1. >
  2. Products
  3. >
  4. AsiDNA™

AsiDNA™

A first-in-class product candidate in the leading field of DNA Damage Response (DDR), AsiDNA™ disrupts and exhausts the ability of tumor cells to repair their DNA by acting upstream of multiple repair pathways. AsiDNA™ and its technology originate from three major French academic centers: Curie Institute, CNRS, and the Museum of Natural History. It aims to offer new treatment options for patients suffering from various types of cancer.

A DIFFERENTIATED MECHANISM OF ACTION IN DNA DAMAGE RESPONSE


AsiDNA™ is a short double-stranded DNA fragment (oligonucleotide) that acts as a decoy, mimicking double-strand breaks in the DNA of the tumor cell. AsiDNA™ molecules trigger false DNA break signals to activate and attract DNA repair proteins, which prevents their recruitment to the site of actual DNA damage. As a result, damages to tumor cells’ DNA remain unrepaired. As cancer cells have lost the ability to regulate cell division, they will continue dividing with damaged DNA, ultimately leading to cancer cell death (mitotic catastrophe). Healthy cells, on the other hand, will halt cell division until the compound is no longer present and damaged DNA can be repaired.

AsiDNA™ mechanism is significantly differentiated in the field of DNA Damage Response as it does not inhibit specific enzymes (such as PARP inhibitors) but targets the entire DNA repair process, acting upstream of multiple DDR pathways as an agonist through a decoy mechanism.

AsiDNA™ mimics DNA breaks in the tumor cell, sends false alarms (decoy mechanism) then binds and activates key proteins of the DNA Damage Response

This sustained artificial DNA damage signaling (agonist effect) leads to exhaustion of the tumor DNA repair mechanisms

The actual tumor DNA breaks are not repaired and accumulate: the cancer cells die when they replicate with damaged DNA.

AsiDNA™ is a multi-target decoy agonist, the only agonist in the field of DDR

Unlike targeted therapies, AsiDNA™ acts on many proteins, particularly PARP and DNA-PK which are involved very early in the damage response, from the detection and signaling stages.

AsiDNA™ does not induce any resistance and reverses resistance to other treatments

AsiDNA™ acts on all repair pathways:  the tumor cell cannot use another protein or repair pathway to resist its action, which is the case with targeted therapies.

The more AsiDNA™ is used as a treatment, the more effective it becomes

AsiDNA™ does not oppose, but on the contrary encourages, hyper-activates and hijacks a natural biological process so essential for its survival that the tumor cell cannot stop it. Thus, AsiDNA™ is increasingly effective as the tumor cell exhausts its ability to respond to DNA damage.

Thanks to these distinctive properties and a favorable safety profile, AsiDNA™ is ideally suited for development in combination with other anti-cancer therapies.

 


PRECLINICAL HIGHLIGHTS

An extensive and robust preclinical package has been built highlighting the differentiated properties of AsiDNA™, notably the absence of resistance after repeated treatment, the prevention and reversion of resistance to PARP inhibitors and a strong synergy with other anti-cancer agents such as PARP inhibitors or platinum-based chemotherapies.


Learn more on the effect of AsiDNA™ on tumor persister cells,
contributing to tumor resistance to treatment and cancer relapse
 


CLINICAL DEVELOPMENT

AsiDNA ™ has already demonstrated a good safety profile in two phase 1 studies, via intratumoral and via intravenous administration, and is currently being evaluated in combination with chemotherapy (carboplatin and paclitaxel) in solid tumors in the DRIIV- 1b study.

  • A first Phase 1 trial (DRIIM study), in which AsiDNA™ administered intratumorally was evaluated in combination with radiotherapy in patients with skin metastases from melanoma, highlighted in 2016 its good safety profile and showed first signals of efficacy.
    First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients with skin metastases from melanoma.
    LeTourneau C et al. Br J Cancer. 2016 May 24;114(11):1199-205.
  • In 2018, the DRIIV-1 (DNA Repair Inhibitor administered IntraVenously) phase 1 study has evaluated AsiDNA™ standalone by systemic administration (IV) in metastatic solid tumors and confirmed active doses as well as a favorable safety profile in 22 patients. In this study, AsiDNA™ has achieved proof-of mechanism through the strong engagement of its biological targets. The active dose of 600 mg was determined as optimal for the ongoing clinical development of AsiDNA™ in various combinations.
    Access the protocol on ClinicalTrials.gov: Identifier NCT03579628
    Access the results in the poster presented at the EORTC-AACR-NCI Conference (October 2019)
    Access the results in the article published in the British Journal of Cancer (August 2020)
  • Initiated in 2019, the DRIIV-1b study is currently evaluating AsiDNA™ in combination with carboplatin, and carboplatin plus paclitaxel in patients with advanced metastatic tumors. Preliminary results from the first cohort with carboplatin alone have shown good tolerance, stabilized disease and increased duration of treatment vs. previous treatment lines. Favorable preliminary results obtained in 2020 showed promising efficacy signals.
    Access the notable clinical cases in the article published in Oncology & Cancer Case Reports (March 2021)
    A randomized phase 2 trial  of this combination in a selected high unmet need indication is scheduled to start in 2021.
  • The phase 1b/2 study REVOCAN, sponsored by Gustave Roussy, was designed to assess the abrogation of resistance to PARP inhibitor niraparib by AsiDNA™ in relapsed ovarian cancer and started in late 2020. Preliminary results are expected in 2021.
  • AsiDNA™ Children, sponsored by Institut Curie, is a phase 1b/2 study designed to assess the effect of AsiDNA™ with combination with radiotherapy to treat children affected with recurrent high grade glioma. It is expected to start in 2021.

Learn more about the role of AsiDNA™ in the new combination strategies


INTELLECTUAL PROPERTY

AsiDNA™ is protected internationally by several patent families covering the chemical composition of the product, its method of use or of administration as well as some combinations with other anti-cancer products.  These patent families give AsiDNA™ a very wide field of protection.

The main patent protects AsiDNA™ until mid-2031 and may be extended until 2036 via the different supplemental protection systems prevailing in the United States and in Europe. The latest patents on methods of use or combinations - such as with PARP inhibitors - will be valid until 2036, before extension period.

AACR VIRTUAL MEETING 2021

ESMO-TAT 2021

AACR VIRTUAL MEETING 2020

PARP & DDR INHIBITORS SUMMIT 2020

TIDES EUROPE 2019

AACR-NCI-EORTC 2019

AACR 2019

AACR 2018

AACR 2017

ASCO 2015

AACR 2013