Cybrexa Therapeutics Reports Positive Final Data on CBX-12 Phase 1 Study at ESMO 2024

Cybrexa Therapeutics, a clinical-stage biotechnology firm specializing in oncology treatments, announced encouraging results from its Phase 1 clinical trial of CBX-12 (alphalex™ exatecan). The data revealed that CBX-12 is well tolerated and shows significant efficacy across different types of advanced or metastatic solid tumors, including ovarian, breast, thymic, gall bladder, non-small cell lung cancer (NSCLC), and colorectal cancers. These findings were discussed at the European Society for Medical Oncology (ESMO) Congress 2024.

CBX-12 utilizes Cybrexa’s proprietary alphalex™ technology, which aims to deliver higher concentrations of the drug exatecan directly to cancer cells, sparing healthy tissues. Unlike antibody-drug conjugates, CBX-12 bypasses the need for antigen expression and instead uses a pH-low insertion peptide (pHLIP) to target cancer cells based on their acidic environment. This approach not only improves the therapeutic index but also reduces the toxicities commonly associated with conventional treatments.

According to Per Hellsund, President and CEO of Cybrexa, CBX-12 could represent a new era in cancer treatment by offering precision targeting and enhanced drug delivery. This potential has led Cybrexa to initiate a randomized Phase 2 study in platinum-resistant ovarian cancer patients, with additional Phase 2 studies planned for 2025 in various solid tumors.

The Phase 1 study demonstrated notable antitumor activity and a favorable safety profile. Key efficacy results included responses across multiple tumors, including breast, ovarian, NSCLC, colorectal, thymic, and gallbladder cancers. In the study, 10 ovarian cancer patients who were TOP1-naïve showed a 40% response rate, while seven HR+ HER2- breast cancer patients demonstrated a 43% response rate. Specifically, 10 ovarian cancer patients saw one complete response, one partial response, and two unconfirmed partial responses, with eight out of 12 patients showing clinical benefit. In seven breast cancer patients, there were two confirmed partial responses and one unconfirmed partial response.

The safety profile of CBX-12 was generally manageable. The most common treatment-related adverse events were anemia, leukopenia, and neutropenia, but no cases of interstitial lung disease or ophthalmic toxicity were reported. Furthermore, gastrointestinal toxicity was minimal. The dose-limiting toxicity was reversible myelosuppression. The pharmacokinetics of CBX-12 indicated linear dose-proportional behavior, with a mean half-life ranging from 14 to 22 hours, supporting further dose optimization in the ongoing Phase 2 trials.

The promising Phase 1 data validate Cybrexa’s alphalex™ Platform, which has enabled the rapid advancement of CBX-12 into further clinical trials. A Phase 2 study in platinum-resistant ovarian cancer has already begun, and another Phase 2 study in colorectal cancer is planned for 2025 in collaboration with the National Cancer Institute (NCI). Additional studies in various solid tumors are also on the horizon.

CBX-12 is a pioneering peptide drug conjugate (PDC) designed to enhance the delivery of exatecan directly to tumor cells while minimizing the impact on healthy tissues. This antigen-independent therapy may be particularly useful for patients who are not eligible for antigen-targeted treatments like monoclonal antibodies and antibody-drug conjugates (ADCs). Moreover, CBX-12 has potential for combination regimens with other anti-cancer agents and immunotherapies.

Cybrexa’s alphalex™ technology platform is a novel means of delivering highly potent anti-cancer treatments, aiming to revolutionize oncology care. The platform comprises a pH-Low Insertion Peptide (pHLIP), a linker, and a small molecule anti-cancer agent, designed to target the acidic environment of cancer cells. pHLIP peptides were developed at Yale University and the University of Rhode Island and are exclusively licensed to pHLIP, Inc., with Cybrexa as a sublicensee.

Founded in 2017 and based in New Haven, Connecticut, Cybrexa Therapeutics is driven by a team of experienced life science entrepreneurs and drug development scientists. The company is dedicated to revolutionizing oncology treatments, with a robust pipeline aimed at combating a range of tumors including breast, ovarian, and NSCLC.