New Preclinical Results on Onxeo’s AsiDNA™, First-in-Class DNA Repair Inhibitor, Point to Strong Synergy and Reversion of Tumor Resistance when combined to PARP inhibitors

  • AsiDNA™ combined with olaparib* more than doubled the complete
    response rate observed with olaparib alone in an in vivo model of
    triple negative breast cancer resistant to PARP inhibitors
  • AsiDNA™ combined with olaparib inhibited tumor growth in an in
    vivo model of ovarian cancer resistant to olaparib
  • AsiDNA™ combined with various PARP inhibitors prevented the
    occurrence of resistance and reversed this resistance to PARP
    inhibitors after repeated exposure in in vitro models of triple
    negative breast cancer and small cell lung cancer
  • Together with the first activity results of the DRIIV-1 study of
    AsiDNA™ expected in Q4 2018, these data support a clinical development
    of the combination of AsiDNA™ with PARP inhibitors

PARIS–(BUSINESS WIRE)–Regulatory News:

Onxeo S.A. (Euronext Paris, NASDAQ Copenhagen: ONXEO), (“Onxeo
or “the Company”), a clinical-stage biotechnology company
specializing in the development of innovative drugs in oncology, in
particular against rare or resistant cancers, today announced new
positive results from preclinical studies of AsiDNA™, its first-in-class
DNA Repair inhibitor, in combination with PARP inhibitors (PARPi). The
results of these extensive studies with different PARPi point to the
ability of AsiDNA™ to prevent the occurrence of resistance and even to
reverse the acquired resistance of the tumor cell after PARPi
treatments. Furthermore, they show that the combination has a strong
synergistic anti-tumor activity in in vitro and in
 models of solid tumors resistant to PARPi (HR proficient).
Together with the preliminary data on the activity and safety of AsiDNA™
expected in Q4 2018 from the DRIIV-1 clinical trial, these results
support clinical development of AsiDNA™ in combination with PARP
inhibitors, which should start from year-end 2018.

Judith Greciet, Chief Executive Officer of Onxeo, said: “Onxeo
is conducting an ambitious development program for AsiDNA™, notably
translational, in combination with various anti-cancer agents in order
to provide strategic information aimed at determining the indications
and combinations to target in further clinical development as soon as
the first results from DRIIV-1 are available. Assessing the combination
of AsiDNA™ with PARPi is a priority, as their mechanisms of action are
very complementary in indications with high unmet medical needs. Sales
for the PARPi class are already substantial in ovarian cancer and are
expected to increase markedly in the near-term as products gain access
to multiple additional oncology indications. Our recent studies indicate
that AsiDNA™ in combination with PARPi could enable PARPi to overcome
the requirement of a genetic mutation such as BRCA-, and show a strong
synergistic activity versus PARPi alone. Moreover, the combination
appears to both prevent the occurrence of resistance to PARPi and
reverse the acquired resistance, which may considerably expand treatment
duration with PARPi. A treatment combining AsiDNA™ and PARPi could
therefore significantly broaden the patient population eligible to PARPi
and improve their efficacy, which is of great interest to the scientific
community, the pharmaceutical industry and the patients for its
potential to address resistant cancers.”

AsiDNA™ is a first-in-class DNA repair inhibitor in the field of DNA
Damage Response (DDR) that mimics double-stranded DNA breaks in tumor
cells, activating repair pathways, diverting repair enzymes from the
target and finally depleting the cell through a unique mechanism of
agonist and decoy.

Data show that in in vitro models of HR proficient TNBC (triple
negative breast cancer) and SCLC (small cell lung cancer), AsiDNA™ maintains
PARP1 expression
, the repair enzyme inhibited by PARP inhibitors,
and abrogates the occurrence of resistance to PARPi, including in
models of cancers resistant to PARPi. Down regulation of the
PARP1 enzyme is one of the mechanisms that supports the occurrence of
resistance to PARPi inhibitors1. As AsiDNA™ hyper-activates
repair enzymes, an up regulation of PARP1 expression following treatment
with AsiDNA™ or with AsiDNA™ associated to PARPi support the use of
AsiDNA™ to maintain the sensitivity to PARPi treatment.

Furthermore, combination treatment of olaparib with AsiDNA™ more than
doubles the complete response rate observed with olaparib alone
vs. 33%) in an in vivo model of HR proficient TNBC model and inhibits
tumor growth
in a humanized Patient-Derived Xenograft (PDX) mice
model of ovarian cancer resistant to olaparib. PDX models are considered
highly predictive of clinical behavior2.

The Company will submit the detailed results of these preclinical
studies to leading peer-reviewed publications and international
scientific conferences.

Francoise Bono, Chief Scientific Officer of Onxeo, concluded: “These
most recent data validate our disruptive approach to DNA-targeting and
confirm the broad opportunities for our lead molecule thanks to its
unique mechanism of action. Our team has built an extremely solid body
of preclinical evidence, both in-vitro and in highly predictive
humanized in-vivo models, which shows the potential of AsiDNA™ to
reverse the resistance to PARP inhibitors and the strong synergy of
their combination. This is the first part of our extensive translational
plan which aims at confirming the full potential of AsiDNA™ in
combination with other anticancer agents such as chemotherapies or
epigenetic compounds, including belinostat. Additional data on these
possible combinations will be available after the summer to
further inform the clinical development of AsiDNA™ in combinations
offering the potential for significant therapeutic improvement.


* Olaparib is the first PARPi approved in December 2014 by both the
FDA and the EMA.

1 Montoni A, Robu M, Pouliot E, Shah GM. Resistance
to PARP-Inhibitors in Cancer Therapy. Front Pharmacol. (2013 Feb)
27;4:18. doi: 10.3389/fphar.2013.00018

2 Tentler JJ, Tan AC, Weekes CD, et al.
Patient-derived tumour xenografts as models for oncology drug
development. (2012 Jun) Nature Reviews. Clinical Oncology (Review). 9 (6):
338–50. doi:10.1038/nrclinonc.2012.61

About Onxeo

Onxeo (Euronext Paris, NASDAQ Copenhagen: ONXEO) is a French
biotechnology company developing innovative oncology drugs based on
DNA-targeting and epigenetics, two of the most sought-after mechanisms
of action in cancer treatment today. The Company is focused on bringing
early-stage first-in-class or disruptive compounds (proprietary,
acquired or in-licensed) from translational research to clinical
proof-of-concept, a value-creating inflection point appealing to
potential partners.

Onxeo is developing AsiDNA™, a first-in-class DNA break repair
inhibitor based on a unique decoy mechanism. AsiDNA™ has already
successfully completed a Phase I trial in metastatic melanoma via local
administration and is currently being evaluated for systemic (IV)
administration in solid tumors in the DRIIV phase I study ((DNA Repair
Inhibitor administered IntraVenously).

AsiDNA™ is the first compound generated from platON™, the
Company’s proprietary chemistry platform of decoy oligonucleotides based
on three components, a sequence of double strand oligonucleotides, a
linker and a cellular uptake facilitator. PlatON™ will continue to
generate innovative compounds targeting tumor DNA functions and broaden
Onxeo’s pipeline.

Onxeo’s R&D pipeline also includes belinostat, an HDAC
inhibitor (epigenetics) currently evaluated in oral form to be used in
combination with other anti-cancer agents for liquid or solid tumors.
Belinostat is already conditionally FDA-approved in the US as a 2nd
line treatment for patients with peripheral T cell lymphoma and marketed
in the US by Onxeo’s partner, Spectrum Pharmaceuticals, under the name
Beleodaq® (belinostat IV form).

For further information, please visit

Forward looking statements

This communication expressly or implicitly contains certain
forward-looking statements concerning Onxeo and its business. Such
statements involve certain known and unknown risks, uncertainties and
other factors, which could cause the actual results, financial
condition, performance or achievements of Onxeo to be materially
different from any future results, performance or achievements expressed
or implied by such forward-looking statements. Onxeo is providing this
communication as of this date and does not undertake to update any
forward-looking statements contained herein as a result of new
information, future events or otherwise. For a discussion of risks and
uncertainties which could cause actual results, financial condition,
performance or achievements of Onxeo to differ from those contained in
the forward-looking statements, please refer to the section
“Risk Factors” (“Facteurs de Risque“) of the 2017
registration document filed with the Autorité des marchés financiers
on April 25, 2018 under number D.18-0389, which is available on the Autorité
des marchés financiers
website (
or on the Company’s website (


Valerie Leroy, +33 1 45 58 76 00

Caroline Carmagnol / Tatiana Vieira, 33 (0) 1 44 54
36 65
Relations / Strategic Communication

Dušan Orešanský / Emmanuel
Huynh, +33 1 44 71 94 92
Relations US

Brian Ritchie, +1 212 915 2578