On April 29, 2025 Innate Pharma SA (Euronext Paris: IPH; Nasdaq: IPHA) ("Innate" or the "Company") reported new preclinical data for IPH4502, its novel and differentiated topoisomerase I inhibitor Antibody Drug Conjugate (ADC) targeting Nectin-4 (Press release, Innate Pharma, APR 29, 2025, View Source [SID1234652337]). The data were presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2025.
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
Nectin-4 targeting is validated by enfortumab vedotin (EV), an ADC with a monomethyl auristatin E (MMAE) payload, approved for urothelial carcinoma (UC), an indication with high Nectin-4 expression. However, EV discontinuation due to toxicity, disease relapse, or treatment ineligibility, along with its limited efficacy in tumors with lower Nectin-4 expression, underscores the need for a differentiated Nectin-4 ADC with improved therapeutic window and improved mechanisms of action.
IPH4502 demonstrated anti-tumor activity in EV-resistant patient-derived xenograft (PDX) model with upregulation of multi-drug resistance protein 1 (MDR1), supporting its potential to overcome resistance mechanisms in EV-refractory disease.
Beyond UC, IPH4502 also exhibited anti-tumor activity in preclinical models of triple-negative breast cancer, head and neck squamous cell carcinoma, and esophageal cancer, suggesting broader potential clinical applicability.
In addition, in preclinical tumor models with low Nectin-4 expression, IPH4502 showed superior anti-tumor activity compared to a clinical-stage Nectin-4-exatecan ADC supported by higher internalization, cytotoxicity, and bystander killing effect.
"We are highly encouraged by these preclinical data, which suggest that IPH4502 has the potential to translate into improved clinical benefit in indications with unmet medical need. These findings also reinforce the rationale for our ongoing Phase 1 trial. We look forward to sharing initial clinical data in 2026 as the program advances," said Sonia Quaratino, Chief Medical Officer of Innate Pharma.
IPH4502 is currently investigated in a Phase 1 trial in advanced solid tumors known to express Nectin-4 (NCT06781983).
The poster is available on Innate Pharma’s website.
About IPH4502
IPH4502 is a differentiated topoisomerase I inhibitor Antibody Drug Conjugate (ADC) conjugated to exatecan targeting Nectin-4, a cell adhesion molecule that is overexpressed in several types of solid tumors, such as urothelial carcinoma, breast cancer, non-small cell lung cancer or gastro-intestinal tract cancer.
IPH4502 is currently investigated in a Phase 1 trial in advanced solid tumors. The Phase 1 trial will assess the safety, tolerability, and preliminary efficacy of IPH4502 in different solid tumors known to express Nectin-4, including but not limited to urothelial carcinoma, non-small cell lung, breast, ovarian, gastric, esophageal, and colorectal cancers. The study plans to enroll approximately 105 patients.
In preclinical models, IPH4502 demonstrates strong bystander killing effect, and efficient internalization, enabling a potent anti-tumor activity in models with various Nectin-4 expression levels. Additionally, IPH4502 shows efficacy in models resistant to MMAE-ADC. These results support its potential for development beyond UC and in cancer patients treated with MMAE-based ADCs.