Evommune Presents Positive Clinical Results of its MRGPRX2 Antagonist (EVO756) at the 7th GA²LEN Global Urticaria Forum

• 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.

SOURCE Evommune, Inc