Clinical Trials

Date: 2016-09-07

Type of information: Publication of results in a medical journal

phase: preclinical

Announcement: publication of results in Clinical Cancer Research

Company: Onxeo (France)

Product: AsiDNA™

Action mechanism:

• nucleotide/signal interfering DNA molecule/DNA break repair inhibitor. AsiDNA™ is a signal-interfering DNA (siDNA) product candidate. This short, double-stranded DNA molecule breaks the cycle of tumor DNA repair by interfering at the core of DNA damage, blocking multiple repair pathways, while sparing healthy cells.
• In March 2016, Onxeo successfully completed the acquisition of DNA Therapeutics for its key innovative DNA repair inhibitor technology platform and lead compound AsiDNA. This first-in-class signal interfering DNA repair compound is a short double-stranded DNA molecule which breaks the cycle of tumor DNA repair by interfering at the core of DNA damages, blocking multiple repair pathways, while sparing healthy cells. AsiDNA and its signal-interfering technology offer potential new treatment options for patients suffering from various types of cancer. This technology has already demonstrated an increase in the efficacy of radiotherapy , radiofrequency ablation , and chemotherapy in a variety of preclinical animal models, making it a promising candidate for both mono and combination therapy.
• A first-in-human Phase I/IIa trial (DRIIM) performed in metastatic melanoma further demonstrated that AsiDNA molecules showed good tolerance and safety when administered intra-tumorally and subcutaneously around the tumors, with no evidence of inflammatory phenomena. Results presented at ASCO 2015 showed, based on 23 patients, an objective response rate (ORR) of 59% and a complete response (CR) rate of 30% compared to 10% CR with radiotherapy alone.

Disease:

Therapeutic area: Cancer - Oncology

Country:

Trial details:

Latest news:

• • On September 7, 2016, Onxeo announced results from a preclinical study demonstrating that the synergistic effect of its lead signal-interfering DNA product candidate AsiDNA™ in combination with various products in the PARP (PolyADP-Ribose Polymerase) inhibitor class of drugsis able to bypassthe genetic restriction of PARP inhibitors. The results, which establish potential for rapid clinical translation, were recently published online in the article “Drug Driven Synthetic Lethality: bypassing tumor cell genetics with a combination of Dbait and PARP inhibitors” in the peer-reviewed journal Clinical Cancer Research. The preclinical study characterized the DNA repair inhibition activity of AsiDNA and olaparib – by monitoring DNA repair and DNA damage, and analyzed cell survival to standalone and combined treatments of 21 different tumor cell lines, including 12 breast cancer cell lines, and 3 non-tumor cells. Results showed that olaparib and AsiDNA prevent recruitment of different targeted repair enzymes to damaged sites, and the combination of both drugs increases the accumulation of unrepaired damage, resulting in a synergistic increase of cell death in all tumor cells. Synergistic efficacy of the combination treatment was observed in all tested tumor models regardless of BRCA status, while no increase of DNA damage, nor lethality was observed in healthy cells, suggesting a good safety and tolerability profile. Analysis also demonstrated different molecular mechanisms underlying the response to AsiDNA and olaparib, suggesting that drug resistance to the combination would be a very rare event. Furthermore, the study also showed that the combination with AsiDNA is effective using six different PARP inhibitors, with no toxicity in non-tumor cells.
• • On June 27, 2016, Onxeo  announced its plan for further development of AsiDNA™, its first-in-class signal interfering DNA molecule which breaks the cycle of tumor DNA repair to induce cancer cell death. In March 2016, Onxeo successfully completed the acquisition of DNA Therapeutics for its key innovative DNA repair inhibitor technology platform and lead compound AsiDNA. Following the acquisition, Onxeo has strategically assessed development options and is now accelerating a deep and comprehensive advancement plan for AsiDNA™ both as monotherapy and in combination with anti-cancer agents. The company is initating the development of AsiDNA through a systemic administration, enabling its potential as a therapy across a broad range of oncology indications. Preclinical programs have been initiated to further define the pharmacokinetic/pharmacodynamic profile following an intravenous administration. Results are expected in Q3/Q4 2016.
• In parallel, Onxeo is collaborating with one of the top U.S. manufacturing expert facilities for complex life science products, in order to optimize the manufacturing process of AsiDNA. Overall, the goal is to improve costs and production duration for future large-scale clinical development and industrialization. First results for this process development are expected in Q4 2016.
• Based on the already deep knowledge generated and the study outcomes set forth above, Onxeo is also exploring opportunities to accelerate the clinical development of AsiDNA and is planning to launch its first clinical trial of AsiDNA as soon as 2017 to assess safety and first indication of anti-cancer activity of AsiDNA as monotherapy via systemic administration.

Is general: Yes