[go: up one dir, main page]

WO2024126431A1 - Agents de liaison anti-ilt7 pour le traitement et la prévention de la myosite - Google Patents

Agents de liaison anti-ilt7 pour le traitement et la prévention de la myosite Download PDF

Info

Publication number
WO2024126431A1
WO2024126431A1 PCT/EP2023/085224 EP2023085224W WO2024126431A1 WO 2024126431 A1 WO2024126431 A1 WO 2024126431A1 EP 2023085224 W EP2023085224 W EP 2023085224W WO 2024126431 A1 WO2024126431 A1 WO 2024126431A1
Authority
WO
WIPO (PCT)
Prior art keywords
weeks
days
aspects
day
subject
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/EP2023/085224
Other languages
English (en)
Inventor
William A. Rees
Gabor G. ILLEI
Theresa Anne Podrebarac
Adina Kay KNIGHT
Annie Wai-Ting KILBY
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Horizon Therapeutics Ireland DAC
Original Assignee
Horizon Therapeutics Ireland DAC
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Horizon Therapeutics Ireland DAC filed Critical Horizon Therapeutics Ireland DAC
Priority to CN202380084938.3A priority Critical patent/CN120435497A/zh
Priority to EP23829009.2A priority patent/EP4634225A1/fr
Priority to AU2023393624A priority patent/AU2023393624A1/en
Publication of WO2024126431A1 publication Critical patent/WO2024126431A1/fr
Priority to MX2025006626A priority patent/MX2025006626A/es
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/21—Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man

Definitions

  • compositions comprising ILT7 binding proteins and methods of using the same in the treatment and prevention of myositis.
  • Idiopathic inflammatory myopathies can result in permanent muscle damage with weakness if not controlled promptly.
  • corticosteroids, intravenous immunoglobulin (IVIG), and other immune modulators are used for treatment, but these medications are also associated with side effects including risk for diabetes, osteoporosis, cataracts, opportunistic infections, and thrombosis.
  • IVIG intravenous immunoglobulin
  • some subjects do not achieve timely control of their disease with these therapies. This, together with the burden of their side effects, yields the clinical need for a therapy to treat these patients.
  • Immunoglobulin-like transcript-7 can be targeted for treatment and prevention of myopathies. Therefore, provided are compositions and methods of utilizing anti-ILT7 antibodies or antigen-binding fragments thereof to reduce or eliminate symptoms or diseases associated with ILT7.
  • the dermatomyositis comprises administering an effective amount of an anti-Immunoglobulin-like transcript-7 (ILT7) antibody or antigenbinding fragment thereof to a subject in need thereof, wherein the ILT7 antibody or antigen- binding fragment thereof comprises Complementarity-Determining Regions (CDRs) HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of SEQ ID NOs: 3, 4, 5, 8, 9, and 10, respectively, wherein the effective amount is about 300 mg, and wherein the antibody is administered once every 4 weeks.
  • the dermatomyositis comprises definite myositis.
  • the dermatomyositis comprises probable myositis.
  • ASIM anti-synthetase inflammatory myositis
  • the methods comprising administering an effective amount of an anti-Immunoglobulin-like transcript-7 (ILT7) antibody or antigen-binding fragment thereof to a subject in need thereof
  • the ILT7 antibody comprises Complementarity-Determining Regions (CDRs) HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of SEQ ID NOs: 3, 4, 5, 8, 9, and 10, respectively, wherein the effective amount is about 300 mg, and wherein the antibody is administered once every 4 weeks.
  • the ASIM comprises definite myositis.
  • the ASIM comprises probable myositis.
  • ILT7 antibody comprises Complementarity-Determining Regions (CDRs) HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of SEQ ID NOs: 3, 4, 5, 8, 9, and 10, respectively, wherein the effective amount comprises a dosage from about 300 mg, and wherein the administering is completed once every 4 weeks.
  • CDRs Complementarity-Determining Regions
  • ILT7 antibody comprises Complementarity-Determining Regions (CDRs) HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of SEQ ID NOs: 3, 4, 5, 8, 9, and 10, respectively, and wherein the administration is effective in reducing disease as compared to: (a) disease in an otherwise comparable subject lacking the administering; or (b) a baseline measurement of disease in the subject in need thereof.
  • CDRs Complementarity-Determining Regions
  • the administering is continued for at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or up to about 15 administrations.
  • the administering is effective in reducing disease as compared to (b) the baseline measurement of disease in the subject in need thereof, and wherein the reduction is determined by detecting a reduced total improvement score in the subject.
  • the administering is effective in reducing disease as compared to (b) the baseline measurement of disease in the subject in need thereof, and wherein the reduction is determined by detecting a reduced level of a symptom of the disease in the subject.
  • the determination is completed after 6 and/or 12 administrations.
  • the total improvement score is > 10, 20, 30, 40, or 50.
  • the total improvement score is > 20.
  • the total improvement score is > 40.
  • the reduced level of the symptom comprises a reduction in a score of an assessment, as compared to baseline, selected from the group consisting of: Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI), Myositis Disease Activity Assessment Tool (MDAAT), myositis damage index (MDI), and combinations thereof.
  • the reduced level of the symptom comprises an increase in lung compliance as determined by an increase in forced vital capacity (FVC) as compared to baseline.
  • FVC forced vital capacity
  • the administering is effective in reducing disease as compared to (b) the baseline measurement of disease in the subject in need thereof, and wherein the reduction is determined by a decrease in use of a corticosteroid, and wherein the determination is completed after 6 administrations.
  • the corticosteroid comprises prednisone.
  • the decrease comprises a reduction in frequency of use at least about 10%, 15%, 20%, 25%, 30%, or 40%. In aspects, the decrease is from about a > 10 mg/day dosage to a 7.5 mg/day dosage.
  • the ILT7 antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH and the VL regions comprise an amino acid sequence at least 80% identical to SEQ ID NO: 2 and SEQ ID NO: 7, respectively.
  • the ILT7 antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH and the VL regions comprise the amino acid sequence of SEQ ID NO: 2 and SEQ ID NO: 7, respectively.
  • the ILT7 antibody is a monoclonal antibody.
  • the ILT7 antibody is afucosylated.
  • a sample of the subject in need is positive for one or more ASIM-associated antibodies.
  • the one or more ASIM-associated antibodies is selected from the group consisting of: anti-Jo-1, anti-PL-12, anti -PL-7, anti-KS, anti-EJ, anti-OJ, anti-ZO, and anti-YRS(HA).
  • the subject in need thereof has a dermatomyositis-related rash.
  • the disease is effectuated by plasmacytoid dendritic cells.
  • the administration is effective in reducing a level of a type I interferon in the subject as compared to a baseline level of the subject. In aspects, the level is reduced by at least about 1-fold, 5-fold, 10-fold, 25-fold, 50-fold, 75-fold, 100- fold, 150-fold, or 250-fold.
  • the administering is effective in eliminating the disease for at least about 3 months, 6 months, 1 year, or 2 years. In aspects, the administering is subcutaneous.
  • ILT7 antibody or antigen-binding fragment thereof comprises Complementarity-Determining Regions (CDRs) HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of SEQ ID NOs: 3, 4, 5, 8, 9, and 10, respectively, wherein the effective amount is about 300 mg.
  • CDRs Complementarity-Determining Regions
  • ILT7 antibody comprises Complementarity- Determining Regions (CDRs) HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of SEQ ID NOs: 3, 4, 5, 8, 9, and 10, respectively, wherein the effective amount is about 300 mg.
  • CDRs Complementarity- Determining Regions
  • FIG. 1 shows an exemplary study flow diagram.
  • the present disclosure provides antibodies and antigen-binding fragments thereof which bind to Immunoglobulin-like transcript-7 (ILT7). Inhibition of binding can reduce or eliminate activation of inflammatory signaling pathways associated with related disease.
  • ILT7 antibodies and antigen-binding fragments disclosed herein can be used to neutralize ILT7.
  • anti-ILT7 antibodies and antigen-binding fragments disclosed herein can be used to regulate pDC activity.
  • anti-ILT7 antibodies and antigenbinding fragments disclosed herein can be used to regulate IFN release.
  • anti- ILT7 antibodies and antigen-binding fragments disclosed herein can be used to reduce or eliminate ILT7/BST2 binding.
  • anti-ILT7 antibodies and antigen-binding fragments encoded polypeptides, and pharmaceutical compositions comprising the same.
  • methods of using the anti-ILT7 antibodies and antigen-binding fragments thereof in methods of treating disease are used in methods of treating dermatomyositis (DM) and/or anti -synthetase inflammatory myositis (ASIM).
  • DM dermatomyositis
  • ASIM anti -synthetase inflammatory myositis
  • the term “about” or “approximately” when immediately preceding a numerical value means a range (e.g., plus or minus 10% of that value).
  • “about 50” can mean 45 to 55
  • “about 25,000” can mean 22,500 to 27,500, etc., unless the context of the disclosure indicates otherwise, or is inconsistent with such an interpretation.
  • “about 50” means a range extending to less than half the interval(s) between the preceding and subsequent values, e.g., more than 49.5 to less than 52.5.
  • the term “subject” refers to any subject, e.g., a human or a nonhuman mammal, for whom diagnosis, prognosis, or therapy is desired.
  • the term “subject” may mean a human or non-human mammal affected, likely to be affected, or suspected to be affected with a disease.
  • the terms “subject” and “subject” are used interchangeably herein. In aspects, the subject is a mammal.
  • a mammal includes primates, such as humans, monkeys, chimpanzee, and apes, and non-primates such as domestic animals, including laboratory animals (such as rabbits and rodents, e.g., guinea pig, rat, or mouse) and household pets and farm animals (e.g., cats, dogs, swine, cattle, sheep, goats, horses, rabbits), and non-domestic animals, such as wildlife, birds, reptile, fish, or the like.
  • laboratory animals such as rabbits and rodents, e.g., guinea pig, rat, or mouse
  • household pets and farm animals e.g., cats, dogs, swine, cattle, sheep, goats, horses, rabbits
  • non-domestic animals such as wildlife, birds, reptile, fish, or the like.
  • a subject in need thereof includes subjects that could or would benefit from the methods described herein.
  • Subjects in need of treatment include, without limitation, those already with the condition or disorder, those prone to having the condition or disorder, those in which the condition or disorder is suspected, as well as those in which the condition or disorder is to be prevented, ameliorated, or reversed.
  • treating describes the management and care of a subject for the purpose of combating a disease, condition, or disorder and includes the administration of an anti-ILT7 antibody or antigen-binding fragment thereof used in the methods described herein to alleviate the symptoms or complications of a disease, condition or disorder, or to eliminate the disease, condition or disorder.
  • the term “treat” or “treating” refers to both therapeutic measures and prophylactic or preventative measures, wherein the objective is to prevent, slow down (lessen), or ameliorate the progression of a disease (e.g., a myositis disease or disorder).
  • Beneficial or desired clinical results include, but are not limited to, alleviation of symptoms, diminishing the extent of the disease, stabilized (i.e., not worsening) state of the disease, delaying or slowing of disease progression, amelioration or palliation of the disease state, and reversing the disease (whether partial or total).
  • the term “treat” can also include treatment of a cell in vitro or an animal model.
  • identity is used to denote similarity between two sequences. Unless otherwise indicated, percent identities described herein are determined using the BLAST algorithm available at the world wide web address: blast.ncbi.nlm.nih.gov/Blast.cgi using default parameters. IMMUNOGLOBULIN-LIKE TRANSCRIPT-7 (ILT7) BINDING PROTEINS
  • Plasmacytoid dendritic cells are important regulators of the immune system and the main source of Type-I interferon (IFN, e.g., IFN-a).
  • IFN-a is a key cytokine in the innate response that enhances activation of all arms of the immune system.
  • pDCs release IFN in response to nucleic acids that are sensed by Toll-like receptors (TLRs) TLR7 and TLR9 expressed on the surface of the pDCs.
  • TLRs Toll-like receptors
  • TLR7 and TLR9 expressed on the surface of the pDCs.
  • TLR-induced response is regulated by receptors containing immunoreceptor tyrosine-based activation motifs (ITAMs).
  • ITAMs immunoreceptor tyrosine-based activation motifs
  • Immunoglobulin-like transcript-7 also called LIRA4, LILRA4, or CD85g
  • ILT7 contains four immunoglobulin-like extracellular domains and a transmembrane domain. The extracellular portion is important for interacting with the ILT7 ligand, bone marrow stromal cell antigen 2 (BST2), and the transmembrane domain of ILT7 contains a positively charged residue that allows it to complex with FcsRIy.
  • BST2-ILT7 interaction negatively regulates the innate immune function of pDCs, where in vitro antibody cross-linking of ILT7 has been shown to negatively regulate the production of IFN- a and TNF-a by pDCs.
  • compositions that bind ILT7 comprise ILT7 antagonists. In aspects, provided compositions bind to and neutralize the activity of ILT7. In aspects, provided compositions comprise an Immunoglobulin G (IgG) human monoclonal antibody (mAb). In aspects, provided herein are compositions that bind ILT7 and have antibody dependent cellular cytotoxicity (ADCC) activity. In aspects, provided herein are compositions that comprise an anti-ILT7 antibody or antigen-binding fragment thereof.
  • IgG Immunoglobulin G
  • mAb human monoclonal antibody
  • ADCC antibody dependent cellular cytotoxicity
  • an anti-ILT7 antibody comprises an antibody that binds to ILT7. Binding of ILT7 can be effectuated by any portion of an antibody.
  • an antibody or antigenbinding fragment binds ILT7 by way of a complementary determining region (CDR).
  • CDR complementary determining region
  • an antibody binds ILT7 by way of VL and/or VH chains.
  • an anti-ILT7 antibody or antigen-binding fragment thereof comprises six complementarity-determining regions (CDRs) designated heavy CDR1 (HCDR1), HCDR2, HCDR3, light CDR1 (LCDR1), LCDR2, and LCDR3.
  • an anti-ILT7 antibody or antigen-binding fragment thereof comprises two light chain variable loop domains (VL) and two heavy chain variable loop domains (VH).
  • VL light chain variable loop domains
  • VH heavy chain variable loop domains
  • Antibodies or antigen-binding fragments, variants, or derivatives thereof include, but are not limited to, polyclonal, monoclonal, human, humanized, or chimeric, antibodies, epitope-binding fragments (e.g., Fab, F(ab')2, Fv, single-chain Fvs (scFv), single-chain antibodies, disulfide-linked Fvs (sdFv), fragments comprising either a VL or VH domain (Fd), fragments produced by a Fab expression library, and other antibody fragments and combinations thereof that retain antigen-binding function, i.e., the ability to bind, for example, ILT7.
  • epitope-binding fragments e.g., Fab, F(ab')2, Fv, single-chain Fvs (scFv), single-chain antibodies, disulfide-linked Fvs (sdFv), fragments comprising either a VL or VH domain (Fd), fragments produced by
  • an anti-ILT7 antibody or antigen-binding fragment thereof comprises a VL domain and a VH domain, where the VH domain comprises the polypeptide of SEQ ID NO: 2 and the VL domain comprises the polypeptide of SEQ ID NO: 7.
  • an anti- ILT7 antibody comprises two VL domains and two VH domains, where the VH domain comprises the polypeptide of SEQ ID NO: 2 and the VL domain comprises the polypeptide of SEQ ID NO: 7.
  • the nucleic acid sequences of the VH and VL domains comprise or consist of nucleic acid SEQ ID NO: 1 and nucleic acid SEQ ID NO: 6, respectively.
  • an anti-ILT7 antibody or antigen-binding fragment thereof comprises six CDR regions designated HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, wherein the HCDR1 comprises the amino acid of SEQ ID NO: 3, the HCDR2 comprises the amino acid of SEQ ID NO: 4, the HCDR3 comprises the amino acid of SEQ ID NO: 5, the LCDR1 comprises the amino acid of SEQ ID NO: 8, the LCDR2 comprises the amino acid of SEQ ID NO: 9, and the LCDR3 comprises the amino acid of SEQ ID NO: 10.
  • an anti-ILT7 antibody or antigen-binding fragment thereof comprises at least or at most about 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or up to about 100% identity with any one of SEQ ID NO: 1 - SEQ ID NO: 10 shown in Table 1.
  • any one of the sequences from Table 1 can be modified.
  • a modification comprises one or more truncations, deletions, insertions, and combinations thereof. A modification can occur at any of the residues provided in Table 1 and in any number of residues from Table 1.
  • a modification can comprise from 1-3, 1-5, 1-10, 1-20, 3-8, 3-10, 3-15, 5-8, 5-10, or 5-20 residues. In aspects, a modification can occur in up to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 20, 30, 40, 50, 60, 70, 80, 90, 100, 200, or up to about 300 residues.
  • Table 1 Exemplary sequences for an ILT7 binding protein.
  • an anti-ILT7 antibody or antigen-binding fragment thereof of the disclosure can comprise variants of the sequences provided they retain the ability to bind ILT7.
  • conservative amino acid substitutions can be made within any one of the disclosed CDRs.
  • Various alterations can be made according to the methods described in Antibody Engineering, 2nd ed., Oxford University Press, ed. Borrebaeck, 1995. These alterations comprise but are not limited to nucleotide sequences that are altered by the substitution of different codons that encode a functionally equivalent amino acid residue within the sequence, thus producing a “silent” change.
  • the nonpolar amino acids comprise alanine (A), leucine (L), isoleucine (I), valine (V), proline (P), phenylalanine
  • the polar neutral amino acids comprise glycine
  • the positively charged (basic) amino acids comprise arginine (R), lysine (K), and histidine
  • the negatively charged (acidic) amino acids comprise aspartic acid (D) and glutamic acid (E).
  • the CDR amino acid sequences disclosed herein can vary by at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or up to about 100%.
  • Derivatives and analogs of antibodies or antigen-binding fragments thereof of the disclosure can be produced by various techniques, including recombinant and synthetic methods (Maniatis (1990) Molecular Cloning, A Laboratory Manual, 2nd ed., Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y., and Bodansky et al. (1995) The Practice of Peptide Synthesis, 2nd ed., Spring Verlag, Berlin, Germany).
  • a method for making a VH domain which is an amino acid sequence variant of a VH domain of the disclosure comprises a step of adding, deleting, substituting, or inserting one or more amino acids in the amino acid sequence of the presently disclosed VH domain, optionally combining the VH domain thus provided with one or more VL domains, and testing the VH domain or VH/VL combination or combinations for specific binding to the antigen.
  • An analogous method can be employed in which one or more sequence variants of a VL domain disclosed herein are combined with one or more VH domains.
  • amino acid and/or nucleic acid VH or VL sequence disclosed herein can vary by at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or up to about 100%.
  • the present disclosure provides methods for the use of Immunoglobulin-like transcript-7 (ILT7) binding molecules, e.g., antibodies and antigen-binding fragments thereof which bind ILT7.
  • the full-length amino acid and nucleotide sequences for ILT7 are known in the art (see, e.g., UniProt Acc. No. P59901 for human ILT7).
  • the ILT7-specific antibodies or antigen-binding fragments of the present disclosure inhibit BST2-mediated activation of ILT7 and thereby decrease proinflammatory signaling and reduce inflammation in a subject.
  • an anti-ILT7 antibody is also known as HZN-7734.
  • an anti-ILT7 antibody is also known as MEDI7734.
  • compositions of the disclosure may comprise any of the amino acid or nucleic acid sequences as described in U.S. Patent No. 11,072,652, which are incorporated herein by reference in their entireties. In aspects, provided compositions may comprise any of the sequences as shown in Table 1.
  • an anti-ILT7 antibody or antigen-binding fragment thereof disclosed herein can be glycosylated.
  • an anti-ILT7 antibody or antigen-binding fragment thereof can have a glycosylation pattern that differs from the wild-type pattern. For example, one or more carbohydrate moieties can be deleted and/or one or more glycosylation sites added. Addition of glycosylation sites to the presently disclosed antibodies or antigenbinding fragments can be accomplished by altering the amino acid sequence to contain glycosylation site consensus sequences known in the art.
  • Another means of increasing the number of carbohydrate moieties on the antibody or antigen-binding fragment is by chemical or enzymatic coupling of glycosides to the amino acid residues of the antibody or antigen-binding fragment.
  • Such methods are described in WO 87/05330, and in Aplin et al. (1981) CRC Crit. Rev. Biochem., 22: 259-306. Removal of any carbohydrate moieties from the antibodies or antigen-binding fragments may be accomplished chemically or enzymatically, for example, as described by Hakimuddin et al. (1987) Arch. Biochem. Biophys., 259: 52; and Edge et al. (1981) Anal. Biochem., 118: 131 and by Thotakura et al. (1987) Meth. Enzymol., 138: 350.
  • an anti-ILT7 antibody or antigen-binding fragment thereof disclosed herein can be afucosylated.
  • an anti-ILT7 antibody or antigen-binding fragment thereof can have a fucosylation pattern that differs from the wild-type pattern.
  • one or more fucose moieties can be deleted. Deletion of fucosylation sites to the presently disclosed antibodies or antigen-binding fragments can be accomplished by altering the amino acid sequence to remove fucosylation site consensus sequences known in the art. Another means of removal of any fucose moieties from the antibodies or antigen-binding fragments may be accomplished chemically or enzymatically, for example, as described by Hakimuddin et al. (1987) Arch.
  • Additional means of generating afucosylated antibodies can comprise use of cell lines, such as the GDP- keto-6-deoxymannose 3,5-epimerase/4 reductase (FX)-knockout CHO cell line that produces antibodies with afucosylated N-glycans.
  • cell lines such as the GDP- keto-6-deoxymannose 3,5-epimerase/4 reductase (FX)-knockout CHO cell line that produces antibodies with afucosylated N-glycans.
  • Other cell lines that can be employed comprise YB2/0 cells which have reduced levels of the Fut8 mRNA.
  • an anti-ILT7 antibody or antigen-binding fragment can be tagged.
  • an anti-ILT7 antibody or antigen-binding fragment can be tagged with a functional agent.
  • a functional agent is an imaging agent (e.g., a radionuclide, a biotin, a fluorescent molecule, a luminescent molecule, or a non-radioactive paramagnetic metal ion).
  • a functional agent is an enzyme (e.g., horseradish peroxidase, alkaline phosphatase, P-galactosidase, or acetylcholinesterase).
  • a functional agent is a drug (e.g., a cytotoxic agent or a radioactive compound).
  • any of the compositions of the disclosure comprising an anti-ILT7 antibody or antigen-binding fragment thereof can be administered in any form.
  • an anti-ILT7 antibody or antigen-binding fragment thereof is administered intravenously, subcutaneously, orally, intramuscularly, intrathecally, sublingually, rectally, vaginally, cutaneously, systemically, topically, transdermally, or by way of inhalation.
  • an anti-ILT7 antibody or antigen-binding fragment thereof is administered subcutaneously.
  • an anti-ILT7 antibody or antigen-binding fragment thereof of the disclosure can be administered at any dose.
  • an anti-ILT7 antibody or antigen-binding fragment thereof is administered at a dose from about: 50 mg, 75 mg, 100 mg, 125 mg, 150 mg, 175 mg, 200 mg, 225 mg, 250 mg, 275 mg, 300 mg, 325 mg, 350 mg, 375 mg, 400 mg, 425 mg, 450 mg, 475 mg, 500 mg, 525 mg, 550 mg, 575 mg, 600 mg, 650 mg, 700 mg, 750 mg, 800 mg, 850 mg, 900 mg, 950 mg, 1000 mg, 1050 mg, 1100 mg, 1150 mg, 1200 mg, 1250 mg, 1300 mg, 1350 mg, 1400 mg, 1450 mg, or about 1500 mg. Any of the aforementioned dosages may be effective dosages for a method comprising prevention, reduction, or elimination.
  • an anti-ILT7 antibody or antigen-binding fragment thereof is administered at a dose of between about: 50-100 mg, 50-150 mg, 100-200 mg, 130-180 mg, 150-250 mg, 200-300 mg, 250-350 mg, 50-1500 mg, 75-1200 mg, 100-800 mg, or 150-500 mg.
  • an anti-ILT7 antibody or antigen-binding fragment thereof is administered at a dose selected from the group consisting of: 150 mg, 175 mg, 200 mg, 225 mg, 250 mg, 275 mg, 300 mg, 325 mg, 350 mg, 375 mg, 400 mg, 425 mg, 450 mg, 500 mg, 525 mg, 550 mg, 575 mg, and 600 mg.
  • an anti-ILT7 antibody or antigen-binding fragment thereof is administered at an effective dose of about 150 mg. In aspects, an anti-ILT7 antibody or antigen-binding fragment thereof is administered at an effective dose of about 200 mg. In aspects, an anti-ILT7 antibody or antigen-binding fragment thereof is administered at an effective dose of about 300 mg. Dosing Frequency
  • an anti-ILT7 antibody or antigen-binding fragment thereof of the disclosure is administered on a schedule that provides optimal results.
  • an anti- ILT7 antibody or antigen-binding fragment thereof disclosed herein is administered to a subject in need thereof about once a week, about twice a week, about every two weeks, about every four weeks, about once a month, about every six weeks, about every two months, about every 3 months, about every 12 weeks, about every fifteen weeks, about every sixteen weeks, about every four months, about every five months, about every six months, or semiannually.
  • a subject is administered an effective dose daily, weekly, biweekly, or up to about the lifetime of the subject.
  • administration are given for up to about 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 1 year, 2 years, 3 years, 4 years, or 5 years.
  • a subject receives an effective dose on Day 1, Day 28, Day 56, Day 84, Day 112, Day 140, Day 168, Day 196, Day 224, Day 252, Day 280, and Day 308 post treatment initiation. In aspects, a subject receives an effective dose on week 0, week 4, week 8, week 12, week 16, week 20, week 24, week 28, week 32, week 36, week 40, and week 44 post treatment initiation. In aspects, a subject receives an effective dose of 300 mg of an anti-ILT7 antibody or antigen-binding fragment thereof on Day 1, Day 28, Day 56, Day 84, Day 112, Day 140, Day 168, Day 196, Day 224, Day 252, Day 280, and Day 308 post treatment initiation.
  • a subject in need thereof is administered an effective dose of 300 mg of an anti-ILT7 antibody or antigen-binding fragment thereof on week 0, week 4, week 8, week 12, week 16, week 20, week 24, week 28, week 32, week 36, week 40, and week 44 post treatment initiation.
  • a subject in need thereof is administered an effective dose of 300 mg of an anti- ILT7 antibody or antigen-binding fragment thereof on Day 1 and then every 4 weeks thereafter as needed.
  • a subject in need thereof is administered 300 mg of an anti- ILT7 antibody or antigen-binding fragment thereof every four weeks. Any of the aforementioned administrations can deviate by about 0-7 days, 0-5 days, 0-4 days, 0-3 days, 0-2 days, or by about 3 days.
  • a subject receives an effective dose of an anti-ILT7 antibody or antigenbinding fragment thereof on Day 1, Day 28 ( ⁇ 3 day), Day 56 ( ⁇ 3 days), Day 84 ( ⁇ 3 days), Day 112 ( ⁇ 3 days), Day 140 ( ⁇ 3 days), Day 168 ( ⁇ 3 days), Day 196 ( ⁇ 3 days), Day 224 ( ⁇ 3 days), Day 252 ( ⁇ 3 days), Day 280 ( ⁇ 3 days), and Day 308 ( ⁇ 3 days) post treatment initiation.
  • an anti-ILT7 antibody or antigen-binding fragment thereof is administered at an effective single dose.
  • a subject in need thereof is administered at least two administrations of an anti-ILT7 antibody or antigen-binding fragment thereof.
  • an anti-ILT7 antibody or antigen-binding fragment thereof is administered as a series of multiple doses.
  • an anti-ILT7 antibody or antigen-binding fragment thereof is administered at an effective single dose or multiple doses.
  • an anti-ILT7 antibody or antigen-binding fragment thereof is administered at a dose of about 300 mg for at least 1 dose and is administered about once a month or every four weeks thereafter. In aspects, an anti-ILT7 antibody or antigen-binding fragment thereof is administered as two doses of about 150 mg for at least 2 doses and is administered at 2 doses about once a month thereafter. In aspects, an anti-ILT7 antibody or antigen-binding fragment thereof is administered at a dose of about 300 mg once about every four weeks, once about every month, once about every two months, or once about every three months. In aspects, an anti-ILT7 antibody or antigen-binding fragment thereof is administered at two doses of about 150 mg about every four weeks, about every month, twice about every two months, or twice about every three months.
  • an anti-ILT7 antibody or antigen-binding fragment thereof is administered for two or more doses.
  • an anti-ILT7 antibody or antigen-binding fragment thereof of the disclosure is administered to a subject in need thereof until myositis is prevented, reduced, or eliminated as determined by a test of the disclosure.
  • an anti-ILT7 antibody or antigen-binding fragment thereof is administered as an effective dose of about 300 mg.
  • a method disclosed herein comprises administration of an antibody or antigen-binding fragment thereof that binds ILT7 to a subject in need thereof, wherein the antibody or antigen-binding fragment thereof is administered at an effective dose of about 300 mg subcutaneously.
  • a method disclosed herein comprises administration of an antibody or antigen-binding fragment thereof that binds ILT7 to a subject in need thereof, wherein the antibody or antigen-binding fragment thereof is administered as two doses of about 150 mg each subcutaneously.
  • a method disclosed herein comprises administration of an antibody or antigen-binding fragment thereof that binds ILT7 to a subject in need thereof, wherein the antibody or antigen-binding fragment thereof is administered as two doses of about 150 mg each every 4 weeks subcutaneously.
  • a method disclosed herein comprises administration of an antibody or antigen-binding fragment thereof that binds ILT7 to a subject in need thereof, wherein the antibody or antigen-binding fragment thereof is administered as two doses of about 150 mg each every 4 weeks for at least 12 administrations subcutaneously.
  • a method disclosed herein comprises administration of an antibody or antigen-binding fragment thereof that binds ILT7 to a subject in need thereof, wherein the antibody or antigen-binding fragment thereof comprise HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of: SEQ ID NOs: 3, 4, 5, 8, 9, and 10, respectively.
  • a method disclosed herein comprises administration of an antibody or antigenbinding fragment thereof that binds ILT7 to a subject in need thereof, wherein the antibody or antigen-binding fragment thereof comprise HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of: SEQ ID NOs: 3, 4, 5, 8, 9, and 10, respectively, and wherein the antibody or antigen-binding fragment thereof is administered as a dose of 300 mg or as two doses of about 150 mg each subcutaneously.
  • a method disclosed herein comprises administration of an antibody or antigen-binding fragment thereof that binds ILT7 to a subject in need thereof, wherein the antibody or antigen-binding fragment thereof comprise HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of: SEQ ID NOs: 3, 4, 5, 8, 9, and 10, respectively, and wherein the antibody or antigen-binding fragment thereof is administered as a dose of 300 mg or as two doses of about 150 mg each subcutaneously every 4 weeks.
  • a method disclosed herein comprises administration of an antibody or antigen-binding fragment thereof that binds ILT7 to a subject in need thereof, wherein the antibody or antigen-binding fragment thereof comprise HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of: SEQ ID NOs: 3, 4, 5, 8, 9, and 10, respectively, and wherein the antibody or antigen-binding fragment thereof is administered as a dose of 300 mg or as two doses of about 150 mg each subcutaneously every 4 weeks for at least 12 administrations.
  • a method disclosed herein comprises administration of an antibody or antigen-binding fragment thereof that binds ILT7 to a subject in need thereof in any of the aspects or methods disclosed herein, wherein the antibody or antigen-binding fragment thereof comprise VH and VL, wherein the VH and VL comprise an amino acid sequence having at least about 80%, 85%, 90%, 95%, 99%, or 100% identity to SEQ ID NOs: 2 and 7, respectively.
  • a method disclosed herein comprises administration of an antibody or antigen-binding fragment thereof that binds ILT7 to a subject in need thereof, wherein the antibody or antigen-binding fragment thereof comprise VH and VL, wherein the VH and VL comprise the amino acid sequences of: SEQ ID NOs: 2 and 7, respectively, and wherein the antibody or antigen-binding fragment thereof is administered as a dose of about 300 mg or as two doses of about 150 mg each.
  • a method disclosed herein comprises administration of an antibody or antigen-binding fragment thereof that binds ILT7 to a subject in need thereof, wherein the antibody or antigen -binding fragment thereof comprise VH and VL, wherein the VH and VL comprise the amino acid sequences of: SEQ ID NOs: 2 and 7, respectively, and wherein the antibody or antigen-binding fragment thereof is administered as a dose of about 300 mg or as two doses of about 150 mg each subcutaneously.
  • a method disclosed herein comprises administration of an antibody or antigen-binding fragment thereof that binds ILT7 to a subject in need thereof, wherein the antibody or antigen-binding fragment thereof comprise VH and VL, wherein the VH and VL comprise the amino acid sequences of: SEQ ID NOs: 2 and 7, respectively, and wherein the antibody or antigen-binding fragment thereof is administered as a dose of about 300 mg subcutaneously every 4 weeks.
  • a method disclosed herein comprises administration of an antibody or antigen-binding fragment thereof that binds ILT7 to a subject in need thereof, wherein the antibody or antigen-binding fragment thereof comprise VH and VL, wherein the VH and VL comprise the amino acid sequences of: SEQ ID NOs: 2 and 7, respectively, and wherein the antibody or antigen-binding fragment thereof is administered as a dose of about 300 mg subcutaneously every 4 weeks.
  • a subject in need thereof is administered an effective dose of an anti-ILT7 antibody or antigen-binding fragment thereof once about every 2-4 weeks.
  • a subject in need thereof is administered an effective dose of an anti-ILT7 antibody or antigenbinding fragment thereof once every 4 weeks.
  • a subject in need thereof is administered 300 mg of an anti-ILT7 antibody or antigen-binding fragment thereof once every 4 weeks for at least 3 doses, once every 4 weeks for at least 4 doses, once every 4 weeks for at least 5 doses, or a combination thereof.
  • an anti-ILT7 antibody or antigen-binding fragment thereof is administered at an effective dose of about 300 mg once every four weeks.
  • an anti-ILT7 antibody or antigen-binding fragment thereof is administered at an effective dose of about 300 mg every month.
  • a subject in need thereof is administered two 150 mg doses of an anti-ILT7 antibody or antigen-binding fragment thereof once every 4 weeks for at least 3 doses, once every 4 weeks for at least 4 doses, once every 4 weeks for at least 5 doses, or a combination thereof.
  • an anti- ILT7 antibody or antigen-binding fragment thereof is administered as two 150 mg doses every four weeks or every month.
  • methods are directed to treat, reduce, or eliminate a myositis disease or disorder.
  • a method comprises administering an anti-ILT7 antibody or antigen-binding fragment thereof of the disclosure.
  • an anti-ILT7 antibody or antigen-binding fragment thereof is administered to prevent, reduce, or eliminate myositis in a subject in need thereof using any of the dosing schedules disclosed herein.
  • Idiopathic inflammatory myopathies such as myositis
  • dermatomyositis including amyopathic dermatomyositis
  • ASIM anti synthetase inflammatory myositis
  • immune-mediated necrotizing myopathy inclusion body myositis, polymyositis, and overlap myositis.
  • a myositis disease or disorder comprises dermatomyositis (DM).
  • a myositis disease or disorder comprises anti -synthetase inflammatory myositis (ASIM).
  • a myositis disease or disorder comprises polymyositis (PM).
  • a myositis disease or disorder comprises sporadic inclusion body myositis (sIBM).
  • a subject with DM has DM with definite or probable myositis. In aspects, a subject with DM has a DM rash. In aspects, a subject with ASIM has ASIM with definite or probable myositis. In aspects, a subject with ASIM has a positive ASIM associated antibody.
  • an anti-ILT7 antibody or antigen-binding fragment thereof is administered to prevent, reduce, or eliminate DM in a subject in need thereof using any of the dosing schedules disclosed herein. In aspects, an anti-ILT7 antibody or antigen-binding fragment thereof is administered to prevent, reduce, or eliminate ASIM in a subject in need thereof using any of the dosing schedules disclosed herein.
  • an anti-ILT7 antibody or antigen-binding fragment thereof is administered to prevent, reduce, or eliminate disease in a subject that tests positive for anti-histidyl tRNA synthetase (e.g., anti-Jo-1) antibodies prior to treatment.
  • an anti-ILT7 antibody or antigen-binding fragment thereof is administered to prevent, reduce, or eliminate disease in a subject that has an ASIM diagnosis and tests positive for anti-histidyl tRNA synthetase (e.g., anti-Jo-1) antibodies prior to treatment.
  • an anti-ILT7 antibody or antigen-binding fragment thereof is administered to prevent, reduce, or eliminate disease in a subject that has an ASIM diagnosis and a positive ASIM associated antibody.
  • an anti-ILT7 antibody or antigenbinding fragment thereof is administered to prevent, reduce, or eliminate disease in a subject has historically tested positive for one or more of anti-alanyl (e.g., anti-PL-12), anti-threonyl (e.g., anti-PL-7), anti-asparaginyl (e.g., anti-KS), anti-glycyl (e.g., anti-EJ), anti -isoleucyl (e.g., anti-OJ), anti-phenylalanyl tRNA synthetase (e.g., anti-ZO), or anti-tyrosil (e.g., anti- YRS(HA)) antibodies.
  • anti-alanyl e.g., anti-PL-12
  • anti-threonyl e
  • an anti-ILT7 antibody or antigen-binding fragment thereof is administered to prevent, reduce, or eliminate disease in a subject that has an ASIM diagnosis and has historically tested positive for one or more of anti-alanyl (e.g., anti-PL- 12), anti-threonyl (e.g., anti-PL-7), anti-asparaginyl (e.g., anti-KS), anti-glycyl (e.g., anti- EJ), anti-isoleucyl (e.g., anti-OJ), anti-phenylalanyl tRNA synthetase (e.g., anti-ZO), or anti- tyrosil (e.g., anti-YRS(HA)) antibodies.
  • anti-alanyl e.g., anti-PL- 12
  • anti-threonyl e.g., anti-PL-7
  • anti-asparaginyl e.g., anti-KS
  • anti-glycyl
  • an anti-ILT7 antibody or antigen-binding fragment thereof is administered to prevent, reduce, or eliminate disease in a subject wherein the subject is not diagnosed with a disease.
  • an anti-ILT7 antibody or antigen-binding fragment thereof is administered to prevent, reduce, or eliminate disease in a subject wherein the subject is not diagnosed with immune-mediate necrotizing myopathy (IMNM), inclusion body myositis (IBM), or drug-induced myositis.
  • IMNM immune-mediate necrotizing myopathy
  • IBM inclusion body myositis
  • a subject is diagnosed with IMNM if the subject has 3 -hydroxy-3 -methylglutaryl -coenzyme A reductase (i.e., anti- HMGR) antibodies, anti-signal recognition particle (i.e., anti-SRP) antibodies, or is autoantibody negative.
  • a subject is diagnosed with IBM if the subject has anti- cytosolic 5 ’-nucleotidase 1A (i.e., anti-CNIA) antibodies.
  • a method of treating a subject in need thereof comprises administering an effective amount of an anti-ILT7 antibody or antigen-binding fragment thereof.
  • an administration is effective in reducing a disease or a disorder as compared to: a) the disease or disorder in an otherwise comparable subject lacking the administration; or b) a baseline measurement of the disease or disorder in the subject in need thereof.
  • an administration is effective in reducing a level of a type I interferon (IFN, e.g., IFN-a) in a subject in need thereof as compared to a baseline level of the subject.
  • IFN type I interferon
  • a level of a type I IFN is reduced in a subject administered an anti-ILT7 antibody or antigen-binding fragment by at least about or at most about: 1-fold, 5-fold, 10-fold, 25-fold, 50-fold, 75-fold, 100-fold, 150-fold, or 250-fold as compared to a baseline level of the subject.
  • an anti-ILT7 antibody or antigen-binding fragment thereof is used to treat a myositis disease or disorder.
  • an anti-ILT7 antibody or antigen-binding fragment thereof is used to treat a subject in need thereof using any of the dosing schedules disclosed herein.
  • an anti-ILT7 antibody or antigen-binding fragment thereof is administered at a dose of about 300 mg. In aspects, an anti-ILT7 antibody or antigen-binding fragment thereof is administered at a dose of about 150 mg twice. In aspects, an anti-ILT7 antibody or antigen-binding fragment thereof is administered at a dose of about 300 mg subcutaneously. In aspects, an anti-ILT7 antibody or antigen-binding fragment thereof is administered at a dose of about 150 mg twice via subcutaneous administration. In aspects, an anti-ILT7 antibody or antigen-binding fragment thereof is administered at a dose of about 300 mg every 4 weeks.
  • an anti-ILT7 antibody or antigen-binding fragment thereof is administered at a dose of about 150 mg twice every 4 weeks. In aspects, an anti- ILT7 antibody or antigen-binding fragment thereof is administered at a dose of about 150 mg twice every 4 weeks for at least 2 doses. In aspects, an anti-ILT7 antibody or antigenbinding fragment thereof is administered at a dose of about 150 mg twice every 4 weeks for at least 3 doses. In aspects, an anti-ILT7 antibody or antigen-binding fragment thereof is administered at a dose of about 300 mg via subcutaneous administration every 4 weeks for at least 2 doses. In aspects, an anti-ILT7 antibody or antigen-binding fragment thereof is administered at a dose of about 300 mg via subcutaneous administration every 4 weeks for at least 3 doses.
  • an anti-ILT7 antibody or antigen-binding fragment thereof effective dose may be formulated at a concentration of about 100 mg/mL. In aspects, an anti-ILT7 antibody or antigen-binding fragment thereof effective dose may be formulated at a concentration of about 150 mg/mL.
  • the dose and dosing regimen of an anti-ILT7 antibody or antigen-binding fragment thereof disclosed herein may be such that any therapeutic effect achieved from administration of an anti-ILT7 antibody or antigen-binding fragment thereof to treat any myositis disease or disorder, may be considered to be “long-lasting.”
  • a “long-lasting” effect of an anti-ILT7 antibody or antigen-binding fragment thereof in the treatment of a myositis disease or disorder is one in which the therapeutic effect achieved by an anti-ILT7 antibody or antigen-binding fragment thereof is maintained (although an anti-ILT7 antibody or antigen-binding fragment thereof is no longer administered) over at least 4 weeks, at least 6 weeks, at least 8 weeks, at least 10 weeks, at least 12 weeks, at least 16 weeks, at least 20 weeks, at least 24, at least 28 weeks, at least 32 weeks, at least 36 weeks, at least 40 weeks, at least 44 weeks, at least 48 weeks, at least 1 year, at least 2 years, or up to about at least 5 years following a prior administration
  • administration of an anti-ILT-7 antibody or antigen-binding fragment thereof is effective in eliminating disease in a subject in need thereof.
  • administration of an anti-ILT-7 antibody or antigen-binding fragment thereof is effective in reducing disease in a subject in need thereof.
  • administration of an anti-ILT7 antibody or antigen-binding fragment thereof is effective in eliminating or reducing disease in a subject in need thereof for at least about 1 week, 2 weeks, 3 weeks, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 1 year, 2 years, 3 years, 4 years, at least about 5 years, or for the lifetime of the subject.
  • administration of an anti-ILT7 antibody or antigen-binding fragment thereof is effective in eliminating disease in a subject in need thereof for at least about 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, or at least about 12 weeks.
  • administration of an anti-ILT7 antibody or antigen-binding fragment thereof is effective in eliminating or reducing disease in a subject in need thereof for at least about 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, or at least about 12 months.
  • administration of an anti-ILT7 antibody or antigen-binding fragment thereof is effective in eliminating or reducing disease in a subject in need thereof for at least about 1 year, 2 years, 3 years, 4 years, 5 years, 6 years, 7 years, 8 years, 9 years, or at least about 10 years. In aspects, administration of an anti-ILT7 antibody or antigen-binding fragment thereof is effective in eliminating or reducing disease for the lifetime of a subject in need thereof.
  • a subject in need thereof has been administered one or more standard of care therapies for the treatment of a myositis disease or disorder prior to the administration of an anti-ILT7 antibody or antigen-binding fragment thereof.
  • a standard of care therapy comprises a corticosteroid, a disease-modifying anti-rheumatic drug (DMARD), and/or an immunomodulatory agent.
  • DMARD disease-modifying anti-rheumatic drug
  • a subject continues on a standard of care therapy while being administered an anti-ILT7 antibody or antigen-binding fragment thereof.
  • a standard of care therapy is administered as a second therapy.
  • any of the referenced therapies may be combined in a therapeutic regimen for the treatment of a myositis disease or disorder.
  • a subject is treated with both an anti-ILT7 antibody or antigen-binding fragment thereof and a standard of care therapy.
  • any of the standard of care therapies are combined as part of a treatment regimen or combination therapy.
  • an anti-ILT7 antibody or antigen-binding fragment thereof is administered sequentially with any therapy disclosed herein.
  • an anti-ILT7 antibody or antigen-binding fragment thereof may generally be administered concurrently with any second therapy disclosed herein.
  • a subject in need thereof has been administered any standard of care therapy for the treatment of a myositis disease or disorder prior to the administration of an anti-ILT7 antibody or antigen-binding fragment thereof.
  • an anti-ILT7 antibody or antigen-binding fragment thereof is administered to a subject in need thereof.
  • a subject in need thereof has a myositis disease or disorder.
  • a subject has a myositis disease or disorder, and the disease is dermatomyositis (DM).
  • DM dermatomyositis
  • ASIM anti-synthetase inflammatory myositis
  • a subject in need thereof is treated with a method comprising concurrent administration of an immunomodulatory agent and an anti-ILT7 antibody or antigen-binding fragment thereof.
  • a subject in need thereof is treated with a method comprising concurrent administration of a DMARD and an anti-ILT7 antibody or antigen-binding fragment thereof.
  • a DMARD and an immunomodulatory agent are the same drug.
  • a subject in need thereof is treated with a method comprising concurrent administration of a corticosteroid and an anti-ILT7 antibody or antigen-binding fragment thereof.
  • Methods of the disclosure can comprise tapering of one or more standard of care therapeutics and/or an anti-ILT7 antibody or antigen-binding fragment thereof.
  • a method comprises tapering of a standard of care therapy.
  • a method comprises tapering of a corticosteroid.
  • a method comprises tapering of prednisone. The tapering can occur at any time.
  • tapering occurs before administration of an anti- ILT7 antibody or antigen-binding fragment thereof.
  • tapering occurs concurrent with administration of an anti-ILT7 antibody or antigen-binding fragment thereof.
  • tapering occurs after administration of an anti-ILT7 antibody or antigen-binding fragment thereof.
  • a subject is administered a DMARD.
  • a subject is administered a DMARD in combination with an anti-ILT7 antibody or antigen-binding fragment thereof as disclosed in any of the methods herein.
  • a DMARD is a conventional DMARD (cDMARD).
  • a DMARD is biologic DMARD (bDMARD).
  • Exemplary DMARDS are selected from the group consisting of, but not limited to, methotrexate, sulfasalazine, leflunomide, hydroxychloroquine, Plaquenil, ciclosporin, etanercept, baricitinib, tofacitinib, upadacitinib, infliximab, adalimumab, certolizumab, and golimumab, and combinations thereof.
  • a DMARD is Plaquenil or ciclosporin.
  • a subject is administered an immunomodulatory agent.
  • a subject is administered a immunomodulatory agent in combination with an anti-ILT7 antibody or antigen-binding fragment thereof as disclosed in any of the methods herein.
  • an immunomodulatory agent comprises a cell -modifying agent, an interleukin, or a pathway modifier.
  • an immunomodulatory agent is selected from the group consisting of, but not limited to, rituximab, ofatumumab, obinutuzumab, ibritumomab, azathioprine, abatacept, Belatacept, adalimumab, cyclophosphamide, mycophenolate mofetil, thymoglobulin, alemtuzumab, basiliximab, ciclosporin, sirolimus, tacrolimus, everolimus, and the like.
  • an immunomodulatory agent is azathioprine, ciclosporin, mycophenolate mofetil, or tacrolimus.
  • a subject is administered a corticosteroid.
  • a subject is administered a corticosteroid in combination with an anti-ILT7 antibody or antigen-binding fragment thereof as disclosed in any of the methods herein.
  • a corticosteroid comprises a glucocorticoid.
  • Glucocorticoids are steroid hormones used for the treatment of inflammation, a myositis disease or disorder, and/or cancer. To exert their broad physiological and therapeutic effects, GCs bind to the GC receptor (GR) which belongs to the nuclear receptor superfamily of transcription factors.
  • GR GC receptor
  • one or more GCs are administered to a subject in need thereof.
  • one or more GCs is selected from the group consisting of, but not limited to, triamcinolone, methylprednisolone, budesonide, dexamethasone, triamcinolone, prednisone, hydrocortisone, dexamethasone, betamethasone, prednisolone, deflazacort, and combinations thereof.
  • a GC is prednisone.
  • a GC is methylprednisolone.
  • treatment with a standard of care therapy in combination with an anti- ILT7 antibody or antigen-binding fragment thereof will be more effective in controlling disease activity than maintaining a standard of care therapy alone or replacing a partially effective standard of care therapy with an anti-ILT7 antibody or antigen-binding fragment thereof.
  • treatment with a standard of care therapy in combination with an anti- ILT7 antibody or antigen-binding fragment thereof is effective in reducing disease or a symptom in a subject in need thereof by at least about 1-fold, 10-fold, 50-fold, 100-fold, 200-fold, 500-fold, or up to about 1000-fold as compared to an otherwise comparable subject not administered an anti-ILT7 antibody or antigen-binding fragment thereof.
  • treatment with a standard of care therapy in combination with an anti-ILT7 antibody or antigen-binding fragment thereof is more effective in stabilizing a disease than maintaining a standard of care therapy alone or replacing a partially effective standard of care therapy with an anti-ILT7 antibody or antigen-binding fragment thereof.
  • one or more standard of care therapies are administered for about 1, about 2, about 3, about 4, about 5, about 6, about 7, about 8, about 9, about 10, about 11, about 12, about 13, about 14, about 15, about 20, about 25, about 30, about 35, about 40, about 52, about 52 weeks or more prior to the administration of an anti-ILT7 antibody or antigen- binding fragment thereof.
  • one or more standard of care therapies are administered for about 4 weeks prior to the administration of an anti-ILT7 antibody or antigen-binding fragment thereof.
  • a dose and dosing regimen of an anti-ILT7 antibody or antigen-binding fragment thereof as disclosed herein may be such that any therapeutic effect achieved from administration of an anti-ILT7 antibody or antigen-binding fragment thereof to treat any myositis disease or disorder, may be considered to be “long-lasting.”
  • a “long-lasting” effect of an anti-ILT7 antibody or antigen-binding fragment thereof in a treatment of a myositis disease or disorder is one in which a therapeutic effect achieved by an anti-ILT7 antibody or antigen-binding fragment thereof is maintained (although the anti-ILT7 antibody or antigen-binding fragment thereof is no longer administered) over at least 4 weeks, at least 6 weeks, at least 8 weeks, at least 10 weeks, at least 12 weeks, at least 16 weeks, at least 20 weeks, least 24 weeks, at least 28 weeks, at least 32 weeks, at least 36 weeks, at least 40 weeks, at least 44 weeks, at least 48 weeks, or at least 52 weeks following administration of the last dose of a course of an anti-
  • less frequent dosing of any of the compositions provided herein may be advantageous.
  • Exemplary advantages of less frequent dosing include but are not limited to reduced frequency of side effects associated with an administered composition, reduced treatment-associated toxicity, increased quality of life for treated subjects, and the like.
  • a subject is assessed. In aspects, a subject is assessed as part of a treatment. In aspects, a subject having a confirmed or probable myositis disease or disorder is assessed as part of a treatment.
  • An assessment can occur at any point before, during, or after administration with an anti-ILT7 antibody or antigen-binding fragment thereof. In aspects, an assessment is performed before an administration initiates. In aspects, an assessment is performed concurrent with an administration. In aspects, an assessment is performed after an administration finishes.
  • a subject is assessed, and a baseline measurement of disease is determined.
  • a subject is assessed, and a baseline measurement of disease is determined at any point before, during, or after administration with an anti-ILT7 antibody or antigen-binding fragment thereof.
  • an assessment is performed, and a baseline measurement of disease is determined before an administration with an anti-ILT7 antibody or antigen-binding fragment thereof.
  • an assessment is performed, and a baseline measurement of disease is determined concurrent with an administration of an anti-ILT7 antibody or antigen-binding fragment thereof.
  • an assessment is performed, and a baseline measurement of disease is determined after an administration of an anti-ILT7 antibody or antigen-binding fragment thereof.
  • a baseline measurement of disease increases or decreases in response to an administration of the disclosure or a lack thereof.
  • a baseline measurement of disease may increase and indicate effective treatment of a disease or disorder.
  • a baseline measurement of disease may decrease and indicate effective treatment of a disease or disorder.
  • a baseline measurement of disease increases or decreases after administration with an anti-ILT7 antibody or antigen-binding fragment thereof.
  • a baseline measurement of disease may increase after administration with an anti-ILT7 antibody or antigen-binding fragment and indicate effective treatment of a disease or disorder.
  • a baseline measurement of disease may decrease after administration with an anti-ILT7 antibody or antigen-binding fragment and indicate effective treatment of a disease or disorder.
  • a baseline measurement of disease is compared to the measurement of disease of the subject after administration of the anti-ILT7 antibody or antigen-binding fragment thereof.
  • a measurement of disease of a subject administered an anti- ILT7 antibody or antigen-binding fragment thereof increases as compared to a baseline measurement of disease measured prior to administration with an anti-ILT7 antibody or antigen-binding fragment.
  • a measurement of disease of a subject administered an anti-ILT7 antibody or antigen-binding fragment thereof decreases as compared to a baseline measurement of disease measured prior to administration with an anti-ILT7 antibody or antigen-binding fragment.
  • a measurement of disease of a subject administered an anti-ILT7 antibody or antigen-binding fragment thereof increases as compared to a baseline measurement of disease measured prior to administration with an anti-ILT7 antibody or antigen-binding fragment and indicates effective treatment.
  • a measurement of disease of a subject administered an anti-ILT7 antibody or antigen-binding fragment thereof decreases as compared to a baseline measurement of disease measured prior to administration with an anti-ILT7 antibody or antigen-binding fragment and indicates effective treatment.
  • an assessment comprises determining treatment efficacy. Efficacy can be determined by any of the assessments of the disclosure.
  • effectiveness at preventing, reducing, or eliminating a myositis disease or disorder is determined by detecting a change in baseline in a subject’s blood level of pDCs.
  • effectiveness at preventing, reducing, or eliminating a myositis disease or disorder is determined evaluating: pharmacokinetic parameters of an anti-ILT7 antibody or antigenbinding fragment thereof used to a treat a subject in need thereof, a change in baseline in a subject’s blood level of pDCs, a presence of anti-drug antibodies (ADA), and combinations thereof.
  • ADA anti-drug antibodies
  • effectiveness at preventing, reducing, or eliminating a myositis disease or disorder is determined by determining pharmacokinetic parameters of an anti-ILT7 antibody or antigen-binding fragment thereof used to a treat a subject in need thereof. In aspects, effectiveness at preventing, reducing, or eliminating a myositis disease or disorder is determined by determining a change in baseline in a subject’s blood level of pDCs. In aspects, effectiveness at preventing, reducing, or eliminating a myositis disease or disorder is determined by determining a presence of ADA. In aspects, a myositis disease or disorder comprises DM or ASIM.
  • any of the below-referenced assessments can occur at any time.
  • a subject is assessed by the minute, hourly, daily, weekly, monthly, quarterly, or yearly.
  • an assessment is completed twice daily, biweekly, bimonthly, or semiannually.
  • an assessment is performed from day -28, -27, -26, -25, -24, -23, -22, - 21, -20, -19, -18, -17, -16, -15, -14, -13, -12, -11, -10, -9, -8, -7, -6, -5, -4, -3, -2, -1, 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82,
  • a subject in need thereof is assessed prior to beginning treatment.
  • An exemplary assessment or inclusion criterion comprises a subject having one or more chronic (i.e., stable) myositis diseases or disorders.
  • a subject in need thereof may be either male or female. In aspects, a subject in need thereof is an adult subject. In aspects, a subject in need thereof may be aged between about 18 and 75 years of age.
  • a subject in need thereof has a diagnosis of definite or probable myositis.
  • a subject in need thereof has a diagnosis of definite or probable myositis according to American College of Rheumatology (ACR) criteria.
  • ACR American College of Rheumatology
  • EULAR European League against Rheumatism
  • a subject in need thereof has a diagnosis of definite or probable myositis according to European League against Rheumatism (EULAR) 2017 criteria.
  • a total aggregated score for ACR or EULAR 2017 is > 5.5 without a muscle biopsy.
  • a total aggregated score for ACR or EULAR 2017 is > 6.7 with muscle biopsy.
  • a subject in need thereof is not assessed by the ACR or EULAR 2017 criteria but does have a pathognomonic skin rash (e.g., heliotrope rash, Gottron’s papules and/or Gottron’s sign).
  • Idiopathic inflammatory myopathies such as myositis
  • dermatomyositis including amyopathic dermatomyositis
  • ASIM anti synthetase inflammatory myositis
  • immune-mediated necrotizing myopathy inclusion body myositis
  • polymyositis includes ASIM and other forms of inflammatory myositis.
  • a subject in need thereof may have a probable or definite myositis diagnosis that comprises, but is not limited to: dermatomyositis (DM), anti-synthetase inflammatory myositis (ASIM), polymyositis, or both DM and ASIM, or DM and polymyositis.
  • DM dermatomyositis
  • ASIM anti-synthetase inflammatory myositis
  • polymyositis or both DM and ASIM, or DM and polymyositis.
  • a subject in need thereof has a diagnosis of DM.
  • a subject in need thereof has a diagnosis of DM with a current DM rash prior to treatment initiation.
  • a subject in need thereof has a diagnosis of DM with a historical DM rash prior to treatment initiation.
  • a subject in need thereof has a diagnosis of ASIM.
  • a subject in need thereof has a diagnosis of ASIM and tests positive for anti-Jo-1 antibodies prior to treatment initiation.
  • a subject in need thereof has a diagnosis of ASIM and has historically tested positive for anti-PL-12, anti-PL-7, anti-KS, anti-EJ, anti-OJ, anti- ZO, or anti-YRS(HA) antibodies prior to treatment initiation.
  • a subject in need thereof has a manual muscle testing (MMT8) score ⁇ 142, at least two abnormal core set measures (CSM), and a global muscle damage score ⁇ 5 on a 10 cm VAS on the myositis damage index (MDI) prior to treatment initiation.
  • two CSM are selected from the group consisting of: PtGDA > 2 cm in a 10 cm visual analog scale (VAS), Physician’s Global Disease Activity (PhGDA) > 2 cm in a 10 cm VAS, extramuscular activity > 2cm in a 10 cm VAS, at least one muscle enzyme 1.5 times upper limit of normal (ULN), and health assessment questionnaire-disability index (HAQ-DI) > 0.5.
  • PtGDA 2 cm in a 10 cm visual analog scale
  • PhGDA Global Disease Activity
  • extramuscular activity > 2cm in a 10 cm VAS
  • HAQ-DI health assessment questionnaire-disability index
  • a subject in need thereof may have prior and/or concomitant therapy for treatment of a myositis disorder at the time of treatment initiation.
  • a subject in need thereof may have stable dosing of azathioprine, tacrolimus, ciclosporin, plaquenil, and/or mycophenolate mofetil for at least 4 weeks prior to treatment initiation.
  • a subject in need thereof may have stable dosing of methotrexate for at least 4 weeks prior to treatment initiation.
  • a subject in need thereof may have stable dosing of corticosteroids (e.g., prednisone or methylprednisolone) for at least 4 weeks prior to treatment initiation.
  • corticosteroids e.g., prednisone or methylprednisolone
  • an assessment comprises determining a level of immunogenicity, if any, of an anti-ILT7 antibody or antigen-binding fragment thereof of the disclosure.
  • Immunogenicity comprises determining the presence of anti-drug antibodies (ADA) to an anti-ILT7 antibody or antigen-binding fragment thereof.
  • ADA anti-drug antibodies
  • the presence of ADA can be evaluated using a plasma sample from a subject administered an anti-ILT7 antibody or antigen-binding fragment thereof.
  • ADA are not detected post administration of an anti-ILT7 antibody or antigen-binding fragment thereof.
  • ADA levels are reduced as compared to an otherwise comparable method wherein the subject of the otherwise comparable method is not administered an anti-ILT7 antibody or antigen-binding fragment thereof; for example, the reduction may be about: 10%, 15%, 20%, 25%, 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, 99%, or up to 100% as compared to ADA levels in an otherwise comparable method wherein the subject of the otherwise comparable method is not administered an anti-ILT7 antibody or antigen-binding fragment thereof.
  • determining ADA levels to an anti-ILT7 antibody or antigen-binding fragment thereof can be assessed on about -28 days, -27 days, -26 days, -25 days, -24 days, -23 days, -22 days, -21 days, -20 days, -19 days, -18 days, -17 days, -16 days, -15 days, -14 days, -13 days, -12 days, -11 days, -10 days, -9 days, -8 days, -7 days, -6 days, -5 days, -4 days, -3 days, -2 days, -1 day, 0 day, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, 20 weeks, 21 weeks, 22 weeks, 23 weeks, 24 weeks, 25 weeks, 26 weeks, 27 weeks, 28 weeks,
  • determining ADA levels to an anti-ILT7 antibody or antigen-binding fragment thereof can be assessed on about Day 1, Week 4 ⁇ 3 days, Week 12 ⁇ 3 days, Week 24 ⁇ 3 days, Week 28 ⁇ 3 days, Week 36 ⁇ 3 days, Week 48 ⁇ 3 days, and Week 56 ⁇ 7 days post treatment initiation.
  • an assessment can comprise assessing a skin microbiome.
  • a skin microbiome is sampled using a skin swab.
  • a profile of skin microbiome is collected and compared to a baseline level.
  • a skin microbiome profile changes by at least about 0.5 fold, 1 fold, 1.5 fold, 1-fold, 2-fold, 3-fold, 4-fold, 5-fold, 10-fold, 20- fold, 40-fold, 60-fold, 80-fold, 100-fold, 120-fold, 140-fold, 160-fold, 180-fold, 200-fold, 220-fold, 240-fold, 260-fold, 280-fold, or up to about 300-fold post administration as compared to baseline.
  • Suitable methods to assess a skin microbiome may comprise qPCR, DNAseq, RNAseq, and exome sequencing, and combinations thereof.
  • determining a change in a profile of a skin microbiome to an anti-ILT7 antibody or antigen-binding fragment thereof can be assessed on about -28 days, -27 days, -26 days, -25 days, -24 days, -23 days, -22 days, -21 days, -20 days, -19 days, -18 days, -17 days, -16 days, -15 days, -14 days, -13 days, -12 days, -11 days, -10 days, -9 days, -8 days, -7 days, -6 days, -5 days, -4 days, -3 days, -2 days, -1 day, 0 day, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, 20 weeks, 21 weeks, 22 weeks, 23 weeks, 24 weeks, 25
  • an assessment comprises quantifying expression levels of genes or gene pathways associated with disease activity by way of whole blood transcriptomics.
  • whole blood transcriptomics may be assessed via RNA isolation from whole blood.
  • RNA testing may be performed to assess changes over time in the expression of genes or gene pathways associated with myositis, mechanism of action of or in response to an anti-ILT7 antibody or antigen-binding fragment thereof administration, or the pathogenesis of myositis.
  • RNA may be isolated at baseline from whole blood to test for changes in expression levels of the genes or gene pathways associated with disease activity.
  • transcriptome profiling is assessed by methods including, but not limited to, qPCR, RNAseq, and exome sequencing.
  • expression levels of genes associated with disease activity by way of RNA analysis may be reduced by at least about 1-fold, 2-fold, 3-fold, 4-fold, 5-fold, 10-fold, 20-fold, 40-fold, 60-fold, 80-fold, 100-fold, 120-fold, 140-fold, 160-fold, 180-fold, 200- fold, 220-fold, 240-fold, 260-fold, 280-fold, or up to about 300-fold post administration as compared to an otherwise comparable method wherein the subject of the otherwise comparable method is not administered an anti-ILT7 antibody or antigen-binding fragment thereof.
  • expression levels of genes associated with disease activity by way of RNA analysis may be reduced by at least about 10%, 15%, 20%, 25%, 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, 99%, or up to 100% as compared to an otherwise comparable method wherein the subject of the otherwise comparable method is not administered an anti-ILT7 antibody or antigen-binding fragment thereof.
  • determining expression levels of genes associated with disease activity by way of RNA analysis to an anti-ILT7 antibody or antigen-binding fragment thereof can be assessed on about -28 days, -27 days, -26 days, -25 days, -24 days, -23 days, -22 days, -
  • determining expression levels of genes associated with disease activity by way of RNA analysis to an anti-ILT7 antibody or antigen-binding fragment thereof can be assessed on about Day 1, Week 4 ⁇ 3 days, Week 12 ⁇ 3 days, Week 24 ⁇ 3 days, Week 36 ⁇ 3 days, Week 48 ⁇ 3 days, and Week 56 ⁇ 7 days post treatment initiation.
  • whole blood samples may be collected and may be assessed by way of RNA analysis.
  • whole blood samples may be collected and may be assessed by way of metabolomics.
  • whole blood samples may be collected and may be assessed by way of proteomics.
  • whole blood samples may be collected and assessed by way RNA analysis, metabolomics, and/or proteomics.
  • an assessment comprises determining the sequence of genes associated with disease activity by way of whole blood DNA analysis.
  • DNA testing may be performed to assess changes over time in the sequence of genes, including: single nucleotide polymorphisms (SNPs) associated with the development of myositis (e.g., DM or ASIM) or Fc gamma receptor in genes that may be related to the mechanism of action of an anti-ILT7 antibody or antigen-binding fragment thereof.
  • whole blood can be collected and may be used to evaluate gene sequences before, during, and after treatment with any of the compositions provided herein. Gene sequences found to be modulated by treatment may be analyzed in whole blood using quantitative methods. Samples may be used to examine gene sequences and their changes over time as assessed by NGS, Sanger Sequencing, or PCR.
  • determining changes in gene sequences associated with disease activity and/or treatment efficacy by way of DNA analysis to an anti-ILT7 antibody or antigenbinding fragment thereof can be assessed on about -28 days, -27 days, -26 days, -25 days, - 24 days, -23 days, -22 days, -21 days, -20 days, -19 days, -18 days, -17 days, -16 days, -15 days, -14 days, -13 days, -12 days, -11 days, -10 days, -9 days, -8 days, -7 days, -6 days, -5 days, -4 days, -3 days, -2 days, -1 day, 0 day, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days,
  • determining changes in gene sequences associated with disease activity and/or treatment efficacy by way of DNA analysis to an anti-ILT7 antibody or antigen-binding fragment thereof can be assessed on about Day 1 post treatment initiation.
  • a method provided herein can comprise determining a concentration of an anti-ILT7 antibody or antigen-binding fragment thereof in a subject in need thereof post administration.
  • a method comprises a pharmacokinetic assessment.
  • a sample is a blood sample or a plasma sample, or a combination of both.
  • a suitable assay to measure pharmacokinetics may comprise electrochemiluminescence (ECL) assay, a bead-based assay, a cell-based assay, and combinations thereof.
  • ECL electrochemiluminescence
  • a sample may comprise plasma and the plasma is assessed for an anti-ILT7 antibody or antigen-binding fragment thereof concentration by measuring: maximum observed concentration (Cmax), area under the concentration-time curve (AUC), clearance (CL), and terminal elimination half-life (ti/2).
  • Cmax maximum observed concentration
  • AUC area under the concentration-time curve
  • CL clearance
  • ti/2 terminal elimination half-life
  • a pharmacokinetic assessment to an anti-ILT7 antibody or antigenbinding fragment thereof can be assessed on about -28 days, -27 days, -26 days, -25 days, - 24 days, -23 days, -22 days, -21 days, -20 days, -19 days, -18 days, -17 days, -16 days, -15 days, -14 days, -13 days, -12 days, -11 days, -10 days, -9 days, -8 days, -7 days, -6 days, -5 days, -4 days, -3 days, -2 days, -1 day, 0 day, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days,
  • a pharmacokinetic assessment to an anti-ILT7 antibody or antigen-binding fragment thereof can be assessed on about Day 1, Week 4 ⁇ 3 days, Week 8 ⁇ 3 days, Week 12 ⁇ 3 days, Week 16 ⁇ 3 days, Week 24 ⁇ 3 days, Week 36 ⁇ 3 days, Week 48 ⁇ 3 days, and Week 56 ⁇ 7 days post treatment initiation.
  • a method comprises a pharmacodynamic assessment.
  • an assessment can occur over a period of time.
  • a sample comprises a blood sample, serum sample, plasma sample, skin sample, or muscle sample.
  • a muscle biopsy location may be identified by MRI.
  • a muscle biopsy may be taken via non- invasive surgery (e.g., biopsy needle) or invasive surgery (i.e., open biopsy).
  • a skin biopsy may be taken by punch biopsy.
  • a method provided herein can comprise determining an amount of reduction or elimination of biomarkers, including but not limited to, pDCs, IFN-a, myxovirus resistance protein A (MxA), IFN gene signatures, and peripheral blood mononuclear cells (PBMCs), by an anti-ILT7 antibody or antigen-binding fragment thereof in a subject in need thereof post administration.
  • biomarkers including but not limited to, pDCs, IFN-a, myxovirus resistance protein A (MxA), IFN gene signatures, and peripheral blood mononuclear cells (PBMCs)
  • a reduction of biomarkers may be detected as compared to an otherwise comparable method wherein the subject of the otherwise comparable method is not administered an anti-ILT7 antibody or antigen-binding fragment thereof.
  • elimination of a biomarker may be detected as compared to an otherwise comparable method wherein the subject of the otherwise comparable method is not administered an anti-ILT7 antibody or antigen-binding fragment thereof as compared to an otherwise comparable method lacking the administering of an anti-ILT7 antibody or antigen-binding fragment thereof.
  • reduction of a biomarker comprises at least about or at most about: 1-fold, 2-fold, 3-fold, 4-fold, 5-fold, 10-fold, 15-fold, 20-fold, 25- fold, 30-fold, 35-fold, 40-fold, 45-fold, 50-fold, 55-fold, 60-fold, 65-fold, 70-fold, 75-fold, 80-fold, 85-fold, 90-fold, 95-fold, 100-fold, 105-fold, 110-fold, 115-fold, 120-fold, 125- fold, 130-fold, 135-fold, 140-fold, 145-fold, 150-fold, 155-fold, 160-fold, 165-fold, 170- fold, 175-fold, 180-fold, 185-fold, 19-fold, 195-fold, 200-fold, 210-fol, 220-fold, 230-fold, 240-fold, 250-fold, 260-fold, 270-fold, 280-fold, 290-fold, or up to about 300-fold reduction as compared to
  • treatment efficacy of an anti-ILT7 antibody or antigen-binding fragment thereof on a biomarker can be assessed over time using a suitable immunoassay.
  • effects of an anti-ILT7 antibody or antigen-binding fragment thereof are assessed over time using a qualified immunoassay.
  • the disclosure provides for an anti-ILT7 antibody containing compositions that efficiently reduce or deplete pDCs in a subject. Because an anti-ILT7 antibody or antigenbinding fragment thereof binds to and depletes a biomarker, the reduction or elimination can be used as a measure of treatment efficacy. In aspects, total pDCs is a measure of target engagement. Suitable assays to assess pDCs levels may comprise flow cytometry, histology, immunohistochemistry, blood analysis, microscopy, PCR, ELISA, and combinations thereof.
  • the disclosure provides for an anti-ILT7 antibody or antigen-binding fragment thereof containing compositions that efficiently reduce or eliminate blood MxA levels, cytokines, chemokines, or other proteins (e.g., IFN-a, IL-17, and IFN-y), PBMCs, or IFN gene signature levels, or a combinations thereof, in a subject.
  • changes in blood MxA levels, cytokines, chemokines, or other proteins may be related to the pathogenesis of myositis, or the action of an anti-ILT7 antibody or antigen-binding fragment thereof.
  • Suitable assays to assess blood MxA levels, cytokines, chemokines, or other proteins may comprise flow cytometry, histology, immunohistochemistry, blood analysis, microscopy, PCR, ELISA, and combinations thereof.
  • an anti-ILT7 antibody or antigen-binding fragment thereof may achieve at least about 10%, 15%, 20%, 25%, 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, 99%, or up to about 100% reduction in pDCs levels as compared to an otherwise comparable method wherein the subject of the otherwise comparable method is not administered an anti- ILT7 antibody or antigen-binding fragment thereof.
  • Reduction or elimination of pDCs, blood MxA levels, cytokines, chemokines, or other proteins (e.g., IFN-a, IL- 17, and IFN- y), PBMCs, or IFN gene signature levels, or a combination thereof, may persist for extended periods of time.
  • depletion of pDCs, blood MxA levels, cytokines, chemokines, or other proteins (e.g., IFN-a, IL-17, and IFN-y), PBMCs, or IFN gene signature levels, or a combination thereof may persist for at least 1 day, at least 2 days, at least 3 days, at least 4 days, at least 5 days, at least 6 days, at least 7 days, at least 8 days, at least 9 days, at least
  • depletion of pDCs, blood MxA levels, cytokines, chemokines, or other proteins (e.g., IFN-a, IL-17, and IFN-y), PBMCs, or IFN gene signature levels, or a combination thereof, may persist for at least 1 week, at least 2 weeks, at least 3 weeks, at least 4 weeks, at least 5 weeks, at least 6 weeks, at least 7 weeks, at least 8 weeks, at least 9 weeks, or at least 10 weeks.
  • depletion of pDCs, blood MxA levels, cytokines, chemokines, or other proteins (e.g., IFN-a, IL- 17, and IFN-y), PBMCs, or IFN gene signature levels, or a combination thereof may persist for at least 1 month, at least 2 months, at least 3 months, at least 4 months, at least 5 months, at least 6 months, at least 7 months, at least 8 months, at least 9 months, at least 10 months, at least 11 months, or at least 12 months.
  • a pharmacodynamic assessment to an anti-ILT7 antibody or antigenbinding fragment thereof can be assessed on about -28 days, -27 days, -26 days, -25 days, - 24 days, -23 days, -22 days, -21 days, -20 days, -19 days, -18 days, -17 days, -16 days, -15 days, -14 days, -13 days, -12 days, -11 days, -10 days, -9 days, -8 days, -7 days, -6 days, -5 days, -4 days, -3 days, -2 days, -1 day, 0 day, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks,
  • a pharmacodynamic assessment to an anti-ILT7 antibody or antigen-binding fragment thereof can be assessed on about Day -28, Day -27, Day -26, Day -25, Day -24, Day -23, Day -22, Day -21, Day -20, Day -19, Day -18, Day -17, Day -16, Day -15, Day -14, Day - 13, Day -12, Day -11, Day -10, Day -9, Day -8, Day -7, Day -6, Day -5, Day -4, Day -3, Day -2, Day -1, Day 0, Day 1, Week 4 ⁇ 3 days, Week 12 ⁇ 3 days, Week 24 ⁇ 3 days, Week
  • HAQ-DI Health Assessment Questionnaire-Disability Index
  • an assessment comprises HAQ-DI.
  • HAQ-DI assesses physical function of a subject in need thereof (HAQ-DI Form 05a).
  • HAQ-DI may be scored from about 0, 1, 2, or up to about 3.
  • a HAQ-DI score is at least about 0, about 1, about 2, or about 3.
  • HAQ-DI may comprise 8 sections: dressing and grooming, arising, eating, walking, hygiene, reach, grip, and common daily activities.
  • each section is scored from 0 (without any difficulty) to 3 (unable to do).
  • a HAQ-DI assessment may comprise assessing a subject in need thereof administered an anti-ILT7 antibody or antigen-binding fragment thereof as compared to baseline.
  • a subj ect’ s HAQ-DI score is reduced as compared to an otherwise comparable method wherein the subject of the otherwise comparable method is not administered an anti-ILT7 antibody or antigen-binding fragment thereof.
  • a HAQ-DI assessment to an anti-ILT7 antibody or antigen-binding fragment thereof can be assessed on about -28 days, -27 days, -26 days, -25 days, -24 days, -23 days, -22 days, -21 days, -20 days, -19 days, -18 days, -17 days, -16 days, -15 days, -14 days, -13 days, -12 days, -11 days, -10 days, -9 days, -8 days, -7 days, -6 days, -5 days, -4 days, -3 days, -2 days, -1 day, 0 day, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, 20 weeks, 21 weeks, 22 weeks, 23 weeks, 24 weeks, 25 weeks, 26 weeks, 27 weeks,
  • a HAQ- DI assessment to an anti-ILT7 antibody or antigen-binding fragment thereof can be assessed on about Day -28, Day -27, Day -26, Day -25, Day -24, Day -23, Day -22, Day -21, Day - 20, Day -19, Day -18, Day -17, Day -16, Day -15, Day -14, Day -13, Day -12, Day -11, Day -10, Day -9, Day -8, Day -7, Day -6, Day -5, Day -4, Day -3, Day -2, Day -1, Day 0, Day 1, Week 4 ⁇ 3 days, Week 8 ⁇ 3 days, Week 12 ⁇ 3 days, Week 16 ⁇ 3 days, Week 20 ⁇ 3 days, Week 24 ⁇ 3 days, Week 28 ⁇ 3 days, Week 32 ⁇ 3 days, Week 36 ⁇ 3 days, Week 40 ⁇ 3 days, Week 44 ⁇ 3 days, Week 48 ⁇ 3 days, and Week 56 ⁇ 7 days post treatment initiation.
  • an assessment comprises MMT8 bilateral.
  • MMT8 bilateral is a set of 8 designated muscles tested bilaterally (MMT8, 2007).
  • axial (neck flexors) testing is included, so the potential MMT8 score is up to about at least 150.
  • MMT8 bilateral may be scored from about 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13,
  • MMT8 bilateral is from about 0-10, about 10-30, about 20-40, about 30-50, about 40-60, about 50-70, about 60-80, about 70-90, about 80-100, about 90-110, about 100-120, about 110-130, about 120-140, or about 130- 150.
  • a MMT8 bilateral assessment may comprise assessing a subject in need thereof administered an anti-ILT7 antibody or antigen-binding fragment thereof as compared to baseline.
  • a subject’s MMT8 bilateral score is increased as compared to an otherwise comparable method wherein the subject of the otherwise comparable method is not administered an anti-ILT7 antibody or antigen-binding fragment thereof.
  • a MMT8 bilateral assessment to an anti-ILT7 antibody or antigen-binding fragment thereof can be assessed on about -28 days, -27 days, -26 days, -25 days, -24 days, -23 days, -22 days, -21 days, -20 days, -19 days, -18 days, -17 days, -16 days, -15 days, -14 days, -13 days, - 12 days, -11 days, -10 days, -9 days, -8 days, -7 days, -6 days, -5 days, -4 days, -3 days, -2 days, -1 day, 0 day, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, 20 weeks, 21 weeks, 22 weeks, 23 weeks, 24 weeks, 25 weeks, 26 weeks, 27 weeks,
  • a MMT8 bilateral assessment to an anti-ILT7 antibody or antigen-binding fragment thereof can be assessed on about Day -28, Day -27, Day -26, Day -25, Day -24, Day -23, Day -22, Day -21, Day -20, Day -19, Day -18, Day -17, Day -16, Day -15, Day -14, Day -13, Day -12, Day - 11, Day -10, Day -9, Day -8, Day -7, Day -6, Day -5, Day -4, Day -3, Day -2, Day -1, Day 0, Day 1, Week 4 ⁇ 3 days, Week 8 ⁇ 3 days, Week 12 ⁇ 3 days, Week 16 ⁇ 3 days, Week 20 ⁇ 3 days, Week 24 ⁇ 3 days, Week 28 ⁇ 3 days, Week 32 ⁇ 3 days, Week 36 ⁇ 3 days, Week 40 ⁇ 3 days, Week 44 ⁇ 3 days, Week 48 ⁇ 3 days, and Week 56 ⁇ 7 days post treatment initiation.
  • MDAAT Global Myositis Disease Activity Assessment Tool
  • PtGDA Patient Global Disease Activity
  • an assessment comprises global MDAAT.
  • Global MDAAT measures the degree of disease activity of extramuscular organ systems and muscles (MDAAT, 2005).
  • global MDAAT may include, but is not limited to, an assessment of physician global disease activity (PhGDA) and an extramuscular global assessment.
  • PhGDA is a physician’s evaluation of overall disease activity (extramuscular organ systems plus muscle disease activity) based on clinical laboratory assessments.
  • global MDAAT may be scored from about 0, about 1, about 2, about 3, and up to about 4.
  • global MDAAT is scored from about 0-4 or about 1-4.
  • PhGDA may be scored using a 10 cm VAS that ranges from 0 (no evidence of disease activity) to 4 (extremely severe disease activity).
  • an extramuscular global assessment evaluates disease activity in all extramuscular systems (excluding muscle disease activity) using a 10 cm VAS that ranges from 0 (no evidence of disease activity) to 4 (extremely severe disease activity).
  • a global MDAAT assessment uses an activity index that range from 0 (“not present in the last 4 weeks”) to 4 (“new in the last four weeks”).
  • a global MDAAT assessment may comprise assessing a subject in need thereof administered an anti-ILT7 antibody or antigen-binding fragment thereof as compared to baseline.
  • a subject’s global MDAAT score is reduced as compared to an otherwise comparable method wherein the subject of the otherwise comparable method is not administered an anti-ILT7 antibody or antigen-binding fragment thereof.
  • a MDAAT assessment to an anti-ILT7 antibody or antigen-binding fragment thereof can be assessed on about -28 days, -27 days, -26 days, -25 days, -24 days, -23 days, -22 days, -21 days, -20 days, -19 days, -18 days, -17 days, -16 days, -15 days, -14 days, -13 days, -12 days, -11 days, -10 days, -9 days, -8 days, -7 days, -6 days, -5 days, -4 days, -3 days, -2 days, -1 day, 0 day, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10
  • a MDAAT assessment to an anti-ILT7 antibody or antigen-binding fragment thereof can be assessed on about Day -28, Day -27, Day -26, Day -25, Day -24, Day -23, Day -22, Day - 21, Day -20, Day -19, Day -18, Day -17, Day -16, Day -15, Day -14, Day -13, Day -12, Day -11, Day -10, Day -9, Day -8, Day -7, Day -6, Day -5, Day -4, Day -3, Day -2, Day -1, Day 0, Day 1, Week 4 ⁇ 3 days, Week 8 ⁇ 3 days, Week 12 ⁇ 3 days, Week 16 ⁇ 3 days, Week 20 ⁇ 3 days, Week 24 ⁇ 3 days, Week 28 ⁇ 3 days, Week 32 ⁇ 3 days, Week 36 ⁇ 3 days, Week 40 ⁇ 3 days, Week 44 ⁇ 3 days, Week 48 ⁇ 3 days, and Week 56 ⁇ 7 days post treatment initiation.
  • an assessment comprises patient global disease activity (PtGDA).
  • PtGDA measures the global evaluation by the patient of the patient’s overall disease activity at the time of assessment (PtGDA Form 03).
  • a PtGDA assessment is scored from about 1, 2, 3, 4, 5, 6, 7, 8, 9, up to about 10.
  • PtGDA assessment is scored from about 0-10, about 1-5, about 4-10, or about 1-10.
  • PtGDA may be measured using a 10 cm visual analog scale (VAS) that ranges from “no evidence of disease activity” to “extreme active or severe disease activity.”
  • VAS 10 cm visual analog scale
  • a PtGDA assessment may comprise assessing a subject in need thereof administered an anti-ILT7 antibody or antigen-binding fragment thereof as compared to baseline.
  • a subject s PtGDA score is reduced as compared to an otherwise comparable method wherein the subject of the otherwise comparable method is not administered an anti-ILT7 antibody or antigen-binding fragment thereof.
  • a PtGDA assessment to an anti-ILT7 antibody or antigen-binding fragment thereof can be assessed on about -28 days, -27 days, -26 days, -25 days, -24 days, -23 days, -22 days, -21 days, -20 days, -19 days, -18 days, -17 days, -16 days, -15 days, -14 days, -13 days, -12 days, -11 days, -10 days, -9 days, -8 days, -7 days, -6 days, -5 days, -4 days, -3 days, -2 days, -1 day, 0 day, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, 20 weeks, 21 weeks, 22 weeks, 23 weeks, 24 weeks, 25 weeks, 26 weeks, 27 weeks, 28
  • a PtGDA assessment to an anti-ILT7 antibody or antigen-binding fragment thereof can be assessed on about Day -28, Day -27, Day -26, Day -25, Day -24, Day -23, Day -22, Day -21, Day -20, Day -19, Day -18, Day -17, Day -16, Day -15, Day -14, Day -13, Day -12, Day -11, Day - 10, Day -9, Day -8, Day -7, Day -6, Day -5, Day -4, Day -3, Day -2, Day -1, Day 0, Day 1, Week 4 ⁇ 3 days, Week 8 ⁇ 3 days, Week 12 ⁇ 3 days, Week 16 ⁇ 3 days, Week 20 ⁇ 3 days, Week 24 ⁇ 3 days, Week 28 ⁇ 3 days, Week 32 ⁇ 3 days, Week 36 ⁇ 3 days, Week 40 ⁇ 3 days, Week 44 ⁇ 3 days, Week 48 ⁇ 3 days, and Week 56 ⁇ 7 days post treatment initiation.
  • an assessment comprises measuring a level of a muscle-associated enzyme.
  • Muscle-associated enzymes assessed may include, but are not limited to, alanine transaminase (ALT), aspartate transaminase (AST), lactate dehydrogenase (LDH), creatine kinase (CK), and aldolase, and combinations thereof.
  • whole blood, plasma, serum, and urine are collected to assessed levels of muscle-associated enzymes.
  • assessing a level of a muscle-associated enzyme may comprise assessing a subject in need thereof administered an anti-ILT7 antibody or antigen-binding fragment thereof as compared to baseline.
  • administration of an anti-ILT7 antibody or antigen-binding fragment thereof of the disclosure is effective in reducing a level of a muscle-associated enzyme in a subject by at least about or at most about 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or up to about 100% of the level prior the administration.
  • administration of an anti-ILT7 antibody or antigen-binding fragment thereof of the disclosure is effective in reducing a level of a muscle-associated enzyme in a subject by at least about or at most about: 3%-5%, 5%-l 0%, 10%-20%, or 5%- 25% as compared to a baseline level prior to the administration.
  • an assessment of a level of a muscle-associated enzyme to an anti-ILT7 antibody or antigen-binding fragment thereof can be assessed on about -28 days, -27 days, -26 days, -25 days, -24 days, -23 days, -22 days, -21 days, -20 days, -19 days, -18 days, -17 days, -16 days, -15 days, -14 days, -13 days, -12 days, -11 days, -10 days, -9 days, -8 days, -7 days, -6 days, -5 days, -4 days, -3 days, -2 days, -1 day, 0 day, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, 20 weeks, 21 weeks, 22 weeks, 23 weeks, 24 weeks, 25 weeks, 26
  • an assessment of a level of a muscle-associated enzyme to an anti-ILT7 antibody or antigen-binding fragment thereof can be assessed on about Day - 28, Day -27, Day -26, Day -25, Day -24, Day -23, Day -22, Day -21, Day -20, Day -19, Day -18, Day -17, Day -16, Day -15, Day -14, Day -13, Day -12, Day -11, Day -10, Day -9, Day -8, Day -7, Day -6, Day -5, Day -4, Day -3, Day -2, Day -1, Day 0, Day 1, Week 4 ⁇ 3 days, Week 8 ⁇ 3 days, Week 12 ⁇ 3 days, Week 16 ⁇ 3 days, Week 20 ⁇ 3 days, Week 24 ⁇ 3 days, Week 28 ⁇ 3 days, Week 32 ⁇ 3 days, Week 36 ⁇ 3 days, Week 40 ⁇ 3 days, Week 44 ⁇ 3 days, Week 48 ⁇ 3 days, and Week 56 ⁇ 7 days post treatment initiation.
  • an assessment comprises a CDASI measurement.
  • a CDASI measurement may be used to assess the severity of cutaneous DM and detect improvement in disease activity.
  • CDASI may be scored from about 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12,
  • CDASI is scored from about 0-10, about 1-10, about 0-30, about 1-30, about 10-30, about 0-40, about 1-40, about 20-40, about 30-50, about 40-60, about 50-70, about 60-80, about 70-90, about 0-100, about 1-100, or about 80-100.
  • a CDASI activity scale may range from 0-100 and the damage scale may range from 0-32.
  • the CDASI scale may rate disease involvement in 15 different body areas using 3 activity (erythema, scale, and erosion/ulceration) and 2 damage (poikiloderma and calcinosis) measures.
  • a CDASI measurement may assess the presence and severity of Gottron’s papules on the hands, periungual changes, alopecia, or combinations thereof.
  • a CDASI assessment may comprise assessing a subject in need thereof administered an anti-ILT7 antibody or antigen-binding fragment thereof as compared to baseline.
  • a subj ect’ s CDASI score is reduced as compared to an otherwise comparable method wherein the subject of the otherwise comparable method is not administered an anti-ILT7 antibody or antigen-binding fragment thereof.
  • a CDASI measurement to an anti-ILT7 antibody or antigen-binding fragment thereof can be assessed on about -28 days, -27 days, -26 days, -25 days, -24 days, -23 days, -22 days, -21 days, -20 days, -19 days, -18 days, -17 days, -16 days, -15 days, -14 days, -13 days, -12 days, -11 days, -10 days, -9 days, -8 days, -7 days, -6 days, -5 days, -4 days, -3 days, -2 days, -1 day, 0 day, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, 20 weeks, 21 weeks, 22 weeks, 23 weeks, 24 weeks, 25 weeks, 26 weeks, 27 weeks, 28 weeks
  • a CDASI measurement to an anti-ILT7 antibody or antigen-binding fragment thereof can be assessed on about Day 1, Week 4 ⁇ 3 days, Week 8 ⁇ 3 days, Week 12 ⁇ 3 days, Week 24 ⁇ 3 days, Week 36 ⁇ 3 days, and Week 48 ⁇ 3 days post treatment initiation.
  • MDI Myositis Damage Index
  • an assessment comprises an MDI survey.
  • An MDI survey may be used to assess the degree of disease damage of all organ systems (MDI Form 08, 2001).
  • an MDI survey may comprise a series of organ-specific questions relating to the presence or absence of a given sign or symptom or problem to measure the extent of damage.
  • an MDI survey is scored from about 0, 1, 2, 3, up to about 4.
  • an MDI survey is scored from about 0-4, or about 1-4.
  • an MDI survey is scored using a 10 cm VAS to measure the severity of damage from 0 (“no evidence of disease”) to 4 (“extreme or maximum disease damage”).
  • an MDI survey may comprise assessing a subject in need thereof administered an anti-ILT7 antibody or antigen-binding fragment thereof as compared to baseline.
  • a subject s MDI score is reduced as compared to an otherwise comparable method wherein the subject of the otherwise comparable method is not administered an anti-ILT7 antibody or antigen-binding fragment thereof.
  • an MDI survey to an anti-ILT7 antibody or antigen-binding fragment thereof can be assessed on about -28 days, -27 days, -26 days, -25 days, -24 days, -23 days, -22 days, -21 days, -20 days, -19 days, -18 days, -17 days, -16 days, -15 days, -14 days, -13 days, -12 days, -11 days, -10 days, -9 days, -8 days, -7 days, -6 days, -5 days, -4 days, -3 days, -2 days, -1 day, 0 day, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, 20 weeks, 21 weeks, 22 weeks, 23 weeks, 24 weeks, 25 weeks, 26 weeks, 27 weeks, 28 weeks, 29
  • an MDI survey to an anti-ILT7 antibody or antigen-binding fragment thereof can be assessed on about Day - 28, Day -27, Day -26, Day -25, Day -24, Day -23, Day -22, Day -21, Day -20, Day -19, Day -18, Day -17, Day -16, Day -15, Day -14, Day -13, Day -12, Day -11, Day -10, Day -9, Day -8, Day -7, Day -6, Day -5, Day -4, Day -3, Day -2, Day -1, Day 0, Day 1, Week 24 ⁇ 3 days, and Week 48 ⁇ 3 days post treatment initiation.
  • an assessment comprises a myositis FI3 assessment.
  • a myositis FI3 assessment may be used to assess the functional outcome of muscle endurance and function of frequently affected muscle groups (MFI3 2016).
  • a myositis FI3 assessment is scored from about 1, 2, 3, 4, 5, 6, 7, 8, 9, up to about 10.
  • myositis FI3 assessment is scored from about 0-10, about 1-5, about 4-10, or about 1-10.
  • a myositis FI3 score ranges from 0 (no exertion) to 10 (maximal exertion).
  • a myositis FI3 assessment is scored as the number of correctly performed repetitions with 60 or 120 maximal number of repetitions depending on the muscle group assessed.
  • a myositis FI3 assessment may comprise assessing a subject in need thereof administered an anti-ILT7 antibody or antigen-binding fragment thereof as compared to baseline.
  • a subject’s myositis FI3 score is reduced as compared to an otherwise comparable method wherein the subject of the otherwise comparable method is not administered an anti-ILT7 antibody or antigen-binding fragment thereof.
  • a myositis FI3 assessment to an anti-ILT7 antibody or antigen-binding fragment thereof can be assessed on about -28 days, -27 days, -26 days, -25 days, -24 days, -23 days, -22 days, -21 days, -20 days, -19 days, -18 days, -17 days, -16 days, -15 days, -14 days, -13 days, -12 days, -11 days, -10 days, -9 days, -8 days, -7 days, -6 days, -5 days, -4 days, -3 days, -2 days, -1 day, 0 day, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, 20 weeks, 21 weeks, 22 weeks, 23 weeks, 24 weeks, 25 weeks, 26 weeks,
  • a myositis FI3 assessment to an anti-ILT7 antibody or antigen-binding fragment thereof can be assessed on about Day 1, Week 12 ⁇ 3 days, Week 24 ⁇ 3 days, Week 36 ⁇ 3 days, and Week 48 ⁇ 3 days post treatment initiation.
  • an assessment comprises a FVC measurement.
  • a FVC measurement may be used to assess pulmonary function (e.g., lung compliance).
  • a FVC measurement measures the amount of air that can be forcibly exhaled from the lungs of a subject in need thereof.
  • an increase in a FVC measurement (e.g., lung compliance) comprises an increase in lung vascularity.
  • a FVC measurement may comprise assessing a subject in need thereof administered an anti-ILT7 antibody or antigenbinding fragment thereof as compared to baseline.
  • a subject’s FVC measurement is increased as compared to an otherwise comparable method wherein the subject of the otherwise comparable method is not administered an anti-ILT7 antibody or antigen-binding fragment thereof.
  • a FVC measurement to an anti-ILT7 antibody or antigen-binding fragment thereof can be assessed on about -28 days, -27 days, -26 days, -25 days, -24 days, -23 days, -22 days, -21 days, -20 days, -19 days, -18 days, -17 days, -16 days, -15 days, -14 days, -13 days, -12 days, -11 days, -10 days, -9 days, -8 days, -7 days, -6 days, -5 days, -4 days, -3 days, -2 days, -1 day, 0 day, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, 20 weeks, 21 weeks, 22 weeks, 23 weeks, 24 weeks, 25 weeks, 26 weeks, 27 weeks, 28 weeks,
  • a FVC measurement to an anti-ILT7 antibody or antigen-binding fragment thereof can be assessed on about Day -28, Day -27, Day -26, Day -25, Day -24, Day -23, Day -22, Day -21, Day - 20, Day -19, Day -18, Day -17, Day -16, Day -15, Day -14, Day -13, Day -12, Day -11, Day -10, Day -9, Day -8, Day -7, Day -6, Day -5, Day -4, Day -3, Day -2, Day -1, Day 0, Day 1, Week 12 ⁇ 3 days, Week 24 ⁇ 3 days, Week 36 ⁇ 3 days, and Week 48 ⁇ 3 days post treatment initiation.
  • an assessment comprises a Skindexl6 score.
  • a Skindexl6 score may be used to rate skin conditions that have occurred within the previous week.
  • Skindexl6 may be scored from about 0, 1, 2, 3, 4, 5, and up to about 6.
  • a Skindexl6 score is a 16 item assessment that uses a scale from 0 (“never bothered”) to 6 (“always bothered”).
  • a Skindexl6 score is at least about 0, about 1, about 2, about 3, about 4, about 5, or about 6.
  • theses scores are categorized into 3 subscales: symptom, emotional, and functional.
  • a Skindexl6 score may comprise assessing a subject in need thereof administered an anti-ILT7 antibody or antigen-binding fragment thereof as compared to baseline.
  • a subject ’s Skindexl6 score is reduced as compared to an otherwise comparable method wherein the subject of the otherwise comparable method is not administered an anti-ILT7 antibody or antigen-binding fragment thereof (Atherton et al., Expert. Opin. Drug Saf., 2009).
  • a Skindexl6 score to an anti-ILT7 antibody or antigen-binding fragment thereof can be assessed on about -28 days, -27 days, -26 days, -25 days, -24 days, -23 days, -22 days, -21 days, -20 days, -19 days, -18 days, -17 days, -16 days, -15 days, -14 days, -13 days, -12 days, -11 days, -10 days, -9 days, -8 days, -7 days, -6 days, -5 days, -4 days, -3 days, -2 days, -1 day, 0 day, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, 20 weeks, 21 weeks, 22 weeks, 23 weeks, 24 weeks, 25 weeks, 26 weeks, 27 weeks, 28
  • a Skindexl6 score to an anti-ILT7 antibody or antigen-binding fragment thereof can be assessed on about Day 1, Week 4 ⁇ 3 days, Week 12 ⁇ 3 days, Week 24 ⁇ 3 days, Week 36 ⁇ 3 days, and Week 48 ⁇ 3 days post treatment initiation.
  • an assessment comprises a SF36 survey.
  • a SF36 survey may measure functional health and wellbeing from a subject with questions that span 8 health domains: physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health.
  • a SF36 survey may comprise assessing a subject in need thereof administered an anti-ILT7 antibody or antigen-binding fragment thereof as compared to baseline.
  • a subject s functional health and wellbeing is improved as compared to an otherwise comparable method wherein the subject of the otherwise comparable method is not administered an anti-ILT7 antibody or antigen-binding fragment thereof.
  • a SF36 survey assessment to an anti-ILT7 antibody or antigen -binding fragment thereof can be assessed on about -28 days, -27 days, -26 days, -25 days, -24 days, -23 days, -22 days, -21 days, -20 days, -19 days, -18 days, -17 days, -16 days, -15 days, -14 days, -13 days, -12 days, -11 days, -10 days, -9 days, -8 days, -7 days, -6 days, -5 days, -4 days, -3 days, -2 days, -1 day, 0 day, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, 20 weeks, 21 weeks, 22 weeks, 23 weeks, 24 weeks, 25 weeks, 26 weeks, 27 weeks,
  • a SF36 survey assessment to an anti-ILT7 antibody or antigen-binding fragment thereof can be assessed on about Day 1, Week 4 ⁇ 3 days, Week 12 ⁇ 3 days, Week 24 ⁇ 3 days, Week 36 ⁇ 3 days, and Week 48 ⁇ 3 days post treatment initiation.
  • an assessment comprises a PROMIS fatigue 8a survey.
  • a PROMIS fatigue 8a survey may assess a range of self-reported symptoms, from mild subjective feelings of tiredness to an overwhelming, debilitating, and sustained sense of exhaustion.
  • fatigue is divided into the experience of fatigue (frequency, duration, and intensity) and the impact of fatigue on physical, mental, and social activities.
  • a PROMIS fatigue 8a survey assesses symptoms over the past week.
  • a PROMIS fatigue 8a survey may comprise assessing a subject in need thereof administered an anti-ILT7 antibody or antigen-binding fragment thereof as compared to baseline.
  • a subject’s selfreported symptoms are improved as compared to an otherwise comparable method wherein the subject of the otherwise comparable method is not administered an anti-ILT7 antibody or antigen-binding fragment thereof.
  • a PROMIS fatigue 8a survey to an anti-ILT7 antibody or antigen-binding fragment thereof can be assessed on about -28 days, -27 days, -26 days, -25 days, -24 days, -23 days, -22 days, -21 days, -20 days, -19 days, -18 days, -17 days, -16 days, -15 days, -14 days, -13 days, -12 days, -11 days, -10 days, -9 days, -8 days, -7 days, -6 days, -5 days, -4 days, -3 days, -2 days, -1 day, 0 day, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, 20 weeks, 21 weeks, 22 weeks, 23 weeks, 24 weeks, 25 weeks, 26 weeks, 27 weeks,
  • a PROMIS fatigue 8a survey to an anti-ILT7 antibody or antigen-binding fragment thereof can be assessed on about Day 1, Week 4 ⁇ 3 days, Week 12 ⁇ 3 days, Week 24 ⁇ 3 days, Week 36 ⁇ 3 days, and Week 48 ⁇ 3 days post treatment initiation.
  • an assessment comprises a PROMIS physical function 8b survey.
  • PROMIS physical function 8b survey may assess a range of self-reported capability.
  • a PROMIS physical function 8b survey may include the functioning of a subject’s upper extremities (e.g., dexterity), lower extremities (e.g., walking or mobility), and central regions (e.g., neck and back), as well as daily activities (e.g., running errands).
  • a PROMIS physical function 8b survey may comprise assessing a subject in need thereof administered an anti-ILT7 antibody or antigen-binding fragment thereof as compared to baseline.
  • a subject’s self-reported capability is improved as compared to an otherwise comparable method wherein the subject of the otherwise comparable method is not administered an anti-ILT7 antibody or antigen-binding fragment thereof.
  • a PROMIS physical function 8b survey to an anti-ILT7 antibody or antigen-binding fragment thereof can be assessed on about -28 days, -27 days, -26 days, -25 days, -24 days, -23 days, -22 days, -21 days, -20 days, -19 days, -18 days, -17 days, -16 days, -15 days, -14 days, -13 days, -12 days, -11 days, -10 days, -9 days, -8 days, -7 days, - 6 days, -5 days, -4 days, -3 days, -2 days, -1 day, 0 day, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, 20 weeks, 21 weeks, 22 weeks, 23 weeks, 24 weeks, 25 weeks, 26 weeks, 27
  • a PROMIS physical function 8b survey to an anti-ILT7 antibody or antigenbinding fragment thereof can be assessed on about Day 1, Week 4 ⁇ 3 days, Week 12 ⁇ 3 days, Week 24 ⁇ 3 days, Week 36 ⁇ 3 days, and Week 48 ⁇ 3 days post treatment initiation.
  • an assessment comprises a PROMIS pain interference 6a survey.
  • a PROMIS pain interference 6a survey may assess the consequences of pain on a subject’s life.
  • a PROMIS pain interference 6a survey may include the extent to which pain hinders engagement with social, cognitive, emotional, physical, and recreational activities.
  • a PROMIS pain interference 6a survey may comprise assessing a subject in need thereof administered an anti-ILT7 antibody or antigen-binding fragment thereof as compared to baseline.
  • a subject’s pain hindrance is improved as compared to an otherwise comparable method wherein the subject of the otherwise comparable method is not administered an anti-ILT7 antibody or antigen-binding fragment thereof.
  • a PROMIS pain interference 6a survey to an anti-ILT7 antibody or antigen-binding fragment thereof can be assessed on about -28 days, -27 days, -26 days, -25 days, -24 days, -23 days, -22 days, -21 days, -20 days, -19 days, -18 days, -17 days, -16 days, -15 days, -14 days, -13 days, -12 days, -11 days, -10 days, -9 days, -8 days, -7 days, - 6 days, -5 days, -4 days, -3 days, -2 days, -1 day, 0 day, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks,
  • a PROMIS pain interference 6a survey to an anti-ILT7 antibody or antigenbinding fragment thereof can be assessed on about Day 1, Week 4 ⁇ 3 days, Week 12 ⁇ 3 days, Week 24 ⁇ 3 days, Week 36 ⁇ 3 days, and Week 48 ⁇ 3 days post treatment initiation.
  • an assessment comprises a PROMIS dyspnea severity survey.
  • a PROMIS dyspnea severity survey may assess the severity of breath of difficulty breathing in a subject experiencing a response to various activities (e.g., dressing oneself without help, preparing meals, walking up 20 stairs).
  • a PROMIS dyspnea severity survey may comprise assessing a subject in need thereof administered an anti-ILT7 antibody or antigen-binding fragment thereof as compared to baseline.
  • a subject’s severity of breathing difficult is improved as compared to an otherwise comparable method wherein the subject of the otherwise comparable method is not administered an anti-ILT7 antibody or antigenbinding fragment thereof.
  • a PROMIS dyspnea severity survey to an anti-ILT7 antibody or antigenbinding fragment thereof can be assessed on about -28 days, -27 days, -26 days, -25 days, - 24 days, -23 days, -22 days, -21 days, -20 days, -19 days, -18 days, -17 days, -16 days, -15 days, -14 days, -13 days, -12 days, -11 days, -10 days, -9 days, -8 days, -7 days, -6 days, -5 days, -4 days, -3 days, -2 days, -1 day, 0 day, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks,
  • a PROMIS dyspnea severity survey to an anti-ILT7 antibody or antigen-binding fragment thereof can be assessed on about Day 1, Week 4 ⁇ 3 days, Week 12 ⁇ 3 days, Week 24 ⁇ 3 days, Week 36 ⁇ 3 days, and Week 48 ⁇ 3 days post treatment initiation.
  • an assessment comprises a global pain 24-hour NRS survey.
  • a global pain 24-hour NRS survey may assess the intensity of pain a subject may have experienced in the past 24 hours.
  • global pain 24-hour NRS survey may be scored from about 1, 2, 3, 4, 5, 6, 7, 8, 9, and up to about 10.
  • a global pain 24-hour NRS survey is from about 0-5, about 0-10, or about 1-10.
  • a global pain 24-hour NRS survey scale may range from 0 (no pain) to 10 (the most intense pain imaginable).
  • a global pain 24-hour NRS survey may comprise assessing a subject in need thereof administered an anti- ILT7 antibody or antigen-binding fragment thereof as compared to baseline.
  • a subject’s score is reduced as compared to an otherwise comparable method wherein the subject of the otherwise comparable method is not administered an anti-ILT7 antibody or antigen-binding fragment thereof.
  • a global pain 24-hour NRS survey to an anti-ILT7 antibody or antigenbinding fragment thereof can be assessed on about -28 days, -27 days, -26 days, -25 days, - 24 days, -23 days, -22 days, -21 days, -20 days, -19 days, -18 days, -17 days, -16 days, -15 days, -14 days, -13 days, -12 days, -11 days, -10 days, -9 days, -8 days, -7 days, -6 days, -5 days, -4 days, -3 days, -2 days, -1 day, 0 day, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days,
  • a global pain 24-hour NRS survey to an anti-ILT7 antibody or antigen-binding fragment thereof can be assessed on about Day -28, Day -27, Day -26, Day -25, Day -24, Day -23, Day -22, Day -21, Day -20, Day -19, Day -18, Day -17, Day -16, Day -15, Day -14, Day - 13, Day -12, Day -11, Day -10, Day -9, Day -8, Day -7, Day -6, Day -5, Day -4, Day -3, Day -2, Day -1, Day 0, Day 1, Week 4 ⁇ 3 days, Week 8 ⁇ 3 days, Week 12 ⁇ 3 days, Week 16 ⁇ 3 days, Week 20 ⁇ 3 days, Week 24 ⁇ 3 days, Week 28 ⁇ 3 days, Week 32 ⁇ 3 days, Week 36 ⁇ 3 days, Week 40 ⁇ 3 days, Week 44 ⁇ 3 days, Week 48 ⁇ 3 days, and Week 56 ⁇ 7 days post treatment initiation.
  • an assessment comprises a PGIC survey.
  • a PGIC survey may use a categorical scale to ask a subject how much their myositis has changed.
  • a PGIC survey may be administered after a subject in need thereof has been administered an anti- ILT7 antibody or antigen-binding fragment thereof of the disclosure.
  • a PGIC survey score is at least about 1, about 2, about 3, about 4, or about 5.
  • a PGIC survey scale may range from 1 (much better) to 5 (much worse).
  • a level of a PGIC survey is reduced by at least about 1, about 2, about 3, or about 4 points post treatment with a composition provided herein.
  • a PGIC survey may comprise assessing a subject in need thereof administered an anti-ILT7 antibody or antigen-binding fragment thereof as compared to baseline.
  • a subject’s score is reduced as compared to an otherwise comparable method wherein the subject of the otherwise comparable method is not administered an anti-ILT7 antibody or antigen-binding fragment thereof.
  • a PGIC survey to an anti-ILT7 antibody or antigen-binding fragment thereof can be assessed on about -28 days, -27 days, -26 days, -25 days, -24 days, -23 days, -22 days, -21 days, -20 days, -19 days, -18 days, -17 days, -16 days, -15 days, -14 days, -13 days, -12 days, -11 days, -10 days, -9 days, -8 days, -7 days, -6 days, -5 days, -4 days, -3 days, -2 days, -1 day, 0 day, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks,
  • a PGIC survey to an anti-ILT7 antibody or antigen-binding fragment thereof can be assessed on about Week
  • Week 8 ⁇ 3 days, Week 12 ⁇ 3 days, Week 16 ⁇ 3 days, Week 20 ⁇ 3 days, Week 24 ⁇ 3 days, Week 28 ⁇ 3 days, Week 32 ⁇ 3 days, Week 36 ⁇ 3 days, Week 40 ⁇ 3 days, Week 44 ⁇ 3 days, Week 48 ⁇ 3 days, and Week 56 ⁇ 7 days post treatment initiation.
  • TIS Total Improvement Score
  • CSM 6 Core Set Measures
  • an assessment comprises TIS.
  • TIS is a composite score that includes an assessment of health assessment questionnaire-disability index (HAQ-DI), patient global disease activity (PtGDA), physician global disease activity (PhGDA), manual muscle testing 8 (MMT8) bilateral, laboratory muscle enzymes, and extramuscular global assessment (MRC 2016).
  • HAQ-DI health assessment questionnaire-disability index
  • PtGDA patient global disease activity
  • PhGDA physician global disease activity
  • MMT8 manual muscle testing 8 bilateral
  • laboratory muscle enzymes and extramuscular global assessment
  • MRC 2016 extramuscular global assessment
  • TIS may be scored from about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12,
  • TIS is from about 1-10, about 10-30, about 20-40, about 30-50, about 40-60, about 50-70, about 60-80, about 70-90, or about 80-100.
  • the TIS may be > 20 or > 40.
  • the criteria may be used as a continuous outcome measure using the TIS.
  • the criteria may be used as a categorical outcome of improvement (minimal, moderate, or major improvement).
  • the criteria may be used as both a continuous outcome measure and a categorical outcome of improvement, and thus are a hybrid measure.
  • a change from baseline is determined.
  • a subject’s score is increased as compared to an otherwise comparable method wherein the subject of the otherwise comparable method is not administered an anti-ILT7 antibody or antigen-binding fragment thereof.
  • a TIS assessment to an anti-ILT7 antibody or antigen-binding fragment thereof can be assessed on about -28 days, -27 days, -26 days, -25 days, -24 days, -23 days, -22 days, -21 days, -20 days, -19 days, -18 days, -17 days, -16 days, -15 days, -14 days, -13 days, -12 days, -11 days, -10 days, -9 days, -8 days, -7 days, -6 days, -5 days, -4 days, -3 days, -2 days, -1 day, 0 day, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, 20 weeks, 21 weeks, 22 weeks, 23 weeks, 24 weeks, 25 weeks, 26 weeks, 27 weeks, 28 weeks,
  • a TIS assessment to an anti-ILT7 antibody or antigen-binding fragment thereof can be assessed on about Day -28, Day -27, Day -26, Day -25, Day -24, Day -23, Day -22, Day -21, Day -20, Day -19, Day -18, Day -17, Day -16, Day -15, Day -14, Day -13, Day -12, Day -11, Day -10, Day - 9, Day -8, Day -7, Day -6, Day -5, Day -4, Day -3, Day -2, Day -1, Day 0, Day 1, Week 4 ⁇ 3 days, Week 8 ⁇ 3 days, Week 12 ⁇ 3 days, Week 16 ⁇ 3 days, Week 20 ⁇ 3 days, Week 24 ⁇ 3 days, Week 28 ⁇ 3 days, Week 32 ⁇ 3 days, Week 36 ⁇ 3 days, Week 40 ⁇ 3 days, Week 44 ⁇ 3 days, Week 48 ⁇ 3 days, and Week 56 ⁇ 7 days post treatment initiation.
  • an assessment comprises 28-Joint Count.
  • 28 specified joints are assessed for tenderness and swelling.
  • 28 specified joints comprise, but are not limited to, left and right shoulder, elbow, wrist, metacarpophalangeal (MCP)l, MCP2, MCP3, MCP4, MCP5, proximal interphalangeal (PIP)l, PIP2, PIP3, PIP4, and PIP5 joints of the upper extremities, and left and right knee of the lower extremities.
  • MCP metacarpophalangeal
  • PIP proximal interphalangeal
  • PIP2 PIP2, PIP3, PIP4, and PIP5 joints of the upper extremities, and left and right knee of the lower extremities.
  • a change in 28-Joint count may be measured versus baseline.
  • a subject’s score is improved as compared to an otherwise comparable method wherein the subject of the otherwise comparable method is not administered an anti-ILT7 antibody or antigen-binding fragment thereof.
  • a 28-Joint Count assessment to an anti-ILT7 antibody or antigen-binding fragment thereof can be assessed on about -28 days, -27 days, -26 days, -25 days, -24 days, -23 days, -22 days, -21 days, -20 days, -19 days, -18 days, -17 days, -16 days, -15 days, -14 days, -13 days, -12 days, -11 days, -10 days, -9 days, -8 days, -7 days, -6 days, -5 days, -4 days, -3 days, -2 days, -1 day, 0 day, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, 20 weeks, 21 weeks, 22 weeks, 23 weeks, 24 weeks, 25 weeks, 26 weeks,
  • a 28- Joint Count assessment to an anti-ILT7 antibody or antigen-binding fragment thereof can be assessed on about Day 1, Week 4 ⁇ 3 days, Week 8 ⁇ 3 days, Week 12 ⁇ 3 days, Week 16 ⁇ 3 days, Week 20 ⁇ 3 days, Week 24 ⁇ 3 days, Week 28 ⁇ 3 days, Week 32 ⁇ 3 days, Week 36 ⁇ 3 days, Week 40 ⁇ 3 days, Week 44 ⁇ 3 days, and Week 48 ⁇ 3 days post treatment initiation.
  • an assessment comprises actigraphy.
  • Actigraphy is a measure of overall activity and sleep patterns, including duration and fragmentation of sleep.
  • an activity monitor device is an ActiGraph, a wearable watch device.
  • overall activity and changes in sleep patterns for a subject administered an anti-ILT7 antibody or antigenbinding fragment thereof are determined as compared to baseline.
  • a subject’s score is improved as compared to an otherwise comparable method wherein the subject of the otherwise comparable method is not administered an anti-ILT7 antibody or antigenbinding fragment thereof.
  • an actigraphy assessment to an anti-ILT7 antibody or antigen-binding fragment thereof can be assessed on about -28 days, -27 days, -26 days, -25 days, -24 days, -23 days, -22 days, -21 days, -20 days, -19 days, -18 days, -17 days, -16 days, -15 days, -14 days, -13 days, -12 days, -11 days, -10 days, -9 days, -8 days, -7 days, -6 days, -5 days, -4 days, -3 days, -2 days, -1 day, 0 day, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, 20 weeks, 21 weeks, 22 weeks, 23 weeks, 24 weeks, 25 weeks, 26 weeks, 27 weeks, 28 weeks,
  • an actigraphy assessment to an anti-ILT7 antibody or antigen-binding fragment thereof can be assessed on about Day 1, Week 4 ⁇ 3 days, Week 8 ⁇ 3 days, Week 12 ⁇ 3 days, Week 16 ⁇ 3 days, Week 20 ⁇ 3 days, Week 24 ⁇ 3 days, Week 28 ⁇ 3 days, Week 32 ⁇ 3 days, Week 36 ⁇ 3 days, Week 40 ⁇ 3 days, Week 44 ⁇ 3 days, and Week 48 ⁇ 3 days post treatment initiation.
  • an assessment comprises handheld dynamometry.
  • handheld dynamometry may assess strong reliability, construct validity, and responsiveness in myositis patients (Saygin et al, 2021), especially to evaluate strength of single muscle groups (Baschung et al, 2018).
  • Handheld dynamometry may be used to evaluate muscle strength.
  • a handheld dynamometry assessment may evaluate strength of a single muscle group at a time.
  • a handheld dynamometry assessment for a subject administered an anti-ILT7 antibody or antigen-binding fragment thereof is determined as compared to baseline.
  • a subject’s score is improved as compared to an otherwise comparable method wherein the subject of the otherwise comparable method is not administered an anti- ILT7 antibody or antigen-binding fragment thereof.
  • a handheld dynamometry assessment to an anti-ILT7 antibody or antigenbinding fragment thereof can be assessed on about -28 days, -27 days, -26 days, -25 days, - 24 days, -23 days, -22 days, -21 days, -20 days, -19 days, -18 days, -17 days, -16 days, -15 days, -14 days, -13 days, -12 days, -11 days, -10 days, -9 days, -8 days, -7 days, -6 days, -5 days, -4 days, -3 days, -2 days, -1 day, 0 day, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days,
  • a handheld dynamometry assessment to an anti-ILT7 antibody or antigen-binding fragment thereof can be assessed on about Day 1, Week 4 ⁇ 3 days, Week 8 ⁇ 3 days, Week 12 ⁇ 3 days, Week 16 ⁇ 3 days, Week 20 ⁇ 3 days, Week 24 ⁇ 3 days, Week 28 ⁇ 3 days, Week 32 ⁇ 3 days, Week 36 ⁇ 3 days, Week 40 ⁇ 3 days, Week 44 ⁇ 3 days, and Week 48 ⁇ 3 days post treatment initiation.
  • a pharmaceutical composition can comprise an anti-ILT7 antibody or antigen-binding fragment thereof.
  • a pharmaceutical composition is part of a therapeutic regimen that comprises an anti-ILT7 antibody or antigen-binding fragment thereof and one or more additional therapeutics provided herein.
  • the one or more additional therapeutics can comprise a corticosteroid, a DMARD, or an immunomodulatory agent, or a combination thereof.
  • drugs can be administered orally as liquids, capsules, tablets, or chewable tablets. Because the oral route is the most convenient and usually the safest and least expensive, it is the one most often used. However, it has limitations because of the way a drug typically moves through the digestive tract. For drugs administered orally, absorption may begin in the mouth and stomach. However, most drugs are usually absorbed from the small intestine. The drug passes through the intestinal wall and travels to the liver before being transported via the bloodstream to its target site. The intestinal wall and liver chemically alter (metabolize) many drugs, decreasing the amount of drug reaching the bloodstream. Consequently, these drugs are often given in smaller doses when injected intravenously to produce the same effect.
  • a needle is inserted into fatty tissue just beneath the skin. After a drug (e.g., an anti-ILT7 antibody or antigen-binding fragment thereof) is injected, it then moves into small blood vessels (capillaries) and is carried away by the bloodstream. Alternatively, a drug reaches the bloodstream through the lymphatic vessels.
  • a drug e.g., an anti-ILT7 antibody or antigen-binding fragment thereof
  • the intramuscular route is preferred to the subcutaneous route when larger volumes of a drug product are needed. Because the muscles lie below the skin and fatty tissues, a longer needle is used. Drugs are usually injected into the muscle of the abdomen (avoiding a 2-inch radius around the umbilicus), upper arm, thigh, or buttock.
  • a needle is inserted directly into a vein.
  • a solution containing the drug may be given in a single dose or by continuous infusion.
  • the solution is moved by gravity (from a collapsible plastic bag) or, more commonly, by an infusion pump through thin flexible tubing to a tube (catheter) inserted in a vein, usually in the forearm.
  • a pharmaceutical composition provided herein is administered via infusion.
  • An infusion can take place over a period of time.
  • an infusion can be an administration of a pharmaceutical over a period of about 5 minutes to about 10 hours.
  • An infusion can take place over a period of about 5 min, 10 min, 20 min, 30 min, 40 min, 50 min, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 3.5 hours, 4 hours, 4.5 hours, 5 hours, 6 hours, 7 hours, 8 hours, 9 hours, or up to about 10 hours.
  • intravenous administration is used to deliver a precise dose quickly and in a well-controlled manner throughout the body.
  • infusion reactions can occur and include headache, nausea, somnolence, dyspnea, fever, myalgia, rash, or other symptoms.
  • an anti-ILT7 antibody or antigen-binding fragment thereof are infection, redness, swelling, pain, and induration at the administration site.
  • Prior to each IV infusion subjects may receive prophylaxis with IV methylprednisolone, oral diphenhydramine, and oral acetaminophen, or equivalent(s) to reduce the risk or severity of potential reactions.
  • a pharmaceutical is administered intrathecally.
  • a needle is inserted between two vertebrae in the lower spine and into the space around the spinal cord.
  • the drug is then injected into the spinal canal.
  • a small amount of local anesthetic is often used to numb the injection site. This route is used when a drug is needed to produce rapid or local effects on the brain, spinal cord, or the layers of tissue covering them (meninges) — for example, to treat infections of these structures.
  • Drugs administered by inhalation through the mouth can be atomized into smaller droplets than those administered by the nasal route, so that the drugs can pass through the windpipe (trachea) and into the lungs. How deeply into the lungs they go depends on the size of the droplets. Smaller droplets go deeper, which increases the amount of drug absorbed. Inside the lungs, they are absorbed into the bloodstream. Drugs applied to the skin are usually used for their local effects and thus are most commonly used to treat superficial skin disorders, such as psoriasis, eczema, skin infections (viral, bacterial, and fungal), itching, and dry skin. The drug is mixed with inactive substances. Depending on the consistency of the inactive substances, the formulation may be an ointment, cream, lotion, solution, powder, or gel.
  • a treatment regime comprising a pharmaceutical composition may be dosed according to a body weight of a subject.
  • a body weight of a subject In subjects who are determined obese (BMI > 35) a practical weight may need to be utilized.
  • body surface area may be utilized to calculate a dosage.
  • a pharmaceutical composition can be administered either alone or together with a pharmaceutically acceptable carrier or excipient, by any routes, and such administration can be carried out in both single and multiple dosages.
  • a pharmaceutical composition can be combined with various pharmaceutically acceptable inert carriers in the form of tablets, capsules, lozenges, troches, hand candies, powders, sprays, aqueous suspensions, injectable solutions, elixirs, syrups, and the like.
  • Such carriers include solid diluents or fillers, sterile aqueous media and various non-toxic organic solvents, etc.
  • pharmaceutical formulations can be suitably sweetened and/or flavored by means of various agents of the type commonly employed for such purposes.
  • Exemplary carriers and excipients can include dextrose, sodium chloride (NaCl), sucrose, lactose, cellulose, xylitol, sorbitol, maltitol, gelatin, PEG, PVP, D-histidine/D-histidine hydrochloride, L-histidine/L-histidine hydrochloride, trehalose dihydrate, polysorbate 80, and any combination thereof.
  • an excipient comprises: L-histidine/L-histidine hydrochloride, sucrose, and polysorbate 80.
  • a method of treating dermatomyositis comprising administering an effective amount of an anti-Immunoglobulin-like transcript-7 (ILT7) antibody or antigenbinding fragment thereof to a subject in need thereof, wherein the ILT7 antibody or antigenbinding fragment thereof comprises Complementarity-Determining Regions (CDRs) HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of SEQ ID NOs: 3, 4, 5, 8, 9, and 10, respectively, wherein the effective amount is about 300 mg, and wherein the antibody is administered once every 4 weeks.
  • CDRs Complementarity-Determining Regions
  • a method of treating anti -synthetase inflammatory myositis comprising administering an effective amount of an anti-Immunoglobulin-like transcript-7 (ILT7) antibody or antigen-binding fragment thereof to a subject in need thereof, wherein the ILT7 antibody comprises Complementarity-Determining Regions (CDRs) HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of SEQ ID NOs: 3, 4, 5, 8, 9, and 10, respectively, wherein the effective amount is about 300 mg, and wherein the antibody is administered once every 4 weeks.
  • CDRs Complementarity-Determining Regions
  • a method of treating a disease comprising administering an effective amount of an anti-Immunoglobulin-like transcript-7 (ILT7) antibody or antigenbinding fragment thereof to a subject in need thereof, wherein the ILT7 antibody comprises Complementarity-Determining Regions (CDRs) HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of SEQ ID NOs: 3, 4, 5, 8, 9, and 10, respectively, wherein the effective amount comprises a dosage from about 300 mg, and wherein the administering is completed once every 4 weeks.
  • ILT7 antibody comprises Complementarity-Determining Regions (CDRs) HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of SEQ ID NOs: 3, 4, 5, 8,
  • a method of treating a disease comprising administering an effective amount of an anti-Immunoglobulin-like transcript-7 (ILT7) antibody or antigenbinding fragment thereof to a subject in need thereof, wherein the ILT7 antibody comprises Complementarity-Determining Regions (CDRs) HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of SEQ ID NOs: 3, 4, 5, 8, 9, and 10, respectively, and wherein the administration is effective in reducing disease as compared to: (a) disease in an otherwise comparable subject lacking the administering; or (b) a baseline measurement of disease in the subject in need thereof.
  • CDRs Complementarity-Determining Regions
  • the reduced level of the symptom comprises a reduction in a score of an assessment, as compared to baseline, selected from the group consisting of: Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI), Myositis Disease Activity Assessment Tool (MDAAT), myositis damage index (MDI), and combinations thereof.
  • CDASI Cutaneous Dermatomyositis Disease Area and Severity Index
  • MDAAT Myositis Disease Activity Assessment Tool
  • MDI myositis damage index
  • the ILT7 antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH and the VL regions comprise an amino acid sequence at least 80% identical to SEQ ID NO: 2 and SEQ ID NO: 7, respectively.
  • the ILT7 antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH and the VL regions comprise the amino acid sequence of SEQ ID NO: 2 and SEQ ID NO: 7, respectively.
  • VH heavy chain variable region
  • VL light chain variable region
  • the ILT7 antibody is a monoclonal antibody.
  • ASIM-associated antibodies is selected from the group consisting of: anti-Jo-1, anti-PL-12, anti-PL-7, anti- KS, anti-EJ, anti-OJ, anti-ZO, and anti-YRS(HA).
  • [0210] 31 The method of embodiment 30, wherein the level is reduced by at least about 1- fold, 5-fold, 10-fold, 25-fold, 50-fold, 75-fold, 100-fold, 150-fold, or 250-fold.
  • a method of treating dermatomyositis comprising subcutaneously administering an effective amount of an anti-Immunoglobulin-like transcript-7 (ILT7) antibody or antigen-binding fragment thereof to a subject in need thereof, wherein the ILT7 antibody or antigen-binding fragment thereof comprises Complementarity-Determining Regions (CDRs) HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of SEQ ID NOs: 3, 4, 5, 8, 9, and 10, respectively, wherein the effective amount is about 300 mg.
  • CDRs Complementarity-Determining Regions
  • a method of treating anti -synthetase inflammatory myositis comprising subcutaneously administering an effective amount of an anti- Immunoglobulin-like transcript-7 (ILT7) antibody or antigen-binding fragment thereof to a subject in need thereof, wherein the ILT7 antibody comprises Complementarity- Determining Regions (CDRs) HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of SEQ ID NOs: 3, 4, 5, 8, 9, and 10, respectively, wherein the effective amount is about 300 mg.
  • CDRs Complementarity- Determining Regions
  • Example 1 A phase 2, randomized, double-blind, placebo-controlled, efficacy and safety study of Daxdilimab subcutaneous injection in adult participants with inadequately controlled dermatomyositis or anti-synthetase inflammatory myositis.
  • ADA anti drug antibodies
  • CDASI cutaneous dermatomyositis disease area and severity index
  • CSM core set measures
  • CTCAE common terminology criteria for adverse events
  • FI3 functional index 3
  • FVC forced vital capacity
  • HAQ-DI health assessment questionnaire-disability index
  • IFN interferon
  • MDAAT myositis disease activity assessment tool
  • MDI myositis damage index
  • MMT8 manual muscle testing
  • MRI magnetic resonance imaging
  • MxA myxovirus resistance protein A
  • NRS numeric rating scale
  • OCS oral corticosteroid
  • PD pharmacodynamics
  • pDCs plasmacytoid dendritic cells
  • PhGDA physician global disease activity
  • PtGDA patient global disease activity
  • PGIC patient global impression of change
  • PK pharmacokinetics
  • PROMIS patient-reported outcomes measurement information system
  • SF36 36- item short form survey
  • TIS total improvement score.
  • This study is a Phase 2, randomized, double-blind, placebo-controlled, proof of concept study to assess the efficacy and safety of Daxdilimab in participants aged >18 to ⁇ 75 years with dermatomyositis (DM) or anti -synthetase inflammatory myositis (ASIM).
  • DM dermatomyositis
  • ASIM anti -synthetase inflammatory myositis
  • ASIM Participants with ASIM with definite or probable myositis according to ACR/EULAR 2017 criteria and a positive ASIM associated antibody.
  • Randomization may take place up to 28 days after successful screening, and it will be stratified by Manual Muscle Testing 8 (MMT8) score ( ⁇ 120 vs >120) at Baseline (Day 1).
  • MMT8 score ⁇ 120 vs >120
  • Randomized control period double-blinded from Day 1 through Week 24
  • IP All administrations of IP will be administered by an unblinded pharmacist or nurse at the clinic and the participant may be observed for at least 60 minutes after the first and second doses and for 20 minutes for all subsequent doses. To maintain the blind for previous treatment, all participants may be observed for at least 60 minutes after the administration of IP at Weeks 24 and 28.
  • Efficacy assessments may include a series of scores, scales, and other measurements to assess disease activity, damage, and improvement.
  • Patient-reported outcomes may be used to record the wellbeing and quality of life of the participants during the study.
  • PK pharmacokinetics
  • PD pharmacodynamics
  • immunogenicity of Daxdilimab blood samples from all participants, and optional muscle and/or skin biopsies from those who agree, may be collected.
  • the study assessments scheduled on Day 1 may be performed before the administration of IP; patient-reported outcomes may be performed first, followed by the physician assessments, measurement of vital signs, and laboratory assessments.
  • the end of study is defined as the date of the last visit of the last participant in the study or last scheduled procedure (Week 56) shown in the Schedule of Assessments (SoA; Table 3) for the last participant in the study globally.
  • a participant is considered to have completed the study if the participant has completed all periods of the study including the last visit or the last scheduled procedure (Week 56) shown in the Table 3.
  • ADA antidrug antibody
  • AESI AE of special interest
  • ALT alanine transaminase
  • AST aspartate transaminase
  • phCG P-human chorionic gonadotropin
  • CBC complete blood count
  • CDASI cutaneous dermatomyositis disease area and severity index
  • CK creatine kinase
  • DC dendritic cells
  • ECG electrocardiogram
  • FI functional index
  • FSH follicle-stimulating hormone
  • HAQ-DI health assessment questionnaire -disability index
  • IFN interferon
  • IP investigational product
  • LDH lactate dehydrogenase
  • MDAAT myositis disease activity assessment tool
  • MDI myositis damage index
  • MMT manual muscle testing
  • MRI magnetic resonance imaging
  • MSA myositis-specific antibodies
  • MxA myxovirus resistance protein A
  • NRS numeric rating scale
  • PBMC peripheral blood mononu
  • Week 48 may correspond to the End of Investigational Product Visit if the participant discontinues IP prior to Week 44. Participants who complete the Week 48 visit will be offered to participate in a long-term extension study for safety and efficacy. Participants who enter this study directly after completion of the Week 48 visit may not complete the visits of the SFU period.
  • c Week 52 visit may be performed as a phone call to the participant.
  • d Week 56 or earlier may correspond to the End of Study/Early Termination Visit if the participant withdraws consent to participate in the study.
  • e Participant eligibility may be checked on Day 1 prior to Randomization.
  • f Questionnaires may be completed before any other procedures are performed.
  • g For participants with interstitial lung disease, testing may be done more frequently if Investigator considers it clinically indicated. h Participants may be asked to wear it for 1 week after each visit, but they will be allowed to wear it longer if they wish to.
  • i A complete physical examination at Screening and a focused physical examination at Weeks 24 and 48 including assessment of head, ears, eyes, nose, throat, lungs, heart, abdomen, skin, and extremities.
  • Vital signs include systolic and diastolic blood pressure may be obtained after at least 5 minutes at rest in a seated position, heart rate, respiratory rate (breaths/min), and body temperature. k May be performed after 10 minutes rest in supine position and after vital signs are collected.
  • Skin biopsy may by performed by punch biopsy. m Participants undergoing muscle biopsy may first undergo an MRI scan either on their first or second visit, followed by the muscle biopsy on the same or the following day. These procedures may be performed before dosing. Day 1 visit procedures for these participants may take up to 3 days to be completed. These participants will be dosed one day after biopsy, once recovered. Day 1 may be counted from their first dosing day. n The results of an IFNy release assay (i.e., QuantiFERON-TB Gold Plus or T-SPOT) performed within 12 weeks of the Screening visit (if available) are acceptable, provided there is no reason to suspect any re-exposure.
  • IFNy release assay i.e., QuantiFERON-TB Gold Plus or T-SPOT
  • o Serum virology does not have to be repeated if performed within 12 weeks prior to Screening (e.g., Rescreening).
  • Table 11 shows a complete list of serology assessments.
  • p To confirm postmenopausal status, as appropriate. Estradiol and FSH tests do not have to be repeated if performed within 12 weeks prior to Screening (e.g., Rescreening).
  • q In women of childbearing potential or women who are postmenopausal for less than 2 years prior to Screening, have nontherapy-induced amenorrhea for less than 12 months prior to Screening, or are not surgically sterile (absence of fallopian tubes, ovaries and/or uterus). r Go to Table 11 for a complete list of routine laboratory assessments.
  • Urine collection can be postponed for up to 14 days in women with menstrual bleeding or a urinary tract infection at the scheduled visit. Go to Table 11 for a complete list of routine urinalysis assessments.
  • t Serum Daxdilimab PK may be obtained at Day 1 at approximately 2 hours or longer postdose, predose on Day 1 and Weeks 4, 8, 12, 16, 24, and 36; and any time on Weeks 48 and 56.
  • u Collection of serum ADA samples may be performed prior to the administration of IP at all applicable visits.
  • the time window for the administration of IPs is -13 days +14 days. All procedures and blood sampling may be collected before the administration.
  • Participants eligible for this study may have DM or ASIM.
  • Pathognomonic skin rash (heliotrope rash, Gottron’s papules and/or Gottron’s sign) is required if no muscle biopsy is available
  • Anti- Jo- 1 antibodies must be positive during Screening by central laboratory testing, or
  • CSM abnormal core set measures
  • Participants should be on stable standard of care therapy if tolerated (a); if they are not able to tolerate it or have failed standard of care, medications should have washed out (b): a. Participants on corticosteroid treatment (up to 20 mg prednisone or equivalent per day) and/or up to 2, non-excluded, immunosuppressants on stable therapy (Table 6) for at least 4 weeks prior to Randomization or b. Participants with previous failure of response or previous intolerance to corticosteroid and at least 1 additional immunosuppressant drug, and with steroid/immunosuppressants washed out (Table 6).
  • a female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies: a. Is a woman of nonchildbearing potential (WONCBP), or b. Is a women of childbearing potential (WOCBP), and: i. Has a negative serum pregnancy test at Screening and a negative urine pregnancy test at Day 1. ii. Agrees to use contraceptive methods that are highly effective from at least 4 weeks prior to Day 1 until at least 3 months after the last administration of IP or the end of the study, whichever is longer. iii. The Investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.
  • WONCBP nonchildbearing potential
  • WOCBP women of childbearing potential
  • Participant who has given > 50 mL of blood or plasma within 30 days of Screening or > 499 mL of blood or plasma within 56 days of Screening (during a clinical study or at a blood bank donation) or plans to give blood or plasma during their participation in the study or up to 6 months after the last administration of IP, whichever is longer.
  • HIV human immunodeficiency virus
  • TB Active tuberculosis
  • IGRA positive IFN-y release assay
  • Any severe herpes virus family infection including Epstein-Barr virus, cytomegalovirus [CMV]
  • CMV cytomegalovirus
  • a participant with a documented positive SARS-CoV-2 test may be rescreened at least 2 weeks after a positive test if the participant is asymptomatic and at least 3 weeks after symptomatic COVID-19 illness.
  • IMNM immune-mediated necrotizing myopathy
  • IBM inclusion body myositis
  • IBM inclusion body myositis
  • B-cells should be detectable after therapy with these treatments prior to Randomization.
  • Exposure to an experimental drug either 30 days, 5 half-lives of the agent, or twice the duration of the biological effect of the agent, whichever is longer, prior to Randomization and through the final study visit.
  • Participants will only be asked to abstain from strenuous exercise for 24 to 48 hours before each blood collection for clinical laboratory tests. Participants may participate in light recreational activities during study visits (e.g., watching television, reading).
  • Investigational Products are all prespecified medicinal products intended to be administered to the study participants during the study conduct (i.e., Daxdilimab and placebo).
  • the IP Daxdilimab may be supplied as a 2R vial with nominal 1 mL of 100 mg/mL Daxdilimab containing 20 mM L histidine/L-histidine HC1, 240 mM sucrose, 0.02% (w/v) polysorbate 80, pH 6.0.
  • the placebo is supplied as a 2R vial with nominal 1 mL of 20 mM L histidine/L- histidine HC1, 240 mM sucrose, 0.02% (w/v) polysorbate 80, pH 6.0.
  • Both IPs may be administered by SC injection Q4W from Day 1 to Week 24. After Week 24 through Week 44, only Daxdilimab may be administered to all participants. To maintain the same number and volume of injections across all groups, the required dose may be administered as 2 injections of 1.5 mL.
  • IPs investigational products
  • ASIM anti-synthetase inflammatory myositis
  • DM dermatomyositis
  • IP investigational product
  • the study may be double-blinded, which means that participants, Investigators, and site personnel will be unaware of the IP given to the participant.
  • Azathioprine, tacrolimus, ciclosporin, plaquenil, and mycophenolate mofetil must be at a stable dosage for at least 4 weeks prior to Screening and through study.
  • Methotrexate oral or SC at stable dosage and route of administration for at least 4 weeks prior to Screening and through study.
  • Participants who start prohibited medications or therapies for other reasons during the study may be withdrawn from study treatment if an impact on efficacy assessment or safety of the participants is expected.
  • Table 7 lists prohibited medications that may not to be used from the defined washout periods before the first administration of IP at the Day 1 visit through the last study visit.
  • Rescue therapy is any new background therapy or increase in dose above on Day 1 baseline of any permitted therapy given to participants.
  • IP may be continued after discussion with and approval by the medical monitor. However, if participants receive a prohibited medication as a rescue, they may be discontinued from IP, but stay in the study for safety assessments.
  • Rescue medication for worsening DM or ASIM may be administered at the discretion of the Investigators as clinically indicated.
  • rescue medications Although the use of rescue medications is allowable for clinical deterioration, it may be delayed, if possible, through 24 weeks.
  • the medical monitor should weigh the urgency of providing it and the proximity of the primary endpoint (Week 24).
  • Participants who receive rescue therapy may be considered treatment failures for subsequent endpoints.
  • Procedures conducted as part of the participant’s routine clinical management and obtained before signing of the ICF may be utilized for screening or baseline purposes provided the procedures met the protocol-specified criteria and were performed within the timeframe defined in Table 3. • In the event of a significant study-continuity issue (e.g., caused by a pandemic), alternate strategies for participant visits, assessments, medication distribution and monitoring may be implemented.
  • TIS Total improvement score based on the 6 CSM: a. Health assessment questionnaire-disability index (HAQ-DI) b. Patient Global Disease Activity (PtGDA) c. Physician global disease activity (PhGDA) (part of the myositis disease activity assessment tool [MDAAT]) d. Manual muscle testing 8 (MMT8) bilateral e. Laboratory muscle enzymes f. Extramuscular global assessment (part of the MDAAT)
  • the TIS is derived from standardized clinical response criteria that are recommended for use as primary endpoint in myositis therapeutic.
  • the criteria use the 6 CSM, combining the absolute percentage change in each with varying weights to obtain a TIS on a scale of 0- 100.
  • Different thresholds of improvement have been set for minimal, moderate, and major response.
  • the criteria may be used as a continuous outcome measure, using the TIS, or as a categorical outcome of improvement (minimal, moderate, or major improvement) and thus are a hybrid measure. Improvement category thresholds for minimal, moderate, and major improvement have been developed and validated for DM and PM. (Find online calculator in MRC 2016).
  • HAQ-DI assesses physical function. It comprises 8 sections: dressing and grooming, arising, eating, walking, hygiene, reach, grip, and common daily activities. For each of these categories, participants report the amount of difficulty they have in performing 2 or 3 specific activities. Scoring within each section is from 0 (without any difficulty) to 3 (unable to do). The time frame for the disability questions is the past week. The disability index is designed to assess participants’ usual abilities using their usual equipment.
  • the PtGDA measures the global evaluation by the patient of the patient's overall disease activity at the time of assessment using a 10 cm VAS that ranges from “no evidence of disease activity” to “extremely active or severe disease activity”.
  • the PhGDA is the physician’s judgment of overall disease activity (extramuscular organ systems plus muscle disease activity) based on all clinical laboratory assessments. It uses a 10 cm VAS that ranges from “no evidence of disease activity” to “extreme or maximum disease activity” and a 5 point Likert scale that ranges from 0 (none activity) to 4 (extremely severe activity).
  • the MMT8 bilateral is a set of 8 designated muscles tested bilaterally (potential score 0-140). Axial (neck flexors) testing is included, so that potential MMT8 score is 150.
  • the extramuscular global assessment provides an overall evaluation for the disease activity in all extramuscular systems (excluding muscle disease activity) using a 10 cm VAS that ranges from “no evidence of disease activity” to “extreme or maximum disease activity”.
  • the MDAAT (V 2.0) measures the degree of disease activity of extramuscular organ systems and muscle combining a 10 cm VAS that ranges from “no evidence of disease activity” to “extreme or maximum disease activity” and an activity index that ranges from 0 (“not present in the last 4 weeks”) to 4 (“new in the last 4 weeks”).
  • the CDASI (V 2.0) is an outcome measure used to assess the severity of cutaneous DM and detect improvement in disease activity.
  • the scale rates disease involvement in 15 different body areas using 3 activity (erythema, scale, erosion/ulceration) and 2 damage (poikiloderma, calcinosis) measures.
  • the presence and severity of Gottron's papules on the hands, periungual changes and alopecia are also captured.
  • the activity score ranges from 0 to 100 and the damage score from 0 to 32. Higher scores indicate greater disease severity.
  • corticosteroid e.g., prednisone or methylprednisone or the like
  • Investigators will taper their dose 2.5mg/day (prednisone equivalent) every 4 weeks from Week 4 through Week 20 (Table 8). Note that is not permitted to change the corticosteroid dose between Weeks 20 and 24 (FIG. 1).
  • Table 8 Exemplary steroid taper during randomized control period (RCP).
  • corticosteroids e.g., prednisone or methylprednisone or the like
  • Recommended taper is 2.5 mg/day every 4 weeks until 5 mg/day, then Img/day every 2 weeks until discontinued (Table 9).
  • steroid taper may be held.
  • Steroid taper may be held if the PhGDA has a global worsening from Baseline by >
  • the MDI assesses the degree of disease damage of all organ systems. It is composed of a series of organ-specific questions relating to the presence or absence of a given sign or symptom or problem to measure the extent of damage, and an overall rating of the disease damage of each system using a 10 cm VAS to measure the severity of damage from “no evidence of disease damage” to “extreme or maximum disease damage”.
  • the myositis FI3 is a functional outcome measure to assess muscle endurance and function of frequently affected muscle groups. Each muscle group is scored as the number of correctly performed repetitions with 60 or 120 maximal number of repetitions depending on muscle group.
  • a pulmonary function test in local pulmonary function laboratories may be performed to measure the FVC of the participants.
  • a handheld dynamometry may be used to evaluate muscle strength.
  • the procedure has demonstrated strong reliability, construct validity, and responsiveness in myositis patients (Saygin et al, 2021), especially to evaluate strength of single muscle groups (Baschung et al, 2018).
  • the painful, swollen, and tender Joint count is based on left and right shoulder, elbow, wrist, metacarpophalangeal (MCP)l, MCP2, MCP3, MCP4, MCP5, proximal interphalangeal (PIP)l, PIP2, PIP3, PIP4, and PIP5 joints of the upper extremities, and left and right knee of the lower extremities (Scott et al, 2014). Participants may be asked at the start of the Joint count (prior to assessment of tenderness and swelling) whether they have experienced or are experiencing pain in any of the 28 joints within the last 30 days. Each of the 28 joints will then be evaluated separately for tenderness (by palpating the joint) and swelling. Joints with intra-articular injection within 4 weeks are not evaluable for the assessment.
  • the Joint count assessment may include questions regarding limitation of range of movements and effects of joint symptoms on basic and functional activity of daily living.
  • participant may wear an actigraphy device for measuring change in daily activity.
  • the actigraphy device can be worn more frequently.
  • a local MRI scan may be used to determine muscle biopsy site.
  • Laboratory tests will include urinalysis, hematology with differential, a standard chemistry panel (chemistry includes liver function tests), and a serum pregnancy test at Screening for WOCBP.
  • ALP alkaline phosphatase
  • ALT alanine transaminase
  • AST aspartate transaminase
  • PhCG P-human chorionic gonadotropin
  • BUN blood urea nitrogen
  • FSH follicle-stimulating hormone
  • HBcAb hepatitis B core antibody
  • HBsAg hepatitis B surface antigen
  • HCV Ab hepatitis C virus antibody
  • HgAlC hemoglobin A1C
  • HIV human immunodeficiency virus
  • IEC Independent Ethics Committee
  • IFN interferon
  • INR international normalized ratio
  • IRB Institutional Review Board
  • LDH lactate dehydrogenase
  • MCH mean corpuscular hemoglobin
  • MCV mean corpuscular volume
  • RBC red blood cell
  • SGOT serum glutamic- oxaloacetic transaminase
  • SGPT serum glutamic-pyruvic transaminase
  • Urine collection can be postponed for up to 14 days in women with menstrual bleeding or a urinary tract infection at the scheduled visit d
  • women of childbearing potential or women who are postmenopausal for less than 2 years prior to Screening have nontherapy-induced amenorrhea for less than 12 months prior to Screening, or are not surgically sterile (absence of fallopian tubes, ovaries and/or uterus).
  • Local urine testing will be standard for the protocol unless serum testing is required by local regulation or IRB/IEC.
  • a serum P human chorionic gonadotropin (phCG) pregnancy test will be performed to all WOCBP by a central laboratory at Screening.
  • Serum samples of approximately 3.5 mL may be collected for measurement of serum concentrations of daxdilimab at the visits and timepoints specified in Table 3.
  • Samples may be collected at additional timepoints during the study if warranted and agreed upon between the Investigator and the Sponsor.
  • Samples collected for analyses of daxdilimab serum concentration may also be used to evaluate safety or efficacy aspects related to concerns arising during or after the study.
  • Intervention concentration information that would unblind the study may not be reported to investigative sites or blinded personnel.
  • PBMC Peripheral blood mononuclear cells
  • the level of circulating pDCs may be measured using multi-parameter flow cytometry on blood.
  • Optional muscle and skin biopsies may be performed at timepoints listed in Table 3 to test whether daxdilimab alters levels of pDCs, inflammatory cells, and/or other biomarkers in tissue.
  • the biopsy may be performed at Baseline prior to dosing on Day 1 or during the screening period, but not until other screening procedures have confirmed that the participant is eligible for the study.
  • the biopsy may require one 4 mm punch biopsy and it is recommended that the punch biopsy site is closed with a single suture.
  • the sample will be formalin-fixed and paraffin-embedded to enable IHC and other analyses.
  • Participants agreeing to muscle biopsy may first undergo an MRI scan either on their first or second visit, followed by the muscle biopsy on the same or the following day. These procedures should be performed before dosing. Day 1 visit procedures for these participants may take up to 3 days to be completed. These participants may be dosed one day after biopsy, once recovered. Day 1 will be counted from their first dosing day.
  • the anatomic site selected for muscle biopsy should be an area with active inflammation on MRI.
  • a sample of muscle tissue may be taken by inserting a biopsy needle into the muscle. If a larger sample is required, an incision in the skin (open biopsy) may be made to remove a larger section of muscle.
  • Serum samples may be collected to assess changes in the levels of cytokines, chemokines, or other proteins (e.g., IFN-a, IL-17, and IFN-y) that may be related to the pathogenesis of DM or ASIM or the mechanism of action of daxdilimab.
  • cytokines e.g., IL-17, and IFN-y
  • other proteins e.g., IFN-a, IL-17, and IFN-y
  • Blood may be collected to assess changes in the level of MxA protein that may be related to the pathogenesis of DM/ASIM or the mechanism of action of daxdilimab.
  • Blood may be collected to assess changes in the level of IFN gene signature that may be related to the pathogenesis of DM or ASIM or the mechanism of action of daxdilimab.
  • PBMC peripheral blood mononuclear cell
  • Peripheral blood mononuclear cells may be collected to monitor changes in the frequency, and possibly gene expression, of immune cell populations in cryopreserved blood leukocytes.
  • Serum may be collected to measure changes in exploratory biomarkers of disease activity, changes in biomarkers related to the mechanism of action of daxdilimab, and changes in biomarkers resulting from daxdilimab administration.
  • Specific proteins to be assessed may include, but are not limited to, IFN-a and MxA to measure the effect of daxdilimab on interferon response. These analyses may be performed using both multiplexed assays for panels of biomarkers, as well as individual immunoassays for specific markers of relevance.
  • Whole blood samples may be collected and RNA isolated (whole blood transcriptomics in Table 3) to assess changes over time in the expression of genes or gene pathways associated with DM or ASIM, mechanism of action of or in response to daxdilimab administration, or the pathogenesis of DM or ASIM.
  • DNA may be isolated from a sample of whole blood collected at Baseline to test for:
  • Fc gamma receptor in genes that may be related to the mechanism of action of daxdilimab.
  • Antibodies to daxdilimab may be assessed by the incidence and titer of ADAs in serum samples collected from all participants according to Table 3.
  • serum samples may also be collected at the final visit from participants who discontinued IP or were withdrawn from the study.
  • Serum samples may be screened for antibodies binding to daxdilimab and the titer of confirmed positive samples may be reported. Other analyses may be performed to verify the stability of antibodies to daxdilimab and/or further characterize the immunogenicity of daxdilimab.
  • Samples may be stored for a maximum of 15 years (or according to local regulations) following the last participant’s last visit for the study.
  • SF36 is a health survey that measures functional health and wellbeing from the participant’s perspective with questions that span 8 health domains: physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health.
  • the Skindexl6 score (Table 11) is used for participants to rate skin conditions that have occurred within the previous week (Atherton et al, 2012; Chren et al, 2001). It is a short 16-item assessment that uses numerical analog scales from 0 (“never bothered”) to 6 (“always bothered”). Responses to the Skindexl6 are categorized into 3 subscales: symptom, emotional, and functional.
  • the PROMIS fatigue 8a assess a range of self-reported symptoms, from mild subjective feelings of tiredness to an overwhelming, debilitating, and sustained sense of exhaustion that likely decreases one’s ability to execute daily activities and function normally in family or social roles. Fatigue is divided into the experience of fatigue (frequency, duration, and intensity) and the impact of fatigue on physical, mental, and social activities. All assess fatigue over the past 7 days.
  • the PROMIS physical function 8b (V 2.0) measures self-reported capability rather than actual performance of physical activities. This includes the functioning of the participant’s upper extremities (dexterity), lower extremities (walking or mobility), and central regions (neck, back), as well as instrumental activities of daily living, such as running errands.
  • the form assesses current function rather than function over a specified period.
  • the PROMIS pain interference 6a evaluates the consequences of pain on relevant aspects of the participant’s life. This includes the extent to which pain hinders engagement with social, cognitive, emotional, physical, and recreational activities.
  • the PROMIS dyspnea severity evaluates the severity of shortness of breath or difficulty breathing that an adult experiences in response to various specific activities (e.g., dressing oneself without help, preparing meals, walking up 20 stairs).
  • the Global pain 24-hour NRS is an 11 -point scale scored from 0 (no pain) to 10 (the most intense pain imaginable). Participants select a value that is most in line with the intensity of pain they have experience in the last 24 hours.
  • the PGIC is a categorical scale (Table 12) in which participants are asked to indicate how much their DM or ASIM has changed since they started taking the IP, from ‘much better’ to ‘no change’ to ‘much worse’.
  • the estimand of primary interest is defined as follows, using hypothetical strategy to address intercurrent event of rescue medications and treatment policy strategy to address intercurrent event of treatment discontinuation.
  • Intercurrent event a. Rescue medications: The data collected after administration of the rescue medications may be excluded. b. Treatment discontinuation: Participants who discontinue IP before Week 24 may be asked to come to scheduled evaluations until Week 24. The data collected after discontinuation of IP may be included in the analysis.
  • the primary efficacy endpoint of TIS at Week 24 may be analyzed using a mixed model for repeated measures (MMRM), with treatment, visit, visit by treatment interaction, and randomization stratification factor included in the model.
  • MMRM mixed model for repeated measures
  • the supplementary analysis may be performed for the primary efficacy endpoint using treatment policy strategy to address intercurrent event of rescue medications (i.e., including data collected after rescue medications). Additional analysis may be performed. The details will be specified in the SAP.
  • the estimand for the binary secondary efficacy endpoints is defined as follows, using composite variable strategy to address intercurrent events.
  • TIS40 Participants in the Full Analysis Set.
  • TIS20 Participants in the Full Analysis Set.
  • OCS Clinically meaningful oral corticosteroid (OCS) reduction: Participants in the Full Analysis Set with OCS dose > 10 mg prednisone or equivalent at Baseline
  • TIS40 at Week 24 is defined by meeting the following criteria: i. TIS score > 40 at Week 24 ii. No deterioration at 2 consecutive visits at or prior to Week 24. iii. No use of rescue medications before Week 24. iv. No discontinuation of IP before Week 24.
  • TIS20 at Week 24 is defined by meeting the following criteria: i. TIS score > 20 at Week 24. ii. No deterioration at 2 consecutive visits at or prior to Week 24. iii. No use of rescue medications before Week 24. iv. No discontinuation of IP before Week 24.
  • Clinically meaningful OCS reduction at Week 24 is defined by meeting the following criteria: i. Either a 25% decrease from Baseline or an OCS dose of 7.5 mg/day of prednisone or equivalent at Week 24. ii. No use of rescue medications before Week 24. iii. No discontinuation of IP before Week 24.
  • Intercurrent event a. Rescue medications: Captured in the variable definition. b. Treatment discontinuation: Captured in the variable definition.
  • the binary secondary endpoints may be analyzed using a logistic regression model with treatment, baseline OCS dose (OCS reduction endpoint only), and randomization stratification factor included in the model.
  • the estimand for the continuous secondary efficacy endpoint of change from Baseline to Week 24 in CDASI activity score is similar to the primary estimand, using hypothetical strategy to address intercurrent event of rescue medications and treatment policy strategy to address intercurrent event of treatment discontinuation.
  • the change from Baseline to Week 24 in CDASI activity score may be analyzed using a MMRM approach, with treatment, visit, visit by treatment interaction, randomization stratification factor and baseline CDASI activity score included in the model.
  • the missing data may be handled by the MMRM approach.
  • the PK analysis may be based on the PK Analysis Set. Descriptive statistics of the serum daxdilimab concentration will be tabulated by visit and by treatment group for each of the DM and ASIM populations. Exposure-response (PD, ADA, safety, and efficacy) analysis may be conducted using serum daxdilimab concentration and available drug response data per the Sponsor’s discretion and as the data will allow.
  • Exposure-response (PD, ADA, safety, and efficacy) analysis may be conducted using serum daxdilimab concentration and available drug response data per the Sponsor’s discretion and as the data will allow.
  • the primary analysis may be conducted separately for each of the DM and ASIM populations after the last participant has completed the Week 24 visit or discontinued from study prior to Week 24 for that population. For the primary analysis, all the efficacy and safety data collected prior to the data cut-off will be analyzed.
  • the final analysis may be conducted separately for each of the DM and ASIM populations after the last participant has completed the study or discontinued early from study for that population.
  • a sample size of approximately 48 participants (up to approximately 24 participants per treatment group) is planned for each population (DM and ASIM). The sample size was calculated based on the primary efficacy endpoint. Twenty-one participants per treatment group will provide approximately 80% power to detect a mean difference of 20 between daxdilimab and placebo at the 2- sided alpha level of 0.10 using a 2-sample t-test, assuming a standard deviation of 25. The minimum detectable difference is 13 between the daxdilimab group and placebo group. Assuming a drop-out rate of 10% for the first 24 weeks of the study, approximately 24 participants per treatment group will be needed.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Immunology (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • General Chemical & Material Sciences (AREA)
  • Neurology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Public Health (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pain & Pain Management (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

La présente divulgation concerne des compositions et des méthodes de traitement de maladies (par exemple, des maladies et des troubles de la myosite) chez un sujet le nécessitant à l'aide d'anticorps anti-ILT7 ou de fragments de liaison à l'antigène de ceux-ci.
PCT/EP2023/085224 2022-12-12 2023-12-11 Agents de liaison anti-ilt7 pour le traitement et la prévention de la myosite Ceased WO2024126431A1 (fr)

Priority Applications (4)

Application Number Priority Date Filing Date Title
CN202380084938.3A CN120435497A (zh) 2022-12-12 2023-12-11 用于治疗和预防肌炎的抗ilt7结合剂
EP23829009.2A EP4634225A1 (fr) 2022-12-12 2023-12-11 Agents de liaison anti-ilt7 pour le traitement et la prévention de la myosite
AU2023393624A AU2023393624A1 (en) 2022-12-12 2023-12-11 Anti-ilt7 binding agents for the treatment and prevention of myositis
MX2025006626A MX2025006626A (es) 2022-12-12 2025-06-06 Agentes de union anti transcrito 7 similar a inmunoglobulina (ilt7) para el tratamiento y la prevencion de la miositis

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US202263387023P 2022-12-12 2022-12-12
US63/387,023 2022-12-12

Publications (1)

Publication Number Publication Date
WO2024126431A1 true WO2024126431A1 (fr) 2024-06-20

Family

ID=89386115

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2023/085224 Ceased WO2024126431A1 (fr) 2022-12-12 2023-12-11 Agents de liaison anti-ilt7 pour le traitement et la prévention de la myosite

Country Status (5)

Country Link
EP (1) EP4634225A1 (fr)
CN (1) CN120435497A (fr)
AU (1) AU2023393624A1 (fr)
MX (1) MX2025006626A (fr)
WO (1) WO2024126431A1 (fr)

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1987005330A1 (fr) 1986-03-07 1987-09-11 Michel Louis Eugene Bergh Procede pour ameliorer la stabilite des glycoproteines
WO2021113702A1 (fr) * 2019-12-06 2021-06-10 Viela Bio, Inc. Méthodes de traitement à l'aide de protéines de liaison à l'ilt7
US11072652B2 (en) 2016-03-10 2021-07-27 Viela Bio, Inc. ILT7 binding molecules and methods of using the same
WO2022235758A1 (fr) * 2021-05-04 2022-11-10 Viela Bio, Inc. Méthodes de traitement de troubles auto-immuns à l'aide de protéines de liaison à il t7

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1987005330A1 (fr) 1986-03-07 1987-09-11 Michel Louis Eugene Bergh Procede pour ameliorer la stabilite des glycoproteines
US11072652B2 (en) 2016-03-10 2021-07-27 Viela Bio, Inc. ILT7 binding molecules and methods of using the same
WO2021113702A1 (fr) * 2019-12-06 2021-06-10 Viela Bio, Inc. Méthodes de traitement à l'aide de protéines de liaison à l'ilt7
WO2022235758A1 (fr) * 2021-05-04 2022-11-10 Viela Bio, Inc. Méthodes de traitement de troubles auto-immuns à l'aide de protéines de liaison à il t7

Non-Patent Citations (12)

* Cited by examiner, † Cited by third party
Title
"UniProt", Database accession no. P59901
ANONYMOUS: "A Study to Evaluate VIB7734 in Participants With Systemic Lupus Erythematosus (SLE), Cutaneous Lupus Erythematosus (CLE), Sjogren's Syndrome, Systemic Sclerosis, Polymyositis, and Dermatomyositis. Record History", 13 August 2020 (2020-08-13), XP093134936, Retrieved from the Internet <URL:https://clinicaltrials.gov/study/NCT03817424?tab=history&a=6> *
APLIN, CRC CRIT. REV. BIOCHEM., vol. 22, 1981, pages 259 - 306
ATHERTON ET AL., EXPERT. OPIN. DRUG SAF., 2009
BIO VIELA: "NCT02780674 A Phase 1 Study of MEDI7734 in Type I Interferon-Mediated Autoimmune Diseases", CLINICALTRIALS.GOV, 21 December 2018 (2018-12-21), XP093103689, Retrieved from the Internet <URL:https://clinicaltrials.gov/study/NCT02780674?term=medi7734%20&cond=sle&rank=1&tab=table> [retrieved on 20231120] *
BODANSKY ET AL.: "The Practice of Peptide Synthesis", 1995, OXFORD UNIVERSITY PRESS
EDGE ET AL., ANAL. BIOCHEM., vol. 118, 1981, pages 131
HAKIMUDDIN ET AL., ARCH. BIOCHEM. BIOPHYS., vol. 259, 1987, pages 52
HARLOW ET AL.: "Antibodies: A Laboratory Manual", 1988, COLD SPRING HARBOR LABORATORY PRESS
MANIATIS: "Molecular Cloning, A Laboratory Manual", 1990, COLD SPRING HARBOR LABORATORY
PEREIRA NACHAN KFLIN PCSONG Z: "The ''less-is-more'' in therapeutic antibodies: Afucosylated anti-cancer antibodies with enhanced antibody-dependent cellular cytotoxicity", MABS, vol. 10, no. 5, July 2018 (2018-07-01), pages 693 - 711, XP055781805, DOI: 10.1080/19420862.2018.1466767
THOTAKURA ET AL., METH. ENZYMOL., vol. 138, 1987, pages 350

Also Published As

Publication number Publication date
MX2025006626A (es) 2025-07-01
EP4634225A1 (fr) 2025-10-22
CN120435497A (zh) 2025-08-05
AU2023393624A1 (en) 2025-05-15

Similar Documents

Publication Publication Date Title
US20220288199A1 (en) Therapeutic RNA and Anti-PD1 Antibodies for Advanced Stage Solid Tumor Cancers
KR20200014298A (ko) Her2 양성 암의 치료
JP7564347B2 (ja) 多発性硬化症を治療するためのｌｏｕ０６４
US20240287176A1 (en) Methods of treatment of autoimmune disorders using ilt7 binding proteins
CN113271962A (zh) 利用靶向TGF-β抑制的三阴性乳腺癌的治疗
KR20220163986A (ko) 브루톤 티로신 키나아제의 억제제를 이용한 재발성 다발성 경화증의 치료 방법
US20240383991A1 (en) Cd40l-specific tn3-derived scaffolds for the treatment and prevention of sjögren&#39;s syndrome
AU2023372400A1 (en) Methods for treating immune thrombocytopenia by administering (r)-2-[3-[4-amino-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-[4-(oxetan-3-yl)piperazin-1-yl]pent-2-enentrile
AU2023393624A1 (en) Anti-ilt7 binding agents for the treatment and prevention of myositis
EP4648787A1 (fr) Échafaudages dérivés de tn3 spécifiques au cd40l pour le traitement et la prévention du syndrome de sjögren
TW201842933A (zh) 使用il-17拮抗劑選擇性治療氣喘的方法
JP2025540348A (ja) 筋炎の処置及び予防のための、抗ｉｌｔ７結合剤
AU2024210360A1 (en) Anti-cd19 binding agents for the treatment and prevention of immune mediated necrotizing myopathy
TW202128172A (zh) 藉由投予(R)-2-[3-[4-胺基-3-(2-氟-4-苯氧基-苯基)吡唑并[3,4-d]嘧啶-1-基]哌啶-1-羰基]-4-甲基-4-[4-(環氧丙烷‐3‐基)哌嗪-1-基]戊-2-烯腈治療天皰瘡的方法
US20240368294A1 (en) Cd40l-specific tn3-derived scaffolds for use in the treatment and prevention of rheumatoid arthritis
AU2024261630A1 (en) Cd40l-specific tn3-derived scaffolds for the treatment and prevention of sjogren&#39;s syndrome
CN118076369A (zh) Cd40l特异性tn3衍生支架及其用于治疗和预防类风湿性关节炎的方法
CN119630422A (zh) 使用白细胞介素-17(il-17)拮抗剂治疗巨细胞动脉炎的方法
CN117940161A (zh) 伊奈利珠单抗及其在治疗或预防IgG4相关疾病中的使用方法
CN118488968A (zh) 用抗light抗体治疗哮喘的方法
CN117561076A (zh) 使用ilt7结合蛋白治疗自体免疫病症的方法
HK40059497A (en) Treatment of triple negative breast cancer with targeted tgf-b inhibition

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 23829009

Country of ref document: EP

Kind code of ref document: A1

WWE Wipo information: entry into national phase

Ref document number: AU2023393624

Country of ref document: AU

ENP Entry into the national phase

Ref document number: 2023393624

Country of ref document: AU

Date of ref document: 20231211

Kind code of ref document: A

ENP Entry into the national phase

Ref document number: 2025533615

Country of ref document: JP

Kind code of ref document: A

WWE Wipo information: entry into national phase

Ref document number: CN2023800849383

Country of ref document: CN

Ref document number: 202380084938.3

Country of ref document: CN

Ref document number: 2025533615

Country of ref document: JP

WWE Wipo information: entry into national phase

Ref document number: 2023829009

Country of ref document: EP

NENP Non-entry into the national phase

Ref country code: DE

ENP Entry into the national phase

Ref document number: 2023829009

Country of ref document: EP

Effective date: 20250714

WWP Wipo information: published in national office

Ref document number: 202380084938.3

Country of ref document: CN

WWP Wipo information: published in national office

Ref document number: 2023829009

Country of ref document: EP