SystImmune, Inc., a clinical-stage biotechnology company, has announced plans to present updated data on izalontamab brengitecan (iza-bren) at the upcoming European Society for Medical Oncology (ESMO) Breast Cancer 2025 Annual Congress in Munich, Germany, scheduled for May 14-17.
The presentation will feature the latest safety and efficacy results from an ongoing Phase 1 clinical trial evaluating iza-bren in patients with locally advanced or metastatic HER2-negative breast cancer. This potentially first-in-class EGFRxHER3 bispecific antibody-drug conjugate (ADC) is being jointly developed by SystImmune and Bristol Myers Squibb under a collaboration and exclusive license agreement.
Promising Clinical Data
According to SystImmune, subgroup analysis of previously disclosed data at the San Antonio Breast Cancer Symposium (SABCS) 2024 shows encouraging efficacy for iza-bren across all HER2 expression levels in HER2-negative breast cancer patients, including those classified as HER2 0. This suggests the therapy may have broad applicability within the HER2-negative breast cancer population.
"These data continue to support our conviction that iza-bren demonstrates strong clinical efficacy across a wide variety of tumors such as breast cancer including HER2-negative breast cancer with a manageable safety profile," said Dr. Jonathan Cheng, Chief Medical Officer of SystImmune. "This positions iza-bren as an important therapeutic option that may address the unmet medical needs of patients with limited treatment options."
Dr. Cheng further emphasized the company's commitment to advancing the therapy through clinical trials, exploring its potential both as a monotherapy and in combination with other agents to improve outcomes for cancer patients globally.
Innovative Mechanism of Action
Iza-bren represents an innovative approach to targeted cancer therapy. The bispecific ADC targets both EGFR and HER3 proteins, which are highly expressed in most epithelial tumors. Its tetravalent structure provides two binding domains for these distinct growth factor receptors that drive cancer cell proliferation and survival.
The mechanism of action is twofold: first, iza-bren blocks EGFR and HER3 signals to cancer cells, reducing proliferation and survival signals; second, upon antibody-mediated internalization, it is trafficked to cancer cell lysosomes where it releases its therapeutic payload—a topoisomerase inhibitor that induces genotoxic stress, activating pathways leading to cancer cell death.
Presentation Details
The data will be presented in a mini oral session at ESMO Breast 2025:
- Presentation Title: Phase I study of iza-bren (BL-B01D1), an EGFR x HER3 Bispecific Antibody-drug Conjugate (ADC), in Patients with Locally Advanced or Metastatic Breast Cancer (BC)
- Presentation Number: 302MO
- Session: Mini Oral Session 2
- Speaker: Yiqun Du (Shanghai, China)
- Date and Time: Friday, May 16, 2025, 8:20 AM-10:10 AM CEST
Addressing Unmet Medical Needs
Breast cancer remains one of the most common cancers worldwide, with HER2-negative subtypes representing approximately 80% of all breast cancer cases. Despite advances in treatment, patients with locally advanced or metastatic disease often face limited therapeutic options after progression on standard therapies.
The development of iza-bren aims to address this significant unmet medical need by targeting multiple growth factor receptors simultaneously. The preliminary efficacy observed across HER2 expression levels, including HER2 0 patients, is particularly noteworthy as these patients typically have fewer targeted therapy options.
About SystImmune
Based in Redmond, Washington, SystImmune is a clinical-stage biopharmaceutical company specializing in developing innovative cancer treatments. The company focuses on bi-specific and multi-specific antibodies, as well as antibody-drug conjugates (ADCs).
Beyond iza-bren, SystImmune has several assets in various stages of clinical trials for both solid tumor and hematologic indications. The company also maintains a robust preclinical pipeline of potential cancer therapeutics in the discovery or IND-enabling stages, representing cutting-edge biologics development.
As SystImmune continues to advance iza-bren through clinical development, the upcoming presentation at ESMO Breast 2025 will provide the oncology community with important insights into this promising therapeutic approach for breast cancer patients.
