Arrowhead Pharmaceuticals (ARWR) Status Update summary

Pulmonary platform and strategy

• The platform targets inflammation, mucus hypersecretion, and fibrosis/interstitial lung disease in asthma, COPD, cystic fibrosis, bronchiectasis, IPF, and other interstitial lung diseases.

• Three lead clinical programs—ARO-RAGE (inflammation), ARO-MUC5AC (mucus), and ARO-MMP7 (fibrosis)—use a pulmonary-targeted TRIM RNAi platform.

• The TRIM platform enables deep, durable gene silencing in lung tissues, leveraging siRNA delivery via alpha-v beta-6 integrin targeting.

• Financial resources and non-dilutive capital from major partners support ongoing and future development.

ARO-RAGE program update

• ARO-RAGE targets the RAGE pathway, implicated in both Type 2 and neutrophilic inflammation, with potential in asthma, COPD, and cystic fibrosis.

• Phase I data show favorable safety, no severe adverse events, and no pro-inflammatory effects in healthy volunteers or asthma patients.

• Achieved up to 94% reduction in airway and 88% in serum soluble RAGE at highest dose, supporting every-2-month dosing.

• High FeNO asthma cohorts are enrolling to explore translational biomarkers, but FeNO is not considered predictive of clinical efficacy.

• Phase II study in severe asthma (Type 2 high and low) is planned for 2025, with endpoints on asthma control, exacerbations, lung function, and quality of life.

ARO-MUC5AC and ARO-MMP7 program updates

• ARO-MUC5AC targets mucus hypersecretion in asthma, COPD, and other muco-obstructive diseases; patient cohorts are enrolling, with top-line data expected in 1H 2025.

• ARO-MMP7 targets fibrosis in IPF, with ongoing patient enrollment and multiple dose cohorts completed; top-line data expected in 1H 2025.

• Both programs use disease-aligned biomarkers (sputum for MUC5AC, BAL/serum for MMP7) to assess target engagement.

• Both ARO-MMP7 and ARO-MUC5AC are expected to have topline Phase 1/2 readouts on safety, tolerability, and target engagement in the first half of 2025.