Cybrexa Therapeutics, a clinical-stage oncology biotechnology company developing a novel class of tumor-targeting peptide-drug conjugate (PDC) therapeutics, today announced that the first patient has been dosed in a Phase 2 clinical trial evaluating CBX-12 in patients with platinum-resistant or refractory ovarian cancer. CBX-12 is a first-in-class PDC that uses Cybrexa’s proprietary alphalex™ technology to enhance the delivery of exatecan, a potent, established topoisomerase 1 (TOP1) inhibitor, directly to tumor cells while sparing healthy tissue. This trial initiation follows promising Phase 1 results, which demonstrated CBX-12’s broad activity across ovarian, breast, non-small cell lung cancer (NSCLC), thymic, gallbladder, and colorectal cancers along with a manageable safety profile.

“Dosing the first patient marks an important milestone for the Phase 2 clinical trial in ovarian cancer and for patients facing this aggressive disease,” said Per Hellsund, President and Chief Executive Officer of Cybrexa. “CBX-12 recently demonstrated significant antitumor activity, broad application potential, and a favorable safety profile in a Phase 1 study, including encouraging response rates in TOP1-naïve ovarian and breast cancer patients. We are particularly excited about the potential for CBX-12 not only as a standalone treatment but also as a promising candidate for future combination therapies and look forward to its continued advancement in this and additional Phase 2 studies in solid tumors, which are planned for 2025.”

The Phase 2 trial is a randomized, open-label study designed to evaluate the safety, tolerability, and efficacy of CBX-12 in women with platinum-resistant or refractory ovarian cancer at two doses: 125 mg/m² every 21 days or 100 mg/m² every 21 days.

Cybrexa plans an additional Phase 2 study of CBX-12 in colorectal cancer in 2025 in collaboration with the National Cancer Institute (NCI), as well as other Phase 2 studies evaluating CBX-12 as a monotherapy and in combination across a range of solid tumors. Leveraging its alphalex platform to develop multiple promising assets in oncology, Cybrexa is progressing its broader pipeline, including CBX-15, which is expected to enter the clinic in 2025 for the treatment of solid tumors using MMAE (monomethyl auristatin E) as its payload.

Unlike antibody-drug conjugates, CBX-12 does not rely on antigen expression for targeting but rather uses a pH-low insertion peptide (pHLIP ^®) to selectively deliver its payload into the cytoplasm of cancer cells. Results from the Phase 1 study demonstrated that CBX-12 is well tolerated and exhibits promising activity across a range of advanced or metastatic solid tumors, highlighting the versatility of the alphalex platform and its ability to enhance the delivery of cancer therapeutics while limiting off-target effects. The Phase 1 study results were recently presented at the European Society for Medical Oncology Congress (ESMO 2024) in a poster session.

To learn more about the Phase 2 study of CBX-12, please visit ClinicalTrials.gov (NCT06315491).

About CBX-12
CBX-12 is a first-in-class peptide-drug conjugate (PDC) that utilizes Cybrexa’s proprietary alphalex™ technology to enhance delivery of exatecan to tumor cells and is composed of a pH-Low Insertion Peptide (pHLIP^®), a linker, and exatecan. CBX-12 is designed to increase the efficacy and reduce the toxicity of topoisomerase 1 inhibition by delivering exatecan, a highly potent, second-generation topoisomerase 1 inhibitor, directly to the tumor cells. As an antigen-independent therapy, CBX-12 may have broad utility in patients who are not eligible for antigen-targeted therapies, including monoclonal antibodies and antibody-drug conjugates (ADCs), and has potential for use in combination regimens with other anti-cancer agents and immunotherapies.

About the alphalex™ Technology Platform
The Cybrexa alphalex technology is a novel antigen-independent, peptide-drug conjugate platform that enables targeted delivery of highly potent anti-cancer 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 anti-cancer 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 anti-cancer 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.