- Proof-of-concept trial of EVO756 in 132 subjects, demonstrated
an excellent safety profile, robust efficacy, and a pharmacokinetic
profile supporting once-daily oral dosing
- The data suggest the potential of EVO756 as a first and
best-in-class opportunity for patients suffering from broad range
of chronic inflammatory diseases
- Evommune has initiated the first of multiple Phase 2 trials
based on these encouraging results
BERLIN, Dec. 4, 2024
/PRNewswire/ -- Evommune, Inc., a clinical stage biotechnology
company discovering and developing new ways to treat
immune-mediated inflammatory diseases, today presented the complete
data set from its first-in-human proof-of-concept (POC) trial with
EVO756 at the 7th GA²LEN Global Urticaria Forum in Berlin, Germany.
The podium clinical presentation entitled "EVO756, an oral
MRGPRX2 antagonist, is well-tolerated and demonstrates target
engagement: Results from a Phase 1 Study", was
presented by world-leading expert Sarbjit
Saini, M.D., Professor of Medicine at Johns Hopkins University in Baltimore, Maryland. The presentation
summarized the comprehensive positive results from the POC trial,
which included 132 subjects.
"We are delighted to share these results at a scientific
meeting, where worldwide experts present the most important and new
clinical data in the field of urticaria. These robust data
provide good translatability to its potential efficacy in patients
with various mast cell mediated diseases, including urticarias,"
commented Dr. Sarbjit Saini.
The POC trial was a randomized, double-blind, placebo-controlled
single and multiple ascending dose (SAD and MAD) study in normal
healthy adults and assessed the safety, tolerability,
pharmacokinetics and pharmacodynamics of orally administered
EVO756. Doses from 1 mg to 500 mg were administered in
ascending order across seven cohorts, targeting eight subjects
each. In the MAD cohorts, ascending doses of 10 mg, 30 mg,
100 mg and 240 mg twice daily, followed by 500 mg once daily, were
administered across five cohorts, targeting 16 subjects each.
Subjects in the MAD cohorts received 14 days of experimental
treatment.
The efficacy potential of EVO756 on mast cell degranulation was
assessed in a skin challenge test, in
which icatibant, a known ligand of the MRGPRX2 receptor, was
administered intradermally. Icatibant induced measurable skin
responses in all subjects. Multiple experimental methods have
determined that mast cell degranulation caused by icatibant is
representative to changes associated with MRGPRX2 disease-relevant
endogenous ligands. This portion of the study allowed for an
evaluation of activity in a highly controlled setting and had the
benefit of mimicking the potential impact of EVO756 versus placebo
in inducible urticarias.
The data from this trial show that EVO756 was well tolerated
with the proportion of subjects reporting adverse events in all
EVO756 dosing cohorts comparable to that observed with placebo
treated subjects. There were no severe or serious adverse events.
In those subjects treated for 14 days, the most common adverse
events reported were headache and IV catheter site pain (used for
pharmacokinetic blood draws). Serum concentrations of EVO756
support a once daily dosing regimen. EVO756, at different doses,
demonstrated the ability to significantly inhibit wheal formation
induced by icatibant in the skin challenge test conducted prior to
and following 14 days of treatment with EVO756. This inhibition
occurred even at doses believed to be significantly above ligand
concentrations in diseased tissue.
"These data serve as the foundation for our current and future
Phase 2 trials of EVO756, including a Phase 2b study in chronic spontaneous urticaria to be
initiated during the first half of 2025," said Eugene Bauer, M.D., Chief Medical Officer at
Evommune. "We are also currently enrolling patients with chronic
inducible urticaria (CIndU) in a Phase 2 trial designed to evaluate
EVO756 in patients with either symptomatic dermographism or cold
urticaria, the two most common forms of CIndU. Data from this trial
are expected in the first half of 2025."
Evommune Scientists Presentation of Preclinical Poster on
Translational Study of EVO756
Entitled "EVO756 inhibits activation of MRGPRX2 in several in
vitro models and correlates to human in vivo data", this
study highlights new preclinical data on MRGPRX2 biology and
EVO756 and, demonstrates that icatibant (as referenced above) is a
reliable proxy for MRGPRX2 disease relevant endogenous ligands.
Evommune's in vitro primary human skin mast
cell data compared with the in vivo icatibant skin challenge
data from the proof-of-concept clinical trial, demonstrate an
excellent correlation between the company's preclinical and
clinical results.
Slides and poster presentations can be accessed on Evommune's
website, https://www.evommune.com/publications-posters/.
About EVO756
EVO756 is a potent, highly selective small molecule antagonist
of mas-related G-protein coupled receptor X2 (MRGPRX2). MRGPRX2 is
most abundantly found on mast cells and peripheral sensory neurons.
MRGPRX2 can trigger IgE-independent activation (degranulation) via
multiple ligands, which can lead to a variety of symptoms depending
on the tissue that is affected. Evommune's pre-clinical data
demonstrates that by blocking activation of MRGPRX2 and
degranulation of mast cells, EVO756 has the potential to be a
first-in-class oral treatment for a variety of mast cell mediated
diseases. In addition, due to its unique function on peripheral
sensory neurons, EVO756 could provide fast relief of itch
associated with inflammatory diseases, such as atopic
dermatitis.
About Evommune
Evommune, Inc., a Palo Alto based
biotech company, is creating game-changing science to treat
immune-mediated inflammatory diseases by discovering, developing,
and delivering therapies that address symptoms and halt progressive
disease. For more information, please visit www.evommune.com or
Evommune's LinkedIn page.
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SOURCE Evommune, Inc