Pharma Focus Asia

Exelixis and Cybrexa Therapeutics Establish Exclusive Collaboration Providing Exelixis the Right to Acquire CBX-12, a Potential First-in-Class Peptide-Drug Conjugate of Exatecan

Wednesday, November 02, 2022

Exelixis, Inc., and Cybrexa Therapeutics announced that the companies have entered into an exclusive collaboration agreement providing Exelixis the right to acquire CBX-12 (alphalex™ exatecan), 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. 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. This collaboration underscores Exelixis’ commitment to expanding its clinical pipeline building upon its biotherapeutics and targeted drug therapy expertise.

CBX-12 is composed of a pH-Low Insertion Peptide (pHLIP®), a linker and exatecan. 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. Data from the ongoing phase 1 trial of CBX-12 in patients with metastatic solid tumors, reported in an oral presentation during a plenary session at the EORTC-NCI-AACR (ENA) 2022 Symposium on October 28, 2022, demonstrated preliminary anti-tumor activity in a heavily pretreated patient population. This included a complete response in a patient with ovarian cancer.

"This agreement aligns with Exelixis’ goal of acquiring first- or best-in-class clinical-stage assets that may provide differentiated benefits to patients with cancer. Today's announcement further highlights our ongoing strategy to leverage our balance sheet to gain access to new assets with compelling potential upside in a risk-sharing model, where we can work with partners to further establish proof of concept before investing more heavily,” said Michael Morrissey, Ph.D., President & CEO, Exelixis. “Robust preclinical data and initial clinical data from the ongoing phase 1 trial suggest that CBX-12 may provide differentiated clinical benefit in several solid tumors. Similar to our interest in antibody-drug conjugates, we believe this novel peptide-drug conjugate has transformative clinical potential, and this collaboration affords us the opportunity to expand our clinical pipeline with a best-in-class exatecan therapy if additional CBX-12 clinical data demonstrate enhanced safety and efficacy.”

Cybrexa’s proprietary alphalex technology is designed to increase the therapeutic index of potent anti-cancer compounds by targeting their delivery to tumor cells, thus reducing systemic exposure and thereby reducing toxicity. Importantly, this targeting is achieved through an antigen-independent mechanism, making the alphalex technology potentially applicable to diverse tumor types and providing a complementary approach to traditional ADCs. The alphalex technology platform utilizes pHLIPs combined with a linker to deliver anti-cancer compounds directly to tumor cells. In the acidic (low pH) tumor microenvironment, the pHLIP forms an alpha-helical structure that inserts itself into and across the tumor cell membrane. It is well established that many tumors have an altered metabolism that results in excretion of lactic acid into the tumor microenvironment, thereby reducing the local pH. The linker is cleaved within the cell, releasing the anti-cancer agent into the cell’s cytoplasm. The alpha-helical structure of the peptide (pHLIP) does not form in the physiologic pH surrounding normal cells, preventing delivery to these cells and reducing toxicity.

“Cybrexa is focused on developing the next generation of cancer therapeutics that specifically target tumors and their underlying biology,” said Per Hellsund, President & CEO, Cybrexa. “With its expanding portfolio of biotherapeutics, including ADCs, Exelixis and its partner network have significant and expanding expertise in PDC chemistries and development. Our alphalex PDC technology is an important complement to ADCs and other targeted therapies, and we are excited to bring Exelixis’ insights and resources to the development of CBX-12.”

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