Upstream Bio (UPB) investor relations material

Key accomplishments and clinical progress

• Transitioned from early to mid-stage development, highlighted by strong phase II data for verekitug in chronic rhinosinusitis with nasal polyps (CRS with NP).

• Phase II results showed robust efficacy and 12-week dosing, supporting advancement to severe asthma trials with data expected in Q1 2026.

• Achieved clinical validation of verekitug’s potency and durability, reinforcing confidence in broader indications.

Differentiation and competitive landscape

• Verekitug uniquely targets the TSLP receptor, not the ligand, resulting in higher potency and longer receptor occupancy compared to competitors like tezepelumab.

• Demonstrated 50% greater predicted exhaled nitric oxide suppression and 300-fold lower EC50/EC90 values than tezepelumab.

• Extended dosing intervals (up to 24 weeks) achieved without compromising efficacy, a key distinction from YTE-modified molecules.

• No current evidence that bispecifics offer superior efficacy in targeted indications, though more data are awaited.

Clinical trial insights and future plans

• Phase II VIBRANT study in CRS with NP met primary and secondary endpoints, including significant reductions in polyp score, congestion, and need for rescue therapy.

• Plans to initiate phase III trials in both CRS with NP and severe asthma after Q1 2026 asthma data, aiming for near-simultaneous launches.

• Asthma trial (VALIANT) designed to match or exceed 50% reduction in exacerbation rate at 12-week dosing, with potential for even greater efficacy.

• Patient demographics in VALIANT expected to closely mirror those in benchmark studies, ensuring generalizability.

• Regulatory strategy may leverage robust phase II data for potential single phase III trials per indication.