InflaRx Presents New Preclinical Findings for INF904 at the 19th European Meeting on Complement in Human Diseases
InflaRx N.V. (Nasdaq: IFRX) presented preclinical data for its novel oral C5aR inhibitor, INF904, at the 2024 European Meeting on Complement in Human Diseases. The findings demonstrate INF904's significant anti-inflammatory properties and strong pharmacokinetic profile. In a hamster neutropenia model, INF904 inhibited C5a-induced neutropenia by 96.5% compared to 51.1% for the same dose of avacopan. INF904 also showed a 2- to 5-fold higher exposure than avacopan across all tested animal species and is a much weaker inhibitor of CYP3A4/5 enzymes.
Results from in vitro and in vivo inflammatory disease models indicated that INF904 reduces neutrophil activation and shows significant anti-inflammatory effects. A first-in-human study demonstrated that INF904 is well-tolerated with no safety signals of concern in single doses up to 240 mg and multiple doses up to 90 mg twice daily for 14 days.
InflaRx N.V. (Nasdaq: IFRX) ha presentato dati preclinici per il suo nuovo inibitore orale del C5aR, INF904, durante il 2024 European Meeting on Complement in Human Diseases. I risultati dimostrano le significative proprietà anti-infiammatorie e un forte profilo farmacocinetico di INF904. In un modello di neutropenia in criceti, INF904 ha inibito la neutropenia indotta dal C5a per il 96,5% rispetto al 51,1% per la stessa dose di avacopan. INF904 ha mostrato anche una esposizione da 2 a 5 volte maggiore rispetto all'avacopan in tutte le specie animali testate ed è un inibitore molto più debole degli enzimi CYP3A4/5.
I risultati ottenuti da modelli di malattie infiammatorie in vitro e in vivo hanno indicato che INF904 riduce l'attivazione dei neutrofili e mostra effetti anti-infiammatori significativi. Uno studio di prima in umani ha dimostrato che INF904 è ben tollerato, senza segnali di sicurezza preoccupanti in dosi singole fino a 240 mg e dosi multiple fino a 90 mg due volte al giorno per 14 giorni.
InflaRx N.V. (Nasdaq: IFRX) presentó datos preclínicos sobre su novedoso inhibidor oral de C5aR, INF904, en la reunión europea de 2024 sobre el complemento en enfermedades humanas. Los hallazgos demuestran las significativas propiedades antiinflamatorias y un sólido perfil farmacocinético de INF904. En un modelo de neutropenia en hámsteres, INF904 inhibió la neutropenia inducida por C5a en un 96.5% en comparación con 51.1% para la misma dosis de avacopan. INF904 también mostró una exposición de 2 a 5 veces mayor que el avacopan en todas las especies animales probadas y es un inductor mucho más débil de las enzimas CYP3A4/5.
Los resultados de modelos de enfermedades inflamatorias in vitro e in vivo indicaron que INF904 reduce la activación de neutrófilos y muestra efectos antiinflamatorios significativos. Un estudio de primera en humanos demostró que INF904 es bien tolerado sin señales de seguridad preocupantes en dosis únicas de hasta 240 mg y múltiples dosis de hasta 90 mg dos veces al día durante 14 días.
InflaRx N.V. (Nasdaq: IFRX)는 2024 유럽 인간 질병에서의 보완 회의에서 새로운 경구 C5aR 억제제인 INF904에 대한 전임상 데이터를 발표했습니다. 연구 결과는 INF904가 상당한 항염증 특성과 강력한 약리학적 프로필을 가지고 있음을 보여줍니다. 햄스터 호중구감소증 모델에서 INF904는 C5a에 의해 유도된 호중구감소증을 51.1%와 비교하여 96.5% 억제했습니다. INF904는 모든 테스트된 동물 종에서 avacopan보다 2배에서 5배 높은 노출을 보였으며 CYP3A4/5 효소의 억제력이 훨씬 낮았습니다.
시험관 내 및 생체 내 염증 질환 모델에서의 결과는 INF904가 호중구 활성화를 감소시키고 상당한 항염증 효과를 보여준다는 것을 나타냈습니다. 첫 번째 인체 연구는 INF904가 240mg까지 단일 복용량에 대해 잘 견딜 수 있으며 우려되는 안전 신호가 없다고 입증했습니다. 14일 동안 하루에 두 번 90mg의 다중 복용량에 대해서도 마찬가지입니다.
InflaRx N.V. (Nasdaq: IFRX) a présenté des données précliniques pour son nouvel inhibiteur oral de C5aR, INF904, lors de la réunion européenne de 2024 sur le complément dans les maladies humaines. Les résultats démontrent les propriétés anti-inflammatoires significatives et le solide profil pharmacocinétique d'INF904. Dans un modèle de neutropénie chez des hamsters, INF904 a inhibé la neutropénie induite par C5a de 96,5 % contre 51,1% pour la même dose d'avacopan. INF904 a également présenté une exposition 2 à 5 fois supérieure à celle d'avacopan dans toutes les espèces animales testées et est un inhibiteur beaucoup plus faible des enzymes CYP3A4/5.
Les résultats des modèles de maladies inflammatoires in vitro et in vivo ont indiqué qu'INF904 réduit l'activation des neutrophiles et montre des effets anti-inflammatoires significatifs. Une étude de première en humains a démontré qu'INF904 est bien toléré, sans signaux de sécurité préoccupants pour des doses uniques allant jusqu'à 240 mg et des doses multiples allant jusqu'à 90 mg deux fois par jour pendant 14 jours.
InflaRx N.V. (Nasdaq: IFRX) hat präklinische Daten zu seinem neuartigen oralen C5aR-Inhibitor INF904 auf dem 2024 European Meeting on Complement in Human Diseases vorgestellt. Die Ergebnisse zeigen die signifikanten entzündungshemmenden Eigenschaften und ein starkes pharmakokinetisches Profil von INF904. In einem Neutropenie-Modell bei Hamstern hemmte INF904 die durch C5a induzierte Neutropenie um 96,5 % im Vergleich zu 51,1 % bei derselben Dosis von Avacopan. INF904 zeigte auch eine 2- bis 5-fach höhere Exposition als Avacopan bei allen getesteten Tierarten und ist ein deutlich schwächerer Inhibitor der CYP3A4/5-Enzyme.
Ergebnisse aus in vitro und in vivo Entzündungserkrankungsmodellen deuteten darauf hin, dass INF904 die Aktivierung von Neutrophilen reduziert und signifikante entzündungshemmende Effekte zeigt. Eine erste Studie am Menschen zeigte, dass INF904 gut vertragen wird und keine besorgniserregenden Sicherheitszeichen aufweist, bei Einzeldosen von bis zu 240 mg und mehrfachen Dosen von bis zu 90 mg zweimal täglich über 14 Tage.
- INF904 demonstrated 96.5% inhibition of C5a-induced neutropenia compared to 51.1% for avacopan in a hamster model
- INF904 showed 2- to 5-fold higher exposure than avacopan across all tested animal species
- INF904 is a much weaker inhibitor of CYP3A4/5 enzymes compared to avacopan, potentially reducing drug interactions
- First-in-human study showed INF904 is well-tolerated with no safety signals of concern in single doses up to 240 mg and multiple doses up to 90 mg twice daily for 14 days
- INF904 achieved ≥90% blockade of C5a-induced neutrophil activation over a 14-day dosing period
- None.
JENA, Germany, Sept. 03, 2024 (GLOBE NEWSWIRE) -- InflaRx N.V. (Nasdaq: IFRX), a biopharmaceutical company pioneering anti-inflammatory therapeutics targeting the complement system, today announced the presentation of preclinical data for the company’s novel oral C5aR inhibitor, INF904, at the 2024 European Meeting on Complement in Human Diseases (EMCHD) being held in Lübeck, Germany, September 2 – 6, 2024.
Members of InflaRx leadership also participated in a satellite symposium highlighting the role of the C5a/C5aR1 axis in driving inflammation and served as the biopharma industry representative on a panel focused on the relevance of targeting C3 and C5. InflaRx also hosted a lunch seminar focused on C5a/C5aR inhibition in human disease with best-in-class compounds.
Camilla Chong, MD, Chief Medical Officer of InflaRx, commented: “We welcome the opportunity to demonstrate our commitment to advancing the science of complement inhibition and progress toward our goal of developing first-in-class and best-in-class anti-inflammatory therapies via inhibition of C5a and C5aR. The preclinical findings presented at EMCHD 2024 from multiple in vivo and ex vivo models provide strong evidence of INF904’s significant anti-inflammatory properties and strong pharmacokinetic properties, further supporting our belief that INF904 may have differentiating advantages as a member of the C5aR inhibitor drug class.”
Preclinical pharmacological characterization of INF904, an oral small molecule antagonist to complement 5a receptor1 (C5aR1)
Rui Liu, Zhongli Xu, Ophelia Chen, Bruce P. Burnett, Maria Habel, Renfeng Guo
Overall, this study demonstrated that INF904 is a highly selective and potent inhibitor of C5aR1 with promising pharmacokinetic (PK) properties, while also exhibiting strong efficacy potential in vivo. Both INF904 and avacopan were evaluated through a series of cell-based, ex vivo, and in vivo assays. In a hamster neutropenia model, INF904 inhibited C5a-induced neutropenia by
INF904, a novel oral C5a receptor 1 (C5aR1) antagonist, shows promising therapeutic effects in inflammatory disease models
Zhongli Xu, Rui Liu, Ophelia Chen, Bruce P. Burnett, Maria Habel, Renfeng Guo
Results from in vitro and in vivo inflammatory disease models indicated that INF904 acts by reducing neutrophil activation. In two in vitro whole blood disease models, INF904 effectively blocked CD11b upregulation on neutrophils in a dose-dependent manner. Further, in three hamster models used to assess INF904’s therapeutic effects after oral dosing, significant anti-inflammatory effects were noted, including reduced influx of neutrophils, significant reductions in plasma levels of CREA and BUN, and histological improvements.
About INF904
INF904 is an orally administered, small molecule inhibitor of the C5a receptor that has shown anti-inflammatory therapeutic effects in several pre-clinical disease models. Further, in contrast to the marketed C5aR inhibitor, in vitro experiments demonstrated that INF904 has minimal inhibition of the cytochrome P450 3A4/5 (CYP3A4/5) enzymes, which play an important role in the metabolism of a variety of metabolites and drugs, including glucocorticoids. Reported results from a first-in-human study demonstrated that INF904 is well tolerated in treated subjects and exhibits no safety signals of concern in single doses ranging from 3 mg to 240 mg or multiple doses ranging from 30 mg once per day (QD) to 90 mg twice per day (BID) for 14 days. Pharmacokinetic / pharmacodynamic data support best-in-class potential of INF904 with a ≥
About InflaRx
InflaRx (Nasdaq: IFRX) is a biopharmaceutical company pioneering anti-inflammatory therapeutics by applying its proprietary anti-C5a and anti-C5aR technologies to discover, develop and commercialize highly potent and specific inhibitors of the complement activation factor C5a and its receptor C5aR. C5a is a powerful inflammatory mediator involved in the progression of a wide variety of inflammatory diseases. InflaRx’s lead product candidate, vilobelimab, is a novel, intravenously delivered, first-in-class, anti-C5a monoclonal antibody that selectively binds to free C5a and has demonstrated disease-modifying clinical activity and tolerability in multiple clinical studies in different indications. InflaRx is also developing INF904, an orally administered, small molecule inhibitor of the C5a receptor. InflaRx was founded in 2007, and the group has offices and subsidiaries in Jena and Munich, Germany, as well as Ann Arbor, MI, USA. For further information, please visit www.inflarx.com.
InflaRx GmbH (Germany) and InflaRx Pharmaceuticals Inc. (USA) are wholly owned subsidiaries of InflaRx N.V. (together, InflaRx).
Contacts:
| InflaRx N.V. | MC Services AG |
| Jan Medina, CFA Vice President, Head of Investor Relations Email: IR@inflarx.de | Katja Arnold, Laurie Doyle, Dr. Regina Lutz Email: inflarx@mc-services.eu Europe: +49 89-210 2280 U.S.: +1-339-832-0752 |
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FAQ
What is INF904 and how does it differ from other C5aR inhibitors?
What were the key findings of INF904's preclinical studies presented at EMCHD 2024?
Has INF904 (IFRX) been tested in humans, and what were the results?
How does INF904's inhibition of CYP3A4/5 enzymes compare to avacopan?
