Asthma treatment by blocking il-13 and tslp

Abstract

The present invention provides compounds for use in the treatment of pulmonary diseases, in particular asthma, wherein said compounds bind the cytokines IL-13 and TSLP. The treatments according to the present invention can lower the level of fractional exhaled nitric oxide (FeNO) by at least 18 ppb compared to placebo. The treatments of the present invention can also reduce eosinophil count, increase FEV1 and / or reduce airway inflammation.

Description

This invention provides compounds for use in the treatment of lung diseases, particularly asthma, wherein said compounds bind the cytokines IL-13 and TSLP. Treatment according to the invention reduces exhaled nitric oxide (FeNO) levels by at least 18 ppb compared to placebo. The treatment of the invention also reduces eosinophil counts, increases FEV1, and / or reduces airway inflammation. Abstract

Claims

CLAIMS1. A compound that binds IL-13 and TSLP for use in the treatment of a pulmonary disease in a subject, wherein said treatment reduces the level of fractional exhaled nitric oxide (FeNO) by at least 18 ppb compared to a control.

2. The compound for use according to claim 1, wherein the treatment reduces the level of FeNO by at least 20 ppb, at least 30 ppb, or by at least 40 ppb, compared to a control.

3. The compound for use according to any of the previous claims, wherein the pulmonary disease is asthma.

4. The compound for use according to claim 3, wherein the asthma is high eosinophilic asthma.

5. The compound for use according to claim 3, wherein the asthma is low eosinophilic asthma.

6. The compound for use according to any of the previous claims, wherein the control is baseline or wherein the control is placebo, optionally wherein baseline means the individual baseline of the subject.

7. The compound for use according to any of the previous claims, wherein said reduction of FeNO level occurs within 4 weeks after the administration of the compound, wherein optionally said reduction of FeNO level occurs within 2 weeks after the administration of the compound, wherein optionally said reduction of FeNO level occurs within 1 week after the administration of the compound.

8. The compound for use according to any of the previous claims, wherein the compound that binds IL-13 and TSLP is a polypeptide, such as an antibody or an antibody fragment.

9. The compound for use according to claim 8, wherein the polypeptide comprises or consists of at least four ISVDs, wherein two ISVDs specifically bind IL-13 and two ISVDs specifically bind TSLP, wherein each of said at least four ISVDs comprises three complementarity determining regions (CDR1 to CDR3, respectively), whereinthe at least four ISVDs are optionally linked via one or more peptidic linkers, and wherein: a first ISVD comprises: a CDR1 that is the amino acid sequence of SEQ ID NO: 7, a CDR2 that is the amino acid sequence of SEQ ID NO: 12 and a CDR3 that is the amino acid sequence of SEQ ID NO: 17, a second ISVD comprises: a CDR1 that is the amino acid sequence of SEQ ID NO: 8, a CDR2 that is the amino acid sequence of SEQ ID NO: 13 and a CDR3 that is the amino acid sequence of SEQ ID NO: 18, a third ISVD comprises: a CDR1 that is the amino acid sequence of SEQ ID NO: 9, a CDR2 that is the amino acid sequence of SEQ ID NO: 14 and a CDR3 that is the amino acid sequence of SEQ ID NO: 19, and a fourth ISVD comprises: a CDR1 that is the amino acid sequence of SEQ ID NO: 11, a CDR2 that is the amino acid sequence of SEQ ID NO: 16 and a CDR3 that is the amino acid sequence of SEQ ID NO: 21.

10. The compound for use according to claim 8 or 9, wherein the polypeptide comprises or consists of the amino acid sequence of SEQ ID NO: 1.

11. The compound for use according to any of the previous claims, wherein the subject has a baseline FeNO level of at least 50 ppb, and an eosinophil count of more than or equal to 0.3 *109cells / L.

12. A compound that binds IL-13 and TSLP for use in the treatment of a pulmonary disease in a subject, wherein said treatment reduces the eosinophil count in blood by at least 30% compared to a control.

13. The compound for use according to claim 12, wherein said reduction of the eosinophil count occurs within 4 weeks after the administration of the compound,wherein optionally said reduction of the eosinophil count occurs within 2 weeks after the administration of the compound, wherein optionally said reduction of the eosinophil count occurs within 1 week after the administration of the compound.

14. A compound that binds IL-13 and TSLP for use in the treatment of a pulmonary disease in a subject, wherein said treatment reduces airway inflammation.

15. The compound for use according to claim 14, wherein said reduction of airway inflammation is characterized by a reduction of FeNO by at least 18 ppb, a reduction of eosinophil count by at least 30% and / or an increase of the forced expiratory volume in one second (FEV1) by at least 0.07 L compared to a control.

16. The compound for use according to claim 15, wherein said reduction of airway inflammation occurs within 4 weeks after the administration of the compound, wherein optionally said reduction of airway inflammation occurs within 2 weeks after the administration of the compound, wherein optionally said reduction of airway inflammation occurs within 1 week after the administration of the compound.

17. A compound which binds TSLP and / or IL-13 for use in reducing the FeNO level in a subject, wherein the reduction of FeNO level prevents a loss of lung function.

18. The compound for use according to claim 17, wherein said reduction of FeNO level is a reduction by at least 18 ppb.

19. The compound for use according to claim 17 or 18, wherein said reduction of FeNO level is a reduction to a level below 25 ppb.

20. The compound for use according to any of claims 17-19, wherein the subject has a baseline FeNO level of at least 50 ppb, at least 35 ppb, or at least 25 ppb.

21. The compound for use according to any of claims 17-20, wherein the subject has a baseline FeNO level of at least 50 ppb, and an eosinophil count of more than or equal to 0.3 *109cells / L.

22. The compound for use according to any of claims 17-21, wherein the compound binds TSLP and IL-13.

23. The compound for use according to any of claims 17-21, wherein said loss of lung function is linked to asthma.

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