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Presentation oF DNV3837 to ECCMID2019


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Georges Gaudriault, CSO of DEINOVE, presented at ECCMID2019 a project update on the clinical development of DNV3837, a first-in-class antibiotic candidate targeting severe Clostridium difficile infections, scheduled to enter Phase II by mid-2019.

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Presentation oF DNV3837 to ECCMID2019

  1. 1. DNV3681/DNV3837 Project update Georges GAUDRIAULT, Chief Scientific Officer ECCMID 2019 Therapeutics Pipeline Corner April 14, 2019
  2. 2. Our long-term commitment to develop new antibiotics DEINOVE strategic developments of antibacterial therapeutics are built through a two-pronged approach Building a long-term product pipeline through AGIR program – “Antibiotics against resistant infectious germs” • Funded by the French government (14.6M€) aiming at developing natural products with antibacterial activities • Start of the project: November 2017 Push innovative and differentiated assets that target unmet medical need to the market • Acquisition of Morphochem & Biovertis in order to develop DNV3837 asset (Phase II ready asset - formerly MCB3837) Q2 2018 2
  3. 3. DNV3681, a new member of the quinolonyl-oxazolidinone class 3 Oxazolidinone DNV3681 Spacer NO CLEAVAGE OF SPACER SPACER IS KEY FOR ANTIBACTERIAL ACTIVITY AND MODE OF ACTIONFluoroquinolone +
  4. 4. DNV3681 has a combined mode of action 4 INHIBITS BACTERIAL PROTEIN SYNTHESIS INHIBITS BACTERIAL DNA GYRASE In vitro translation (µM) E. Coli DNA Gyrase (µM) Human Top. II (µM) DNV3681 1.2 4.9 200 Ciprofloxacin N/A 0.43 400 Linezolid 3.2 >100 N/A
  5. 5. A prodrug approach to improve water solubility of DNV3681 5 DNV3681 DNV3837 Solvent Solubility (mg/ml) DNV3681 DNV3837 Dimethyl sulfoxide >200 >200 Water <0.01 >200 0.9% (w/v) NaCl in water <0.01 20 pH7 aqueous buffer <0.01 21
  6. 6. Active against Clostridioides difficile clinical isolates (n=199) 6 µg/ml MIC range MIC50 MIC90 Fidaxomicin 0.004 to 0.25 0.06 0.125 DNV3681 0.008 to 0.5 0.125 0.25 Vancomycin 0.5 to 8 1 2 Metronidazole <0.125 to 4 0.25 1 Tigecycline 0.03 to 0.125 0.06 0.06 Ciprofloxacin 8 to >128 64 256 Linezolid 2 to >64 4 8 BETTER THAN MOST STANDARD OF CARE (VANCOMYCIN AND METRONIDAZOLE SIMILAR TO FIDAXOMICIN
  7. 7. DNV3837 is rapidly converted in DNV3681 in vivo 7 DNV3837 In vivo dephosphorylation DNV3681 Pharmacokinetic in healthy volunteers (n=6) DNV3681 is generated by hydrolysis of DNV3837 and excreted in human feces Fecal concentrations of DNV3681 (mean ± SD; n=12) Pre-dose mg/kgfeces 50 100 150 200 117 ± 92 250 Day 2 Last day of infusion 0 171 ± 43
  8. 8. DNV3837 A DIFFERENTIATED THERAPEUTIC OPTION FOR CDI 8 SHORTER DEVELOPMENT PROCESS & PRIORITY REVIEW Fast Track Status & QIDP designation already granted by FDA STARTING PHASE IIA Scheduled by mid-2019 Tolerability tested in Phase I (3 Phases I, 90 healthy patients) FIRST-IN-CLASS SMALL MOLECULE Novel class: quinolonyl-oxazolidinone Mechanism of action identified Proof of Principle for intravenous (IV) treatment of CDI 1ST LINE TREATMENT for severe Clostridium difficile infections TREATMENT BY INTRAVENOUS INJECTION Oral treatments often not effective for severe cases (colitis, intestinal paralysis…)
  9. 9. THANK YOU