Upstream Bio, Inc. · NASDAQ:UPB
Upstream Bio — Investor Presentation (May 2025)
30 slides from Upstream Bio's investor presentation, May 2025
Slide 1: Corporate Presentation May 2025
Corporate Presentation May 2025
Slide 2: Disclaimer
Disclaimer This presentation contains forward-looking statements of Upstream Bio, Inc. (“Upstream,” “the Company,” “we,” “us,” or “our”) that involve substantial risks and uncertainties. All statements other than statements of historical facts contained in this presentation, including statements reg
Slide 3: Corporate Overview
Corporate Overview • Clinical-stage company developing verekitug for severe respiratory diseases • Verekitug is the only known clinical-stage antibody targeting the TSLP receptor – Antibody discovered by Astellas/Regeneron, acquired by Upstream • Phase 1 clinical trials have demonstrated a different
Slide 4: Asthma MAD data provide proof of concept, support differentiated profile
Asthma MAD data provide proof of concept, support differentiated profile Attribute Verekitug Tezepelumab Dupilumab Mepolizumab Target TSLP Receptor TSLP Ligand IL-4/-13 Receptor IL-5 Ligand Dosing Interval 12, 24 weeks 4 weeks2 2 weeks3 4 weeks5 0.5 mL (100 mg) Injection Volume 1.91 mL2 2 mL3 1 mL5
Slide 5: Developing verekitug in multiple indications with unmet need
Developing verekitug in multiple indications with unmet need DEVELOPMENT TARGET PRECLINICAL PHA SE 1 PHA SE 2 † PHA SE 3 NEX T ANTICIPATE D MIL ESTONE(S) Phase 2 Top-line Data 1H 2026 Severe Asthma Phase 2 LTE initiation 2Q 2025 Chronic Rhinosinusitis with Nasal Polyps Phase 2 Top -line D ata 3Q 202
Slide 6: Leadership team
Leadership team Deep experience and complementary areas of expertise Executive Team Functional Leadership Maryse Courval, MS Lisa Fiering Amy Iannelli Ashish Kalra, PhD Rohan Lathia Rand Sutherland, MD Aaron Deykin, MD VP, Clinical Operations SVP, People & Culture VP, Finance VP, Translational VP, B
Slide 7: Targeting TSLP receptor with verekitug: Severe Asthma, COPD and CRSwNP
Targeting TSLP receptor with verekitug: Severe Asthma, COPD and CRSwNP
Slide 8: TSLP is an upstream mediator of key inflammatory pathways
TSLP is an upstream mediator of key inflammatory pathways • An “alarmin” cytokine at mucosal surfaces – Produced by epithelial cells, keratinocytes and fibroblasts response to stress, injury • Broadly-expressed heterodimeric receptor TSLP TSLP TSLP comprised of the TSLP receptor and IL-7R • Signali
Slide 9: TSLP signaling is linked to a variety of indications
TSLP signaling is linked to a variety of indications Verekitug TSLP receptor inhibitor potentially has broad applicability Respiratory Dermatology – Severe Asthma* – Atopic Dermatitis – CRSwNP* – Bullous Pemphigoid – COPD* – Prurigo Nodularis – Bronchiectasis – Eczema Herpeticum – Idiopathic Pulmona
Slide 10: Asthma is a chronic inflammatory disease of the airways
Asthma is a chronic inflammatory disease of the airways Pathogenesis • Characterized by episodic symptoms – Chest tightness – Shortness of breath – Cough • Caused by narrowing of the bronchioles – Edema – Hyperresponsiveness → muscle contraction – Mucus production Epidemiology • >25M Americans affec
Slide 11: COPD is a chronic inflammatory disease of the lung and airways
COPD is a chronic inflammatory disease of the lung and airways Pathogenesis • COPD is characterized by structural abnormalities Healthy COPD of the airway, lung parenchyma and pulmonary vasculature due to chronic inflammation caused by recurrent exposure to external irritants (e.g., tobacco smoke, a
Slide 12: CRSwNP is a chronic upper airway inflammatory disease with significant unmet need
CRSwNP is a chronic upper airway inflammatory disease, with significant unmet need and a strong association with asthma Pathogenesis Coronal CT Scans • CRSwNP is characterized by chronic inflammation Healthy1 CRSwNP2 of the sinonasal mucosa with the presence of nasal polyps • It is estimated that 40
Slide 13: Clinical Data Overview
Clinical Data Overview
Slide 14: Verekitug has demonstrated a differentiated profile to date
Verekitug has demonstrated a differentiated profile to date Phase 1 data from 120 Attribute Verekitug Tezepelumab Dupilumab Mepolizumab participants (88 healthy Target TSLP Receptor TSLP Ligand IL-4/-13 Receptor IL-5 Ligand volunteers and 32 patients with asthma) indicate: Dosing Interval 12, 24 wee
Slide 15: First-in-human study supported tolerability and potential for extended dosing intervals
First-in-human study supported tolerability and potential for extended dosing intervals • Single doses of verekitug ranging from 0.03-10 Predicted mean serum verekitug (μg/mL) mg/kg were generally well tolerated in healthy volunteers – No treatment-emergent adverse events leading to study withdrawal
Slide 16: MAD study designed to evaluate PD effects in asthma patients and inform Phase 2
MAD study designed to evaluate PD effects in asthma patients and inform Phase 2 dose selection Study results presented at American Thoracic Society International Conference in May 2024 Key eligibility criteria Primary objective: • Adults with asthma, aged 18-60 years 100 mg verekitug (n=6) or PBO (n
Slide 17: MAD study showed a generally favorable tolerability profile
MAD study showed a generally favorable tolerability profile Treatment emergent adverse events were mild or moderate >90% of TEAEs were deemed unrelated to study drug 100 mg Q4W 200 mg Q4W 300 mg Q12W 25 mg X 1 Placebo Overall (N=6) (N=6) (N=6) (N=6) (N=8) (N=32) Number of TEAE 19 17 12 9 25 82 Numbe
Slide 18: Verekitug MAD data support potentially differentiating extended interval dosing
Verekitug MAD data Observed PK data aligned with SAD study-based support potentially PK model simulations differentiating extended interval dosing UPB-101 (ug/mL) (ug/mL) 100 mg Q4W (3 doses) 100 200 mg Q4W (3 doses) 300 mg Q12W (2 doses) Serumverekitug 25 mg SD 10 1 MeanSerum 0.1 Mean LLOQ 0.01 0 4
Slide 19: 32-week data showed substantial PD effects up to 24 weeks after last dose
Blood Eos FENO 32-week data showed substantial 500 80 (cells/μl, mean ± SEM) (ppb, mean ± SEM) 400 60 Eosinophils PD effects for up to 24 weeks 300 FeNO 40 200 20 100 after last dose 0 500 0 4 8 12 16 20 Elapsed Time (Weeks) 24 28 32 0 80 0 4 8 12 16 20 Elapsed Time (Weeks) 24 28 32 (cells/μl, mean
Slide 20: In Phase 1, verekitug led to a larger decrease in FENO than tezepelumab
In Phase 1, verekitug led to a larger decrease in FENO than reported with tezepelumab 20 FEFeNO (Change from BL) NO (Change from BL) Tezepelumab (Phase 2 and Phase 3) Change from baseline (ppb, mean ± SEM) 0 -28 at W12 -20 -47 at W12 -37 at w12 -40 ~-17 ppb 1000 Eosinophils (% Change from BL) at W12
Slide 21: Verekitug has shown high potency in asthma patients
Verekitug has shown high potency in asthma patients Modeled effect of verekitug on FENO is substantially greater than that published for tezepelumab Verekitug FENO PK/PD Model Parameters with Tezepelumab Verekitug Tezepelumab1 EMAX EC50 EC90 EMAX EC50 EC90 (reduction from BL) (µg/ml) (µg/ml) (reduct
Slide 22: PK modeling predicts selected doses will sustain concentrations above the FENO EC90
PK modeling predicts selected doses will sustain concentrations above the FENO EC90 throughout the dosing interval 100 mg Q12W 400 mg Q24W Solid line: median LLOQ: Lower Limit of PK Quantification 22
Slide 23: Phase 2 Clinical Trials
Phase 2 Clinical Trials
Slide 24: Summary of ongoing verekitug Phase 2 Clinical Trials
Summary of ongoing verekitug Phase 2 Clinical Trials Severe Asthma Phase 2 Study* CRSwNP Phase 2 Study Design • 4 arm, randomized (1:1:1:1), parallel group • 2 arm, randomized (1:1), parallel group Duration • 24 week minimum→ 60 week maximum treatment • 24 week treatment Doses • PBO, 100 mg Q24W, 40
Slide 25: Commercial Opportunity
Commercial Opportunity
Slide 26: Biologics sales in major asthma markets are growing at ~6% CAGR through 2032
Biologics sales in major asthma markets are growing at ~6% CAGR through 2032 to over $12B • Currently, ~1.3M biologic eligible Total Estimated 2023 Asthma severe asthma patients in the US1 Biologic Sales ~$7.5B Current Biologic Sales • 5 of 6 asthma biologics have across JP, EU, US2 Distribution2 ac
Slide 27: Biologics sales in major COPD markets expected to be approximately $23B by 2033
Biologics sales in major COPD markets are expected to be approximately $23B by 2033 • Currently ~1.1M severe COPD Total Estimated 2033 COPD patients in the US, expected to be Estimated Biologic Biologic Sales ~$23B ~3.5M globally by 20331 Sales Distribution in across JP, EU, US1 20331 • 5 of 7 COPD
Slide 28: Asthma biologics: A large and growing market
Asthma biologics: A large and growing market Market forecast to expand based on growth of both biologic use and asthma prevalence $12 Depemokimab (assuming approval) $10 Tezspire® (tezepelumab-ekko) Subcutaneous Injection 210 mg WW Annual Revenues ($B) $8 $6 Dupixent® (dupilumab) $4 Fasenra®(benrali
Slide 29: Market research suggests verekitug's clinical profile could drive high adoption
Market research suggest verekitug's clinical profile could drive high adoption ~90% of asthma and CRSwNP patients would “consider” switching to a product with a less-frequent dosing interval High Patient Interest of patients are moderately or highly likely to ask their provider >95% about a treatmen
Slide 30: Corporate Overview
Corporate Overview • Clinical-stage company developing verekitug for severe respiratory diseases • Verekitug is the only known clinical-stage antibody targeting the TSLP receptor – Antibody discovered by Astellas/Regeneron, acquired by Upstream • Phase 1 clinical trials have demonstrated a different