Upstream Bio : Corporate Presentation May 2026 (May 13, 2026)

Published: 2026-05-13 15:42:18 ET UPB

Published on 05/13/2026 at 03:42 pm EDT

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Corporate Presentation

May 2026

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About Upstream Bio

Clinical-stage immunology company focused on severe respiratory diseases

Pursuing Phase 3 development strategy designed to deliver best-in-class efficacy with a single quarterly at-home injection in broad patient populations

Robust clinical data and comprehensive market research in severe asthma and CRSwNP provide a clear path to maximize the potential commercial value of verekitug

The Company plans to:

Engage with FDA in mid-2026 and initiate Phase 3 trials in severe asthma and CRSwNP in Q1 2027

Begin preparations for Phase 3 trial in COPD; enrollment in VENTURE capped, with data expected in H2 2027

Developing verekitug, the only known clinical-stage antagonist of the TSLP receptor

→ Verekitug's pharmacology is unique and characterized by high-potency inhibition of TSLP signaling

→ Focused on multiple indications with high unmet need:

Completed Phase 2 trials in severe asthma and CRSwNP

Ongoing Phase 2 trial in COPD

Addressing significant commercial opportunities

→ Severe asthma and COPD markets expected to drive a

Existing capital is expected to fund planned operations through 2027

$35B+ global biologics market by 2033

3 TSLP, thymic stromal lymphopoietin; CRSwNP, chronic rhinosinusitis with nasal polyps; COPD, chronic obstructive pulmonary disease.

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Leadership team

Deep experience and complementary areas of expertise

E X EC UT IVE T E A M

Rand Sutherland, MD

Chief Executive Officer

Aaron Deykin, MD

Chief Medical Officer & Head of R&D

Mike Gray

Chief Financial Officer & Chief Operating Officer

Allison Ambrose

General Counsel

Lisa Fiering

SVP, People & Culture

Adam Houghton, PhD

Chief Business Officer

Stacy Price

Chief Technology Officer

4 All trademarks are property of their respective owners

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Mechanism of verekitug inhibition of TSLP signaling1,2,3

About verekitug

Verekitug is the only known clinical-stage antagonist of the TSLP receptor

Fully-human IgG1 antibody, discovered by Astellas/Regeneron and acquired by Upstream Bio

Verekitug's potency is approximately 300-fold greater than that of tezepelumab, enabling both robust efficacy and extended interval dosing

Comprehensive dataset from ~500 participants treated with verekitug across Phase 1 & 2 trials

Demonstrated strong clinical benefit and favorable safety with every 12-week dosing in both severe asthma and CRWsNP

1 Verstraete et al, Nat Commun, (2017). 2 Numazaki et al, J Pharmacol Exp Ther, (2022). 3 Chowdhury et al, ERS presentation, (2025).

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Developing verekitug in TSLP-driven severe respiratory diseases

DEVELOPMENT

INDICATIONS PRECLINICAL

PHASE 1

PHASE 2

PHASE 3

MILESTONES

Chronic Rhinosinusitis with Nasal Polyps (CRSwNP)

Phase 3 Initiation Q1 2027*

Severe Asthma

Phase 3 Initiation Q1 2027*

Enrollment Completed March 2026†

Chronic Obstructive Pulmonary Disease (COPD)

Data Expected H2 2027*

* Anticipated timing. Phase 3 preparations ongoing in CRSwNP and severe asthma.

6 † VALOUR is a Phase 2 long-term safety and efficacy study of verekitug in eligible participants with severe asthma who completed the Phase 2 VALIANT study.

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Market Research Overview

Prioritizing a high-efficacy quarterly regimen to maximize verekitug's commercial value

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Large and growing commercial opportunity in core indications, with asthma and COPD alone expected to be a $35B+ global biologics market in 2033

Severe

Asthma

2023: $7.5B2

Biologic eligible severe asthma patients in the US1

of biologic sales

of eligible patients with severe asthma are currently estimated to

Projected global sales for all approved biologics in severe asthma by 20332

Tezspire is projected to reach global annual sales of over $3B for severe asthma alone in 20322

2032e: $12.6B2

are in the US2

receive biologic therapies1,3

CRSwNP

2025: >$1.5B5,6

~300K

Biologic eligible CRSwNP patients in the US1

>$1.5B

Current global biologics sales in CRSwNP alone estimated to be $1.5B+ annually5,6

>$600M

Tezspire is projected to reach global annual sales of over

$600M for CRSwNP by early 2030s7

COPD

2033e: $23B2

~1.1M

COPD patients inadequately controlled on triple-therapy in the US2

~3.5M

Projected COPD patients inadequately controlled on triple-therapy in the US by 20332

~70%

of 2033 COPD biologic sales are expected to be in the US2

>$5B

Tezspire is projected to reach global annual sales of over $5B for COPD alone in 20332, if approved in this indication

1 Upstream Bio Analysis 2025. 2 Datamonitor. 3 IQVIA Claims Data (Unique Asthma Pts on Biologics FY '24, Pt Growth Rate '20-'24). 4 Amgen Investor Presentation May 2024. 5 Symphony Claims Data

8 (June '24 - May '25). 6 Manufacturer Sales and Pricing Disclosures. 7 Analyst projections.

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Targeting best-in-class efficacy with quarterly at-home dosing to address patient needs and maximize commercial value

Efficacy differentiation is the primary driver of clinical impact and commercial success

Market research to date shows:

Physician treatment decisions in asthma and CRSwNP primarily driven by efficacy

Physicians unwilling to trade off reductions in efficacy for extended dosing intervals

Strong efficacy must be delivered as a component of extended-dosing regimens

The majority of dosing convenience value is captured with quarterly administration

Market research to date shows:

Most of the benefit from improved dosing frequency is achieved by moving from every 2- or 4-week to quarterly dosing

Incremental increases in product value with less frequent dosing are modest and eroded by even minor losses in efficacy

Prioritizing verekitug development strategy to deliver best-in-class efficacy with quarterly dosing

In Phase 2 trials in both severe asthma and CRSwNP, quarterly dosing delivered efficacy outcomes that met or exceeded available biologics

A high-dose quarterly regimen is predicted to deliver the optimal combination of efficacy and convenience

These findings are consistent across multiple waves of qualitative and quantitative market research conducted with HCPs, patients, and payers

Trinity Quantitative Research with N=100 HCPs and N=120 Patients; Trinity Qualitative Research with N=10 Payers Insights represent Trinity's interpretation of market research findings

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Market research shows efficacy is the primary driver for decision-making among HCPs in both asthma and CRSwNP

For instance, ~70% of HCPs reported that they would switch their asthma patients to another biologic if they observed waning efficacy of a q24w drug

Importance of Product Attributes for Asthma and CRSwNP

% HCPs ranking attribute as the top 3 most important when selecting biologics for asthma & CRSwNP patients

Product Attributes

Asthma

i.e., AAER, FEV1, and symptomology

CRSwNP

i.e., reduction NPS and improvement in NCS

Efficacy

100%

Safety

28%

21%

Dosing frequency

14%

July 2025 Trinity Research; N=210 Quantitative Survey

10 CRSwNP, chronic rhinosinusitis with nasal polyps; HCP, healthcare provider; NCS, nasal congestion score; NPS, nasal polyp score

Insights represent Trinity's interpretation of market research findings

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Phase 2 Top-Line Clinical Data Overview in Severe Asthma and CRSwNP

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Phase 3 strategy designed to maximize verekitug's commercial value by targeting best-in-class efficacy with at-home quarterly dosing

Deliver best-in-class efficacy with quarterly dosing in both severe asthma and CRSwNP

Strategy supported by strong clinical data package and comprehensive market research in both indications

Single high-dose injection, up to 400 mg* Convenient quarterly dosing regimen High and low-eosinophil populations

Self-administration via autoinjector at launch Parallel Phase 3 trials in severe asthma & CRSwNP

12 *Final dose and design pending FDA engagement

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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

Top-line results for Phase 2 VIBRANT study of verekitug in CRSwNP

Potential to deliver best-in-class efficacy in severe asthma and CRSwNP with a single high-dose quarterly injection

Phase 2 trials demonstrate positive treatment effects in high and low eosinophil subgroups in severe asthma and CRSwNP

Well-characterized immunogenicity profile has no meaningful impact on safety or efficacy

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Top-line 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)

100 mg q12w vs placebo

Met key secondary endpoints,

including NCS reduction of -0.8 (p=0.0003*) and 76% reduction in need for surgery/steroids (p=0.03*)

Generally well tolerated, no SAEs observed

Observed clinical benefit at 12-week dosing interval supports potential utility in severe asthma

and other Type 2 inflammatory diseases

*Nominal p values

14 NPS, nasal polyp score; NCS, nasal congestion score; q12w, every 12 weeks; SAEs, serious adverse events. Top-line data reported Sept 2025.

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Top-line 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

Clinically meaningful improvements

in lung function (FEV1) and exhaled nitric oxide (FeNO)

56% reduction in AAER (p<0.0003) 122mL1improvement in FEV1 20.4ppb1reduction in FeNO 43.5%1reduction vs baseline

0.21 point1,2reduction in ACQ-6

Generally well tolerated, with a safety profile consistent with prior studies

100 mg q12w vs placebo dataset

1 Placebo-corrected. 2 At 24 week

15 AAER, annualized asthma exacerbation rates; FEV1, forced expiratory volume in 1 second; FeNO, fractional exhaled nitric oxide; ACQ-6, asthma control questionnaire. Top-line data reported Feb 2026.

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Consistent and favorable safety profile across both Phase 2 trials

1 * 3

→ Overall incidence of AEs was similar across treatment groups

→ TEAEs related to study treatment occurred more frequently in placebo

→ No SAEs reported

→ Most common TEAEs in study population (>5%) were consistent with CRSwNP symptoms, which occurred frequently in the placebo group

→ Overall incidence of TEAEs was similar across treatment groups

→ Serious TEAEs were similar across treatment groups

*Safety follow-up is ongoing.

AE, adverse event; q×w, every × weeks; TEAE, treatment-emergent adverse event. SAEs, serious adverse events.

16 1 Top-line data reported Sept 2025. 2 Data on file. 14.3.1.2.

3 Top-line data reported Feb 2026. 4 Data on File. Table 14.3.1.1. 5 Data on File. Table 14.3.1.2. 3.

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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

Top-line results for Phase 2 VIBRANT study of verekitug in CRSwNP

Phase 2 trials delivered efficacy outcomes meeting or exceeding approved biologics in both severe asthma and CRSwNP with 100 mg dosed every 12 weeks

Favorable safety profile, consistent across clinical development program

Phase 2 trials demonstrate positive treatment effects in high and low eosinophil subgroups in severe asthma and CRSwNP

Well-characterized immunogenicity profile has no meaningful impact on safety or efficacy

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In CRSwNP, verekitug led to significant and clinically meaningful improvements in NPS and all key secondary endpoints

Verekitug

Placebo

Treatment difference

Primary Endpoint

Key

NPS change from baseline* -2.1 (0.26) -0.3 (0.27) -1.8 (-2.51, -1.03)

p<0.0001

NCS change from baseline* -1.5 (0.14) -0.8 (0.14) -0.8 (-1.17, -0.37)

p=0.0003†

LMK change from baseline* -9.0 (0.8) -1.0 (0.8) -8.0 (-10.2, -5.9)

p<0.0001†

-4.3 (-6.94, -1.65)

Secondary Endpoints

TSS change from baseline* -10.1 (0.94) -5.8 (0.95)

p=0.0018†

DSS change from baseline* -1.5 (0.15) -0.6 (0.16) -0.9 (-1.29, -0.42)

p=0.0002†

% requiring sinus surgery and/or SCS

7.3% 25.0% 76% reduction** p=0.03†

*Change from baseline is least square (LS) mean (standard error) and treatment difference is LS mean difference vs placebo (95% confidence interval)

**Risk reduction vs placebo

†p values for secondary endpoints are nominal and not adjusted for multiple comparisons.

LMK, Lund-Mackay; TSS, total symptom score; DSS, difficulty with smell score; SCS, systemic corticosteroids.

18 NPS range: 0-8; NCS range: 0-3 over 2 weeks; LMK CT score (0-24); TSS range: 0-24; 8 symptoms over 2 weeks; DSS range: 0-3 over 2 weeks.

Top-line data reported Sept 2025. Data on file: Tables 14.2.1.1.1, 14.2.2.1.1, 14.2.2.2.1, 14.2.2.3.1, 14.2.2.9.1, 14.2.2.4.1

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In severe asthma, verekitug led to meaningful improvements in primary and secondary endpoints at week 24 that were generally sustained to week 60

Timing

Endpoint

Verekitug 100 mg q12w

Verekitug 400 mg q24w

Verekitug 100 mg q24w

Baseline

AAER*

N=121

N=118

N=120

through week

Rate ratio vs placebo (95% CI)

0.44 (0.28, 0.69)

0.61 (0.40, 0.93)

0.51 (0.33, 0.79)

P value

0.0003

0.0227

0.0028

Change from baseline to week 24*

Pre-BD FEV1

LSM difference vs placebo mL (95% CI) P value

N=106

112 (8, 216)

0.0350

N=107

133 (30, 237)

0.0119

N=103

-4 (-108, 100)

0.9419

ACQ-6

LSM difference vs placebo (95% CI)

N=114

-0.21 (-0.43, 0.01)

N=111

-0.34 (-0.57, -0.12)

N=112

-0.23 (-0.45, -0.01)

P value

0.0651

0.0027

0.0447

Change from baseline to week 60*

Pre-BD FEV1

LSM difference vs placebo mL (95% CI) P value

N=18

122 (-90, 335)

0.2589

N=18

139 (-76, 353)

0.2047

N=17

18 (-198, 235)

0.8678

ACQ-6

LSM difference vs placebo (95% CI)

N=19

0.06 (-0.42, 0.55)

N=19

-0.21 (-0.70, 0.28)

N=17

-0.24 (-0.74, 0.26)

P value

0.8000

0.3928

0.3541

*AAER, Rate Ratio, 95% confidence intervals, and p-values are from a negative binomial regression model with number of asthma exacerbations as the dependent variable and fixed effects for study treatment, region, baseline steroid use as randomized, and baseline eosinophil level as randomized.

19 Top-line data reported Feb 2026. Data on File. Table 14.2.1.1.1; Table 14.2.2.2.1.3; Table 14.2.2.3.2; Table 14.2.2.4.2

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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

LSM change from baseline in FEV1(liters)

0.5

FEV1over 60 weeks1

FeNO over 60 weeks2

LSM percent change from baseline in

FeNO (ppb)

0.4 40

0.3 20

0.2 0

0.1 -20

0.0 -40

-0.1

No. of participants

0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60

Week

Verekitug 100 mg q12w

Verekitug 400 mg q24w

Verekitug 100 mg q24w

Placebo

118 114 111 110 106 109 106 66 43 35 21 18

-60

No. of participants

0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60

Week

Verekitug 100 mg q12w

Verekitug 400 mg q24w

Verekitug 100 mg q24w

Placebo

121 118 117 114 108 115 113 78 69 64 47 40 38 23 19

117 110 111 111 110 114 107 67 44 32 20 18

116 110 110 109 112 109 103 62 40 31 21 17

119 113 110 110 109 105 106 64 43 32 22 18

118 115 115 112 109 112 109 82 66 60 46 38 34 21 18

119 115 115 113 113 113 111 84 66 62 42 35 31 21 17

119 109 110 113 110 108 108 83 67 60 43 40 32 23 19

Secondary endpoints were not powered for statistical significance.

20 FeNO, fractionated exhaled nitric oxide; FEV1, forced expiratory volume in 1 second; LSM, least squares mean; ppb, parts per billion; q×w, every × weeks. Top-line data reported Feb 2026. 1 Data on file. Table 14.2.2.2.1.3. 2 Data on file. Table 14.2.2.3.5.

Disclaimer

Upstream Bio Inc. published this content on May 13, 2026, and is solely responsible for the information contained herein. Distributed via Public Technologies (PUBT), unedited and unaltered, on May 13, 2026 at 19:41 UTC.