Methods of treating scleroderma

Abstract

The present disclosure generally relates to scleroderma and methods of treating scleroderma. For example, the present disclosure provides methods of treating scleroderma in a subject having any number of specifically identified genes having particular expression levels, the methods comprising administering FT011 or a pharmaceutically acceptable salt thereof.

Description

Related Application Data The present application claims priority from United States Provisional Patent Application No. 63 / 626,182 filed on 29 January 2024 entitled “Methods of treating scleroderma”. The entire contents of which is hereby incorporated by reference. Technical field The present disclosure generally relates to scleroderma and methods of treating scleroderma. Background Scleroderma is a debilitating, potentially life-threatening autoimmune condition characterised by inflammation and fibrosis of the skin and other organs (commonly the lungs, kidneys, and heart). This condition results in high morbidity with substantial detriment to quality of life, with patients commonly experiencing loss of mobility and function, pain, and fatigue, often accompanied with a significant impact to their mental health. Scleroderma has the highest mortality among rheumatic diseases and presents a serious and unmet clinical need. Summary The present disclosure is based on the unexpected finding that FT011 or a pharmaceutically acceptable salt thereof is capable of treating scleroderma, delivering important therapeutic benefits to a range of patients. In addition, the inventors identified a unique set of genetic markers which correlate with treatment of scleroderma following administration with FT011 or a pharmaceutically acceptable salt thereof. Thus, the present disclosure provides a method of treating scleroderma in a subject having an elevated level of expression of one or more genes selected from those listed in Table 1, the method comprising administering to the subject a therapeutically effective amount of FT011 or a pharmaceutically acceptable salt thereof, wherein the subject has an elevated level of expression of one or more genes selected from those listed in Table 1. The present disclosure also provides a method of treating scleroderma in a subject having an elevated level of expression of one or more genes selected from those listed in Table 1, the method comprising administering to the subject a therapeutically effective amount of FT011 or a pharmaceutically acceptable salt thereof, thereby lowering the level of expression of the one or more genes. The present disclosure also provides a method of treating scleroderma in a subject having an elevated level of expression of the one or more genes, comprising administering to the subject an amount of FT011 or the pharmaceutically acceptable salt thereof effective to lower the level of expression of one or more of the genes listed in Table 1 having the elevated level of expression. The present disclosure also provides a method of treating scleroderma in a subject, the method comprising administering to the subject a therapeutically effective amount of FT011 or a pharmaceutically acceptable salt thereof, wherein the subject has an elevated level of expression of one or more genes selected from those listed in Table 1. The present disclosure also provides a method of treating scleroderma in a subject, the method comprising administering to the subject a therapeutically effective amount of FT011 or a pharmaceutically acceptable salt thereof, thereby lowering the level of expression of one or more genes selected from those listed in Table 1. The present disclosure also provides a method of lowering a level of expression of one or more genes selected from those listed in Table 1 in a subject having scleroderma, the method comprising administering to the subject FT011 or a pharmaceutically acceptable salt thereof in an amount sufficient to lower the level of expression of the one or more genes. The present disclosure also provides a method of lowering a level of expression of one or more genes selected from those listed in Table 1 in a subject having scleroderma, the method comprising administering to the subject FT011 or a pharmaceutically acceptable salt for a treatment period sufficient to lower the level of expression of the one or more genes. The present disclosure also provides a method of lowering a level of expression of one or more genes selected from those listed in Table 1 in a subject having scleroderma, the method comprising administering to the subject FT011 or a pharmaceutically acceptable salt thereof in an amount and for a treatment period sufficient to lower the level of expression of the one or more genes. The present disclosure also provides a method of treating scleroderma, the method comprising administering FT011 or a pharmaceutically acceptable salt thereof to a subject diagnosed as suffering from scleroderma, wherein the therapeutically effective amount of FT011 or a pharmaceutically acceptable salt thereof has previously been shown to lower the level of expression of one or more genes selected from those listed in Table 1 when administered to a subject suffering from scleroderma. The present disclosure also provides a method of treating scleroderma in a subject, the method comprising administering to the subject a therapeutically effective amount of FT011 or a pharmaceutically acceptable salt thereof, wherein the subject has a decreased level of expression of MTF2. The present disclosure also provides a method of treating scleroderma in a subject, the method comprising administering to the subject a therapeutically effective amount of FT011 or a pharmaceutically acceptable salt thereof, thereby elevating the level of expression of MTF2. The present disclosure also provides a method of elevating the level of expression of MTF2 in a subject having scleroderma, the method comprising administering to the subject a therapeutically effective amount of FT011 or a pharmaceutically acceptable salt thereof. The present disclosure also provides a method of treating scleroderma, the method comprising administering a therapeutically effective amount of FT011 or a pharmaceutically acceptable salt thereof to a subject diagnosed as suffering from scleroderma, wherein the therapeutically effective amount of FT011 or a pharmaceutically acceptable salt thereof has previously been shown to elevate the level of expression of MTF2 when administered to a subject suffering from scleroderma. The present disclosure also provides a kit comprising FT011 or pharmaceutically acceptable salt of thereof for treating scleroderma. The kit may contain instructions for use. The present disclosure also provides a method of improving an American College of Rheumatology (ACR) Composite Response Index in Diffuse Cutaneous Systemic Sclerosis (CRISS) score in a subject having scleroderma, the method comprising administering to the subject FT011 or a pharmaceutically acceptable salt thereof in an amount sufficient to provide in an improvement in said score in the subject. The present disclosure also provides a method of improving an American College of Rheumatology (ACR) Composite Response Index in Diffuse Cutaneous Systemic Sclerosis (CRISS) score in a subject having scleroderma, the method comprising administering to the subject FT011 or a pharmaceutically acceptable salt for a treatment period sufficient to provide in an improvement in said score in the subject. The present disclosure also provides a method of selecting a subject having scleroderma as being suitable for treatment with FT011 or a pharmaceutically acceptable salt thereof, the method comprising determining the level of expression of one or more genes in Table 1 in the subject. The present disclosure also provides a method of treating scleroderma, the method comprising: i. selecting a subject having scleroderma and an elevated level of expression of one or more genes selected from those listed in Table 1, the selecting comprising determining the level of expression of the one or more genes; and ii. administering to the subject a therapeutically effective amount of FT011 or a pharmaceutically acceptable salt thereof. The present disclosure also provides a method of monitoring a subject’s response to treatment of scleroderma with FT011 or a pharmaceutically acceptable salt thereof, the method comprising monitoring the level of expression of one or more genes selected from those listed in Table 1 after the subject has been administered a therapeutically effective amount of FT011 or a pharmaceutically acceptable salt thereof. Particularly preferred embodiments are described herein, including in the independent claims. Detailed description General Throughout this specification, unless specifically stated otherwise or the context requires otherwise, reference to a single step, feature, composition of matter, group of steps or group of features or compositions of matter shall be taken to encompass one and a plurality (i.e. one or more) of those steps, features, compositions of matter, groups of steps or groups of features or compositions of matter. Those skilled in the art will appreciate that the present disclosure is susceptible to variations and modifications other than those specifically described. It is to be understood that the disclosure includes all such variations and modifications. The disclosure also includes all of the steps, features, compositions and compounds referred to or indicated in this specification, individually or collectively, and any and all combinations or any two or more of said steps or features. Thus, each feature of any particular example or embodiment of the present disclosure may be applied mutatis mutandis to any other example or embodiment of the present disclosure unless specifically stated otherwise. The present disclosure is not to be limited in scope by the specific examples described herein, which are intended for the purpose of exemplification only. Functionally-equivalent products, compositions and methods are clearly within the scope of the present disclosure. Unless specifically defined otherwise, all technical and scientific terms used herein shall be taken to have the same meaning as commonly understood by one of ordinary skill in the art (for example, in cell culture, molecular genetics, immunology, immunohistochemistry, chemistry, organic chemistry, protein chemistry, and biochemistry). Unless otherwise indicated, any recombinant DNA, recombinant protein, cell culture, and immunological techniques utilised in the present disclosure are standard procedures, well known to those skilled in the art. Such techniques are described and explained throughout the literature in sources such as, J. Perbal, A Practical Guide to Molecular Cloning, John Wiley and Sons (1984), J. Sambrook et al. Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory Press (1989), T.A. Brown (editor), Essential Molecular Biology: A Practical Approach, Volumes 1 and 2, IRL Press (1991), D.M. Glover and B.D. Hames (editors), DNA Cloning: A Practical Approach, Volumes 1-4, IRL Press (1995 and 1996), and F.M. Ausubel etal. (editors), Current Protocols in Molecular Biology, Greene Pub. Associates and Wiley-Interscience (1988, including all updates until present), Ed Harlow and David Lane (editors) Antibodies: A Laboratory Manual, Cold Spring Harbor Laboratory, (1988), and J.E. Coligan et al. (editors) Current Protocols in Immunology, John Wiley & Sons (including all updates until present). Throughout this specification, unless the context requires otherwise, the word “comprise”, or variations such as “comprises” or “comprising”, is understood to imply the inclusion of a stated step or element or integer or group of steps or elements or integers but not the exclusion of any other step or element or integer or group of elements or integers. The term “and / or”, e.g., “X and / or Y” shall be understood to mean either “X and Y” or “X or Y” and shall be taken to provide explicit support for both meanings or for either meaning. As used herein, the singular forms of “a”, “and” and “the” include plural forms of these words, unless the context clearly dictates otherwise. The term “about” in relation to a numerical value x is optional and means, for example, any number within 1%, 5% or 10% of the referenced number. The term “about” also encompasses the exact number recited. Genetic Markers The inventors have, for the first time, identified a specific set of genes (referred to herein as differentially expressed genes (DEGs)) whose expression increases with scleroderma progression and whose expression decreases upon treatment with FT011. These genes are set forth in Table 1. Table 1. Significant DEGs correlating with a positive clinical response to treatment with FT011 Genes Placebo 200 mg 400 mg Main function log2FC P value log2 FC P value log2 FC P value GFRA2 0,658 0.001 0,079 0.519 -0.631 0.001 neuron survival and differentiation PDE1B 0,467 0.021 -0.370 0.173 -0.540 0.002 inflammation (macrophage diff) DYSF 0.371 0.033 -0.077 0.766 -0.518 0.001 muscles repair COL6A3 0,527 0.004 -0.013 0.995 -0.490 0.004 Extracellular matrix organisation D0K1 0.365 0.025 -0.250 0.459 -0.478 0.006 Cell proliferation COL15A1 0,408 0.038 -0.164 0.706 -0.475 0.001 Extracellular matrix organisation SEC24D 0.445 0.000 0.085 0.602 -0.461 0.005 Protein transport for ECM COL4A1 0,363 0.018 -0.366 0.268 -0.444 0.003 Extracellular matrix organisation ABCA8 0,642 0.001 -0.149 0.650 -0.435 0.005 Lipid metabolism / homeostasis TRIL 0.598 0.012 -0.231 0.469 -0.434 0.008 Inflammation COL5A2 0,393 0.022 -0.008 0.953 -0.407 0.012 Extracellular matrix organisation SLC5A8 0.320 0.005 0.084 0.666 -0.405 0.012 Transporter RHOJ 0,511 0.011 -0.012 0.913 -0.395 0.018 Angiogenesis / fibronectin dep. ANGPTL2 0.454 0.008 -0.147 0.539 -0.392 0.010 Angiogenesis, tissue repair ITIH5 0,321 0.022 -0.451 0.233 -0.376 0.008 Extracellular matrix protein LOXL2 0,451 0.035 -0.258 0.460 -0.373 0.030 Extracellular matrix reorganisation USP35 0.593 0.001 -0.045 0.924 -0.372 0.018 Cell death COL5A1 0,422 0.014 0,135 0.549 -0.371 0.023 Extracellular matrix organisation HEPH 0.389 0.047 0.100 0.720 -0.361 0.029 Iron transport COL6A1 0,428 0.021 0,074 0.644 -0.361 0.026 Extracellular matrix organisation ZNF347 0.408 0.019 -0.279 0.160 -0.355 0.039 tumour suppressor gene C1R 0,386 0.024 0,158 0.402 -0.354 0.046 Inflammation / Complement activation PREX2 0,357 0.043 -0.412 0.081 -0.353 0.010 PI3K signalling (angiogenesis, proliferation, metabolism) AL 13 8976.2 0.465 0.034 -0.074 0.937 -0.343 0.018 - STS 0.400 0.026 -0.102 0.678 -0.309 0.048 Hormone metabolism *Upregulated values are underlined; downregulated values are italicised; genes whose functions have been reported to be related to fibrosis or inflammation, or potentially play a role in systemic sclerosis, are indicated by bold text in ‘Main function’ column. The inventors also identified a gene (MTF2) whose expression decreases with scleroderma progression and whose expression increases upon treatment with FT011. Accordingly, the methods described herein relating to treatment of a subject having an elevated level of expression of one or more genes selected from those listed in Table 1, or relating to methods of decreasing the level of expression of one or more genes selected from those listed in Table 1, may be performed in the same manner but with respect to a subject having a decreased level of expression of MTF2, or with respect to methods of increasing the level of expression of MTF2. For example, the methods described herein may comprise administering to the subject a therapeutically effective amount of FT011 or a pharmaceutically acceptable salt thereof to elevate the level of expression of MTF2. For the purposes of nomenclature only and without limitation to exact nucleotide sequences, particular genes are referred to herein by use of their accepted names in the art. Exemplary sequences of the one or more genes described herein by way of their accepted names may be found on publicly available genetic databases, such as at the NCBI GenBank Database. As used herein, reference to “one or more genes selected from those listed in Table 1” may refer each individual gene listed in Table 1. For example, the term “one or more genes selected from those listed in Table 1” may refer to any individual gene GFRA2, or PDE1B or DYSF or COL6A3 or D0K1 or COL15A1 or SEC24D or COL4A1 or ABCA8 or TRIL or COL5A2 or SLC5A8 or RHOJ or ANGPTL2 or ITIH5 or L0XL2 or USP35 or COL5A1 or HEPH or COL6A1 or ZNF347 or C1R or PREX2 or AL138976.2 or STS. The term “one or more genes selected from those listed in Table 1” may also refer to any combination of the individual genes listed in Table 1. Alternatively, reference to “one or more genes selected from those listed in Table 1” may refer to the entire group consisting of GFRA2, PDE1B, DYSF, COL6A3, D0K1, COL15A1, SEC24D, COL4A1, ABCA8, TRIL, COL5A2, SLC5A8, RHOJ, ANGPTL2, ITIH5, LOXL2, USP35, COL5A1, HEPH, COL6A1, ZNF347, C1R, PREX2, AL138976.2 and STS. Thus, the methods described herein may be applicable to subjects having an elevated level of each and every one of the individual genes listed in Table 1. That is, the methods described herein may be applicable to subjects having an elevated level of all of the individual genes listed in Table 1. The level of expression of one or more genes may be determined by performing an analysis of the level of expression of one or more genes. Thus, any of the methods described herein may comprise a step of performing an analysis of the level of expression of one or more genes, for example, in a sample taken from a subject. Any of the methods described herein may also comprise a step of taking a sample from a subject in order to perform the expression analysis. A suitable sample may include a skin biopsy, for example, a punch biopsy. Suitably, a punch biopsy may comprise taking a skin sample ranging from 3 mm to 5 mm thickness. Suitable methods of taking a sample from a subject are described, for example, in Nischal U, Nischal Kc, Khopkar U. Techniques of skin biopsy and practical considerations. J Cutan Aesthet Surg. 2008; 1(2): 107-111. doi: 10.4103 / 0974-2077.44174, the disclosure of which is incorporated herein by reference in its entirety. Methods of determining the level of expression of a gene are known in the art. Methods of determining the level of expression of a gene are also described herein. Thus, for example, the level of expression can be performed as described in the examples herein. The level of expression of a gene may be determined using RNA sequencing. RNA may be isolated from a sample taken from a subject. RNA may be isolated using, for example, an RNeasy Mini kit (Qiagen). RNA libraries may be prepared using a sequencing kit. The sequencing kit may be, for example, SMART-Seq v4 PLUS Kit (Takara). The prepared RNA libraries may be sequenced using a sequencing platform. The sequencing platform may be, for example, an Illumina NovaSeq platform (NovaSeq S4 300 cycle, 150bp paired-end, 30 million reads per sample). The RNA sequences may be aligned to a human reference genome. The alignment may be completed, for example, using STAR with alignment to the Genome Reference Consortium Human Build 37 (GRCh37), using GENCODE as a database. The level of expression of one or more genes may be quantified using data processing tools, for example, using a high-throughput sequence analysis package in Python. Analysis of genes may be performed using data analysis tools, for example, using DESeq2. DESeq2 provides methods to test for differential expression using a negative binomial generalised linear model, which is described in detail, for example, in Love, M.I., Huber, W. & Anders, S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol 15, 550 (2014), the disclosure of which is incorporated herein by reference in its entirety. The generalised linear model may be controlled for individual effects. All such tools and methods may suitably be performed in accordance with the respective manufacturer's or supplier’s protocols. Thus, determining the level of expression of a gene in any of the methods described herein may comprise, for example: isolating RNA from a sample taken from a subject using an RNeasy Mini kit (Qiagen); preparing RNA libraries using a SMART-Seq v4 PLUS Kit (Takara) sequencing kit; sequencing the prepared RNA libraries using an Illumina NovaSeq sequencing platform (in particular, NovaSeq S4 300 cycle, 150bp paired-end, 30 million reads per sample); aligning the RNA sequences to a human reference genome using STAR with alignment to the Genome Reference Consortium Human Build 37 (GRCh37), using GENCODE as a database; quantifying the level of expression of one or more genes using a high-throughput sequence analysis package in Python; analysing genes using DESeq2 comprising a negative binomial generalised linear model, wherein the generalised linear model is controlled for individual effects Alternatively, or in addition, the level of expression of one or more genes may be determined by having performed an analysis of the expression level of the one or more genes. For example, any of the methods described herein may not comprise a step of taking a sample from a subject and performing an analysis of the level of expression of one or more genes in the sample. Instead, the level of expression may have been determined previously. The level of expression of one or more genes may be determined by an analysis which includes a comparison of an expression level in healthy cells with an expression level in diseased cells. A healthy cell may be a cell in or from a subject that has not been affected by scleroderma. Alternatively, a healthy cell may be a cell in or from a tissue in a subject that has been affected by scleroderma, but which tissue is not a diseased tissue or does not display any symptoms of scleroderma. A diseased cell may be a cell in or from a subject that has been affected by scleroderma and which displays one or more symptoms of the disease. Alternatively, or in addition, the level of expression of one or more genes may be determined by an analysis which includes a comparison of an expression level in a cell that has been treated with FT011 or a pharmaceutically acceptable salt thereof with an expression level in a cell that has not been treated with FT011 or a pharmaceutically acceptable salt thereof. Any of the methods described herein may comprise a step of establishing a reference level of expression of one or more genes. The reference level may be different for each gene. Reference levels may be determined based on the level of expression of one or more genes listed in Table 1. A “reference” level of expression of one or more genes can be determined by selecting any suitable population of cells (e.g., healthy cells or diseased cells; or cells not treated with FT011 or a pharmaceutically acceptable salt thereof, or cells treated with FT011 or a pharmaceutically acceptable salt thereof) from which to derive the level of expression of one or more genes. That population of cells may be taken from any suitable tissue in a subject, such as any tissue in which scleroderma disease pathology manifests. For example, but without limitation, the population of cells may be taken from a subject’s skin. Suitable statistical analyses can be performed to provide a reference level that is indicative of a typical level of expression of diseased or healthy patients. It will be appreciated that the exact expression levels may vary depending on the particular methodology used to perform the expression analysis, or the particular cell populations chosen in order to provide a suitable reference level. Once calculated, the reference level may be stored in a database and / or made accessible for the performance of the methods described herein. Alternatively, any of the methods described herein may comprise a step of comparing a measurement and / or analysis of the level of expression of one or more genes to a predetermined reference level. For example, the predetermined reference level may be stored in a database including such information. Suitable threshold levels can be determined according to the particular methodology used to identify and / or measure gene expression. Again, it will be appreciated that the precise thresholds will vary depending on the samples used to establish those threshold levels and according to the particular analytical methodology used in each instance. The change in the level of expression of a gene, that is lowering or elevating thereof, may depend on the dosage amount and / or the treatment period. An “elevated” or “high” level of expression of one or more genes is a level of expression of one or more genes that is greater than a reference level of expression of one or more genes. Conversely, a “decreased” or “lowered” level of expression is a level of expression of one or more genes that is reduced relative to a reference level of expression of one or more genes. The level of expression of one or more genes may be determined over a treatment period. This “treatment period” may refer to any period of time where FT011 or a pharmaceutically acceptable salt thereof is or has been provided for administration to a subject or is administered to a subject. For example, a treatment period may refer to at least or about 1 week, or 2 weeks, or 3 weeks, or 4 weeks, or 5 weeks, or 6 weeks, or 7 weeks, or 8 weeks, or 9 weeks, or 10 weeks, or 11 weeks, or 12 weeks, or 4 months, or 5 months, or 6 months, or 7 months, or 8 months, or 9 months, or 10 months, or 11 months, or 12 months, or 13 months, or 14 months, or 15 months, or 16 months, or 17 months, or 18 months, or 19 months, or 20 months, or 21 months, or 22 months, or 23 months or 24 months. For example, the level of expression of one or more genes may be determined after a treatment period of 12 weeks. Thus, the level of expression of one or more genes may be determined prior to administration of FT011 or a pharmaceutically acceptable salt thereof. Alternatively or in addition, the level of expression of one or more genes may be determined after administration of FT011 or a pharmaceutically acceptable salt thereof for any treatment period described herein. The expression level can also be determined at one or more intervals during the treatment period. It will be appreciated that the level of expression of one or more genes may be determined prior to and after administration of FT011 or a pharmaceutically acceptable salt thereof (e.g., at the start and end of the treatment period). Administering to the subject a therapeutically effective amount of FT011 or a pharmaceutically acceptable salt thereof may lower the level of expression of one or more genes selected from those listed in Table 1. For example, administering to the subject a therapeutically effective amount of FT011 or a pharmaceutically acceptable salt thereof may be sufficient to lower the level of expression of one or more genes selected from those listed in Table 1. A lowering or decrease in the level of expression of one or more genes selected from those listed in Table 1 may be determined relative to the level of expression of the one or more genes prior to administration of a therapeutically effective amount of FT011 or a pharmaceutically acceptable salt thereof, or to a reference level of expression. The level of expression of one or more genes selected from those listed in Table 1 may be lowered by a factor of at least 2, or 3, or 4, or 5. For example, the level of expression of one or more genes selected from those listed in Table 1 may be lowered by at least half relative to the level of expression of the one or more genes prior to administration of a therapeutically effective amount of FT011 or a pharmaceutically acceptable salt thereof. The level of expression of one or more genes selected from those listed in Table 1 may be lowered by at least one third relative to the level of expression of the one or more genes prior to administration of a therapeutically effective amount of FT011 or a pharmaceutically acceptable salt thereof. The level of expression of one or more genes selected from those listed in Table 1 may be lowered by at least a quarter relative to the level of expression of the one or more genes prior to administration of a therapeutically effective amount of FT011 or a pharmaceutically acceptable salt thereof. The level of expression of one or more genes selected from those listed in Table 1 may be lowered by at least one fifth relative to the level of expression of the one or more genes prior to administration of a therapeutically effective amount of FT011 or a pharmaceutically acceptable salt thereof. The level of expression of one or more genes selected from those listed in Table 1 may be lowered by a fold change of at least 1.23. The level of expression of one or more genes selected from those listed in Table 1 may be lowered by a fold change of at least 1.23 relative to the level of expression of the one or more genes prior to administration of a therapeutically effective amount of FT011 or a pharmaceutically acceptable salt thereof. The level of expression of one or more genes selected from those listed in Table 1 may be lowered by a log2 fold change of at least 0.3. The level of expression of one or more genes selected from those listed in Table 1 may be lowered by a log2 fold change of at least 0.3 relative to the level of expression of the one or more genes prior to administration of a therapeutically effective amount of FT011 or a pharmaceutically acceptable salt thereof. Conversely, administering to the subject a therapeutically effective amount of FT011 or a pharmaceutically acceptable salt thereof may elevate the level of expression of MTF2. For example, administering to the subject a therapeutically effective amount of FT011 or a pharmaceutically acceptable salt may be sufficient to elevate the level of expression of MTF2. An elevation or increase in the level of expression of MTF2 may be determined relative to the level of expression of the MTF2 prior to administration of a therapeutically effective amount of FT011 or a pharmaceutically acceptable salt thereof, or to a reference level of expression. The level of expression of MTF2 may be elevated by a factor of at least 2, or 3, or 4, or 5. For example, the level of expression of MTF2 may be elevated by at least half relative to the level of expression of the MTF2 prior to administration of a therapeutically effective amount of FT011 or a pharmaceutically acceptable salt thereof. The level of expression of MTF2 may be elevated by at least one third relative to the level of expression of the MTF2 prior to administration of a therapeutically effective amount of FT011 or a pharmaceutically acceptable salt thereof. The level of expression of MTF2 may be elevated by at least a quarter relative to the level of expression of the MTF2 prior to administration of a therapeutically effective amount of FT011 or a pharmaceutically acceptable salt thereof. The level of expression of MTF2 may be elevated by at least one fifth relative to the level of expression of the MTF2 prior to administration of a therapeutically effective amount of FT011 or a pharmaceutically acceptable salt thereof. The level of expression of MTF2 may be elevated by a log2 fold change of at least 1.23. The level of expression of MTF2 may be elevated by a log2 fold change of at least 1.23 relative to the level of expression of the MTF2 prior to administration of a therapeutically effective amount of FT011 or a pharmaceutically acceptable salt thereof. FT011 “FT011”, also known as “(£)-2-[[3-(3-methoxy-4-propargyloxy)phenyl)-l-oxo-2-propenyl]amino]benzoic acid”, “(£)-2-(3-(3-methoxy-4-(prop-2-yn-l-yloxy)phenyl) acrylamidojbenzoic acid”, “(E)-2-[[3-(3-methoxy-4-propargyloxy)phenyl)-l-oxo-2-propenyl] amino]benzoic acid”, and “3-methoxy-4-propargyloxycinnamoyl anthranilic acid” has been described, including its preparation and biological evaluation, in International Patent Application WO 2008 / 003141, the disclosure of which is incorporated herein by reference in its entirety. “FT011” is also referred herein as the “non-salt form,” “free form,” or “free acid form”. FT011 has the structure of Formula (I): Formula (I). Pharmaceutically acceptable salts and crystalline forms of FT011 are described herein, including their preparation and biological evaluation. The term “FT011 or a pharmaceutically acceptable salt”, as used herein, refers to any salt, solid form, crystalline form, polymorph, hydrate or solvate of FT011 which retains its biological properties and which is not toxic or otherwise undesirable for pharmaceutical use. Such salts may be derived from a variety of organic and inorganic counter-ions well known in the art. Such salts include, but are not limited to salts formed when an acidic proton present in the parent compound (i.e., FT011) either (a) is replaced by a metal ion, e.g., an alkali metal ion, an alkaline earth ion or an aluminium ion, or alkali metal or alkaline earth metal hydroxides, such as sodium, potassium, or magnesium, or (b) reacts with an organic base, such as aliphatic, alicyclic, or aromatic organic amines, such as ammonia, ethanolamine (also referred to as monoethanolamine, or ‘MEA’), lysine, arginine, choline, meglumine, tertbutylamine (also referred to as ‘TBA’, 2-methylpropan-2-amine, or 2-amino-2-methylpropane), tris(hydroxymethyl)aminomethane (also referred to as ‘Tris’ or ‘Tris base’), and the like. The term “solid form” of FT011 can refer to any crystalline form or any amorphous form of FT011 as a free acid, as a free base, as an acid addition salt, a base addition salt, a complex, or a solvate (including hydrate), or a co-precipitation. The term “crystalline form” of FT011 as used herein refers to any crystalline form of FT011 as a free acid, FT011 as a free base, as an acid addition salt of FT011, a base addition salt of FT011, a complex of FT011, a solvate (including hydrate) of FT011, or a co-crystal of FT011. In many instances, the terms “crystalline form” and “solid form” can refer to those that are pharmaceutically acceptable, including, for example, those of pharmaceutically acceptable addition salts, pharmaceutically acceptable complexes, pharmaceutically acceptable solvates, pharmaceutically acceptable co-crystals, and pharmaceutically acceptable co-precipitations. The term “solvate” refers to a complex or aggregate formed by one or more molecules of a solute, e.g., FT011, and one or more molecules of a solvent, which present in stoichiometric or non-stoichiometric amounts. Suitable solvents include, but are not limited to, water, methanol, ethanol, n-propanol, isopropanol, and acetic acid. In certain embodiments, the solvent is pharmaceutically acceptable. In one embodiment, the complex or aggregate is in a crystalline form. In another embodiment, the complex or aggregate is in a noncrystalline form. Where the solvent is water, the solvate is a hydrate. Examples of hydrates include, but are not limited to, a hemihydrate, monohydrate, dihydrate, trihydrate, tetrahydrate, and pentahydrate. The term “therapeutically effective amount” of FT011 is the quantity which, when administered, at least partly stabilises, ameliorates, eliminates or reduces a symptom or pathological sign of scleroderma. Alternatively, a therapeutically effective amount is a quantity which, when administered prevents the exacerbation of one or more symptoms or pathological signs of scleroderma. Symptoms or pathological signs of scleroderma in a subject include one or more of, but are not limited to, fingers or toes that turn blue or white in response to cold temperatures (e.g., Raynaud phenomenon); stiffness and tightness of skin of fingers, hands, forearm, and face, hair loss (e.g., skin thickened on the fingers of both hands, extending proximal to the metacarpophalangeal joints, skin on fingers thickened, puffy fingers, and sclerodactyly); skin that is darker or lighter than normal; abnormal nail fold capillaries; small white lumps of calcium beneath the skin; sores (e.g., ulcers on tip of digits, lesions on fingertips and pitting scars on fingertips); tight and mask-like skin; telangiectasias; joint pain, stiffness, and swelling, resulting in loss of motion; numbness and pain in the feet; breathing problems (e.g., dry cough, shortness of breath, wheezing); difficulty swallowing; oesophageal reflux; heartbum; constipation; diarrhea; abnormal heart rhythm; pulmonary arterial hypertension; interstitial lung disease; fluid around the heart; kidney failure; erectile dysfunction; vaginal dryness; presence of any one or more of a centromere antibody, a Scl-70 antibody and a RNA polymerase III antibody; fibrosis and inflammation. Scleroderma may be diagnosed according to any one or more national or institute provided guidelines. Scleroderma may be diagnosed in accordance with the American College of Rheumatology and European League Against Rheumatism (ACR-EULAR) available at https: / / www.rarediseaseadvisor.com / disease-info-pages / systemic-sclerosis-guidelines / . The amount to be administered may depend on the characteristics of the subject, such as general health, other diseases, age, sex, genotype, and body weight. A person skilled in the art will be able to determine appropriate dosages depending on these and other factors. Accordingly, this term is not to be construed to limit the present disclosure to a specific quantity, e.g., weight or amount of compound. FT011 or a pharmaceutically acceptable salt thereof may be provided in a pharmaceutical composition comprising a pharmaceutically acceptable excipient. FT011 or a pharmaceutically acceptable salt thereof may be formulated for single dose administration. FT011 or a pharmaceutically acceptable salt thereof may be formulated as an oral, parenteral, or intravenous dosage form. For example, FT011 or a pharmaceutically acceptable salt thereof formulated as an oral dosage form may be provided as a tablet or a capsule. FT011 or pharmaceutically acceptable salt of thereof may be delivered to a subject by any suitable means. FT011 or a pharmaceutically acceptable salt thereof may be administered in an amount of from about 1 mg to about 1000 mg, or about 100 mg to about 500 mg, or about 200 mg to about 400 mg. For example, FT011 may be administered in an amount of about 50 mg, or about 100 mg, or about 150 mg, or about 200 mg, or about 250 mg, or about 300 mg, or about 350 mg, or about 400 mg, or about 450 mg, or about 500 mg, or about 550 mg, or about 600 mg, or about 650 mg, or about 700 mg, or about 750 mg, or about 800 mg, or about 850 mg, or about 900 mg, or about 950 mg, or about 1000 mg. A pharmaceutically acceptable salt of FT011 may be administered in an amount corresponding to from about 1 mg to about 1000 mg, or about 100 mg to about 500 mg, or about 200 mg to about 400 mg of FT011. For example, a pharmaceutically acceptable salt of FT011 may be administered in an amount corresponding to about 1 mg, or about 2 mg, or about 3 mg, or about 4 mg, or about 5 mg, or about 6 mg, or about 7 mg, or about 8 mg, or about 9 mg, or about 10 mg, or about 11 mg, or about 12 mg, or about 13 mg, or about 14 mg, or about 15 mg, or about 16 mg, or about 17 mg, or about 18 mg, or about 19 mg, or about 20 mg, or about 30 mg, or about 40 mg, or about 50 mg, or about 100 mg, or about 150 mg, or about 200 mg, or about 250 mg, or about 300 mg, or about 350 mg, or about 400 mg, or about 450 mg, or about 500 mg, or about 550 mg, or about 600 mg, or about 650 mg, or about 700 mg, or about 750 mg, or about 800 mg, or about 850 mg, or about 900 mg, or about 950 mg, or about 1000 mg ofFTOll. FT011 or a pharmaceutically acceptable salt thereof may be administered in an amount effective to provide a dose of from about 0.5 mg / kg to about 200 mg / kg. FT011 may be administered in an amount effective to provide a dose of about 0.5 mg / kg, or about 1 mg / kg, or about 2 mg / kg, or about 3 mg / kg, or about 4 mg / kg, or about 5 mg / kg, or about 6 mg / kg, or about 7 mg / kg, or about 8 mg / kg, or about 9 mg / kg, or about 10 mg / kg, or about 20 mg / kg, or about 30 mg / kg, or about 40 mg / kg, or about 50 mg / kg, or about 60 mg / kg, or about 70 mg / kg, or about 80 mg / kg, or about 90 mg / kg, or about 100 mg / kg, or about 110 mg / kg, or about 120 mg / kg, or about 130 mg / kg, or about 140 mg / kg, or about 150 mg / kg, or about 160 mg / kg, or about 170 mg / kg, or about 180 mg / kg, or about 190 mg / kg, or about 200 mg / kg. A pharmaceutically acceptable salt of FT011 may be administered in an amount effective to provide a dose of about 10 mg / kg, or about 20 mg / kg, or about 30 mg / kg, or about 40 mg / kg, or about 50 mg / kg, or about 60 mg / kg, or about 70 mg / kg, or about 80 mg / kg, or about 90 mg / kg, or about 100 mg / kg, or about 110 mg / kg, or about 120 mg / kg, or about 130 mg / kg, or about 140 mg / kg, or about 150 mg / kg, or about 160 mg / kg, or about 170 mg / kg, or about 180 mg / kg, or about 190 mg / kg, or about 200 mg / kg. FT011 may be administered in an amount effective to provide a concentration of from about 10 pM to about 200 pM, or from about 10 pM to about 100 pM, or from about 10 pM to about 50 pM of the FT011. For example, FT011 may be administered in an amount effective to provide a concentration of about 20 pM to about 40 pM, or about 25 pM to about 35 pM, or about 30 pM of the FT011. A pharmaceutically acceptable salt of FT011 may be administered in an amount effective to provide a concentration of from about 10 pM to about 200 pM, or from about 10 pM to about 100 pM, or from about 10 pM to about 50 pM of the pharmaceutically acceptable salt of FT011. For example, the pharmaceutically acceptable salt of FT011 may be administered in an amount effective to provide a concentration of about 20 pM to about 40 pM, or about 25 pM to about 35 pM, or about 30 pM of the FT011. FT011 may be administered in an amount effective to provide a maximum concentration (cmax, or cmax, steady state) of FT011 from about 3 pg / mL to about 20 pg / mL, or about 3 pg / mL to about 15 pg / mL or about 5 pg / mL to about 11 pg / mL, or about 4 pg / mL to about 6 pg / mL, or about 9 pg / mL to about 11 pg / mL. For example, FT011 may be administered in an amount effective to provide a cmax of FT011 of about 3 pg / mL, 4 pg / mL, or about 5 pg / mL, or about 6 pg / mL, or about 7 pg / mL, or about 8 pg / mL, or about 9 pg / mL, or about 10 pg / mL, or about 11 pg / mL, or about 12 pg / mL, or about 13 pg / mL, or about 14 pg / mL, or about 15 pg / mL, or about 16 pg / mL, or about 17 pg / mL, or about 18 pg / mL, or about 19 pg / mL, or about 20 pg / mL. A pharmaceutically acceptable salt of FT011 may be administered in an amount effective to provide a cmax or cmax, steady state of the pharmaceutically acceptable salt of FT011 from about 3 pg / mL to about 20 pg / mL, or about 3 pg / mL to about 15 pg / mL or about 5 pg / mL to about 11 pg / mL, or about 4 pg / mL to about 6 pg / mL, or about 9 pg / mL to about 11 pg / mL. For example, a pharmaceutically acceptable salt of FT011 may be administered in an amount effective to provide a cmax of the pharmaceutically acceptable salt of FT011 of about 3 pg / mL, 4 pg / mL, or about 5 pg / mL, or about 6 pg / mL, or about 7 pg / mL, or about 8 pg / mL, or about 9 pg / mL, or about 10 pg / mL, or about 11 pg / mL, or about 12 pg / mL, or about 13 pg / mL, or about 14 pg / mL, or about 15 pg / mL, or about 16 pg / mL, or about 17 pg / mL, or about 18 pg / mL, or about 19 pg / mL, or about 20 pg / mL. FT011 may be administered in an amount effective to provide an area under the concentration time curve (AUC) of FT011 from about 18 h* pg / mL to about 100 h* pg / mL, or about 18 h*pg / mL to about 87 h* pg / mL, or about 28 h* pg / mL to about 60 h* pg / mL, or about 28 h*pg / mL to about 30 h*pg / mL, or about 56 h*pg / mL to about 59 h*pg / mL. For example, FT011 may be administered in an amount effective to provide an AUC of FT011 of at least 18 h* pg / mL, or 19 h* pg / mL, or 20 h* pg / mL, or 21 h* pg / mL, or 22 h* pg / mL, or 23 h* pg / mL, or 24 h* pg / mL, or 25 h* pg / mL, or 26 h* pg / mL, or 27 h* pg / mL, or 28 h*pg / mL, or 29 h*pg / mL, or 30 h*pg / mL, or 31 h*pg / mL, or 32 h*pg / mL, or 33 h*pg / mL, or 34 h*pg / mL, or 35 h*pg / mL, or 36 h*pg / mL, or 37 h*pg / mL, or 38 h*pg / mL, or 39 h*pg / mL, or 40 h* pg / mL, or 41 h* pg / mL, or 42 h* pg / mL, or 43 h* pg / mL, or 44 h* pg / mL, or 45 h*pg / mL, or 46 h*pg / mL, or 47 h*pg / mL, or 48 h*pg / mL, or 49 h*pg / mL, or 50 h*pg / mL, or 51 h*pg / mL, or 52 h*pg / mL, or 53 h*pg / mL, or 54 h*pg / mL, or 55 h*pg / mL, or 56 h*pg / mL, or 57 h*pg / mL, or 58 h*pg / mL, or 59 h*pg / mL, or 60 h*pg / mL, or 61 h*pg / mL, or 62 h*pg / mL, or 63 h*pg / mL, or 64 h*pg / mL, or 65 h*pg / mL, or 66 h*pg / mL, or 67 h*pg / mL, or 68 h*pg / mL, or 69 h*pg / mL, or 70 h*pg / mL. A pharmaceutically acceptable salt of FT011 may be administered in an amount effective to provide an AUC of the pharmaceutically acceptable salt of FT011 from about 18 h*pg / mL to about 100 h*pg / mL, or about 18 h*pg / mL to about 87 h*pg / mL, or about 28 h*pg / mL to about 60 h*pg / mL, or about 28 h*pg / mL to about 30 h*pg / mL, or about 56 h*pg / mL to about 59 h*pg / m. For example, a pharmaceutically acceptable salt of FT011 may be administered in an amount effective to provide an AUC of the pharmaceutically acceptable salt of FT011 of at least 18 h*pg / mL, or 19 h*pg / mL, or 20 h*pg / mL, or 21 h*pg / mL, or 22 h*pg / mL, or 23 h*pg / mL, or 24 h*pg / mL, or 25 h*pg / mL, or 26 h*pg / mL, or 27 h*pg / mL, or 28 h*pg / mL, or 29 h*pg / mL, or 30 h*pg / mL, or 31 h*pg / mL, or 32 h*pg / mL, or 33 h*pg / mL, or 34 h*pg / mL, or 35 h*pg / mL, or 36 h*pg / mL, or 37 h*pg / mL, or 38 h*pg / mL, or 39 h*pg / mL, or 40 h*pg / mL, or 41 h*pg / mL, or 42 h*pg / mL, or 43 h*pg / mL, or 44 h*pg / mL, or 45 h*pg / mL, or 46 h*pg / mL, or 47 h*pg / mL, or 48 h*pg / mL, or 49 h*pg / mL, or 50 h*pg / mL, or 51 h*pg / mL, or 52 h*pg / mL, or 53 h*pg / mL, or 54 h*pg / mL, or 55 h*pg / mL, or 56 h*pg / mL, or 57 h*pg / mL, or 58 h*pg / mL, or 59 h*pg / mL, or 60 h*pg / mL, or 61 h*pg / mL, or 62 h*pg / mL, or 63 h*pg / mL, or 64 h*pg / mL, or 65 h*pg / mL, or 66 h*pg / mL, or 67 h*pg / mL, or 68 h*pg / mL, or 69 h*pg / mL, or 70 h*pg / mL. FT011 or pharmaceutically acceptable salt of thereof may be administered for a treatment period of from about 12 weeks to about 12 months. FT011 or pharmaceutically acceptable salt of thereof may be administered once daily. For example, FT011 or pharmaceutically acceptable salt of thereof may be administered once daily (e.g., once per day) for a treatment period of from about 12 weeks to about 12 months. FT011 or pharmaceutically acceptable salt of thereof may be administered once daily for a treatment period of at least 12 weeks. It will be understood, however, that the specific dose level and frequency of dosage for any particular subject may be varied and will depend upon a variety of factors including the activity of the specific compound employed, the metabolic stability and length of action of that compound, the age, body weight, general health, gender, diet, mode and time of administration, rate of excretion, drug combination, the severity of the particular condition, and the subject undergoing therapy. Methods of treatment The inventors have surprisingly shown that FT011 or a pharmaceutically acceptable salt thereof is capable of treating scleroderma. For example, this has been shown to be achieved in a subpopulation of subjects that have a specific set of genetic markers. Accordingly, the present disclosure provides a method of treating scleroderma in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of FT011 or a pharmaceutically acceptable salt thereof, to thereby treat scleroderma in the subject. The present disclosure also provides a method of treating scleroderma in a subject having an elevated level of expression of one or more genes selected from those listed in Table 1, the method comprising administering to the subject a therapeutically effective amount of FT011 or a pharmaceutically acceptable salt thereof, wherein the subject has an elevated level of expression of one or more genes selected from those listed in Table 1. The present disclosure also provides a method of treating scleroderma in a subject having an elevated level of expression of one or more genes selected from those listed in Table 1, the method comprising administering to the subject a therapeutically effective amount of FT011 or a pharmaceutically acceptable salt thereof, thereby lowering the level of expression of the one or more genes. The present disclosure also provides a method of treating scleroderma in a subject having an elevated level of expression of the one or more genes, comprising administering to the subject an amount of FT011 or the pharmaceutically acceptable salt thereof effective to lower the level of expression of one or more of the genes listed in Table 1 having the elevated level of expression. The present disclosure also provides a method of treating scleroderma in a subject, the method comprising administering to the subject a therapeutically effective amount of FT011 or a pharmaceutically acceptable salt thereof, wherein the subject has an elevated level of expression of one or more genes selected from those listed in Table 1. The present disclosure also provides a method of treating scleroderma in a subject, the method comprising administering to the subject a therapeutically effective amount of FT011 or a pharmaceutically acceptable salt thereof, thereby lowering the level of expression of one or more genes selected from those listed in Table 1. The present disclosure also provides a method of lowering a level of expression of one or more genes selected from those listed in Table 1 in a subject having scleroderma, the method comprising administering to the subject FT011 or a pharmaceutically acceptable salt thereof in an amount sufficient to lower the level of expression of the one or more genes. The present disclosure also provides a method of lowering a level of expression of one or more genes selected from those listed in Table 1 in a subject having scleroderma, the method comprising administering to the subject FT011 or a pharmaceutically acceptable salt for a treatment period sufficient to lower the level of expression of the one or more genes. The present disclosure also provides a method of lowering a level of expression of one or more genes selected from those listed in Table 1 in a subject having scleroderma, the method comprising administering to the subject FT011 or a pharmaceutically acceptable salt thereof in an amount and for a treatment period sufficient to lower the level of expression of the one or more genes. The method of lowering a level of expression of one or more genes in a subject having scleroderma may comprise administering to the subject the FT011 or the pharmaceutically acceptable salt thereof in an amount sufficient to treat scleroderma in the subject. The method of lowering a level of expression of one or more genes in a subject having scleroderma may comprise administering to the subject the FT011 or the pharmaceutically acceptable salt thereof for a treatment period sufficient to treat scleroderma in the subject. The method of lowering a level of expression of one or more genes in a subject having scleroderma may comprise administering to the subject the FT011 or the pharmaceutically acceptable salt thereof in an amount and for a treatment period sufficient to treat scleroderma in the subject. The method of lowering a level of expression of one or more genes in a subject having scleroderma may comprise administering to the subject the FT011 or the pharmaceutically acceptable salt thereof in an amount sufficient to delay the progression of, stabilise, ameliorate, eliminate and / or reduce one or more symptoms or pathological signs of scleroderma in the subject. The method of lowering a level of expression of one or more genes in a subject having scleroderma may comprise administering to the subject the FT011 or the pharmaceutically acceptable salt thereof for a treatment period sufficient to delay the progression of, stabilise, ameliorate, eliminate and / or reduce one or more symptoms or pathological signs of scleroderma in the subject. The method of lowering a level of expression of one or more genes in a subject having scleroderma may comprise administering to the subject the FT011 or the pharmaceutically acceptable salt thereof in an amount and for a treatment period sufficient to delay the progression of, stabilise, ameliorate, eliminate and / or reduce one or more symptoms or pathological signs of scleroderma in the subject. The present disclosure also provides a method of treating scleroderma, the method comprising administering FT011 or a pharmaceutically acceptable salt thereof to a subject diagnosed as suffering from scleroderma, wherein the therapeutically effective amount of FT011 or a pharmaceutically acceptable salt thereof has previously been shown to lower the level of expression of one or more genes selected from those listed in Table 1 when administered to a subject suffering from scleroderma. The present disclosure also provides a method of treating scleroderma in a subject, the method comprising administering to the subject a therapeutically effective amount of FT011 or a pharmaceutically acceptable salt thereof, wherein the subject has a decreased level of expression of MTF2. The present disclosure also provides a method of treating scleroderma in a subject, the method comprising administering to the subject a therapeutically effective amount of FT011 or a pharmaceutically acceptable salt thereof, thereby elevating the level of expression of MTF2. The present disclosure also provides a method of elevating the level of expression of MTF2 in a subject having scleroderma, the method comprising administering to the subject a therapeutically effective amount of FT011 or a pharmaceutically acceptable salt thereof. The present disclosure also provides a method of treating scleroderma, the method comprising administering a therapeutically effective amount of FT011 or a pharmaceutically acceptable salt thereof to a subject diagnosed as suffering from scleroderma, wherein the therapeutically effective amount of FT011 or a pharmaceutically acceptable salt thereof has previously been shown to elevate the level of expression of MTF2 when administered to a subject suffering from scleroderma. As used herein, “treating”, “treat” or “treatment” and variations thereof, refers to a therapeutic intervention that at least partly delays the progression of, stabilises, ameliorates, eliminates or reduces a symptom or pathological sign of scleroderma after it has begun to develop. Treatment need not be absolute to be beneficial to the subject. The beneficial effect can be determined using any methods or standards known to the ordinarily skilled artisan. A “prophylactic” treatment is a treatment administered to a subject who does not exhibit signs of scleroderma, or exhibits only early signs for the purpose of decreasing the risk of developing a symptom or pathological sign of scleroderma. Thus, the methods described herein include prophylactic methods of treatment. As used herein, the term “subject”, “patient” and “individual” refers to any animal, for example, a mammalian animal, including, but not limited to humans, non-human primates, livestock (e.g. sheep, horses, cattle, pigs, donkeys), companion animals (e.g. pets such as dogs and cats), laboratory test animals (e.g. mice, rabbits, rats, guinea pigs), performance animals (e.g. racehorses, camels, greyhounds) or captive wild animals. Typically, the terms “subject” and “patient” are used interchangeably, particularly in reference to a human subject. The subject may be a subject suffering from, suspected of suffering from, or predisposed to, scleroderma. The present disclosure also provides a kit comprising FT011 or pharmaceutically acceptable salt of thereof for treating scleroderma. The kit may contain instructions for use. Scleroderma As used herein, the term “scleroderma” refers to an autoimmune disease characterised by inflammation and fibrosis (thickening) in the skin and other areas of the body (e.g., blood vessels, internal organs and the digestive tract). Scleroderma may be categorised as “diffuse” or “limited”, which refers to the degree of skin involvement. Both types can involve any of the other vascular or organ problems. The scleroderma may be diffuse scleroderma. Diffuse scleroderma, also known as systemic scleroderma or systemic sclerosis, involves widespread fibrosis of the skin. Internal organs may also be affected. The scleroderma may be limited scleroderma. Limited scleroderma only involves fibrosis of the skin. There are two types of limited scleroderma: morphea or linear. Limited scleroderma may restrict normal joint movement, due to fibrosis of the skin over the joint. Administering to the subject a therapeutically effective amount of FT011 or a pharmaceutically acceptable salt thereof may be sufficient to treat one or more symptoms or pathological signs of scleroderma in the subject. Administering to the subject a therapeutically effective amount of FT011 or a pharmaceutically acceptable salt thereof may treat scleroderma in the subject. Administering to the subject of a therapeutically effective amount of FT011 or the pharmaceutically acceptable salt thereof may be sufficient to delay the progression of one or more symptoms or pathological signs of scleroderma in the subject. Administering to the subject of a therapeutically effective amount of FT011 or the pharmaceutically acceptable salt thereof may be sufficient to stabilise one or more symptoms or pathological signs of scleroderma in the subject. Administering to the subject of a therapeutically effective amount of FT011 or the pharmaceutically acceptable salt thereof may be sufficient to ameliorate one or more symptoms or pathological signs of scleroderma in the subject. Administering to the subject of a therapeutically effective amount of FT011 or the pharmaceutically acceptable salt thereof may be sufficient to eliminate one or more symptoms or pathological signs of scleroderma in the subject. Administering to the subject of a therapeutically effective amount of FT011 or the pharmaceutically acceptable salt thereof may be sufficient to reduce one or more symptoms or pathological signs of scleroderma in the subject. Administering to the subject a therapeutically effective amount of FT011 or a pharmaceutically acceptable salt thereof may treat, delay the progression of, stabilise, ameliorate, eliminate and / or reduce inflammation in the subject. Inflammation can be determined by any known method in the art or as described herein. Administering to the subject a therapeutically effective amount of FT011 or a pharmaceutically acceptable salt thereof may treat, delay the progression of, stabilise, ameliorate, eliminate and / or reduce fibrosis in the subject. Fibrosis can be determined by any known method in the art or as described herein. A therapeutically effective amount of FT011 or a pharmaceutically acceptable salt thereof may be effective to improve one or more of the following: i) American College of Rheumatology (ACR) Composite Response Index in Diffuse Cutaneous Systemic Sclerosis (CRISS) score; ii) one or more non-Raynauds symptoms; iii) modified Rodnan Skin Score (mRSS); iv) skin thickness; v) forced vital capacity (FVC); vi) Scleroderma Health Assessment Questionnaire - Disability Index (SHAQ-DI); and vii) one or more histological characteristics observed from a subject biopsy. A therapeutically effective amount of FT011 or a pharmaceutically acceptable salt thereof may be administered for a treatment period sufficient to improve one or more of the following: i) American College of Rheumatology (ACR) Composite Response Index in Diffuse Cutaneous Systemic Sclerosis (CRISS) score; ii) one or more non-Raynaud’s symptoms; iii) modified Rodnan Skin Score (mRSS); iv) skin thickness; v) forced vital capacity (FVC); vi) Scleroderma Health Assessment Questionnaire - Disability Index (SHAQ-DI); and vii) one or more histological characteristics observed from a subject biopsy. The subject may exhibit an improvement in an ACR CRISS score. An ACR CRISS score includes determination of mRSS, FVC, Physician Global Assessment, Patient Global Assessment and SHAQ-DI. Methods of determining an ACR CRISS score are described in Khanna D et al. Arthritis Rheumatol. 2016 Feb;68(2):299-311), the disclosure of which is incorporated herein by reference in its entirety. Specifically, an ACR CRISS score can be determined as described in the following table: Attributable to systemic sclerosis An improvement in ACR CRISS score may be an improvement of at least 0.1, or 0.2, or 0.3, or 0.4, or 0.5, or 0.6, or 0.7, or 0.8, or 0.9, or 1. For example, the subject may have a ACR CRISS score of at least 0.25, or 0.3, or 0.35, or 0.4, or 0.45, or 0.5, or 0.55, or 0.6, or 0.65, or 0.7, or 0.75, or 0.8, or 0.85, or 0.9, or 0.95, or 1 after administering to the subject a therapeutically effective amount of FT011 or a pharmaceutically acceptable salt thereof. The subject may exhibit an improvement in one or more non-Raynaud’s symptoms. For example, the one or more non-Raynaud’s symptoms may comprise digital ulceration, calcinosis secondary to the subcutaneous deposition of calcium hydroxyapatite, secondary infections, skin thickening, fingertip lesion, telangiectasia, and other symptoms as described herein. An improvement in the one or more non-Raynaud’s symptoms may comprise a reduction in pain, lethargy, fatigue, joint mobility, skin tightness, and other functional measures of disability as described herein. The subject may exhibit an improvement in skin thickness. For example, the subject may exhibit an improvement in a mRSS. The mRSS is a validated physical evaluation of patient's skin thickness rated by clinical palpation for surface anatomic areas of the body. Suitable methods of determining FVC are described, for example, in Khanna D, Clements PI, Volkmann ER, et al. Minimal clinically important differences for the modified Rodnan Skin Score: results from the Scleroderma Lung Studies (SLS-I and SLS-II). Arthritis Res Ther. 2019;21 (1):23, the disclosure of which is incorporated herein by reference in its entirety. An improvement in mRSS may be an improvement of at least 3, or 4, or 5, or 6, or 7, or 8, or 9, or 10, or 11, or 12, or 13, or 14, or 15, or 16, or 17, or 18, or 19, or 20, or 21, or 22, or 23, or 24, or 25, or 26, or 27, or 28, or 29, or 30, or 31, or 32, or 33, or 34, or 35, or 36, or 37, or 38, or 39, or 40. For example, the subject may have a mRSS of less than 2, or 3, or 4, or 5, or 6, or 7 , or 8, or 9, or 10, or 11, or 12, or 13, or 14, or 15, or 16, or 17, or 18, or 19, or 20, or 21, or 22, or 23, or 24, or 25, or 26, or 27, or 28, or 29, or 30, or 31, or 32, or 33, or 34, or 35, or 36, or 37, or 38, or 39, or 40 after administering to the subject a therapeutically effective amount of FT011 or a pharmaceutically acceptable salt thereof. The subject may exhibit an improvement in FVC. Suitable methods of determining FVC are described, for example, in Miller MR, Hankinson I, Brusasco V, Burgos F, Casaburi R, Coates A, Crapo R, Enright P, Grinten CPM van der, Gustafsson P, lensen R, lohnson DC, MacIntyre N, McKay R, Navajas D, Pedersen OF, Pellegrino R, Viegi G, Wanger I. Standardisation of spirometry. Eur Respir I 2005. 26(2):319-338, the disclosure of which is incorporated herein by reference in its entirety. An improvement in FVC may be an improvement of at least 1%, or 2%, or 3%, or 3.1%, or 3.2%, or 3.3%, or 3.4%, or 3.5%, or 3.6%, or 3.7%, or 3.8%, or 3.9%, or 4%, or 4.1%, or 4.2%, or 4.3%, or 4.4%, or 4.5%, or 4.6%, or 4.7%, or 4.8%, or 4.9%, or 5%, or 5.1%, or 5.2%, or 5.3%, or 5.4%, or 5.5%, or 5.6%, or 5.7%, or 5.8%, or 5.9%, or 6%. For example, the subject may have a FVC of at least 2%, or 3%, or 4%, or 5%, or 6%, or 7%, or 8%, or 9%, or 10%, or 11%, or 12%, or 13%, or 14%, or 15%, or 16%, or 17%, or 18%, or 19%, or 20% after administering to the subject a therapeutically effective amount of FT011 or a pharmaceutically acceptable salt thereof. The subject may exhibit an improvement in SHAQ-DI. SHAQ-DI indicates a patient's self-assessed level of disability. Suitable methods of determining SHAQ-DI are described, for example, in Steen VD, Medsger TA Jr. The value of the Health Assessment Questionnaire and special patient-generated scales to demonstrate change in systemic sclerosis patients over time. Arthritis Rheum, the disclosure of which is incorporated herein by reference in its entirety. An improvement in SHAQ-DI may be an improvement of at least 0.05, or 0.06, or 0.07, or 0.08, or 0.09, or 0.1, or 0.11, or 0.12, or 0.13, or 0.14, or 0.15, or 0.16, or 0.17, or 0.18, or 0.19, or 0.2. For example, the subject may have a SHAQ-DI of less than 0.1, or 0.11, or 0.12, or 0.13, or 0.14, or 0.15, or 0.16, or 0.17, or 0.18, or 0.19, or 00.2, or 2.1, or 0.22, or 0.23, or 0.24, or 0.25, or 0.26, or 0.27, or 0.28, or 0.29, or 0.3 after administering to the subject a therapeutically effective amount of FT011 or a pharmaceutically acceptable salt thereof. The subject may exhibit an improvement in one or more histological characteristics observed from a subject biopsy or sample. For example, as the one or more histological characteristics observed from a subject biopsy or sample may be presence of myofibroblasts, mononuclear cell infiltration, epidermal thickness and fibroplasia. Suitable methods of determining histological characteristics are described, for example, in Van Praet JT, Smith V, Haspeslagh M, Degryse N, Elewaut D, De Keyser F. Histopathological cutaneous alterations in systemic sclerosis: a clinicopathological study. Arthritis Res Ther. 2011;13(1):R35, the disclosure of which is incorporated herein by reference in its entirety. The subject may exhibit an improvement in Scleroderma Clinical Trial Consortium Damage Index (SCTC-DI). SCTC-DI represents a composite damage index to quantify organ damage in systemic sclerosis. Suitable methods of determining SCTC-DI are described, for example, in Ferdowsi N, Huq M, Stevens W, et al. Development and validation of the Scleroderma Clinical Trials Consortium Damage Index (SCTC-DI): a novel instrument to quantify organ damage in systemic sclerosis [published correction appears in Ann Rheum Dis. 2019 Aug;78(8):e88] Ann Rheum Dis. 2019;78(6):807-816, the disclosure of which is incorporated herein by reference in its entirety. An improvement in SCTC-DI may be an improvement of at least 0.7, or 0.8, or 0.9, or 1, or 1.1, or 1.2, or 1.3, or 1.4, or 1.5, or 1.6, or 1.7, or 1.8, or 1.9, or 2, or 2.1, or 2.2, or 2.3, or 2.4, or 2.5, or 2.6, or 2.7, or 2.8, or 2.9, or 3. For example, the subject may have a SCTC-DI of less than 2.5, or 2.4, or 2.3, or 2.2, or 2.1, or 2, or 1.9, or 1.8, or 1.7, or 1.6, or 1.5, or 1.4, or 1.3, or 1.2, or 1.1, or 1, or 0.9, or 0.8, or 0.7, or 0.6, or 0.5, or 0.4, or 0.3, or 0.2, or 0.1 after administering to the subject a therapeutically effective amount of FT011 or a pharmaceutically acceptable salt thereof. In view of the above, the present disclosure also provides a method of improving an American College of Rheumatology (ACR) Composite Response Index in Diffuse Cutaneous Systemic Sclerosis (CRISS) score in a subject having scleroderma, the method comprising administering to the subject FT011 or a pharmaceutically acceptable salt thereof in an amount sufficient to provide in an improvement in said score in the subject. The present disclosure also provides a method of improving an American College of Rheumatology (ACR) Composite Response Index in Diffuse Cutaneous Systemic Sclerosis (CRISS) score in a subject having scleroderma, the method comprising administering to the subject FT011 or a pharmaceutically acceptable salt for a treatment period sufficient to provide in an improvement in said score in the subject. The subject may have one or more of the following: i) a classification of systemic sclerosis as defined by the American College of Rheumatology (ACR) and / or the European League Against Rheumatism (EULAR); ii) a diagnosis of diffuse cutaneous systemic sclerosis defined as systemic sclerosis with skin thickening on the upper arms proximal to the elbows, on the upper legs proximal to the knees, or on the trunk; iii) modified Rodnan Skin Score (mRSS) at Screening of >15 to <40; and iv) a FVC >50% at screening. The subject may have a classification of systemic sclerosis as defined by the ACR. For example, the subject may have a classification of systemic sclerosis as defined by the ACR with disease duration of equal to or more than 6 years from first non-Raynaud phenomenon manifestation. Alternatively, or in addition, the subject may have a classification of systemic sclerosis as defined by the EULAR. For example, the subject may have a classification of systemic sclerosis as defined by the EULAR with disease duration of equal to or more than 6 years from first non-Raynaud phenomenon manifestation. The subject may have a diagnosis of diffuse cutaneous systemic sclerosis defined as systemic sclerosis with skin thickening on the upper arms proximal to the elbows, on the upper legs proximal to the knees, or on the trunk. The subject may have skin thickening in a body area suitable for repeat biopsy. The subject may have a modified Rodnan Skin Score (mRSS) at Screening of >15 to <40 The subject may have a FVC >50% at screening. The subject may be on a stable dose of azathioprine, mycophenolate mofetil, or hydroxychloroquine for at least 2 months prior to treatment. The subject may not be receiving treatment with an immunosuppressant, an antiinflammatory agent, an anti-fibrotic agent, a biologic drug, a monoclonal antibody and / or a corticosteroid. Alternatively, or in addition the subject: i) may have received prior treatment with an immunosuppressant, an antiinflammatory agent, an anti-fibrotic agent, a biologic drug, a monoclonal antibody and / or a corticosteroid; ii) may receive simultaneous treatment with an immunosuppressant, an antiinflammatory agent, an anti-fibrotic agent, a biologic drug, a monoclonal antibody and / or a corticosteroid; and / or iii) may subsequently receive treatment with an immunosuppressant, an antiinflammatory agent, an anti-fibrotic agent, a biologic drug, a monoclonal antibody and / or a corticosteroid. The subject may have received treatment with an immunosuppressant. The subject may be receiving treatment with an immunosuppressant. The subject may receive treatment with an immunosuppressant. An immunosuppressant may, for example, be selected from the group consisting of: methotrexate, cyclophosphamide, cyclosporine, tacrolimus, azathioprine, mycophenolate mofetil, sirolimus and everolimus. The subject may have received treatment with an anti-inflammatory agent. The subject may be receiving treatment with an anti-inflammatory agent. The subject may receive treatment with an anti-inflammatory agent. An anti-inflammatory agent may, for example, be selected from the group consisting of: non- steroi dal anti -infl ammatori es. The subject may have received treatment with an anti-fibrotic agent. The subject may be receiving treatment with an anti-fibrotic agent. The subject may receive treatment with an anti-fibrotic agent. An anti-fibrotic agent may be selected, for example, from the group consisting of: nintedanib and pirfenidone. The subject may have received treatment with a biologic drug. The subject may be receiving treatment with a biologic drug. The subject may receive treatment with a biologic drug. A biologic drug may, for example, be selected from the group consisting of: an anti-IL-1, an anti-TNF, an anti-IL-6 and a complement. The subject may have received treatment with a monoclonal antibody. The subject may be receiving treatment with a monoclonal antibody. The subject may receive treatment with a monoclonal antibody. A monoclonal antibody may, for example, be selected from the group consisting of: rituximab, alemtuzumab, and tocilizumab. The subject may have received treatment with a corticosteroid. The subject may be receiving treatment with a corticosteroid. The subject may receive treatment with a corticosteroid. A corticosteroid may, for example, be selected from the group consisting of: IV steroid, prednisone (also known as prednisolone), methylprednisolone and dexamethasone. Methods of selection and monitoring The present disclosure also provides a method of selecting a subject having scleroderma as being suitable for treatment with FT011 or a pharmaceutically acceptable salt thereof, the method comprising determining the level of expression of one or more genes in Table 1 in the subject. The present disclosure also provides a method of treating scleroderma, the method comprising: i. selecting a subject having scleroderma and an elevated level of expression of one or more genes selected from those listed in Table 1, the selecting comprising determining the level of expression of the one or more genes; and ii. administering to the subject a therapeutically effective amount of FT011 or a pharmaceutically acceptable salt thereof. A subject having scleroderma may be determined to be suitable for treatment with FT011 or a pharmaceutically acceptable salt thereof if the subject has an elevated level of expression of one or more genes selected from those listed in Table 1. A subject having scleroderma may be determined as unsuitable for treatment with FT011 or a pharmaceutically acceptable salt thereof if the subject does not have an elevated level of expression of one or more genes selected from those listed in Table 1. A subject having scleroderma may be selected for treatment with FT011 or a pharmaceutically acceptable salt thereof if the subject has an elevated level of expression of one or more genes selected from those listed in Table 1. The method of selecting a subject having scleroderma may further comprise a step of administering to the subject an amount of FT011 or a pharmaceutically acceptable salt thereof effective to treat scleroderma. The present disclosure also provides a method of monitoring a subject’s response to treatment of scleroderma with FT011 or a pharmaceutically acceptable salt thereof, the method comprising monitoring the level of expression of one or more genes selected from those listed in Table 1 after the subject has been administered a therapeutically effective amount of FT011 or a pharmaceutically acceptable salt thereof. The method of monitoring a subject’s response to treatment of scleroderma may further comprise continuing treatment of scleroderma by administering the FT011 or the pharmaceutically acceptable salt thereof if the level of expression of one or more of the one or more genes is elevated. As described herein, a subject’s response to treatment of scleroderma with FT011 or a pharmaceutically acceptable salt thereof may be determined by an improvement in one or more of the following: i) American College of Rheumatology (ACR) Composite Response Index in Diffuse Cutaneous Systemic Sclerosis (CRISS) score; ii) one or more non-Raynauds symptoms; iii) modified Rodnan Skin Score (mRSS); iv) skin thickness; v) forced vital capacity (FVC); vi) Scleroderma Health Assessment Questionnaire - Disability Index (SHAQ-DI); and vii) one or more histological characteristics observed from a subject biopsy. It will be appreciated by persons skilled in the art that numerous variations and / or modifications may be made to the above-described embodiments, without departing from the broad general scope of the present disclosure. The present embodiments are, therefore, to be considered in all respects as illustrative and not restrictive. Any discussion of documents, acts, materials, devices, articles or the like which has been included in the present specification is not to be taken as an admission that any or all of these matters form part of the prior art base or were common general knowledge in the field relevant to the present disclosure as it existed before the priority date of each of the appended claims. In order that preferred embodiments of the present disclosure may be fully understood and put into practical effect, reference is made to the following non-limiting examples. Examples Example 1: Phase II clinical trial in scleroderma A phase II, multi-centre, randomised, double blind, placebo-controlled study of the pharmacokinetics, pharmacodynamic effects, and safety of oral FT011 in patients with diffuse systemic sclerosis was conducted (Effects of FT011 in Systemic Sclerosis; ClinicalTrials.gov Identifier: NCT04647890). The study randomised 30 participants (n = 10 / group) to: placebo, FT011 200 mg, or FT011 400 mg treatment groups. FT011 was provided for administration once daily for 12 weeks in each of the 200 mg and 400 mg treatment groups. A statistical study was also undertaken to identify differentially expressed genes (DEGs) associated with FT011 drug response as determined by RNA sequencing of skin biopsies. Methods The American College of Rheumatology Combined Response Index in Diffuse Cutaneous Systemic Sclerosis (ACR-CRISS) score was determined after 12 weeks of treatment using composite measurements collected before FT011 treatment (i.e., baseline) and at 12 weeks post FT011 treatment (Khanna D et al. Arthritis Rheumatol. 2016 Feb;68(2):299-311). 3mm Skin biopsies were collected from an area of sclerosed skin before FT011 treatment (i.e., baseline) and at 12 weeks post FT011 treatment. A total of 52 skin biopsies were analysed using RNA sequencing: 9 paired samples from the Placebo and the FT011 200 mg cohort, as well as 8 paired biopsies from the FT011 400 mg cohort. RNA from biopsy samples was isolated using the RNeasy Mini kit (Qiagen). Stranded mRNA libraries were prepared using the SMART-Seq v4 PLUS Kit (Takara) and sequenced on the Illumina NovaSeq platform (NovaSeq S4 300 cycle, 150bp paired-end, 30 million reads per sample). STAR was used for alignment to the Genome Reference Consortium Human Build 37 (GRCh37), using GENCODE as database and HTSeq analysis tool to quantify the gene expression. DESeq2, which provides a method to test for differential expression by use of negative binomial generalised linear models, was used to identify significantly differentially expressed genes between baseline and 12 weeks for each cohort controlling for individual effects. Results Treatment with FT011 400 mg resulted in significant and clinically meaningful improvements in the ACR-CRISS score and its composites. By week 12, 60% of patients in the FT011 400 mg arm were classified as clinical responders with improvement in ACR-CRISS (defined by predicted probability >0.60; Khanna D et al. Arthritis Rheumatol. 2016 Feb;68(2):299-311) vs 10.0% in the placebo arm (nominal p-value = 0.046). Median ACR-CRISS score was 0.660 vs 0.015, FT011 400 mg vs placebo, respectively. The mean ACR-CRISS score was 0.542 in the FT011 400 mg arm vs 0.131 in the placebo arm (nominal p-value = 0.019). FT011 also led to significant and clinically meaningful improvements across multiple efficacy measures including % predicted Forced Vital Capacity (FVC), Scleroderma Health Assessment Questionnaire-Disability Index (SHAQ-DI) and physician global assessments. 50% of patients in the FT011 400 mg arm exceeded the % predicted FVC minimally important clinically difference (MICD) (defined as a change of >3.3 - 5.3%; Kafaja S, et al. Am J Respir Crit Care Med. 2018 Mar l;197(5):644-652) vs no patients in the placebo arm meeting these criteria. Furthermore, 60% of patients in the FT011 400 mg arm met the MICD for SHAQ-DI (defined as a change of-0.13; Daste C, et al. Semin Arthritis Rheum. 2019 Feb;48(4):694-700) vs 22% in the placebo arm. Compared to placebo, FT011 demonstrated numerically larger improvements from baseline to week 12 for mRSS and patient global assessment. FT011 was safe and well tolerated, with no differences in drug-related treatment-emergent adverse events between placebo and active treatment groups. There were no serious adverse events reported, nor any adverse events resulting in study drug interruption, withdrawal, or discontinuation. RNA sequencing of skin biopsies led to the identification of 25,169 gene transcripts with detectable expression in both placebo and FT011 400mg groups. Based on an unadjusted p-value of 0.05, 981 DEGs were identified that showed significant changes in expression from baseline to Week 12 of treatment with 400 mg FT011. Table 2 summarises the DEGs’ fluctuation in the placebo and the FT011 400mg group. Table 2. Overview of DEGs in treatment groups Placebo FT011 400mg # of genes t t 12 t 4 47 (25 with absolute Log2FC>0.3) 4 t 10 (1 with absolute Log2FC> 0.3) 4 4 16 - t 426 - 4 470 t - 968 4 - 474 - - 22,746 T = significantly upregulated; = significantly downregulated; - = no significant change between baseline and 12 weeks of treatment based on an un-adjusted p-value of 0.05 As summarised in Table 2, 47 DEGs were significantly upregulated in the placebo group and significantly downregulated in the FT011 400 mg group. 10 DEGs were significantly downregulated in the placebo group and significantly upregulated in the FT011 400mg group. From the 25,169 gene transcripts, the present inventors were able to identify a unique subset of DEGs, using the combination of an un-adjusted p-value of <0.05 and a log2 fold change of >0.3 or <-0.3, that were particularly indicative of a positive patient response to FT011 (Table 3). Of this unique subset, 25 DEGs were found to be significantly upregulated in the placebo group and significantly downregulated in the FT011 400mg group and 1 DEG (MTF2) was found to be significantly downregulated in the placebo group and significantly upregulated in the FT011 400mg group. Of this subset of genes indicative of a positive FT011 response in patients, 17 genes were found to have a function that is related to fibrosis or inflammation or to have been reported to potentially play a role in systemic sclerosis (Table 3; indicated in bold in ‘Main function’ column). Other usefully indicative DEGs were identified in this subset despite having functions not previously identified as being specifically related to fibrosis or inflammation. Table 3. Significant DEGs in both the Placebo and FT011 groups, with opposite treatment effect Genes Placebo 200 mg 400 mg Main function log2FC P value log2 FC P value log2 FC P value GFRA2 0,658 0.001 0,079 0.519 -0.631 0.001 neuron survival and differentiation PDE1B 0,467 0.021 -0.370 0.173 -0.540 0.002 inflammation (macrophage diff) DYSF 0,371 0.033 -0.077 0.766 -0.518 0.001 muscles repair COL6A3 0,527 0.004 -0.013 0.995 -0.490 0.004 Extracellular matrix organisation DOK1 0,365 0.025 -0.250 0.459 -0.478 0.006 Cell proliferation COL15A1 0,408 0.038 -0.164 0.706 -0.475 0.001 Extracellular matrix organisation SEC24D 0,445 0.000 0,085 0.602 -0.461 0.005 Protein transport for ECM COL4A1 0,363 0.018 -0.366 0.268 -0.444 0.003 Extracellular matrix organisation ABCA8 0,642 0.001 -0.149 0.650 -0.435 0.005 Lipid metabolism / homeostasis TRIL 0,598 0.012 -0.231 0.469 -0.434 0.008 Inflammation COL5A2 0,393 0.022 -0.008 0.953 -0.407 0.012 Extracellular matrix organisation SLC5A8 0,320 0.005 0,084 0.666 -0.405 0.012 Transporter RHOJ 0,511 0.011 -0.012 0.913 -0.395 0.018 Angiogenesis / fibronectin dep. ANGPTL2 0,454 0.008 -0.147 0.539 -0.392 0.010 Angiogenesis, tissue repair ITIH5 0,321 0.022 -0.451 0.233 -0.376 0.008 Extracellular matrix protein LOXL2 0,451 0.035 -0.258 0.460 -0.373 0.030 Extracellular matrix reorganisation USP35 0,593 0.001 -0.045 0.924 -0.372 0.018 Cell death COL5A1 0,422 0.014 0,135 0.549 -0.371 0.023 Extracellular matrix organisation HEPH 0,389 0.047 0,100 0.720 -0.361 0.029 Iron transport COL6A1 0,428 0.021 0,074 0.644 -0.361 0.026 Extracellular matrix organisation ZNF347 0,408 0.019 -0.279 0.160 -0.355 0.039 tumour suppressor gene C1R 0,386 0.024 0,158 0.402 -0.354 0.046 Inflammation / Complement activation PREX2 0,357 0.043 -0.412 0.081 -0.353 0.010 PI3K signalling (angiogenesis, proliferation, metabolism) AL 13 8976.2 0,465 0.034 -0.074 0.937 -0.343 0.018 - STS 0,400 0.026 -0.102 0.678 -0.309 0.048 Hormone metabolism MTF2 -0.411 0.002 -0.058 0.737 0,311 0.018 Epithelial to mesenchymal transition *Upregulated values are underlined; downregulated values are italicised; genes whose functions have been reported to be related to fibrosis or inflammation, or potentially play a role in systemic sclerosis, are indicated by bold text in ‘Main function’ column. As summarised in Table 2, 12 DEGs were significantly upregulated in both the placebo and FT011 400 mg group, and 16 DEGs were significantly downregulated in both the placebo and FT011 400 mg group. Table 4 demonstrates the functional role of these genes, including those with a reported role in systemic sclerosis, fibrosis or inflammation (Table 4; indicated in bold in ‘Main function’ column). Surprisingly, this analysis indicated that FT011 does not modulate all molecular pathways related to fibrosis disease pathogenesis. Table 4. Significant DEGs in both the Placebo and FT011 400 mg group, with same treatment effect Genes Placebo 200 mg 400 mg Main function log2FC P value log2 FC P value log2 FC P value ZNF69 0.628 0.001 0.110 0.076 0.395 0.011 Gene expression regulation ZNF311 0.382 0.039 0.024 0.960 0.321 0.013 Gene expression regulation GLYATL2 0.477 0.012 0.063 0.957 0.332 0.017 Fatty acid synthesis DLG1-AS1 0.320 0.006 -0.190 0.130 0.111 0.026 Cell proliferation CCL20 0.462 0.027 0.222 0.359 0.123 0.032 Inflammation and fibrosis RPGRIP1L 0.431 0.044 0.337 0.118 0.358 0.034 Cilium function ADAM32 0.347 0.037 -0.245 0.406 0.192 0.038 Unknown METTL21A 0.390 0.008 0.072 0.696 0.328 0.038 Unknown ZNF667-AS1 0.419 0.021 0.170 0.414 0.320 0.043 Unknown GALNTL6 0.295 0.048 0.139 0.105 0.078 0.044 Immunoregulatory PARM1 0.398 0.040 0.225 0.242 0.290 0.046 Cardiomyogenic differentiation HTR7 0.201 0.045 0.181 0.596 0.027 0.046 Neurosignalling, inflammation and fibrosis IGHG2 -0.146 0.012 0.329 0.202 -0.819 0.000 Immunity RASAL1 -0.320 0.020 0.000 0.848 -0.348 0.010 Tumor suppressor gene PLIN3 -0.350 0.000 -0.005 0.981 -0.286 0.015 Lipophagy RNH1 -0.244 0.003 0.070 0.623 -0.224 0.019 Inflammasome GRN -0.157 0.022 -0.026 0.864 -0.327 0.019 Inflammation / tissue injury GGT6 -0.265 0.025 -0.010 0.791 -0.258 0.023 Glutathione synthesis GABRQ -0.319 0.002 -0.060 0.698 -0.222 0.023 Neuro signalling ENDOU -0.449 0.000 -0.029 0.963 -0.324 0.024 Gene expression regulation LTB4R -0.284 0.012 -0.024 0.923 -0.337 0.029 Inflammation ALS2CL -0.475 0.004 0.170 0.457 -0.334 0.030 Unknown TRIM29 -0.250 0.049 0.087 0.646 -0.253 0.030 Inflammation BHLHE40 -0.303 0.045 0.272 0.176 -0.223 0.032 Inflammation EZR -0.261 0.037 0.214 0.308 -0.271 0.034 Cytoskeleton remodelling MAP7D2 -0.349 0.029 0.132 0.792 -0.209 0.034 Microtubule function DHRS1 -0.250 0.005 0.041 0.834 -0.188 0.041 Metabolism ZFP30 -0.476 0.033 -0.020 0.728 -0.280 0.046 Unknown Moreover, FT011 treatment did not significantly alter the expression of some key inflammatory genes reported to be modulated by mycophenolate moefetil, an immunomodulatory agent and standard of care treatment for scleroderma (Table 5; Hinchcliff et al. J Invest Dermatol. 2018; 138(6): 1301-1310). Table 5. Significant DEGs in both the Placebo and FT011 400 mg group, with no treatment effect Genes Placebo 200 mg 400 mg log2FC P value log2 FC P value log2 FC P value CCL2 0.041 0.624 0.303 0.174 -0.154 0.393 NFKB2 -0.052 0.949 0.240 0.301 -0.078 0.641 TLR3 0.045 0.766 0.043 0.756 0.062 0.899 TAPI -0.205 0.064 0.247 0.346 -0.149 0.236 IRF7 0.258 0.122 0.375 0.130 0.072 0.607 STAT1 0.221 0.108 0.132 0.654 -0.085 0.666 Conclusion Overall, the present inventors surprisingly found that FT011 modulates a unique subset of fibrotic and inflammatory pathways, and that modulation of these pathways by administration of FT011 was associated with a surprising clinical benefit in patients. The inventors have also provided a particular set of genetic markers correlating with a positive clinical response to treatment with FT011. Example 2: Solid forms, pharmaceutically acceptable salts and crystalline forms ofFTOll Particular solid forms, pharmaceutically acceptable salts and crystalline forms ofFTOll were produced as follows. Regents and materials All inorganic reagents, organic solvents and water are at least of the standard of analytical laboratory reagent grade. Preparation of salts of (E)-2-rr3-(3-methoxy-4-propargyloxy)phenyl)-l-oxo-2-propenyHaminolbenzoic acid Approximately 100 mg of (E)-2-[[3-(3-methoxy-4-propargyloxy)phenyl)-l-oxo-2-propenyl]amino]benzoic acid (‘FT011 free form’; also referred to as ‘API’ below) was accurately weighed into each glass vial, and then the appropriate amount of solvent, selected from ethyl acetate (EA) and 90% isopropanol (90% IP A), was added to the glass vial, and the mixture was heated to 50°C. A counter-ion source, selected from potassium hydroxide, meglumine, ethanolamine (MEA), tris(hydroxymethyl)aminomethane (Tris base), tertbutylamine (TBA), ammonia, lysine, L-arginine, and choline, was added into each vial, respectively, at a suitable molar ratio (e.g., 5% molar excess). In the case of meglumine, and Tris base, they were accurately weighed and mixed with FT011 free form, and then the solvent was added to that mixture. The respective mixtures were stirred at 50°C for 1 h, then allowed to cool to room temperature (20-25 °C) and kept being stirred for 24-48 h, after which time the solid precipitate was isolated by centrifugation. If there was no precipitation in the system, the clear solution was evaporated at room temperature by compressed air or nitrogen blowing. The obtained samples were dried under vacuum at 40°C overnight. Dried samples were analysed by tH NMR, TGA, DSC and PLM. Detailed procedures of the formation of the salts and their physical properties are summarized in Table 6. Table 6. Experimental details of salt formation. Counter-ion Molar ratio (API: base) Solvent (mL) Experimental observations and processes Form Base Amount / concentration Sodium hydroxide 59.9 pL (5M in water) 1:1.05 EA (2 mL) 1. The suspension became clear immediately after adding counter ion. 2. Stirred overnight to obtain suspension and centrifuged to separate the wet solids and dry under reduced pressure at 40 °C overnight. Low Crystallinity Solid Potassium hydroxide 59.8 pL (5M in water) 1:1.05 EA (1.5 mL) 1. The suspension became clear immediately after adding counter ion, but then solids precipitated. 2. Stirred overnight to obtain suspension and centrifuged to separate the wet solids and dry under reduced pressure at 40 °C overnight. Crystalline Solid Meglumine 59.0 mg (99%) 1:1.05 EA (1 mL) 1. The sample was presented as suspension. 2. Stirred overnight to obtain suspension and centrifuged to separate the wet solid and dry under reduced pressure at 40 °C overnight. Ciystalline Solid Ethanolamine 18.1 pL (99%) 1:1.05 EA (1.8 mL) 1. The sample was presented as suspension. 2. Stirred overnight to obtain suspension and centrifuged to separate the wet solids and dry under reduced pressure at 40 °C overnight. Crystalline Solid Tris base 36.5 mg (99.5%) 1:1.05 EA (1.5 mL) 1. The sample was presented as suspension. 2. Stirred overnight to obtain suspension and centrifuged to separate the wet solids and dry under reduced pressure at 40 °C overnight. Crystalline Solid tert-Butylamine (TBA) 32.0 pL (99%) 1:1.05 EA (1 mL) 1. The sample was presented as suspension. Crystalline Solid Counter-ion Molar ratio (API: base) Solvent (mL) Experimental observations and processes Form Base Amount / concentration 2. Stirred overnight to obtain suspension and centrifuged to separate the wet solids and dry under reduced pressure at 40 °C overnight. Ammonia 22.4 pL (25% in water) 1:1.05 90%IPA in water (1.5 mL) 1. The suspension became clear immediately after adding counter ions. Solids precipitated about 5 minutes later. 2. Stirred overnight to obtain suspension and centrifuged to separate the wet solid and dry under reduced pressure at 40 °C overnight. Crystalline Solid Lysine 149.5 pL (2M in water) 1:1.05 EA (1 mL) 1. The suspension became oily after adding counter ions, but then a small amount of solids precipitated about 5 minutes later. 2. Stirred overnight, still as oil, but solids existed, evaporated using compressed air. Crystalline Solid L-Arginine 299.2 pL (IM in water) 1:1.05 EA (1 mL) 1. The suspension became oily after adding counter ions. 2. Stirred overnight, still as oil, evaporated using compressed air. 3. Dried under reduced pressure at 40 °C overnight, but still oil. Oil Choline 76.5 pL (45% in water) 1:1.05 EA (1 mL) 1. The suspension became oily after adding counter ions. 2. Stirred overnight, still as oil, evaporated using compressed air. 3. Dried under reduced pressure at 40 °C overnight, but still oil. Oil Based on the experimental results, potassium hydroxide, meglumine, ethanolamine (MEA), tris(hydroxymethyl)aminomethane (Tris base), tert-butylamine (TBA), ammonia, and lysine formed crystalline solid salt forms with (E)-2-[[3-(3-methoxy-4-propargyloxy)phenyl)-l-oxo-2-propenyl]amino]benzoic acid. Sodium hydroxide formed a solid salt form of low crystallinity, while L-Arginine and choline did not form solid salt forms and formed an oil instead.

Claims

1. A method of treating scleroderma in a subject, the method comprising administering to the subject a therapeutically effective amount of FT011 or a pharmaceutically acceptable salt thereof, wherein the subject has an elevated level of expression of one or more genes selected from those listed in Table 1.

2. The method of claim 1, wherein the administering to the subject of the therapeutically effective amount of FT011 or the pharmaceutically acceptable salt is sufficient to lower the level of expression, in the subject, of the one or more genes.

3. The method of claim 1 or claim 2, wherein the administering to the subject of the therapeutically effective amount of FT011 or the pharmaceutically acceptable salt thereof is sufficient to lower the level of expression of the one or more genes by at least a factor of 3.

4. The method of claim 1, wherein the method comprises administering the therapeuticallyeffective amount of FT011 or the pharmaceutically acceptable salt or to the subject for a treatment period sufficient to lower the level of expression of the one or more of the genes having the elevated level of expression.

5. The method of claim 1 or claim 4, wherein the method comprises administering the therapeutically effective amount of FT011 or the pharmaceutically acceptable salt thereof to the subject for a treatment period sufficient to lower the level of expression of the one or more genes having the elevated level of expression by at least a factor of 3.

6. A method of treating scleroderma in a subject having an elevated level of expression of one or more genes selected from those listed in Table 1, the method comprising administering to the subject a therapeutically effective amount of FT011 or a pharmaceutically acceptable salt thereof, thereby lowering the level of expression of the one or more genes.

7. A method of treating scleroderma in a subject having an elevated level of expression of one or more genes selected from those listed in Table 1, the method comprising administering to the subject an amount of FT011 or a pharmaceutically acceptable salt thereof effective to lower the level of expression of one or more of the genes listed in Table 1 having the elevated level of expression.

8. The method of any one of claims 1 to 7, wherein the administering to the subject of the therapeutically effective amount of FT011 or the pharmaceutically acceptable salt thereof is sufficient to treat scleroderma in the subject.

9. The method of any one of claims 1 to 8, wherein the level of expression of the one or more genes is determined by performing or having performed an analysis of the expression level of the one or more genes.

10. The method of any one of claims 1 to 9, wherein the level of expression of the one or more genes is determined over a treatment period.

11. A method of treating scleroderma in a subject in need thereof, the method comprising administering to the subject FT011 or a pharmaceutically acceptable salt thereof sufficient to treat scleroderma in the subject.

12. The method of any one of claims 1 to 11, wherein the administering to the subject of the FT011 or the pharmaceutically acceptable salt thereof is sufficient to delay the progression of, stabilise, ameliorate, eliminate and / or reduce one or more symptoms or pathological signs of scleroderma in the subject.

13. The method of any one of claims 1 to 12, wherein the scleroderma is diffuse or limited scleroderma.

14. The method of any one of claims 1 to 13, wherein the administering to the subject of the FT011 or the pharmaceutically acceptable salt thereof reduces inflammation and / or fibrosis in the subject.

15. The method of any one of claims 1 to 14, wherein the FT011 or the pharmaceutically acceptable salt or crystalline form thereof is effective to improve one or more of the following:i) American College of Rheumatology (ACR) Composite Response Index in Diffuse Cutaneous Systemic Sclerosis (CRISS) score;ii) one or more non-Raynauds symptoms;iii) modified Rodnan Skin Score (mRSS);iv) skin thickness;v) forced vital capacity (FVC);vi) Scleroderma Health Assessment Questionnaire - Disability Index (SHAQ-DI); and vii) one or more histological characteristics observed from a subject biopsy.

16. The method of any one of claims 1 to 15, wherein the method comprises administering the FT011 or pharmaceutically acceptable salt thereof for a treatment period sufficient to improve one or more of the following:i) American College of Rheumatology (ACR) Composite Response Index in Diffuse Cutaneous Systemic Sclerosis (CRISS) score;ii) one or more non-Raynauds symptoms;iii) modified Rodnan Skin Score (mRSS);iv) skin thickness;v) forced vital capacity (FVC);vi) Scleroderma Health Assessment Questionnaire - Disability Index (SHAQ-DI); and vii) one or more histological characteristics observed from a subject biopsy.

17. The method of any one of claims 1 to 16, wherein the subj ect is not receiving treatmentwith an immunosuppressant, an anti-inflammatory agent, an anti-fibrotic agent, a biologic drug, a monoclonal antibody and / or a corticosteroid.

18. The method of any one of claims 1 to 17, wherein the method comprises administering once daily 200mg or 400mg of the FT1011 or an amount of the pharmaceutically acceptable salt of FT011 corresponding to 200mg or 400mg.

19. The method of any one of claims 1 to 18, wherein the method comprises administering the FT011 or the pharmaceutically acceptable salt thereof for a treatment period of from about 12 weeks to about 12 months.

20. The method of any one of claims 1 to 19, wherein the subject:i) has received prior treatment with an immunosuppressant, an anti-inflammatory agent, an anti-fibrotic agent, a biologic drug, a monoclonal antibody and / or a corticosteroid;ii) receives simultaneous treatment with an immunosuppressant, an anti-inflammatory agent, an anti-fibrotic agent, a biologic drug, a monoclonal antibody and / or a corticosteroid; and / oriii) subsequently receives treatment with an immunosuppressant, an antiinflammatory agent, an anti-fibrotic agent, a biologic drug, a monoclonal antibody and / or a corticosteroid.

21. The method of any one of claims 1 to 20, wherein the subject has received, is receiving, or will receive treatment with an immunosuppressant.

22. The method of any one of claims 1 to 21, wherein the subject has any one or more of the following:i) a classification of systemic sclerosis as defined by the American College of Rheumatology (ACR) and / or the European League Against Rheumatism (EULAR);ii) a diagnosis of diffuse cutaneous SSc defined as systemic sclerosis with skin thickening on the upper arms proximal to the elbows, on the upper legs proximal to the knees, or on the trunk;iii) modified Rodnan Skin Score (mRSS) at Screening of >15 to <40; andiv) a FVC >50% at screening.

23. A method of selecting a subj ect having scleroderma as being suitable for treatment with FT011 or a pharmaceutically acceptable salt thereof, the method comprising determining the level of expression of one or more genes in Table 1 in the subject.

24. A method of treating scleroderma, the method comprising:i. selecting a subject having scleroderma and an elevated level of expression of one or more genes selected from those listed in Table 1, the selecting comprising determining the level of expression of the one or more genes; andii. administering to the subject a therapeutically effective amount of FT011 or a pharmaceutically acceptable salt thereof.

25. The method of claim 23 or claim 24, wherein the subject having scleroderma is determined to be suitable for treatment with FT011 or the pharmaceutically acceptable salt thereof if they have an elevated level of expression of the one or more genes in diseased cells in the subject.

26. The method of any one of claims 23 to 25, wherein the method comprises administering to the subject an amount of FT011 or a pharmaceutically acceptable salt thereof that is effective to treat scleroderma in the subject.

27. The method of any one of claims 23 to 26, wherein the method comprises administering to the subject an amount of FT011 or a pharmaceutically acceptable salt thereof that is effective to delay the progression of, stabilise, ameliorate, eliminate and / or reduce one or more symptoms or pathological signs of scleroderma in the subject.

28. A method of monitoring a subject’s response to treatment of scleroderma with FT011 or a pharmaceutically acceptable salt thereof, the method comprising monitoring the level of expression of one or more genes selected from those listed in Table 1 after the subject has beenadministered a therapeutically effective amount of FT011 or a pharmaceutically acceptable salt thereof.

29. The method of claim 28, wherein the method comprises continuing treatment of scleroderma by administering the FT011 or the pharmaceutically acceptable salt thereof if the level of expression of one or more of the one or more genes is elevated.

30. A method of lowering a level of expression of one or more genes selected from those listed in Table 1 in a subject having scleroderma, the method comprising administering to the subject FT011 or a pharmaceutically acceptable salt in an amount sufficient to lower the level of expression of the one or more genes.

31. A method of lowering a level of expression of one or more genes selected from those listed in Table 1 in a subject having scleroderma, the method comprising administering to the subject FT011 or a pharmaceutically acceptable salt for a treatment period sufficient to lower the level of expression of the one or more genes.

32. The method of claim 30 or claim 31, wherein the method comprises administering to the subject the FT011 or the pharmaceutically acceptable salt thereof in an amount and / or for a treatment period sufficient to treat scleroderma in the subject.

33. The method of any one of claims 30 to 32, wherein the method comprises administering to the subject the FT011 or the pharmaceutically acceptable salt thereof in an amount and / or for a treatment period sufficient to delay the progression of, stabilise, ameliorate, eliminate and / or reduce one or more symptoms or pathological signs of scleroderma in the subject.

34. A method of improving an American College of Rheumatology (ACR) Composite Response Index in Diffuse Cutaneous Systemic Sclerosis (CRISS) score in a subject having scleroderma, the method comprising administering to the subject FT011 or a pharmaceutically acceptable salt in an amount sufficient to provide in an improvement in said score in the subject.

35. A method of improving an American College of Rheumatology (ACR) Composite Response Index in Diffuse Cutaneous Systemic Sclerosis (CRISS) score in a subject having scleroderma, the method comprising administering to the subject FT011 or a pharmaceutically acceptable salt for a treatment period sufficient to provide in an improvement in said score in the subject.

36. The method of claim 34 or claim 35, wherein the subject has one or more of the following:i) a classification of systemic sclerosis as defined by the American College of Rheumatology (ACR) and / or the European League Against Rheumatism (EULAR);ii) a diagnosis of diffuse cutaneous SSc defined as systemic sclerosis with skin thickening on the upper arms proximal to the elbows, on the upper legs proximal to the knees, or on the trunk;iii) modified Rodnan Skin Score (mRSS) at Screening of >15 to <40; andiv) a FVC >50% at screening.

37. The method of any one of claims 34 to 36, wherein the therapeutically effective amount of FT011 is an amount of 200mg or 400mg administered once daily, or wherein the therapeutically effective amount of the pharmaceutically acceptable salt of FT011 is an amount corresponding to from 200mg or 400mg of FT011 administered once daily.

38. A method of treating scleroderma, the method comprising administering a therapeutically effective amount of FT011 or a pharmaceutically acceptable salt thereof to a subject diagnosed as suffering from scleroderma, wherein the therapeutically effective amount of FT011 or the pharmaceutically acceptable salt thereof has previously been shown to lower the level of expression of one or more genes selected from those listed in Table 1 when administered to a subject suffering from scleroderma.