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Pipeline
platON™ is Valerio Therapeutics’ proprietary chemistry platform of oligonucleotides acting as decoy agonists, which generates new innovative compounds that broaden the Company’s product pipeline.
AsiDNA™, the first compound sourced from platON™, is a first-in-class, highly differentiated DNA Damage Response (DDR) inhibitor based on a decoy mechanism with an agonist effect, acting upstream of multiple DDR pathways. AsiDNA™ has the ability to abrogate tumor resistance to PARP inhibitors regardless of the genetic mutation status. AsiDNA™ has also shown a strong synergy with other tumor DNA-damaging agents such as chemotherapy, radiotherapy and PARP inhibitors. Thanks to a good safety profile, AsiDNA™ is particularly amenable to combination treatment, a standard of care in aggressive or resistant cancers. AsiDNA™ was evaluated in the DRIIV-1b phase 1b study in combination with chemotherapy and is currently evaluated in the REVOCAN phase 1b/2 study in combination with PARP inhibitors in relapsed ovarian cancer.
OX401 is the second drug candidate from platON™ acting on both the DNA Damage Response and the activation of immune response, without inducing resistance. In vivo, OX401 has shown a potent antitumoral activity and a strong immune response activation. Optimization of this new molecule is in progress.
OX425, the second compound from platON, is a novel DDR Decoy Agonist with high antitumor activity. It also mediates multiple immunostimulatory effects by activating the STING pathway. OX425 is currently in IND-enabling preclinical development.
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.
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.
OX401 is the second candidate utilizing Valerio Therapeutics’ proprietary platform of decoy agonists, platON™.
OX401 was designed by capitalizing on Valerio Therapeutics’ expertise of oligonucleotides acting as decoy agonists and exhibits very original properties.
During optimization, OX401 has demonstrated that it inhibited the DNA Damage Response by acting on PARP proteins.
In parallel, OX401 activated the STING pathway, a recent and promising field of research in immuno-oncology, which makes it amenable to combinations with immuno-oncology agents such as checkpoint inhibitors.
While the clinical relevance of PARP inhibitors is now well-established, this class still has a number of limiting factors, particularly the relatively rapid onset of resistance. Its decoy agonist mechanism of action positions OX401 as a next-generation PARP inhibitor that should not present these limitations and instead offer a lack of acquired resistance and more specificity to cancer cells.
OX401 was also developed to induce a strong immune response through the activation of the STING pathway, an area of significant interest in immuno-oncology. However, current molecules have experienced challenges, notably in terms of toxicity. OX401 is based on the same decoy agonist mechanism as AsiDNA™, Valerio Therapeutics’ first-in-class DNA repair inhibitor, which showed good tolerance in the DRIIV-1 Phase 1 study and should trigger a rapid and significant inducing effect of innate immunity against tumor cells.
OX401 is currently undergoing proof-of-concept preclinical studies, alone and in combination with cancer immunotherapies.
Patents has been filed to protect Valerio Therapeutics’ intellectual property rights on OX401 , alone and in combination with cancer immunotherapies.
OX401
