Upstream Bio, Inc. · NASDAQ:UPB

Upstream Bio — Investor Presentation (September 2026)

26 slides from Upstream Bio's investor presentation, Sep 8, 2026

Slide 2: Disclaimer
No Image Disclaimer This presentation contains “forward-looking statements” within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934, each as amended. These statements may be identified by words such as “aims,” “anticipates,” “believes,”
Slide 3: About Upstream Bio
No Image About Upstream Bio Clinical-stage company developing treatments for severe inflammatory respiratory diseases Developing verekitug, the only known clinical- Pursuing Phase 3 development strategy designed to stage antagonist of the TSLP receptor deliver best-in-class efficacy with convenient
Slide 4: Leadership team
No Image Leadership team Deep experience and complementary areas of expertise EXECUTIVE TEAM Rand Sutherland, MD Aaron Deykin, MD Mike Gray Chief Executive Officer Chief Medical Officer & Head of R&D Chief Financial Officer & Chief Operating Officer © 2026 Upstream Bio, Inc. Allison Ambrose Lisa Fie
Slide 5: About verekitug
No Image About verekitug  Verekitug is the only known clinical-stage antagonist of Mechanism of verekitug inhibition the TSLP receptor of TSLP signaling1,2,3  Fully-human IgG1 antibody, discovered by Astellas/Regeneron and acquired by Upstream Bio  Verekitug’s potency is approximately 300-fold gr
Slide 6: Multiple upcoming milestones anticipated in 2027
No Image Multiple upcoming milestones anticipated in 2027 DEVELOPMENT INDICATIONS PRECLINICAL PHASE 1 PHASE 2 PHASE 3 NEXT ANTICIPATED MILESTONES Chronic Rhinosinusitis with Nasal Polyps Phase 3 Initiation Q1 2027* (CRSwNP) Phase 3 Initiation Q1 2027* Severe Asthma Data Expected H2 2027 † © 2026 Ups
Slide 7: Market Research Overview
No Image Market Research Overview Prioritizing a high-efficacy quarterly regimen to maximize verekitug’s potential commercial value © 2026 Upstream Bio, Inc.
Slide 8: Large and growing commercial opportunity in core indications
No Image Large and growing commercial opportunity in core indications, with asthma and COPD alone expected to be a $35B+ global biologics market in 2033 Severe ~1.3M <25% >$12.5B >$3B Asthma Biologic eligible severe asthma of eligible patients with Projected global sales for all Tezspire is projecte
Slide 9: Optimizing development strategy to address patient needs and maximize potential commercial value
No Image Optimizing development strategy to address patient needs and maximize potential commercial value Efficacy differentiation is the primary driver of treatment decisions and commercial success* Prioritizing verekitug development strategy to deliver potential best-in-class efficacy with quarter
Slide 10: Market research shows efficacy is the primary driver for decision-making among HCPs
No Image Market research shows efficacy is the primary driver for decision- making among HCPs in both asthma and CRSwNP Importance of Product Attributes for Asthma and CRSwNP % HCPs ranking attribute as the top 3 most important when selecting biologics for asthma & CRSwNP patients Asthma CRSwNP Prod
Slide 11: Phase 2 Clinical Data Overview in Severe Asthma and CRSwNP
No Image Phase 2 Clinical Data Overview in Severe Asthma and CRSwNP © 2026 Upstream Bio, Inc.
Slide 12: Phase 3 strategy designed to maximize verekitug's potential commercial value
No Image Phase 3 strategy designed to maximize verekitug’s potential commercial value by targeting best-in-class efficacy with at-home quarterly dosing Single 400 mg subcutaneous injection Target product profile Convenient quarterly dosing regimen Deliver potential best-in-class efficacy with quarte
Slide 13: Verekitug's profile supports potential for best-in-class efficacy & quarterly dosing
No Image Verekitug’s profile supports potential for best-in-class efficacy & quarterly dosing in severe asthma and CRSwNP 5 clinical studies completed to date with ~500 participants dosed with verekitug 1 2 3 4 5 Phase 2 trials Favorable Top-line safety results for PhasePotential 2 VIBRANT to delive
Slide 14: Results for Phase 2 VIBRANT study in CRSwNP
No Image Results for Phase 2 VIBRANT study in CRSwNP Verekitug dosed every 12 weeks, treatment period 24 weeks Met primary endpoint, with NPS reduction of -1.8 (p<0.0001) Phase 2 Met key secondary endpoints, VIBRANT including NCS reduction of -0.8 (p=0.0003*) and 76% reduction in need for surgery/st
Slide 15: Results for Phase 2 VALIANT study in severe asthma
No Image Results for Phase 2 VALIANT study in severe asthma Verekitug dosed every 12 weeks, treatment period up to 60 weeks Statistically significant and clinically meaningful reductions in AAER for up to 60 weeks Phase 2 Clinically meaningful improvements VALIANT in lung function (FEV1) and exhaled
Slide 16: Consistent and favorable safety profile across both Phase 2 trials
No Image Consistent and favorable safety profile across both Phase 2 trials 1 *3 → Overall incidence of AEs was similar across treatment groups → Overall incidence of TEAEs was similar across treatment groups → TEAEs related to study treatment occurred more frequently in placebo → Serious TEAEs were
Slide 17: In CRSwNP, verekitug led to significant improvements in NPS and key secondary endpoints
No Image In CRSwNP, verekitug led to significant and clinically meaningful improvements in NPS and all key secondary endpoints Verekitug Placebo Treatment difference Primary -1.8 (-2.51, -1.03) NPS change from baseline* -2.1 (0.26) -0.3 (0.27) Endpoint p<0.0001 -0.8 (-1.17, -0.37) NCS change from ba
Slide 18: In severe asthma, meaningful improvements sustained to week 60
No Image In severe asthma, verekitug led to meaningful improvements in primary and secondary endpoints at week 24 that were generally sustained to week 60 Verekitug Verekitug Verekitug Timing Endpoint 100 mg q12w 400 mg q24w 100 mg q24w (high exposure at Ctrough) (medium exposure at Ctrough) (low ex
Slide 19: Improvements in lung function and FeNO sustained over 60 weeks
No Image Verekitug 100 mg q12w and 400 mg q24w doses led to numerical improvements in lung function and FeNO as early as week 2 and sustained over 60 weeks FEV1 over 60 weeks1 FeNO over 60 weeks2 60 LSM change from baseline in FEV1 (liters) 0.5 LSM percent change from baseline in 0.4 40 0.3 20 FeNO
Slide 20: Patients with highest verekitug exposures experienced the greatest clinical benefit
No Image In both CRSwNP and severe asthma, patients with highest verekitug exposures experienced the greatest clinical benefit Placebo Verekitug (All) VIBRANT 100 mg q12w VALIANT 100 mg q12w Verekitug (group1,low) NCS by Exposure Tertiles1 FEV1 by Exposure Tertiles2 Verekitug (group2,mid) Verekitug
Slide 21: Modeling predicts 400 mg q12w could optimize proportion achieving therapeutic levels
No Image Modeling of data through Phase 2 predicts that 400 mg q12w could optimize proportion of patients achieving maximally therapeutic levels 400 mg q12w up to 72 weeks* Verekitug 100 Concentration (μg/mL) 10 Verekitug 1 High exposure tertile from Phase 2 studies 0.1 FENO EC90 LLOQ 0.01 © 2026 Up
Slide 22: Verekitug demonstrated clinical effect in NPS across all subgroups in VIBRANT
No Image Verekitug demonstrated clinical effect in NPS across all subgroups analyzed in the VIBRANT study Subgroups Verekitug Placebo Least Squares Mean Difference (95% CI) n n Overall 41 40 -1.8 (-2.51 to -1.03) Age (years) <65 36 34 -1.8 (-2.68 to -0.98) ≥65 5 6 -0.7 (-2.91 to 1.44) Sex Male 26 26
Slide 23: Analysis of VALIANT data supports evaluation in broad populations in Phase 3
No Image Analysis of VALIANT data supports evaluation in broad populations in Phase 3 FEV1 (L) by subgroup1,2 AAER by subgroup3,4 Verekitug Placebo LSM difference vs Verekitug Placebo Rate ratio Subgroups n LSM n LSM placebo (95% CI) Subgroups n AAER n AAER (95% CI) Overall 108 0.157 106 0.063 0.094
Slide 24: No meaningful impact of immunogenicity on AAER or FEV1 in VALIANT
No Image No meaningful impact of immunogenicity on AAER or FEV1 in VALIANT FEV1 AAER 100 mg q12w 2.0 ADA+ (Change from baseline) 100 mg Q12W Annualized Asthma Exacerbation Rate 0.3 400 mg Q24W 1.5 100 mg Q24W 0.2 0.97 FEV1 1.0 0.92 0.90 0.94 ADA- 0.84 0.78 0.66 0.53 0.1 0.5 0.45 © 2026 Upstream Bio,
Slide 26: Focused on disciplined execution
No Image Focused on disciplined execution 2026 Q1 2027 H2 2027 Completed productive End-of-Phase 2 Initiation of Phase 3 trials in severe Data from Phase 2 trial in COPD interactions with FDA asthma and CRSwNP expected expected Continue accelerated operational Data from severe asthma LTE expected pl

Upstream Bio — Investor Presentation (September 2026) on 6ix

Upstream Bio — Investor Presentation (September 2026)

Slide 1: Corporate Presentation

Slide 2: Disclaimer

Slide 3: About Upstream Bio

Slide 4: Leadership team

Slide 5: About verekitug

Slide 6: Multiple upcoming milestones anticipated in 2027

Slide 7: Market Research Overview

Slide 8: Large and growing commercial opportunity in core indications

Slide 9: Optimizing development strategy to address patient needs and maximize potential commercial value

Slide 10: Market research shows efficacy is the primary driver for decision-making among HCPs

Slide 11: Phase 2 Clinical Data Overview in Severe Asthma and CRSwNP

Slide 12: Phase 3 strategy designed to maximize verekitug's potential commercial value

Slide 13: Verekitug's profile supports potential for best-in-class efficacy & quarterly dosing

Slide 14: Results for Phase 2 VIBRANT study in CRSwNP

Slide 15: Results for Phase 2 VALIANT study in severe asthma

Slide 16: Consistent and favorable safety profile across both Phase 2 trials

Slide 17: In CRSwNP, verekitug led to significant improvements in NPS and key secondary endpoints

Slide 18: In severe asthma, meaningful improvements sustained to week 60

Slide 19: Improvements in lung function and FeNO sustained over 60 weeks

Slide 20: Patients with highest verekitug exposures experienced the greatest clinical benefit

Slide 21: Modeling predicts 400 mg q12w could optimize proportion achieving therapeutic levels

Slide 22: Verekitug demonstrated clinical effect in NPS across all subgroups in VIBRANT

Slide 23: Analysis of VALIANT data supports evaluation in broad populations in Phase 3

Slide 24: No meaningful impact of immunogenicity on AAER or FEV1 in VALIANT

Slide 25: Looking Ahead

Slide 26: Focused on disciplined execution