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

Mechanistic Drivers for Potent Pharmacodynamic Activity of Verekitug, a novel anti-TSLPR antibody (ERS 2025) - No abstract available

PK/PD data • CRLF2

Upstream Bio Announces First Patient Dosed in Phase 2 Clinical Trial of Verekitug in Chronic Obstructive Pulmonary Disease (COPD) (GlobeNewswire) - "Upstream Bio, Inc...announced that the first patient has been dosed in the Company’s Phase 2 clinical trial evaluating verekitug in patients with COPD, broadening the global development program for verekitug into a third indication...VENTURE (NCT06981078) is a randomized, double-blind, placebo-controlled trial designed to assess the efficacy and safety of verekitug in approximately 670 adults with moderate-to-severe COPD. Participants will be randomized to receive verekitug at doses of 100 mg once every 12 weeks, 400 mg once every 24 weeks, or placebo, over treatment periods of between 60 weeks and up to 108 weeks."

Trial status • Chronic Obstructive Pulmonary Disease

A Phase 2b Study to Assess the Efficacy and Safety of Verekitug in Participants With COPD (clinicaltrials.gov) - P2 | N=666 | Recruiting | Sponsor: Upstream Bio Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases

Translational Data Illustrate a Mechanism of Greater Potency with Verekitug, a Novel Antibody Antagonist of the TSLP Receptor (GlobeNewswire) - "'We look forward to further assessing the potential translation of this unique mechanism into clinical benefit in patients with severe respiratory diseases, first with top-line Phase 2 clinical data in CRSwNP in the third quarter of this year followed by data in severe asthma in the first half of 2026'....Across a range of doses, PK/PD model simulations predict complete and sustained inhibition of the TSLP/TSLPR complex with verekitug compared to tezepelumab. Dose-response model simulations predict that potent inhibition of the TSLP/TSLPR complex would result in a greater reduction in fractional exhaled nitric oxide (FeNO), a biomarker of lung inflammation...These data indicate the differentiated mechanism of TSLP receptor targeting with verekitug may drive the greater potency observed with this approach as compared with targeting the TSLP ligand."

Clinical • P2 data • PK/PD data • Asthma • Chronic Rhinosinusitis With Nasal Polyps • Immunology

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) - "Conclusion The semi-mechanistic PK/PD modeling using clinical pharmacodynamic data, model assumptions and parameterization, provides a mechanistic understanding for the observed greater potency of targeting TSLPR with verekitug as compared to the ligand. Whether this difference in potency translates into augmented clinical efficacy with verekitug is currently under investigation."

Immunology • CRLF2 • TSLP

A Study to Investigate the Efficacy and Safety of Verekitug (UPB-101) in Adult Participants With Severe Asthma (VALIANT) (clinicaltrials.gov) - P2 | N=479 | Active, not recruiting | Sponsor: Upstream Bio Inc. | Recruiting ➔ Active, not recruiting

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

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

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

Upstream Bio to Present Mechanistic Insights into Verekitug’s Enhanced Potency via TSLP Receptor Targeting at European Academy of Allergy and Clinical Immunology (EAACI) Congress 2025 (GlobeNewswire) - "Upstream Bio, Inc...announced an upcoming presentation at the European Academy of Allergy and Clinical Immunology (EAACI) Congress 2025 in Glasgow, UK, on Sunday, June 15, 2025. The presentation features translational pharmacology modeling data that supports Thymic Stromal Lymphopoietin (TSLP) receptor targeting with verekitug as a mechanism for greater potency when compared to treatment approaches that target the TSLP ligand."

Clinical • Immunology

Biologic Therapies for Severe Asthma: Current Insights and Future Directions. (PubMed, J Clin Med) - "The current biologics for severe asthma treatment include omalizumab (anti-IgE), mepolizumab and reslizumab (anti-IL-5), benralizumab (anti-IL-5 receptor), dupilumab (anti-IL-4/IL-13), and tezepelumab (anti-TSLP)...Depemokimab is an ultra-long-acting anti-IL-5 antibody with promising results in phase III trials as a twice-yearly biologic for T2-high asthma. Verekitug follows a similar dosing concept, targeting TSLP, but is still undergoing phase II trials. Itepekimab and astegolimab are two anti-IL-33 antibodies that could have a role in the future treatment of severe asthma. Tezepelumab is in a phase III clinical trial for CRSwNP. Besides new drugs, there is still a need for major research into biologics in severe asthma cases, namely with comparative studies, better biomarkers for predicting response, and the determination of optimal treatment duration."

Journal • Review • Asthma • Chronic Rhinosinusitis With Nasal Polyps • Immunology • Inflammation • Nasal Polyps • Otorhinolaryngology • Pulmonary Disease • Respiratory Diseases • Sinusitis • IL13 • IL33 • IL4 • IL5

A Phase 2b Study to Assess the Efficacy and Safety of Verekitug in Participants With COPD (clinicaltrials.gov) - P2 | N=666 | Not yet recruiting | Sponsor: Upstream Bio Inc.

New P2 trial • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases

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

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