Cybrexa Therapeutics’ alphalex Platform Enables Tumor Targeting of Multiple PARP Inhibitors
Cybrexa Therapeutics recently announced preclinical data supporting the potential of its proprietary alphalex technology platform. Results from multiple preclinical studies demonstrate that alphalex successfully enables the combination of a diverse range of structurally unique PARP inhibitors with DNA damaging chemotherapies in doses that effectively induce significant tumor cell killing, representing a new approach to target homologous recombination deficiency (HRD)-negative cancers without causing significant bone marrow toxicity.
The studies showed that each of the alphalex-PARP inhibitor conjugated molecules was successfully delivered to tumor cells while sparing other tissues. Researchers observed significant reductions in PARylation activity and strong synergy with DNA damaging agents in vitro. Researchers then demonstrated that alphalex-PARP inhibitor conjugates in combination with both temozolomide and irinotecan induced significant tumor cell killing in HRD-negative tumors in vivo. Importantly, they found that the alphalex tumor-targeting approach significantly reduced normal tissue toxicity, with almost complete sparing of the bone marrow relative to temozolomide alone.
“Cybrexa’s unique alphalex platform enables multiple PARP inhibitor combinations with clinically relevant chemotherapies, providing a new way to target HRD-negative cancers without significant bone marrow toxicity,” said Vishwas Paralkar, PhD, Chief Scientific Officer of Cybrexa. “Based on these successful proof-of-concept data, we are now performing IND-enabling studies for our lead program, CBX-11 (alphalex-rucaparib), and plan to initiate our first Phase I clinical trial in the first quarter of 2020 in solid tumors independent of HRD status. This is the first of several programs we plan to bring to the clinic that have the ability to leverage the efficacy of known potent anticancer agents without inducing associated toxicities.”
The data were published in an online only abstract, titled Unlocking PARP inhibitor efficacy for HRD-negative cancers using the alphalex tumor targeting platform, accepted by the American Society for Clinical Oncology (ASCO) Annual Meeting 2019.
The Cybrexa alphalex technology platform enables the delivery of small molecules across the cell membrane under low pH conditions, which is a universal feature of cancer cells. As a result, alphalex technology – which consists of a novel peptide, linker, and small molecule anti-cancer agent – allows for antigen-independent, intracellular delivery of small molecule anti-cancer agents directly into the tumor cell. View a video of the mechanism of action of the technology at http://www.cybrexa.com/our-technology/.
Cybrexa is a privately held biotechnology company dedicated to developing an entirely new class of cancer therapies using its alphalex platform to deliver anti-cancer agents directly into tumor cells. The company’s lead candidate, CBX-11 (alphalex-rucaparib), is in preclinical development with advancing plans to initiate clinical development by 1Q 2020. Cybrexa was founded by physician-scientists, and has an experienced management team that has built numerous successful life sciences companies and raised hundreds of millions of dollars in venture capital. For more information, visit www.cybrexa.com.
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