Cybrexa Therapeutics presented preclinical data at the ESMO Targeted Anticancer Therapies Congress 2025, showcasing their alphalex™ peptide-drug conjugates (PDCs). These PDCs demonstrate tumor-selective delivery of potent microtubule inhibitors, resulting in significant tumor suppression and a durable anti-tumor immune response. This approach leverages tumor acidity for precise drug delivery, potentially mitigating the toxicities associated with antigen-based targeting seen in antibody-drug conjugates (ADCs).
This development is crucial because it offers a potential alternative for patients who have progressed after treatment with TOP1-based ADCs, a common class of cancer therapies. The alphalex platform’s antigen-agnostic nature broadens its applicability across various tumor types, potentially addressing limitations encountered with current targeted therapies. The demonstrated synergy with existing standard-of-care treatments, like doxorubicin and anti-PD-L1 therapy, further strengthens its potential clinical impact.
Preclinical findings revealed complete tumor suppression in colorectal cancer models using alphalex PDCs as a monotherapy. Additionally, enhanced tumor suppression was observed when combined with standard treatments in various cancer models. Importantly, data confirms tumor-selective drug delivery, sparing healthy immune cells. The activation of T- and B-cell responses, coupled with evidence of long-term immune memory, suggests sustained anticancer effects.
Cybrexa is actively translating these findings into clinical practice. A Phase 2 clinical trial for CBX-12, an alphalex PDC delivering the TOP1 inhibitor exatecan, is underway for platinum-resistant or refractory ovarian cancer. This follows promising Phase 1 data demonstrating activity across multiple tumor types with a manageable safety profile. These advancements position alphalex PDCs as a potential next-generation cancer therapy, offering new treatment options for patients with hard-to-treat solid tumors. The continued clinical development of this platform, particularly its combination potential with existing therapies, holds significant promise for improving cancer treatment outcomes.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
