IPH4502 is a differentiated exatecan ADC targeting Nectin-4, currently investigated in a Phase 1 clinical trial in advanced solid tumors.
IPH4502 demonstrated superior preclinical anti-tumor activity compared to enfortumab vedotin (EV) in urothelial carcinoma models with low or heterogeneous Nectin-4 expression, as well as in models resistant to EV.
IPH4502 showed strong preclinical activity across multiple tumor types, including triple-negative breast cancer, head and neck, and esophageal cancers, supporting its potential for broad clinical application.
MARSEILLE, France, April 29, 2025--(BUSINESS WIRE)--Regulatory News:
Innate Pharma SA (Euronext Paris: IPH; Nasdaq: IPHA) ("Innate" or the "Company") today shared new preclinical data for IPH4502, its novel and differentiated topoisomerase I inhibitor Antibody Drug Conjugate (ADC) targeting Nectin-4. The data were presented at the American Association for Cancer Research (AACR) Annual Meeting 2025.
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).
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.
About Innate Pharma
Innate Pharma S.A. is a global, clinical-stage biotechnology company developing immunotherapies for cancer patients. Its innovative approach aims to harness the innate immune system through three therapeutic approaches: multi-specific NK Cell Engagers via its ANKET® (Antibody-based NK cell Engager Therapeutics) proprietary platform and Antibody Drug Conjugates (ADC) and monoclonal antibodies (mAbs).
Innate’s portfolio includes several ANKET® drug candidates to address multiple tumor types as well as IPH4502, a differentiated ADC in development in solid tumors. In addition, anti-KIR3DL2 mAb lacutamab is developed in advanced form of cutaneous T cell lymphomas and peripheral T cell lymphomas, and anti-NKG2A mAb monalizumab is developed with AstraZeneca in non-small cell lung cancer.
Innate Pharma is a trusted partner to biopharmaceutical companies such as Sanofi and AstraZeneca, as well as leading research institutions, to accelerate innovation, research and development for the benefit of patients.
Headquartered in Marseille, France with a US office in Rockville, MD, Innate Pharma is listed on Euronext Paris and Nasdaq in the US.
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