Targeting Key Antibacterial R&D Challenges - Day 2



2014 Targeting Key Antibacterial R&D Challenges 

Day 1 | Day 2 | Download Brochure 


Tuesday, October 28

7:15 am Breakout Discussions with Continental Breakfast

 Platforms or Single Compounds for Antimicrobial Discovery

KimLewisModerator: Kim Lewis, Ph.D., University Distinguished Professor, Director, Antimicrobial Discovery Center, Department of Biology, Northeastern University 

 

Topics to be discussed:

 

  • Old platforms and their revival - natural product discovery and species-selective screening
  • Knowledge-based rescue of failed platforms - HTS and rational design
  • What are the knowledge gaps in platform development?
 

 

Gram Negative: Issues and Solutions

 MichaelDudleyModerator: Michael N. Dudley, Senior Vice President and CSO, Rempex Pharmaceuticals, now a wholly-owned subsidiary of The Medicines Company

 

Topics to be discussed:

 

  • MDR resistance in gram negatives
  • Major agents and development approaches
  • Issues in product development and value-based reimbursement
 

    

NGS as a Tool for Antibacterial Drug Development 

BrownJamesModerator: James Brown, Ph.D., Director, Computational Biology (US), GSK  

 

Topics to be discussed:

 

  • How is NGS being used now in antibacterial drug discovery?
  • What are the future opportunities for NGS in infectious disease therapeutics and diagnostics?
  • What are the bottlenecks and barriers?
 

 

  

Broad Spectrum Versus Selective Antibiotics – Where is the Future? 

Moderators: Daniel Obrecht, Ph.D., CSO, Polyphor AG

Helmut Kessmann, Ph.D., Head, Business Development, Polyphor AG

Topics to be discussed:

 

  • State of the art - current trends
  • Opportunities and challenges to develop and commercialize selective antibiotics
  • Potential role of diagnostics in use of selective antibiotic
 

 

 

NOVEL PATHOGEN-SPECIFIC APPROACHES AND STERILIZING COMPOUNDS  

8:00 Chairperson’s Remarks

David W. Martin, M.D., CEO, AvidBiotics  

8:05 Sterilizing Antibiotics

KimLewisKim Lewis, Ph.D., University Distinguished Professor, Director, Antimicrobial Discovery Center, Department of Biology, Northeastern University

Currenty available antibiotics are largely inactive against dormant persister cells produced by microbial pathogens. Persisters are largely responsible for the chronic, relapsing nature of the disease. We find that different natural compounds targeting the Clp protease kill persisters, achieving sterilization of the infection. We will also present data on prodrugs which convert into generally-reactive compounds as a platform for developing sterilizing compounds.

 

8:35 A Strategy and a Platform to Address the Current Antibiotic Conundrum: Targetable Bacteriocins

DavidMartinDavid W. Martin, M.D., CEO, AvidBiotics

Antibiotics are the most important ever pharmaceutical contribution to the survival and health of humans. Today the high prevalence of drug resistance, its rampant horizontal spread, and the unintended damage to important microbiota pose major threats. Precisely targeted bactericidal agents will not select for spread of antibiotic resistance nor damage microbiota diversity—off-target bacteria are already insensitive. Targetable R-type bacteriocins as prophylactic and therapeutic agents meet these critical needs.

9:05 Product Biosynthesis for Local and Global Antibacterial Discovery

Blaine PfeiferBlaine Pfeifer, Ph.D., Associate Professor, Chemical & Biological Engineering, SUNY Buffalo

Heterologous natural product biosynthesis is an enabling strategy to access molecular diversity.  The approach features a surrogate host system that provides technical advantages and engineering capabilities relative to native natural product producers.  In this presentation, heterologous biosynthetic design will be the basis for antibacterial discovery schemes featuring “local” engineering of a single natural product system and “global” isolation of novel pathways from the metagenome.

9:35 Genetic Strategies to Identify ß-Lactam Potentiating Agents to Restore Imipenem Spectrum against Drug Resistant Gram-Positive Pathogens

SangHoLeeSang Ho Lee, Ph.D., Associate Principal Scientist, Merck Research Laboratories, Infectious Disease, Antibacterial/Antifungal

A genetic strategy was implemented to identify agents when combined with known clinically relevant antibiotics, ß-lactams, can restore their susceptibility against drug resistant bacterial pathogens, such as Methicillin-Resistant Staphylococcus aureus (MRSA). The resulting genetic potentiation network includes peptidoglycan biosynthesis and crosslinking, cell wall remodeling, cell division, signal transduction and signaling pathways. Pharmacological validation of this approach is achieved by demonstrating the potent synergy with a broad set of ß-lactam antibiotics against MRSA.

 Basilea Pharmaceutica10:05 Overcoming Resistance with Beta-Lactams 

Mark_JonesMark E. Jones, Ph.D., PMP, Head, Project Management & Microbiology, Basilea Pharmaceutica International Ltd, Switzerland

Despite resistance beta-lactams continue to be our most important class of antibiotics. Continued innovation around the beta-lactam core structure ensures the utility of this class in the future. BAL30072, an innovative monosulfactam, demonstrates potent activity against carbapenem-resistant Gram-negative bacteria, including Pseudomonas and Acinetobacter spp. Ceftobiprole a novel cephalosporin demonstrates activity against both Gram negatives including P. aeruginosa, but also MRSA.

10:20 Coffee Break with Exhibit and Poster Viewing

10:50 When Antibiotics Don't Work: Development of Novel Monoclonal Antibody Strategies for Serious Bacterial Infections

AntonioDiGiandomenicoAntonio DiGiandomenica, Ph.D., Scientist II, Infectious Diseases, MedImmune.

It is now widely held that an over reliance on broad-spectrum antibiotics and empiric therapy is a major reason for the emergence of multi-drug resistant (MDR) bacteria. The severe and growing antibiotic resistance crisis has renewed interest in pathogen-specific monoclonal antibodies for the most problematic drug-resistant organisms. Monoclonal antibodies offer considerable potential give their long half-lives and ability to neutralize pathogenic factors on in promoting bacterial clearance. In addition, mAbs may augment host defense against infection in adjunctive treatment with antibiotics while also helping to reduce antibiotic usage. In this presentation, I will discuss the promising mAb-based activities and new strategies to prevent, treat and augment antibiotic therapy for investigational mAb clinical candidates targeting Staphylococus aureus and Psedomonas aeruginosa; two of the most problematic MDR pathogens that we face today.

11:20 Targeting Antibiotics to Bacteria

NirenMurthyNiren Murthy, Ph.D., Professor, Bioengineering, U.C. Berkeley

The poor membrane permeability of bacteria is major challenge in developing new antibiotics. We have developed a new strategy for targeting antibiotics into bacteria via conjugating them to maltodextrin. We can increase the permeability of antibiotics into gram negative and gram positive bacteria by 2-3 orders of magnitude via conjugation to maltodextrins. In addition maltodextrin antibiotics are not permeable to mammalian cells.

11:50 Integrating Pathogen, Human and Microbiome Genomics in Antibacterial Drug Development

BrownJamesJames Brown, Ph.D., Director, Computational Biology (US), GSK

The severity of bacterial infections is driven by complex interactions between the pathogen, the human host and our ecosystem of beneficial microorganisms. Understanding the diversity of the microbiome and its role in human health could help guide the development of next generation antibiotics. Conversely, new insights into the interplay between human and pathogen genes during infection, the host-pathogen interactome, could potentially provide new therapeutic approaches to infectious disease. Integrating these diverse yet interconnected genomic data is an important challenge and opportunity for antibiotic drug discovery.

12:20 pm Enjoy Lunch on Your Own

                  >>Registration for Track 2: Solving the Antibacterial Commercialization Equation

 

Meeting The challenges of clinical development and regulatory compliance  

1:20 Chairperson’s Remarks

KarenShawKaren Joy Shaw, Ph.D., President, Hearts Consulting Group





 

1:30 Combined Plenary Keynote Presentation: Overcoming the Challenges of Developing Antibiotics for Resistant Bacteria with New Regulatory Support

Barry Eisenstein, M.D., Senior Vice President, Scientific Affairs, Cubist Pharmaceuticals; Editor, Antimicrobial Agents and Chemotherapy

Increasing antibiotic resistance among the most important bacterial pathogens together with a thin pipeline of new agents, particularly the Gram-negative bacteria, is causing major therapeutic issues in the US and abroad. Recently, though, the US Congress together with the major regulatory agencies in the US (FDA) and Europe (EMA) have responded to this impending crisis with expedited pathways for approval of new key agents. This talk will review this progress.

2:00 End of Targeting Key Antibacterial R&D Challenges

 

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