Onxeo announces compelling preclinical data in combination for its two innovative compounds, AsiDNA™ and belinostat
- Results demonstrate a very strong synergistic effect between AsiDNA™, first-in-class DNA break repair inhibitor (DBRi), and histone deacetylase inhibitors (HDACi)
- This synergy is particularly high for the combination of its two proprietary assets, AsiDNA™ and belinostat,
- Potential application of AsiDNA™ in combination with any HDACi fully covered by a key worldwide patent application
Paris (France), September 28, 2017 – 08:00 am CEST– Onxeo S.A. (Euronext Paris, NASDAQ Copenhagen: ONXEO), (“Onxeo” or the “Company”), a French biotechnology company specializing in the development of innovative drugs in oncology, in particular orphan cancers, today announced compelling results from extensive in-vitro preclinical studies of combinations of AsiDNA™ a first-in-class DNA break repair inhibitor (DBRi) with histone deacetylase inhibitor (HDACi), including belinostat, on various tumor cell lines. These data and potential future applications have been fully protected by a patent application filed today covering the use of AsiDNA™ in combination with any HDAC inhibitor in any treatment scheme.
Based on scientific evidence that HDAC inhibitors increase two-strand DNA breaks in tumor cells, the company has performed combination experiments demonstrating the synergistic effect of the association of AsiDNA™, its first-in-class DBRi, with HDAC inhibitors, including with its other key strategic asset belinostat, a multi-potent HDACi.
The study evaluated the efficacy of the combination on tumor cells lines and healthy cells compared to each compound alone. The results are expressed as percentage of living cells relative to non-treated condition.
The combination shows (pink bars) a very high level of efficacy (very limited detectable surviving cancer cells) compared to each compound alone, with statistical significance, on both the liquid and the solid tumor cell line. On the contrary, there was no effect on healthy cells lines, neither from compounds alone or the combination which is encouraging in terms of safety profile of the combination
Notable highlights from these in-vitro preclinical studies are:
The combination is strongly synergistic and leads to tumor cells death, as shown in the above graph.
Unlike when HDAC inhibitors are used alone, the combination of AsiDNA™ with HDACi remains synergistic over time after repeated administration: this may open the way to very relevant combination treatment schemes.
Experiments have been repeated with other HDACi such as vorinostat, entinostat, romidepsin and generated a similar type of data showing strong synergistic effects.
The company plans to pursue this development and to begin the in-vivo demonstration shortly.
“These preclinical results widely open the potential of our two proprietary assets, strengthening Onxeo’s position as innovation leader in DNA-targeting and epigenetics, two mechanisms of action at the forefront of oncology research and highly sought after,” said Judith Greciet, Chief Executive Officer of Onxeo. “AsiDNA™ had already shown a significant synergistic effect in combination with PARP inhibitors, another class of DNA repair inhibitors. These new data give us the ability to leverage another type of combination of AsiDNA™ with HDAC inhibitors. As Onxeo owns both AsiDNA™ and a potent HDACi, belinostat, we enjoy the full flexibility to further advance this development in the most appropriate way for the Company.”
AsiDNA offers multiple paths forward, in monotherapy or combination and these recent data further expand the potential of this promising first-in-class candidate. Additional preclinical results will be disclosed on an on-going basis and the Company has planned an extensive publication plan, stating at the upcoming AACR meeting in April 2018.
Under the commercial name Beleodaq®, belinostat is already approved in the US for the 2nd line treatment of patients with peripheral T-cell lymphoma (PTCL) and marketed by Onxeo’s partner Spectrum Pharmaceuticals (SPPI). For the past months, the Company has also been developing and protecting an oral formulation of belinostat. The patent application filed by Onxeo for oral belinostat would extend its protection until 2038.
These compelling preclinical data together with the long patent coverage of the oral formulation could leapfrog the current scope of belinostat to a largely wider clinical potential, far beyond PTCL, to address other types of liquid or solid tumors, with a tremendously enhanced efficacy profile when combined with AsiDNA™.
 Epigenetics refers to changes that affect gene activity and expression, without directly modifying the DNA. E.g. HDACi such as belinostat encourage DNA alterations, in particular double-strand breaks, by acting on histone and other proteins.
 Jdey W, et al. Clin Cancer Res. 2017 Feb 15;23(4):1001-1011