Upstream Bio, Inc. · NASDAQ:UPB

Upstream Bio — Technical Presentation (September 2026)

11 slides from Upstream Bio's technical presentation, September 2026

1. Slide 1: VALIANT: a phase 2 trial of verekitug for severe asthma

   VALIANT: a phase 2 trial of the efficacy and safety of verekitug, a thymic stromal lymphopoietin (TSLP) receptor antagonist, for severe asthma M icha e l E . We chsler , 1 Ia n Pa vo rd , 2 Gra z y n a P u lk a , 3 S h a h r u k h Ku r e ishy, 4 D im o D im o v, 5 A h me d A . A r if, 6 To d o r A .

2. Slide 2: Conflict of interest disclosure

   Conflict of interest disclosure Presenter: Michael E. Wechsler ✓ have the following real or perceived conflicts of interest that relate to this presentation: ❑I Affiliation / Financial interest Commercial company Grants/research support: AstraZeneca, GlaxoSmithKline, and Sanofi/Regeneron Honoraria o

3. Slide 3: Introduction

   Introduction • Verekitug is a novel, unmodified, fully human monoclonal Verekitug mechanism of action1,3,7 antibody antagonist to the receptor for TSLP, and the only known TSLP receptor antagonist antibody in clinical development1–6 • Low circulating verekitug concentrations are sufficient to satura

4. Slide 4: Study design

   Study design Multicenter, randomized, placebo-controlled phase 2 trial with up to 60-week treatment period (NCT06196879) Key inclusion criteria Primary endpoint Verekitug 100 mg SC q12w • Annualized asthma • Aged 18–80 years (high exposure at Ctrough) exacerbation rate (AAER) • Physician-diagnosed a

5. Slide 5: Baseline characteristics generally balanced across arms

   Baseline characteristics generally balanced across arms Verekitug Verekitug Verekitug Placebo 100 mg q12w 400 mg q24w 100 mg q24w N=119 N=121 N=118 N=120 Age, mean (SD), years 54.6 (12.2) 53.8 (11.7) 51.7 (15.4) 54.0 (13.1) Race, n (%) White 91 (75.2) 90 (76.3) 90 (75.0) 93 (78.2) Black/African Amer

6. Slide 6: Primary endpoint: asthma exacerbations were significantly reduced with verekitug

   Primary endpoint: asthma exacerbations were significantly reduced with verekitug Annualized asthma exacerbation rate Rate ratio, 0.44 (95% CI, 0.28–0.69) Rate ratio, 0.61 2 P < 0.001 (95% CI, 0.40–0.93) P = 0.023 Rate ratio, 0.51 1.5 (95% CI, 0.33–0.79) P = 0.003 1.52 1 0.92 0.78 0.5 0.66 0 N=121 N=

7. Slide 7: Verekitug led to meaningful improvements in secondary endpoints at week 24

   Verekitug led to meaningful improvements in secondary endpoints at week 24 that were generally sustained to week 60 Verekitug Verekitug Verekitug 100 mg q12w 400 mg q24w 100 mg q24w Endpoint N=121 N=118 N=120 Pre-BD FEV1 N=108 N=108 N=105 LSM difference vs placebo (95% CI), mL 99 (9–189) 157 (67–248

8. Slide 8: Subgroup analysis demonstrated an 87% AAER reduction among high BECs

   Subgroup analysis demonstrated an 87% AAER reduction among high BECs and robust FEV1 improvement across most subgroups (100 mg q12w vs placebo) AAER by subgroup FEV1 at week 24 by subgroup Verekitug Placebo Rate ratio Verekitug Placebo LSM difference vs Subgroups n AAER n AAER (95% CI) Subgroups n L

9. Slide 9: Verekitug was well tolerated, with a similar safety profile to placebo

   Verekitug was well tolerated, with a similar safety profile to placebo Verekitug Verekitug Verekitug Most common TEAEs Placebo 100 mg q12w 400 mg q24w 100 mg q24w • Nasopharyngitis N=119 N=121 N=118 N=119 • Urinary tract infections Any TEAE 75 (62.0) 69 (58.5) 74 (62.2) 78 (65.5) • Headache TEAE rel

10. Slide 10: Conclusions

    Conclusions • Verekitug every 12 or 24 weeks led to statistically significant, clinically meaningful reductions in asthma exacerbations • Verekitug improved secondary outcomes of FEV1, ACQ-6, and FeNO, with improvements observed as early as week 2 in all regimens • AAER reductions were up to 87% and

11. Slide 11: Acknowledgments and funding

    Acknowledgments and funding • We would like to thank all trial participants, their families and caregivers, as well as investigators and site staff • Under the direction of the authors, medical writing assistance was provided by Lewis Cawkwell, PhD, of Parexel International, and supported by Upstrea

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