TRATAMENTO DE ASMA POR BLOQUEIO DE IL-13 E 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

1 / 126 “ASTHMA TREATMENT BY IL-13 BLOCKADE AND TSLP” DESCRIPTION Field of the present invention

[0001] The present invention relates to the treatment of asthma by administering a compound that binds to IL-13 and TSLP. Blocking these two cytokines shows one or more notable effects, such as reducing the level of fractionated exhaled nitric oxide (FeNO) by at least 18 ppb compared to a control, such as placebo, and reducing the blood eosinophil count by at least 30% compared to a control, such as placebo. The treatment may also reduce airway inflammation and reduce small airway obstruction. Background

[0002] Although necessary for host defense, unrestrained immune responses can lead to a range of inflammatory diseases, such as asthma, atopic dermatitis, and rheumatoid arthritis. A cascade of immune responses mediated by the innate and adaptive arms of the immune system (e.g., antigen recognition, antigen processing, antigen presentation, cytokine production, antibody production, target cell killing) drives the onset and spread of a range of immunological diseases. Inflammatory diseases are often chronic and can even be fatal. Allergic and atopic diseases, such as asthma, are often driven predominantly by type 2 immune responses and characterized by salient features of type 2 immunity, such as high IgE production and eosinophilia.

[0003] Thymic stromal lymphopoietin (TSLP) and interleukin-13 (IL13) are soluble cytokine targets produced by stromal and / or immune cells (Ziegler & Artis, Nat Rev Immunol (2010) 11:289, Gieseck III et al., Nat Rev Immunol (2018) 18:62). Human TSLP and IL-13 lead Petition 870250085505, dated 09 / 22 / 2025, p. 10 / 173 2 / 126 distinct, overlapping, and synergistic aspects of immunity and autoimmunity, such as type 2 inflammation.

[0004] TSLP signaling begins via a heterodimeric receptor complex composed of thymic stromal lymphopoietin receptor (TSLPR) and the alpha chain of IL-7R (IL-7Ra). Similarly, IL-13 signaling begins with binding to a heterodimeric receptor complex consisting of IL-4 alpha receptor (IL-4Ra) and interleukin-13 alpha receptor (IL-13R1a). The high affinity of IL-13 for IL-13R1 leads to their complex formation, which further increases the likelihood of heterodimer formation with IL-4Ra.

[0005] TSLP drives dendritic cell maturation, mast cell development and proliferation, as well as the activation of other immune cells, such as basophils and innate lymphoid cells (ILC2). Similarly, IL-13 exerts a range of immunopathologies, such as epithelial barrier disruption, mucus production from mucosal-epithelial surfaces, airway remodeling, as well as the induction of eosinophil recruitment chemokines, such as eotaxin. These mechanisms are central to the initiation and propagation of the type 2 inflammatory response and are central to the development of a range of immunopathologies in diseases such as atopic dermatitis and asthma.

[0006] Not all patients with moderate / severe asthma are responding adequately to currently available standard of care treatments, including biologics such as anti-IL4Ra monoclonal antibody Dupixent (dupilumab; marketed), anti-IL5s (marketed), anti-IgE monoclonal antibody Xolair (omalizumab; marketed), there is a particular unmet need in asthma patients with a low eosinophilic phenotype. Although monoclonal antibodies exist Petition 870250085505, dated 09 / 22 / 2025, page 11 / 173 3 / 126 antagonists against TSLP (tezepelumab, marketed) and IL-13 (lebriquizumab), there is no marketed compound that targets both TSLP and IL-13. Dual targeting of TSLP and IL-13 with a single compound may have the potential to confer efficacy in both low- and high-eosinophilic asthma, with the potential to confer efficacy in subpopulations within these indications where a single monospecific agent therapy may not be fully effective.

[0007] Targeting multiple disease factors can be achieved, for example, by co-administration or combinatorial use of two separate biological products, for example, antibody binding to different therapeutic targets. However, co-administration or combinatorial use of separate biological products can be challenging, both practically and commercially. For example, two injections of separate products result in a more inconvenient and painful treatment regimen for patients, which can negatively affect adherence. Compared to a single injection of two separate products, it may be difficult or impossible to provide formulations that allow acceptable viscosity at the required concentrations and adequate stability of both products. Additionally, co-administration and co-formulation require the production of two separate drugs, which can increase overall costs.Bispecific antibodies, which are capable of binding to two different antigens, have been suggested as a strategy to address such limitations associated with the co-administration or combinational use of separate biological products, such as antibodies.

[0008] These factors hinder the development of multispecific therapies for asthma. There is a significant need for additional therapies to treat asthma that target multiple pathological pathways. The present invention addresses this need. Petition 870250085505, dated 09 / 22 / 2025, page 12 / 173 4 / 126 providing a compound that links TSLP and IL-13 for use in the treatment of a lung disease, for example, asthma. The present invention shows for the first time that the simultaneous targeting of TSLP and IL-13 is highly effective in patients with asthma. In particular, the present invention shows that treatment with a compound that blocks TSLP and IL-13 leads to improvement in specific clinical parameters, such as FeNO levels, to a much greater extent than existing asthma medication. Summary of the present invention

[0009] The present invention demonstrates for the first time the strong effect of simultaneously blocking TSLP and IL-13 in human subjects suffering from a pulmonary disease such as asthma. In particular, this effect materializes in a reduction of FeNO level by at least 18 ppb compared to baseline FeNO level or placebo and / or a reduction in eosinophil count by at least 30% compared to baseline eosinophil count or placebo and / or an increase in forced expiratory volume in one second (FEV1) by at least 0.07 L compared to baseline FEV1 or placebo. The present invention shows that simultaneously blocking TSLP and IL-13 in human subjects reduces airway inflammation and improves pulmonary function.

[00010] In another aspect, the present invention relates to a preventive aspect. As the present invention provides ways to reduce FeNO levels to a greater extent than known treatments, this opens the possibility of preventive administration to treat individuals with elevated FeNO levels, to prevent a loss of lung function before it even occurs. This preventive administration can be for patients with asthma and individuals at risk of developing asthma, as well as patients with other lung diseases and individuals at risk of developing other diseases. Petition 870250085505, dated 09 / 22 / 2025, p. 13 / 173 5 / 126 pulmonary. Thus, the present invention relates to compounds for use in reducing the level of FeNO in an individual wherein the reduction of the FeNO level prevents a loss of pulmonary function.

[00011] The present invention provides the following exemplary embodiments: [1] A compound that binds to IL-13 and TSLP for use in the treatment of a lung disease in an individual, wherein said treatment reduces the fractionated exhaled nitric oxide (FeNO) level by at least 18 ppb compared with a control. [2] The compound for use according to embodiment [1], in which the treatment reduces the FeNO level by at least 20 ppb, at least 30 ppb or at least 40 ppb, compared with a control. [3] The compound for use in accordance with any of the above modalities, where the lung disease is asthma. [4] The compound for use according to the modality [3], in which asthma is elevated eosinophilic asthma. [5] The compound for use according to the modality [3], in which the asthma is low eosinophilic asthma. [6] The compound for use in accordance with any of the preceding modalities, wherein the control is the baseline or wherein the control is placebo, optionally wherein the baseline means the individual's individual baseline. [7] The compound for use in accordance with any of the foregoing embodiments, wherein said reduction in FeNO level occurs within 4 weeks after administration of the compound, wherein optionally said reduction in FeNO level occurs within 2 weeks after administration of the compound, wherein optionally said reduction in FeNO level occurs within 1 week after administration of the compound. [8] The compound for use in accordance with any of the modalities Petition 870250085505, dated 09 / 22 / 2025, page 14 / 173 6 / 126 previous, in which the compound that binds to IL-13 and TSLP is a polypeptide, such as an antibody or an antibody fragment. [9] The compound for use according to embodiment [8], wherein the polypeptide comprises or consists of at least four ISVDs, wherein two ISVDs bind specifically to IL-13 and two ISVDs bind specifically to TSLP, wherein each of said at least four ISVDs comprises three complementarity-determining regions (CDR1 to CDR3, respectively), wherein the at least four ISVDs are optionally linked via one or more peptide linkers, and wherein: A first ISVD comprises: A CDR1, which is the amino acid sequence with SEQ ID NO: 7; a CDR2, which is the amino acid sequence with SEQ ID NO: 12; and a CDR3, which is the amino acid sequence with SEQ ID NO: 17; a second ISVD comprises: A CDR1, which is the amino acid sequence with SEQ ID NO: 8; a CDR2, which is the amino acid sequence with SEQ ID NO: 13; and a CDR3, which is the amino acid sequence with SEQ ID NO: 18; a third ISVD comprises: a CDR1 which is the amino acid sequence of SEQ ID NO: 9, a CDR2 which is the amino acid sequence of SEQ ID NO: 14 and a CDR3 which is the amino acid sequence of SEQ ID NO: 19, and a fourth ISVD comprises: CDR1, which is the amino acid sequence with SEQ ID NO: 11; CDR2, which is the amino acid sequence with SEQ ID NO: 16; and CDR3, which is the amino acid sequence with SEQ ID NO: 21.

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

[11] The compound for use in accordance with any of Petition 870250085505, dated 09 / 22 / 2025, p. 15 / 173 7 / 126 previous modalities, in which the individual has a baseline FeNO level of at least 50 ppb and an eosinophil count greater than or equal to 0.3 *109 cells / l.

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

[13] The compound for use according to the embodiment

[12] , wherein said reduction in eosinophil count occurs within 4 weeks after administration of the compound, wherein optionally said reduction in eosinophil count occurs within 2 weeks after administration of the compound, wherein optionally said reduction in eosinophil count occurs within 1 week after administration of the compound.

[14] A compound that binds to IL-13 and TSLP for use in the treatment of a lung disease in an individual, wherein said treatment reduces airway inflammation.

[15] The compound for use according to the modality

[14] , in which said reduction of airway inflammation is distinguished by a reduction in FeNO of at least 18 ppb, a reduction in eosinophil count of at least 30% and / or an increase in forced expiratory volume in one second (FEV1) of at least 0.07 L compared with a control.

[16] The compound for use according to the modality

[15] , wherein said reduction of airway inflammation occurs within 4 weeks after administration of the compound, wherein optionally said reduction of airway inflammation occurs within 2 weeks after administration of the compound, wherein optionally said reduction of airway inflammation occurs within 1 week after administration of the compound. Petition 870250085505, dated 09 / 22 / 2025, page 16 / 173 8 / 126 In another aspect, the present invention provides the following illustrative embodiments:

[17] A compound that binds TSLP and / or IL-13 for use in reducing FeNO levels in an individual, wherein reducing FeNO levels prevents a loss of lung function.

[18] The compound for use according to embodiment

[17] , wherein the said reduction in FeNO level is a reduction of at least 18 ppb.

[19] The compound for use in accordance with either of the embodiments

[18] and

[19] , wherein the said reduction in FeNO level is a reduction to a level below 25 ppb.

[20] The compound for use in accordance with any of the embodiments

[17] ,

[18] and

[19] , in which the individual has a baseline FeNO level of at least 50 ppb, at least 35 ppb or at least 25 ppb.

[21] The compound for use in accordance with any of the embodiments

[17] ,

[18] ,

[19] and

[20] , in which the individual has a baseline FeNO level of at least 50 ppb and an eosinophil count greater than or equal to 0.3 *109 cells / l.

[22] The compound for use in accordance with any of the embodiments

[17] ,

[18] ,

[19] ,

[20] and

[21] , in which the compound binds to TSLP and IL-13.

[23] The compound for use in accordance with any of the modalities

[17] ,

[18] ,

[19] ,

[20] ,

[21] and

[22] , in which the said loss of lung function is linked to asthma. Brief description of the drawings

[00012] Figure 1: Timeline of the Example 1 clinical trial (PDY16622). The timeline indicates the treatments / measurements that were performed at the indicated time points (D for day) of the clinical trial.

[00013] Figure 2: FeNO measurements from the Example 1 clinical trial (PDY16622). The change in exhaled nitric oxide level is shown. Petition 870250085505, dated 09 / 22 / 2025, p. 17 / 173 9 / 126 fractionated (in parts per billion, ppb) relative to baseline for the SAR443765 group (dashed line) and the placebo group (solid line).

[00014] Figure 3: FeNO measurements from the Example 1 clinical trial (PDY16622), analyzed according to low / high eosinophil subgroups. Shown is the change in fractionated exhaled nitric oxide level (in parts per billion, ppb) relative to baseline for the SAR443765 high eosinophil group (lower dashed line, dark gray), the SAR443765 low eosinophil group (lower solid line, dark gray), the high eosinophil placebo group (upper dashed line, light gray), and the low eosinophil placebo group (upper dashed line).

[00015] Figure 4: Eosinophil count from the clinical trial of example 1 (PDY16622). The median change in eosinophil count compared to baseline at D29 (4 weeks) is shown for the SAR443765 group (right) and the placebo group (left).

[00016] Figure 5: Eosinophil count from the Example 1 clinical trial (PDY16622, right bar) compared with three other biologics: lebriquizumab (left bar), tezepelumab (second bar from the left), and dupilumab (second bar from the right) at D29.

[00017] Figure 6: FEV1 measurements from the Example 1 clinical trial (PDY16622). The change in FEV1 (in liters, compared to baseline) of the SAR443765 group (dashed line) and the placebo group (solid line) is shown. All measurements were included.

[00018] Figure 7: FEV1 measurements from the Example 1 clinical trial (PDY16622). The change in FEV1 (in liters, compared to baseline) of the SAR443765 group (dashed line) and the placebo group (solid line) is shown. Only measurements that met all quality criteria were included.

[00019] Figure 8: FEV1 measurements from the clinical trial of example 1 Petition 870250085505, dated 09 / 22 / 2025, page 18 / 173 10 / 126 (PDY16622). The change in FEV1 (in liters, compared to baseline) is shown in Figure 7. The SAR443765 group and the placebo group were each divided into two subpopulations depending on the baseline percentage of predicted FEV1 (ppFEV1). The subpopulations are: SAR443765, baseline ppFEV1 > 80% (dark gray solid line); SAR443765, baseline ppFEV1 < 80% (dark gray dashed line); placebo, baseline ppFEV1 > 80% (light gray solid line); placebo, baseline ppFEV1 < 80% (light gray dashed line).

[00020] Figure 9: Forced Expiratory Flow 25-75% (FEF25-75) measurements from the Example 1 clinical trial (PDY16622). The change in FEF25-75 (in liters / s, compared to baseline) is shown. The top panel shows the change in FEF25-75 of the SAR443765 group (dashed line) and the placebo group (solid line). In the bottom panel, the SAR443765 group and the placebo group were each divided into two subpopulations depending on the baseline percentage of predicted FEV1 (ppFEV1). The subpopulations are: SAR443765, baseline ppFEV1 > 80% (dark gray solid line); SAR443765, baseline ppFEV1 < 80% (dark gray dashed line); placebo, baseline ppFEV1 > 80% (light gray solid line); Placebo, baseline ppFEV1 < 80% (light gray dashed line).

[00021] Figure 10: Measurements of the difference in respiratory resistances at 5 Hz and 20 Hz (R5-20) from the clinical trial of example 1 (PDY16622). The change (in cmH2O*s / l, compared to baseline) in the difference between respiratory resistance at 5 Hz and respiratory resistance at 20 Hz is shown. The upper panel shows the change in R5-20 of the SAR443765 group (dashed line) and the placebo group (solid line). In the lower panel, the SAR443765 group and the placebo group were each divided into two subpopulations depending on the baseline percentage of predicted FEV1 (ppFEV1). The subpopulations are: Petition 870250085505, dated 09 / 22 / 2025, page 19 / 173 11 / 126 SAR443765, baseline ppFEV1 > 80% (dark gray solid line); SAR443765, baseline ppFEV1 < 80% (dark gray dashed line); placebo, baseline ppFEVI > 80% (light gray solid line); placebo, baseline ppFEV1 < 80% (light gray dashed line).

[00022] Figure 11: Reactance area (AX) measurements from the Example 1 clinical trial (PDY16622). The change in reactance area (in cmH2O / l) compared to baseline is shown. The top panel shows the change in reactance area of ​​the SAR443765 group (dashed line) and the placebo group (solid line). In the bottom panel, the SAR443765 group and the placebo group were each divided into two subpopulations depending on the baseline percentage of predicted FEV1 (ppFEV1). The subpopulations are: SAR443765, baseline ppFEV1 > 80% (dark gray solid line); SAR443765, baseline ppFEV1 < 80% (dark gray dashed line); placebo, baseline ppFEV1 > 80% (light gray solid line); Placebo, baseline ppFEV1 < 80% (light gray dashed line).

[00023] Figure 12: Additional biomarker measurements from the Example 1 clinical trial (PDY16622). Shown are changes in serum IL-5 levels (upper left panel); plasma CCL26 (eotaxin-3) levels (upper right panel), serum IgE levels (lower left panel), and serum TARC (CCL17) levels (lower right panel) compared to baseline. Each panel shows results for placebo (left) and SAR443765 (right).

[00024] Figure 13: Change in cell types in nasal brushing samples from the Example 1 clinical trial (PDY16622). The change between samples from D1 (baseline, before SAR443765 or placebo administration) and D29 is shown. The change in the cell type proportions of each cell type (indicated as log2 of fold change (FC)) on the geometric x-axis is plotted against the p-value. Petition 870250085505, dated 09 / 22 / 2025, page 20 / 173 12 / 126 for this change (indicates -log10 of the p value) on the geometric y-axis.

[00025] Figure 14: The change in cell types in peripheral blood leukocyte (PBL) samples from the Example 1 clinical trial (PDY16622). The change between samples from D1 (baseline, before SAR443765 or placebo administration) and D29 is shown. The change in the cell type proportions of each cell type (indicated as log2 of fold change (FC)) on the geometric x-axis is plotted against the p-value for that change (indicated as -log10 of the p-value) on the geometric y-axis.

[00026] Figure 15: Correlation of the change in the proportion of NK cells (in PBL samples) and the change in FeNO level in the clinical trial of example 1 (PDY16622). The change between samples / measurements from D1 (baseline, before SAR443765 or placebo administration) and D29 is shown. The change in FeNO on the geometric x-axis is plotted against the change in the cell type ratio (D29-D1) of NK cells (indicated as log10 of fold change (FC)) on the geometric y-axis.

[00027] Figure 16: CCL26 expression in D1 and D29 in nasal brushing samples from the Example 1 clinical trial (PDY16622). In the SAR443765 group, there is a significant difference in CCL26 expression between D1 and D29 for basal epithelial, multiciliated epithelial, and secretory epithelial cell types.

[00028] Figure 17: HBB expression in CD8 effector memory T cells (EM) in PBL samples from the Example 1 clinical trial (PDY16622). The fold change in HBB gene expression (D29 compared to D1) relative to the p-value is shown. In the SAR443765 group (left), there is a much stronger downregulation of HBB expression than in the placebo group (right). Detailed description of the present invention Petition 870250085505, dated 09 / 22 / 2025, page 21 / 173 13 / 126

[00029] In a first aspect, the present invention relates to a compound that blocks TSLP and IL-13 for use in the treatment of a lung disease in an individual, for example, in the treatment of asthma. This treatment is distinguished by the enhancement of certain biomarkers, in particular, a reduction in the level of FeNO and a reduction in the eosinophil count.

[00030] In another aspect, the present invention relates to compounds for use in reducing the level of FeNO in an individual wherein the reduction of the FeNO level prevents a loss of lung function. This loss of lung function may be linked to asthma or other lung disease. 5.1 Definitions

[00031] Unless stated below, the following terms used in this application, including the descriptive report and the claims, have the meanings usually given to them in the respective scientific field.

[00032] As used in the descriptive report and attached claims, the indefinite articles “a” and “an” and the definite articles “the” and “the” include the plural, just like the singular referents, unless the context clearly dictates otherwise.

[00033] All indications of time periods in this application count the day of drug administration as day 1 (“D1”). This means that the day after drug administration is counted as day 2 (“D2”), so that, for example, a measurement that occurs 24 h after drug administration is on D2 and a measurement that occurs 72 h after drug administration is on D4. This also means that a one-week time interval ends on D8, a two-week time interval ends on D15, a three-week time interval ends on D22, a four-week time interval ends on D29, an eight-week time interval ends on D30 Petition 870250085505, dated 09 / 22 / 2025, p. 22 / 173 A 14 / 126 week period ends on D57 and a 10-week time interval ends on D71. In the present invention, “day” is often abbreviated as “D”. The terms “day” and “D” are used interchangeably in this invention.

[00034] A lung disease is a disease of the lungs. An example of a lung disease is asthma.

[00035] An inflammatory disease is a disease characterized by autoinflammation. There are inflammatory diseases of the lung. An example of such an inflammatory lung disease is asthma.

[00036] Asthma is a lung disease characterized by long-term inflammation of the airways. Asthma involves airflow obstruction and triggered bronchospasms. Symptoms often include episodes of wheezing, coughing, chest tightness, and shortness of breath. Asthma includes allergic asthma, non-allergic asthma, high Th2 asthma, low Th2 asthma, high eosinophilic asthma, and low eosinophilic asthma.

[00037] Elevated eosinophilic asthma, as used herein, is asthma in which the patient shows an eosinophil count greater than or equal to 0.3 *109 cells / L. An exemplary eosinophil count range in elevated eosinophilic asthma is 0.3 *109 to 0.5 *109 cells / L.

[00038] Low eosinophilic asthma, as used herein, is asthma in which the patient shows an eosinophil count of less than 0.3 *109 cells / l. An exemplary eosinophil count range in low eosinophilic asthma is 0 to less than 0.3 *109 cells / l.

[00039] Airway inflammation is inflammation that is located in the respiratory tract. Airway inflammation can be assessed directly, for example, by induced sputum analysis, bronchial lavage, bronchial biopsy, or exhaled volatile markers such as FeNO; or indirectly, for example, by increased eosinophil count in the blood. Airway inflammation is Petition 870250085505, dated 09 / 22 / 2025, page 23 / 173 15 / 126 distinguished by an elevated FeNO level, a high blood eosinophil count, and decreased lung function (e.g., decreased FEV1).

[00040] Type 2 inflammation is an immune response distinguished by the activation of type 2 helper T cells and / or type 2 innate lymphoid cells. The immune response of type 2 inflammation is distinguished by the release of alarmins (IL-23, IL-33, TSLP) which leads to the activation of type 2 helper T cells and / or type 2 innate lymphoid cells. These cells secrete IL-4, IL-5, and IL-13, which promotes isotype switching to IgE in B cells and eosinophil recruitment. Type 2 inflammation can be useful for the body's defense against helminths, but it is involved in a variety of autoinflammatory diseases. Airway inflammation in patients with asthma is frequently type 2 inflammation.

[00041] Fractionated exhaled nitric oxide (FeNO) is the fraction of nitric oxide (NO) in exhaled air. It is measured in parts per billion (ppb). An elevated FeNO level is a sign of airway inflammation. When the present application refers to a “reduction in FeNO level compared with placebo,” this refers to the average individual changes from baseline in FeNO level of the composite group (in ppb) and the placebo group (in ppb) at a certain point in time. The difference between these two values ​​(in ppb) is the “reduction in FeNO level compared with placebo.”

[00042] Management of elevated FeNO levels, as used in this document, means administering treatment that reduces elevated FeNO levels, which may reduce airway inflammation and / or prevent exacerbation of airway inflammation.

[00043] Management of airway inflammation, as used in this document, means administering treatment that reduces airway inflammation where symptoms associated with Petition 870250085505, dated 09 / 22 / 2025, p. 24 / 173 16 / 126 airway inflammation is reduced and / or the exacerbation of symptoms associated with airway inflammation is prevented.

[00044] Eosinophil count, as used in this document, is the number of eosinophilic granulocytes. In treatments according to the present invention, the eosinophil count is measured in whole blood. Methods for measuring the eosinophil count are known in the art, for example, flow cytometry or counting under a microscope after H&E staining. The eosinophil count is measured in cells / l. When the present application refers to a “reduction in eosinophil count compared with placebo”, this means that, at a certain point in time after the start of treatment, the change from baseline in the eosinophil count of the composite group (in cells / l or %) and the change from baseline in the eosinophil count of the placebo group (in cells / l or %) are measured. The difference between these two values ​​(in cells / l or %) is the “reduction in eosinophil count compared with placebo”.

[00045] Forced expiratory volume in one second (FEV1) is the volume of air in liters that is exhaled in the first second during forced expiration after maximal inspiration. FEV1 can be measured by spirometry. When the present application refers to an “increase in FEV1 compared with placebo,” this means that, at a given time after the start of treatment, the change from baseline in FEV1 of the composite group (in l) and the change from baseline in FEV1 of the placebo group (in l) are measured. The difference between these two values ​​(in l) is the “increase in FEV1 compared with placebo.”

[00046] A placebo, as used in this document, is a treatment or a substance used in such treatment that does not include a pharmacologically active compound. In clinical trials, a placebo may be administered to a fraction of the participants to Petition 870250085505, dated 09 / 22 / 2025, page 25 / 173 17 / 126 generate a control group for the fraction of participants who receive the pharmacologically active compound to be tested. To serve as an adequate control, the placebo treatment is identical to the treatment with which it is compared, the only exception being that a placebo (e.g., an inert pill such as a sugar pill) and not the pharmacologically active compound is administered.

[00047] In the present invention, the change in a biomarker (e.g., FeNO, eosinophil count) is determined in comparison to a “control.” The control is the individuals’ baseline, i.e., the individuals’ biomarker level before administration of the compound of the invention; or “placebo,” i.e., the biomarker level after administration of a placebo instead of the compound of the invention. When the change in biomarker level is determined in comparison to baseline, this means that the difference between the baseline biomarker level and the biomarker level at a certain point in time is calculated for each individual who was treated with the compound. This calculation can be done for a single individual as well as a group of individuals. If done for a single individual, this difference is directly indicated as the change in biomarker level compared to baseline.If done for a group of individuals, the mean or median of all differences calculated for individual individuals is indicated as the change in biomarker level compared to baseline.

[00048] When the change in biomarker level is determined compared to placebo, this means that the change compared to baseline is determined for a group of individuals treated with the compound (as explained in the previous sentence) and the same value is determined for a group of individuals treated with placebo; the difference between these two values ​​is indicated as the change in biomarker level compared to placebo. Petition 870250085505, dated 09 / 22 / 2025, page 26 / 173 18 / 126 This means that the change in biomarker level compared to placebo is equal to the “change in biomarker level compared to baseline” minus the change in biomarker level of a placebo group.

[00049] Small airways refer to airways that have a diameter equal to or less than 2 mm, as commonly defined in the literature (see, for example, McNulty and Usmani, Eur Clin Respir J, 2014 and Stockley et al., Int J Chron Obstructive Pulmon Dis. 2017; 12: 2343-2353).

[00050] Large airways refer to airways that have a diameter of more than 2 mm.

[00051] The participants in the clinical trial in example 1 (PDY16622) consisted of patients with asthma (see below in example 1). Thus, the terms “participant” and “patient” are used synonymously throughout this application.

[00052] The expressions treatment of a disease in an individual and treatment of a disease are used interchangeably in this document, since it is evident that a treatment takes place in an individual. The same applies to variations of these expressions, for example, “the treatment of a lung disease in an individual” is used interchangeably with “treatment of a lung disease”. 5.2 Treatment of the present invention

[00053] The present invention provides compounds that bind to IL13 and TSLP for use in the treatment of a lung disease in an individual. These treatments are distinguished by improvements in biomarkers and / or physiological characteristics, such as a reduction in FeNO levels, a reduction in blood eosinophil count, an increase in FEV1, and / or a reduction in airway inflammation.

[00054] The treatment subject of the present invention can be any animal, and more specifically a mammal. Among the Petition 870250085505, dated 09 / 22 / 2025, page 27 / 173 19 / 126 mammals, a distinction can be made between humans and non-human mammals. Non-human animals can be, for example, pets (e.g., dogs, cats), livestock (e.g., cattle, horses, sheep, goats, or pigs), or animals generally used for research purposes and / or for antibody production (e.g., mice, rats, rabbits, cats, dogs, goats, sheep, horses, pigs, non-human primates such as cynomolgus monkeys, or camelids such as llamas or alpacas). In one embodiment, the individual is a human individual.

[00055] In the context of the preventive purposes of the present invention, the individual may be the same as defined in the preceding section. In one embodiment, the individual is a human individual.

[00056] Compounds (including polypeptides and nucleic acid molecules) or compositions according to the present invention may be administered to an individual by any suitable route of administration, for example, by enteral administration (such as oral or rectal) or parenteral administration (such as epicutaneous, sublingual, buccal, nasal, intra-articular, intradermal, intramuscular, intraperitoneal, intravenous, subcutaneous (SC), transdermal or transmucosal). In one embodiment, the substances are administered by parenteral administration, such as intramuscular, subcutaneous or intradermal administration. In one embodiment, subcutaneous administration is used.

[00057] An effective amount of a polypeptide, a nucleic acid molecule, or a composition comprising the polypeptide or nucleic acid molecule, may be administered to an individual in order to provide the intended treatment results.

[00058] One or more doses may be administered. If more than one dose is administered, the doses may be given at appropriate intervals in order to maximize the effect of the polypeptide, compound, nucleic acid molecule, or vector. Petition 870250085505, dated 09 / 22 / 2025, p. 28 / 173 20 / 126

[00059] In some embodiments, the administered amount of the TSLP- and IL-13-binding compound is 400 mg. In some embodiments, the TSLP- and IL-13-binding compound is administered subcutaneously (SC). In some embodiments, only one dose of the TSLP- and IL-13-binding compound is administered.

[00060] In some embodiments, the administered amount of the TSLP and IL-13 binding compound is 400 mg, and the TSLP and IL-13 binding compound is administered subcutaneously (SC). In some embodiments, the administered amount of the TSLP and IL-13 binding compound is 400 mg, and only one dose of the TSLP and IL-13 binding compound is administered. In some embodiments, the TSLP and IL-13 binding compound is administered subcutaneously (SC), and only one dose of the TSLP and IL-13 binding compound is administered. In some embodiments, the administered amount of the TSLP and IL-13 binding compound is 400 mg, the TSLP and IL-13 binding compound is administered subcutaneously (SC), and only one dose of the TSLP and IL-13 binding compound is administered. 5.2.1 Reduction of FeNO levels

[00061] The reduction in FeNO levels reflects reduced airway inflammation and is therefore beneficial for patients with lung diseases, for example, asthma. In some modalities, lung disease is an inflammatory disease. In some modalities, lung disease is asthma. In some modalities, asthma is high eosinophilic asthma. In some modalities, asthma is low eosinophilic asthma.

[00062] In the present invention, the reduction in FeNO level is determined in comparison with a control. The control is the baseline of the individuals, that is, the FeNO level of the individuals before administration of the compound of the invention; or the “placebo”, that is, the FeNO level after administration of a placebo instead of the compound of the invention. Petition 870250085505, dated 09 / 22 / 2025, p. 29 / 173 21 / 126 invention. When the reduction in FeNO level is determined in comparison to the baseline, this means that the difference between the baseline FeNO level and the FeNO level at a certain point in time is calculated for each individual who was treated with the compound. This calculation can be done for a single individual as well as a group of individuals. If done for a single individual, this difference is directly indicated as the change in FeNO level compared to the baseline. If done for a group of individuals, the average or median of all the differences calculated for individual individuals is indicated as the change in FeNO level compared to the baseline.

[00063] When the reduction in FeNO level is determined compared to placebo, this means that the reduction compared to baseline is determined for a group of individuals treated with the compound (as explained in the previous sentence) and the same value is determined for a group of individuals treated with placebo; the difference between these two values ​​is indicated as the reduction in FeNO level compared to placebo. This means that the reduction in FeNO level compared to placebo is equal to the reduction in FeNO level compared to baseline minus the change compared to baseline in FeNO level for a placebo group. In some modalities, the reduction in FeNO level is calculated for the mean of a group of individuals. In some modalities, the reduction in FeNO level is calculated for the median of a group of individuals.

[00064] In some embodiments of the present invention, the reduction in FeNO level is determined in comparison with placebo. In some embodiments of the present invention, the reduction in FeNO level is determined in comparison with baseline. In some embodiments of the present invention, the reduction in FeNO level is Petition 870250085505, dated 09 / 22 / 2025, p. 30 / 173 22 / 126 determined in comparison to the baseline, where baseline means the individual's baseline. In some embodiments of the present invention, the FeNO level is reduced by at least 18 ppb. In some embodiments of the present invention, the FeNO level is reduced by at least 20 ppb. In some embodiments of the present invention, the FeNO level is reduced by at least 25 ppb. In some embodiments of the present invention, the FeNO level is reduced by at least 30 ppb. In some embodiments of the present invention, the FeNO level is reduced by at least 35 ppb. In some embodiments of the present invention, the FeNO level is reduced by at least 40 ppb.

[00065] Exemplary ranges for reducing FeNO levels are 18 ppb to 50 ppb; 18 ppb to 40 ppb; 18 ppb to 35 ppb; 18 ppb to 30 ppb; ppb to 25 ppb; 18 ppb to 20 ppb; 20 ppb to 50 ppb; 20 ppb to 40 ppb; ppb to 35 ppb; 20 ppb to 30 ppb; 20 ppb to 25 ppb; 25 ppb to 50 ppb; ppb to 40 ppb; 25 ppb to 35 ppb; 25 ppb to 30 ppb; 30 ppb to 50 ppb; ppb to 40 ppb; 30 ppb to 35 ppb; 35 ppb to 50 ppb; 35 ppb to 40 ppb; ppb to 50 ppb.

[00066] The reduction in FeNO levels can be evaluated at different times after administration of the compound of the present invention. In some embodiments, the reduction in FeNO levels is evaluated 1 week after administration of the compound of the present invention. In some embodiments, the reduction in FeNO levels is evaluated 2 weeks after administration of the compound of the present invention. In some embodiments, the reduction in FeNO levels is evaluated 3 weeks after administration of the compound of the present invention. In some embodiments, the reduction in FeNO levels is evaluated 4 weeks after administration of the compound of the present invention. In some embodiments, the reduction in FeNO levels is evaluated 8 weeks after administration of the compound of the present invention. Petition 870250085505, dated 09 / 22 / 2025, p. 31 / 173 23 / 126

[00067] The treatment of the present invention can be used to manage elevated FeNO levels. In some embodiments, managing the FeNO level comprises decreasing the FeNO level to a value below 40 ppb. In some embodiments, managing the FeNO level comprises decreasing the FeNO level to a value below 35. In some embodiments, managing the FeNO level comprises decreasing the FeNO level to a value below 30. In some embodiments, managing the FeNO level comprises decreasing the FeNO level to a value below 25. In some embodiments, managing the FeNO level comprises decreasing the FeNO level to a value below 20.

[00068] The baseline FeNO level, that is, the level before administration of the compound, can also be a parameter for the treatment of the present invention. In some embodiments, the treatment of the present invention is used to manage an elevated baseline FeNO level of at least 25 ppb. In some embodiments, the treatment of the present invention is used to manage an elevated baseline FeNO level of at least 30 ppb. In some embodiments, the treatment of the present invention is used to manage an elevated baseline FeNO level of at least 40 ppb. In some embodiments, the treatment of the present invention is used to manage an elevated baseline FeNO level of at least 50 ppb. In some embodiments, the treatment of the present invention is used to manage an elevated baseline FeNO level of at least 60 ppb. In some embodiments, the treatment of the present invention is used to manage an elevated baseline FeNO level of at least 70 ppb.

[00069] In some embodiments, the treatment of the present invention is used to manage an elevated baseline FeNO level of at least 50 ppb, where the individual also has an eosinophil count greater than or equal to 0.3 *109 cells / L. A baseline level range Petition 870250085505, dated 09 / 22 / 2025, page 32 / 173 An exemplary 24 / 126 FeNO range is 50 ppb to 150 ppb, and an exemplary eosinophil count range is 0.3 *109 to 0.5 *109 cells / l. 5.2.2 Reduction in blood eosinophil count

[00070] A reduction in blood eosinophil count correlates with reduced airway inflammation, particularly type 2 airway inflammation, and is therefore beneficial for patients with lung diseases, for example, asthma. In some modalities, lung disease is an inflammatory disease. In some modalities, lung disease is asthma. In some modalities, asthma is high eosinophilic asthma. In some modalities, asthma is low eosinophilic asthma.

[00071] In the present invention, the reduction in eosinophil count is determined in comparison to a control. The control is the individuals' baseline, i.e., the individuals' eosinophil count before administration of the compound of the invention; or placebo, i.e., the eosinophil count after administration of a placebo instead of the compound of the invention. When the reduction in eosinophil count is determined in comparison to baseline, this means that the difference between the baseline eosinophil count and the eosinophil count at a certain point in time is calculated for each individual who was treated with the compound. This calculation can be done for a single individual as well as a group of individuals. If done for a single individual, this difference is directly indicated as the change in eosinophil count compared to baseline.If performed for a group of individuals, the mean or median of all differences calculated for individual individuals is indicated as the reduction in eosinophil count compared to baseline. When the reduction in eosinophil count is determined in comparison to placebo... Petition 870250085505, dated 09 / 22 / 2025, page 33 / 173 25 / 126 means that the reduction compared to baseline is determined for a group of individuals treated with the compound (as explained in the previous sentence) and the same value is determined for a group of individuals treated with placebo; the difference between these two values ​​is indicated as the reduction in eosinophil count compared to placebo. This means that the reduction in eosinophil count compared to placebo is equal to the “reduction in eosinophil count compared to baseline” minus the change in eosinophil count of a placebo group. In some modalities, the reduction in eosinophil count refers to the median. In some modalities, the reduction in eosinophil count refers to the mean. In some modalities, the reduction in eosinophil counts refers to the median change compared to baseline, expressed as a percentage.

[00072] In some modalities, the reduction in eosinophil counts refers to the difference between the median change from baseline, expressed as a percentage, for a group of individuals treated with the compound and the median change from baseline, expressed as a percentage, for a group of individuals treated with placebo.

[00073] In some embodiments of the present invention, the reduction in eosinophil count (relative to baseline) is determined in comparison with placebo. In some embodiments of the present invention, the reduction in eosinophil count is determined in comparison with baseline. In some embodiments of the present invention, the reduction in FeNO level (relative to baseline) is determined in comparison with baseline, wherein baseline means the individual's individual baseline.

[00074] In some embodiments of the present invention, the eosinophil count is reduced by at least 30%. In some Petition 870250085505, dated 09 / 22 / 2025, p. 34 / 173 In some embodiments of the present invention, the eosinophil count is reduced by at least 30% compared to the median of a group of individuals. In some embodiments of the present invention, the eosinophil count is reduced by at least 30% compared to the average of a group of individuals. In some embodiments of the present invention, the eosinophil count is reduced by at least 35%. In some embodiments of the present invention, the eosinophil count is reduced by at least 35% compared to the median of a group of individuals. In some embodiments of the present invention, the eosinophil count is reduced by at least 35% compared to the average of a group of individuals. In some embodiments of the present invention, the eosinophil count is reduced by at least 40%. In some embodiments of the present invention, the eosinophil count is reduced by at least 40% compared to the median of a group of individuals.In some embodiments of the present invention, the eosinophil count is reduced by at least 40% relative to the average of a group of individuals. Exemplary ranges by which the eosinophil count is reduced are 30% to 80%; 35% to 80%; and 40% to 80%.

[00075] In some embodiments, the reduction in eosinophil count occurs within 4 weeks after administration of the compound. In some embodiments, the reduction in eosinophil count occurs within 2 weeks after administration of the compound. In some embodiments, the reduction in eosinophil count occurs within 1 week after administration of the compound. In some embodiments, the reduction in eosinophil count occurs within 3 days after administration of the compound. In some embodiments, the reduction in eosinophil count occurs within 1 day after administration of the compound.

[00076] In some embodiments, the compound that binds to IL-13 and Petition 870250085505, dated 09 / 22 / 2025, p. 35 / 173 27 / 126 TSLP, which reduces eosinophil count, is a polypeptide, such as an antibody or an antibody fragment. In some embodiments, the IL-13-binding and TSLP-reducing eosinophil count compound is a polypeptide, wherein the polypeptide comprises or consists of at least four ISVDs, wherein two ISVDs bind specifically to IL-13 and two ISVDs bind specifically to TSLP, wherein each of said at least four ISVDs comprises three complementarity-determining regions (CDR1 to CDR3, respectively), wherein the ISVDs are optionally linked via one or more peptide linkers, and where: A first ISVD comprises: A CDR1, which is the amino acid sequence with SEQ ID NO: 7; a CDR2, which is the amino acid sequence with SEQ ID NO: 12; and a CDR3, which is the amino acid sequence with SEQ ID NO: 17; a second ISVD comprises: A CDR1, which is the amino acid sequence with SEQ ID NO: 8; a CDR2, which is the amino acid sequence with SEQ ID NO: 13; and a CDR3, which is the amino acid sequence with SEQ ID NO: 18; a third ISVD comprises: a CDR1 which is the amino acid sequence of SEQ ID NO: 9, a CDR2 which is the amino acid sequence of SEQ ID NO: 14 and a CDR3 which is the amino acid sequence of SEQ ID NO: 19, and a fourth ISVD comprises: CDR1, which is the amino acid sequence with SEQ ID NO: 11; CDR2, which is the amino acid sequence with SEQ ID NO: 16; and CDR3, which is the amino acid sequence with SEQ ID NO: 21.

[00077] In some embodiments, the compound that binds to IL-13 and TSLP and reduces eosinophil count comprises or consists of the amino acid sequence SEQ ID NO: 1. Petition 870250085505, dated 09 / 22 / 2025, p. 36 / 173 28 / 126 5.2.3 Increase in FEV1

[00078] An increase in FEV1 levels indicates improved lung function and is therefore beneficial for patients with lung diseases, for example, asthma. In some modalities, lung disease is an inflammatory disease. In some modalities, lung disease is asthma. In some modalities, asthma is elevated eosinophilic asthma. In some modalities, asthma is low eosinophilic asthma.

[00079] In the present invention, the increase in FEV1 (relative to baseline) is determined in comparison with a control, such as a baseline or placebo. In some embodiments of the present invention, FEV1 is increased by at least 0.05 l. In some embodiments of the present invention, FEV1 is increased by at least 0.07 l. In some embodiments of the present invention, FEV1 is increased by at least 0.1 l. In some embodiments of the present invention, FEV1 is increased by at least 0.15 l. In some embodiments of the present invention, FEV1 is increased by at least 0.2 l. In some embodiments of the present invention, FEV1 is increased by at least 0.25 l. In some embodiments of the present invention, FEV1 is increased by at least 0.3 l. An exemplary range by which FEV1 is increased is 0.07 l ± 0.3 l. Exemplary ranges by which FEV1 is increased are 0.07 l to 0.3 l; 0.1 l to 0.3 l; 0.15 l to 0.3 l; 0.2 l to 0.3 l; and 0.25 l to 0.3 l.

[00080] The present invention provides a compound that binds to IL-13 and TSLP for use in the treatment of a pulmonary disease in an individual, wherein FEV1 is increased by at least 0.05 l compared to placebo. The present invention provides a compound that binds to IL-13 and TSLP for use in the treatment of a pulmonary disease in an individual, wherein FEV1 is increased by at least 0.07 l compared to placebo. The present invention Petition 870250085505, dated 09 / 22 / 2025, page 37 / 173 29 / 126 provides a compound that binds to IL-13 and TSLP for use in the treatment of a lung disease in an individual where FEV1 is increased by at least 0.1 l compared to placebo.

[00081] In some embodiments, the increase in FEV1 occurs within 4 weeks after administration of the compound. In some embodiments, the increase in FEV1 occurs within 2 weeks after administration of the compound. In some embodiments, the increase in FEV1 occurs within 1 week after administration of the compound.

[00082] In some embodiments, the compound that binds to IL-13 and TSLP and increases FEV1 is a polypeptide, such as an antibody or an antibody fragment. In some embodiments, the compound that binds to IL-13 and TSLP and increases FEV1 is a polypeptide, wherein the polypeptide comprises or consists of at least four ISVDs, wherein two ISVDs bind specifically to IL-13 and two ISVDs bind specifically to TSLP, wherein each of said at least four ISVDs comprises three complementarity-determining regions (CDR1 to CDR3, respectively), wherein the at least four ISVDs are optionally linked via one or more peptide linkers, and where: A first ISVD comprises: A CDR1, which is the amino acid sequence with SEQ ID NO: 7; a CDR2, which is the amino acid sequence with SEQ ID NO: 12; and a CDR3, which is the amino acid sequence with SEQ ID NO: 17; a second ISVD comprises: A CDR1, which is the amino acid sequence with SEQ ID NO: 8; a CDR2, which is the amino acid sequence with SEQ ID NO: 13; and a CDR3, which is the amino acid sequence with SEQ ID NO: 18; a third ISVD comprises: a CDR1 which is the amino acid sequence with SEQ ID NO: 9, a CDR2 which is the amino acid sequence with SEQ ID NO: 14 and a Petition 870250085505, dated 09 / 22 / 2025, p. 38 / 173 30 / 126 CDR3, which is the amino acid sequence of SEQ ID NO: 19, and a fourth ISVD, which comprises: CDR1, which is the amino acid sequence with SEQ ID NO: 11; CDR2, which is the amino acid sequence with SEQ ID NO: 16; and CDR3, which is the amino acid sequence with SEQ ID NO: 21.

[00083] In some embodiments, the compound that binds to IL-13 and TSLP and that increases FEV1 comprises or consists of the amino acid sequence of SEQ ID NO: 1. 5.2.4 Reduction of airway inflammation

[00084] Reduced airway inflammation indicates improved lung function and is therefore beneficial for patients with lung diseases, for example, asthma. In some modalities, airway inflammation is type 2 airway inflammation. In the present invention, the reduction of airway inflammation can be determined by analyzing clinical parameters, especially FeNO, eosinophil count, and FEV1. The reduction or increase of these parameters is determined in comparison to a control that is baseline or placebo (as explained above for the individual clinical parameters).

[00085] In some modalities, airway inflammation is distinguished by a reduction in FeNO of at least 18 ppb and a reduction in eosinophil count of at least 30%. In some modalities, airway inflammation is distinguished by a reduction in FeNO of at least 18 ppb, and an increase in forced expiratory volume in one second (FEV1) of at least 0.07 L. In some modalities, airway inflammation is distinguished by a reduction in eosinophil count of at least 30% and an increase in forced expiratory volume in one second (FEV1) of at least 0.07 L. In some modalities, airway inflammation is distinguished by a reduction in FeNO of at least 18 ppb, Petition 870250085505, dated 09 / 22 / 2025, p. 39 / 173 31 / 126 a reduction in eosinophil count by at least 30% and an increase in forced expiratory volume in one second (FEV1) by at least 0.07 L. Exemplary ranges are a reduction in FeNO of 18 ppb to 70 ppb, a reduction in eosinophil count of 30% to 80%, and an increase in FEV1 of 0.07 L to 0.3 L.

[00086] In some modalities, airway inflammation is distinguished by a reduction in FeNO of at least 20 ppb and a reduction in eosinophil count of at least 30%. In some modalities, airway inflammation is distinguished by a reduction in FeNO of at least 20 ppb and an increase in forced expiratory volume in one second (FEV1) of at least 0.07 L. In some modalities, airway inflammation is distinguished by a reduction in FeNO of at least 20 ppb, a reduction in eosinophil count of at least 30%, and an increase in forced expiratory volume in one second (FEV1) of at least 0.07 L.

[00087] In some modalities, airway inflammation is distinguished by a reduction in FeNO of at least 30 ppb and a reduction in eosinophil count of at least 30%. In some modalities, airway inflammation is distinguished by a reduction in FeNO of at least 30 ppb and an increase in forced expiratory volume in one second (FEV1) of at least 0.07 L. In some modalities, airway inflammation is distinguished by a reduction in FeNO of at least 30 ppb, a reduction in eosinophil count of at least 30%, and an increase in forced expiratory volume in one second (FEV1) of at least 0.07 L.

[00088] In some modalities, airway inflammation is distinguished by a reduction in FeNO of at least 40 ppb and a reduction in eosinophil count of at least 30%. In some modalities, airway inflammation is distinguished by a reduction in FeNO of at least 40 ppb and an increase in volume Petition 870250085505, dated 09 / 22 / 2025, p. 40 / 173 32 / 126 forced expiratory volume in one second (FEV1) by at least 0.07 l. In some modalities, airway inflammation is distinguished by a reduction in FeNO by at least 40 ppb, a reduction in eosinophil count by at least 30%, and an increase in forced expiratory volume in one second (FEV1) by at least 0.07 l.

[00089] In some modalities, airway inflammation is distinguished by a reduction in FeNO by at least 18 ppb, a reduction in eosinophil count by at least 30%, and an increase in forced expiratory volume in one second (FEV1) by at least 0.07 l and a reduction in one or more of the IL-5 level, CCL26 (eotaxin-3) level, TARC (CCL17) level, and IgE (serum) level.In some modalities, airway inflammation is distinguished by a reduction in FeNO of at least 18 ppb, a reduction in eosinophil count of at least 30%, and an increase in forced expiratory volume in one second (FEV1) of at least 0.07 l, and a reduction in IL-5 level, CCL26 (eotaxin-3) level, TARC (CCL17) level, and IgE level.

[00090] In some modalities, airway inflammation is distinguished by a reduction in FeNO of at least 20 ppb, a reduction in eosinophil count of at least 30%, and an increase in forced expiratory volume in one second (FEV1) of at least 0.07, and a reduction in one or more of the IL-5 level, CCL26 level (eotaxin-3), TARC level (CCL17), and IgE level (serum). In some modalities, airway inflammation is distinguished by a reduction in FeNO of at least 20 ppb, a reduction in eosinophil count of at least 30%, and an increase in forced expiratory volume in one second (FEV1) of at least 0.07, and a reduction in the IL-5 level, CCL26 level (eotaxin-3), TARC level (CCL17), and IgE level.

[00091] In some modalities, inflammation of the airways is Petition 870250085505, dated 09 / 22 / 2025, p. 41 / 173 33 / 126 distinguished by a reduction in FeNO by at least 30 ppb, a reduction in eosinophil count by at least 30%, and an increase in forced expiratory volume in one second (FEV1) by at least 0.07, and a reduction in one or more of the IL-5 level, CCL26 (eotaxin-3) level, TARC (CCL17) level, and IgE level. In some modalities, airway inflammation is distinguished by a reduction in FeNO by at least 30 ppb, a reduction in eosinophil count by at least 30%, and an increase in forced expiratory volume in one second (FEV1) by at least 0.07, and a reduction in the IL-5 level, CCL26 (eotaxin-3) level, TARC (CCL17) level, and IgE level.

[00092] In some modalities, airway inflammation is distinguished by a reduction in FeNO of at least 40 ppb, a reduction in eosinophil count of at least 30%, and an increase in forced expiratory volume in one second (FEV1) of at least 0.07, and a reduction in one or more of the IL-5 level, CCL26 level (eotaxin-3), TARC level (CCL17), and IgE level (serum). In some modalities, airway inflammation is distinguished by a reduction in FeNO of at least 40 ppb, a reduction in eosinophil count of at least 30%, and an increase in forced expiratory volume in one second (FEV1) of at least 0.07, and a reduction in the IL-5 level, CCL26 level (eotaxin-3), TARC level (CCL17), and IgE level.

[00093] In some embodiments, reduction of airway inflammation occurs within 4 weeks after administration of the compound. In some embodiments, reduction of airway inflammation occurs within 2 weeks after administration of the compound. In some embodiments, reduction of airway inflammation occurs within 1 week after administration of the compound.

[00094] In some embodiments, the compound that binds to IL-13 and Petition 870250085505, dated 09 / 22 / 2025, page 42 / 173 34 / 126 TSLP, which reduces airway inflammation, is a polypeptide, such as an antibody or an antibody fragment. In some embodiments, the compound that binds to IL-13 and TSLP and reduces airway inflammation is a polypeptide, wherein the polypeptide comprises or consists of at least four ISVDs, wherein two ISVDs bind specifically to IL-13 and two ISVDs bind specifically to TSLP, wherein each of said at least four ISVDs comprises three complementarity-determining regions (CDR1 to CDR3, respectively), wherein the at least four ISVDs are optionally linked via one or more peptide linkers, and where: A first ISVD comprises: A CDR1, which is the amino acid sequence with SEQ ID NO: 7; a CDR2, which is the amino acid sequence with SEQ ID NO: 12; and a CDR3, which is the amino acid sequence with SEQ ID NO: 17; a second ISVD comprises: A CDR1, which is the amino acid sequence with SEQ ID NO: 8; a CDR2, which is the amino acid sequence with SEQ ID NO: 13; and a CDR3, which is the amino acid sequence with SEQ ID NO: 18; a third ISVD comprises: a CDR1 which is the amino acid sequence of SEQ ID NO: 9, a CDR2 which is the amino acid sequence of SEQ ID NO: 14 and a CDR3 which is the amino acid sequence of SEQ ID NO: 19, and a fourth ISVD comprises: CDR1, which is the amino acid sequence with SEQ ID NO: 11; CDR2, which is the amino acid sequence with SEQ ID NO: 16; and CDR3, which is the amino acid sequence with SEQ ID NO: 21.

[00095] In some embodiments, the compound that binds to IL-13 and TSLP and reduces airway inflammation comprises or consists of the amino acid sequence SEQ ID NO: 1. Petition 870250085505, dated 09 / 22 / 2025, p. 43 / 173 35 / 126 5.2.5 Management of airway inflammation

[00096] The present invention can be used to manage airway inflammation. In some embodiments, managing airway inflammation involves decreasing the FeNO level to a value less than 40 ppb. In some embodiments, managing airway inflammation involves decreasing the FeNO level to a value less than 35. In some embodiments, managing airway inflammation involves decreasing the FeNO level to a value less than 30. In some embodiments, managing airway inflammation involves decreasing the FeNO level to a value less than 25. In some embodiments, managing airway inflammation involves decreasing the FeNO level to a value less than 20.

[00097] In some modalities, airway inflammation management involves lowering FeNO levels to less than 40 ppb and blood eosinophil counts to less than 0.2 *109 cells / L. In some modalities, airway inflammation management involves lowering FeNO levels to less than 35 ppb and blood eosinophil counts to less than 0.2 *109 cells / L. In some modalities, airway inflammation management involves lowering FeNO levels to less than 30 ppb and blood eosinophil counts to less than 0.2 *109 cells / L. In some modalities, airway inflammation management involves lowering FeNO levels to less than 25 ppb and blood eosinophil counts to less than 0.2 *109 cells / L.In some modalities, the management of airway inflammation involves lowering the FeNO level to a value below 20 ppb and to a blood eosinophil count below 0.2 *109 cells / l. Petition 870250085505, dated 09 / 22 / 2025, p. 44 / 173 36 / 126

[00098] In some modalities, airway inflammation management also includes decreasing one or more of the IL-5, CCL26 (eotaxin-3), TARC (CCL17), and IgE levels. In some modalities, airway inflammation management also includes decreasing the IL-5, CCL26 (eotaxin-3), TARC (CCL17), and IgE levels.

[00099] The present invention can be used to manage type 2 airway inflammation. In some embodiments, managing type 2 airway inflammation involves decreasing the FeNO level to a value below 40 ppb. In some embodiments, managing type 2 airway inflammation involves decreasing the FeNO level to a value below 35. In some embodiments, managing type 2 airway inflammation involves decreasing the FeNO level to a value below 30. In some embodiments, managing type 2 airway inflammation involves decreasing the FeNO level to a value below 25. In some embodiments, managing type 2 airway inflammation involves decreasing airway inflammation to a value below 20. [000100] In some modalities, the management of type 2 airway inflammation includes lowering the FeNO level to less than 40 ppb and the blood eosinophil count to less than 0.2 *10⁹ cells / L. In some modalities, the management of type 2 airway inflammation includes lowering the FeNO level to less than 35 ppb and the blood eosinophil count to less than 0.2 *10⁹ cells / L. In some modalities, the management of type 2 airway inflammation includes lowering the FeNO level to less than 30 ppb and the blood eosinophil count to less than 0.2 *10⁹ cells / L. In some modalities, the management of inflammation of Petition 870250085505, dated 09 / 22 / 2025, page 45 / 173 37 / 126 Type 2 airway inflammation management involves lowering the FeNO level to less than 25 ppb and the blood eosinophil count to less than 0.2 *109 cells / L. In some modalities, the management of type 2 airway inflammation involves lowering the FeNO level to less than 20 ppb and the blood eosinophil count to less than 0.2 *109 cells / L. 5.3 Compounds for use according to the present invention [000101] The compound linking TSLP and IL-13 for use in the present invention may be a polypeptide. Suitable polypeptides have been described in patent application no. WO2021116182, which is incorporated herein in its entirety. [000102] In some embodiments, the polypeptide is an antibody or an antibody fragment. Exemplary polypeptides for use in the present invention are polypeptides comprising immunoglobulin single variable domains (ISVDs). ISVDs that bind to TSLP and IL-13 can be found in Tables A-1 to A-6 of WO2021116182. [000103] In some embodiments, the polypeptide comprises or consists of at least four ISVDs, wherein two ISVDs specifically bind to IL-13 and two ISVDs specifically bind to TSLP, wherein each of said at least four ISVDs comprises three complementarity-determining regions (CDR1 to CDR3, respectively), wherein the at least four ISVDs are optionally linked through one or more peptide linkers, and wherein: A first ISVD comprises: A CDR1, which is the amino acid sequence with SEQ ID NO: 7; a CDR2, which is the amino acid sequence with SEQ ID NO: 12; and a CDR3, which is the amino acid sequence with SEQ ID NO: 17; a second ISVD comprises: Petition 870250085505, dated 09 / 22 / 2025, p. 46 / 173 38 / 126 a CDR1 which is the amino acid sequence of SEQ ID NO: 8, a CDR2 which is the amino acid sequence of SEQ ID NO: 13 and a CDR3 which is the amino acid sequence of SEQ ID NO: 18, a third ISVD comprises: a CDR1 which is the amino acid sequence of SEQ ID NO: 9, a CDR2 which is the amino acid sequence of SEQ ID NO: 14 and a CDR3 which is the amino acid sequence of SEQ ID NO: 19, and a fourth ISVD comprises: CDR1, which is the amino acid sequence with SEQ ID NO: 11; CDR2, which is the amino acid sequence with SEQ ID NO: 16; and CDR3, which is the amino acid sequence with SEQ ID NO: 21. SEQ ID NO: 7 is GRTFSSYRMG; SEQ ID NO: 12 is ALSGDGYSTY; SEQ ID NO: 17 is KLQYVSGWSYDYPY. SEQ ID NO: 8 is GFTFNNYAMK; SEQ ID NO: 13 is SITTGGGSTD; SEQ ID NO: 18 is VPFGYYSEHFSGLSFDY. SEQ ID NO: 9 is GSGFGVNILY; SEQ ID NO: 14 is SITSGGITN; SEQ ID NO: 19 is RNIFDGTTE. SEQ ID NO: 11 is GFTFADYDYDIG; SEQ ID NO: 16 is CISNRDGSTY; SEQ ID NO: 21 is EIHCDDYGVENFDFDP. [000104] In some forms, the compound comprises: a first ISVD comprising the amino acid sequence of SEQ ID NO: 2, a second ISVD comprising the amino acid sequence of SEQ ID NO: 3, a third ISVD comprising the amino acid sequence of SEQ ID NO: 4, and a fourth ISVD comprising the amino acid sequence of SEQ ID NO: 6. [000105] In some embodiments, the order of the ISVDs above indicates the relative position between them considered from the N-terminal to the C-terminal of said ISVD. Petition 870250085505, dated 09 / 22 / 2025, p. 47 / 173 39 / 126 polypeptide. [000106] In some embodiments, the compound comprises an additional ISVD that binds to human serum albumin, wherein the additional ISVD comprises: a CDR1 which is the amino acid sequence of SEQ ID NO: 10, a CDR2 which is the amino acid sequence of SEQ ID NO: 15; and a CDR3 which is the amino acid sequence of SEQ ID NO: 20. In some embodiments, this additional ISVD is positioned between the third and fourth ISVDs above. [000107] In some forms, the compound comprises: a first ISVD comprising the amino acid sequence of SEQ ID NO: 2, a second ISVD comprising the amino acid sequence of SEQ ID NO: 3, a third ISVD comprising the amino acid sequence of SEQ ID NO: 4, a fourth ISVD comprising the amino acid sequence of SEQ ID NO: 6, and an additional ISVD that binds to human serum albumin and comprises the amino acid sequence of SEQ ID NO: 5. [000108] An exemplary polypeptide that binds to TSLP and IL-13 is SAR443765 (also called lunsekimig) (SEQ ID NO: 1). In some embodiments, the polypeptide that binds to TSLP and IL-13 is SAR443765 (SEQ ID NO: 1). SEQ ID NO: 1 is: DVQLVESGGGVVQPGGSLRLSCAASGRTFSSYRMGWFRQAPGKER EFVAALSGDGYSTYTANSVKGRFTISRDNSKNTVYLQMNSLRPEDTA LYYCAAKLQYVSGWSYDYPYWGQGTLVTVSSGGGGGSGGGGSGGG GSGGGGSGGGGSGGGGSGGGGSEVQLVESGGGVVVQPGGSLRLS CAASGFTFNNYAMKWVRQAPGKGLEWVSSITTGGGSTDYADSVKG RFTISRDNSKNTLYLQMNSLRPEDTALYYCANVPFGYYSEHFSGLSF Petition 870250085505, dated 09 / 22 / 2025, page 48 / 173 40 / 126 DYRGQGTLVTVSSGGGGSGGGSEVQLVESGGGVVQPGGSLRLSCA ASSGGFGVNILYWYRQAAGIERELIASITSGGITNYVDSVKGRFTISRD NSENTMYLQMNSLRAEDTGLYYCASRNIFDGTTEWGQGTLVTVSSG GGGSGGGSEVQLVESGGGVVQPGGSLRLSCAASGFTFRSFGMSW VRQAPGKGPEWVSSISGSGSDTLYADSVKGRFTISRDNSKNTLYLQ MNSRLRPEDTALYYCTIGGSLSRSSQGTLVTVSSGGGGSGGGSEVQL VESGGGVVQPGGSLRLSCAASGFTFADYDYDIGWFRQAPGKEREG VSCISNRDGSTYYADSVKGRFTISRDNSKNTVYLQMNSLRPEDTALY YCAVEIHCDDYGVENFDFDPWGQGTLVTVSSA. 5.3.1 Unique variable immunoglobulin domains [000109] As indicated above, in some embodiments, the polypeptide for use in the present invention is a polypeptide comprising immunoglobulin unique variable domains (ISVDs). [000110] The term “immunoglobulin single variable domain” (ISVD), used interchangeably with “single variable domain”, defines immunoglobulin molecules in which the antigen-binding site is present and formed by a single immunoglobulin domain. This differentiates ISVDs from conventional immunoglobulins (e.g., monoclonal antibodies) or their fragments (such as Fab, Fab', F(ab')2, scFv, di-scFv), in which two immunoglobulin domains, in particular, two variable domains, interact to form an antigen-binding site. Typically, in conventional immunoglobulins, a heavy chain variable domain (VH) and a light chain variable domain (VL) interact to form an antigen-binding site. In this case, the complementarity-determining regions (CDRs) of VH and VL will contribute to the antigen-binding site, i.e., a total of 6 CDRs will be involved in the formation of the antigen-binding site. [000111] In view of the above definition, the antigen-binding domain of a conventional 4-chain antibody (such as an IgG, IgM, IgA, IgD, or IgE molecule; known in the art) or of a Fab fragment, Petition 870250085505, dated 09 / 22 / 2025, page 49 / 173 41 / 126 a fragment of F(ab')2, an Fv fragment such as a disulfide-linked Fv or an scFv fragment, or a diabody (all known in the art) derived from a conventional 4-chain antibody, would not normally be considered an ISVD, since in these cases the binding to the respective epitope of an antigen would not normally occur by a (single) immunoglobulin domain, but by a pair of immunoglobulin domains (in association), such as variable light and heavy chain domains, i.e., a VH-VL pair of immunoglobulin domains, which together bind to an epitope of the respective antigen. [000112] On the other hand, ISVDs have the ability to bind specifically to an antigen epitope without pairing with an additional immunoglobulin variable domain. The binding site of an ISVD is formed by a single VH, VHH, or VL domain. [000113] Thus, the single variable domain can be a light chain variable domain sequence (e.g., a VL sequence) or a suitable fragment thereof; or a heavy chain variable domain sequence (e.g., a VH or VHH sequence) or a suitable fragment thereof; provided that it is capable of forming a single antigen-binding unit (i.e., a functional antigen-binding unit consisting essentially of the single variable domain, such that the single antigen-binding domain does not need to interact with another variable domain to form a functional antigen-binding unit). [000114] An ISVD can, for example, be a heavy-chain ISVD, such as a VH, VHH, including a camelized VH or humanized VHH. In one embodiment, it is a VHH, including a camelized VH or humanized VHH. Heavy-chain ISVDs can be derived from a conventional four-chain antibody or from a chain antibody. Petition 870250085505, dated 09 / 22 / 2025, p. 50 / 173 42 / 126 heavy. [000115] For example, ISVD may be a single-domain antibody (or an amino acid sequence that is suitable for use as a single-domain antibody), a dAb or dAb (or an amino acid sequence that is suitable for use as a dAb), or an ISVD Nanobody® (as defined herein, and including, but not limited to, a Vhh); other single variable domains or any suitable fragment thereof. [000116] In particular, ISVD may be an ISV Nanobody® (such as a VHH, including a humanized VHH or camelized VHH) or a suitable fragment thereof. Nanobody®, Nanobodies®, and Nanoclone® are registered trademarks of Sanofi or its affiliates. [000117] “Vhh domains”, also known as VhhS, VHH antibody fragments and VHH antibodies, were originally described as the antigen-binding immunoglobulin variable domain of “heavy chain antibodies” (i.e., “antibodies devoid of light chains”; Hamers-Casterman et al., Nature 363: 446-448, 1993). The term “Vhh domain” was chosen in order to distinguish these variable domains from the heavy chain variable domains that are present in conventional 4-chain antibodies (which are referred to herein as “Vh domains”) and from the light chain variable domains that are present in conventional 4-chain antibodies (which are referred to herein as “Vl domains”). For a further description of VhhS, reference is made to the analysis article by Muyldermans (Reviews in Molecular Biotechnology 74: 277-302, 2001). [000118] Typically, the generation of immunoglobulins involves immunizing experimental animals, fusing immunoglobulin-producing cells to create hybridomas, and screening for desired specificities. Alternatively, immunoglobulins Petition 870250085505, dated 09 / 22 / 2025, page 51 / 173 43 / 126 can be generated by screening virgin or synthetic libraries, for example, by displaying phages. [000119] The generation of immunoglobulin sequences, such as Nanobodies®, has been extensively described in several publications, including WO 94 / 04678, Hamers-Casterman et al. 1993 and Muyldermans, 2001, can be cited as examples. In these methods, camelids are immunized with the target antigen in order to induce an immune response against said target antigen. The repertoire of nanobodies obtained from this immunization is further screened for nanobodies that bind to the target antigen. [000120] In these cases, antibody generation requires purified antigen for immunization and / or screening. Antigens can be purified from natural sources or in the course of recombinant production. [000121] Immunization and / or screening for immunoglobulin sequences can be performed using peptide fragments of such antigens. [000122] The present invention may use immunoglobulin sequences of different origins, including mouse, rat, rabbit, donkey, human, and camelid immunoglobulin sequences. The present invention may also use fully human, humanized, or chimeric sequences. For example, the present invention uses camelid immunoglobulin sequences and humanized camelid immunoglobulin sequences, or camelized domain antibodies, for example, camelized dAb, as described by Ward et al. (see, for example, document no. WO 94 / 04678 and Davies and Riechmann (1994 and 1996)). Furthermore, in some embodiments, the present invention also uses fused immunoglobulin sequences, for example, forming a multivalent and / or multispecific construct (for multivalent polypeptides and Petition 870250085505, dated 09 / 22 / 2025, p. 52 / 173 44 / 126 multispecific immunoglobulins containing one or more Vhh domains and their preparation (reference is also made to Conrath et al., J. Biol. Chem., Vol. 276, 10. 7346-7350, 2001, as well as, for example, documents no. WO 96 / 34103 and WO 99 / 23221), and immunoglobulin sequences that include labels or other functional fractions, for example, toxins, identifications, radiochemical products, etc., which are derivable from the immunoglobulin sequences of the compound used in the present invention. 5.3.2 Antibodies [000123] As indicated above, in some embodiments, the polypeptide for use in the present invention is an antibody. Antibodies that bind to TSLP and IL-13 can be found in Venkataramani et al. (Biochem Biophys Res Commun. September 26, 2018; 504(1):19-24). 5.3.3 Connection / Blocking [000124] The compounds of the present invention bind to TSLP and IL13. In some embodiments, the compound of the present invention can block its target molecules. For example, the compound can block the interaction between IL-13 and IL-13Ra1 (interleukin 13, alpha 1 receptor) and / or the interaction between the IL-13 / IL-4Ra complex and IL-13Ra1 (interleukin-4 alpha receptor) and / or it can block the interaction between TSLP and TSLPR (TSLP receptor) and / or the TSLP / TSLP complex and IL-7Ra (interleukin-7 subalpha receptor unit). In some embodiments, the compound of the present invention can block the interaction between IL-13 and IL-13Ra1 (interleukin 13, alpha 1 receptor) and / or the interaction between the IL-13 / IL-13Rα1 complex and IL-4Rα (interleukin-4 alpha receptor), and can block the interaction between TSLP and TSLPR (TSLP receptor) and / or the TSLP / TSLP complex and IL-7Rα (interleukin 7 subalpha receptor unit). [000125] In some embodiments, the compound for use in this Petition 870250085505, dated 09 / 22 / 2025, p. 53 / 173 45 / 126 invention can bind to human IL-13 (Uniprot access P35225) and human TSLP (Uniprot access Q969D9). In some embodiments, the compound for use in the present invention can bind to IL-13 and TSLP from other mammals, for example IL-13 and TSLP from mice, rats, rabbits, cats, dogs, goats, sheep, horses, pigs, non-human primates such as cynomolgus monkeys (also referred to herein as "cyno"), or camelids such as llamas or alpacas.[000126] With respect to the compounds of the present invention, binding to IL-13 and TSLP means specific binding to IL-13 and TSLP. The binding of a compound to its target can be determined based on affinity. Affinity denotes the strength or stability of a molecular interaction. Affinity is commonly given as KD, or dissociation constant, which has units mol / liter (or M). [000127] Affinity is a measure of the binding strength between a chemical moiety and a binding site on the target molecule: the lower the KD value, the stronger the binding strength between a target molecule and a bleaching chemical moiety. [000128] Typically, the linking units used in the present invention will be linked to their targets with a dissociation constant (KD) of 10-5 to 10-12 moles / liter or less, or 10-7 to 10-12 moles / liter or less, or 10-8 to 10-12 moles / liter (i.e., with an association constant (KA) of 105 to 1012 liters / moles or more, or 107 to 1012 liters / moles or more, or 108 to 1012 liters / moles). [000129] Any KD value greater than 10-4 mol / liter (or any KA value less than 104 liters / mol) is generally considered indicative of nonspecific interaction. [000130] The KD for biological interactions, such as the binding of immunoglobulin sequences to an antigen, which are considered Petition 870250085505, dated 09 / 22 / 2025, page 54 / 173 Specific 46 / 126 molecules are typically in the range of 10⁻⁵ moles / liter (10,000 nM or 10 μM) to 10⁻¹² moles / liter (0.001 nM or 1 pM) or less. [000131] Consequently, specific / selective binding can mean that – using the same measurement method, for example, SPR – a compound binds to IL13 and / or TSLP with a KD value of 10⁻⁵ to 10⁻¹² mol / liter or less and binds to related cytokines with a KD value greater than 10⁻⁴ mol / liter. Examples of IL13-related targets are human IL⁴. Examples of TSLP-related cytokines are human IL⁷. Thus, in some embodiments, the compound used in the present invention binds to IL13 with a KD value of 10-5 to 10-12 moles / liter or less and binds to IL4 of the same species with a KD value greater than 10-4 moles / liter, and binds to TSLP with a KD value of 10-5 to 10-12 moles / liter or less and binds to human IL7 of the same species with a KD value greater than 10-4 moles / liter. [000132] In some embodiments, the polypeptides used in the present invention have at least the binding affinity, or at least the same binding affinity, to IL13 and human TSLP compared to a polypeptide consisting of the amino acid of SEQ ID NO: 1, wherein the binding affinity is measured using the same method as SPR. [000133] Specific binding to a certain target in a certain species does not preclude the binding unit from also specifically binding to an analogous target in a different species. For example, specific binding to human IL13 does not preclude the binding unit (or a polypeptide comprising it) from also specifically binding to IL13 in cynomolgus monkeys. Similarly, for example, specific binding to human TSLP does not preclude the binding unit (or a polypeptide comprising it) from also specifically binding to Petition 870250085505, dated 09 / 22 / 2025, p. 55 / 173 47 / 126 TSLP of cynomolgus monkeys (“cyno”). [000134] The specific binding of a binding unit to its designated target can be determined by any suitable method known per se, including, for example, Scatchard analyses and / or competitive binding assays, such as radioimmunoassays (RIA), enzyme immunoassays (EIA) and sandwich competition assays and the different variants known to you in the art, as well as the other techniques mentioned in this document. [000135] The dissociation constant can be the actual or apparent dissociation constant, as will be evident to those skilled in the art. The methods for determining the dissociation constant will be evident to those skilled in the art and, for example, include the techniques mentioned below. In this respect, it will also be clear that it may not be possible to measure dissociation constants greater than 10⁻⁴ moles / liter or 10⁻³ moles / liter (e.g., 10⁻² moles / liter). Optionally, as will also be evident to those skilled in the art, the dissociation constant (actual or apparent) can be calculated based on the association constant (actual or apparent) (KA), using the relation [KD = 1 / KA]. [000136] The affinity of a molecular interaction between two molecules can be measured through different techniques known per se, such as the well-known surface plasmon resonance (SPR) biosensor technique (see, for example, Ober et al., 2001, Intern. Immunology 13: 1551-1559). The term surface plasmon resonance, as used in this document, refers to an optical phenomenon that allows the analysis of biospecific interactions in real time through the detection of changes in protein concentrations within a biosensor array, where one molecule is immobilized on the biosensor chip and the other molecule is passed over the immobilized molecule under flow conditions, producing measurements of Petition 870250085505, dated 09 / 22 / 2025, page 56 / 173 48 / 126 kon, koff and therefore Kd (or Ka) values. This can, for example, be accomplished using the well-known BIAcore® system (BIAcore International AB, a GE Healthcare company, Uppsala, Sweden and Piscataway, NJ). For further descriptions, see Jonsson et al. (1993, Ann. Biol. Clin. 51: 19-26), Jonsson et al. (1991 Biotechniques 11: 620-627), Johnsson et al. (1995, J. Mol. Recognit. 8: 125-131), and Johnnson et al., (1991, Anal. Biochem. 198: 268-277). [000137] Another well-known biosensor technique for determining affinities of biomolecular interactions is biolayer interferometry (BLI) (see, for example, Abdiche et al., 2008, Anal. Biochem. 377: 209-217). The term biolayer interferometry or BLI, as used in this document, refers to an identification-free optical technique that analyzes the interference pattern of light reflected from two surfaces: an internal reference layer (reference beam) and a protein layer immobilized at the tip of the biosensor (signal beam). A change in the number of molecules bound to the biosensor tip causes a shift in the interference pattern, reported as a wavelength (nm) shift, the magnitude of which is a direct measure of the number of molecules bound to the surface of the biosensor tip. Since the interactions can be measured in real time, association and dissociation rates and affinities can be determined.BLI can, for example, be performed using the well-known Octet® systems (ForteBio, a division of Pall Life Sciences, Menlo Park, USA). [000138] Alternatively, affinities can be measured in Kinetic Exclusion Assay (KinExA) (see, for example, Drake et al., 2004, Anal. Biochem., 328: 35-43), using the KinExA® platform (Sapidyne Instruments Inc, Boise, USA). The term KinExA, as used in this document, refers to a solution-based method for measuring equilibrium binding affinity. Petition 870250085505, dated 09 / 22 / 2025, page 57 / 173 49 / 126 true and the kinetics of unmodified molecules. Equilibrated solutions of an antibody / antigen complex are passed over a column with microspheres pre-coated with antigen (or antibody), allowing the free antibody (or antigen) to bind to the coated molecule. Detection of the antibody (or antigen) thus captured is performed with a fluorescently identified protein that binds the antibody (or antigen). [000139] The GYROLAB® immunoassay system provides a platform for automated bioanalysis and rapid sample retrieval (Fraley et al., 2013, Bioanalysis 5: 1765-74). 5.3.4 Nucleic acid molecules [000140] In some embodiments, the present invention relates to a nucleic acid for use in the treatment of a lung disease in an individual, wherein the nucleic acid encodes a compound that binds to IL-13 and TSLP, wherein the treatment reduces the level of fractionated exhaled nitric oxide (FeNO) by at least 18 ppb compared with placebo. In some embodiments, the lung disease is an inflammatory disease. In some embodiments, the lung disease is asthma. In some embodiments, the asthma is high eosinophilic asthma. In some embodiments, the asthma is low eosinophilic asthma. [000141] A “nucleic acid molecule” (used interchangeably with “nucleic acid”) is a chain of nucleotide monomers linked together through a phosphate backbone to form a nucleotide sequence. A nucleic acid can be used to transform / transfect a host cell or host organism, for example, for the expression and / or production of a polypeptide. Suitable hosts or host cells for production purposes will be clear to those skilled in the art and may, for example, be any suitable fungal, prokaryotic or eukaryotic cell or cell line or any organism. Petition 870250085505, dated 09 / 22 / 2025, page 58 / 173 50 / 126 suitable fungal, prokaryotic or eukaryotic. A host or host cell comprising the polypeptide of the present invention is also covered by the present invention. [000142] A nucleic acid can be, for example, DNA, RNA, or a hybrid thereof, and can also comprise modified nucleotides (e.g., chemically), such as PNA. It can be single-stranded or double-stranded. In one embodiment, it is in the form of double-stranded DNA. For example, the nucleotide sequences of the present invention can be genomic DNA, cDNA. [000143] The nucleic acids of the present invention can be prepared or obtained in a known manner per se and / or can be isolated from a suitable natural source. Nucleotide sequences encoding naturally occurring (poly)peptides can, for example, be subjected to site-directed mutagenesis in order to provide a nucleic acid molecule encoding a sequence-variant polypeptide. Furthermore, as will be evident to those skilled in the art, to prepare a nucleic acid, several nucleotide sequences can also be used, such as at least one nucleotide sequence encoding a chemical bleaching moiety and, for example, nucleic acids encoding one or more ligands that can be suitably linked together. [000144] Nucleic acid generation techniques will be clear to those skilled in the art and may include, for example, but not limited to, automated DNA synthesis; site-directed mutagenesis; combination of two or more natural and / or synthetic sequences (or two or more parts thereof); introduction of mutations leading to the expression of a truncated expression product; introduction of one or more restriction sites (e.g., to create cassettes and / or regions that can be easily digested and / or ligated using appropriate restriction enzymes); and / or the introduction of mutations. Petition 870250085505, dated 09 / 22 / 2025, page 59 / 173 51 / 126 via a PCR reaction using one or more “misaligned” primers. 5.3.5 Compositions [000145] The present invention also provides a pharmaceutical composition for use in the present invention, wherein the pharmaceutical composition comprises at least one compound that binds to TSLP and IL-13 and / or at least one nucleic acid molecule encoding a compound that binds to TSLP and IL-13. The composition may further comprise at least one pharmaceutically acceptable carrier, diluent or excipient and / or adjuvant, and optionally comprise one or more additional polypeptides and / or pharmaceutically active compounds. [000146] In some embodiments, the invention provides a pharmaceutical composition comprising a compound that binds to IL-13 and TSLP for use in the treatment of a lung disease in an individual, wherein the composition further comprises at least one pharmaceutically acceptable vehicle, diluent or excipient and / or adjuvant and optionally comprises one or more additional polypeptides and / or pharmaceutically active compounds, wherein the treatment reduces the level of exhaled fractionated nitric oxide (FeNO) by at least 18 ppb compared with placebo. In some embodiments, the lung disease is an inflammatory disease. In some embodiments, the lung disease is asthma. In some embodiments, the asthma is high eosinophilic asthma. In some embodiments, the asthma is low eosinophilic asthma. [000147] In some embodiments, the invention provides a pharmaceutical composition comprising a compound that binds to IL-13 and TSLP for use in the treatment of a pulmonary disease in an individual, wherein the composition further comprises at least one vehicle, diluent or excipient and / or pharmaceutically produced adjuvant. Petition 870250085505, dated 09 / 22 / 2025, p. 60 / 173 52 / 126 acceptable and optionally comprises one or more additional polypeptides and / or pharmaceutically active compounds, wherein the treatment reduces the level of exhaled fractionated nitric oxide (FeNO) by at least 20 ppb compared with placebo. In some modalities, the lung disease is an inflammatory disease. In some modalities, the lung disease is asthma. In some modalities, the asthma is high eosinophilic asthma. In some modalities, the asthma is low eosinophilic asthma. [000148] In some embodiments, the invention provides a pharmaceutical composition comprising a compound that binds to IL-13 and TSLP for use in the treatment of a lung disease in an individual, wherein the composition further comprises at least one pharmaceutically acceptable vehicle, diluent or excipient and / or adjuvant and optionally comprises one or more additional polypeptides and / or pharmaceutically active compounds, wherein the treatment reduces the level of exhaled fractionated nitric oxide (FeNO) by at least 30 ppb compared with placebo. In some embodiments, the lung disease is an inflammatory disease. In some embodiments, the lung disease is asthma. In some embodiments, the asthma is high eosinophilic asthma. In some embodiments, the asthma is low eosinophilic asthma. [000149] In some embodiments, the invention provides a pharmaceutical composition comprising a compound that binds to IL-13 and TSLP for use in the treatment of a pulmonary disease in an individual, wherein the composition further comprises at least one pharmaceutically acceptable vehicle, diluent or excipient and / or adjuvant and optionally comprises one or more additional polypeptides and / or pharmaceutically active compounds, wherein the treatment reduces the level of exhaled fractionated nitric oxide (FeNO) by at least 40 ppb compared with placebo. In some embodiments, the Petition 870250085505, dated 09 / 22 / 2025, p. 61 / 173 53 / 126 Lung disease is an inflammatory disease. In some forms, lung disease is asthma. In some forms, asthma is elevated eosinophilic asthma. In some forms, asthma is low eosinophilic asthma. 5.4 Inventional Embodiments [000150] The following exemplary embodiments of the present invention are given for illustrative purposes. 5.4.1 Compound that binds to IL-13 and TSLP for use in the treatment of a lung disease. [000151] These embodiments refer to a compound that binds to IL-13 and TSLP for use in the treatment of a lung disease in an individual, wherein said treatment reduces the level of fractionated exhaled nitric oxide (FeNO) by at least 18 ppb compared with a control. FeNO level + points over time [000152] In some modalities, treatment reduces the level of fractionated exhaled nitric oxide (FeNO) by at least 18 ppb compared with placebo within 4 weeks after administration of the compound. [000153] In some modalities, the treatment reduces the level of fractionated exhaled nitric oxide (FeNO) by at least 18 ppb compared with placebo within 2 weeks after administration of the compound. [000154] In some modalities, the treatment reduces the level of fractionated exhaled nitric oxide (FeNO) by at least 18 ppb compared with placebo within 1 week after administration of the compound. [000155] In some modalities, treatment reduces the level of fractionated exhaled nitric oxide (FeNO) by at least 20 ppb compared with placebo within 4 weeks of administration. Petition 870250085505, dated 09 / 22 / 2025, page 62 / 173 54 / 126 of the compound. [000156] In some modalities, the treatment reduces the level of fractionated exhaled nitric oxide (FeNO) by at least 20 ppb compared with placebo within 2 weeks after administration of the compound. [000157] In some modalities, the treatment reduces the level of fractionated exhaled nitric oxide (FeNO) by at least 20 ppb compared with placebo within 1 week after administration of the compound. [000158] In some modalities, the treatment reduces the level of fractionated exhaled nitric oxide (FeNO) by at least 25 ppb compared with placebo within 4 weeks after administration of the compound. [000159] In some modalities, the treatment reduces the level of fractionated exhaled nitric oxide (FeNO) by at least 25 ppb compared with placebo within 2 weeks after administration of the compound. [000160] In some modalities, the treatment reduces the level of fractionated exhaled nitric oxide (FeNO) by at least 25 ppb compared with placebo within 1 week after administration of the compound. [000161] In some modalities, the treatment reduces the level of fractionated exhaled nitric oxide (FeNO) by at least 30 ppb compared with placebo within 4 weeks after administration of the compound. [000162] In some modalities, the treatment reduces the level of fractionated exhaled nitric oxide (FeNO) by at least 30 ppb compared with placebo within 2 weeks after administration of the compound. [000163] In some modalities, the treatment reduces the level of Petition 870250085505, dated 09 / 22 / 2025, page 63 / 173 55 / 126 fractionated exhaled nitric oxide (FeNO) increased by at least 30 ppb compared with placebo within 1 week after administration of the compound. [000164] In some modalities, treatment reduces the level of fractionated exhaled nitric oxide (FeNO) by at least 35 ppb compared with placebo within 4 weeks after administration of the compound. [000165] In some modalities, the treatment reduces the level of fractionated exhaled nitric oxide (FeNO) by at least 35 ppb compared with placebo within 2 weeks after administration of the compound. [000166] In some modalities, the treatment reduces the level of fractionated exhaled nitric oxide (FeNO) by at least 35 ppb compared with placebo within 1 week after administration of the compound. [000167] In some modalities, the treatment reduces the level of fractionated exhaled nitric oxide (FeNO) by at least 40 ppb compared with placebo within 4 weeks after administration of the compound. [000168] In some modalities, the treatment reduces the level of fractionated exhaled nitric oxide (FeNO) by at least 40 ppb compared with placebo within 2 weeks after administration of the compound. [000169] In some modalities, the treatment reduces the level of fractionated exhaled nitric oxide (FeNO) by at least 40 ppb compared with placebo within 1 week after administration of the compound. Basal level of FeNO [000170] In some modalities, treatment is applied to individuals who have a baseline level of FeNO (before administration of Petition 870250085505, dated 09 / 22 / 2025, p. 64 / 173 56 / 126 compound) of at least 25. [000171] In some modalities, the treatment is applied to individuals who have a baseline FeNO level (before administration of the compound) of at least 30. [000172] In some modalities, the treatment is applied to individuals who have a baseline FeNO level (before administration of the compound) of at least 40. [000173] In some modalities, the treatment is applied to individuals who have a baseline FeNO level (before administration of the compound) of at least 50. [000174] In some modalities, the treatment is applied to individuals who have a baseline FeNO level (before administration of the compound) of at least 60. [000175] In some modalities, the treatment is applied to individuals who have a baseline FeNO level (before administration of the compound) of at least 70. [000176] In some modalities, treatment is applied to individuals to manage a baseline FeNO level (before administration of the compound) of at least 25. [000177] In some modalities, treatment is applied to individuals to manage a baseline FeNO level (before administration of the compound) of at least 30. [000178] In some modalities, treatment is applied to individuals to manage a baseline FeNO level (before administration of the compound) of at least 40. [000179] In some modalities, treatment is applied to individuals to manage a baseline FeNO level (before administration of the compound) of at least 50. [000180] In some modalities, treatment is applied to individuals to manage a baseline level of FeNO (before the Petition 870250085505, dated 09 / 22 / 2025, page 65 / 173 57 / 126 administration of the compound) of at least 60. [000181] In some modalities, treatment is applied to individuals to manage a baseline FeNO level (before administration of the compound) of at least 70. Eosinophil count + time points [000182] In some embodiments of the present invention, the eosinophil count is reduced by at least 30% compared with placebo within 4 weeks after administration of the compound. [000183] In some embodiments of the present invention, the eosinophil count is reduced by at least 30% compared with placebo within 2 weeks after administration of the compound. [000184] In some embodiments of the present invention, the eosinophil count is reduced by at least 30% compared with placebo within 1 week after administration of the compound. [000185] In some embodiments of the present invention, the eosinophil count is reduced by at least 30% compared with placebo within 3 days after administration of the compound. [000186] In some embodiments of the present invention, the eosinophil count is reduced by at least 30% compared with placebo within 1 day after administration of the compound. [000187] In some embodiments of the present invention, the eosinophil count is reduced by at least 35% compared with placebo within 4 weeks after administration of the compound. [000188] In some embodiments of the present invention, the eosinophil count is reduced by at least 35% compared with placebo within 2 weeks after administration of the compound. [000189] In some embodiments of the present invention, the eosinophil count is reduced by at least 35% compared with placebo within 1 week after administration of the compound. [000190] In some embodiments of the present invention, the counting Petition 870250085505, dated 09 / 22 / 2025, page 66 / 173 The 58 / 126 eosinophil count is reduced by at least 35% compared to placebo within 3 days after administration of the compound. [000191] In some embodiments of the present invention, the eosinophil count is reduced by at least 35% compared with placebo within 1 day after administration of the compound. [000192] In some embodiments of the present invention, the eosinophil count is reduced by at least 40% compared with placebo within 4 weeks after administration of the compound. [000193] In some embodiments of the present invention, the eosinophil count is reduced by at least 40% compared with placebo within 2 weeks after administration of the compound. [000194] In some embodiments of the present invention, the eosinophil count is reduced by at least 40% compared with placebo within 1 week after administration of the compound. [000195] In some embodiments of the present invention, the eosinophil count is reduced by at least 40% compared with placebo within 3 days after administration of the compound. [000196] In some embodiments of the present invention, the eosinophil count is reduced by at least 40% compared with placebo within 1 day after administration of the compound. FeNO level + eosinophil count + time points [000197] In some modalities, the treatment reduces the level of fractionated exhaled nitric oxide (FeNO) by at least 18 ppb and reduces the eosinophil count by at least 30% compared with placebo within 4 weeks after administration of the compound. [000198] In some modalities, the treatment reduces the level of fractionated exhaled nitric oxide (FeNO) by at least 20 ppb and reduces the eosinophil count by at least 30% compared with placebo within 4 weeks after administration of the compound. [000199] In some modalities, the treatment reduces the level of Petition 870250085505, dated 09 / 22 / 2025, page 67 / 173 59 / 126 fractionated exhaled nitric oxide (FeNO) by at least 30 ppb and reduces eosinophil count by at least 30% compared with placebo within 4 weeks after administration of the compound. [000200] In some modalities, the treatment reduces the level of fractionated exhaled nitric oxide (FeNO) by at least 40 ppb and reduces the eosinophil count by at least 30% compared with placebo within 4 weeks after administration of the compound. [000201] In some modalities, the treatment reduces the level of fractionated exhaled nitric oxide (FeNO) by at least 18 ppb and reduces the eosinophil count by at least 30% compared with placebo within 2 weeks after administration of the compound. [000202] In some modalities, the treatment reduces the level of fractionated exhaled nitric oxide (FeNO) by at least 20 ppb and reduces the eosinophil count by at least 30% compared with placebo within 2 weeks after administration of the compound. [000203] In some modalities, the treatment reduces the level of fractionated exhaled nitric oxide (FeNO) by at least 30 ppb and reduces the eosinophil count by at least 30% compared with placebo within 2 weeks after administration of the compound. [000204] In some modalities, the treatment reduces the level of fractionated exhaled nitric oxide (FeNO) by at least 40 ppb and reduces the eosinophil count by at least 30% compared with placebo within 2 weeks after administration of the compound. [000205] In some modalities, the treatment reduces the level of fractionated exhaled nitric oxide (FeNO) by at least 18 ppb and reduces the eosinophil count by at least 30% compared with placebo within 1 week after administration of the compound. [000206] In some modalities, treatment reduces the level of fractionated exhaled nitric oxide (FeNO) by at least 20 ppb and reduces the eosinophil count by at least 30% compared to Petition 870250085505, dated 09 / 22 / 2025, page 68 / 173 60 / 126 placebo within 1 week after administration of the compound. [000207] In some modalities, the treatment reduces the level of fractionated exhaled nitric oxide (FeNO) by at least 30 ppb and reduces the eosinophil count by at least 30% compared with placebo within 1 week after administration of the compound. [000208] In some modalities, the treatment reduces the level of fractionated exhaled nitric oxide (FeNO) by at least 40 ppb and reduces the eosinophil count by at least 30% compared with placebo within 1 week after administration of the compound. SEQ ID NO: 1 + asthma [000209] In some embodiments, the present invention provides a compound that binds to IL-13 and TSLP for use in the treatment of asthma in an individual, wherein said compound is a polypeptide comprising or consisting of the amino acid sequence of SEQ ID NO: 1. [000210] In some embodiments, the present invention provides a compound that binds to IL-13 and TSLP for use in the treatment of elevated eosinophilic asthma in an individual, wherein said compound is a polypeptide comprising or consisting of the amino acid sequence of SEQ ID NO: 1. [000211] In some embodiments, the present invention provides a compound that binds to IL-13 and TSLP for use in the treatment of eosinophilic asthma in an individual, wherein said compound is a polypeptide comprising or consisting of the amino acid sequence SEQ ID NO: 1. SEQ ID NO: 1 + asthma + FeNO level [000212] In some embodiments, the present invention provides a compound that binds to IL-13 and TSLP for use in the treatment of asthma in an individual, wherein the treatment reduces the level of fractionated exhaled nitric oxide (FeNO) by at least 18 ppb compared with Petition 870250085505, dated 09 / 22 / 2025, p. 69 / 173 61 / 126 placebo, wherein said compound is a polypeptide comprising or consisting of the amino acid sequence of SEQ ID NO: 1. [000213] In some embodiments, the present invention provides a compound that binds to IL-13 and TSLP for use in the treatment of asthma in an individual, wherein the treatment reduces the fractionated exhaled nitric oxide (FeNO) level by at least 20 ppb compared with placebo, wherein said compound is a polypeptide comprising or consisting of the amino acid sequence SEQ ID NO: 1. [000214] In some embodiments, the present invention provides a compound that binds to IL-13 and TSLP for use in the treatment of asthma in an individual, wherein the treatment reduces the fractionated exhaled nitric oxide (FeNO) level by at least 30 ppb compared with placebo, wherein said compound is a polypeptide comprising or consisting of the amino acid sequence SEQ ID NO: 1. [000215] In some embodiments, the present invention provides a compound that binds to IL-13 and TSLP for use in the treatment of asthma in an individual, wherein the treatment reduces the fractionated exhaled nitric oxide (FeNO) level by at least 40 ppb compared with placebo, wherein said compound is a polypeptide comprising or consisting of the amino acid sequence SEQ ID NO: 1. SEQ ID NO: 1 + asthma + FeNO level + points in time [000216] In some embodiments, the present invention provides a compound that binds to IL-13 and TSLP for use in the treatment of asthma in an individual, wherein the treatment reduces the fractionated exhaled nitric oxide (FeNO) level by at least 18 ppb compared with a control, wherein said reduction in FeNO level occurs within 4 weeks after administration of the compound, wherein said compound is a polypeptide comprising or consisting of the amino acid sequence of SEQ ID NO: 1. [000217] In some embodiments, the present invention provides a Petition 870250085505, dated 09 / 22 / 2025, pp. 70 / 173 62 / 126 compound that binds to IL-13 and TSLP for use in the treatment of asthma in an individual, wherein the treatment reduces the fractionated exhaled nitric oxide (FeNO) level by at least 20 ppb compared with a control, wherein said reduction in FeNO level occurs within 4 weeks after administration of the compound, wherein said compound is a polypeptide comprising or consisting of the amino acid sequence SEQ ID NO: 1. [000218] In some embodiments, the present invention provides a compound that binds to IL-13 and TSLP for use in the treatment of asthma in an individual, wherein the treatment reduces the fractionated exhaled nitric oxide (FeNO) level by at least 30 ppb compared with a control, wherein said reduction in FeNO level occurs within 4 weeks after administration of the compound, wherein said compound is a polypeptide comprising or consisting of the amino acid sequence SEQ ID NO: 1. [000219] In some embodiments, the present invention provides a compound that binds to IL-13 and TSLP for use in the treatment of asthma in an individual, wherein the treatment reduces the fractionated exhaled nitric oxide (FeNO) level by at least 40 ppb compared with a control, wherein said reduction in FeNO level occurs within 4 weeks after administration of the compound, wherein said compound is a polypeptide comprising or consisting of the amino acid sequence SEQ ID NO: 1. SEQ ID NO: 1 + asthma + FeNO level + time points + placebo [000220] In some embodiments, the present invention provides a compound that binds to IL-13 and TSLP for use in the treatment of asthma in an individual, wherein the treatment reduces the fractionated exhaled nitric oxide (FeNO) level by at least 18 ppb compared with placebo, wherein said reduction in FeNO level occurs within 4 weeks after administration of the compound, wherein said compound is Petition 870250085505, dated 09 / 22 / 2025, pp. 71 / 173 63 / 126 a polypeptide comprising or consisting of the amino acid sequence of SEQ ID NO: 1. [000221] In some embodiments, the present invention provides a compound that binds to IL-13 and TSLP for use in the treatment of asthma in an individual, wherein the treatment reduces the level of fractionated exhaled nitric oxide (FeNO) by at least 20 ppb compared with placebo, wherein said reduction in FeNO level occurs within 4 weeks after administration of the compound, wherein said compound is a polypeptide comprising or consisting of the amino acid sequence of SEQ ID NO: 1. [000222] In some embodiments, the present invention provides a compound that binds to IL-13 and TSLP for use in the treatment of asthma in an individual, wherein the treatment reduces the fractionated exhaled nitric oxide (FeNO) level by at least 30 ppb compared with placebo, wherein said reduction in FeNO level occurs within 4 weeks after administration of the compound, wherein said compound is a polypeptide comprising or consisting of the amino acid sequence of SEQ ID NO: 1. [000223] In some embodiments, the present invention provides a compound that binds to IL-13 and TSLP for use in the treatment of asthma in an individual, wherein the treatment reduces the fractionated exhaled nitric oxide (FeNO) level by at least 40 ppb compared with placebo, wherein said reduction in FeNO level occurs within 4 weeks after administration of the compound, wherein said compound is a polypeptide comprising or consisting of the amino acid sequence of SEQ ID NO: 1. SEQ ID NO: 1 + asthma + FeNO level + time points + baseline [000224] In some embodiments, the present invention provides a compound that binds to IL-13 and TSLP for use in the treatment of asthma. Petition 870250085505, dated 09 / 22 / 2025, p. 72 / 173 64 / 126 in an individual, wherein the treatment reduces the fractionated exhaled nitric oxide (FeNO) level by at least 18 ppb compared to baseline, wherein said reduction in FeNO level occurs within 4 weeks after administration of the compound, wherein said compound is a polypeptide comprising or consisting of the amino acid sequence SEQ ID NO: 1, wherein baseline means the individual's baseline. [000225] In some embodiments, the present invention provides a compound that binds to IL-13 and TSLP for use in the treatment of asthma in an individual, wherein the treatment reduces the fractionated exhaled nitric oxide (FeNO) level by at least 20 ppb compared to baseline, wherein said reduction in FeNO level occurs within 4 weeks after administration of the compound, wherein said compound is a polypeptide comprising or consisting of the amino acid sequence SEQ ID NO: 1, wherein baseline means the individual's baseline. [000226] In some embodiments, the present invention provides a compound that binds to IL-13 and TSLP for use in the treatment of asthma in an individual, wherein the treatment reduces the fractionated exhaled nitric oxide (FeNO) level by at least 30 ppb compared to baseline, wherein said reduction in FeNO level occurs within 4 weeks after administration of the compound, wherein said compound is a polypeptide comprising or consisting of the amino acid sequence SEQ ID NO: 1, where baseline means the individual's baseline. [000227] In some embodiments, the present invention provides a compound that binds to IL-13 and TSLP for use in the treatment of asthma in an individual, wherein the treatment reduces the level of fractionated exhaled nitric oxide (FeNO) by at least 40 ppb compared to baseline, wherein said reduction in FeNO level occurs within Petition 870250085505, dated 09 / 22 / 2025, pp. 73 / 173 65 / 126 4 weeks after administration of the compound, wherein said compound is a polypeptide comprising or consisting of the amino acid sequence SEQ ID NO: 1, wherein baseline means the individual's baseline. SEQ ID NO: 1 + asthma + FeNO level + human + baseline [000228] In some embodiments, the present invention provides a compound that binds to IL-13 and TSLP for use in the treatment of asthma in a human individual, wherein the treatment reduces the fractionated exhaled nitric oxide (FeNO) level by at least 18 ppb compared to baseline, wherein said compound is a polypeptide comprising or consisting of the amino acid sequence of SEQ ID NO: 1, wherein baseline means the individual's baseline. [000229] In some embodiments, the present invention provides a compound that binds to IL-13 and TSLP for use in the treatment of asthma in a human individual, wherein the treatment reduces the fractionated exhaled nitric oxide (FeNO) level by at least 20 ppb compared to baseline, wherein said compound is a polypeptide comprising or consisting of the amino acid sequence SEQ ID NO: 1, wherein baseline means the individual's baseline. [000230] In some embodiments, the present invention provides a compound that binds to IL-13 and TSLP for use in the treatment of asthma in a human individual, wherein the treatment reduces the fractionated exhaled nitric oxide (FeNO) level by at least 30 ppb compared to baseline, wherein said compound is a polypeptide comprising or consisting of the amino acid sequence SEQ ID NO: 1, wherein baseline means the individual's baseline. [000231] In some embodiments, the present invention provides a Petition 870250085505, dated 09 / 22 / 2025, pp. 74 / 173 66 / 126 compound that binds to IL-13 and TSLP for use in the treatment of asthma in a human individual, wherein the treatment reduces the fractionated exhaled nitric oxide (FeNO) level by at least 40 ppb compared to baseline, wherein said compound is a polypeptide comprising or consisting of the amino acid sequence SEQ ID NO: 1, wherein baseline means the individual's baseline. SEQ ID NO: 1 + asthma + FeNO level + human + points in time + baseline [000232] In some embodiments, the present invention provides a compound that binds to IL-13 and TSLP for use in the treatment of asthma in a human subject, wherein the treatment reduces the fractionated exhaled nitric oxide (FeNO) level by at least 18 ppb compared to baseline, wherein said reduction in FeNO level occurs within 4 weeks after administration of the compound, wherein said compound is a polypeptide comprising or consisting of the amino acid sequence SEQ ID 1, wherein baseline means the individual's baseline. [000233] In some embodiments, the present invention provides a compound that binds to IL-13 and TSLP for use in the treatment of asthma in a human subject, wherein the treatment reduces the fractionated exhaled nitric oxide (FeNO) level by at least 20 ppb compared to baseline, wherein said reduction in FeNO level occurs within 4 weeks after administration of the compound, wherein said compound is a polypeptide comprising or consisting of the amino acid sequence SEQ ID 1, wherein baseline means the individual's baseline. [000234] In some embodiments, the present invention provides a compound that binds to IL-13 and TSLP for use in the treatment of asthma in a human subject, wherein the treatment reduces the level of oxide Petition 870250085505, dated 09 / 22 / 2025, pp. 75 / 173 67 / 126 fractionated exhaled nitric oxide (FeNO) by at least 30 ppb compared to baseline, wherein said reduction in FeNO level occurs within 4 weeks after administration of the compound, wherein said compound is a polypeptide comprising or consisting of the amino acid sequence SEQ ID of 1, wherein baseline means the individual's baseline. [000235] In some embodiments, the present invention provides a compound that binds to IL-13 and TSLP for use in the treatment of asthma in a human subject, wherein the treatment reduces the fractionated exhaled nitric oxide (FeNO) level by at least 40 ppb compared to baseline, wherein said reduction in FeNO level occurs within 4 weeks after administration of the compound, wherein said compound is a polypeptide comprising or consisting of the amino acid sequence SEQ ID 1, wherein baseline means the individual's baseline. SEQ ID NO: 1 + asthma + eosinophil count + time points [000236] In some embodiments, the present invention provides a compound that binds to IL-13 and TSLP for use in the treatment of asthma in an individual, wherein the treatment reduces the blood eosinophil count by at least 30% compared to a control, wherein said reduction in eosinophil count occurs within 4 weeks after administration of the compound, wherein said compound is a polypeptide comprising or consisting of the amino acid sequence of SEQ ID NO: 1. [000237] In some embodiments, the present invention provides a compound that binds to IL-13 and TSLP for use in the treatment of asthma in an individual, wherein the treatment reduces the blood eosinophil count by at least 35% compared to a control, wherein said reduction in eosinophil count occurs within 4 weeks after administration of the compound, wherein said compound is Petition 870250085505, dated 09 / 22 / 2025, pp. 76 / 173 68 / 126 a polypeptide comprising or consisting of the amino acid sequence of SEQ ID NO: 1. [000238] In some embodiments, the present invention provides a compound that binds to IL-13 and TSLP for use in the treatment of asthma in an individual, wherein the treatment reduces the blood eosinophil count by at least 40% compared to a control, wherein said reduction in eosinophil count occurs within 4 weeks after administration of the compound, wherein said compound is a polypeptide comprising or consisting of the amino acid sequence SEQ ID NO: 1. SEQ ID NO: 1 + asthma + eosinophil count + time points + placebo [000239] In some embodiments, the present invention provides a compound that binds to IL-13 and TSLP for use in the treatment of asthma in an individual, wherein the treatment reduces the blood eosinophil count by at least 30% compared with placebo, wherein said reduction in eosinophil count occurs within 4 weeks after administration of the compound, wherein said compound is a polypeptide comprising or consisting of the amino acid sequence SEQ ID NO: 1. [000240] In some embodiments, the present invention provides a compound that binds to IL-13 and TSLP for use in the treatment of asthma in an individual, wherein the treatment reduces the blood eosinophil count by at least 35% compared with placebo, wherein said reduction in eosinophil count occurs within 4 weeks after administration of the compound, wherein said compound is a polypeptide comprising or consisting of the amino acid sequence SEQ ID NO: 1. [000241] In some embodiments, the present invention provides a compound that binds to IL-13 and TSLP for use in the treatment of asthma. Petition 870250085505, dated 09 / 22 / 2025, pp. 77 / 173 69 / 126 in an individual, wherein the treatment reduces the blood eosinophil count by at least 40% compared with placebo, wherein said reduction in eosinophil count occurs within 4 weeks after administration of the compound, wherein said compound is a polypeptide comprising or consisting of the amino acid sequence SEQ ID NO: 1. SEQ ID NO: 1 + asthma + eosinophil count + time points + baseline [000242] In some embodiments, the present invention provides a compound that binds to IL-13 and TSLP for use in the treatment of asthma in an individual, wherein the treatment reduces the blood eosinophil count by at least 30% compared to baseline, wherein said reduction in eosinophil count occurs within 4 weeks after administration of the compound, wherein said compound is a polypeptide comprising or consisting of the amino acid sequence SEQ ID: 1, wherein baseline means the individual's baseline. [000243] In some embodiments, the present invention provides a compound that binds to IL-13 and TSLP for use in the treatment of asthma in an individual, wherein the treatment reduces the blood eosinophil count by at least 35% compared to baseline, wherein said reduction in eosinophil count occurs within 4 weeks after administration of the compound, wherein said compound is a polypeptide comprising or consisting of the amino acid sequence SEQ ID: 1, wherein baseline means the individual's baseline. [000244] In some embodiments, the present invention provides a compound that binds to IL-13 and TSLP for use in the treatment of asthma in an individual, wherein the treatment reduces the blood eosinophil count by at least 40% compared to baseline, Petition 870250085505, dated 09 / 22 / 2025, pp. 78 / 173 70 / 126 wherein said reduction in eosinophil count occurs within 4 weeks after administration of the compound, wherein said compound is a polypeptide comprising or consisting of the amino acid sequence SEQ ID: 1, wherein baseline means the individual baseline of the individual. SEQ ID NO: 1 + asthma + airway inflammation + time points [000245] In some embodiments, the present invention provides a compound that binds to IL-13 and TSLP for use in the treatment of asthma in an individual, wherein the treatment reduces airway inflammation wherein said reduction in airway inflammation is distinguished by a reduction in FeNO by at least 18 ppb, a reduction in eosinophil count by at least 30% and / or an increase in forced expiratory volume in one second (FEV1) by at least 0.07 l compared with a control, wherein said reduction in airway inflammation occurs within 4 weeks after administration of the compound, wherein said compound is a polypeptide comprising or consisting of the amino acid sequence of SEQ ID NO: 1. [000246] In some embodiments, the present invention provides a compound that binds to IL-13 and TSLP for use in the treatment of asthma in an individual, wherein the treatment reduces airway inflammation, wherein said reduction in airway inflammation is distinguished by a reduction in FeNO by at least 20 ppb, a reduction in eosinophil count by at least 30%, and / or an increase in forced expiratory volume in one second (FEV1) by at least 0.07 l compared with a control, wherein said reduction in airway inflammation occurs within 4 weeks after administration of the compound, wherein said compound is a polypeptide comprising or consisting of the amino acid sequence SEQ ID NO: 1. Petition 870250085505, dated 09 / 22 / 2025, page 79 / 173 71 / 126 [000247] In some embodiments, the present invention provides a compound that binds to IL-13 and TSLP for use in the treatment of asthma in an individual, wherein the treatment reduces airway inflammation, wherein said reduction in airway inflammation is distinguished by a reduction in FeNO by at least 30 ppb, a reduction in eosinophil count by at least 30%, and / or an increase in forced expiratory volume in one second (FEV1) by at least 0.07 l compared with a control, wherein said reduction in airway inflammation occurs within 4 weeks after administration of the compound, wherein said compound is a polypeptide comprising or consisting of the amino acid sequence SEQ ID NO: 1. [000248] In some embodiments, the present invention provides a compound that binds to IL-13 and TSLP for use in the treatment of asthma in an individual, wherein the treatment reduces airway inflammation, wherein said reduction in airway inflammation is distinguished by a reduction in FeNO by at least 40 ppb, a reduction in eosinophil count by at least 30%, and / or an increase in forced expiratory volume in one second (FEV1) by at least 0.07 l compared with a control, wherein said reduction in airway inflammation occurs within 4 weeks after administration of the compound, wherein said compound is a polypeptide comprising or consisting of the amino acid sequence SEQ ID NO: 1. SEQ ID NO: 1 + asthma + airway inflammation + time points + placebo [000249] In some embodiments, the present invention provides a compound that binds to IL-13 and TSLP for use in the treatment of asthma in an individual, wherein the treatment reduces airway inflammation where said reduction in airway inflammation is Petition 870250085505, dated 09 / 22 / 2025, page 80 / 173 72 / 126 distinguished by a reduction in FeNO of at least 18 ppb, a reduction in eosinophil count of at least 30%, and / or an increase in forced expiratory volume in one second (FEV1) by at least 0.07 l compared with placebo, wherein said reduction in airway inflammation occurs within 4 weeks after administration of the compound, wherein said compound is a polypeptide comprising or consisting of the amino acid sequence SEQ ID NO: 1. [000250] In some embodiments, the present invention provides a compound that binds to IL-13 and TSLP for use in the treatment of asthma in an individual, wherein the treatment reduces airway inflammation, wherein said reduction in airway inflammation is distinguished by a reduction in FeNO by at least 20 ppb, a reduction in eosinophil count by at least 30%, and / or an increase in forced expiratory volume in one second (FEV1) by at least 0.07 l compared with placebo, wherein said reduction in airway inflammation occurs within 4 weeks after administration of the compound, wherein said compound is a polypeptide comprising or consisting of the amino acid sequence SEQ ID NO: 1. [000251] In some embodiments, the present invention provides a compound that binds to IL-13 and TSLP for use in the treatment of asthma in an individual, wherein the treatment reduces airway inflammation, wherein said reduction in airway inflammation is distinguished by a reduction in FeNO by at least 30 ppb, a reduction in eosinophil count by at least 30%, and / or an increase in forced expiratory volume in one second (FEV1) by at least 0.07 L compared with placebo, wherein said reduction in airway inflammation occurs within 4 weeks after administration of the compound, wherein said compound is a polypeptide. Petition 870250085505, dated 09 / 22 / 2025, page 81 / 173 73 / 126 comprising or consisting of the amino acid sequence of SEQ ID NO: 1. [000252] In some embodiments, the present invention provides a compound that binds to IL-13 and TSLP for use in the treatment of asthma in an individual, wherein the treatment reduces airway inflammation, wherein said reduction in airway inflammation is distinguished by a reduction in FeNO by at least 40 ppb, a reduction in eosinophil count by at least 30%, and / or an increase in forced expiratory volume in one second (FEV1) by at least 0.07 l compared with placebo, wherein said reduction in airway inflammation occurs within 4 weeks after administration of the compound, wherein said compound is a polypeptide comprising or consisting of the amino acid sequence SEQ ID NO: 1. 5.4.2 Treatment methods for a lung disease [000253] The present invention also provides methods for treating a lung disease in an individual comprising administering to the individual an effective amount of a compound that binds to IL-13 and TSLP, wherein said treatment reduces the level of fractionated exhaled nitric oxide (FeNO) compared to a control. [000254] In some embodiments, the invention provides methods for treating a lung disease in an individual, comprising administering to the individual an effective amount of a compound that binds to IL-13 and TSLP, wherein said treatment reduces the level of fractionated exhaled nitric oxide (FeNO) by at least 18 ppb compared with a control. [000255] All the above modalities and examples for compounds that bind to IL-13 and TSLP for use in the treatment of a lung disease in an individual, wherein said treatment reduces the Petition 870250085505, dated 09 / 22 / 2025, p. 82 / 173 74 / 126 The level of exhaled fractionated nitric oxide (FeNO) compared to a control can be transferred to methods for treating a lung disease in an individual, comprising administering to the individual an effective amount of a compound that binds to IL-13 and TSLP, wherein said treatment reduces the level of exhaled fractionated nitric oxide (FeNO) compared to a control. This applies, in particular, to the reduction of the FeNO level, the time points, the nature of the compound, the type of lung disease, and the control. For example, in some embodiments, the invention provides a method for treating a lung disease in an individual comprising administering to the individual an effective amount of a compound that binds to IL-13 and TSLP, wherein said treatment reduces the level of exhaled fractionated nitric oxide (FeNO) by at least 20 ppb, at least 30 ppb, or at least 40 ppb compared to a control. [000256] The present invention also provides methods for treating a lung disease in an individual comprising administering to the individual an effective amount of a compound that binds to IL-13 and TSLP, wherein said treatment reduces the blood eosinophil count compared to a control. [000257] In some embodiments, the invention provides methods for treating a lung disease in an individual comprising administering to the individual an effective amount of a compound that binds to IL-13 and TSLP, wherein said treatment reduces the blood eosinophil count by at least 30% compared to a control. [000258] All the above embodiments and examples for compounds that bind to IL-13 and TSLP for use in the treatment of a lung disease in an individual, wherein said treatment reduces the blood eosinophil count compared with a control, Petition 870250085505, dated 09 / 22 / 2025, page 83 / 173 75 / 126 can be transferred to methods for treating a lung disease in an individual, comprising administering to the individual an effective amount of a compound that binds to IL-13 and TSLP, wherein said treatment reduces the eosinophil count compared to a control. This applies, in particular, to the reduction in eosinophil count, the time points, the nature of the compound, the type of lung disease, and the control. For example, in some embodiments, the invention provides a method for treating a lung disease in an individual comprising administering to the individual an effective amount of a compound that binds to IL-13 and TSLP, wherein said treatment reduces the blood eosinophil count by at least 35% or by at least 40% compared to a control. [000259] The invention also provides methods for treating a lung disease in an individual comprising administering to the individual an effective amount of a compound that binds to IL-13 and TSLP, wherein said treatment reduces airway inflammation. All embodiments and examples given above for compounds that bind to IL-13 and TSLP for use in treating a lung disease in an individual, wherein said treatment reduces airway inflammation, can be transferred to methods for treating a lung disease in an individual comprising administering to the individual an effective amount of a compound that binds to IL-13 and TSLP, wherein said treatment reduces airway inflammation. This applies, in particular, to the definition of airway inflammation reduction, time points, the nature of the compound, the type of lung disease, and the control. 5.4.3 Use of a compound that binds to IL-13 and TSLP in the preparation of a pharmaceutical composition for the treatment of a pulmonary disease. Petition 870250085505, dated 09 / 22 / 2025, page 84 / 173 76 / 126 [000260] The present invention also provides the use of a compound that binds to IL-13 and TSLP in the preparation of a pharmaceutical composition for the treatment of a lung disease in an individual, wherein said treatment reduces the level of fractionated exhaled nitric oxide (FeNO) compared with a control. [000261] In some embodiments, the invention provides the use of a compound that binds to IL-13 and TSLP in the preparation of a pharmaceutical composition for the treatment of a lung disease in an individual, wherein said treatment reduces the level of fractionated exhaled nitric oxide (FeNO) by at least 18 ppb compared with a control. [000262] All embodiments and examples given above for compounds that bind to IL-13 and TSLP for use in the treatment of a lung disease in an individual, wherein said treatment reduces the level of exhaled fractionated nitric oxide (FeNO) compared with a control, can be transferred to the use of a compound that binds to IL-13 and TSLP in the preparation of a pharmaceutical composition for the treatment of a lung disease in an individual, wherein said treatment reduces the level of fractionated nitric oxide (FeNO) compared with a control. This applies, in particular, to the reduction of FeNO level, time points, nature of the compound, type of lung disease and control.For example, in some embodiments, the invention provides the use of a compound that binds to IL-13 and TSLP in the preparation of a pharmaceutical composition for the treatment of a lung disease in an individual, wherein said treatment reduces the level of fractionated exhaled nitric oxide (FeNO) by at least 20 ppb, at least 30 ppb, or at least 40 ppb compared with a control. [000263] The present invention also provides the use of a compound that binds to IL-13 and TSLP in the preparation of a composition Petition 870250085505, dated 09 / 22 / 2025, page 85 / 173 77 / 126 pharmaceutical for the treatment of a lung disease in an individual, wherein said treatment reduces the eosinophil count in the blood compared to a control. [000264] In some embodiments, the invention provides the use of a compound that binds to IL-13 and TSLP in the preparation of a pharmaceutical composition for the treatment of a lung disease in an individual, wherein said treatment reduces the blood eosinophil count by at least 30% compared to a control. [000265] All embodiments and examples given above for compounds that bind to IL-13 and TSLP for use in the treatment of a lung disease in an individual, wherein said treatment reduces the blood eosinophil count compared with a control, can be transferred to the use of a compound that binds to IL-13 and TSLP in the preparation of a pharmaceutical composition for the treatment of a lung disease in an individual, wherein said treatment reduces the eosinophil count compared with a control. This applies, in particular, to the reduction in eosinophil count, the time points, the nature of the compound, the type of lung disease, and the control.For example, in some embodiments, the invention provides the use of a compound that binds to IL-13 and TSLP in the preparation of a pharmaceutical composition for the treatment of a lung disease in an individual, wherein said treatment reduces the blood eosinophil count by at least 35% or by at least 40% compared to a control. [000266] The invention also provides the use of a compound that binds to IL-13 and TSLP in the preparation of a pharmaceutical composition for the treatment of a lung disease in an individual, wherein said treatment reduces airway inflammation. All embodiments and examples given above for compounds that bind to IL-13 and TSLP for use in the treatment of a lung disease in an individual Petition 870250085505, dated 09 / 22 / 2025, page 86 / 173 78 / 126 individual, in which said treatment reduces airway inflammation, can be transferred to the use of a compound that binds to IL-13 and TSLP in the preparation of a pharmaceutical composition for the treatment of a lung disease in an individual, in which said treatment reduces airway inflammation. This applies, in particular, to the definition of reduction of airway inflammation, to the time points, to the nature of the compound, to the type of lung disease and to the control. 5.4.4 Use of a compound that binds to IL-13 and TSLP for the treatment of a lung disease. [000267] The present invention also provides the use of a compound that binds to IL-13 and TSLP for the treatment of a lung disease in an individual, wherein said treatment reduces the level of fractionated exhaled nitric oxide (FeNO) compared to a control. [000268] In some embodiments, the invention provides the use of a compound that binds to IL-13 and TSLP for the treatment of a lung disease in an individual, wherein said treatment reduces the level of fractionated exhaled nitric oxide (FeNO) by at least 18 ppb compared with a control. [000269] All embodiments and examples given above for compounds that bind to IL-13 and TSLP for use in the treatment of a lung disease in an individual, wherein said treatment reduces the level of fractionated exhaled nitric oxide (FeNO) compared to a control, can be transferred to the use of a compound that binds to IL-13 and TSLP for the treatment of a lung disease in an individual, wherein said treatment reduces the level of fractionated nitric oxide (FeNO) compared to a control. This applies, in particular, to the reduction of FeNO level, the time points, the nature of the compound, the type of lung disease, and the control. For example, in some embodiments, the invention provides the use of a compound Petition 870250085505, dated 09 / 22 / 2025, p. 87 / 173 79 / 126 which binds to IL-13 and TSLP for the treatment of a lung disease in an individual, wherein said treatment reduces the level of fractionated exhaled nitric oxide (FeNO) by at least 20 ppb, at least 30 ppb or at least 40 ppb compared with a control. [000270] The present invention also provides the use of a compound that binds to IL-13 and TSLP for the treatment of a lung disease in an individual, wherein said treatment reduces the blood eosinophil count compared to a control. [000271] In some embodiments, the invention provides the use of a compound that binds to IL-13 and TSLP for the treatment of a lung disease in an individual, wherein said treatment reduces the blood eosinophil count by at least 30% compared to a control. [000272] All embodiments and examples given above for compounds that bind to IL-13 and TSLP for use in the treatment of a lung disease in an individual, wherein said treatment reduces the blood eosinophil count compared to a control, can be transferred to the use of a compound that binds to IL-13 and TSLP for the treatment of a lung disease in an individual, wherein said treatment reduces the blood eosinophil count compared to a control. This applies, in particular, to the reduction in eosinophil count, the time points, the nature of the compound, the type of lung disease, and the control. For example, in some embodiments, the invention provides the use of a compound that binds to IL-13 and TSLP for the treatment of a lung disease in an individual, wherein said treatment reduces the blood eosinophil count by at least 35% or by at least 40% compared to a control. [000273] The invention also provides the use of a compound that binds to IL-13 and TSLP for the treatment of a lung disease in a Petition 870250085505, dated 09 / 22 / 2025, p. 88 / 173 80 / 126 individual, in which said treatment reduces airway inflammation. All the modalities and examples given above for compounds that bind to IL-13 and TSLP for use in the treatment of a lung disease in an individual, in which said treatment reduces airway inflammation, can be transferred to the use of a compound that binds to IL-13 and TSLP for the treatment of a lung disease in an individual, in which said treatment reduces airway inflammation. This applies, in particular, to the definition of airway inflammation reduction, the time points, the nature of the compound, the type of lung disease, and the control. 5.4.5 Method for reducing FeNO levels [000274] The present invention also provides compounds for use in reducing the level of FeNO in an individual and methods for reducing the level of FeNO in an individual. [000275] In some embodiments, the invention provides a compound that binds to IL-13 and TSLP for use in reducing the level of fractionated exhaled nitric oxide (FeNO) in an individual, wherein said compound reduces the FeNO level by at least 18 ppb compared to a control. The embodiments and examples given above for compounds that bind to IL-13 and TSLP for use in treating a lung disease in an individual, wherein said treatment reduces the level of fractionated exhaled nitric oxide (FeNO) compared to a control, can be transferred to compounds that bind to IL-13 and TSLP for use in reducing the level of fractionated exhaled nitric oxide (FeNO) in an individual. This applies, in particular, to the reduction of the FeNO level, the time points, the nature of the compound, and the control.For example, in some embodiments, the invention provides a compound that binds to IL-13 and TSLP for use in reducing the level of fractionated exhaled nitric oxide (FeNO) in an individual, wherein said compound reduces the FeNO level by at least 20 ppb. Petition 870250085505, dated 09 / 22 / 2025, p. 89 / 173 81 / 126 less than 30 ppb or at least 40 ppb compared to a control. [000276] In some embodiments, the invention provides a method for reducing the level of fractionated exhaled nitric oxide (FeNO) in an individual, wherein said compound reduces the FeNO level by at least 18 ppb compared with a control. The embodiments and examples given above for compounds that bind to IL-13 and TSLP for use in the treatment of a lung disease in an individual, wherein said treatment reduces the level of fractionated exhaled nitric oxide (FeNO) compared with a control, can be transferred to methods for reducing the level of fractionated exhaled nitric oxide (FeNO) in an individual. This applies, in particular, to the reduction of the FeNO level, the time points, the nature of the compound, and the control.For example, in some embodiments, the invention provides a method for reducing the level of fractionated exhaled nitric oxide (FeNO) in an individual, wherein said compound reduces the FeNO level by at least 20 ppb, at least 30 ppb, or at least 40 ppb compared to a control. 5.5 Preventive reduction of FeNO levels [000277] In another aspect, the present invention relates to a preventive aspect. As the present invention provides ways to reduce FeNO levels to a greater extent than known treatments, this opens the possibility of preventive administration to individuals with elevated FeNO levels to prevent a loss of lung function before it even occurs. This preventive administration can be for patients with asthma and individuals at risk of developing asthma, as well as patients with other lung diseases and individuals at risk of developing other lung diseases. Accordingly, the present invention also provides compounds for use in reducing FeNO levels in an individual and Petition 870250085505, dated 09 / 22 / 2025, p. 90 / 173 82 / 126 methods to reduce FeNO levels in an individual, where reducing FeNO levels prevents a loss of lung function. FeNO level [000278] The preventive reduction of FeNO levels according to the present invention refers to individuals with an elevated FeNO level prior to the start of preventive administration (hereinafter referred to as the baseline FeNO level). An elevated baseline FeNO level is a FeNO level that is above 25 ppb (see, for example, Miskoff et al., Cureus. June 2019; 11 (6): e4864). [000279] In some embodiments, the present invention provides compounds for use in reducing FeNO levels in an individual with a baseline FeNO level of at least 90 ppb, wherein the reduction in FeNO levels prevents a loss of lung function. In some embodiments, the present invention provides compounds for use in reducing FeNO levels in an individual with a baseline FeNO level of at least 80 ppb, wherein the reduction in FeNO levels prevents a loss of lung function. In some embodiments, the present invention provides compounds for use in reducing FeNO levels in an individual with a baseline FeNO level of at least 75 ppb, wherein the reduction in FeNO levels prevents a loss of lung function. In some embodiments, the present invention provides compounds for use in reducing FeNO levels in an individual with a baseline FeNO level of at least 70 ppb, wherein the reduction in FeNO levels prevents a loss of lung function.In some embodiments, the present invention provides compounds for use in reducing FeNO levels in an individual with a baseline FeNO level of at least 65 ppb, wherein the reduction in FeNO levels prevents a loss of lung function. In some embodiments, the present invention provides compounds for use in reducing FeNO levels in an individual with a baseline FeNO level of at least 60. Petition 870250085505, dated 09 / 22 / 2025, p. 91 / 173 83 / 126 ppb, wherein the reduction of FeNO levels prevents a loss of lung function. In some embodiments, the present invention provides compounds for use in reducing FeNO levels in an individual with a baseline FeNO level of at least 55 ppb, wherein the reduction of FeNO levels prevents a loss of lung function. In some embodiments, the present invention provides compounds for use in reducing FeNO levels in an individual with a baseline FeNO level of at least 50 ppb, wherein the reduction of FeNO levels prevents a loss of lung function. In some embodiments, the present invention provides compounds for use in reducing FeNO levels in an individual with a baseline FeNO level of at least 45 ppb, wherein the reduction of FeNO levels prevents a loss of lung function.In some embodiments, the present invention provides compounds for use in reducing FeNO levels in an individual with a baseline FeNO level of at least 40 ppb, wherein the reduction in FeNO levels prevents a loss of lung function. In some embodiments, the present invention provides compounds for use in reducing FeNO levels in an individual with a baseline FeNO level of at least 35 ppb, wherein the reduction in FeNO levels prevents a loss of lung function. In some embodiments, the present invention provides compounds for use in reducing FeNO levels in an individual with a baseline FeNO level of at least 30 ppb, wherein the reduction in FeNO levels prevents a loss of lung function. In some embodiments, the present invention provides compounds for use in reducing FeNO levels in an individual with a baseline FeNO level of at least 25 ppb, wherein the reduction in FeNO levels prevents a loss of lung function. [000280] In some embodiments, the present invention provides compounds for use in reducing the FeNO level in an individual with a baseline FeNO level of at least 50 ppb, wherein the individual Petition 870250085505, dated 09 / 22 / 2025, p. 92 / 173 84 / 126 also has an eosinophil count greater than or equal to 0.3 *109 cells / l, where the reduction in FeNO levels prevents a loss of lung function. Reduction of FeNO [000281] In some embodiments, the so-called reduction in FeNO level is a reduction of at least 18 ppb. In some embodiments, the so-called reduction in FeNO level is a reduction of at least 20 ppb. In some embodiments, the so-called reduction in FeNO level is a reduction of at least 25 ppb. In some embodiments, the so-called reduction in FeNO level is a reduction of at least 30 ppb. In some embodiments, the so-called reduction in FeNO level is a reduction of at least 35 ppb. In some embodiments, the so-called reduction in FeNO level is a reduction of at least 40 ppb. In some embodiments, the so-called reduction in FeNO level is a reduction to a normal level, which means a reduction to a level below 25 ppb. FeNO level + reduction of FeNO [000282] In some embodiments, the present invention provides compounds for use in reducing the FeNO level in an individual with a baseline FeNO level of at least 50 ppb, wherein the reduction in FeNO level prevents a loss of lung function and wherein said reduction in FeNO level is a reduction of at least 25 ppb. In some embodiments, the present invention provides compounds for use in reducing the FeNO level in an individual with a baseline FeNO level of at least 50 ppb, wherein the reduction in FeNO level prevents a loss of lung function and wherein said reduction in FeNO level is a reduction of at least 20 ppb. In some embodiments, the present invention provides compounds for use in reducing the FeNO level in an individual with a baseline FeNO level of at least 50 ppb, wherein the reduction in FeNO level prevents a loss of lung function and wherein said reduction in FeNO level is a reduction of at least 20 ppb. Petition 870250085505, dated 09 / 22 / 2025, p. 93 / 173 85 / 126 of FeNO is a reduction of at least 18 ppb. In some embodiments, the present invention provides compounds for use in reducing the FeNO level in an individual with a baseline FeNO level of at least 50 ppb, wherein the reduction in FeNO level prevents a loss of lung function and wherein said reduction in FeNO level is a reduction to a level below 25 ppb. [000283] In some embodiments, the present invention provides compounds for use in reducing the FeNO level in an individual with a baseline FeNO level of at least 35 ppb, wherein the reduction in FeNO level prevents a loss of lung function and wherein said reduction in FeNO level is a reduction of at least 25 ppb. In some embodiments, the present invention provides compounds for use in reducing the FeNO level in an individual with a baseline FeNO level of at least 35 ppb, wherein the reduction in FeNO level prevents a loss of lung function and wherein said reduction in FeNO level is a reduction of at least 20 ppb. In some embodiments, the present invention provides compounds for use in reducing the FeNO level in an individual with a baseline FeNO level of at least 35 ppb, wherein the reduction in FeNO level prevents a loss of lung function and wherein said reduction in FeNO level is a reduction of at least 18 ppb.In some embodiments, the present invention provides compounds for use in reducing the FeNO level in an individual with a baseline FeNO level of at least 35 ppb, wherein the reduction in FeNO level prevents a loss of lung function and wherein said reduction in FeNO level is a reduction to a level below 25 ppb. [000284] In some embodiments, the present invention provides compounds for use in reducing the level of FeNO in an individual with a baseline FeNO level of at least 25 ppb, wherein the reduction in FeNO level prevents a loss of lung function and wherein said Petition 870250085505, dated 09 / 22 / 2025, p. 94 / 173 86 / 126 reduction in FeNO level is a reduction of at least 25 ppb. In some embodiments, the present invention provides compounds for use in reducing the FeNO level in an individual with a baseline FeNO level of at least 25 ppb, wherein the reduction in FeNO level prevents a loss of lung function and wherein said reduction in FeNO level is a reduction of at least 20 ppb. In some embodiments, the present invention provides compounds for use in reducing the FeNO level in an individual with a baseline FeNO level of at least 25 ppb, wherein the reduction in FeNO level prevents a loss of lung function and wherein said reduction in FeNO level is a reduction of at least 18 ppb.In some embodiments, the present invention provides compounds for use in reducing the level of FeNO in an individual with a baseline FeNO level of at least 25 ppb, wherein the reduction in FeNO level prevents a loss of lung function and wherein said reduction in FeNO level is a reduction to a level below 25 ppb. Compounds for use in the preventive reduction of FeNO levels [000285] In some embodiments, said compound is a compound that binds to IL-13. Exemplary compounds that bind to IL-13 are the antibodies anrukinzumab, lebrikinzumab and tralokinumab. [000286] In some embodiments, said compound is a compound that binds to TSLP. An exemplary compound that binds to TSLP is the antibody tezepelumab. [000287] In some embodiments, said compound is a compound that binds to IL-13 and TSLP. Exemplary compounds that bind to IL-13 and TSLP are given above (section 5.3). In some embodiments, said compound is a polypeptide comprising or consisting of the amino acid sequence of SEQ ID NO: 1. FeNO level + FeNO reduction + Compound [000288] In some embodiments, the present invention provides Petition 870250085505, dated 09 / 22 / 2025, p. 95 / 173 87 / 126 compounds for use in reducing FeNO levels in an individual with a baseline FeNO level of at least 50 ppb, wherein the reduction in FeNO levels prevents a loss of lung function, wherein said reduction in FeNO levels is a reduction of at least 25 ppb, and wherein said compound is a compound that binds to IL-13 and TSLP. In some embodiments, the present invention provides compounds for use in reducing FeNO levels in an individual with a baseline FeNO level of at least 50 ppb, wherein said reduction in FeNO levels prevents a loss of lung function, wherein said reduction in FeNO levels is a reduction of at least 25 ppb, and wherein said compound is a polypeptide comprising or consisting of the amino acid sequence SEQ ID NO: 1.In some embodiments, the present invention provides compounds for use in reducing the level of FeNO in an individual with a baseline FeNO level of at least 50 ppb, wherein the reduction in FeNO level prevents a loss of lung function, wherein said reduction in FeNO level is a reduction of at least 25 ppb, and wherein said compound is tezepelumab. [000289] In some embodiments, the present invention provides compounds for use in reducing FeNO levels in an individual with a baseline FeNO level of at least 50 ppb, wherein the reduction in FeNO levels prevents a loss of lung function, wherein said reduction in FeNO levels is a reduction to a level below 25 ppb, and wherein said compound is a compound that binds to IL-13 and TSLP. In some embodiments, the present invention provides compounds for use in reducing FeNO levels in an individual with a baseline FeNO level of at least 50 ppb, wherein said reduction in FeNO levels prevents a loss of lung function, wherein said reduction in FeNO levels is a reduction to a level below 25 ppb, and wherein said compound is a polypeptide comprising or consisting of the amino acid sequence SEQ ID NO: 1. In some Petition 870250085505, dated 09 / 22 / 2025, p. 96 / 173 88 / 126 embodiments, the present invention provides compounds for use in reducing the level of FeNO in an individual with a baseline FeNO level of at least 50 ppb, wherein the reduction in FeNO level prevents a loss of lung function, wherein said reduction in FeNO level is a reduction to a level below 25 ppb, and wherein said compound is Tezepelumab. [000290] In some embodiments, the present invention provides compounds for use in reducing FeNO levels in an individual with a baseline FeNO level of at least 35 ppb, wherein the reduction in FeNO levels prevents a loss of lung function, wherein said reduction in FeNO levels is a reduction of at least 18 ppb, and wherein said compound is a compound that binds to IL-13 and TSLP. In some embodiments, the present invention provides compounds for use in reducing FeNO levels in an individual with a baseline FeNO level of at least 35 ppb, wherein said reduction in FeNO levels prevents a loss of lung function, wherein said reduction in FeNO levels is a reduction of at least 18 ppb, and wherein said compound is a polypeptide comprising or consisting of the amino acid sequence SEQ ID NO: 1.In some embodiments, the present invention provides compounds for use in reducing the level of FeNO in an individual with a baseline FeNO level of at least 35 ppb, wherein the reduction in FeNO level prevents a loss of lung function, wherein said reduction in FeNO level is a reduction of at least 18 ppb, and wherein said compound is tezepelumab. [000291] In some embodiments, the present invention provides compounds for use in reducing the FeNO level in an individual with a baseline FeNO level of at least 35 ppb, wherein the reduction in FeNO level prevents a loss of lung function, wherein said reduction in FeNO level is a reduction to a level below 25 ppb, and wherein said compound is a compound that binds to IL-13 and Petition 870250085505, dated 09 / 22 / 2025, p. 97 / 173 89 / 126 TSLP. In some embodiments, the present invention provides compounds for use in reducing FeNO levels in an individual with a baseline FeNO level of at least 35 ppb, wherein the reduction in FeNO level prevents a loss of lung function, wherein said reduction in FeNO level is a reduction to a level below 25 ppb, and wherein said compound is a polypeptide comprising or consisting of the amino acid sequence SEQ ID NO: 1. In some embodiments, the present invention provides compounds for use in reducing FeNO levels in an individual with a baseline FeNO level of at least 35 ppb, wherein said reduction in FeNO level prevents a loss of lung function, wherein said reduction in FeNO level is a reduction to a level below 25 ppb, and wherein said compound is Tezepelumab. [000292] In some embodiments, the present invention provides compounds for use in reducing FeNO levels in an individual with a baseline FeNO level of at least 25 ppb, wherein the reduction in FeNO levels prevents a loss of lung function, wherein said reduction in FeNO levels is a reduction of at least 18 ppb, and wherein said compound is a compound that binds to IL-13 and TSLP. In some embodiments, the present invention provides compounds for use in reducing FeNO levels in an individual with a baseline FeNO level of at least 25 ppb, wherein said reduction in FeNO levels prevents a loss of lung function, wherein said reduction in FeNO levels is a reduction of at least 18 ppb, and wherein said compound is a polypeptide comprising or consisting of the amino acid sequence SEQ ID NO: 1.In some embodiments, the present invention provides compounds for use in reducing the level of FeNO in an individual with a baseline FeNO level of at least 25 ppb, wherein the reduction in FeNO level prevents a loss of lung function, wherein said reduction in FeNO level is a reduction in... Petition 870250085505, dated 09 / 22 / 2025, p. 98 / 173 90 / 126 at least 18 ppb, and wherein the said compound is Tezepelumab. Cause of loss of lung function [000293] Elevated FeNO levels are linked to multiple lung diseases, including asthma or idiopathic pulmonary fibrosis (Cameli et al., Int J Mol Sci. September 2020; 21(17): 6187). Individuals with elevated baseline FeNO levels may already exhibit asthma symptoms from another lung disease or are at risk of developing asthma symptoms or another lung disease. Among these symptoms is loss of lung function. This loss of lung function can be prevented by preventively reducing FeNO levels according to the present invention. [000294] In some embodiments, the reduction of FeNO levels according to the present invention prevents a loss of lung function linked to asthma. In some embodiments, the reduction of FeNO levels according to the present invention prevents a loss of lung function linked to a lung disease other than asthma. FeNO level + FeNO reduction + Compound + Cause of lung function loss [000295] In some embodiments, the present invention provides compounds for use in reducing the FeNO level in an individual with a baseline FeNO level of at least 50 ppb, wherein the reduction in FeNO level prevents a loss of lung function, wherein said reduction in FeNO level is a reduction to a level below 25 ppb, wherein said compound is a compound that binds to IL-13 and TSLP, and wherein said loss of lung function is linked to asthma. In some embodiments, the present invention provides compounds for use in reducing the FeNO level in an individual with a baseline FeNO level of at least 50 ppb, wherein said reduction in FeNO level prevents a loss of lung function, wherein said reduction in FeNO level is a reduction to a level below 25 ppb, wherein said Petition 870250085505, dated 09 / 22 / 2025, p. 99 / 173 91 / 126 compound is a polypeptide comprising or consisting of the amino acid sequence SEQ ID NO: 1, and in which the so-called loss of lung function is linked to asthma. In some embodiments, the present invention provides compounds for use in reducing the FeNO level in an individual with a baseline FeNO level of at least 50 ppb, wherein the reduction of the FeNO level prevents a loss of lung function, wherein said reduction of the FeNO level is a reduction to a level below 25 ppb, wherein said compound Tezepelumab, and wherein said loss of lung function is linked to asthma. [000296] In some embodiments, the present invention provides compounds for use in reducing the FeNO level in an individual with a baseline FeNO level of at least 50 ppb, wherein the reduction in FeNO level prevents a loss of lung function, wherein said reduction in FeNO level is a reduction to a level below 25 ppb, wherein said compound is a compound that binds to IL-13 and TSLP, and wherein said loss of lung function is linked to a lung disease other than asthma.In some embodiments, the present invention provides compounds for use in reducing the FeNO level in an individual with a baseline FeNO level of at least 50 ppb, wherein the reduction in FeNO level prevents a loss of lung function, wherein said reduction in FeNO level is a reduction to a level below 25 ppb, wherein said compound is a polypeptide comprising or consisting of the amino acid sequence SEQ ID NO: 1, and wherein said loss of lung function is linked to a lung disease other than asthma. In some embodiments, the present invention provides compounds for use in reducing the FeNO level in an individual with a baseline FeNO level of at least 50 ppb, wherein said reduction in FeNO level prevents a loss of lung function, wherein said reduction in FeNO level is a reduction to a level below 25 ppb, wherein said compound Tezepelumab, e. Petition 870250085505, dated 09 / 22 / 2025, pp. 100 / 173 92 / 126 where the said loss of lung function is linked to a lung disease other than asthma. [000297] The present invention also provides methods for reducing the level of FeNO in an individual, wherein the reduction of the FeNO level prevents a loss of lung function. All embodiments and examples given above for compounds for use in reducing the level of FeNO in an individual, wherein the reduction of the FeNO level prevents a loss of lung function, can be transferred to methods for reducing the level of FeNO in an individual, wherein the reduction of the FeNO level prevents a loss of lung function. [000298] The present invention also provides the use of a compound to prevent a loss of lung function in an individual, wherein said compound reduces the individual's FeNO level. All embodiments and examples given above for compounds for use in reducing the FeNO level in an individual, wherein the reduction of the FeNO level prevents a loss of lung function, can be transferred to uses of a compound to prevent a loss of lung function in an individual, wherein said compound reduces the individual's FeNO level. 5.6 Other aspects of the present invention 5.6.1 Treatment of small airway obstruction [000299] The present invention also provides compounds for use in the treatment of a lung disease in an individual, wherein said treatment reduces small airway obstruction. Thus, the present invention provides the possibility of specifically treating patients suffering from small airway obstruction, for example, the subgroup of asthma patients suffering from small airway obstruction. [000300] Accordingly, the present invention provides a compound that binds to IL-13 and TSLP for use in the treatment of a Petition 870250085505, dated 09 / 22 / 2025, pp. 101 / 173 93 / 126 lung disease in an individual, wherein said treatment reduces the level of fractionated exhaled nitric oxide (FeNO) by at least 18 ppb compared with a control, wherein said treatment reduces small airway obstruction. In some embodiments, the lung disease is asthma. In some embodiments, the control is placebo. In some embodiments, the compound is a polypeptide comprising or consisting of the amino acid sequence SEQ ID NO: 1. In some embodiments, the lung disease is asthma and the control is placebo. In some embodiments, the lung disease is asthma and the compound is a polypeptide comprising or consisting of the amino acid sequence SEQ ID NO: 1. In some embodiments, the control is placebo and the compound is a polypeptide comprising or consisting of the amino acid sequence SEQ ID NO: 1.In some modalities, the lung disease is asthma, the control is a placebo, and the compound is a polypeptide comprising or consisting of the amino acid sequence SEQ ID NO: 1. 5.6.2 Reduction in eosinophil count [000301] The present invention also provides compounds for use in reducing the blood eosinophil count in an individual and methods for reducing the blood eosinophil count in an individual. [000302] In some embodiments, the invention provides a compound that binds to IL-13 and TSLP for use in reducing the level of fractionated exhaled nitric oxide (FeNO) in an individual, wherein said treatment reduces the blood eosinophil count by at least 30% compared to a control. The embodiments and examples given above for compounds that bind to IL-13 and TSLP for use in treating a lung disease in an individual, wherein said treatment reduces the blood eosinophil count by at least 30% compared to a control, can be transferred to compounds Petition 870250085505, dated 09 / 22 / 2025, pp. 102 / 173 94 / 126 that bind to IL-13 and TSLP for use in reducing eosinophil count in an individual. This applies, in particular, to the reduction of eosinophil count, time points, nature of the compound, and control. For example, in some embodiments, the invention provides a compound that binds to IL-13 and TSLP for use in reducing the level of fractionated exhaled nitric oxide (FeNO) in an individual, wherein said treatment reduces the blood eosinophil count by at least 35% or by at least 40% compared to a control. [000303] In some embodiments, the invention provides a method for use in reducing the eosinophil count in an individual, wherein said treatment reduces the blood eosinophil count by at least 30% compared to a control. The embodiments and examples given above for compounds that bind to IL-13 and TSLP for use in treating a lung disease in an individual, wherein said treatment reduces the blood eosinophil count compared to a control, can be transferred to methods for reducing the eosinophil count in an individual. This applies, in particular, to the reduction of the eosinophil count, the time points, the nature of the compound, and the control. For example, in some embodiments, the invention provides a method for reducing the eosinophil count in an individual, wherein said treatment reduces the blood eosinophil count by at least 35% or by at least 40% compared to a control. 5.6.3 Reduction in the proportion of non-classical monocytes [000304] The present invention also provides compounds for use in reducing the proportion of non-classical monocytes in an individual's respiratory tract and methods for reducing the proportion of non-classical monocytes in an individual's respiratory tract. [000305] Monocytes are a heterogeneous cell population with Petition 870250085505, dated 09 / 22 / 2025, pp. 103 / 173 95 / 126 potential to become activated, infiltrate blood tissue, and differentiate into macrophages. When activated, monocytes and macrophages release several inflammatory cytokines implicated in the pathogenesis of asthma, and monocyte activation and respiratory tissue infiltration have been described in asthma in numerous studies, suggesting an important role for this cell type in the pathobiology of the disease (Li et al., Tomita et al.). Monocytes have been observed to rapidly accumulate in the nasal mucosa after local allergenic challenge, where they promote the recruitment of Th2 cells and eosinophils. A recent analysis of bronchoalveolar lavage fluid by single-cell RNAseq further identified multiple monocyte clusters and a monocyte-derived macrophage subpopulation as being increased in patients with asthma exacerbations. Another recent study found monocytes accumulating in the lungs of children and adolescents with fatal asthma attacks (Eguíluz-Gracia et al.)., Clin Exp Allergy. December 2018;48(12):1631-1639), results that also strongly support the direct involvement of monocytes in the immunopathology of asthma as pro-inflammatory cells and suggest that preventing their entry into respiratory tissue by SAR may have beneficial effects in preventing asthma symptoms and exacerbations. [000306] Therefore, reducing the proportion of a monocyte subpopulation, for example, non-classical monocytes, may be useful for the treatment of asthma. The present invention can achieve such a reduction, as shown below in the Example section. [000307] In some embodiments, the invention provides a compound that binds to IL-13 and TSLP for use in reducing the level of fractionated exhaled nitric oxide (FeNO) in an individual, wherein said treatment reduces the proportion of non-classical monocytes in the individual's blood. The embodiments and examples given above for compounds that bind to IL-13 and TSLP for use in the treatment of a pulmonary disease in Petition 870250085505, dated 09 / 22 / 2025, pp. 104 / 173 96 / 126 an individual can be transferred to compounds that bind to IL13 and TSLP for use in reducing the proportion of non-classical monocytes in the individual's blood. This applies, in particular, to the time points and the nature of the compound. For example, in some embodiments, the IL-13 and TSLP-binding compound is a polypeptide comprising or consisting of the amino acid sequence SEQ ID NO: 1. [000308] In some embodiments, the invention provides a method for reducing the proportion of non-classical monocytes in an individual's blood. The embodiments and examples given above for compounds that bind to IL-13 and TSLP for use in treating a lung disease in an individual can be transferred to methods for reducing the proportion of non-classical monocytes in an individual's blood. This applies, in particular, to the time points and the nature of the compound. For example, in some embodiments, the compound that binds to IL-13 and TSLP is a polypeptide comprising or consisting of the amino acid sequence SEQ ID NO: 1. 5.6.4 Reduction in the proportion of NK cells [000309] The present invention also provides compounds for use in reducing the proportion of NK cells in an individual's blood and methods for reducing the proportion of NK cells in an individual's blood. [000310] In some embodiments, the invention provides a compound that binds to IL-13 and TSLP for use in reducing the level of fractionated exhaled nitric oxide (FeNO) in an individual, wherein said treatment reduces the proportion of NK cells in the individual's blood. The embodiments and examples given above for compounds that bind to IL-13 and TSLP for use in the treatment of a lung disease in an individual can be transferred to compounds that bind to IL-13. Petition 870250085505, dated 09 / 22 / 2025, pp. 105 / 173 97 / 126 and TSLP for use in reducing the proportion of NK cells in an individual's blood. This applies, in particular, to the time points and the nature of the compound. For example, in some embodiments, the compound that binds to IL-13 and TSLP is a polypeptide comprising or consisting of the amino acid sequence SEQ ID NO: 1. [000311] In some embodiments, the invention provides a method for reducing the proportion of NK cells in an individual's blood. The embodiments and examples given above for compounds that bind to IL-13 and TSLP for use in treating a lung disease in an individual can be transferred to methods for reducing the proportion of NK cells in an individual's blood. This applies, in particular, to the time points and the nature of the compound. For example, in some embodiments, the compound that binds to IL-13 and TSLP is a polypeptide comprising or consisting of the amino acid sequence SEQ ID NO: 1. 5.6.5 Reduction of CCL26 expression in endothelial cells [000312] The present invention also provides compounds for use in reducing the expression of CCL26 in endothelial cells, such as basal epithelial cells, multiciliated epithelial cells and secretory epithelial cells, of an individual and methods for reducing the expression of CCL26 in endothelial cells, such as basal epithelial cells, multiciliated epithelial cells and secretory epithelial cells, of an individual. [000313] In some embodiments, the invention provides a compound that binds to IL-13 and TSLP for use in reducing the level of fractionated exhaled nitric oxide (FeNO) in an individual, wherein said treatment reduces the expression of CCL26 in the individual's endothelial cells. The embodiments and examples given above for compounds that bind to IL-13 and TSLP for use in the treatment of a lung disease in an individual are described above. Petition 870250085505, dated 09 / 22 / 2025, pp. 106 / 173 98 / 126 individuals can be transferred to compounds that bind to IL-13 and TSLP for use in reducing CCL26 expression in an individual's endothelial cells. This applies, in particular, to the time points and the nature of the compound. For example, in some embodiments, the IL-13 and TSLP-binding compound is a polypeptide comprising or consisting of the amino acid sequence SEQ ID NO: 1. [000314] In some embodiments, the invention provides a method for reducing the expression of CCL26 in endothelial cells of an individual. The embodiments and examples given above for compounds that bind to IL-13 and TSLP for use in the treatment of a lung disease in an individual can be transferred to methods for reducing the expression of CCL26 in endothelial cells of an individual. This applies, in particular, to the time points and the nature of the compound. For example, in some embodiments, the compound that binds to IL-13 and TSLP is a polypeptide comprising or consisting of the amino acid sequence SEQ ID NO: 1. 5.6.6 Reduction of HBB expression in T cells [000315] The present invention also provides compounds for use in reducing HBB expression in T cells, such as CD8 effector memory T cells (em), of an individual and methods for reducing HBB expression in T cells, such as CD8 effector memory T cells (em), of an individual. [000316] In some embodiments, the invention provides a compound that binds to IL-13 and TSLP for use in reducing the level of fractionated exhaled nitric oxide (FeNO) in an individual, wherein said treatment reduces HBB expression in the individual's T cells. The embodiments and examples given above for compounds that bind to IL-13 and TSLP for use in treating a lung disease in an individual can be transferred to compounds that bind to IL-13 and TSLP. Petition 870250085505, dated 09 / 22 / 2025, pp. 107 / 173 99 / 126 for use in reducing HBB expression in an individual's T cells. This applies, in particular, to the time points and the nature of the compound. For example, in some embodiments, the compound that binds to IL-13 and TSLP is a polypeptide comprising or consisting of the amino acid sequence SEQ ID NO: 1. [000317] In some embodiments, the invention provides a method for reducing HBB expression in an individual's T cells. The embodiments and examples given above for compounds that bind to IL-13 and TSLP for use in treating a lung disease in an individual can be transferred to methods for reducing HBB expression in an individual's T cells. This applies, in particular, to the time points and the nature of the compound. For example, in some embodiments, the compound that binds to IL-13 and TSLP is a polypeptide comprising or consisting of the amino acid sequence SEQ ID NO: 1. 5.7 Industrial Applicability [000318] The compound for use according to the present invention can be used in the treatment of individuals suffering from lung diseases, such as asthma. Examples 6.1 Example 1: PDY16622 - A double-blind, randomized, placebo-controlled, parallel-design, single-dose study in three centers. [000319] The efficacy of SAR443765 for the treatment of asthma was tested in a phase I trial (PDY16622) detailed below. A timeline of the trial is shown in Figure 1. 6.1.1 Methods Patient cohort [000320] A total of up to 36 participants with mild to moderate asthma Petition 870250085505, dated 09 / 22 / 2025, pp. 108 / 173 100 / 126 were enrolled in this study. Participants were randomized into SAR443765 and placebo groups (24 SAR443765 and 12 placebo). Participants received a single dose at the highest safe and well-tolerated dose level, as previously assessed in a portion of the study with healthy adult participants (400 mg SC max). [000321] Participants had to meet the following criteria: • Diagnosis of asthma for at least 12 months and confirmed in screening based on the 2020 Global Initiative for Asthma (GINA) Guidelines, all stages except Stage 4 with high-dose inhaled corticosteroid (HSC) and Stage 5. • Controlled asthma defined as a score of Asthma Control Questionnaire (ACQ)-5 <1.5. • Participants using short-acting beta-agonist as needed (SABA), stable treatment without ICS, or existing stable treatment (for at least 3 months prior to screening) with low- to medium-dose daily ICS (<500 mcg fluticasone propionate or comparable total daily ICS dosage) potentially in combination with a long-acting beta-agonist (LABA) and / or long-acting muscarinic agonist (LAMA) as a second controller, and / or with a stable daily leukotriene receptor antagonist, leukotriene synthesis inhibitor, and / or cromones. • Participants with elevated FeNO levels defined as >25 ppb at screening and baseline. • Participants with pre-bronchodilator FEV1 >60% of predicted normal at screening. • Reversibility of at least 12% and 200 ml in FEV1 or forced vital capacity (FVC) after administration of 4 sprays (400 mcg) of albuterol / salbutamol or levalbuterol / levosalbutamol during screening or documented history of a reversibility test that Petition 870250085505, dated 09 / 22 / 2025, pp. 109 / 173 101 / 126 meets these criteria within 5 years prior to screening or has a documented positive response to methacholine challenge (a 20% decrease in FEV1 [PC20] of <8 mg / ml) within 5 years prior to the screening visit. • Normal or clinically acceptable vital signs (pulse rate, blood pressure, and bronchopulmonary dysplasia) after 10 minutes of rest in the supine position during screening and at baseline. • Normal or clinically acceptable standard-lead electrocardiogram (ECG) parameters and tracking after 10 minutes at rest in the supine position at screening and baseline; normal ECG tracking unless the Investigator considers an ECG tracking abnormality not clinically relevant. • Laboratory parameters within the normal range (or screening limit defined for the Investigator's site) at screening and baseline unless the Investigator considers an abnormality clinically irrelevant; however, serum creatinine, alkaline phosphatase, liver enzymes (aspartate aminotransferase, alanine aminotransferase) should not exceed 1.25 times the upper laboratory normal. Total bilirubin outside the normal range may be acceptable if total bilirubin does not exceed 1.5 times the upper limit with normal values ​​for conjugated bilirubin (unless the participant has documented Gilbert's syndrome). • Body weight between 50.0 kg and 105.0 kg, inclusive, if male, and between 40.0 kg and 95.0 kg, inclusive, if female, body mass index between 18.0 kg / m2 and 32.0 kg / m2, inclusive, at screening and at baseline. Dosage [000322] Participants were dosed in subgroups of no more than 4 participants, with at least a 10-minute interval, with a dosing interval of at least 2 days between subgroups. The Petition 870250085505, dated 09 / 22 / 2025, pp. 110 / 173 The 102 / 126 asthma cohort initiation was based on blinded safety and PK data from a previous part of the study with healthy adult participants. [000323] All participants were screened within 28 days to ensure they met the study requirements. Eligible participants were admitted the day before each dosing, and participants included in the study remained institutionalized for 1 day after administration of the study drug in the asthma cohort, taking into account emerging safety, PK, and PD data. Before each drug administration, participants were assessed for SARS-CoV-2 infection and underwent intensive monitoring, including physical examination, AE assessment, vital signs, ECGs, and routine laboratory evaluation (complete blood count with differential, chemistry, aPTT, PT-INR, high-sensitivity cardiac troponin T, and urinalysis). After the institutionalization period(s), participants underwent clinical evaluation including vital signs, ECG, routine laboratory evaluation, and ADA assessment at varying intervals until study completion.Taking into account the half-life range of serum nanobodies binding to albumin, the observation period for treatment-emergent adverse events for this study was therefore terminated 70 days after the last dose. Analysis of Fractionated Exhaled Nitric Oxide (FeNO) Levels [000324] The fraction of exhaled nitric oxide (FeNO) was measured at the time points specified in the study schedule (Figure 1), i.e., baseline, D8, D15, D29, and D57. FeNO is a measure of NO production by epithelial cells in the lung and is considered a biomarker for airway inflammation in asthma. [000325] The FeNO level (ppb) was collected on-site with a dedicated medical device, such as a handheld device. Petition 870250085505, dated 09 / 22 / 2025, pp. 111 / 173 103 / 126 commercially available (NIOX VERO®). The FeNO test needs to be completed before impulse oscillometry and spirometry in order to avoid any impact on the nitric oxide measurement. Considering the diurnal variation in FeNO, the assessment needs to be performed at approximately the same time of day throughout the study (±2 hours). Participants should not eat or drink 1 hour before the FeNO measurement, as this may affect the results. All carbonated beverages and foods high in nitrate (e.g., vegetable juices, salads, lettuce, radishes, celery, broccoli, cauliflower, spinach, arugula, beets, parsley, leeks, cabbage, fennel, turnips, carrots, cured meats, sausage, bacon) should be withheld for at least 2 hours before the FeNO measurement. ICS, if present, should be withheld for at least 4 hours before the FeNO measurement. The participant should be seated during the FeNO test; However, if the participant is unable to sit down, then standing is acceptable.The position (sitting or standing) must remain the same for a participant throughout the study. Participants must inhale to full lung capacity through the handheld device (NIOX VERO®) and then exhale for 10 seconds at 50 ml / s (assisted by visual and auditory cues). Eosinophil count [000326] Eosinophil counts in whole blood were determined at the time points specified in the study schedule (Figure 1), i.e., at baseline and at D2 (24 h), D4 (72 h), D8 (1 week), D15 (2 weeks), D29 (4 weeks), D57 (8 weeks), and D71 (10 weeks) using flow cytometry. Spirometry measurements (FEV1 and FEF25-75) [000327] FEV1 and FEF25-75 were determined by spirometry at the time points specified in the study schedule (Figure 1). [000328] Spirometry was performed in accordance with the guidelines of Petition 870250085505, dated 09 / 22 / 2025, pp. 112 / 173 104 / 126 American Thoracic Society (ATS) / European Respiratory Society (ERS) (2019 update). For the measured parameters, including FEV1, peak exploratory flow (PEF), FVC, and forced exploratory flow (FEF) 25%-75%, spirometry was performed after a bronchodilator washout period according to their duration of action as detailed in the ATS guidelines. For example, the bronchodilator retention time is at least 6 hours for SABA, at least 24 hours for LABA, and 36-48 hours for LAMA. Cromonas need to be retained for at least 24 hours before spirometry. Inhaled corticosteroids (ICS), leukotriene receptor antagonists, and leukotriene synthesis inhibitors do not need to be retained before spirometry; however, ICS need to be retained before FeNO assessment. [000329] At all visits, spirometry was preferably performed in the morning; the afternoon was permitted in the exceptional circumstance where morning spirometry could not be performed. Spirometry was performed at approximately the same time at each visit throughout the study (±2 hours). The same spirometer and standard spirometric techniques, including calibration, were used to perform spirometry at all visits, and whenever possible, the same person performed the measurements. Three measurements that meet the acceptability and repeatability criteria of the ATS should be obtained at each visit. [000330] Reversibility was determined by a post-bronchodilator spirometry measurement. Reversibility is defined as an increase in absolute FEV1 and / or FVC after bronchodilator administration and is measured by spirometry as a post-bronchodilator increase in FEV1 or FVC as a percentage of pre-bronchodilator FEV1 or FVC, respectively. After spirometry to measure pre-bronchodilator FEV1, participants received 4 sprays of albuterol / salbutamol or levalbuterol / levosalbutamol from a Petition 870250085505, dated 09 / 22 / 2025, pp. 113 / 173 105 / 126 metered-dose inhaler (MDI). Post-bronchodilator spirometry should be performed after a waiting period of at least 10 minutes and may be repeated several times within approximately 30 minutes after bronchodilator administration. Impulse oscillometry measurements (R5-20 and AX) [000331] R5-20 and AX were determined by oscillometry at the time points specified in the study schedule (Figure 1). [000332] Oscillometry is a technique complementary to spirometry that determines the mechanical properties of the lung. Although spirometry is the most commonly used technique to examine airway function, it is unable to sensitively assess small airways, becoming abnormal only when approximately 75% of the small airways are obstructed. Oscillometry is more sensitive in detecting small airway disease, which correlates with poor disease control and type 2 inflammation. Thus, oscillometry allows for the assessment of the relative contribution of large and small airways in asthma. Oscillometry was conducted during tidal breathing using the Tremoflo® device (Thorasys, Montreal, Canada) according to the guidelines recommended by the ERS (Oostveen et al., Eur Respir J. 2003;22(6):1026-41). Oscillometry was performed immediately before spirometry according to the study protocol. [000333] A multifrequency signal of 5 to 37 Hz superimposed pressure and oscillatory flow on the participant's spontaneous breathing. 20 s measurements were repeated with breaks of approximately 20 s. Artifacts due to coughing or glottal closure were removed by automatic rejection by the software. A minimum of 3 records that achieved a coefficient of variation of <15% was required for quality control (Peters et al., Appl Physiol Nutr Metab. 2016;41(5):538-47). Only these data were used for data analysis. Petition 870250085505, dated 09 / 22 / 2025, pp. 114 / 173 106 / 126 [000334] Low frequencies (e.g., 5 Hz) reach the small airways and reflect the total airway, while high frequencies (e.g., 20 Hz) do not reach the small airways and therefore reflect only the central airways. Respiratory resistance (Rrs) reflects the energy required to propagate the pressure wave through the airways and distend the lung parenchyma. Total airway resistance is predominantly determined by the central airways (80%) and, to a lesser extent, by the smaller airways (20%). As such, in health there is a low-frequency dependence of Rrs (Pride, Thorax. 1992;47(4):317-20) and R5-20 (the difference between Rrs at 5 Hz (R5) and at 20 Hz (R20)) is low. Central airway obstruction, a component of asthmatic airflow limitation, increases Rrs at all frequencies (i.e., both R5 and R20 are increased) and R5-20 is low (Làndsér et al., Chest. 1982;81(5):586-91).In small airway disease, also frequently observed in asthma, Rrs increase in a frequency-dependent manner at low frequencies (i.e., R5 increases more than R20). (Clément et al., Chest. 1983;83(2):215-20). Thus, the frequency dependence of Rrs (called R5-20; the difference between Rrs at 5 Hz and 20 Hz) reflects airway heterogeneity and increases with small airway obstruction (Otis et al., J Appl Physiol. 1956;8(4):427-43). [000335] Respiratory reactance (Xrs) is driven by the capacitance (backlash) properties of the respiratory system at low frequencies, where it reflects the soft tissue and lung parenchyma. At higher frequencies, however, Xrs is driven by the inertia of the moving air column in the conducting airways. The resonant frequency (fres) is the point at which the magnitudes of capacitive and inertial reactance are equal; fres is increased in obstructive and restrictive lung diseases (Pride, Thorax. 1992;47(4):317-20, Petition 870250085505, dated 09 / 22 / 2025, pp. 115 / 173 107 / 126 Clément et al., Chest. 1983;83(2):215-20). The AX is an integrative index of total respiratory reactance at all frequencies between 5 Hz and fres (area under the reactance curve) and has units of elastance, and is a measure of disease and closure of small airways, as seen in asthma. [000336] R5, R5-20, and AX are the most sensitive oscillometry metrics of small airway function (Goldman et al., Respir Physiol Neurobiol. 2005;148(1-2):179-94, Oostveen et al., Eur Respir J. 2003;22(6):1026-41, Oostveen et al., Eur Respir J. 2013;42(6):1513-23). ​​Thus, AX, R5, and R5-20 were the focus of the analysis for detecting the treatment effect. Transcriptomic analysis: [000337] To enhance the understanding of the effect of SAR443765 at a cellular level, single-cell RNA sequencing (scRNA-seq) was used. This technique allows the study of gene expression patterns at the individual cellular level, enabling a more detailed and comprehensive analysis. By comparing gene expression patterns before and after treatment with SAR443765, as well as treatment with SAR443765 versus the placebo group, specific cellular alterations linked to SAR443765 treatment can be identified. [000338] In the present study, scRNAseq was performed on nasal brushing (NB) and peripheral blood leukocyte (PBL) samples, collected on D1 (before administration of SAR443765 or placebo) and D29 from the SAR443765 group as well as the placebo group. [000339] scRNAseq was performed as described in the literature (see, for example, Haque et al., Genome Med. August 18, 2017;9(1):75 and Slovin et al., Methods Mol Biol. 2021;2284:343-365). Analyses were performed separately for nasal brushing and PBL data. Results for cell populations and expression Petition 870250085505, dated 09 / 22 / 2025, pp. 116 / 173 108 / 126 genetic data from different samples were compared as a follow-up analysis to assess consistency between samples. [000340] SignacX v 2.2.4 was used to annotate B.memory, B.naive, macrophage, Mon.Classical, Mon.NonClassical, neutrophil, eosinophil, NK, Plasma, CD4.T.memory, CD4.T.naive, CD8.T.CM, CD8.T.EM, CD8.T.naive, Tregs, Fibroblast, endothelial, and epithelial cell types (Chamberlain et al.). Because SignacX provides detailed algorithmic annotation of multiple immune types but only a general classification for non-immune cell types, running Louvain clustering during SPRING preprocessing followed by marker gene expression analysis was applied for annotation of non-immune epithelial cell subtypes of NB, dendritic cell subtypes (Villani et al.), and mast cells and eosinophils. Manual annotation of the nasal epithelium was performed based on cluster-level expression of previously published marker sets and ranked expression of marker gene sets (Deprez et al., Am J Respir Crit Care Med.December 15, 2020;202(12):1636-1645, Legebeke et al., Front Cell Dev Biol. June 15, 2022;10:907511, Vieira Braga et al., Nat Med. July 2019;25(7):1153-1163). The annotated SPRING Pipeline objects were converted into common data structures in scRNAseq format (Seurat and SingleCellExperiment objects) which were used as inputs to other single-cell data analysis packages for further analysis. [000341] To summarize the results of preprocessing and annotation, with dimensionality reduction of normalized count data, clustering and cell type annotation were performed, including identification of new cell types and subtypes. The summarized outputs showed the distribution of cell type abundance in terms of proportion and percentages, marker genes Petition 870250085505, dated 09 / 22 / 2025, pp. 117 / 173 109 / 126 superior values ​​per cell type were reported to confirm assignments. These outputs were presented graphically. [000342] Samples collected at baseline were analyzed to assess the presence of cell subsets and / or genetic signatures potentially predictive of reduced FeNO. FeNO values ​​at week 4 (D29) and / or changes in FeNO relative to baseline were used for correlation analyses. In particular, cell types that emerged as prominent in scRNASeq analyses were subjected to Spearman correlation analysis with FeNO values ​​at week 4 (D29) and / or changes in FeNO between D29 and D1 (baseline). Several correlation analyses were performed, such as change in cell type proportions relative to baseline vs. change in FeNO, gene expression at baseline vs. change in FeNO. Correlation values ​​along with p-values ​​were reported for these analyses. [000343] To obtain more information on the biological significance and asthma-related relevance of the data produced above, gene sets identified by differential expression analyses (D29 vs. D1) were studied using pathway analysis, which was performed using integrated knowledge databases and provided software such as Ingenuity Pathway Analysis (Qiagen) and Gene Set Enrichment Analysis (GSEA), such as scGSEA. These tools allowed the identification of pathway activation or inhibition through pathway module scoring analysis. Lists of specific genes have been investigated due to their relationship with allergy and asthma and / or the biology of the TSLP / IL13 pathway, including, but not limited to, genes in the TSLP and IL-13 pathways (e.g., IL-4, IL-13, IFNα, IFNγ) (Giovannini-Chami et al., Eur Respir J. 2012;39(5):1197-205, Kramer et al., Bioinformatics. 2014;30(4):523-30, Adhikary et al., Pharmacol Ther. 2021;217:107-648). 6.1.2 Results Petition 870250085505, dated 09 / 22 / 2025, pp. 118 / 173 110 / 126 [000344] The following data were collected at the time points indicated in Figure 1: FeNO level (Figures 2 and 3); blood eosinophil count (Figures 4 and 5), FEV1 (Figures 6, 7, 8), FEF25-75 (Figure 9), R5-20 (Figure 10), AX (Figure 11), other serum / plasma biomarkers (Figure 12), transcriptomic analysis (Figures 13, 14, 15, 16). FeNO level [000345] Figure 2 shows the change from baseline in FeNO levels in participants treated with SAR443765 (dashed line) or placebo (solid line). The dose of SAR443765 was 400 mg, and FeNO levels were measured one week (D8), two weeks (D15), four weeks (D29), and eight weeks (D57) after administration of SAR443765 or placebo. Table 1 shows the results of the FeNO level measurements. The baseline value is defined as the last available value before and closest to the first dose of the investigational medicinal product. Treatment with SAR443765 was determined to reduce FeNO levels by 31.1 ppb (-31.9 ppb - -0.8 ppb) after one week (D8), by 54.0 ppb (-35.2 ppb - 18.8 ppb) after 2 weeks (D15), by 39.9 ppb (-39.1 ppb - 0.8 ppb) after 4 weeks (D29), and by 35.9 ppb (-32.0 ppb - 3.9 ppb) after 8 weeks (D57) compared with placebo. [000346] In the SAR443765 group, 37% of participants had a normal FeNO level (below 25 ppb) at the end of the study, while this was only the case for 8% of the placebo group. Table 1: Change in FeNO level after treatment with SAR443765. All FeNO levels are indicated in ppb. Treatment group / time point FeNO level Change from baseline Mean Standard Deviation Median Mean Standard Deviation Median Petition 870250085505, dated 09 / 22 / 2025, pp. 119 / 173 111 / 126 Standard Standard Placebo Baseline 71.9 44.8 54.5 - - - D8 71.1 50.2 49.5 -0.8 29.6 0.5 D15 90.7 70.6 69.5 18.8 38.9 11.5 D29 72.8 54.5 48.5 0.8 28.8 2.0 D57 75.8 46.4 73.5 3.9 24.3 6.5 SAR443765 (400 mg) Baseline 67.9 36.1 60.5 - - - D8 34.1 16.7 30.0 -31.9 24.9 -25.0 D15 32.7 15.9 31.5 -35.2 29.1 -27.0 D29 28.8 10.9 26.0 -39.1 29.6 -29.5 D57 35.9 21.5 29.5 -32.0 25.3 -25.5 [000347] Table 2 presents baseline FeNO values, as well as the reduction after 4 weeks (D29) from the present study and multiple published results from studies with other biologics, including tezepelumab (anti-TSLP), lebrikizumab (anti-IL-13), tralokinumab (anti-IL-13), benralizumab (anti-IL-5Ra), dupilimab (anti-IL4Ra), and itepekimab (anti-IL-33). SAR443765 shows a stronger reduction in FeNO levels than all other compounds, with a reduction more than 2 times greater compared to the highest reduction achieved in an assay with another compound (18 ppb in a lebrikizumab assay). The present assay shows that administration of a compound that blocks both IL-13 and TSLP can massively increase the reduction of FeNO by a factor of approximately 2 to 4 compared to monospecific approaches. Table 2: Comparison of FeNO reduction for SAR443765 and other biological products used for asthma treatment. All levels Petition 870250085505, dated 09 / 22 / 2025, pp. 120 / 173 112 / 126 of FeNO are indicated in ppb. Treatment arms Baseline (standard deviation) Change from baseline D29 Drug vs. difference Placebo Reference SAR443765 (N=24) 67.9 (36.1) -39.1 -39.9 Present invention Placebo (N=12) 71.9 (44.8) 0.8 Published results Tezepelumab (N=15) 58.9 (55) -18.1 -12.6 Gauvreau, 2014 Placebo (N=16) 42.3 (17) -5.5 Tezepelumab (N=112) 31.5 (39.8) -8.5 -8 Corren, 2017 Placebo (N=119) 37.8 (39.7) -0.5 Tezepelumab (N=491) 41.4 (36.3) -15 -12 Menzies-Gow, 2021 Placebo (N=491) 46.3 (44.7) -3 Tezepelumab (N=69) 38.7 (40.8) -11.7 -10.3 Wechsler, 2022 Placebo (N=68) 42.3 (37.4) -1.4 Lebrikizumab (N=104) 34 (6-242) -28 -18 Korenblat, 2018 Placebo (N=105) 37 (6-232) -10 Lebrikizumab (N=107) 31.0 (24.6) -11.8 -8.3 Corren, 2011 Placebo (N=112) 30.2 (27.7) -3.5 Tralokinumab (N=39) 39.54 (30.05) -14.2 -11.7 Russell, 2018 Petition 870250085505, dated 09 / 22 / 2025, pp. 121 / 173 113 / 126 Placebo (N=40) 32.23 (24.82) -2.5 Tralokinumab (N=363) 29.8 (29.7) «-7.0 -6.5 Panettieri, 2018 Placebo (N=400) 29.7(28.5) «-0.5 Benralizumab (N=81) 37.8 (31.7) -4 -5 Castro, 2014 Placebo (N=80) 39.9 (31.9) +1 Dupilumab (N=157) 38.13 (35.11) -16 -11 Wenzel, 2016 Placebo (N=158) 38.95 (34.79) -5 Itepequimab (N=73) 30.3 (24.3) -7 -9 Wechsler, 2021 Placebo (N=74) 33.3 (42.6) 2 Subgroup analysis [000348] Figure 3 shows the same measurements as Figure 2 separated according to the baseline eosinophil count of the participants. The following groups are represented: SAR443765 with elevated baseline eosinophil count (> 0.3 *109 cells / L (lower dashed line)), SAR443765 with low baseline eosinophil count (< 0.3 *109 cells / L (lower solid line)), placebo with elevated baseline eosinophil count (> 0.3 * 109 cells / L (upper dashed line)), placebo with low baseline eosinophil count (< 0.3 *109 cells / L (upper solid line)). The results of these four groups at D29 (4 weeks) are also represented in Table 3. Table 3: Change in FeNO level after treatment with SAR443765 for high and low eosinophilic subgroups. All FeNO levels are indicated in ppb. Petition 870250085505, dated 09 / 22 / 2025, pp. 122 / 173 114 / 126 Treatment Group FeNO Baseline Mean (Standard Deviation) Change from Baseline D29 (Standard Deviation) Percent Change from Baseline D29 (Standard Deviation) Placebo with EOS <0.3 (N=8) 56.1 (38.7) 1.4 (13.9) -1.87 (23.46) Placebo with EOS >0.3 (N=4) 103.5 (43.3) -0.3 (50.9) 3.94 (47.83) SAR443765 with EOS <0.3 (N=16) 59.3 (35.9) -32.1 (30.1) -49.45 (21.24) SAR443765 with EOS >0.3 (N=8) 85.1 (31.8) -53.3 (24.3) -60.40 (9.81) [000349] The present treatment led to a notable reduction in FeNO levels in both groups. For participants with high eosinophil counts, the reduction compared to placebo is 53.0 ppb (64.34% of baseline), for participants with low eosinophil counts, the reduction compared to placebo is 33.5 ppb (47.58% of baseline). This shows that the present treatment led, in both participant groups, to a similar relative reduction in FeNO that exceeds the FeNO reductions observed for any other biological product (see Table 2). Eosinophil count [000350] Figure 4 shows the change in eosinophil count of participants who were treated with SAR443765 (right column) or placebo (left column) at D29 (4 weeks). Treatment with SAR443765 led to a median change in eosinophil count of -42.42%, while the placebo group showed a median change of Petition 870250085505, dated 09 / 22 / 2025, pp. 123 / 173 115 / 126 in eosinophil count of -0.38%. This demonstrated that SAR443765 led to a strong reduction in eosinophil count compared to placebo. Figure 5 shows the change in eosinophil count on D29 for SAR443765 and other biologics (lebriquizumab, tezepelumab, and dupilumab). SAR443765 shows a decrease in the same range as tezepelumab. Note that dupilumab, which like SAR443765 blocks IL-13 signaling, shows an increase in eosinophil count here. Such an increase in eosinophils was not observed for SAR443765. [000351] Table 4 shows the results of eosinophil counts after treatment with SAR443765 on D2, D4, D8, D15, D29, D57 and D71. Table 4: Change in eosinophil count after treatment with SAR443765. All eosinophil counts are indicated as 10⁹ cells / L. Treatment Group / Time Point Eosinophil Count Percentage Change from Baseline Mean Standard Deviation Median Median Min Max Placebo Baseline 0.280 0.119 0.275 - - - D2 (24 h) 0.256 0.087 0.235 -12.90 -26.1 37.5 D4 (72 h) 0.259 0.172 0.195 -4.85 -46.9 30.5 D8 0.225 0.181 0.225 3.13 -43.5 42.9 D15 0.395 0.183 0.395 38.39 -48.1 168.8 D29 0.255 0.238 0.255 -0.38 -33.3 306.3 D57 0.307 0.158 0.290 -4.82 -50.0 156.3 D71 0.299 0.185 0.245 -14.78 -56.0 150.0 Petition 870250085505, dated 09 / 22 / 2025, pp. 124 / 173 116 / 126 SAR443765 (400 mg) Baseline 0.281 0.143 0.250 - - - D2 (24 h) 0.247 0.143 0.220 -20.00 -40.0 71.4 D4 (72 h) 0.180 0.088 0.170 -34.67 -77.8 40.7 D8 0.194 0.141 0.140 -40.83 -77.8 318.8 D15 0.186 0.095 0.165 -30.91 -70.6 137.5 D29 0.161 0.119 0.150 -42.42 -100.0 268.8 D57 0.215 0.309 0.140 -46.25 -83.8 263.6 D71 0.180 0.159 0.115 -51.00 -80.0 143.8 FEB1 [000352] FEV1 (forced expiratory volume in one second) is the volume of air in liters that is exhaled in the first second during forced expiration after maximal inspiration. In this study, FEV1 was determined by spirometry, as described above. Figure 6 shows the change (compared to baseline) in FEV1 of participants who were treated with SAR443765 (dashed line) or placebo (solid line). The dose of SAR443765 was 400 mg. Figure 6 represents all available FEV1 measurements. Figure 7 shows the same measurements but excludes values ​​where the measurement did not meet all quality standards, meaning that the difference between the 2 highest FEV1 values ​​in a triplicate was > 0.150 l. Based on the results in Figure 6, the present treatment led to an increase in FEV1 of approximately 0.25 l after one week (D8), approximately 0.2 l after 2 weeks (D15), approximately 0.07 l after 4 weeks (D29) and 8 weeks (D57) compared with placebo.The results in Figure 7 are similar for D8 and D29, but show a smaller difference for D15 and no significant difference for D57. These results indicate that SAR443765 improves FEV1. However, further studies with a larger patient cohort and more impaired FEV1 at baseline are needed to corroborate this. Petition 870250085505, dated 09 / 22 / 2025, pages 125 / 173 117 / 126 found. [000353] To obtain more information about different patient subpopulations, FEV1 improvement was analyzed for subpopulations with normal and impaired lung function at baseline. The criterion for classifying a participant into one of these groups was the “percentage of predicted FEV1” at baseline, that is, before the start of treatment with SAR443765 or placebo. The percentage of predicted FEV1 (abbreviated as ppFEV1) is the ratio (in %) between the participant's actual FEV1 and a reference FEV1, which reflects the average value for a person with the participant's demographic data, such as age, sex, and body composition. Participants whose baseline ppFEV1 was >80% were classified in the normal baseline lung function subpopulation, while participants whose baseline ppFEV1 was <80% were classified in the impaired baseline lung function subpopulation. Thus, the data for the SAR443765 group and the placebo group were divided into two subpopulations according to this criterion.The FEV1 results for these 4 subgroups are shown in Figure 8. The results indicate that the overall improvement in FEV1 observed in Figure 7, especially for D8, D15, and D29 after treatment with SAR443765, is mainly due to an improvement in the subpopulation with impaired baseline lung function (ppFEV1 < 80%), while the subpopulation with normal baseline lung function (ppFEV1 > 80%) showed almost no improvement, probably due to a ceiling effect. FEF25-75 [000354] FEF25-75 (Forced Expiratory Flow 25-75%) refers to a fraction of FVC (forced vital capacity), which is the maximum volume of air a patient can exhale after maximal inspiration. FEF2575 is the fraction of FVC that is exhaled in the time interval between exhaling 25% of FVC and exhaling 75% of FVC, divided by Petition 870250085505, dated 09 / 22 / 2025, pp. 126 / 173 118 / 126 time in which this volume is exhaled. Impairment in FEF25-75 may be indicative of small airway obstruction. In this study, FEF25-75 was determined by spirometry, as described above. [000355] Figure 9 shows the FEF25-75 for the entire patient population (upper panel), as well as for the subpopulations (lower panel) with normal baseline lung function (ppFEV1 >80%) and impaired baseline lung function (ppFEV1 <80%), as explained above for the FEV1 results in Figure 8. SAR443765 improved the FEF25-75 across the entire patient population (left panel), especially for D8 and D15. The results for the subpopulations (right panel) indicate that this overall improvement in FEF25-75 observed in the left panel is primarily due to the SAR443765 subpopulation with impaired baseline lung function (ppFEV1 <80%), which shows an improvement of approximately 0.4-0.5 l / s, while the subpopulation with normal baseline lung function (ppFEV1 >80%) showed almost no improvement compared to baseline. This result is evidence that treatment with SAR443765 reduces small airway obstruction in patients with asthma. R5-20 [000356] As noted above, R5-20 is the difference between respiratory resistance at 5 Hz and respiratory resistance at 20 Hz. Resistance at 5 Hz indicates the resistance of the entire respiratory system (small and large airways), while resistance at 20 Hz indicates the resistance within the large airways. Consequently, a high R5-20 indicates increased resistance (and therefore obstruction) of the small airways. R5-20 was determined by impulse oscillometry, as described above. [000357] Figure 10 shows the R5-20 for the entire patient population (top panel), as well as for the subpopulations (panel Petition 870250085505, dated 09 / 22 / 2025, pp. 127 / 173 119 / 126 lower) with normal baseline lung function (ppFEVI >80%) and impaired baseline lung function (ppFEVI <80%), as explained above for the FEV1 results in Figure 8. R5-20 was reduced across the entire patient population, the reduction exceeding the value of 0.31 cmH2O*s / L (0.03 kPa*s / L), which is considered the clinically significant threshold (Foy B, et al. Am J Respir Crit Care. 2019;200(8):982-991). The effect was most pronounced on D8 and D15. Although there was virtually no effect of SAR443765 in the normal baseline lung function subpopulation (ppFEVI >80%), there was a notable reduction in R5-20 in the impaired baseline lung function subpopulation (ppFEV1 <80%). This indicates that treatment with SAR443765 reduces small airway obstruction, especially in asthma patients with impaired lung function. [000358] As noted above, the reactance area (AX) is calculated from the measurement of lung reactance (see also Desiraju and Agrawal, 2016). This includes the total area dominated by capacitance and reflects the capacitance (backlash) properties of the lung. As seen with reactance and fres, AX also increases in any peripheral lung disease. AX was determined by impulse oscillometry, as described above. [000359] Figure 11 shows AX for the entire patient population (upper panel), as well as for the subpopulations (lower panel) with normal baseline lung function (ppFEV1 >80%) and impaired baseline lung function (ppFEV1 <80%), as explained above for the FEV1 results in Figure 8. SAR443765 reduced AX in the entire patient population, with the reduction exceeding the value of 6.65 cmH2O / l (0.65 kPa / l), which is considered the clinically significant threshold (Abdo et al. Eur Respir J. 2023;61(5): 2201793). The effect was most pronounced on D8 and D15. Although there was virtually no effect in the subpopulation with normal baseline lung function (ppFEV1 Petition 870250085505, dated 09 / 22 / 2025, pp. 128 / 173 (120 / 126 >80%), there was a notable reduction in the subpopulation with impaired baseline lung function (ppFEV1 <80%) with the administration of SAR443765. This indicates that treatment with SAR443765 reduces small airway obstruction, especially in asthma patients with impaired lung function. Additional biomarkers [000360] In addition to the parameters shown above, the following biomarkers were determined in the above clinical trial with SAR443765: serum IL-5 level; plasma CCL26 (eotaxin-3) level; serum TARC (CCL17) level; and serum IgE level. The determination of these biomarker levels was performed according to methods commonly known in the field. The results at D29 are shown in Figure 12. Treatment with SAR443765 led to a reduction from baseline for all observed biomarkers. Transcriptomic analysis: [000361] Transcriptomic analysis was performed by single-cell RNA sequencing (scRNAseq). scRNAseq was used to determine gene expression at the single-cell level in nasal swab (NS) samples as well as peripheral blood leukocyte (PBL) samples. Samples were collected on D1 (baseline, before administration of SAR443765 or placebo) and D29. Gene expression analysis allowed the identification of cell types and their proportion (Figures 13, 14), correlation of changes in this proportion with changes in FeNO levels (Figure 15), as well as analysis of single gene expression by cell type (Figure 16). [000362] Figure 13 represents the different cell types found in nasal brushing samples. The change (D29 compared to D1) in the cell type ratio of each cell type (indicated as log2 of fold change (FC)) on the geometric x-axis is Petition 870250085505, dated 09 / 22 / 2025, pp. 129 / 173121 / 126 plotted against the p-value for this change (indicated as -log 10 of the p-value) on the geometric y-axis. In this analysis, p-values ​​< 0.05 (corresponding to a value of at least approximately 1.3 on the geometric y-axis) were considered significant. Reduced cell types (“downregulated”) are marked by a triangle, unchanged cell types are marked by a dot, and increased cell types (“upregulated”) are marked by a square. It was found that in the SAR443765 group, the proportion of non-classical monocytes was significantly reduced, while there was no significant change in the placebo group. As nasal brushing samples can be considered indicative for the entire respiratory tract, this is a first indication that the proportion of non-classical monocytes may also be reduced in the pulmonary airways.Reducing airway inflammation through SAR443765 may include reducing the proportion of non-classical monocytes in the airways. [000363] There was no significant change in the SAR443765 group or the placebo group for the other immune cell types identified. [000364] Figure 14 represents the different cell types found in peripheral blood leukocyte (PBL) samples. The change (D29 compared to D1) in the cell type ratio of each cell type (indicated as log2 of fold change (FC)) on the geometric x-axis is plotted against the p-value for this change (indicated as -log10 of the p-value) on the geometric y-axis. In this analysis, p-values ​​< 0.05 (corresponding to a value of at least 1.3 on the geometric y-axis) were considered significant. It was found that in the SAR443765 group, the proportion of NK cells, as well as the proportion of CD8 effector T memory cells (em), were significantly reduced. The proportion of neutrophils was significantly increased, while additional measurements indicated that the total number of Petition 870250085505, dated 09 / 22 / 2025, pp. 130 / 173 The 122 / 126 neutrophil count did not increase. This is evidence for a rebalancing of the immune system through reduced type 2 inflammation and therefore a reduced number of cells linked to type 2 inflammation. There were no significant changes in the placebo group. This indicates that the anti-inflammatory effect of SAR443765 may include a reduction in the ratio of NK cells to CD8 T cells. [000365] There was no significant change in the SAR443765 group or in the placebo group for the other types of immune cells identified. [000366] Figure 15 represents the correlation between the change (D29 compared to D1) in FeNO level and the change (D29 compared to D1) in the proportion of NK cells in PBL samples. The y-axis shows the change in the proportion of NK cells (log10 of foldchange (FC) of NK cells), while the geometric x-axis shows the change in FeNO level in bbp. Each point indicates the value for a participant. The left panel shows the SAR443675 group and the placebo group, while the right panel shows only the SAR443765 group. It is evident that the correlation between the change in FeNO level and the change in the proportion of NK cells is much better only for the SAR443765 group, compared to the SAR443765 group combined with the placebo group. This suggests that there may be a link between the reduction of FeNO induced by SAR443765 and a reduction in the proportion of NK cells in the blood, which could be part of the therapeutic effect of SAR443765. [000367] Figure 16 shows the change (D29 compared to D1) in CCL26 gene expression for different cell types in nasal brushing samples. For each cell type, there are two bars, the left corresponding to D1, the right corresponding to D29. Although CCL26 expression was not significantly reduced in the placebo group (top panel), it was significantly reduced in basal epithelial cells, multiciliated epithelial cells and Petition 870250085505, dated 09 / 22 / 2025, pp. 131 / 173 123 / 126 secretory epithelial cells after treatment with SAR443765 (bottom panel). The result for multiciliated epithelial cells is shown again in enlarged form in the upper right corner of the figure. These results corroborate the finding for CCL26 / Eotaxin-3 at the protein level (see Figure 12). [000368] As shown above (see Figure 14), treatment with SAR443765 reduced the proportion of effector memory (em) CD8 T cells in PBL samples. Additionally, SAR443765 led to a significant downregulation (adjusted p-value <0.05) of the HBB gene, encoding beta-globin, in CD8 T cells (Figure 17). Elevated HBB expression has been described as associated with low FEV1 in asthma. Thus, reduced HBB expression may be an indication of successful treatment. Route analysis [000369] As observed above, in PBL samples, the proportion of neutrophils was significantly increased in the SAR443765 group, while additional measurements indicated that the total number of neutrophils did not increase (Figure 14). To investigate the activation state of neutrophils, scRNAseq gene expression data were subjected to pathway analysis. Gene lists for specific pathways are known from the literature (Giovannini-Chami et al., Kramer et al., Adhikary et al.), and can be grouped into so-called “pathway modules”. Pathway modules were determined for IL-4, IL-13, interferon alpha (IFNa), and interferon gamma (IFNg). Each pathway module was assigned a score at each time point (D1 and D29), corresponding to the expression of the module's genes. The difference in pathway module scores relative to D29 and D1 (score) indicates upregulation or downregulation of the respective pathway. Table 5 shows these score differences for SAR443765 and placebo. Petition 870250085505, dated 09 / 22 / 2025, pages 132 / 173 124 / 126 Table 5: Pathway module scores for neutrophils in PBL samples. P-values ​​below 0.05 indicate significance. Neutrophils (PBL), Pathway Module Score Pathway Module SAR443765 D29 vs D1 Placebo D29 vs D1 IL-4 Δscore=-0.003,P=0.00 Δscore=0.001,P=0.00 IL-13 Δscore=-0.000,P=1.00 Δscore=0.000,P=0.29 IFNa Δscore=-0.006,P=0.00 Δscore=0.000,P=0.00 IFNg Δscore=-0.005,P=0.00 Δscore=0.000,P=0.00 [000370] For SAR443765, it can be seen that the pathway modules for IL-4, IFNα, and IFNγ show a negative score difference, signifying a decrease in the activity of the IL-4, IFNα, and IFNγ pathways in neutrophils in peripheral blood. Since this decrease is not observed for placebo, the effect may be attributed to SAR443765. References Abdiche et al. Anal Biochem. 15 Jun 2008;377(2):209-17 Abdo et al., 2023 Eur Respir J. May 5, 2023;61(5):2201793 Adhikary et al., Pharmacol Ther. 2021;217:107648 American Thoracic Society (ATS) / European Respiratory Society (ERS) Guidelines, 2019 update: Graham et al., Am J Respir Crit Care Med. 15 October 2019;200(8):e70-e88 Jameli et al., Int J Mol Sci. September 2020; 21(17): 6187 Castro et al., Lancet Respir Med. November 2014;2(11):879-890 Chamberlain et al., Fortune Journals 2023 ; 6(3), 152-177 Clément et al., Chest. 1983;83(2):215-20 Conrath et al., J Biol Chem. 9 March 2001;276(10):7346-50 Corren et al., N Engl J Med. 22 Sep 2011;365(12):1088-98 Corren et al., N Engl J Med. 7 Sep 2017;377(10):936-946 Davies and Riechmann, Protein Eng., June 1996;9(6):531-7 Deprez et al. Am J Respir Crit Care Med. 15 December 2020;202(12):1636-1645 Desiraju e Agrawal, Lung India. Jul-Aug 2016;33(4): 410-416. Petition 870250085505, of 22 / 09 / 2025, p. 133 / 173 125 / 126 Drake et al., Anal Biochem. 1 May 2004; 328(1):35-43 Eguíluz-Gracia et al., Clin Exp Allergy. December 2018;48(12):16311639 Foy B, et al. Am J Respir Crit Care. 2019;200(8):982-991 Fraley et al., Bioanalysis. Jul 2013;5(14):1765-74 Gauvreau et al., N Engl J Med. 29 May 2014;370(22):2102-10 Gieseck III et al., Nat Rev Immunol. January 2018;18(1):62-76 Giovannini-Chami et al., Eur Respir J. 2012;39(5):1197-205 Global Initiative for Asthma 2020 Guidelines: Global strategy for asthma management and prevention, 2020 [cited 07 May 2021]. Available from: URL:www.ginasthma.org. Goldman et al., Respir Physiol Neurobiol. 2005;148(1-2):179-94 Hamers-Casterman et al., Nature. 3 June 1993;363(6428):446-8 Haque et al., Genome Med. 18 August 2017;9(1):75 Johnnson et al. Anal Biochem. 1 Nov 1991;198(2):268-77 Johnsson et al., J Mol Recognit. Janeiro-April de 1995;8(1-2):125-31 Jonsson et al., Ann Biol Clin (Paris). 1993;51(1):19-26 Jonsson et al., Biotechniques. Nov. 1991;11(5):620-7. Korenblat et al., Respir Med. January 2018;134:143-149 Kramer et al., Bioinformatics. 2014;30(4):523-30 Làndsér et al., Chest. 1982;81(5):586-91 Legebeke et al., Front Cell Dev Biol. 15 June 2022;10:907511 Li et al., J Allergy Clin Immunol. March 2021;147(3):941-954 McNulty and Usmani, Eur Clin Respir J, 2014;1:10.3402 / ecrj.v1.25898 Menzies-Gow et al., N Engl J Med. 13 May 2021;384(19):18001809 Miskoff et al., Cureus. June 2019; 11(6): e4864 Muyldermans, J Biotechnol. June 2001;74(4):277-302 Ober et al., Int Immunol. December 2001;13(12):1551-9 Oostveen E, et al. Eur Respir J. 2013;42(6):1513-23 Petition 870250085505, of 22 / 09 / 2025, p. 134 / 173 126 / 126 Oostveen et al., Eur Respir J. 2003;22(6):1026-41 Ordovas-Montanes et al., Nature. 2018;560(7720):649-54. Otis et al., J Appl Physiol. 1956;8(4):427-43 Panettieri et al., Immunotherapy. 1 March 2018;10(6):473-490 Panettieri et al., Lancet Respir Med. Jul 2018;6(7):511-525 Peters et al., Appl Physiol Nutr Metab. 2016; 41(5):538-47 Pride, Thorax. 1992;47(4):317-20 Russell et al., Lancet Respir Med. Jul 2018;6(7):499-510 Slovin et al., Methods Mol Biol. 2021;2284:343-365 Stockley et al., Int J Chron Obstruct Pulmon Dis. 2017;12: 2343-2353 Tomita et al., J Allergy Clin Immunol. agosto de 1995;96(2):230-8 Venkataramani et al., Biochem Biophys Res Commun. 26 de setembro de 2018; 504(1):19-24 Vieira Braga et al., Nat Med. Julho de 2019;25(7):1153-1163 Villani et al., Science. 21 de abril de 2017;356(6335) Wechsler et al., Lancet Respir Med. Julho de 2022;10(7):650-660 Wechsler et al., N Engl J Med. 28 de outubro de 2021;385(18):16561668 Wenzel et al., Lancet. 2 de julho de 2016;388(10039):31-44 WO 94 / 04678 - IMMUNOGLOBULINS DEVOID OF LIGHT CHAINS WO 96 / 34103 - VARIABLE FRAGMENTS OF IMMUNOGLOBULINS USE FOR THERAPEUTIC OR VETERINARY PURPOSES WO 99 / 23221 - MULTIVALENT ANTIGEN-BINDING PROTEINS WO2021116182 - POLYPEPTIDES COMPRISING IMMUNOGLOBULIN SINGLE VARIABLE DOMAINS TARGETING IL-13 AND TSLP Ziegler & Artis, Nat Rev Immunol (2010) 11:289-93 Petition 870250085505, dated 09 / 22 / 2025, pp. 135 / 173

Claims

1 / 4 CLAIMS 1. Compound, characterized in that it binds to IL13 and TSLP for use in the treatment of a lung disease in an individual, said treatment reducing the level of fractionated exhaled nitric oxide (FeNO) by at least 18 ppb compared with a control.

2. Compound for use, according to claim 1, characterized in that the treatment reduces the level of FeNO by at least 20 ppb, at least 30 ppb or at least 40 ppb, compared with a control.

3. Compound for use, according to claim 1 or 2, characterized in that the lung disease is asthma.

4. Compound for use according to claim 3, characterized in that it is eosinophilic asthma.

5. Compound for use according to claim 3, characterized in that it treats low-grade eosinophilic asthma.

6. Compound for use, according to any of the preceding claims, characterized in that the control is the baseline or that the control is a placebo, optionally wherein the baseline means the individual's baseline.

7. Compound for use, according to any of the preceding claims, characterized in that said reduction in FeNO level occurs within 4 weeks after administration of the compound, wherein optionally said reduction in FeNO level occurs within 2 weeks after administration of the compound, wherein optionally said reduction in FeNO level occurs within 1 week after administration of the compound.

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

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

21.

10. Compound for use, according to any one of claims 8 to 9, characterized in that the polypeptide comprises or consists of an amino acid sequence of SEQ ID NO:

1. Petition 870250085505, dated 09 / 22 / 2025, pp. 137 / 173 3 / 4 11. Compound for use, according to any of the preceding claims, characterized in that the individual has a basal FeNO level of at least 50 ppb and an eosinophil count greater than or equal to 0.3 *109 cells / l.

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

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

14. A compound that binds to IL-13 and TSLP for use in the treatment of a lung disease in an individual, characterized in that said treatment reduces airway inflammation.

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

16. Compound for use, according to claim 15, characterized in that said reduction of airway inflammation occurs within 4 weeks after administration of the compound, wherein optionally said reduction of airway inflammation occurs within 2 weeks after administration of the compound, wherein Petition 870250085505, dated 09 / 22 / 2025, page 138 / 173 4 / 4 optionally said reduction of airway inflammation occurs within 1 week after administration of the compound.

17. A compound that binds TSLP and / or IL-13 for use in reducing FeNO levels in an individual, characterized in that the reduction in FeNO levels prevents a loss of lung function.

18. Compound for use according to claim 17, characterized in that said reduction in FeNO level is a reduction of at least 18 ppb.

19. Compound for use, according to any one of claims 17 to 18, characterized in that said reduction in FeNO level is a reduction to a level below 25 ppb.

20. Compound for use, according to any one of claims 17 to 19, characterized in that the individual has a basal FeNO level of at least 50 ppb, at least 35 ppb, or at least 25 ppb.

21. Compound for use, according to any one of claims 17 to 20, characterized in that the individual has a basal FeNO level of at least 50 ppb and an eosinophil count greater than or equal to 0.3 *109 cells / l.

22. Compound for use according to any one of claims 17 to 21, characterized in that the compound binds to TSLP and IL-13.

23. Compound for use, according to any one of claims 17 to 21, characterized in that said loss of lung function is linked to asthma. Petition 870250085505, dated 22 / 09 / 2025, pp. 139 / 173

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