NEW HAVEN, Conn. – September 16, 2024 – 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 (alphalex™ 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 alphalex™ 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 alphalex™ 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 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 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 alphalex™ 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 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.

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