Upstream Bio (UPB) TD Cowen 46th Annual Health Care Conference summary

Key clinical data and efficacy insights

• Phase II VALIANT study for verekitug showed 56% reduction in asthma exacerbations at 100 mg Q12W and 39% at 400 mg Q24W, with strong improvements in lung function and airway inflammation markers.

• Efficacy was consistent with leading competitor Tezepelumab, especially at quarterly dosing, and robust across subgroups, with highest efficacy in high eosinophil populations.

• In CRSwNP, verekitug demonstrated significant benefit on primary and secondary endpoints, including nasal polyp score and reduced need for steroids or surgery, with efficacy comparable to or exceeding competitors.

• New analyses accounting for steroid use further improved efficacy estimates, reinforcing the drug's strong profile at quarterly dosing.

• Safety profile remains clean and consistent with other biologics, with ADA prevalence not impacting efficacy or exposure.

Strategic development plans and regulatory outlook

• Ongoing PK/PD modeling and exposure-response analyses will inform final dose and interval selection for phase III, with a single dose likely for both asthma and CRSwNP.

• Phase III trials in severe asthma and CRSwNP are targeted to start by year-end or early next year, aiming for rapid execution and potential timeline advantage.

• Manufacturing and device development are advanced, with a concentrated formulation enabling high-dose delivery in a single injection compatible with auto-injectors.

• The company is preparing regulatory briefing materials and phase III designs at risk to maintain momentum.

• $341 million in cash supports ongoing and planned clinical programs.

Competitive positioning and market considerations

• Efficacy is prioritized over dosing convenience, with quarterly dosing seen as optimal if efficacy is not compromised.

• The molecule targets the TSLP receptor, offering a differentiated mechanism, and is supported by extensive clinical data across multiple indications.

• In COPD, the phase II trial is over 60% enrolled, with primary analysis focused on patients with elevated eosinophils; dose selection may be adjusted based on asthma findings.

• The company aims to be the second long-acting drug to market in severe asthma and potentially the first in CRSwNP.

• Regulatory strategy may leverage a single pivotal phase III trial augmented by phase II data for approval, consistent with respiratory disease precedent.