Upstream Bio Presents Results from a Dose Ranging Study of Verekitug (UPB-101) in Adults with Asthma at the American Thoracic Society International Conference
23 May 2024 - 1:15AM
Upstream Bio, Inc., a clinical-stage company focused on the
development of verekitug, a potential first-in-class antagonist of
the Thymic Stromal Lymphopoietin (TSLP) receptor that may deliver
best-in-class efficacy for people with severe asthma and related
diseases, today presented clinical data from its dose-ranging study
of verekitug (UPB-101) in adults with asthma, at the American
Thoracic Society International Conference being held in San Diego,
CA.
In all doses of verekitug, a rapid and complete TSLP receptor
(TSLPR) occupancy within 2 weeks after the first dose was observed,
and in doses >100 mg, TSLPR occupancy was sustained for up to 24
weeks after the last dose. As a result, a substantial reduction of
FENO within 2 weeks after the first dose was observed in all doses
of verekitug. With 100 mg of verekitug, a 54% reduction of FENO
from baseline that was sustained for up to 24 weeks after the last
dose was observed. Similar rapid, substantial and sustained
reductions were observed in blood eosinophils, a type of white
blood cell found in increased numbers in many patients with asthma.
FENO is an accepted biomarker for underlying Type 2 lung
inflammation in patients with asthma; higher levels of FENO are
associated with an increased risk for future asthma
exacerbations.
Verekitug was well-tolerated at all dose levels tested; the most
common treatment emergent adverse event was headaches.
“These clinical data add to the growing scientific evidence that
blocking the TSLPR may be an effective and durable approach to
blocking the TSLP signaling pathway driving inflammatory diseases
such as severe asthma. The rapid, substantial and sustained
reduction in FENO and blood eosinophils observed for up to 24 weeks
supports verekitug’s potential to deliver significant beneficial
effects on clinical outcomes with potential administration every 12
or 24 weeks,” said Aaron Deykin, M.D., Upstream Bio's Chief Medical
Officer and Head of R&D.
“The clinical results presented today further support
translation of our preclinical data to patients with severe asthma
and suggest that the high potency of verekitug could lead to a
potentially differentiated treatment profile with respect to both
dosing interval and efficacy,” said Rand Sutherland, M.D., Upstream
Bio’s Chief Executive Officer. “We continue to advance our two
Phase 2 trials of verekitug in severe asthma and in chronic
rhinosinusitis with nasal polyps, with the goal of observing
continued durable effect with extended dosing intervals, a
treatment paradigm that has the potential to advance care for
patients with these diseases.”
The MAD study was a multicenter, randomized, double-blind,
placebo-controlled trial that enrolled adults with mild to moderate
asthma and elevated blood eosinophils. Four dosing cohorts were
included: 100 mg every 4 weeks, 200 mg every 4 weeks, 300 mg every
12 weeks and 25 mg single dose. Participants were observed for 32
weeks following randomization (NCT05448651).
A digital version of the poster can be found on Upstream’s
website.
About TSLP and TSLPR Blockade
Thymic Stromal Lymphopoietin (TSLP) is a cytokine that is a key
driver of the inflammatory response in major allergic and
inflammatory diseases, such as asthma, where disruption of TSLP
signaling has been clinically validated as an effective therapeutic
strategy.
TSLP activation is one of the first events in the inflammatory
cascade stimulated by allergens, viruses and other triggers,
initiating the activation of downstream targets such as IL-4, IL-5,
IL-13, IL-17 and IgE. Because TSLP is a target upstream in the
inflammatory cascade, blocking the TSLP receptor (TSLPR) presents
an opportunity for a single treatment to impact the drivers of
multiple pathological inflammatory processes across a broad set of
diseases.
About Verekitug
Verekitug is a novel recombinant fully human immunoglobulin G1
(IgG1) monoclonal antibody (mAb) that binds to the TSLPR and
inhibits proinflammatory signaling initiated by TSLP. Verekitug is
currently being evaluated in two Phase 2 clinical trials, the
VALIANT trial in patients with severe asthma (NCT06196879) and the
VIBRANT trial in patients with chronic rhinosinusitis with nasal
polyps (CRSwNP) (NCT06164704). In preclinical studies, verekitug
demonstrated high occupancy of the TSLPR 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 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, showed a predictable and consistent pharmacokinetic
profile, and had high subcutaneous bioavailability.
About Upstream Bio
The focus of Upstream Bio is to maximize the potential of
verekitug as a potential first-in-class antagonist of the TSLP
receptor that may deliver best-in-class efficacy for people with
severe asthma, CRSwNP, and other related diseases. Beyond these
initial indications, Upstream Bio believes verekitug has broad
potential in other inflammatory diseases, and it intends to
leverage verekitug’s differentiated attributes to develop it as a
potential therapy for diseases where TSLP signaling has been shown
to play a significant role.
Company Contact
Michael Gray
Chief Financial Officer and Chief Operating Officer
info@upstreambio.com
Media Contact:
Teri Dahlman
Red House Communications
teri@redhousecomms.com