verekitug (UPB-101) / Upstream Bio - LARVOL DELTA

A Long-Term Safety and Efficacy Study of Verekitug (UPB-101) in Adult Participants With Severe Asthma (VALOUR) (clinicaltrials.gov) - P2 | N=436 | Not yet recruiting | Sponsor: Upstream Bio Inc.

New P2 trial • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases

In silico system pharmacology modeling provides insights into a mechanism for greater potency of TSLP/TSLPR pathway inhibition with verekitug, a novel antibody antagonist of TSLPR, as compared to tezepelumab (EAACI 2025) - No abstract available

Immunology • CRLF2 • TSLP

Upstream Bio Reports Fourth Quarter and Full Year 2024 Financial Results and Recent Business Highlights (GlobeNewswire) - "'We closed 2024 and started 2025 with strong continued momentum, marked by the successful completion of enrollment in our Phase 2 clinical trial of verekitug in patients with CRSwNP in January 2025. We expect to report top-line data from this trial in the second half of 2025'...'We remain on track to dose the first patient in our COPD program in the second half of 2025 and, as previously reported, we expect to report top-line data from our ongoing Phase 2 clinical trial in severe asthma in the second half of 2026.'"

New trial • P2 data • Asthma • Chronic Obstructive Pulmonary Disease • Chronic Rhinosinusitis With Nasal Polyps

VIBRANT: A Study to Investigate the Efficacy and Safety of Verekitug (UPB-101) in Participants with Chronic Rhinosinusitis with Nasal Polyps (clinicaltrials.gov) - P2 | N=80 | Active, not recruiting | Sponsor: Upstream Bio Inc. | Enrolling by invitation ➔ Active, not recruiting | Trial completion date: Dec 2025 ➔ Aug 2025 | Trial primary completion date: Nov 2025 ➔ Jul 2025

Enrollment closed • Trial completion date • Trial primary completion date • Chronic Rhinosinusitis With Nasal Polyps • Immunology • Nasal Polyps • Otorhinolaryngology • Respiratory Diseases • Sinusitis

VIBRANT: A Study to Investigate the Efficacy and Safety of Verekitug (UPB-101) in Participants with Chronic Rhinosinusitis with Nasal Polyps (clinicaltrials.gov) - P2 | N=70 | Enrolling by invitation | Sponsor: Upstream Bio Inc. | Recruiting ➔ Enrolling by invitation

Enrollment status • Chronic Rhinosinusitis With Nasal Polyps • Immunology • Nasal Polyps • Otorhinolaryngology • Respiratory Diseases • Sinusitis

Upstream Bio Reports Third Quarter 2024 Financial Results and Recent Business Highlights (GlobeNewswire) - P1 | N=32 | NCT05448651 | Sponsor: Upstream Bio Inc. | "Commenced startup for a Phase 2 clinical trial in COPD; on track for first patient to be dosed in H2 2025....Upstream Bio presented clinical data from its Phase 1b multiple ascending dose trial of verekitug in adults with asthma....As previously reported, verekitug was well tolerated at all dose levels tested. Verekitug also demonstrated rapid and substantial treatment effects, including 100% TSLP receptor occupancy after one dose, up to 54% reduction in FeNO and up to 65% reduction in blood eosinophils at 12 weeks. These findings were sustained for up to 24 weeks after the last dose."

P1 data • Asthma • Chronic Obstructive Pulmonary Disease • Immunology

32-week data from a multiple ascending-dose study with verekitug, a novel antibody to the human TSLP receptor (TSLPR), in adults with asthma (ERS 2024) - "Verekitug was well tolerated and safe at all dose levels tested. Reductions in FeNO and EOS were rapid, substantial, and sustained. These data inform the phase 2 development of verekitug as a potential therapy for severe asthma and CRSwNP at dose intervals of up to 24 wks."

Clinical • Asthma • Chronic Rhinosinusitis With Nasal Polyps • Immunology • Inflammation • Nasal Polyps • Otorhinolaryngology • Respiratory Diseases • Sinusitis • CRLF2 • TSLP

VIBRANT: A Study to Investigate the Efficacy and Safety of Verekitug (UPB-101) in Participants With Chronic Rhinosinusitis With Nasal Polyps (clinicaltrials.gov) - P2 | N=70 | Recruiting | Sponsor: Upstream Bio Inc. | Trial completion date: Apr 2025 ➔ Dec 2025 | Trial primary completion date: Mar 2025 ➔ Nov 2025

Trial completion date • Trial primary completion date • Chronic Rhinosinusitis With Nasal Polyps • Immunology • Nasal Polyps • Otorhinolaryngology • Respiratory Diseases • Sinusitis

A Multiple Ascending-dose Study With Verekitug, A Novel Antibody to the Human Thymic Stromal Lymphopoietin Receptor, in Adults With Asthma (ATS 2024) - "Verekitug was well-tolerated and safe at all dose levels tested. PK was linear and dose-proportional following multiple dosing with complete receptor occupancy at the first post-dose measurement. Reductions in blood eosinophils and FeNO were rapid and substantial."

Clinical • Stroma • Asthma • Chronic Rhinosinusitis With Nasal Polyps • Immunology • Inflammation • Nasal Polyps • Otorhinolaryngology • Pain • Pulmonary Disease • Respiratory Diseases • Sinusitis • CRLF2 • TSLP

Upstream Bio to Present Results from a Dose Ranging Study of Verekitug (UPB-101) in Adults with Asthma at the American Thoracic Society (ATS) International Conference (GlobeNewswire) - "Upstream Bio...today announced an upcoming presentation featuring clinical data from its dose-ranging study of verekitug (UPB-101) in adults with asthma, at the American Thoracic Society (ATS) International Conference in San Diego, CA on Wednesday, May 22, 2024, at 8:15 A.M. PT."

Clinical data • Asthma

Upstream Bio Initiates a Phase 2 Clinical Trial of Verekitug (UPB-101) in Severe Asthma and Doses First Patients (Businesswire) - "Upstream Bio....today announced the dosing of the first patients in its Phase 2 VALIANT clinical trial of verekitug (UPB-101) in patients with severe asthma....The study will evaluate verekitug’s efficacy in the treatment of severe asthma as reflected by the registrational primary endpoint of the annual asthma exacerbation rate (AAER)."

Trial status • Asthma • Immunology

A Study to Investigate the Efficacy and Safety of Verekitug (UPB-101) in Adult Participants With Severe Asthma (VALIANT) (clinicaltrials.gov) - P2 | N=436 | Recruiting | Sponsor: Upstream Bio Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases

A Study to Investigate the Efficacy and Safety of Verekitug (UPB-101) in Adult Participants With Severe Asthma (VALIANT) (clinicaltrials.gov) - P2 | N=436 | Not yet recruiting | Sponsor: Upstream Bio Inc.

New P2 trial • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases

Investigational thymic stromal lymphopoietin inhibitors for the treatment of asthma: a systematic review. (PubMed, Expert Opin Investig Drugs) - "Currently, the only TSLP inhibitor approved for the treatment of severe asthma is the immunoglobulin G (IgG) 2λ anti-TSLP monoclonal antibody (mAb) tezepelumab...Ecleralimab, an inhaled antibody fragment antigen binding, shows promising evidence in enhancing efficacy and reducing systemic adverse events. SAR443765, with its NANOBODY® formulation and bispecific inhibition of TSLP and IL-13, offers improved tissue penetration and efficacy. The mAB TQC2731 exhibits high in vitro bioactivity, and the strength of the mAb UPB-101 is to act against the TSLP receptor...This systematic review highlights the potential of TSLP inhibitors as valuable additions to asthma treatment, even in milder forms of the disease. Future research and cost-reduction efforts are needed to expanding access to these promising therapies."

Journal • Review • Stroma • Asthma • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • CRLF2 • IL13 • TSLP

Upstream Bio Announces Dosing of First Patients in a Phase 2 Clinical Trial of Verekitug (UPB-101) in Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) (Yahoo Finance) - "Upstream Bio...today announced the dosing of the first patients in a Phase 2 clinical trial of verekitug in patients with chronic rhinosinusitis with nasal polyps (CRSwNP)....The CRSwNP Phase 2 study is a randomized, double-blind, placebo-controlled study evaluating a dose of 100 mg administered subcutaneously in a single injection every 12 weeks. The study will evaluate verekitug’s efficacy in the treatment of CRSwNP with a primary endpoint of reduction in nasal polyp score. Data from the combination of Upstream Bio’s Phase 2 studies in CRSwNP and asthma will inform the dose regimen for Phase 3 in both indications."

Trial status • Chronic Rhinosinusitis With Nasal Polyps • Immunology

VIBRANT: A Study to Investigate the Efficacy and Safety of Verekitug (UPB-101) in Participants With Chronic Rhinosinusitis With Nasal Polyps (clinicaltrials.gov) - P2 | N=70 | Recruiting | Sponsor: Upstream Bio Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Chronic Rhinosinusitis With Nasal Polyps • Immunology • Nasal Polyps • Otorhinolaryngology • Respiratory Diseases • Sinusitis

VIBRANT: A Study to Investigate the Efficacy and Safety of UPB-101 in Participants With Chronic Rhinosinusitis With Nasal Polyps (clinicaltrials.gov) - P2 | N=70 | Not yet recruiting | Sponsor: Upstream Bio Inc.

New P2 trial • Chronic Rhinosinusitis With Nasal Polyps • Immunology • Nasal Polyps • Otorhinolaryngology • Respiratory Diseases • Sinusitis

Upstream Bio Announces Positive Phase 1b Interim Data in Asthma and Company Progress Toward Phase 2 (Businesswire) - P1 | N=32 | NCT05448651 | Sponsor: Upstream Bio Inc. | "Upstream Bio...announced positive interim results in its Phase 1b clinical study of UPB-101, a thymic stromal lymphopoietin receptor (TSLPR) inhibitor....The interim data results demonstrated favorable safety, tolerability, immunogenicity, pharmacokinetic (PK) and pharmacodynamic (PD) markers that strongly support moving to Phase 2....At the week 24 interim evaluation, UPB-101 was safe and well tolerated and demonstrated full receptor saturation in all doses studied. Furthermore, UPB-101 was demonstrated to be a potent suppressor of the disease-related biomarker, fractional exhaled nitric oxide (FeNO). PK/PD modelling indicated a maximal FeNO reduction from baseline (Emax) of 43%....Detailed topline results are expected to be presented at an upcoming congress."

P1 data • Asthma • Immunology

Safety and Biologic Impact (Pharmacodynamics) of Repeated Injections and Increasing Amounts of UPB-101 in Asthmatics (clinicaltrials.gov) - P1 | N=32 | Completed | Sponsor: Upstream Bio Inc. | Active, not recruiting ➔ Completed

Trial completion • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases

Safety and Blood Levels After a Single Injection of UPB-101 in Healthy Japanese and Non-Japanese Non-East Asian Adults (clinicaltrials.gov) - P1 | N=32 | Completed | Sponsor: Upstream Bio Inc. | Active, not recruiting ➔ Completed

Trial completion

Upstream Bio Announces $200M Series B Financing to Advance UPB-101 for Allergic and Inflammatory Diseases (Businesswire) - "Upstream Bio...today announced the completion of a $200 million Series B financing....The capital raised will fund Upstream’s next stage of clinical development for UPB-101, a monoclonal antibody targeting the TSLP receptor (TSLPR) currently in Phase 1b development for the treatment of asthma. Upstream will pursue registrational Phase 2 clinical trials in asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) thereafter. In parallel with Phase 2 studies, Upstream plans to conduct substantial translational, manufacturing and device development activities to be prepared for a swift transition to Phase 3 development. The Series B raise is sized to support development of a highly differentiated target product profile that will be compelling for regulatory, market access and commercialization activities."

Financing • Asthma • Chronic Rhinosinusitis With Nasal Polyps • Immunology • Respiratory Diseases

A Phase 1 First-in-Human Single Ascending-dose Study With a Novel Antibody to the Human Thymic Stromal Lymphopoietin Receptor (ATS 2023) - " UPB-101 was well-tolerated, safe, and displayed linear and dose proportional PK. A low titer ADA response was detected in some subjects; however, there was no significant impact on either safety or PK. UPB-101 has been advanced to Phase 1b development."

P1 data • Stroma • Inflammation • Nephrology • Pain • Renal Calculi • Women's Health • CRLF2 • TSLP

Upstream Bio to Present New Clinical Data from Phase 1 Study of UPB-101 at the American Thoracic Society (ATS) International Conference (Businesswire) - "Upstream Bio...today announced an upcoming poster presentation featuring new clinical data from its Phase 1 clinical study of UPB-101 at the American Thoracic Society (ATS) International Conference, happening May 19-24 in Washington, DC. The poster...will be presented on Monday, May 22, 2023, at 11:30am ET. An e-poster will also be made available to conference attendees during the event."

P1 data • Asthma • Immunology • Respiratory Diseases

Safety and Biologic Impact (Pharmacodynamics) of Repeated Injections and Increasing Amounts of UPB-101 in Asthmatics (clinicaltrials.gov) - P1 | N=32 | Active, not recruiting | Sponsor: Upstream Bio Inc. | Recruiting ➔ Active, not recruiting | Trial completion date: Jul 2023 ➔ Oct 2023 | Trial primary completion date: May 2023 ➔ Aug 2023

Enrollment closed • Trial completion date • Trial primary completion date • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases

Safety and Blood Levels After a Single Injection of UPB-101 in Healthy Japanese and Non-Japanese Non-East Asian Adults (clinicaltrials.gov) - P1 | N=32 | Active, not recruiting | Sponsor: Upstream Bio Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed