereof, wherein huml3B8-b comprises: (i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO: 1, and (ii) a heavy chain polypeptide comprising theMBHB Ref. 24-0818-WO amino acid sequence of SEQ ID NO: 2; and wherein huml3B8-b is administered to the patient for up to about at least 52 weeks.

[0040] In another embodiment, provided herein is a method for maintaining a 100% reduction in the Psoriasis Area and Severity Index (PASI 100) in a patient with plaque psoriasis comprising administering an anti-IL-23pl9 antibody huml3B8-b to a patient in need thereof, wherein huml3B8-b comprises: (i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO: 1, and (ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO: 2; and wherein huml3B8-b is administered to the patient for up to about at least 52 weeks.

[0041] In another embodiment, provided herein is a method of treating genital psoriasis comprising administering an anti-IL-23pl9 antibody huml3B8-b to a patient in need thereof, wherein huml3B8-b comprises: (i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO: 1, and (ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO: 2; and wherein administration of huml3B8-b results in the patient experiencing no increase in adverse events (AEs), drug-related AEs, severe adverse events (SAEs), Tier 1 AEs, or Tier 2 AEs for at least up to about 72 weeks to at least up to about 72 weeks as compared to treatment for up to about 52 weeks to at least about 72 weeks.

[0042] The present disclosure also relates to pharmaceutical compositions of an anti-IL- 23pl9 antibody huml3B8-b or antigen binding fragment thereof forthe treatment of genital psoriasis in a patient. In one embodiment, the present disclosure provides a pharmaceutical composition of an anti-IL-23pl9 antibody huml3B8-b for the treatment of genital psoriasis in a patient, wherein huml3B8-b comprises: (i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO: 1, and (ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO: 2; and wherein the pharmaceutical composition is administered to the patient for at least up to about 52 weeks.

[0043] In another embodiment, provided herein is a pharmaceutical composition of an anti-IL-23pl9 antibody huml3B8-b for maintaining a modified Static Physician's Global Assessment of Genitalia (sPGA-G) score of "clear" or "minimal" with at least a 2-point reduction from Baseline in a patient with genital psoriasis comprising administering an anti- IL-23pl9 antibody huml3B8-b to a patient in need thereof, wherein huml3B8-b comprises: (i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO: 1, and (ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO: 2; and wherein huml3B8-b is administered to the patient for up to at least about 52 weeks.MBHB Ref. 24-0818-WO

[0044] In another embodiment, provided herein is a pharmaceutical composition of an anti-IL-23pl9 antibody huml3B8-b for maintaining at least a 75% reduction in the Psoriasis Area and Severity Index (PASI 75) in a patient with plaque psoriasis comprising administering an anti-IL-23pl9 antibody huml3B8-b to a patient in need thereof, wherein huml3B8-b comprises: (i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO: 1, and (ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO: 2; and wherein huml3B8-b is administered to the patient for up to about at least 52 weeks.

[0045] In another embodiment, provided herein is a pharmaceutical composition of an anti-IL-23pl9 antibody huml3B8-b for maintaining at least a 90% reduction in the Psoriasis Area and Severity Index (PASI 90) in a patient with plaque psoriasis comprising administering an anti-IL-23pl9 antibody huml3B8-b to a patient in need thereof, wherein huml3B8-b comprises: (i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO: 1, and (ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO: 2; and wherein huml3B8-b is administered to the patient for up to about at least 52 weeks.

[0046] In another embodiment, provided herein is a pharmaceutical composition of an anti- IL-23pl9 antibody huml3B8-b for maintaining a 100% reduction in the Psoriasis Area and Severity Index (PASI 100) in a patient with plaque psoriasis comprising administering an anti-IL-23pl9 antibody huml3B8-b to a patient in need thereof, wherein huml3B8-b comprises: (i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO: 1, and (ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO: 2; and wherein huml3B8-b is administered to the patient for up to about at least 52 weeks.

[0047] In another embodiment, provided herein is a pharmaceutical composition of an anti-IL-23pl9 antibody huml3B8-b to a patient in need thereof, wherein huml3B8-b comprises: (i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO: 1, and (ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO: 2; and wherein administration of huml3B8-b results in the patient experiencing no increase in adverse events (AEs), drug-related AEs, severe adverse events (SAEs), Tier 1 AEs, or Tier 2 AEs for at least up to about 52 weeks to at least up to about 72 weeks as compared to treatment for up to about 52 weeks to at least about 72 weeks.

[0048] The present disclosure also relates to the use of an anti-IL-23pl9 antibody huml3B8-b or antigen binding fragment thereof for the manufacture of a medicament for treating genital psoriasis in a patient. In one embodiment, the present disclosure provides theMBHB Ref. 24-0818-WO use of an anti-IL-23pl9 antibody huml3B8-b for the manufacture of a medicament for treating genital psoriasis in a patient, wherein huml3B8-b comprises: (i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO: 1, and (ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO: 2; and wherein the medicament is administered to the patient for at least up to about 52 weeks.

[0049] In another embodiment, provided herein is the use of an anti-IL-23pl9 antibody huml3B8-b for the manufacture of a medicament for maintaining a modified Static Physician's Global Assessment of Genitalia (sPGA-G) score of "clear" or "minimal" with at least a 2-point reduction from Baseline in a patient with genital psoriasis comprising administering an anti-IL-23pl9 antibody huml3B8-b to a patient in need thereof, wherein huml3B8-b comprises: (i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO: 1, and (ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO: 2; and wherein huml3B8-b is administered to the patient for up to at least about 52 weeks.

[0050] In another embodiment, provided herein is the use of an anti-IL-23pl9 antibody huml3B8-b for the manufacture of a medicament for maintaining at least a 75% reduction in the Psoriasis Area and Severity Index (PASI 75) in a patient with plaque psoriasis comprising administering an anti-IL-23pl9 antibody huml3B8-b to a patient in need thereof, wherein huml3B8-b comprises: (i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO: 1, and (ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO: 2; and wherein huml3B8-b is administered to the patient for up to about at least 52 weeks.

[0051] In another embodiment, provided herein is the use of an anti-IL-23pl9 antibody huml3B8-b for the manufacture of a medicament for maintaining at least a 90% reduction in the Psoriasis Area and Severity Index (PASI 90) in a patient with plaque psoriasis comprising administering an anti-IL-23pl9 antibody huml3B8-b to a patient in need thereof, wherein huml3B8-b comprises: (i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO: 1, and (ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO: 2; and wherein huml3B8-b is administered to the patient for up to about at least 52 weeks.

[0052] In another embodiment, provided herein is the use of an anti-IL-23pl9 antibody huml3B8-b for the manufacture of a medicament for maintaining a 100% reduction in the Psoriasis Area and Severity Index (PASI 100) in a patient with plaque psoriasis comprising administering an anti-IL-23pl9 antibody huml3B8-b to a patient in need thereof, whereinMBHB Ref. 24-0818-WO huml3B8-b comprises: (i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO: 1, and (ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO: 2; and wherein huml3B8-b is administered to the patient for up to about at least 52 weeks.

[0053] In another embodiment, provided herein is the use of an anti-IL-23pl9 antibody huml3B8-b to a patient in need thereof, wherein huml3B8-b comprises: (i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO: 1, and (ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO: 2; and wherein administration of huml3B8-b results in the patient experiencing no increase in adverse events (AEs), drug-related AEs, severe adverse events (SAEs), Tier 1 AEs, or Tier 2 AEs for at least up to about 52 weeks to at least up to about 72 weeks as compared to treatment for up to about 52 weeks to at least about 72 weeks.

[0054] The term "antibody" as used herein refers to a protein that is capable of recognizing and specifically binding to an antigen. Ordinary or conventional mammalian antibodies comprise a tetramer, which is typically composed of two identical pairs of polypeptide chains, each pair consisting of one "light" chain (typically having a molecular weight of about 25 kDa) and one "heavy" chain (typically having a molecular weight of about 50-70 kDa). The terms "heavy chain" and "light chain," as used herein, refer to any immunoglobulin polypeptide having sufficient variable domain sequence to confer specificity for a target antigen. The amino-terminal portion of each light and heavy chain typically includes a variable domain of about 100 to 110 or more amino acids that typically is responsible for antigen recognition. The carboxyl-terminal portion of each chain typically defines a constant domain responsible for effector function. Thus, in a naturally occurring antibody, a full-length heavy chain immunoglobulin polypeptide includes a variable domain (VH) and three constant domains (CHI, CH2, and CHQ and a hinge region between CHI and CH2, wherein the VH domain is at the amino-terminus of the polypeptide and the CH3 domain is at the carboxyl-terminus, and a full-length light chain immunoglobulin polypeptide includes a variable domain (VL) and a constant domain (CL), wherein the VL domain is at the amino-terminus of the polypeptide and the CL domain is at the carboxyl-terminus.

[0055] Within full-length light and heavy chains, the variable and constant domains typically are joined by a "J" region of about 12 or more amino acids, with the heavy chain also including a "D" region of about 10 more amino acids. The variable regions of each light / heavy chain pair typically form an antigen binding site. The variable domains of naturally occurring antibodies typically exhibit the same general structure of relativelyMBHB Ref. 24-0818-WO conserved framework regions (FR) joined by three hypervariable regions, also called complementarity determining regions or CD Rs. The CDRs from the two chains of each pair typically are aligned by the framework regions, which may enable binding to a specific epitope. From the amino-terminus to the carboxyl-terminus, both light and heavy chain variable domains typically comprise the domains FR1, CDR1, FR2, CDR2, FR3, CDR3, and FR4.

[0056] The term "antigen binding fragment" as used herein refers to a portion of an intact antibody and / or refers to the antigenic determining variable domains of an intact antibody. It is known that the antigen binding function of an antibody can be performed by fragments of a full-length antibody. Examples of antibody fragments include, but are not limited to, Fab, Fab', F(ab')2, and Fv fragments, linear antibodies, single chain antibodies, diabodies, and multispecific antibodies formed from antibody fragments.

[0057] In particular embodiments, the anti-IL-23pl9 antibody huml3B8-b is tildrakizumab. The term "tildrakizumab" as used herein refers to a humanized anti-IL-23pl9 monoclonal antibody, also known as SCH 900222 or MK-3222. Tildrakizumab is a high- affinity (297 picomolar [pM]) humanized immunoglobulin Gl / kappa (IgG I / K) antibody that specifically binds to the pl 9 protein of the IL-23 heterodimer but does not bind human IL- 12 (IL-12 / 23p40 and IL12p35 heterodimer) or human IL-12 / 23p40. Pharmacokinetics: Tildrakizumab pharmacokinetics increases proportionally over a dose range from 50 mg to 200 mg (0.5 to 2 times the approved recommended dosage) following subcutaneous administration in subjects with plaque psoriasis. Steady-state concentrations were achieved by Week 16 following subcutaneous administration of tildrakizumab at Weeks 0, 4, and every 12 weeks thereafter. At the 100 mg dose at Week 16, the mean (± SD) steady-state trough concentrations ranged from 1.22 ± 0.94 mcg / mL to 1.47 ± 1.12 mcg / mL. The geometric mean (CV%) steady-state Cmax was 8.1 mcg / mL (34%). The absolute bioavailability of tildrakizumab was estimated to be 73-80% following subcutaneous injection. The peak concentration (Cmax) was reached by approximately 6 days.

[0058] In some embodiments, the anti-IL-23pl9 antibody tildrakizumab can refer to ILUMYA®. ILUMYA® is administered by subcutaneous injection at a recommended dosage of 100 mg at weeks 0, 4, and every 12 weeks thereafter. In some embodiments, tildrakizumab is formulated in a 1 mL single-dose prefilled syringe containing 100 mg of tildrakizumab (z.e., 100 mg / mL). In some embodiments, ILUMYA® (tildrakizumab-asmn) injection, for subcutaneous use, is a sterile, clear to slightly opalescent, colorless to slightly yellow solution. ILUMYA® is supplied in a single-dose prefilled syringe with a glass barrelMBHB Ref. 24-0818-WO and 29-gauge fixed, 1 / 2 -inch needle. In some embodiments, tildrakizumab can be formulated in: L-histidine, L-histidine hydrochloride monohydrate, polysorbate 80, and / or sucrose, in Water for Injection, with a pH of 5.7-6.3. In some embodiments, tildrakizumab is formulated in a 1 mb single-dose prefilled syringe containing 100 mg of tildrakizumab-asmn formulated in: L-histidine (0.495 mg), L-histidine hydrochloride monohydrate (1.42 mg), polysorbate 80 (0.5 mg), sucrose (70.0 mg), and Water for Injection, USP with a pH of 5.7-6.3.

[0059] In particular embodiments, the anti-IL-23pl9 antibody huml3B8-b (tildrakizumab) comprises a light chain polypeptide comprising the amino acid sequence of SEQ ID NO: 1 and a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO: 2, and which is disclosed in U.S. Patent Nos. 8,404,813 and 8,293,883, the disclosures of each of which are hereby incorporated by reference in their entireties. In other embodiments, the anti-IL-23pl9 antibody huml3B8-b or an antigen-binding fragment thereof comprises a heavy chain variable domain and a light chain variable domain, wherein the heavy chain variable domain comprises CDR1, CDR2, and CDR3 sequences of the amino acid sequences of SEQ ID NOs: 3-5, and wherein the light chain variable domain comprises CDR1, CDR2, and CDR3 sequences of the amino acid sequences of SEQ ID NOs: 6-8.

[0060] Huml3B8-b Light Chain (SEQ ID NO: 1)DIQMTQSPSSLSASVGDRVTITCRTSENIYSYLAWYQQKPGKAPKLLIYNAKTLA EGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQHHYGIPFTFGQGTKVEIKRTVA APSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQ DSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC

[0061] Huml3B8-b Heavy Chain (SEQ ID NO: 2) QVQLVQSGAEVKKPGASVKVSCKASGYIFITYWMTWVRQAPGQGLEWMGQIFP ASGSADYNEKFEGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCARGGGGFAYW GQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGA LTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEP KSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV KFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSN KALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEW ESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNH YTQKSLSLSPGK

[0062] Huml3B8-b Heavy Chain CDR1 (SEQ ID NO: 3) GYIFITYWMTMBHB Ref. 24-0818-WO

[0063] Huml3B8-b Heavy Chain CDR2 (SEQ ID NO: 4)QIFPASGSADYNEKFE

[0064] Huml3B8-b Heavy Chain CDR3 (SEQ ID NO: 5) GGGGFAY

[0065] Huml3B8-b Light Chain CDR1 (SEQ ID NO: 6) RTSENIYSYLA

[0066] Huml3B8-b Light Chain CDR2 (SEQ ID NO: 7) NAKTLAE

[0067] Huml3B8-b Light Chain CDR3 (SEQ ID NO: 8) QHHYGIPFT

[0068] As used herein, the term "subject" and "patient" are interchangeable. In some embodiments, subjects and / or patients are mammals.

[0069] A "disorder" is any condition that would benefit from treatment using the antibodies of the disclosure. "Disorder" and "condition" are used interchangeably herein and include chronic and acute disorders or diseases, including those pathological conditions that predispose a patient to the disorder in question.

[0070] The terms "treatment" or "treat" as used herein refer to both therapeutic treatment and prophylactic or preventative measures. Those in need of treatment include patients having genital psoriasis as well as those prone to have genital psoriasis or those in which plaque psoriasis is to be prevented. The presence of genital psoriasis can be independent or accompany plaque psoriasis. In some embodiments, the genital psoriasis is moderate to severe genital psoriasis. Those in need of treatment also include patients having plaque psoriasis as well as those prone to have plaque psoriasis or those in which plaque psoriasis is to be prevented. In some embodiments, the plaque psoriasis is moderate to severe plaque psoriasis.

[0071] The terms "administration" or "administering" as used herein refer to providing, contacting, and / or delivering an antibody or fragment thereof by any appropriate route to achieve the desired effect. Administration may include, but is not limited to, oral, sublingual, parenteral (e.g., intravenous, subcutaneous, intracutaneous, intramuscular, intraarticular, intraarterial, intrasynovial, intrastemal, intrathecal, intralesional, or intracranial injection), transdermal, topical, buccal, rectal, vaginal, nasal, ophthalmic, via inhalation, and implants. In one embodiment, administration is subcutaneous via a pre-filled syringe (PFS).

[0072] In some embodiments, the anti-IL-23pl9 antibody huml3B8-b or an antigenbinding fragment thereof, pharmaceutical composition of an anti-IL-23pl9 antibodyMBHB Ref. 24-0818-WO huml3B8-b, or anti-IL-23pl9 antibody huml3B8-b medicament is administered to the patient subcutaneously. In some embodiments, the anti-IL-23pl9 antibody huml3B8-b or an antigen-binding fragment thereof, pharmaceutical composition of an anti-IL-23pl9 antibody huml3B8-b, or anti-IL-23pl9 antibody huml3B8-b medicament is administered to the patient by subcutaneous injection. In some embodiments, the anti-IL-23pl9 antibody huml3B8-b or an antigen-binding fragment thereof, pharmaceutical composition of an anti- IL-23pl9 antibody huml3B8-b, or anti-IL-23pl9 antibody huml3B8-b medicament is administered to the patient using an auto-injector device or prefdled syringe. In some embodiments of the compositions or methods of the disclosure, the prefdled syringe or autoinjector device, intravenous (IV) bag, prefdled ampule, single dose vial, or wearable device comprises a pharmaceutical composition comprising an anti-IL-23pl9 antibody or antigen binding fragment thereof

[0073] In some embodiments, the anti-IL-23pl9 antibody huml3B8-b or an antigenbinding fragment thereof, pharmaceutical composition of an anti-IL-23pl9 antibody huml3B8-b, or anti-IL-23pl9 antibody huml3B8-b medicament is administered about every two weeks, about every four weeks, about every six weeks, about every eight weeks, about every ten weeks, or about every twelve weeks.

[0074] As used herein, the term "Week 0" refers to the first day the anti-IL-23pl9 antibody huml3B8-b or an antigen-binding fragment thereof, pharmaceutical composition of an anti-IL-23pl9 antibody huml3B8-b, or anti-IL-23pl9 antibody huml3B8-b medicament is administered. "Week 0" can also refer to the first day a placebo is administered to the patient.

[0075] In some embodiments, the anti-IL-23pl9 antibody huml3B8-b or an antigenbinding fragment thereof, pharmaceutical composition of an anti-IL-23pl9 antibody huml3B8-b, or anti-IL-23pl9 antibody huml3B8-b medicament is administered to the patient for at least up to about 4 weeks, for at least up to about 12 weeks, for at least up to about 16 weeks, for at least up to about 28 weeks, for at least up to about 40 weeks, for at least up to about 52 weeks, or for more than at least about 52 weeks.

[0076] The therapy dose or therapeutically effective amount of the anti-IL-23pl9 antibody huml3B8-b or an antigen-binding fragment thereof, pharmaceutical composition of an anti-IL-23pl9 antibody huml3B8-b, or anti-IL-23pl9 antibody huml3B8-b medicament will vary depending, in part, upon the size (body weight, body surface, or organ size) and condition (the age and general health) of the patient. In some embodiments, the patient is administered one or more doses of the anti-IL-23p!9 antibody huml3B8-b or an antigen-MBHB Ref. 24-0818-WO binding fragment thereof, wherein the dose is about 20 mg, 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, 160 mg, 180 mg, or 200 mg.

[0077] The term "therapeutically effective amount" as applied to dose or amount refers to the quantity of a compound or pharmaceutical composition that is sufficient to result in a desired effect upon administration to a patient in need thereof. As used herein with respect to the pharmaceutical compositions comprising the anti-IL-23pl9 antibody huml3B8-b (z.e., tildrakizumab), the term "therapeutically effective amount" also refers to the dose of a compound or pharmaceutical composition that is sufficient to produce an effective response upon administration to a patient. In some embodiments, a therapeutically effective amount of the anti-IL-23pl9 antibody huml3B8-b (z.e., tildrakizumab) refers to a dose of 20 mg, 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, 160 mg, 180 mg, or 200 mg. In some embodiments, a therapeutically effective amount of the anti-IL-23pl9 antibody huml3B8-b (z.e., tildrakizumab) is a dose of 100 mg. In some embodiments, a therapeutically effective amount of the anti-IL-23pl9 antibody huml3B8-b (z.e., tildrakizumab) is a dose of 100 mg administered at weeks 0, 4, and every 12 weeks thereafter.

[0078] In some embodiments, the first dose, the second dose, and the subsequent dose of the anti-IL-23pl9 antibody huml3B8-b or an antigen-binding fragment thereof, pharmaceutical composition of an anti-IL-23pl9 antibody huml3B8-b, or anti-IL-23pl9 antibody huml3B8-b medicament are the same. In some embodiments, the first dose, the second dose, and the subsequent dose of the anti-IL-23pl9 antibody huml3B8-b or an antigen-binding fragment thereof, pharmaceutical composition of an anti-IL-23pl9 antibody huml3B8-b, or anti-IL-23pl9 antibody huml3B8-b medicament are different. In some embodiments, the first dose is 100 mg. In some embodiments, the first dose is 200 mg. In some embodiments, the second dose is 100 mg. In some embodiments, the second dose is 200 mg. In some embodiments, the subsequent dose is 100 mg. In some embodiments, the subsequent dose is 200 mg. In some embodiments, the first dose, the second dose, and the subsequent dose are 100 mg. In some embodiments, the first dose, the second dose, and the subsequent dose are 200 mg. In some embodiments, the first dose, the second dose, and the subsequent dose contain 100 mg huml3B8-b. In some embodiments, the first dose, the second dose, and the subsequent dose contain 200 mg huml3B8-b.

[0079] Physician Global Assessment (PGA) of Skin (sPGA;Whole body; see Appendix C) refers to a 5 -point, 0-4 measure that is a useful clinician assessment of psoriasis lesions on the skin based on degree of erythema, thickness, and scale averaged over the entire body. Each of the clinical signs are assessed on a 0-5 scale (0=clear, l=almost clear, 2=mild,MBHB Ref. 24-0818-WO3=moderate, and 4=severe). The sPGA scale is provided in Appendix C. Briefly, a score of 0 ("clear") is characterized by a lack of plaque elevation, no evidence of scaling, and no erythema except for hyperpigmentation / hypopigmentation. A score of 1 ("almost clear") is characterized by slight elevation of the skin, scaling characterized by surface dryness, and faint, diffuse pink or slightly red erythema. A score of 2 ("mild") is characterized by slight plaque elevation, fine scaling, and mild erythema. A score of 3 ("moderate") is characterized by marked plaque elevation, coarse scaling over most lesions, and moderate erythema with definite red coloration. A score of 4 ("severe") is characterized by marked plaque elevation with hard or sharp edges, coarse non-tenacious scale over most lesions, and severe erythema characterized by very bright red coloration.

[0080] In some embodiments, a significant improvement of plaque psoriasis as assessed by the sPGA can refer to subjects with a PGA of skin (whole body) score of "clear" or "almost clear" with at least a 2-point reduction from Baseline. In some embodiments, a significant improvement of plaque psoriasis as assessed by Physician Global Assessment of Skin (Whole body) can refer to subjects with a PGA of skin (whole body) score of "clear" with at least a 2-point reduction from Baseline. In some embodiments, a significant improvement of plaque psoriasis as assessed by Physician Global Assessment of Skin (Whole body) can refer to subjects with a PGA of skin (whole body) score of "clear" or "almost clear" with at least a 2-point reduction from Baseline for at least up to about 4 weeks, for at least up to about 12 weeks, for at least up to about 16 weeks, for at least up to about 28 weeks, for at least up to about 40 weeks, for at least up to about 52 weeks, or for more than at least about 52 weeks.

[0081] In some embodiments, a significant improvement of plaque psoriasis as assessed by Physician Global Assessment of Skin (Whole body) can refer to subjects with a PGA of skin (whole body) score of "clear" with at least a 2-point reduction from Baseline for at least up to about 4 weeks, for at least up to about 12 weeks, for at least up to about 16 weeks, for at least up to about 28 weeks, for at least up to about 40 weeks, for at least up to about 52 weeks, or for more than at least about 52 weeks.

[0082] The modified Static Physician's Global Assessment of Genitalia (sPGA-G; see Appendix B) score refers to a 5 -point, 0-4 measure (0=clear, l=minimal, 2=mild, 3=moderate, and 4=severe) that is a useful clinician assessment of genital psoriasis lesions based on the combination of erythema, elevation, and scale of the plaque. The sPGA scale is provided in Appendix C. A score of 0 ("clear") indicates only no erythema or residual post inflammatory hyperpigmentation or hypopigmentation, no plaque elevation, and no scaling.MBHB Ref. 24-0818-WOA score of 1 ("minimal") indicates erythema characterized by faint light pink coloration, barely perceptible plaque elevation, and surface dryness with some white coloration, but no oozing or crusting. A score of 2 ("mild") is characterized by mild erythema that is pink to light red in color; slight plaque elevation wherein edges are indistinct or sloped, and a fine scale covering most lesions. A score of 3 ("moderate") is characterized by moderate erythema that has a definite red coloration; moderate plaque elevation with rough or sloped edges, and coarse scaling that covers most of the lesions. A score of 4 ("severe") is characterized by severe erythema with bright red coloration, a marked plaque elevation with hard or sharp edges, and coarse scaling in which covers, non-tenacious scale predominates covering most or all of the lesions. In some embodiments, a significant improvement of genital psoriasis as assessed by modified sPGA-G can refer to subjects with a PGA of skin (whole body) score of "clear" or "minimal" with at least a 2-point reduction from Baseline for at least up to about 4 weeks, for at least up to about 12 weeks, for at least up to about 16 weeks, for at least up to about 28 weeks, for at least up to about 40 weeks, for at least up to about 52 weeks, or for more than at least about 52 weeks.

[0083] In some embodiments, a significant improvement of plaque psoriasis as assessed by modified sPGA-G can refer to subjects with a score of 0 (clear) with at least a 2-point reduction from Baseline for at least up to about 4 weeks, for at least up to about 12 weeks, for at least up to about 16 weeks, for at least up to about 28 weeks, for at least up to about 40 weeks, for at least up to about 52 weeks, or for more than at least about 52 weeks.

[0084] Psoriasis Area and Severity Index (PASI) is used to determine the treatment response (PASI 75, PASI 90, and PASI 100) in subjects with plaque psoriasis. The PASI includes scores on erythema, thickness, scaling, and percentage of body surface area (BSA) affected. In some embodiments, a significant improvement of plaque psoriasis as assessed by PASI can refer to a subject achieving at least a 75% improvement in the PASI score from Baseline for at least up to about 16 weeks. In some embodiments, a significant improvement of plaque psoriasis as assessed by PASI can refer to a subject achieving at least a 90% improvement in the PASI score from Baseline for at least up to about 16 weeks. In some embodiments, a significant improvement of plaque psoriasis as assessed by PASI can refer to a subject achieving at least a 100% improvement in the PASI score from Baseline for at least up to about 16 weeks. In some embodiments, a significant improvement of plaque psoriasis as assessed by PASI can refer to a subject achieving at least a 75%, 90%, or 100% improvement in the PASI score from Baseline for at least up to about 4 weeks, for at least up to about 12 weeks, for at least up to about 16 weeks, for at least up to about 28 weeks, for atMBHB Ref. 24-0818-WO least up to about 40 weeks, for at least up to about 52 weeks, or for more than at least about 52 weeks.

[0085] As used herein, the term "significant improvement" refers to significant positive effect in a response in patients taking the anti-IL-23pl9 antibody huml3B8-b or an antigenbinding fragment thereof, pharmaceutical composition of an anti-IL-23pl9 antibody huml3B8-b, or anti-IL-23pl9 antibody huml3B8-b medicament relative to patients taking a placebo. In some embodiments, a significant improvement of plaque and / or genital psoriasis is assessed by Physician Global Assessment (PGA) of Skin (Whole body), modified Static Physician's Global Assessment of Genitalia (sPGA-G) score, genital psoriasis itch numerical rating scale (GPI-NRS) or Psoriasis Area and Severity Index (PASI). In certain embodiments, the significant improvement refers to a statistically significant improvement. In certain embodiments, the term "statistically significant" means having a probability of less than 10% under the relevant null hypothesis (z.e., p<0.1). In some embodiments, a p-value less than 0.05 is considered to be statistically significant. In some embodiments, a p-value less than 0.01 is considered to be statistically significant. In some embodiments, a p-value less than 0.005 is considered to be statistically significant. In some embodiments, a p-value less than 0.0025 is considered to be statistically significant. In some embodiments, a p-value less than 0.001 is considered to be statistically significant. In certain embodiments, statistical tests will be 2-sided at the 5% significance level, and point estimates are accompanied with 2- sided 95% confidence intervals (Cis), where applicable.

[0086] In some embodiments, a significant improvement can refer to an improvement of plaque psoriasis of at least 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 100%, 150%, or 200% or more as assessed by Physician Global Assessment (PGA) of Skin (Whole body), modified Static Physician's Global Assessment of Genitalia (sPGA-G) score, genital psoriasis itch numerical rating scale (GPI-NRS), or Psoriasis Area and Severity Index (PASI).

[0087] In some embodiments, a significant improvement can refer to an at least 2-fold, 3- fold, 4-fold, 5 -fold, or 10-fold, or more than 10-fold improvement of plaque psoriasis as assessed by Physician Global Assessment (PGA) of Skin (Whole body), modified Static Physician's Global Assessment of Genitalia (sPGA-G) score, genital psoriasis itch numerical rating scale (GPI-NRS), or Psoriasis Area and Severity Index (PASI).

[0088] The terms "pharmaceutical composition" or "therapeutic composition" as used herein refer to a compound or composition capable of inducing a desired therapeutic effect when properly administered to a patient. One embodiment of the disclosure provides aMBHB Ref. 24-0818-WO pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of at least one antibody of the disclosure.

[0089] The terms "pharmaceutically acceptable carrier" or "physiologically acceptable carrier" as used herein refer to one or more formulation materials suitable for accomplishing or enhancing the delivery of one or more antibodies of the disclosure.

[0090] Pharmaceutical compositions comprising tildrakizumab, either alone or in combination with prophylactic agents, therapeutic agents, and / or pharmaceutically acceptable carriers are provided. The pharmaceutical compositions comprising tildrakizumab provided herein are for use in, but not limited to, diagnosing, detecting, or monitoring a disorder, in preventing, treating, managing, or ameliorating a disorder or one or more symptoms thereof, and / or in research. The formulation of pharmaceutical compositions, either alone or in combination with prophylactic agents, therapeutic agents, and / or pharmaceutically acceptable carriers, is known to one skilled in the art.Embodiments:

[0091] Embodiment 1 : A method of treating genital psoriasis comprising administering an anti-IL-23pl9 antibody huml3B8-b to a patient in need thereof, wherein huml3B8-b comprises:(i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO: 1, and(ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO: 2; and wherein huml3B8-b is administered to the patient for at least up to about 52 weeks.

[0092] Embodiment 2: A method of improving a modified Static Physician Global Assessment of Genitalia (sPGA-G) score in genital psoriasis, comprising administering an anti-IL-23pl9 antibody huml3B8-b to a patient in need thereof, wherein huml3B8-b comprises:(i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO: 1, and(ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO: 2; and wherein huml3B8-b is administered to the patient for at least up to about 52 weeks.

[0093] Embodiment 3 : The method of embodiment 1 or of embodiment 2, wherein the genital psoriasis is moderate to severe genital psoriasis.

[0094] Embodiment 4: The method of embodiment 3, wherein the moderate to severe genital psoriasis is characterized by a modified Static Physician's Global Assessment of Genitalia (sPGA-G) baseline score greater than or equal to 3.MBHB Ref. 24-0818-WO

[0095] Embodiment 5 : The method of embodiment 1 or of embodiment 2, wherein the patient has moderate to severe genital psoriasis characterized by a modified sPGA-G of >3 and plaque psoriasis affecting greater than or equal to 1% Body Surface Area (BSA).

[0096] Embodiment 6: The method of embodiment of claim 5, wherein the psoriasis has been inadequately controlled or the patient intolerant to topical therapy.

[0097] Embodiment 7 : The method of embodiment 1 or embodiment 2, wherein huml3B8-b is administered to the patient for at least up to about 52 weeks.

[0098] Embodiment 8: The method of embodiment 1 or embodiment 2, wherein huml3B8-b is administered to the patient about every 12 weeks.

[0099] Embodiment 9: The method of embodiment 7, wherein huml3B8-b is administered to the patient subcutaneously.

[0100] Embodiment 10: The method of embodiment 7, wherein huml3B8-b is administered to the patient by subcutaneous injection.

[0101] Embodiment 11: The method of embodiment 9, wherein huml3B8-b is administered to the patient using an auto-injector or prefilled syringe.

[0102] Embodiment 12: The method of embodiment 1 or of embodiment 2, wherein a therapeutically effective amount of huml3B8-b is administered to the patient.

[0103] Embodiment 13: The method of embodiment 1 or of embodiment 2, wherein about 100 mg of huml3B8-b is administered to the patient.

[0104] Embodiment 14: The method of embodiment 1, wherein a first dose of huml3B8- b is administered to the patient on week 0, a second dose of huml3B8-b is administered at week 4, and subsequent doses of huml3B8-b are administered to the patient at week 16 and every 12 weeks thereafter.

[0105] Embodiment 15: The method of embodiment 14, wherein 100 mg of huml3B8-b is administered to the patient.

[0106] Embodiment 16: The method of embodiment 14, wherein the first dose, the second dose, and the subsequent doses are the same.

[0107] Embodiment 17: The method of embodiment 14, wherein the first dose is 100 mg.

[0108] Embodiment 18: The method of embodiment 14, wherein the second dose is 100 mg.

[0109] Embodiment 19: The method of embodiment 14, wherein the first dose, the second dose, and the subsequent doses are 100 mg.MBHB Ref. 24-0818-WO

[0110] Embodiment 20: The method of embodiment 19, wherein the second dose is administered at 4 weeks after the first dose and the subsequent doses are administered about every 12 weeks after the second dose, for at least up to about 52 weeks.

[0111] Embodiment 21 : The method of embodiment 1 or of embodiment 2, wherein a first dose of huml3B8-b is administered to the patient on week 0, a second dose of huml3B8-b is administered to the patient at about 4 weeks, and subsequent doses of huml3B8-b is administered to the patient about every 4 to 12 weeks thereafter until about week 52.

[0112] Embodiment 22: The method of embodiment 21, wherein the first dose, the second dose, and the subsequent dose are the same.

[0113] Embodiment 23: The method of embodiment 22, wherein the first dose, the second dose, and the subsequent dose are 100 mg.

[0114] Embodiment 24: The method of embodiment 21, wherein the subsequent doses are administered about every 12 weeks for at least up to about 52 weeks.

[0115] Embodiment 25 : The method of embodiment 1 or of embodiment 2, wherein administration of huml3B8-b results in the patient maintaining a modified Static Physician's Global Assessment of Genitalia (sPGA-G) score of 0 "clear" or 1 "minimal" with at least a 2- point reduction from baseline for at least up to about 52 weeks.

[0116] Embodiment 26: The method of embodiment 1 or of embodiment 2, wherein the patient has a Genital Psoriasis Itch Numeric Rating Scale (GPI-NRS) baseline score greater than or equal to 4, wherein administration of the huml3B8-b results in at least a 4-point improvement in the average weekly GPI-NRS score when compared to the patient's baseline weekly GPI-NRS score.

[0117] Embodiment 27 : The method of embodiment 1 or of embodiment 2, wherein administration of huml3B8-b results in at least a four-point reduction in the patient's Dermatology Life Quality Index (DLQI) score when compared to a patient's baseline DLI score.

[0118] Embodiment 28: The method of embodiment 1 or of embodiment 2, wherein administration of huml3B8-b results in the patient achieving at least a four-point reduction in a Genital Psoriasis Symptoms Scale (GPSS) score when compared to the patient's baseline GPSS score.

[0119] Embodiment 29: The method of embodiment 1 or of embodiment 2, wherein the patient has a baseline Psoriasis Area and Severity Index (PASI) score of at least 2.MBHB Ref. 24-0818-WO

[0120] Embodiment 30: The method of embodiment 29, wherein administration of huml3B8-b results in the patient achieving an absolute PASI score of 1.

[0121] Embodiment 31 : The method of embodiment 29, wherein administration of huml3B8-b results in the patient achieving an absolute PASI score of 0.

[0122] Embodiment 32: The method of embodiment 1 or of embodiment 2, wherein administration of huml3B8-b results in the patient maintaining at least a 75% reduction in the Psoriasis Area and Severity Index (PASI 75) for at least up to about 52 weeks.

[0123] Embodiment 33: The method of embodiment 1 or of embodiment 2, wherein administration of huml3B8-b results in the patient maintaining at least a 90% reduction in the Psoriasis Area and Severity Index (PASI 90) for at least up to about 52 weeks.

[0124] Embodiment 34: The method of embodiment 1 or of embodiment 2, wherein administration of huml3B8-b results in the patient maintaining a 100% reduction in the Psoriasis Area and Severity Index (PASI 100) for at least up to about 52 weeks.

[0125] Embodiment 35: A method for achieving a modified Static Physician's Global Assessment of Genitalia (sPGA-G) score of "clear" or "minimal" with at least a 2-point reduction from baseline in a patient with genital psoriasis comprising administering an anti- IL-23pl9 antibody huml3B8 to a patient in need thereof, wherein huml3B8-b comprises:(i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO: 1, and(ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO: 2; and wherein huml3B8-b is administered to the patient for at least up to about 52 weeks.

[0126] Embodiment 36: A method for maintaining a modified Static Physician's Global Assessment of Genitalia (sPGA-G) score of "clear" or "minimal" with at least a 2-point reduction from baseline in a patient with genital psoriasis comprising administering an anti- IL-23pl9 antibody huml3B8 to a patient in need thereof, wherein huml3B8-b comprises:(i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO: 1, and(ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO: 2; and wherein huml3B8-b is administered to the patient for at least up to about 52 weeks.

[0127] Embodiment 37: A method for achieving at least a four-point improvement of a Genital Psoriasis Itch Numeric Rating Scale (GPI-NRS) baseline score of greater than or equal to 4 in a patient with genital psoriasis comprising administering an anti-IL-23pl9 antibody huml3B8 to a patient in need thereof, wherein huml3B8-b comprises:(i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO: 1, and(ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO: 2; and wherein huml3B8-b is administered to the patient for at least up to about 52 weeks.MBHB Ref. 24-0818-WO

[0128] Embodiment 38: A method for achieving at least a four-point reduction in a Dermatology Life Quality Index (DLQI) score compared to a baseline DLQI, comprising, administering an anti-IL-23pl9 antibody huml3B8 to a patient in need thereof, wherein huml3B8-b comprises:(i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO: 1, and(ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO: 2; and wherein huml3B8-b is administered to the patient for at least up to about 52 weeks.

[0129] Embodiment 39: A method for achieving at least a four-point reduction in a genital psoriasis Symptoms Scale (GPSS) score when compared a baseline GPSS score comprising administering an anti-IL-23pl9 antibody huml3B8 to a patient in need thereof, wherein huml3B8-b comprises:(i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO: 1, and(ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO: 2; and wherein huml3B8-b is administered to the patient for at least up to about 52 weeks.

[0130] Embodiment 40: A method of maintaining a 75% reduction in the Psoriasis Area and Severity Index (PASI 75) in a patient with genital psoriasis comprising administering an anti-IL-23pl9 antibody huml3B8-b to a patient in need thereof, wherein huml3B8-b comprises:(i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO: 1, and(ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO: 2; and wherein huml3B8-b is administered to the patient for at least up to about 52 weeks.

[0131] Embodiment 41: A method of maintaining a 90% reduction in the Psoriasis Area and Severity Index (PASI 90) in a patient with genital psoriasis comprising administering an anti-IL-23pl9 antibody huml3B8-b to a patient in need thereof, wherein huml3B8-b comprises:(i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO: 1, and(ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO: 2; and wherein huml3B8-b is administered to the patient for at least up to about 52 weeks.

[0132] Embodiment 42: A method of maintaining a 100% reduction in the Psoriasis Area and Severity Index (PASI 100) in a patient with genital psoriasis comprising administering an anti-IL-23pl9 antibody huml3B8-b to a patient in need thereof, wherein huml3B8-b comprises:(i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO: 1, andMBHB Ref. 24-0818-WO(ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO: 2; and wherein huml3B8-b is administered to the patient for at least up to about 52 weeks.

[0133] Embodiment 43: A pharmaceutical composition comprising an anti-IL-23pl9 antibody huml3B8-b for the treatment of genital psoriasis in a patient in need thereof, wherein huml3B8-b comprises:(i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO: 1, and(ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO: 2; and wherein huml3B8-b is administered to the patient for at least up to about 52 weeks.

[0134] Embodiment 44: A pharmaceutical composition comprising an anti-IL-23pl9 antibody huml3B8-b for the treatment of genital psoriasis in a patient in need thereof, wherein huml3B8-b comprises:(i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO: 1, and(ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO: 2; and wherein huml3B8-b is administered to the patient for at least up to about 52 weeks.

[0135] Embodiment 45: A pharmaceutical composition comprising an anti-IL-23pl9 antibody huml3B8-b for improving a modified Static Physician Global Assessment of Genitalia (sPGA-G) in genital psoriasis in a patient in need thereof, wherein huml3B8-b comprises:(i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO: 1, and(ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO: 2; and wherein huml3B8-b is administered to the patient for at least up to about 52 weeks.

[0136] Embodiment 46: The pharmaceutical composition of embodiment 44 or of embodiment 45, wherein the genital psoriasis is moderate to severe genital psoriasis.

[0137] Embodiment 47 : The pharmaceutical composition of embodiment 46, wherein the patient has moderate to severe genital psoriasis has a sPGA-G baseline score greater than or equal to 3.

[0138] Embodiment 48: The pharmaceutical composition of embodiment 44 or of embodiment 45, wherein the patient has moderate to severe genital psoriasis characterized by a sPGA-G of >3 and plaque psoriasis affecting equal to, or greater than 1% of Body Surface Area (BSA).

[0139] Embodiment 49: The pharmaceutical composition of embodiment 48, wherein the psoriasis has been inadequately controlled or the patient intolerant to topical therapy.MBHB Ref. 24-0818-WO

[0140] Embodiment 50: The pharmaceutical composition of embodiment 44 or of embodiment 45, wherein huml3B8-b is administered to the patient for at least up to about 52 weeks.

[0141] Embodiment 51 : The pharmaceutical composition of embodiment 44 or of embodiment 45, wherein huml3B8-b is administered to the patient about every 12 weeks.

[0142] Embodiment 52: The pharmaceutical composition of embodiment 51, wherein huml3B8-b is administered to the patient subcutaneously.

[0143] Embodiment 53: The pharmaceutical composition of embodiment 51, wherein huml3B8-b is administered to the patient by subcutaneous injection.

[0144] Embodiment 54: The pharmaceutical composition of embodiment 53, wherein huml3B8-b is administered to the patient using an auto-injector or prefdled syringe.

[0145] Embodiment 55: The pharmaceutical composition of embodiment 44 or of embodiment 45, wherein a therapeutically effective amount of huml3B8-b is administered to the patient.

[0146] Embodiment 56: The pharmaceutical composition of embodiment 44 or of embodiment 45, wherein about 100 mg of huml3B8-b is administered to the patient.

[0147] Embodiment 57: The pharmaceutical composition of embodiment 44 or of embodiment 45, wherein a first dose of huml3B8-b is administered to the patient on week 0 a second dose of huml3B8-b is administered at week 4, and subsequent doses of huml3B8-b are administered to the patient at week 16 and every 12 weeks thereafter.

[0148] Embodiment 58: The pharmaceutical composition of embodiment 57, wherein the first dose, second dose, and the subsequent dose are the same.

[0149] Embodiment 59: The pharmaceutical composition of embodiment 57, wherein the first dose is 100 mg.

[0150] Embodiment 60: The pharmaceutical composition of embodiment 57, wherein the second dose is 100 mg.

[0151] Embodiment 61: The pharmaceutical composition of embodiment 57, wherein the subsequent doses are 100 mg.

[0152] Embodiment 62: The pharmaceutical composition of embodiment 58, wherein the first dose and the subsequent doses are 100 mg.

[0153] Embodiment 63: The pharmaceutical composition of embodiment 59, wherein the second dose is administered at 4 weeks after the first dose and the subsequent doses are administered about every 12 weeks after the second dose, for at least up to about 52 weeks.MBHB Ref. 24-0818-WO

[0154] Embodiment 64: The pharmaceutical composition of embodiment 44 or of embodiment 45, wherein a first dose of huml3B8-b is administered to the patient on week 0, a second dose of huml3B8-b is administered to the patient at about 4 weeks, and subsequent doses of huml3B8-b is administered to the patient about every 4 to 12 weeks thereafter.

[0155] Embodiment 65 : The pharmaceutical composition of embodiment 64, wherein the first dose, the second dose, and the subsequent dose are the same.

[0156] Embodiment 66: The pharmaceutical composition of embodiment 65, wherein the first dose, the second dose, and the subsequent dose are 100 mg.

[0157] Embodiment 67 : The pharmaceutical composition of embodiment 64, wherein the subsequent dose is administered about every 12 weeks for at least up to about 52 weeks.

[0158] Embodiment 68: The pharmaceutical composition of embodiment 44 or of embodiment 45, wherein administration of huml3B8-b results in the patient maintaining a modified Static Physician's Global Assessment of Genitalia (sPGA-G) score of "clear" or "minimal" with at least a 2-point reduction from baseline for at least up to about 52 weeks.

[0159] Embodiment 69: The pharmaceutical composition of embodiment 57, wherein administration of huml3B8-b results in the patient maintaining a modified Static Physician's Global Assessment of Genitalia (sPGA-G) score of "clear" or "minimal" with at least a 2- point reduction from baseline for at least up to about 52 weeks.

[0160] Embodiment 70: The pharmaceutical composition of embodiment 44 or of embodiment 45, wherein the patient has a Genital Psoriasis Itch Numeric Rating Scale (GPI- NRS) baseline score greater than or equal to 4, wherein administration of the huml3B8-b results in at least a 4-point improvement in the GPI-NRS score when compared to the patient's baseline GPI-NRS score.

[0161] Embodiment 71 : The pharmaceutical composition of embodiment 44 or of embodiment 45, wherein administration of huml3B8-b results in at least a four-point reduction in the patient's Dermatology Life Quality Index (DLQI) score when compared to a patient's baseline DLI score.

[0162] Embodiment 72: The pharmaceutical composition of embodiment 44 or of embodiment 45, wherein administration of huml3B8-b results in the patient achieving at least a four-point reduction in a Genital Psoriasis Symptoms Scale (GPSS) score when compared to the patient's baseline GPSS score.

[0163] Embodiment 73: The pharmaceutical composition of embodiment claim 44 or of embodiment 45, wherein the patient has a baseline Psoriasis Area and Severity Index (PASI) score of at least 2.MBHB Ref. 24-0818-WO

[0164] Embodiment 74: The pharmaceutical composition of embodiment 73, wherein the patient achieves a PASI score of 1.

[0165] Embodiment 75: The pharmaceutical composition of embodiment 73, wherein the patient achieves a PASI score of 0.

[0166] Embodiment 76: The pharmaceutical composition of embodiment 44 or of embodiment 45, wherein administration of huml3B8-b results in the patient maintaining at least a 75% reduction in the Psoriasis Area and Severity Index (PASI 75) for at least up to about 52 weeks.

[0167] Embodiment 77: The pharmaceutical composition of embodiment 44 or of embodiment 45, wherein administration of huml3B8-b results in the patient maintaining at least a 90% reduction in the Psoriasis Area and Severity Index (PASI 90) for at least up to about 52 weeks.

[0168] Embodiment 78: The pharmaceutical composition of embodiment 44 or of embodiment 45, wherein administration of huml3B8-b results in the patient maintaining a 100% reduction in the Psoriasis Area and Severity Index (PASI 100) for at least up to about 52 weeks.

[0169] Embodiment 79: A pharmaceutical composition comprising an anti-IL-23pl9 antibody huml3B8-b for the treatment of genital psoriasis in a patient in need thereof, wherein huml3B8-b comprises:(i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO: 1, and(ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO: 2; and wherein huml3B8-b is administered to the patient for at least up to about 52 weeks.

[0170] Embodiment 80: A pharmaceutical composition comprising an anti-IL-23pl9 antibody huml3B8-b for maintaining a modified Static Physician's Global Assessment of Genitalia (sPGA-G) score of "clear" or "minimal" with at least a 2-point reduction from baseline in a patient with genital psoriasis, wherein huml3B8-b comprises:(i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO: 1, and(ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO: 2; and wherein huml3B8-b is administered to the patient for at least up to about 52 weeks.

[0171] Embodiment 81: A pharmaceutical composition comprising an anti-IL-23pl9 antibody huml3B8-b for achieving at least a four-point improvement of a Genital Psoriasis Itch Numeric Rating Scale (GPI-NRS) baseline score of greater than or equal to 4 in a patient with genital psoriasis, wherein huml3B8-b comprises:(i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO: 1, andMBHB Ref. 24-0818-WO(ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO: 2; and wherein huml3B8-b is administered to the patient for at least up to about 52 weeks.

[0172] Embodiment 82: A pharmaceutical composition comprising an anti-IL-23pl9 antibody huml3B8-b for achieving at least a four-point reduction in a Dermatology Life Quality Index (DLQI) score compared to a baseline DLQI, wherein huml3B8-b comprises:(i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO: 1, and(ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO: 2; and wherein huml3B8-b is administered to the patient for at least up to about 52 weeks.

[0173] Embodiment 83: A pharmaceutical composition comprising an anti-IL-23pl9 antibody huml3B8-b for achieving at least a four-point reduction in a genital psoriasis Symptoms Scale (GPSS) score when compared a baseline GPSS score, wherein huml3B8-b comprises:(i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO: 1, and(ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO: 2; and wherein huml3B8-b is administered to the patient for at least up to about 52 weeks.

[0174] Embodiment 84: A pharmaceutical composition comprising an anti-IL-23pl9 antibody huml3B8-b for maintaining a 75% reduction in the Psoriasis Area and Severity Index (PASI 75) in a patient with genital psoriasis, wherein huml3B8-b comprises:(i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO: 1, and(ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO: 2; and wherein huml3B8-b is administered to the patient for at least up to about 52 weeks.

[0175] Embodiment 85: A pharmaceutical composition comprising an anti-IL-23pl9 antibody huml3B8-b for maintaining a 90% reduction in the Psoriasis Area and Severity Index (PASI 90) in a patient with genital psoriasis, wherein huml3B8-b comprises:(i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO: 1, and(ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO: 2; and wherein huml3B8-b is administered to the patient for at least up to about 52 weeks.

[0176] Embodiment 86: A pharmaceutical composition comprising an anti-IL-23pl9 antibody huml3B8-b for maintaining a 100% reduction in the Psoriasis Area and Severity Index (PASI 100) in a patient with genital psoriasis comprising administering an anti-IL- 23pl9 antibody huml3B8-b to a patient in need thereof, wherein huml3B8-b comprises:(i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO: 1, and(ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO: 2; and wherein huml3B8-b is administered to the patient for at least up to about 52 weeks.MBHB Ref. 24-0818-WOEXAMPLES

[0177] The Examples that follow are illustrative of specific embodiments of the disclosure, and various uses thereof. They are set forth for explanatory purposes only and should not be construed as limiting the scope of the disclosure in any way.Study Design

[0178] Disclosed herein is a Phase 3, randomized, double-blind, placebo controlled, multi-center trial to evaluate the efficacy and safety of subcutaneous (SC) tildrakizumab in subjects with moderate to severe genital psoriasis as evidenced by a (sPGA-G > 3). Approximately 192 subjects (approximately 96 per arm) with moderate to severe genital psoriasis were enrolled in the study. The timeline of the study is shown in Table 1.Table 1. Clinical Study Timeline.

[0179] Subjects (>18 years of age)_will be randomized 1: 1 to receive either tildrakizumab 100 mg SC injection on Day 1, Week 4, and every 12 weeks thereafter (Arm A), or placebo SC injection at Day 1 and Week 4 (Arm B). Randomization was stratified by prior use of anti-TNF and body surface area (<10% vs. >10%). Once a subject in Arm B reaches Week 16, the subject entered the active tildrakizumab treatment period and received SC injection of 100 mg tildrakizumab at week 16 and every 12 weeks for 36 weeks until the end of the treatment (EoT) at Week 52. A schematic of the study design is shown in Figure 1.

[0180] The end of treatment (EoT) is defined as the last visit of the 36-week active tildrakizumab treatment period. After Week 52, all subjects entered the 20-week safety follow-up period. The end of study (EoS) visit was the last visit of the safety follow up period.

[0181] Subjects that discontinued from investigational medicinal product (IMP) at any time (apart from withdrawal of informed consent) were required to complete the end of treatment (EoT; Week 52) assessment at a minimum of 4 weeks after the last dose of IMP and entered the 20-week safety follow-up period.MBHB Ref. 24-0818-WO

[0182] Subjects who discontinue study treatment any time before completing the 16-week assessment were not considered withdrawn from the study and continued to attend all subsequent scheduled efficacy and safety assessments until Week 16, if the consent was not withdrawn.Screening

[0183] Subjects undergo screening evaluations within 4 weeks prior to administration of study medication to determine eligibility. Adult subjects (>18 years of age) with a diagnosis of moderate to severe genital psoriasis (defined as sPGA-G > 3 at screening and baseline) and whole-body plaque psoriasis (BSA >1%) at screening and baseline were eligible to participate in the trial. Subjects were screened within 4-weeks of administration of study medication and must have been inadequately controlled with topical therapy or intolerant to topical therapy for the treatment of psoriasis affecting the genital area.

[0184] Screening laboratory assessments which fell outside the defined exclusionary limit are repeated once within the screening window with all screening procedures repeated.Randomization

[0185] Following the screening process, qualified subjects were randomized in a 1 : 1 ratio stratified by prior use of TNF-a inhibitors (Y es / No) and baseline non-genital plaque psoriasis -involved body surface area (BSA) (<10% and >10%), to receive one of the following 2 treatment arms as presented in Table 2.Table 2: Treatment Arms

[0186] At Week 16, subjects initially randomized to placebo (Arm B) were switched to receive tildrakizumab 100 mg SC at Weeks 16, 20, 32 and 44. To maintain blinding, all subjects received corresponding placebo in Part 2 of the study.

[0187] After Week 52 (or early termination of study treatment prior to Week 52), study treatment was stopped and all subjects, entered the 20-week safety follow-up period (part 3) to monitor safety and tolerability for 20-weeks following the last dose of study treatment.

[0188] During the safety follow-up period, subjects continued on study-approved concomitant medications only and were placed on appropriate therapies for safety concernsMBHB Ref. 24-0818-WO or significant worsening of psoriasis. Subjects did not receive study treatment during the safety follow-up period.

[0189] Subjects who withdrew from the study undergo the assessment corresponding to the last assessment of the study part from which they are leaving.

[0190] Subjects discontinued from study treatment at any time (apart from consent withdrawal) completed the EoT (Week 52) assessment a minimum of 4 weeks after the last dose of study treatment and enter the 20-week safety follow-up.

[0191] Subjects who withdrew from the study during Part 3 undergo the Week 72 (End of Study [EoS]) assessments at least 4 weeks after their last visit.

[0192] Subjects who discontinued study treatment any time before completing the 16- week assessment were not considered to be withdrawn from the study and continued to attend all subsequent scheduled efficacy and safety assessments until Week 16, if the consent was not withdrawn. All safety assessments as scheduled for the EoS visit were performed on the last scheduled visit for such subjects.Blood Samples for Determination of Anti-Drug Antibodies

[0193] A sample of blood to obtain sufficient serum for ADA determination was collected prior to IMP administration at the specified time points as defined in Appendix A. Sample collection times were recorded and sample collection time deviations were determined using the actual collection times provided and did not require recordation.Blood Samples for Determination of Serum Concentration of Tildrakizumab

[0194] A sample of blood to obtain sufficient serum for ADA determination was collected prior to IMP administration. The sample was collected into the appropriate tubes and collection times recorded.Withdrawal and Replacement Rules

[0195] Subjects were able to voluntarily withdraw consent to participate in the study for any reason at any time. Consent withdrawal occurred when a subject did not want to participate in the study anymore and did not want to attend any further visits or assessments, have further study related contact, or allow analysis of already obtained biologic material.

[0196] If a subject withdrew consent, subjects were requested to continue attending study visits up to Week 52 according to the study visit schedule. However, a subject could withdraw from the study at any time without giving any reason. If the subject decided to completely withdraw from the study (refusing any further study participation or contact), all study participation for that subject was ceased and data to be collected at subsequent visits was considered missing.MBHB Ref. 24-0818-WO

[0197] Following a subject's withdrawal, the IMP was discontinued and no further assessments were conducted. Subjects who withdrew from the double-blind, placebo- controlled treatment were not eligible for the active treatment. Further attempts to contact the subject were not allowed unless safety findings required communication or follow-up.

[0198] Table 3 lists the following circumstances and further steps to be discussed with study physicians.Table 3. IMP Physician Discussion CriteriaStudy Assessments After Subject's Withdrawal

[0199] For safety reasons, Week 52 (EoT) assessments were conducted for subjects withdrawing during double-blind period and active-treatment period, if the withdrawn subject was willing to undergo the assessments. For subjects withdrawing during follow-up period and willing to undergo final assessments, the Week 72 (EoS) assessments were conducted at least 4 weeks after their last visit (but not later than 12 weeks).

[0200] Subjects that discontinued study treatment any time before completing the 16- week assessment were not considered withdrawn from the study and continued to attend all subsequent scheduled efficacy and safety assessments until Week 16, if consent was not withdrawn.

[0201] All the safety assessments were performed on the last scheduled visit for each subject as scheduled for the EoS visit.

[0202] Table 4 lists circumstances under which a subject can be withdrawn.Table 4. Withdrawal CircumstancesMBHB Ref. 24-0818-WO

[0203] Subjects withdrawn from the study undergo study-related procedures for assessment of safety events, if any. All procedures outlined for EoS or EoT visits were performed at the early termination visit.Study Population

[0204] The study population consisted of subjects (>18 years of age) with a diagnosis of moderate-to-severe psoriasis in the genital area (defined by <10% body surface area involvement and PGA score > 3) (see Table 5). Patients further experienced inadequate control or intolerance to topical therapy, were negative for Tuberculosis via QuantiFERON test, and were otherwise in good physical health.Table 5. Study Population Inclusion CriteriaMBHB Ref. 24-0818-WOExclusion Criteria

[0205] Subjects meeting any of the following criteria in Table 6 were excluded from participating in the study.Table 6: Exclusion CriteriaMBHB Ref. 24-0818-WOMBHB Ref. 24-0818-WOScreen Failures

[0206] Screen failures are defined as subjects who consent to participate in the clinical study but are not subsequently entered in the study. A minimal set of screen failureMBHB Ref. 24-0818-WO information are required to ensure transparent reporting of screen failure subjects to meet the 'Consolidated standards of reporting trials publishing requirements' and to respond to queries from regulatory authorities. The minimal information includes demography, screen failure details, eligibility criteria, and any SAE.

[0207] Individuals who do not meet the criteria for participation in this study (screen failure) could be rescreened once at the discretion of the Investigator, with a minimum of 2 weeks between each rescreening. When a subject was rescreened, all screening procedures were repeated; however, depending upon timing of re-screening [within 3 months from initial screening], repeat chest x-ray were not required.Study Treatments

[0208] The study drug was supplied as a pre-fdled syringe (PFS), administered subcutaneously. Subjects received either 100 mg Tildrakizumab at Week 0 (Day 1), Week 4, and every 12 weeks thereafter at Week 16, 28, 40, and 52 (Arm A), or a 100 mg placebo at Week 0 (Day 1) and Week 4, but then switched to receive 100 mg Tildrakizumab at Week 16, 20, 32, and 44 (Arm B).

[0209] After Week 52 (or early termination of study treatment prior to Week 52), study treatment was stopped and all subjects, entered the 20-week safety follow-up period (part 3) to monitor safety and tolerability for 20-weeks following last dose of study treatment.Dosing Instructions and Schedule

[0210] Subjects in the study received tildrakizumab or placebo. All subjects were dosed at the same time points to maintain the blind during the study. The study arms received study treatment during the course of the study as follows in Table 7.Table 7. Study Treatment Dosage and ScheduleMBHB Ref. 24-0818-WOConcomitant Medications

[0211] Any medication or vaccine (including over-the-counter or prescription medicines, vitamins, and / or herbal supplements) that the subject was receiving at the time of enrollment or received during the study were recorded, as well as the reason for use, dates of administration, dosage information, and the frequency of use. All prior medications used to treat the disease conditions and any other disease conditions and any other medications taken within 6 months prior to enrollment were also recorded.

[0212] Tables 8 and 9 document the allowed and prohibited medications during the study.Table 8. Allowed Concomitant MedicationsTable 9. Prohibited MedicationsMBHB Ref. 24-0818-WODose Modifications

[0213] No dose modifications were allowed in this study. Study treatment could be interrupted temporarily or permanently if deemed necessary as per the Investigator's discretion.ASSESSMENTSEfficacy AssessmentsModified sPGA-G

[0214] The modified sPGA of Genitalia is used to determine a subject's psoriasis lesions in the genital area (labia majora, labia minora, and perineum in females; penis, scrotum, and perineum in males) at a given time point. The modified sPGA score is selected using the descriptors that best describe the overall appearance of the lesions. It is a 5-point numerical scale that ranges from 0 (clear) to 4 (severe) at a given time point and is determined by a combination of and secondary features (elevation, and scale). A score of 0 (clear) indicates that there is residual or no erythema, no plaque elevation, and no scaling. A score of 1 (minimal) indicates a faint, light-pink erythema with slight plaque elevation and some fine, white surface dryness or scales. A score of 2 (mild) indicates that there is mild erythema, slight plaque elevation, and fine scaling. A score of 3 (moderate) represents moderate amount of erythema, moderate plaque elevation with well-defined edges, and coarse scales onMBHB Ref. 24-0818-WO most to all lesions. A score of 4 (severe) represents bright-red erythema with marked plaque elevation and thick, coarse scaling that cover most or all lesions. An instrument called the GPSS has also been developed to record patient-reported outcome measures specific for genital psoriasis.BSA

[0215] Body Surface Area is a commonly used measure of severity of skin disease. It is defined as the percentage of the total BSA affected by psoriasis, it represents the area of affected scalp. The BSA will be measured using the palm method where the palm of the subject's hand (including the palmar aspect of the fingers) represents 1% of the BSA. The affected areas are then calculated by their size compared to the subject's palm.PASI

[0216] A subject's PASI is a measure of overall psoriasis severity and coverage. It is a commonly used measure in clinical studies for psoriasis treatments. PASI consists of 2 major steps: 1) calculating the BSA covered with lesions and 2) assessment of the severity of lesions. The second step in turn consists of assessing the lesions' erythema (redness), induration (thickness) and scaling. The PASI combines the assessment of the severity of lesions and the area affected into a single score in the range 0 (no psoriasis on the body) to 72 (the most severe case of psoriasis). All PASI evaluation was performed prior to study medication administration. sPGA

[0217] The sPGA is a subjective measurement of the severity of psoriasis proven to highly correlate with other clinical measurements of psoriasis such as PASI. It was first introduced by U.S. FDA in 1998, and has since been widely used in clinical trials of psoriasis. It is a five-point scale to measure the degree of erythema, scaling, and plaque elevation of psoriasis: 0 = clear; 1 = almost clear; 2 = mild; 3 = moderate; and 4 = severe. GPI-NRS

[0218] The GPI-NRS is a self-reported measure where participants are asked to assess their psoriasis symptoms in the genital area and select a number on a scale of 0-10, where 0 represents no itch, and 10 represents the worst imaginable itch. A GPI-NRS response is defined as > 4 point reduction (improvement) from Baseline. The GPI-NRS score is collected daily and evaluated as the weekly average. Patients complete the assessments by responding how would he / she rate the worst itch experienced during previous 24 hours, daily. This daily assessment consists of only GPI-NRS questions out of GPSS scale. Patients record the assessment preferably at the same time every day. The complete observation will be performedMBHB Ref. 24-0818-WO on the average score for each visit that will be based on the seven consecutive daily scores. The complete score at a given visit will be based on an average of GPI-NRS scale, using no less than four of the seven prompted valid daily recall observations.DLQI

[0219] The DLQI questionnaire was used to assess treatment response on the subject's QoL. The aim of this questionnaire is to measure how much the skin condition has affected the subject's life during the previous week.

[0220] Subjects were asked to recall their experiences during the previous week by responding to 10 questions. The DLQI is completed by the subject in the patient reported outcomes prior to any safety or efficacy evaluations. The questionnaire is self-explanatory and handed to the subject who is asked to fill it in without the need for a detailed explanation. GPSS

[0221] The GPSS contains eight items regarding genital psoriasis symptoms and has a recall period of 24 h. The items separately address itch, pain, discomfort, stinging, burning, redness, scaling, and cracking on an 11 -point scale where 0 represents "no symptom" and 10 represents "worst symptom imaginable". Each of the eight items are scored separately; in addition, a total score ranging from 0 (no genital psoriasis symptoms) to 80 (worst imaginable genital psoriasis symptoms) is reported. If any item score is missing, the GPSS total score will be missing.Adverse EventsAdverse Event (AE) I Reaction

[0222] An AE is defined as "any untoward medical occurrence in a subject, or clinical investigation subject administered a pharmaceutical product, and which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom or disease temporally associated with the use of a medicinal (investigation) product, whether or not related to the medicinal (investigational) product."

[0223] Any relevant observations made at the Screening and Baseline visit (including Screening laboratory test results, and until the first dose of IMP) are to be recorded on the AE eCRF, but were not be considered as treatment-emergent AEs (TEAEs), and were reported separately from TEAEs. Any relevant observations following the first dose of IMP were recorded as an AE in the subject's AE eCRF; this included physical examination findings, clinically relevant abnormal vital signs, clinically relevant laboratory abnormalities, and clinically relevant ECG findings. An AE relating to a pre-existing condition was onlyMBHB Ref. 24-0818-WO recorded if there was a worsening of the pre-existing condition during study conduct with regard to nature, severity or frequency.

[0224] An adverse drug reaction is an "untoward and unintended response to an IMP related to any dose administered."

[0225] All AEs judged by either the reporting Investigator or the Sponsor as having a reasonable causal relationship to a medicinal product qualify as adverse drug reactions. The expression of "reasonable causal relationship" means to convey in general that there are facts or arguments which suggest a causal relationship.Serious Adverse Events

[0226] Severe Adverse Events (SAEs) are defined as, but not limited to the following(see Table 10):Table 10. Serious Adverse EventsMBHB Ref. 24-0818-WOAdverse Events of Special Interest (AESIs)

[0227] The events of severe infections, malignancies (including non-melanoma and melanoma skin cancer), major adverse cardiovascular events (MACE), and drug -related hypersensitivity reactions) were identified a priori as AESIs for summarizing in the study. Major adverse cardiovascular events include non-fatal stroke, nonfatal myocardial infarction and cardiovascular death. An AESI was reported as if it were an SAE. Injection site reactions were also considered as an AESI for this study.Events of Clinical Interest (ECI)

[0228] An ECI is a non-serious AE or occurrence that is designated to be of special interest and was reported as though it were an SAE. Table 11 lists the events considered to be ECIs for the study.Table 11. Events of Clinical Interest (ECI)MBHB Ref. 24-0818-WOTreatment-Emergent Adverse Events

[0229] TEAEs are defined as any adverse event occurring or worsening on or after the first dose of IMP.Overdose

[0230] A drug overdose is defined as the accidental or intentional use of a drug or medicine or an administration error in an amount that is higher than is normally used. Every overdose was reported to within 24 hours of awareness, irrespective of whether the overdose was associated with an AE / SAE. Overdose in this study is specifically defined as any dose greater than the intended protocol dose. In case of overdose, it was recommended that the subject be monitored for any signs or symptoms of adverse reactions or effects and appropriate symptomatic treatment be instituted immediately.Planned Hospitalizations

[0231] A hospitalization planned by the subject prior to signing the ICF is considered a therapeutic intervention and not the result of a new SAE and was recorded as medical history. If the planned hospitalization or procedure was executed as planned, the record in the subject's medical history was considered complete. However, if the event / condition worsened during the study, it was reported as an AE.Device Deficiency

[0232] A device deficiency is any inadequacy in the identity, quality, durability, reliability, safety, or performance of an investigational device, including malfunction, use errors, or inadequacy in information supplied by the manufacturer.Incident

[0233] A device-related incident is any product complaint that led to or might have led to death or serious deterioration of health / serious injury / serious illness for the user of the product or any other person. Note that "device" refers to the PFS for this study. The incident was reported within 24 hours.Recording of Adverse Events

[0234] Any relevant observations made before the end of the Screening and Baseline visit (prior to first dose of IMP) were recorded, but were not considered TEAEs and reported separately from TEAEs. Any relevant observations made after the first dose of IMP were recorded as a TEAE.

[0235] In view of the long T1 / 2 of tildrakizumab at doses previously studied, subjects continued to be monitored throughout the 12-week follow-up period following the EoT visit. For the purposes of this study, any detrimental change in the subject's condition, after the firstMBHB Ref. 24-0818-WO dose of IMP and up to completion of the EoS visit, were considered an AE. Forthose subjects who may withdraw during the follow-up period, at least two attempts should be made to collect AEs.

[0236] The following variables were recorded for each AE: verbatim / AE description and date for AE start and stop, severity, seriousness, causality rating, whether or not the AE caused the subject to discontinue, and the outcome. A new AE was recorded if the severity of the AE changed.

[0237] All AEs / SAEs had to be reported to the Sponsor, whether or not considered causally related to the IMP or to the study procedure(s).

[0238] All ongoing AEs / SAEs were followed up until resolution or stabilization or the last visit if in the Investigator's opinion, the AE is unlikely to resolve due to the subject's underlying disease. Table 12 provides the assessment of intensity for adverse events.Table 12. Adverse EventsAbnormal Laboratory Values / Vital Signs / Electrocardiograms

[0239] Laboratory, vital signs, or ECG abnormalities should be reported as AEs / SAEs if clinically significant and if the following criteria was met: the result is associated with signs / symptoms, requires additional diagnostic testing and / or intervention, and leads to discontinuation or interruption of the IMP.

[0240] Any test results determined to be an error or simple repetition of a laboratory test was not required to be reported as an AE.Pregnancy

[0241] Females of childbearing potential must not be pregnant or lactating. However, if the female subject became pregnant during the study, the pregnancy was recorded as a significant medical event and reported per SAE reporting procedure and subject was withdrawn from the study immediately.Laboratory Assessments

[0242] Laboratory measurements for blood chemistry, hematology, and urinalysis were performed according to the Schedule of Assessments. All laboratory tests with valuesMBHB Ref. 24-0818-WO considered clinically significantly abnormal during participation in the study including the subject's last EoS visit were repeated until the values return to normal, Baseline, stabilized, or were no longer considered clinically significant.

[0243] For visits where lipid panel laboratory parameters were assessed, blood samples were collected (pre-dose where applicable) after at least 8 hours of fasting, and after ECG and vital sign measurements. Table 13 outlines the laboratory assessments and parameters collected in this study.Table 13. Laboratory AssessmentsElectrocardiogram

[0244] A single computerized 12-lead ECG recordings was obtained at scheduled study visits after the subject has rested for at least 5 minutes in the supine position. The ECG dataMBHB Ref. 24-0818-WO in single recording was submited to a central laboratory for measurement. The Investigator documented the occurrence of any clinically significant 12-lead ECG abnormalities based on correlation between the central reading report and clinical findings. Repeat measurements will be performed if needed.

[0245] The following ECG parameters will be obtained directly from the computerized 12-lead ECG recordings: rhythm, ventricular rate, P-R interval (the portion of the ECG between the onset of the P wave and the QRS complex), QRS duration and QT / QTcF where, according to the Fredericia formula, (QTcF) is the observed QT interval (the time from the beginning of the Q wave to the end of the T wave) divided by the cubed root of the R-R interval (interval from the peak of a QRS complex to the peak of the next) in seconds.Physical Examination

[0246] A standard complete physical examination was performed at the weeks specified in the Schedule of Assessments. A complete physical examination included general appearance, vital signs, eyes, ears, nose, mouth, throat, neck, respiratory, cardiovascular, respiratory, gastro-intestine / abdomen, lymphatic, musculoskeletal, skin, psychiatric, and neurologic examination. Subjects were examined for presence of psoriasis in women on labia minora, labia majora and / or perineum and in men on penis (glass and / or shaft), scrotum, and / or perineum.Vital Signs

[0247] Body temperature (preferably oral), systolic and diastolic cuff blood pressure (measured after at least 5 minutes in the supine position) and pulse rate (measured after at least 5 minutes in the supine position) were recorded according to the Schedule of Assessments. Automatic or manual devices may be used, but the same device was used for any given subject throughout the study. Preferably the same method of measuring body temperature was used throughout the study. The same arm was used for all measurements preferably. All devices must hold valid calibration at the time of use. Change in vital signs (respiratory rate, pulse rate, blood pressure), ECG, and laboratory parameters were measured throughout the study to assess the safety and tolerability of tildrakizumab.Anti-Drug Antibodies

[0248] Samples were drawn and the presence of ADA for tildrakizumab to be assessed at the time points specified the Schedule of Assessments. Incidence of ADA and correlations with PK, safety, and efficacy endpoints were investigated during the double-blind treatment period, open label period and across into the follow-up period.Safety Assessments and ReportingMBHB Ref. 24-0818-WOSuspected Unexpected Serious Adverse Reactions and Unexpected Adverse Reactions

[0249] Any suspected adverse reaction that is serious, unexpected, and considered to be related to IMP exposure is defined as a SUS AR. An unexpected AE is any adverse drug event, which is not listed in the current Investigator's Brochure or is not listed at the specificity, nature, outcome or severity that has been observed.

[0250] Suspected adverse reaction means any AE for which there is a reasonable possibility that the IMP caused the AE. The following examples provide types of evidence that would suggest a causal relationship between the IMP and the AE:1. A single occurrence of an event that is uncommon (not reported in the literature or Investigator's Brochure) and known to be strongly associated with IMP exposure (e.g., angioedema, hepatic injury, Stevens-Johnson Syndrome)2. One or more occurrences of an event that is not commonly associated with IMP exposure, but is otherwise uncommon in the population exposed to the IMP (e.g., tendon rupture)3. An aggregate analysis of specific events observed in a clinical study (such as known consequences of the underlying disease or condition under investigation or other events that commonly occur in the study population independent of IMP therapy) that indicates those events occur more frequently in the IMP treatment group than in a concurrent or historical control group.

[0251] An untoward and unintended post-dosing response to a non-study drug is, by definition, not a SUSAR, but is, however, an AE.Eliciting, Documentation, and Reporting of Adverse Events

[0252] Information on AEs was derived by questioning the subjects in general terms (e.g., "How do you feel?" or "How have you been feeling since the last questioning?" respectively), by subjects' spontaneous reports, or by observation.

[0253] AEs were documented on the source document. Trained monitors checked the entries on the source document. The following information was given for each AE: Description of the AE, start date, stop date, severity, pattern, action taken, outcome, seriousness, dose of study drug, and relationship to the study medications. The dose of study drug assigned to an AE will be the dose the subject was assigned to take on the date the subject reported the AE first began.

[0254] The AE / SAE collection period for safety surveillance begins when the subject signs the ICF and continued until the follow-up visit (visit number as per study), or if the follow-up visit did not occur within the defined time window, then 30 days post the end ofMBHB Ref. 24-0818-WO treatment visit or 30 days post the last dose of study drug for subjects with early discontinuation. AEs with an onset before the subject receives first dose of the study drug were categorized as non-treatment emergent AEs. The AEs with an onset after at least one dose of study drug is received were reported as treatment emergent AEs (TEAEs).Reporting of Serious Adverse Events, Adverse Events of Special Interest, and Events of Clinical Interest

[0255] All SAEs were reported according to ICH GCP or local regulations, applying the regulation with the stricter requirements.

[0256] Investigators and other site personnel must inform appropriate CRO pharmacovigilance and safety services of any SAE that occurs during the course of the study (from the time of informed consent until 30 days after the last EoS visit), irrespective of the causal relationship with the IMP or study related procedure(s) within 24 hours of when he or she became aware of it.The reportable events are:1) any serious adverse event with the investigational device or the investigation procedure2) any device deficiency that might have led to a serious adverse event if appropriate action had not been taken, intervention had not occurred, or circumstances had been less fortunate3) any new findings in relation to any event referred to in points (a) and (b)

[0257] An SAE with an onset after the EoS visit were recorded only for fatal SAEs and for those deemed by the Investigator to be drug-related or AESIs / ECIs. Efforts were made to obtain follow-up information on the outcome until the event is considered resolved, chronic and / or stable.

[0258] If a non-serious AE becomes serious, this and other relevant follow-up information must also be provided to Sponsor within 24 hours as described above. The start date of the SAE is not the start date, but the date when the AE becomes serious; analogously, the stop date is the date when any seriousness criterion is no longer applicable, not the date when the AE is resolved.

[0259] There may be situations when an SAE (or AESI / ECI) has occurred and the Investigator has minimal information to include in the initial SAE report. Minimum criteria include identifiable subject (number), a suspect product (z.e., IMP or concomitant medication), an identifiable reporting source (Investigator / study site identification), and an event or outcome that can be identified as serious.MBHB Ref. 24-0818-WOAssessment of Severity, Outcome, and Expectedness of Adverse Events Intensity

[0260] The severity of an adverse event is characterized in Table 14. Table 14. Severity of Adverse Events

[0261] Event outcome or time last follow-up is recorded or categorized as "Fatal", "Resolved", "Resolved with Sequelae", "Resolving", "Not Resolved", or "Unknown".

[0262] Action taken with respect to study drug is categorized "none", "study drug discontinued / withdrawn", "study drug discontinued and restarted", "required concomitant medication", "required procedure", or "other".

[0263] Assessment of expectedness was determined by the version of the IB effective at the time of onset of the adverse event.

[0264] An expected AE is one that is consistent with the known risk information described in the product label (if applicable) or applicable Investigator's Brochure. The assessment of the expectedness of an SAE was done by Sponsor on receipt of the initial SAE report.

[0265] Any AE that changes in severity or grade during its course will be recorded in the CRF at the highest-level experience by the subject during a single course.

[0266] An AE that is assessed as severe should not be confused with an SAE. Severity is a category used for rating the intensity of an AE (such as mild, moderate, or severe myocardial infarction). However, the event itself may be of relatively minor medical significance, such as a severe headache. Both AEs and SAEs can be assessed as severe. An AE is defined as serious when it meets one of the pre-defined outcomes (see Serious Adverse Events).Assessment of Causality

[0267] The Investigator estimated the relationship between the investigational product and the occurrence of each AE or SAE. Elements considered, include the history of the underlying disease, concomitant therapy, other risk factors and the temporal relationship ofMBHB Ref. 24-0818-WO the event to the investigational product. The Investigator also consulted the Investigator's Brochure or product label for marketed products in estimating the relationship.

[0268] The following system was used as a guiding tool to assess treatment relationship: Unrelated, unlikely, possibly, probably and certainly. Treatment emergent adverse events that are assessed as possibly, probably or certainly related were reported as study drug related AEs see Table 15).Table 15. Assessment of CausalityMBHB Ref. 24-0818-WOFollow-Up of Adverse Events and Serious Adverse EventsUnresolved Events

[0269] If an AE / SAE continued when the subject completed the study, the event was followed and reported until resolution / stabilization or as per medical judgment of the Investigator.Post-Study Events

[0270] Any AE / SAE that occurred up until the follow-up visit (Visit 16 / Week 72) or if the follow-up visit did not occur within the defined time window, then 30 days post the end of treatment visit or 4 weeks post the last dose of study drug for subjects with early discontinuation, was reported and included in the safety analysis of the study. Any AE / SAE which occurred past this date was reported if considered related to the study drug by the Investigator.Pharmacokinetic Assessments

[0271] Tildrakizumab concentration was measured at all sampling time points.Statistical Methods and Data AnalysisMBHB Ref. 24-0818-WO

[0272] The statistical analysis was performed using statistical analysis system (SAS®) Version 9.3 or higher if available. All details regarding the statistical analysis and the preparation of tables, listings and figures was described in the statistical analysis plan that was developed and finalized before database freeze that occurred after the completion of the 16-week placebo controlled treatment period.

[0273] Summary statistics were presented by treatment group. The following descriptive statistics were used as applicable to summarize the study data unless otherwise specified:1) Continuous variables: sample size, mean, standard deviation, median, minimum, and maximum2) Categorical variables: frequencies and percentages

[0274] Unless otherwise specified, "Baseline" is defined as the last observed value of the parameter of interest prior to the first administration of study treatment (this includes unscheduled visits). For numerical variables, change from Baseline was calculated as the difference between the post Baseline value and the corresponding Baseline value.

[0275] Unless otherwise specified, all formal statistical tests were 2-sided at the 5% significance level. Point estimates weree accompanied with 2-sided 95% confidence intervals, where applicable. Statistical comparisons for the primary and key secondary endpoints were performed for inferential purpose following the testing approach described below. Other statistical comparisons were performed for descriptive purpose. Individual subject data will be presented in listings. A more detailed description of study analyses was presented in the SAP.Data Collection and Processing

[0276] Electronic CRF (eCRF)s were used to capture study assessments and data. The study coordinator or other delegated study personnel will enter data from source documents into the eCRFs. All eCRFs were reviewed and source verified by the study monitor during periodic site visits, and the study monitor ensured that all data in the eCRF are correct and complete. Before or between visits, the medical monitor or study monitor may look at the eCRFs for preliminary medical review. Once the eCRFs were completed and source -verified, the Investigator signed and dated all required pages, verifying the accuracy of all data contained in the eCRF.

[0277] Training was provided for the electronic data capture (EDC) system. All clinical trial personnel using the EDC system had the necessary education, training, and experience or any combination of these. The Investigator was responsible for documenting employeeMBHB Ref. 24-0818-WO education, training, and previous experience that pertain to the EDC system for all site personnel using the EDC system.

[0278] The Investigator maintained adequate security of the EDC system, including documentation that all users have been trained on the appropriate standard operating procedure and a list of authorized users. To ensure all data entries can be tracked, all personnel responsible for data entry must obtain a unique electronic signature before any data can be entered in the eCRFs. The EDC system was configured to ensure that the signer's electronic signature cannot be forged. Authorized study personnel were assigned a unique password and associated electronic signature after receiving standard operating procedure training.Statistical HypothesisSample Size Justification

[0279] Since at the time of planning this study, no prior sPGA of genitalia (primary outcome measure) data was available from the tildrakizumab Phase 2 and Phase 3 studies in moderate to severe plaque psoriasis, therefore, the sample size has been calculated using three different approaches, z.e., the assessment of DLQI Item 9 score (Over the last one week, how much has your skin caused any sexual difficulties?), overall sPGA response rate [assuming that sPGA-G response (moderate to severe) will be similar to historic sPGA response in moderate to severe psoriasis], and the key secondary endpoint of PASI 100 (based on the clinical importance of achieving complete resolution in this patient population with BSA >1%). Outcomes of the prior studies at week 12 / 16 (Phase 2 and Phase 3) with tildrakizumab 100 mg dose were used for the assumptions about the response rate.

[0280] For DLQI Item 9 response, the sample size was calculated assuming a treatment difference of 45% (response rates under placebo and tildrakizumab are assumed to be 36% and 81%, respectively, in the group for the patients who have "a lot" and "very much" sexual impairment at baseline), a 2-sided alpha of 0.05, 90% power and a 10% attrition rate were assumed. Under these assumptions, 54 subjects are needed to be randomized overall to achieve 90% power.

[0281] For sPGA response, assuming a treatment difference of 27% (z.e., assuming a response rate of 3% and 30% in the placebo and tildrakizumab groups, respectively), 86 subjects are needed to be randomized overall to achieve 90% power assuming a 2-sided alpha of 0.05 and 10% attrition rate.MBHB Ref. 24-0818-WO

[0282] However, the required sample size is driven by the key secondary endpoint of PASI 100, as this endpoint is clinically important and requires the larger sample size for the study to be adequately powered. Considering the assumptions of a 2% response rate in the placebo arm and 16% in the tildrakizumab arm for the PASI 100 end-point, approximately 192 subjects were needed to be randomized into two treatment arms (z.e., approximately 96 subjects per arm) in a 1: 1 ratio to yield over 90% power at the 0.05 alpha level and 10% attrition

[0283] The sample size was calculated using PASS 2023, version 23.0.2, statistical software. The two-sided, two-sample Z-test with pooled variance and a Type I error rate (a) of 0.05 was used to calculate the sample size.Randomization

[0284] Following screening process, qualified subjects will be randomized in Part 1 in a 1 : 1 ratio to receive one of the following two treatment arms:1. Tildrakizumab 100 mg SC injection at Week 0 (Day 1), Week 4 and every 12 weeks thereafter (Weeks 16, 28, 40, and 52) (Arm A)2. Placebo SC injection at Day 1 and Week 4 (Arm B)

[0285] At Week 16, subjects initially randomized to placebo (Arm B) were switched to receive tildrakizumab 100 mg SC at Weeks 16, 20, 32 and 44. To maintain blinding, all subjects shall receive corresponding placebo in Part 2 of the study.Analysis Populations

[0286] The primary evaluation of the primary efficacy endpoint was performed using the intention-to-treat (ITT) population. Safety endpoints will be analyzed using the Safety Analysis Set (SAF). PK data will be analyzed using the PK Analysis Set. The analysis sets are defined as follows:1) ITT population: The ITT population will consist of all randomized subjects regardless of whether they received the IMP. This population will be the main population for the efficacy analyses.2) Safety Population: The safety population will include all randomized subjects who received at least 1 dose of IMP. All safety analyses will be performed based on the safety population according to the actual treatment subjects were administered.Subject Disposition

[0287] Table 16 outlines the subject disposition related to subject enrollment, study completion and discontinuation.MBHB Ref. 24-0818-WOTable 16. Subject Disposition.Demographic and Baseline Characteristics

[0288] Unless otherwise specified, "Baseline" is defined as the last observed value of the parameter of interest prior to the first administration of study treatment (this includes unscheduled visits). For numerical variables, change from Baseline will be calculated as the difference between the post Baseline value and the corresponding Baseline value.

[0289] Demographic and Baseline characteristics was summarized for the ITT and safety population. These summaries included demographics, medical history, and Baseline disease characteristics like time from onset of disease to randomization, demographic data and subject characteristics at Baseline will be summarized descriptively. Exposure and compliance with IMP was summarized descriptively.Efficacy AnalysisPrimary Efficacy Endpoint

[0290] The primary efficacy endpoint is the proportion of subjects with sPGA-G score of clear (0) or minimal (1) with at-least a 2-point reduction from baseline.Statistical Analysis of Primary Efficacy Endpoint

[0291] The primary endpoint of the proportion of subjects with an sPGA-G score of"clear (0)" or "minimal (1)," with at least a 2-grade reduction from baseline at Week 16, were analyzed using the Cochran-Mantel-Haenszel test stratified by stratified by prior use of anti- TNF and baseline non-genital psoriasis involved body surface area (<10% vs. >10%). No more than 70% of subjects with BSA <10% are enrolled. The stratified difference of proportions between treatment groups and associated 95% confidence intervals stratified by stratification factors will be derived using the Miettinen-Nurminen method. Missing data was imputed assuming missing-at-random.MBHB Ref. 24-0818-WO

[0292] All efficacy data, regardless of whether the patient remains on study treatment or discontinues the study treatment but remains in the study, were used for analysis.Specifically, if a patient stays in the study until the end of the study planned placebo- controlled treatment period, all efficacy data collected up to the study planned end of treatment visit will be included in the primary analysis, regardless of whether the patient is on treatment or not.Primary Estimand

[0293] The estimand assesses a population-level estimate of the treatment effect based on a clinically meaningful difference in the proportion of responders between the Tildrakizumab and placebo groups in patients without the use of prohibited medications / therapies and without the discontinuation of treatment (see Table 17).Table 17. Primary EstimandMBHB Ref. 24-0818-WOSupportive Analyses

[0294] A generalized linear mixed model that includes treatment group, stratification factor, and study visit and study visit by treatment group interaction with logit link was also used as supportive analysis assuming binomial distribution for the primary endpoint.Sensitivity Analysis

[0295] A control-based pattern-mixture model was used to explore the possibility of data missing not at random values after study discontinuation will be imputed under the assumption that their outcome would be similar to those in the placebo group with similar background characteristics. Control-based pattern-mixture model was used for the subjects who discontinued the study without any further follow-up data (or had intercurrent event), however, for subjects who did not discontinue the study (or had intercurrent event), their intermittent missing values will be imputed based on the missing-at-random assumption. Multiple imputations will be used to account for uncertainty in the imputation process and results from the imputed datasets will be combined using Rubin's method. Further details will be provided in the SAP.

[0296] To explore the plausible missingness assumptions, supportive analyses, such as such as generalized linear mixed models for binary outcome, and sensitivity analysis controlbased multiple imputation method, analysis by assuming missing data as non-responders, will also be performed. In addition, a tipping point sensitivity analysis was also performed.Key Secondary Efficacy AnalysisTable 18. Tildrakizumab vs Placebo at Week 16_Statistical AnalysisMBHB Ref. 24-0818-WO

[0297] All key secondary analyses were performed using the ITT. Binary secondary endpoints up to Week 16 were analyzed based on the methods described for the modified sPGA-G score.

[0298] Continuous endpoints during the double-blinded period were analyzed using an analysis of covariance model with treatment, randomization stratification factors, and relevant baseline value included in the model. Stratification of subjects wss determined by baseline non-genital psoriasis involved body surface area [<10% and >10%]. No more than 70% of subjects with BSA <10% are enrolled. Missing efficacy data through week 16 after the treatment discontinuation or initiation of concomitant medication was imputed by MI assuming missing-at-random.

[0299] Additionally, a supportive analysis, such as mixed model with repeated measures and control-based MI approach may also be performed.

[0300] Efficacy hypothesis testing was controlled for multiplicity using a step-down sequential testing approach for the primary and key secondary endpoints. The second test was not conducted if the first test was not rejected. Assuming the test on the primary endpoint is rejected, the testing on the key secondary endpoints then followed. Table 19 depicts the order of the tests.Table 19. Statistical Analysis - Order of TestsKey Secondary Estimand (Proportion)

[0301] The estimand assesses a population-level estimate of the treatment effect based on a clinically meaningful difference in the proportion of responders between the Tildrakizumab and placebo groups in patients without the use of prohibited medications / therapies and without the discontinuation of treatment.Table 20. Key Secondary Estimand (Proportion)MBHB Ref. 24-0818-WOKey secondary Estimand (Continuous)

[0302] The estimand assesses a population-level estimate of the treatment effect between the Tildrakizumab and placebo groups in patients without the use of prohibited medications / therapies and without the discontinuation of treatment.Table 21. Key Secondary Estimand (Continuous)MBHB Ref. 24-0818-WOOther Secondary Efficacy EndpointsTable 22. Tildrakizumab vs placebo at Week 16Table 23. Clinical Efficacy of Tildrakizumab at Weeks 32 and 52, Measured by:Table 24. Safety and Tolerability of Tildrakizumab (Items 1-4 Measured throughout study)MBHB Ref. 24-0818-WOExploratory Endpoints

[0303] Table 25 lists the exploratory endpoints.Table 25. Exploratory Endpoints

[0304] Statistical comparisons for the primary and key secondary endpoints was performed for inferential purposes; other statistical comparisons were performed for descriptive purposes.Safety Analysis

[0305] Table 26 lists the data collected for assessment of safety. These safety parameters were assessed using the Safety Population. All the safety parameters were summarized by the treatment arm, and by-subject listings were provided.Table 26. Safety DataClinical Laboratory Evaluation, Vital Sign Analysis and ECGMBHB Ref. 24-0818-WO

[0306] Individual summaries including change from Baseline results will be provided for clinical laboratory values, vital signs, and ECG parameters. Categorical variables will be summarized using frequency and percent and continuous data will be summarized using descriptive statistics including number of observations, arithmetic mean, median, standard deviation and minimum and maximum, as appropriate. For the laboratory safety data, out of range values will be flagged in the data listings, and a list of clinically significantly abnormal values will be presented. Individual results were reviewed for any treatment-emergent changes of possible clinical significance.Physical Examination

[0307] The frequency of subjects with abnormal evaluations of body system findings for physical examinations were summarized by visit and treatment group; abnormal physical examination findings were also presented in a by-subject listing.PK Analysis

[0308] Tildrakizumab concentration was measured at all sampling time points.Anti-Drug Antibodies Endpoints

[0309] Incidence of ADA and correlations with PK, safety, and efficacy endpoints was investigated during all parts of the study.Prior and Concomitant Medications

[0310] All prior and concomitant medications were coded to anatomical therapeutic chemical level 3 classification and preferred name using the latest version of the World Health Organization - Drug Dictionary. The incidence of prior and concomitant medications was summarized by treatment group. Prior medications included medications with a documented stop date / time prior to the first dose of IMP. Concomitant medications are those with start date / time on or after the date / time of first study drug dosing, or those that started prior to the date / time of first dosing but are indicated as continuing into the treatment period. Any medications with partial start and / or stop dates may be considered concomitant if the assignment is uncertain.MBHB Ref. 24-0818-WOAppendix A - Schedule of ActivitiesAppendix A- Schedule of Activities (Continuted)Appendix A Schedule of Activities (Cont.)MBHB Ref. 24-0818-WOAppendix BModified Static Physician Global Assessment of Genitalia Scale (sPGA-G™)The modified sPGA of Genitalia is used to determine a subject's psoriasis lesions in the genital area (labia majora, labia minora, and perineum in females; penis, scrotum, and perineum in males) at a given time point. The modified sPGA score should be selected using the descriptors below that best describe the overall appearance of the lesions.It is not necessary that all three criteria be fulfilled. The modified sPGA of Genitalia score should be based on a combination of erythema and the secondary features (plaque elevation and / or scale). Since erythema is the most robust finding, it should be the dominant feature influencing the modified sPGA of Genitalia rating in the majority of cases.Adapted from Copyright ©2017 Eli Lilly and Company - Used with the permission of Eli Lilly and Company under a Creative Commons Attribution-No Derivatives 4.0 International License - https: / / creativecommons.Org / licenses / by-nd / 4.0 / MBHB Ref. 24-0818-WOAppendix CStatic Physician Global Assessment (sPGA) of Whole-Body Psoriasis(Feldman & Krueger, 2005)

Claims

MBHB Ref. 24-0818-WOWHAT IS CLAIMED IS:Claim 1 : A method of treating genital psoriasis comprising administering an anti-IL-23pl9 antibody huml3B8-b to a patient in need thereof, wherein huml3B8-b comprises:(i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO: 1, and(ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO: 2; and wherein huml3B8-b is administered to the patient for at least up to about 52 weeks.Claim 2: A method of improving a modified Static Physician Global Assessment ofGenitalia (sPGA-G) score in genital psoriasis, comprising administering an anti-IL-23pl9 antibody huml3B8-b to a patient in need thereof, wherein huml3B8-b comprises:(i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO: 1, and(ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO: 2; and wherein huml3B8-b is administered to the patient for at least up to about 52 weeks.Claim 3: The method according to either claim 1 or claim 2, wherein the genital psoriasis is moderate to severe genital psoriasis.Claim 4: The method according to claim 3, wherein the moderate to severe genital psoriasis is characterized by a sPGA-G baseline score greater than or equal to 3.Claim 5: The method according to either claim 1 or claim 2, wherein the patient has moderate to severe genital psoriasis characterized by a sPGA-G of >3 and plaque psoriasis affecting greater than or equal to 1% of Body Surface Area (BSA).Claim 6: The method of claim 5, wherein the psoriasis has been inadequately controlled or the patient intolerant to topical therapy.Claim 7: The method according to either claim 1 or claim 2, wherein huml3B8-b is administered to the patient for at least up to about 52 weeks.MBHB Ref. 24-0818-WOClaim 8: The method according to either claim 1 or claim 2, wherein huml3B8-b is administered to the patient about every 12 weeks.Claim 9: The method according to claim 7, wherein huml3B8-b is administered to the patient subcutaneously.Claim 10: The method according to claim 7, wherein huml3B8-b is administered to the patient by subcutaneous injection.Claim 11 : The method according to claim 9, wherein huml3B8-b is administered to the patient using an auto-injector or prefilled syringe.Claim 12: The method according to either claim 1 or claim 2, wherein a therapeutically effective amount of huml3B8-b is administered to the patient.Claim 13: The method according to either claim 1 or claim 2, wherein about 100 mg of huml3B8-b is administered to the patient.Claim 14: The method according to claim 1, wherein a first dose of huml3B8-b is administered to the patient on week 0, a second dose of huml3B8-b is administered at week 4, and subsequent doses of huml3B8-b are administered to the patient at week 16 and every 12 weeks thereafter.Claim 15: The method according to claim 14, wherein 100 mg of huml3B8-b is administered to the patient.Claim 16: The method according to claim 14, wherein the first dose, the second dose, and the subsequent doses are the same.Claim 17: The method according to claim 14, wherein the first dose is 100 mg.Claim 18: The method according to claim 14, wherein the second dose is 100 mg.MBHB Ref. 24-0818-WOClaim 19: The method according to claim 14, wherein the first dose, the second dose, and the subsequent doses are 100 mg.Claim 20: The method according to claim 19, wherein the second dose is administered at 4 weeks after the first dose and the subsequent doses are administered about every 12 weeks after the second dose, for at least up to about 52 weeks.Claim 21 : The method according to either claim 1 or claim 2, wherein a first dose of huml3B8-b is administered to the patient on week 0, a second dose of huml3B8-b is administered to the patient at about 4 weeks, and subsequent doses of huml3B8-b is administered to the patient about every 4 to 12 weeks thereafter until about week 52.Claim 22: The method according to claim 21, wherein the first dose, the second dose, and the subsequent dose are the same.Claim 23 : The method according to claim 22, wherein the first dose, the second dose, and the subsequent dose are 100 mg.Claim 24: The method according to claim 21, wherein the subsequent doses are administered about every 12 weeks for at least up to about 52 weeks.Claim 25 : The method according to either claim 1 or claim 2, wherein administration of huml3B8-b results in the patient maintaining a modified Static Physician's Global Assessment of Genitalia (sPGA-G) score of 0 "clear" or 1 "almost clear" with at least a 2- point reduction from baseline for at least up to about 52 weeks.Claim 26: The method according to either claim 1 or claim 2, the patient has a Genital Psoriasis Itch Numeric Rating Scale (GPI-NRS) baseline score greater than or equal to 4, wherein administration of the huml3B8-b results in at least a 4-point improvement in the GPI-NRS score when compared to the patient's baseline GPI-NRS score.Claim 27 : The method according to either claim 1 or claim 2, wherein administration of huml3B8-b results in at least a four-point reduction in the patient's Dermatology Life Quality Index (DLQI) score when compared to a patient's baseline DLI score.MBHB Ref. 24-0818-WOClaim 28: The method according to either claim 1 or claim 2, wherein administration of huml3B8-b results in the patient achieving at least a four-point reduction in a Genital Psoriasis Symptoms Scale (GPSS) score when compared to the patient's baseline GPSS score.Claim 29: The method according to either claim 1 or claim 2, wherein the patient has a baseline Psoriasis Area and Severity Index (PASI) score of at least 2.Claim 30: The method according to claim 29, wherein administration of huml3B8-b results in the patient achieving an absolute PASI score of 1.Claim 31 : The method according to claim 29, wherein administration of huml3B8-b results in the patient achieving an absolute PASI score of 0.Claim 32: The method according to either claim 1 or claim 2, wherein administration of huml3B8-b results in the patient maintaining at least a 75% reduction in the Psoriasis Area and Severity Index (PASI 75) for at least up to about 52 weeks.Claim 33: The method according to either claim 1 or claim 2, wherein administration of huml3B8-b results in the patient maintaining at least a 90% reduction in the Psoriasis Area and Severity Index (PASI 90) for at least up to about 52 weeks.Claim 34: The method according to either claim 1 or claim 2, wherein administration of huml3B8-b results in the patient maintaining a 100% reduction in the Psoriasis Area and Severity Index (PASI 100) for at least up to about 52 weeks.Claim 35: A method for achieving a modified Static Physician's Global Assessment of Genitalia (sPGA-G) score of "clear" or "almost clear" with at least a 2-point reduction from baseline in a patient with genital psoriasis comprising administering an anti-IL-23pl9 antibody huml3B8 to a patient in need thereof, wherein huml3B8-b comprises:(i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO: 1, andMBHB Ref. 24-0818-WO(ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO: 2; and wherein huml3B8-b is administered to the patient for at least up to about 52 weeks.Claim 36: A method for maintaining a modified Static Physician's Global Assessment of Genitalia (sPGA-G) score of "clear" or "almost clear" with at least a 2-point reduction from baseline in a patient with genital psoriasis comprising administering an anti-IL-23pl9 antibody huml3B8 to a patient in need thereof, wherein huml3B8-b comprises:(i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO: 1, and(ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO: 2; and wherein huml3B8-b is administered to the patient for at least up to about 52 weeks.Claim 37: A method for achieving at least a four-point improvement of a Genital Psoriasis Itch Numeric Rating Scale (GPI-NRS) baseline score of greater than or equal to 4 in a patient with genital psoriasis comprising administering an anti-IL-23pl9 antibody huml3B8 to a patient in need thereof, wherein huml3B8-b comprises:(i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO: 1, and(ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO: 2; and wherein huml3B8-b is administered to the patient for at least up to about 52 weeks.Claim 38: A method for achieving at least a four-point reduction in a Dermatology Life Quality Index (DLQI) score compared to a baseline DLQI, comprising, administering an anti- IL-23pl9 antibody huml3B8 to a patient in need thereof, wherein huml3B8-b comprises:(i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO: 1, and(ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO: 2; and wherein huml3B8-b is administered to the patient for at least up to about 52 weeks.MBHB Ref. 24-0818-WOClaim 39: A method for achieving at least a four-point reduction in a genital psoriasis Symptoms Scale (GPSS) score when compared a baseline GPSS score comprising administering an anti-IL-23pl9 antibody huml3B8 to a patient in need thereof, wherein huml3B8-b comprises:(i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO: 1, and(ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO: 2; and wherein huml3B8-b is administered to the patient for at least up to about 52 weeks.Claim 40: A method of maintaining a 75% reduction in the Psoriasis Area and Severity Index (PASI 75) in a patient with genital psoriasis comprising administering an anti-IL-23pl9 antibody huml3B8-b to a patient in need thereof, wherein huml3B8-b comprises:(i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO: 1, and(ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO: 2; and wherein huml3B8-b is administered to the patient for at least up to about 52 weeks.Claim 41: A method of maintaining a 90% reduction in the Psoriasis Area and Severity Index (PASI 90) in a patient with genital psoriasis comprising administering an anti-IL-23pl9 antibody huml3B8-b to a patient in need thereof, wherein huml3B8-b comprises:(i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO: 1, and(ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO: 2; and wherein huml3B8-b is administered to the patient for at least up to about 52 weeks.Claim 42: A method of maintaining a 100% reduction in the Psoriasis Area and Severity Index (PASI 100) in a patient with genital psoriasis comprising administering an anti-IL- 23pl9 antibody huml3B8-b to a patient in need thereof, wherein huml3B8-b comprises:(i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO: 1, andMBHB Ref. 24-0818-WO(ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO: 2; and wherein huml3B8-b is administered to the patient for at least up to about 52 weeks.Claim 43: A pharmaceutical composition comprising an anti-IL-23pl9 antibody huml3B8-b for the treatment of genital psoriasis in a patient in need thereof, wherein huml3B8-b comprises:(i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO: 1, and(ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO: 2; and wherein huml3B8-b is administered to the patient for at least up to about 52 weeks.Claim 44: A pharmaceutical composition comprising an anti-IL-23pl9 antibody huml3B8-b for the treatment of genital psoriasis in a patient in need thereof, wherein huml3B8-b comprises:(i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO: 1, and(ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO: 2; and wherein huml3B8-b is administered to the patient for at least up to about 52 weeks.Claim 45: A pharmaceutical composition comprising an anti-IL-23pl9 antibody huml3B8-b for improving modified Static Physician Global Assessment of Genitalia (sPGA- G) in genital psoriasis in a patient in need thereof, wherein huml3B8-b comprises:(i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO: 1, and(ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO: 2; and wherein huml3B8-b is administered to the patient for at least up to about 52 weeks.Claim 46: The pharmaceutical composition according to claim 44 or claim 45, wherein the genital psoriasis is moderate to severe genital psoriasis.MBHB Ref. 24-0818-WOClaim 47 : The pharmaceutical composition according to claim 46, wherein the patient has moderate to severe genital psoriasis has a sPGA-G baseline score greater than or equal to 3.Claim 48: The pharmaceutical composition according to either claim 44 or claim 45, wherein the patient has moderate to severe genital psoriasis characterized by a sPGA-G of >3 and plaque psoriasis affecting more than 1% of Body Surface Area (BSA).Claim 49: The pharmaceutical composition according to claim 48, wherein the psoriasis has been inadequately controlled or the patient intolerant to topical therapy.Claim 50: The pharmaceutical composition according to either claim 44 or claim 45, wherein huml3B8-b is administered to the patient for at least up to about 52 weeks.Claim 51 : The pharmaceutical composition according to either claim 44 or claim 45, wherein huml3B8-b is administered to the patient about every 12 weeks.Claim 52: The pharmaceutical composition according to claim 51, wherein huml3B8-b is administered to the patient subcutaneously.Claim 53: The pharmaceutical composition according to claim 51, wherein huml3B8-b is administered to the patient by subcutaneous injection.Claim 54: The pharmaceutical composition according to claim 53, wherein huml3B8-b is administered to the patient using an auto-injector or prefdled syringe.Claim 55: The pharmaceutical composition according to either claim 44 or claim 45, wherein a therapeutically effective amount of huml3B8-b is administered to the patient.Claim 56: The pharmaceutical composition according to either claim 44 or claim 45, wherein about 100 mg of huml3B8-b is administered to the patient.MBHB Ref. 24-0818-WOClaim 57: The pharmaceutical composition according to either claim 44 or claim 45, wherein a first dose of huml3B8-b is administered to the patient on week 0 a second dose of huml3B8-b is administered at week 4, and subsequent doses of huml3B8-b are administered to the patient at week 16 and every 12 weeks thereafter.Claim 58: The pharmaceutical composition according to claim 57, wherein the first dose, second dose, and the subsequent dose are the same.Claim 59: The pharmaceutical composition according to claim 57, wherein the first dose is 100 mg.Claim 60: The pharmaceutical composition according to claim 57, wherein the second dose is 100 mg.Claim 61 : The pharmaceutical composition according to claim 57, wherein the subsequent doses are 100 mg.Claim 62: The pharmaceutical composition according to claim 58, wherein the first dose and the subsequent doses are 100 mg.Claim 63: The pharmaceutical composition according to claim 59, wherein the second dose is administered at 4 weeks after the first dose and the subsequent doses are administered about every 12 weeks after the second dose, for at least up to about 52 weeks.Claim 64: The pharmaceutical composition according to either claim 44 or claim 45, wherein a first dose of huml3B8-b is administered to the patient on week 0, a second dose of huml3B8-b is administered to the patient at about 4 weeks, and subsequent doses of huml3B8-b is administered to the patient about every 4 to 12 weeks thereafterClaim 65 : The pharmaceutical composition according to claim 64, wherein the first dose, the second dose, and the subsequent dose are the same.Claim 66: The pharmaceutical composition according to claim 65, wherein the first dose, the second dose, and the subsequent dose are 100 mg.MBHB Ref. 24-0818-WOClaim 67 : The pharmaceutical composition according to claim 64, wherein the subsequent dose is administered about every 12 weeks for at least up to about 52 weeks.Claim 68: The pharmaceutical composition according to either claim 44 or claim 45, wherein administration of huml3B8-b results in the patient maintaining a modified Static Physician's Global Assessment of Genitalia (sPGA-G) score of "clear" or "almost clear" with at least a 2-point reduction from baseline for at least up to about 52 weeks.Claim 69: The pharmaceutical composition according to claim 57, wherein administration of huml3B8-b results in the patient maintaining a modified Static Physician's Global Assessment of Genitalia (sPGA-G) score of "clear" or "almost clear" with at least a 2- point reduction from baseline for at least up to about 52 weeks.Claim 70: The pharmaceutical composition according to either claim 44 or claim 45, wherein the patient has a Genital Psoriasis Itch Numeric Rating Scale (GPI-NRS) baseline score greater than or equal to 4, wherein administration of the huml3B8-b results in at least a 4-point improvement in the GPI-NRS score when compared to the patient's baseline GPI- NRS score.Claim 71 : The pharmaceutical composition according to either claim 44 or claim 45, wherein administration of huml3B8-b results in at least a four-point reduction in the patient's Dermatology Life Quality Index (DLQI) score when compared to a patient's baseline DLI scoreClaim 72: The pharmaceutical composition according to either claim 44 or claim 45, wherein administration of huml3B8-b results in the patient achieving at least a four-point reduction in a Genital Psoriasis Symptoms Scale (GPSS) score when compared to the patient's baseline GPSS score.Claim 73: The pharmaceutical composition according to either claim 44 or claim 45, wherein the patient has a baseline Psoriasis Area and Severity Index (PASI) score of at least 2.MBHB Ref. 24-0818-WOClaim 74: The pharmaceutical composition according to claim 73, wherein the patient achieves a PASI score of 1.Claim 75: The pharmaceutical composition according to claim 73, wherein the patient achieves a PASI score of 0.Claim 76: The pharmaceutical composition according to either claim 44 or claim 45, wherein administration of huml3B8-b results in the patient maintaining at least a 75% reduction in the Psoriasis Area and Severity Index (PASI 75) for at least up to about 52 weeks.Claim 77: The pharmaceutical composition according to either claim 44 or claim 45, wherein administration of huml3B8-b results in the patient maintaining at least a 90% reduction in the Psoriasis Area and Severity Index (PASI 90) for at least up to about 52 weeks.Claim 78: The pharmaceutical composition according to either claim 44 or claim 45, wherein administration of huml3B8-b results in the patient maintaining a 100% reduction in the Psoriasis Area and Severity Index (PASI 100) for at least up to about 52 weeks.Claim 79: A pharmaceutical composition comprising an anti-IL-23pl9 antibody huml3B8-b for the treatment of genital psoriasis in a patient in need thereof, wherein huml3B8-b comprises:(i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO: 1, and(ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO: 2; and wherein huml3B8-b is administered to the patient for at least up to about 52 weeks.Claim 80: A pharmaceutical composition comprising an anti-IL-23pl9 antibody huml3B8-b for maintaining a modified Static Physician's Global Assessment of Genitalia (sPGA-G) score of "clear" or "almost clear" with at least a 2-point reduction from baseline in a patient with genital psoriasis, wherein huml3B8-b comprises:MBHB Ref. 24-0818-WO(i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO: 1, and(ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO: 2; and wherein huml3B8-b is administered to the patient for at least up to about 52 weeks.Claim 81: A pharmaceutical composition comprising an anti-IL-23pl9 antibody huml3B8-b for achieving at least a four-point improvement of a Genital Psoriasis Itch Numeric Rating Scale (GPI-NRS) baseline score of greater than or equal to 4 in a patient with genital psoriasis, wherein huml3B8-b comprises:(i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO: 1, and(ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO: 2; and wherein huml3B8-b is administered to the patient for at least up to about 52 weeks.Claim 82: A pharmaceutical composition comprising an anti-IL-23pl9 antibody huml3B8-b for achieving at least a four-point reduction in a Dermatology Life Quality Index (DLQI) score compared to a baseline DLQI, wherein huml3B8-b comprises:(i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO: 1, and(ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO: 2; and wherein huml3B8-b is administered to the patient for at least up to about 52 weeks.Claim 83: A pharmaceutical composition comprising an anti-IL-23pl9 antibody huml3B8-b for achieving at least a four-point reduction in a genital psoriasis Symptoms Scale (GPSS) score when compared a baseline GPSS score, wherein huml3B8-b comprises:(i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO: 1, and(ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO: 2; and wherein huml3B8-b is administered to the patient for at least up to about 52 weeks.MBHB Ref. 24-0818-WOClaim 84: A pharmaceutical composition comprising an anti-IL-23pl9 antibody huml3B8-b for maintaining a 75% reduction in the Psoriasis Area and Severity Index (PASI 75) in a patient with genital psoriasis, wherein huml3B8-b comprises:(i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO: 1, and(ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO: 2; and wherein huml3B8-b is administered to the patient for at least up to about 52 weeks.Claim 85: A pharmaceutical composition comprising an anti-IL-23pl9 antibody huml3B8-b for maintaining a 90% reduction in the Psoriasis Area and Severity Index (PASI 90) in a patient with genital psoriasis, wherein huml3B8-b comprises:(i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO: 1, and(ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO: 2; and wherein huml3B8-b is administered to the patient for at least up to about 52 weeks.Claim 86: A pharmaceutical composition comprising an anti-IL-23pl9 antibody huml3B8-b for maintaining a 100% reduction in the Psoriasis Area and Severity Index (PASI 100) in a patient with genital psoriasis comprising administering an anti-IL-23pl9 antibody huml3B8-b to a patient in need thereof, wherein huml3B8-b comprises:(i) a light chain polypeptide comprising the amino acid sequence of SEQ ID NO: 1, and(ii) a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO: 2; and wherein huml3B8-b is administered to the patient for at least up to about 52 weeks.

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