On March 25, 2019 Onxeo SA (Euronext Paris, NASDAQ Copenhagen: ONXEO), (" Onxeo " or "the Company "), a clinical stage biotechnology company specializing in the development of innovative oncology drugs targeting tumor DNA damage response mechanisms (DDR), in particular to fight against rare or resistant cancers, reported that information on the five study presentations presenting important data on AsiDNA , its most advanced candidate, which will be presented in the form of posters in Congress American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting , March 29 – April 3, 2019, Atlanta, Georgia, United States (Press release, Onxeo, MAR 25, 2019, View Source [SID1234534611]).
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Françoise Bono, Scientific Director of Onxeo, says :"We are very pleased that these five studies have been accepted for presentation at the prestigious AACR (Free AACR Whitepaper) Conference. This recognition illustrates the interest, quality and diversity of translational research that we are currently conducting with AsiDNA . Our data once again demonstrate the singularity of our lead compound and its unique properties, particularly to prevent the emergence of treatment resistance, one of the most troubling issues in oncology today. All these data complement and reinforce our arguments for the further clinical development of AsiDNA , which is scheduled to begin in the coming weeks, now that we know the doses for which AsiDNA activates its cellular targets and confirmed its favorable safety profile, in the phase 1 study, DRIIV. We look forward to presenting the very promising results we have achieved and discussing them at this conference. "
Details of the sittings of April 1st and 2nd, 2019:
Abstract 2095 / Poster 2 – AsiDNA , a targeted treatment with no acquired resistance
Session: PO.ET03.03. Drug Resistance 3
Date: Monday 1 st April
Time: 1:00 p.m. to 5:00 p.m. AND
Location: Section 11
AsiDNA is the first antitumor drug in the field of DDR acting as an agonist 1. It causes a strong warning signal of the presence of DNA damage. This study demonstrates that long-term exposure of cancer cells to this warning signal does not promote the emergence of AsiDNA resistance. In contrast, repeated exposure downregulates the targeted repair pathways, a condition that persists for several months after AsiDNA treatment. This property is due to the singular mechanism of action of AsiDNA , which simulates a signal of DNA damage through over-activation (agonist effect) of the DNA-PK and PARP enzymes. This property is not observed with other DNA repair inhibitors such as PARP inhibitors olaparib and talazoparib which all eventually induce resistance. Long-term treatment with AsiDNA instead decreases the "vigilance" of the tumor cells, which improves the effectiveness of the product. These results indicate that agonist drugs such as AsiDNA may induce tumor cell evolution with a reduction in their ability to respond when signaling lesions on their DNA.
Abstract 2130/7 – Development of a biomarker-based patient selection strategy for AsiDNA treatment (collaboration with Institut Curie)
Session: PO.ET04.04 – Molecular Classification of Tumors
Date: Monday 1 st April
Time: 1:00 p.m. to 5:00 p.m.
Location: Section 12
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1 Agonist: who has the property to activate
It remains very difficult to accurately assess and predict the response to cancer treatment. Stratification biomarkers are a valuable aid in identifying the patients most likely to respond to a particular drug, or even to distinguish between early and delayed responses. In this study, we identified a genetic signature that predicts the efficacy of AsiDNA treatment in patients. AsiDNA is currently in clinical trial and rapid validation of the most sensitive gene cluster is possible, with a view to developing a biomarker-based patient selection strategy for AsiDNA treatment.
Abstract 2918/6 – Molecular analysis of the mechanism of action of AsiDNA provides new clues to the regulation of DNA damage response
Session: PO.TB09.01 – Tumor Radiosensitivity or Resistance
Date: Tuesday, April 2
Time: 8:00 – 12:00
Location: Section 8
In this study, the different stages of AsiDNA activity were analyzed. The data show that AsiDNA inhibits the joining of non-homologous ends of DNA (NHEJ) and the repair of DNA double-strand breaks by homologous recombination by preventing the recruitment of key enzymes at the site of the break. Inhibition of recruitment of proteins involved in NHEJ is the first event and requires the activity of PARPs. Inhibition of homologous recombination proteins occurs late and depends on the activation of DNA-PK. PARP activation induces a metabolic change that could participate in the antitumor activity of AsiDNA .
Abstract 2865/6 – AsiDNA , a novel DNA repair inhibitor for sensitizing aggressive subtypes of medulloblastoma (Institut Curie)
Session: PO.TB09.01 – Targets and Therapies in Pediatric Cancer
Date: Tuesday, April 2
Time: 8:00 – 12:00
Location: Section 6
Medulloblastoma is a tumor of the cerebellum, and is the most common malignant brain tumor in children. There is often significant treatment-related mortality. It is therefore important to improve treatment efficacy for the most aggressive subgroups and to reduce treatment-related mortality for all subgroups. In this study, no increase in post-irradiation toxicity was observed with AsiDNA . In vivo, AsiDNA alone significantly improves survival rates (p = 0.005) and the effectiveness of radiotherapy. In combination with radiation therapy, AsiDNA can delay tumor growth and improve survival compared to radiotherapy alone.
Abstract 3797/2 – AsiDNA abrogates acquired resistance to PARP inhibitors
Session: PO.ET03.05 – Drug Resistance 5
Date: Tuesday, April 2
Time: 1:00 pm – 5:00 pm
Location: Section 10
PARP inhibitors (PARPi) are approved for the treatment of cancers with a deficient homologous recombination pathway. Despite the success of this approach, resistance to these drugs remains a clinical problem. In this study, long-term exposure of cancer cells to PARPi showed resistance in all independent populations tested, raising the question of the clinical benefits of long-term continuation of PARPi monotherapy. Interestingly, populations treated with AsiDNA (2.5 μM – low non-cytotoxic dose) in combination with talazoparib or olaparib had a significantly lower probability of resistance. Furthermore, AsiDNA partially blocks resistance to talazoparib in resistant populations. The results indicate that AsiDNA may be able to abrogate and reverse the acquired resistance to PARPi by normalizing the expression and activity of the proteins involved.