alphalex™ peptide-drug conjugates (PDCs) demonstrate tumor-selective delivery and potent anticancer activity
Preclinical data show robust efficacy as monotherapy and in combination with standard-of-care treatments
- Findings potentially position alphalex PDCs in patients who have progressed following TOP1-based antibody-drug conjugates
NEW HAVEN, Conn., March 04, 2025 (GLOBE NEWSWIRE) -- Cybrexa Therapeutics, a clinical-stage oncology biotechnology company developing a novel class of tumor-targeting peptide-drug conjugate (PDC) therapeutics, today announced new preclinical data from its alphalex™ technology, which were presented at the ESMO Targeted Anticancer Therapies (TAT) Congress 2025 being held March 3-5 in Paris, France. The findings demonstrate that Cybrexa’s antigen-agnostic PDC platform selectively delivers highly potent microtubule inhibitors to tumor cells, suppressing tumor growth while inducing a durable anti-tumor immune response.
Unlike antibody-drug conjugates (ADCs), alphalex PDCs use a pH-driven targeting approach to enable broad tumor applicability and avoid the toxicities often associated with antigen-based drug targeting. By exploiting tumor acidity, the alphalex platform ensures precise intracellular drug delivery to potentially reduce off-target effects while enhancing therapeutic impact.
Preclinical Findings at ESMO TAT 2025
The poster, “Characterization of Antigen-Agnostic Tumor-Selective Delivery and Immunomodulatory Activities of Auristatin and Maytansinoid alphalex™ Peptide-Drug Conjugates,” highlighted preclinical results evaluating the efficacy, safety, and immune-modulating effects of alphalex conjugates across mouse and rat xenograft and syngeneic models, including colorectal, melanoma, renal, and breast cancers. The data demonstrate that alphalex PDCs achieved tumor-selective delivery, long-term stability in plasma, and potent anti-tumor effects as both monotherapy and in combination with standard-of-care therapies.
“These data reinforce the potential of the alphalex platform to overcome the challenges of antigen-based therapies, while providing a powerful, tumor-selective approach to delivering cytotoxic agents,” said Vishwas Paralkar, Ph.D., Chief Scientific Officer of Cybrexa Therapeutics. “In bypassing the limitations of antibody-drug conjugates, we are opening new therapeutic possibilities for patients with hard-to-treat solid tumors.”
Key findings:
- Tumor-selective drug delivery
- Plasma stability and in vivo analyses confirmed that alphalex conjugates selectively deliver microtubule inhibitors to tumor tissue while sparing healthy immune cells.
- Potent efficacy in multiple tumor models
- Monotherapy: alphalex conjugates led to complete tumor suppression in HCT116 human colorectal cancer models.
- Combination therapy: In flank and metastatic models, alphalex PDCs demonstrated synergy with doxorubicin and anti-PD-L1 therapy, further enhancing tumor suppression.
- Induction of durable anti-tumor immunity
- Immunogenic cell death following alphalex treatment-activated T- and B-cell responses, with evidence of tumor-binding IgG and long-term immune memory, support the potential for sustained anticancer effects.
- Potential following a topoisomerase-1 (TOP1)-based ADC
- The antigen-agnostic delivery of auristatin and maytansinoid payloads potentially positions alphalex PDCs in patients who have progressed following TOP1-based ADCs.
- The antigen-agnostic delivery of auristatin and maytansinoid payloads potentially positions alphalex PDCs in patients who have progressed following TOP1-based ADCs.
Clinical Progress: Advancing alphalex in the Clinic
Cybrexa is actively advancing its alphalex platform into clinical development. In October 2024, the company dosed the first patient in its Phase 2 clinical trial of CBX-12 in platinum-resistant or refractory ovarian cancer. CBX-12 is a first-in-class PDC that utilizes Cybrexa’s proprietary alphalex technology to enhance the intracellular delivery of exatecan, a highly potent, well-established TOP1 inhibitor.
This trial builds upon promising Phase 1 data, which demonstrated broad activity across multiple tumor types, including ovarian, breast, non-small cell lung cancer (NSCLC), thymic, gallbladder, and colorectal cancers, alongside a manageable safety profile.
About the alphalex™ Technology Platform
Cybrexa’s alphalex technology is a novel antigen-independent, peptide-drug conjugate (PDC) platform that enables targeted delivery of highly potent anticancer treatments and aims to revolutionize the standard of care in oncology. The platform consists of a pH-Low Insertion Peptide (pHLIP®), a linker, and a small molecule anticancer agent. pHLIP peptides are a family of pH-low insertion peptides that target acidic cell surfaces. pHLIP was developed at Yale University and the University of Rhode Island and is exclusively licensed to pHLIP, Inc., and Cybrexa is a sublicensee of pHLIP, Inc.
About Cybrexa Therapeutics
Cybrexa is a privately held clinical-stage biotechnology company pioneering novel antigen-independent, tumor-targeting peptide-drug conjugate (PDC) therapeutics. The company is led by a dynamic team of highly successful life science entrepreneurs and veteran drug development scientists. Cybrexa is on a mission to create therapeutics that revolutionize the standard of care in oncology, and its robust pipeline aims to combat breast, ovarian, non-small cell lung cancer, and a range of other tumors. Its assets are built on Cybrexa’s alphalex™ technology platform, which enables intracellular delivery of highly potent anticancer treatments. Cybrexa is based in New Haven, Connecticut and was founded in 2017. For more information, please visit www.cybrexa.com or follow us on LinkedIn and X.
CONTACT: Investor Contact: Per Hellsund, CEO, Cybrexa Therapeutics 860-717-2731 per.hellsund@cybrexa.com Media Contact: Dan Boyle, SCIENT PR dan@scientpr.com
