Synergistic combination selectively kills tumors and prevents bone marrow toxicities
Poster presentation today during 30th EORTC-NCI-AACR Molecular Targets and Cancer Therapeutics Symposium
Marks initial introduction to company’s alphalex™ tumor-selective technology platform
NEW HAVEN, Conn., Nov. 13, 2018 (GLOBE NEWSWIRE) — Cybrexa Therapeutics, a biotechnology company developing a new class of cancer therapeutics through its alphalex™ tumor targeting platform, today announced that the company presented preclinical data regarding the alphalex™ platform’s application to a poly (ADP- ribose) polymerase (PARP) inhibitor. These data were presented today during the 30th EORTC-NCI-AACR Molecular Targets and Cancer Therapeutics Symposium, being held November 13-16 in Dublin, Ireland. This work was presented by Dr. Ranjit Bindra, Cybrexa scientific Co-founder and Associate Professor at the Yale School of Medicine.
Per Hellsund, President and Chief Executive Officer of Cybrexa Therapeutics, commented, “PARP inhibitors have emerged as an effective treatment option for some solid tumors, especially following DNA damaging chemotherapy. PARP inhibitors have enormous potential in combination with chemotherapy, but these combinations are often associated with life-threatening limitations of toxicity and bone marrow suppression. This preclinical study demonstrates that our alphalex™ technology is able to successfully combine a potent PARP inhibitor with chemotherapy in doses that effectively kill cancer cells, while at the same time preventing bone marrow suppression through intracellular, antigen-independent targeting of anti-cancer agents.”
Researchers attached talazoparib (BMN673, marketed as Talzenna™), a PARP inhibitor recently approved by the FDA for the treatment of breast cancer patients with BRCA1/2 mutations, to its novel alphalex™ peptide, which forms an alpha helix in the low-pH tumor microenvironment that is able to cross the cell membrane and release the combination therapy directly into tumor cells.
In the study, the conjugation of talazoparib to the alphalex™ peptide demonstrated:
- pH-dependent delivery of functional talazoparib into tumor cells in vitro;
- Sustained and selective in vivo tumor localization of talazoparib;
- Target engagement and penetration by talazoparib specifically in tumor tissue;
- Prevention of bone marrow toxicity when combined with chemotherapy; and
- Selective tumor cell killing in both non-HRD and HRD xenografts, including patient-derived xenografts (PDXs).
About alphalex™ Platform
The Cybrexa alphalex™ platform consists of a novel peptide-based technology developed from research at Yale University. This technology 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 of its low-pH dependent peptide, alphalex™ allows for antigen independent, intracellular delivery of small molecule anti-cancer agents. View a video of the mechanism of action of the technology at www.cybrexa.com.
Cybrexa is a privately-held biotechnology company dedicated to developing an entirely new class of cancer therapies using the alphalex™ platform to attach existing anti-cancer agents to the alphalex™ peptide that directly target the tumor microenvironment. The Company’s lead candidate, an alphalex™-PARP inhibitor combination, is in preclinical development with advancing plans for initiating clinical development. Cybrexa was founded by physician-scientists and an experienced management team that has built numerous successful life sciences ventures and raised hundreds of millions of dollars in venture capital. For more information about Cybrexa, please visit www.cybrexa.com.