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Anti-Infective Drug Discovery

Objective & Challenges: Objective was to identify an optimized anti-bacterial lead molecule with in vivo efficacy in relevant infection models an acceptable safety profile, and a patentable series. Challenge was to develop a more efficacious compound than the reference standard.

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Anti-Infective Drug Discovery

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  1. Case Study Anti-infective drug discovery 1

  2. Objective & Challenges: Objective was to identify an optimized anti-bacterial lead molecule with in vivo efficacy in relevant infection models an acceptable safety profile, and a patentable series. Challenge was to develop a more efficacious compound than the reference standard. Study design: • Compounds were designed and synthesized with variation. • 232 compounds were generated from 8 different series. • 3 molecules were identified from different series meeting the early lead criteria & 148 compounds were generated from 3 series. • 2 patentable leads were identified from structurally diverse series out which AU-XXX was nominated as candidate molecule. Outcome: • Improved potency (1-4x) with expanded spectrum of activity was observed. • In vitro to in vivo translation. • Favourable DMPK properties – Metabolically stable (MLM, RLM, PHLM) with good solubility and low serum protein binding. • No CYP liability. • Probe toxicity studies indicate better safety profile than the reference compound. 2

  3. Results: • AU-XXX Concentration (MIC) of 1-2 µg/mL against different phenotypes pathogens S. aureus, E. faecalis and E. faecium. • AU-XXX exhibited good in vitro antibacterial activity against respiratory S. pneumoniae, H. influenzae, and M. cattarrhalis. • AU-XXX was evaluated systemic and lung infection models and it demonstrated in vivo efficacy better than comparator reference drug. • Absorption, distribution, metabolism and excretion (ADME) of AU-XXX in mouse, rat and dog was favourable in support of preclinical safety studies and clinical development. • Toxicity studies were conducted in rats with dosage 200 mg/kg/day for 14 days. The incidence and severity observed was less compared to the reference compound. exhibited Minimum Inhibitory of Gram-positive pathogens in murine Microbiology capabilities: • Anti-infective research and development is a core research facility. • Key resources are fully dedicated to enable multiple anti-infectives research programs to be conducted to proof of concept. • Ability to reproduce and setup in-house assays rapidly. • Best/first in class medicinal chemistry expertise. • Full toxicology back-up to achieve IND optimally. 3

  4. Thank You For more information please visit https:/ /www.aurigeneservices.com/ To place an inquiry please visit https:/ /www.aurigeneservices.com/form/contact Mail us at contactapsl@aurigeneservices.com 4

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