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Data demonstrate broad activity of CBX-12 across six tumor types with a strong response rate in TOP1-naïve patients with ovarian (40%; N=10) and HR+ HER2- breast (43%; N=7) cancer, in addition to a favorable safety profile
Phase 2 study in platinum-resistant ovarian cancer initiated in Q3 2024
NEW HAVEN, Conn., Sept. 16, 2024 (GLOBE NEWSWIRE) -- Cybrexa Therapeutics, a clinical-stage oncology biotechnology company developing a novel class of tumor-targeting peptide drug conjugate (PDC) therapeutics, today announced positive final results from its Phase 1 clinical trial of CBX-12 (alphalexTM exatecan). These data demonstrate that CBX-12 is well tolerated and exhibits promising activity across a range of advanced or metastatic solid tumors, including ovarian, breast, thymic, gall bladder, non-small cell lung cancer (NSCLC) and colorectal cancers, underscoring its potential as a highly differentiated conjugate with broad antitumor activity. The study results were presented in a poster session at the European Society for Medical Oncology (ESMO) Congress 2024.
“These Phase 1 study results highlight the potential of our alphalexTM Platform to create meaningful therapies that deliver a payload with an improved therapeutic index while sharply reducing the toxicities that often limit conventional therapies,” said Per Hellsund, President and Chief Executive Officer of Cybrexa.“We believe CBX-12 marks a new era in cancer therapy that potentially offers precision targeting and enhanced drug delivery that could redefine patient outcomes. These data support the continued development of CBX-12 across a wide range of tumor types, validating the broad applicability of the platform, and led us to initiate a randomized Phase 2 study in platinum-resistant ovarian cancer patients. Additional Phase 2 studies in solid tumors are planned to begin in 2025.”
CBX-12 is designed to deliver higher concentrations of exatecan, a topoisomerase 1 (TOP1) inhibitor, directly to tumor cells while sparing healthy tissue. Unlike antibody-drug conjugates, CBX-12 doesn't 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.
"In this study of CBX-12, we've seen encouraging clinical activity across six tumor types, including exciting response rates in TOP1-naïve ovarian and breast cancer patients," said Mike Needle, M.D., Chief Medical Officer of Cybrexa.“Importantly, the manageable safety profile of CBX-12 further enhances its potential not only as a standalone treatment but also as a promising candidate for future combination therapies. By bypassing the need for antigens and focusing on a universal feature of tumor microenvironments, we believe CBX-12 could benefit a larger population than currently available therapies."
Study Highlights
The Phase 1 study of CBX-12 demonstrated significant antitumor activity, broad application potential, and a favorable safety profile in patients with various advanced and metastatic cancers.
Efficacy:
CBX-12 treatment resulted in activity across multiple different types of solid tumors, including breast, ovarian, NSCLC, colorectal (CRC), thymic and gallbladder cancers. Responses were observed in ovarian cancer, breast cancer, NSCLC and CRC. Specifically, in 10 ovarian cancer patients who were TOP1-naïve, there was one confirmed complete response, one confirmed partial response (PR), and two unconfirmed PRs, with eight out of 12 patients showing clinical benefit. In seven TOP1-naïve breast cancer patients, there were two confirmed PRs and one unconfirmed PR. All evaluable breast participants were HER-2 negative and HR positive.
Safety:
The most frequent treatment-related adverse events included anemia (53.6%, with 24.6% Grade 3-4), leukopenia (42.0%, with 21.7% Grade 3-4), and neutropenia (40.6%, with 27.5% Grade 3-4). Notably, no cases of interstitial lung disease or ophthalmic toxicity, commonly associated with ADCs, were reported, and minimal GI toxicity was observed. The dose-limiting toxicity was myelosuppression, which was reversible.
Pharmacokinetics (PK) and Dose Optimization:
The PK of CBX-12 and exatecan exhibited linear dose-proportional behavior, with a mean half-life ranging from 14 to 22 hours across the dose range studied. Two doses, 100 mg/m2 and 125 mg/m2, every 21 days are being studied in an ongoing Phase 2 trial, supporting further dose optimization to balance safety and efficacy in future studies.
The promising Phase 1 data provides strong validation for Cybrexa's alphalexTM Platform, which enables multiple opportunities for value creation as Cybrexa deepens its efforts in oncology. This foundational science has enabled the rapid advancement of CBX-12 into a recently initiated Phase 2 study in platinum-resistant ovarian cancer. An additional Phase 2 study in colorectal cancer is planned for 2025 in collaboration with the National Cancer Institute (NCI), as well as other Phase 2 studies in solid tumors as a monotherapy and in combination. CBX-15 is also being developed for solid tumors and is expected to be in the clinic in 2025 utilizing MMAE as the warhead.
About CBX-12
CBX-12 is a clinical-stage, first-in-class peptide drug conjugate (PDC) that utilizes Cybrexa's proprietary alphalexTM 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 I inhibition by delivering exatecan, a highly potent, second-generation topoisomerase I 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 alphalexTM Technology Platform
The Cybrexa alphalex technology is a novel antigen-independent, peptide-drug conjugate (PDC) 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 alphalexTM 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 or follow us on LinkedIn and X .
Investor Contact:
Per Hellsund, CEO, Cybrexa Therapeutics
860-799-1517
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Media Contact:
Robin Fastenau, Scient PR
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