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Tumor-selective CBX-11 allows full dose co-administration with chemotherapy, enabling synergistic efficacy in HRD negative tumors
Poster presentation today during AACR Annual Meeting 2019
NEW HAVEN, Conn., April 02, 2019 (GLOBE NEWSWIRE) -- Cybrexa Therapeutics, a biotechnology company developing a new class of cancer therapeutics through its alphalex™ tumor targeting platform, today announced that the FDA- and EMA-approved poly ADP-ribose polymerase (PARP) inhibitor rucaparib (marketed as Rubraca®) is conjugated in lead candidate CBX-11 (alphalex™-rucaparib). The first set of preclinical data supporting CBX-11 demonstrate that Cybrexa’s proprietary alphalex™ platform can enable full dose administration with DNA damaging chemotherapy, creating synergistic efficacy in destroying solid tumors independent of homologous recombination deficiency (HRD) status. In particular, CBX-11 selectively delivers rucaparib to tumor tissue, avoiding the bone marrow toxicity that has prevented optimal dosing of DNA damaging chemotherapy in combination with PARP inhibitors.
These data were exhibited today in a poster presentation by Vishwas Paralkar, PhD, Chief Scientific Officer of Cybrexa, during the American Association for Cancer Research (AACR) Annual Meeting 2019.
“These mark the first results demonstrating that combination of the potent PARP inhibitor rucaparib and chemotherapy is able to effectively kill cancer cells independent of HRD status and without the extreme bone marrow toxicity historically observed in this combination, which previously resulted in significant dose reduction and therefore efficacy reduction,” said Vishwas Paralkar, PhD, Chief Scientific Officer of Cybrexa. “The synergistic efficacy allowing full dose administration of both rucaparib and chemotherapy is a direct result of our alphalex™ technology platform that selectively targets tumor cells to overcome this barrier for combination therapies.”
In the study, tumor targeting of rucaparib was achieved using the alphalex™ platform, which allows small molecule anti-cancer agents to penetrate cell membranes only at the low pH associated with the tumor microenvironment. These data demonstrate that the alphalex™ conjugate inserts only across cancer cell membranes to deliver its cargo directly into the cancer cell. The safety and efficacy of the approach was confirmed in vivo using CBX-11, which was safely administered with cytotoxic chemotherapies to selectively kill both HRD-positive and HRD-negative tumors with significant sparing of bone marrow.
Per Hellsund, President and CEO of Cybrexa, commented, “These preclinical results highlight an entirely new approach to applying PARP inhibitors against solid tumors independent of HRD status and directly support our Phase 1 clinical trial evaluating CBX-11 in combination with chemotherapy, which is planned to start in the first quarter of 2020. Furthermore, our alphalex™ platform approach can be applied to a diverse range of DNA damage repair inhibitors to enable combinations with chemotherapy and chemo-radiation in a tissue-agnostic manner and we look forward to discussing these applications.”
About the alphalex™ Technology Platform
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, an alphalex™-rucaparib combination, 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 about Cybrexa, please visit www.cybrexa.com.
The Ruth Group