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09/30/2025 – 04:15 AM
– Data show verekitug prevents TSLP binding to the TSLP receptor by occupying ligand binding
sites –
– Additionally, findings show that verekitug outcompetes TSLP in the presence of preformed
heterodimeric receptor complexes –
– Data support the potential of verekitug’s unique mechanism of action to achieve a
differentiated therapeutic effect across a broad range of TSLP-driven severe respiratory diseases –
WALTHAM, Mass., Sept. 30, 2025 (GLOBE NEWSWIRE) — Upstream Bio, Inc. (Nasdaq: UPB), a clinical-stage
company focused on developing treatments for inflammatory diseases, with an initial emphasis on severe
respiratory disorders, has unveiled structural and mechanistic data demonstrating the potent pharmacodynamic
activity of verekitug. This activity stems from its unique approach to targeting the thymic stromal
lymphopoietin (TSLP) receptor. The findings were presented at the European Respiratory Society (ERS)
Congress, held in Amsterdam, Netherlands, from September 27 – October 1, 2025.
“We are continually enhancing our understanding of verekitug’s distinct TSLP receptor-targeting mechanism and
its critical role in producing the rapid and sustained effects observed to date,” stated Aaron Deykin, MD,
Chief Medical Officer and Head of R&D at Upstream Bio. “Early clinical data suggests the potency inherent in
this mechanism of action has the potential to translate to a differentiated clinical profile. In our recently
reported Phase 2 top-line data in chronic rhinosinusitis with nasal polyps (CRSwNP) patients, verekitug
achieved statistically significant and clinically meaningful improvements across multiple endpoints with only
once-every-12-weeks administration. We anticipate a Phase 2 read-out in severe asthma in Q1 2026 and look
forward to growing the verekitug clinical dataset.”
Preclinical and clinical data to date highlight verekitug’s strong inhibitory action on the TSLP receptor. Recent
clinical trials have shown rapid, substantial, and sustained TSLP receptor inhibition for up to 24 weeks
following the last dose. This mechanism potentially offers a unique clinical profile characterized by less
frequent dosing compared to existing approved biological therapies.
The presented data stems from mechanistic studies designed to clarify the factors driving the high magnitude of
effect seen with verekitug’s TSLP receptor inhibition. Key findings are summarized below:
- Verekitug demonstrates high affinity binding (KD <20pM) to the TSLP receptor. This high affinity
contributes to its ability to effectively block TSLP signaling. - High-resolution crystal structure analysis reveals that verekitug binds to and occupies the majority of the
TSLP binding sites on the TSLP receptor, effectively preventing TSLP from binding and initiating
downstream signaling. - Semi-mechanistic pharmacokinetic/pharmacodynamic (PK/PD) models suggest that the lower abundance and slower
turnover rate of the TSLP receptor, compared to the TSLP ligand, may contribute to the heightened potency
of verekitug observed both in vitro and throughout clinical datasets, comparatively to published data for
tezepelumab. This represents a key differentiator in targeting strategy, suggesting receptor-based
approaches could offer substantial advantages. - These findings offer a mechanistic rationale for the empirically observed greater potency of targeting the
TSLP receptor with verekitug relative to targeting the TSLP ligand directly. This has significant
implications for dosing strategies and potential clinical outcomes.
This latest data adds to the growing body of evidence supporting the potential of verekitug in treating a variety
of inflammatory and respiratory diseases, positioning Upstream Bio as a key player in the biologics space.
Investors will be watching closely for the upcoming Phase 2 data readout in severe asthma, which is expected
to further validate the clinical profile of verekitug and potentially drive significant value for the company.
About TSLP and TSLP Receptor Blockade
Thymic stromal lymphopoietin (TSLP) is a cytokine that
plays a critical role in driving inflammatory responses in major allergic and inflammatory conditions, such as
asthma. Targeting TSLP signaling has been clinically validated as an effective therapeutic strategy.
TSLP activation is one of the initial events in the inflammatory cascade, triggered by allergens, viruses, and
other stimuli. It initiates the activation of downstream targets, including IL-4, IL-5, IL-13, IL-17, and IgE.
Because TSLP is situated upstream in the inflammatory cascade, blocking the TSLP receptor offers a potential
single-treatment approach to affecting multiple pathological inflammatory processes across a wide range of
diseases.
About Verekitug
Verekitug is a novel recombinant fully human immunoglobulin G1 (IgG1)
monoclonal antibody that binds to the TSLP receptor and inhibits proinflammatory signaling initiated by TSLP.
It is the only known monoclonal antibody currently in clinical development that targets and inhibits the TSLP
receptor. Verekitug has advanced into three separate global, placebo-controlled, randomized Phase 2 clinical
trials including the recently completed VIBRANT trial (NCT06164704) in patients with chronic rhinosinusitis
with nasal polyps (CRSwNP), which demonstrated that verekitug, dosed at 100 mg once every 12 weeks, met both
the primary and secondary endpoints at Week 24 and was generally well tolerated. Two additional ongoing
clinical trials include the VALIANT trial (NCT06196879) in patients with severe asthma and the VENTURE trial
(NCT06981078) in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD). Additionally,
in May 2025, Upstream Bio initiated the VALOUR trial (NCT06966479), a long-term extension study in eligible
participants with severe asthma who completed the VALIANT Phase 2 clinical trial.
In preclinical studies, verekitug demonstrated high occupancy of the TSLP receptor and potent inhibition of TSLP
signaling. Additionally, verekitug inhibited cytokine production from both CD4+ T cells and ILC2 cells and
completely suppressed skin allergic reactions in a non-human primate model, suggesting that it may be
effective against multiple types of inflammation.
Three Phase 1 clinical trials have been completed for verekitug, including a Phase 1 single-ascending dose (SAD)
clinical trial and a Phase 1b multiple-ascending dose (MAD) clinical trial. In these trials, verekitug was
well tolerated, had no clinically meaningful immunogenicity, and showed a predictable and consistent
pharmacokinetic profile and high subcutaneous bioavailability. In patients with asthma, verekitug led to
>50% reductions in fractional exhaled nitric oxide (FeNO) and blood eosinophils that were rapid and
sustained for up to 24 weeks after the last dose in the Phase 1b MAD trial.
About Upstream Bio
Upstream Bio is a clinical-stage biotechnology company developing
treatments for inflammatory diseases, with an initial focus on severe respiratory disorders. Upstream Bio is
developing verekitug, the only known antagonist currently in clinical development that targets the receptor for
thymic stromal lymphopoietin (TSLP), a cytokine which is a clinically validated driver of inflammatory
response positioned upstream of multiple signaling cascades that affect a variety of immune mediated diseases.
Upstream Bio has advanced this highly potent monoclonal antibody into separate Phase 2 trials for the treatment
of chronic rhinosinusitis with nasal polyps (CRSwNP), severe asthma and chronic obstructive pulmonary disease
(COPD). Upstream Bio’s team is committed to maximizing verekitug’s unique attributes to address the
substantial unmet needs for patients underserved by today’s standard of care.
Forward-Looking Statements
This press release contains “forward-looking statements” within
the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of
1934, each as amended. These statements may be identified by words such as “aims,” “anticipates,” “believes,”
“continue,” “could,” “estimates,” “expects,” “forecasts,” “goal,” “intends,” “may,” “plans,” “possible,”
“potential,” “predict,” “project,” “seeks,” “should,” “target,” “will” and variations of these words or
similar expressions. Any statements in this press release that are not statements of historical fact may be
deemed to be forward-looking statements. These forward-looking statements include, without limitation, express
or implied statements regarding: the clinical development of verekitug for the treatment of severe asthma,
CRSwNP and COPD, including the initiation, timing, progress and results of ongoing and planned clinical
trials; expectations for future discussions with regulatory authorities and the potential of the endpoints of
the Company’s clinical trials to produce data that could support submissions for product approval;
expectations regarding the differentiation, safety, efficacy or tolerability of verekitug; expectations
regarding the translation of PK/PD modeling data of verekitug to clinical effects; and assessments comparing
non-head-to-head clinical data of verekitug to published data for tezepelumab. Any forward-looking statements
in this press release are based on the Company’s current expectations, estimates and projections only as of the
date of this release and are subject to a number of risks and uncertainties that could cause actual results to
differ materially and adversely from those set forth in or implied by such forward-looking statements. Readers
are cautioned that actual results, levels of activity, safety, efficacy, performance or events and
circumstances could differ materially from those expressed or implied in the Company’s forward-looking
statements due to a variety of risks and uncertainties, which include, without limitation, risks and
uncertainties related to: Upstream Bio’s ability to advance verekitug through clinical development, and to
obtain regulatory approval of and ultimately commercialize verekitug on the expected timeline, if at all; the
initiation, timing, progress and results of clinical trials; Upstream Bio’s ability to fund its development
activities and achieve development goals; Upstream Bio’s dependence on third parties to conduct clinical
trials and manufacture verekitug, and commercialize verekitug, if approved; Upstream Bio’s ability to attract,
hire and retain key personnel, and protect its intellectual property; Upstream Bio’s financial condition and
need for substantial additional funds in order to complete development activities and commercialize verekitug,
if approved; regulatory developments and approval processes of the U.S. Food and Drug Administration and
comparable foreign regulatory authorities; Upstream Bio’s competitors and industry; and other risks and
uncertainties described in greater detail under the caption “Risk Factors” in Upstream Bio’s most recent Annual
Report on Form 10-K and Quarterly Report on Form 10-Q, as well as any subsequent filings with the SEC. Any
forward-looking statements represent Upstream Bio’s views only as of today and should not be relied upon as
representing its views as of any subsequent date. Upstream Bio explicitly disclaims any obligation or
undertaking to update any forward-looking statements contained herein to reflect any change in its
expectations or any changes in events, conditions or circumstances on which any such statement is based except
to the extent required by law, and claims the protection of the safe harbor for forward-looking statements
contained in the Private Securities Litigation Reform Act of 1995.
NASDAQ:UPB
UPB Stock Data
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14.81%
90.42%
5.75%
Biotechnology
Pharmaceutical Preparations
United States
WALTHAM
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