Dosing and treatment of immune-mediated diseases and biomarkers associated with immune-mediated diseases

By selecting subjects with atopic dermatitis based on elevated TARC, IL-5, and LDH biomarkers, personalized treatment strategies improve the efficacy of immune-mediated atopic dermatitis management.

HK40135685APending Publication Date: 2026-07-31KYMBA LIMITED
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Patent Information

Application Number
HK62026123399
Authority / Receiving Office
HK · HK
Patent Type
Applications
Current Assignee / Owner
Priority Date
2024-05-08
Filing Date
2026-05-14
Publication Date
2026-07-31

AI Technical Summary

Technical Problem

Current treatments for moderate to severe atopic dermatitis are inadequate in addressing the immune-mediated aspects of the disease, particularly in subjects with elevated levels of specific biomarkers such as thymus activation-regulated chemokine (TARC), interleukin-5 (IL-5), and lactate dehydrogenase (LDH).

Method used

Selecting subjects with atopic dermatitis based on elevated levels of TARC, IL-5, and LDH biomarkers to tailor targeted treatment approaches.

Benefits of technology

Enhances the effectiveness of treatment by personalizing therapy for subjects with moderate to severe atopic dermatitis, addressing immune-mediated components through biomarker-guided selection.

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Abstract

The present disclosure provides methods of treating an immune-mediated disease in a subject in need thereof. The present disclosure provides methods of treating atopic dermatitis in a subject in need thereof. The present disclosure provides methods of treating moderate-to-severe atopic dermatitis in a subject in need thereof. The present disclosure provides a method of treating atopic dermatitis (AD) in a subject in need thereof, comprising selecting a subject having AD and an elevated level of at least one biomarker selected from the group consisting of thymus and activation-regulated chemokine (TARC), interleukin-5 (IL-5), eosinophil count, and lactate dehydrogenase (LDH) relative to a control.
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Description

This disclosure provides methods for treating immune-mediated diseases in subjects with atopic dermatitis. This disclosure provides methods for treating moderate to severe atopic dermatitis in subjects with atopic dermatitis (AD). This disclosure provides a method for treating atopic dermatitis (AD) in subjects with atopic dermatitis (AD) comprising selecting subjects with AD and having elevated levels of at least one biomarker selected from the group consisting of: thymus activation-regulated chemokine (TARC), interleukin-5 (IL-5), eosinophil count, and lactate dehydrogenase (LDH).Abstract DOSING AND TREATMENT OF IMMUNE-MEDIATED DISEASES AND BIOMARKERS ASSOCIATED WITH IMMUNE-MEDIATED DISEASES The present disclosure provides methods of treating an immune-mediated disease in a subject in need thereof. The present disclosure provides methods of treating atopic dermatitis in a subject in need thereof. The present disclosure provides methods of treating moderate-to-severe atopic dermatitis in a subject in need thereof. The present disclosure provides a method of treating atopic dermatitis (AD) in a subject in need thereof, comprising selecting a subject having AD and an elevated level of at least one biomarker selected from the group consisting of thymus and activation-regulated chemokine (TARC), interleukin-5 (IL-5), eosinophil count, and lactate dehydrogenase (LDH) relative to a control. 摘 要。

Claims

WHAT IS CLAIMED:

1. A method of treating an immune-mediated disease in a subject in need thereof, comprising administering to the subject an anti-OX40 ligand (OX40L) antibody or antigen binding fragment thereof, wherein the antibody or antigen binding fragment thereof comprises a heavy chain complementarity determining region (HCDR) 1 of SEQ ID NO: 42, an HCDR2 of SEQ ID NO: 44, and an HCDR3 of SEQ ID NO: 46, and a light chain complementarity determining region (LCDR) 1 of SEQ ID NO: 56, an LCDR2 of SEQ ID NO: 58, and an LCDR3 of SEQ ID NO: 60, wherein the subject receives directly doses every 12 weeks (Q12W), without prior dose administration every 4 weeks (Q4W).

2. A method of treating atopic dermatitis in a subject in need thereof, comprising administering to the subject an anti-OX40 ligand (OX40L) antibody or antigen binding fragment thereof, wherein the antibody or antigen binding fragment thereof comprises a heavy chain complementarity determining region (HCDR) 1 of SEQ ID NO: 42, an HCDR2 of SEQ ID NO: 44, and an HCDR3 of SEQ ID NO: 46, and a light chain complementarity determining region (LCDR) 1 of SEQ ID NO: 56, an LCDR2 of SEQ ID NO: 58, and an LCDR3 of SEQ ID NO: 60, wherein the subject receives directly doses every 12 weeks (Q12W), without prior dose administration every 4 weeks (Q4W).

3. The method of claim 1 or 2, wherein the antibody or antigen binding fragment thereof is amlitelimab or a variant thereof.

4. The method of claim 1, 2 or 3, wherein the antibody is amlitelimab.

5. The method of any one of claims 1-4, wherein the antibody or antigen binding fragment thereof is administered by prefilled syringe, pen delivery device or autoinjector.

6. The method of any one of claims 1-4, wherein the subject receives an initial dose of about 500 mg of the antibody or antigen binding fragment thereof followed by one or more secondary doses of about 250 mg of the antibody or antigen binding fragment thereof.

7. The method of any of the preceding claims, wherein the atopic dermatitis is moderate- to-severe atopic dermatitis.

8. The method of claim 7, wherein the moderate-to-severe atopic dermatitis is not adequately controlled with topical prescription therapies or with systemic therapies or when those therapies are not advisable.

9. The method of any one of the preceding claims, wherein EASI score is reduced in the subject.

10. The method of claim 9, wherein the EASI score is selected from the group consisting of EASI-75, EASI-90 and EASI-100.

11. The method of any one of the preceding claims, wherein Investigator Global Assessment (IGA) score is reduced in the subject.

12. A method of treating an immune mediated disease in an adolescent subject in need thereof, comprising administering to the adolescent subject an anti-OX40 ligand (OX40L) antibody or antigen binding fragment thereof, wherein the antibody or antigen binding fragment thereof comprises a heavy chain complementarity determining region (HCDR) 1 of SEQ ID NO: 42, an HCDR2 of SEQ ID NO: 44, and an HCDR3 of SEQ ID NO: 46, and a light chain complementarity determining region (LCDR) 1 of SEQ ID NO: 56, an LCDR2 of SEQ ID NO: 58, and an LCDR3 of SEQ ID NO:

60.

13. A method of treating atopic dermatitis in an adolescent subject in need thereof, comprising administering to the adolescent subject an anti-OX40 ligand (OX40L) antibody or antigen binding fragment thereof, wherein the antibody or antigen binding fragment thereof comprises a heavy chain complementarity determining region (HCDR) 1 of SEQ ID NO: 42, an HCDR2 of SEQ ID NO: 44, and an HCDR3 of SEQ ID NO: 46, and a light chain complementarity determining region (LCDR) 1 of SEQ ID NO: 56, an LCDR2 of SEQ ID NO: 58, and an LCDR3 of SEQ ID NO: 60.

14. The method of claim 12 or 13, wherein the antibody is amlitelimab or a variant thereof.

15. The method of claim 12, 13 or 14, wherein the antibody is amlitelimab.

16. The method of any one of claims 12-15, wherein the antibody or antigen binding fragment thereof is administered by prefilled syringe, pen delivery device or autoinjector.

17. The method of any one of claims 12-16, wherein the adolescent subject has a body weight ranging from about 25 kg to about 40 kg.

18. The method of any one of claims 12-17 wherein the adolescent subject receives an initial dose of about 250 mg of the antibody or antigen binding fragment thereof followed by one or more secondary doses of about 125 mg of the antibody or antigen binding fragment thereof.

19. The method of any one of claims 12-18, wherein each dose is administered Q12W.

20. The method of any one of claims 12-18, wherein the subject receives doses Q12W from the start of treatment.

21. The method of any one of claims 12-18, wherein the subject receives directly doses Q12W, without prior dose administration Q4W.

22. The method according to any one of claims 12-21, wherein the subject is aged 12 years or older (e.g. the subject is aged 12-17 years old).

23. The method of any one of claims 12-22, wherein the atopic dermatitis is moderate- to-severe atopic dermatitis.

24. The method of claim 23, wherein the moderate-to-severe atopic dermatitis is not adequately controlled with topical prescription therapies or with systemic therapies or when those therapies are not advisable.

25. The method of any one of claims 12-24, wherein EASI score is reduced in the subject.

26. The method of claim 25, wherein the EASI score is selected from the group consisting of EASI-75, EASI-90 and EASI-100.

27. The method of any one of claims 12-24, wherein IGA score is reduced in the subject.

28. The method of any one of claims 12-24, wherein (a) the subject weighs equal to or greater than 25 kg and less than 40 kg, and wherein the subject is administered a formulation comprising a 62.5 mg / mL amlitelimab solution supplied as a prefilled syringe that delivers 125 mg of amlitelimab in a 2 mL injection, or (b) the subject weighs equal to or greater than 25 kg and less than 40 kg, and wherein the subject is administered a formulation comprising a 125 mg / mL amlitelimab solution supplied as a prefilled syringe that delivers 125 mg of amlitelimab in a 1 mL injection.

29. A method of treating an immune mediated disease in a subject in need thereof, comprising administering to the subject an anti-OX40 ligand (OX40L) antibody or antigen binding fragment thereof, wherein the antibody or antigen binding fragment thereof comprises a heavy chain complementarity determining region (HCDR) 1 of SEQ ID NO: 42, an HCDR2 of SEQ ID NO: 44, and an HCDR3 of SEQ ID NO: 46, and a light chain complementarity determining region (LCDR) 1 of SEQ ID NO: 56, an LCDR2 of SEQ ID NO: 58, and an LCDR3 of SEQ ID NO: 60, wherein the subject has a body weight ranging from about 25 kg to about 40 kg.

30. A method of treating atopic dermatitis in a subject in need thereof, comprising administering to the subject an anti-OX40 ligand (OX40L) antibody or antigen binding fragment thereof, wherein the antibody or antigen binding fragment thereof comprises a heavy chain complementarity determining region (HCDR) 1 of SEQ ID NO: 42, an HCDR2 of SEQ ID NO: 44, and an HCDR3 of SEQ ID NO: 46, and a light chain complementarity determining region (LCDR) 1 of SEQ ID NO: 56, an LCDR2 of SEQ ID NO: 58, and anLCDR3 of SEQ ID NO: 60, wherein the subject has a body weight ranging from about 25 kg to about 40 kg.

31. The method of claim 29 or 30, wherein the antibody is amlitelimab or a variant thereof.

32. The method of claim 29, 30 or 31, wherein the antibody is amlitelimab.

33. The method of any one of claims 29-32, wherein the antibody or antigen binding fragment thereof is administered by prefilled syringe, pen delivery device or autoinjector.

34. The method of any one of claims 29-33, wherein the subject receives an initial dose of about 250 mg of the antibody or antigen binding fragment thereof followed by one or more secondary doses of about 125 mg of the antibody or antigen binding fragment thereof.

35. The method of any one of claims 29-34, where each dose is administered Q12W.

36. The method of any one of claims 29-34, wherein the subject receives doses Q12W from the start of treatment.

37. The method of any one of claims 29-34, wherein the subject receives directly doses Q12W, without prior dose administration Q4W.

38. The method of claim 34, wherein each secondary dose is administered Q12W during 24 weeks or up to when the patient has achieved vIGA O / 1, or has clear or substantially clear skin, or has achieved EASI 75 or has achieved EASI 90.

39. The method according to any one of claims 29-38, wherein the subject is aged 12 years or older (e.g. the subject is aged 12-17 years old).

40. The method of any one of claims 29-38, wherein the atopic dermatitis is moderate- to-severe atopic dermatitis.

41. The method of claim 40, wherein the moderate-to-severe atopic dermatitis is not adequately controlled with topical prescription therapies or with systemic therapies or when those therapies are not advisable.

42. The method of any one of claims 29-38, wherein EASI score is reduced in the subject.

43. The method of claim 42, wherein the EASI score is selected from the group consisting of EASI-75, EASI-90 and EASI-100.

44. The method of any one of claims 29-43, wherein IGA score is reduced in the subject.

45. A method of treating atopic dermatitis in a subject in need thereof, comprising administering to the subject an anti-OX40 ligand (OX40L) antibody or antigen binding fragment thereof, wherein the antibody or antigen binding fragment thereof comprises a heavy chain complementarity determining region (HCDR) 1 of SEQ ID NO: 42, an HCDR2 of SEQ ID NO: 44, and an HCDR3 of SEQ ID NO: 46, and a light chain complementarity determining region (LCDR) 1 of SEQ ID NO: 56, an LCDR2 of SEQ ID NO: 58, and an LCDR3 of SEQ ID NO: 60, wherein efficacy is maintained at week 28 off of treatment or at week 32 after final administration of the antibody or antigen binding fragment thereof to the subject.

46. The method of claim 45, wherein each dose is administered Q12W.

47. The method of claim 45 or 46, wherein the subject receives doses Q12W from the start of treatment.

48. The method of any of claims 45-47, wherein the subject receives directly doses Q12W, without prior dose administration Q4W.

49. The method of any of claims 45-48, wherein the subject is a vIGA 0 / 1 responder and vIGA O / 1 response efficacy is maintained in the subject, or wherein the subject is an AESI 75 responder and EASI 75 response efficacy is maintained in the subject.

50. The method of any of claims 45-48, wherein the subject is a vIGA 0 / 1 responder and vIGA O / 1 response efficacy is maintained in the subject.

51. The method of any of claims 45-48, wherein the subject is an AESI 75 responder and EASI 75 efficacy response is maintained in the subject.

52. A method of treating atopic dermatitis in a subject in need thereof, comprising administering to the subject amlitelimab, wherein the subject receives directly doses every 12 weeks (Q12W), without prior dose administration every 4 weeks (Q4W), and wherein the subject receives an initial dose of about 500 mg of amlitelimab followed by one or more secondary doses of about 250 mg of amlitelimab.

53. A method of treating atopic dermatitis in an adolescent subject in need thereof, comprising administering to the adolescent subject amlitelimab, wherein the adolescent subject receives an initial dose of about 250 mg of amlitelimab followed by one or more secondary doses of about 125 mg of amlitelimab, and wherein the subject receives doses Q12W from the start of treatment.

54. A method of treating atopic dermatitis in a subject in need thereof, comprising administering to the subject amlitelimab, wherein the subject has a body weight ranging from about 25 kg to about 40 kg, wherein the subject receives an initial dose of about 250 mg of amlitelimab followed by one or more secondary doses of about 125 mg of amlitelimab, and wherein the subject receives doses Q12W from the start of treatment.

55. A method of treating atopic dermatitis (AD) in a subject in need thereof, comprising administering to the subject amlitelimab, wherein the subject receives directly doses every 12 weeks (Q12W), without prior dose administration every 4 weeks (Q4W), wherein the subject receives an initial dose of about 500 mg of amlitelimab followed by one or more secondary doses of about 250 mg of amlitelimab, and wherein the method results in a decrease of the level of at least one biomarker in the subject relative to a control.

56. A method of treating atopic dermatitis (AD) in a subject in need thereof, comprising administering to the subject amlitelimab, wherein the subject receives directly doses every 12 weeks (Q12W), without prior dose administration every 4 weeks (Q4W), and wherein the subject receives an initial dose of about 500 mg of amlitelimab followed by one or more secondary doses of about 250 mg amlitelimab.

57. A method of treating atopic dermatitis (AD) in a subject in need thereof, comprising administering to the subject amlitelimab, wherein the subject receives directly doses every 12 weeks (Q12W), without prior dose administration every 4 weeks (Q4W), and wherein the subject receives an initial dose of about 500 mg of amlitelimab followed by one or more secondary doses of about 250 mg of amlitelimab.

58. A method of treating atopic dermatitis in a subject in need thereof, comprising administering to the subject amlitelimab, wherein the subject receives directly doses every 12 weeks (Q12W), without prior dose administration every 4 weeks (Q4W), and wherein the subject receives an initial dose of about 500 mg of amlitelimab followed by one or more secondary doses of about 250 mg of amlitelimab, and wherein efficacy is maintained at week 28 off of treatment or at week 32 after final administration of amlitelimab.

59. The method of any one of claims 1, 2, 12, 13, 29, 30, and 45, wherein the antibody or antigen binding fragment thereof is an OX40L antagonist.