Targeting Key Antibacterial R&D Challenges - Day 2



2014 Targeting Key Antibacterial R&D Challenges 

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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?

 

 

 

 

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 Novel Approaches for Species-Specific Antibacterial Agents Development: The Age of Phage

PhillipYoungPhilip J. Young, President and CEO, AmpliPhi Biosciences Corporation

We believe that a pathogen specific approach represents the best opportunity to combat the rising incidence of bacterial resistance. AmpliPhi Biosciences is a biotechnology company focused on the discovery and development of targeted bacteriophage(phage) therapeutics. Phages are a family of viruses that infect only bacteria. Our proprietary platform approach allows for the identification, characterization and manufacturing of human therapeutics. Phages are highly selective and will target and kill specific bacteria, including the multi-drug-resistant strains.

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.

10:05 Sponsored Presentations (Opportunities Available)

10:35 Coffee Break in the Exhibit Hall with Poster Viewing

11:00 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.

11:30 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.

12:00 pm Luncheon Presentation (Sponsorship Opportunity Available) or Lunch on Your Own

12:30 Conference Registration

12:55 Chairperson’s Remarks

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





1:00 Combined Plenary Keynote Presentation: Who Will Mourn the Passing of the Pharmaceutical Industry?

StevenProjanSteven J. Projan, Ph.D., Senior Vice President, R&D, Innovative Medicines, Head, Infectious Disease & Vaccines MedImmune

The second decade of the twenty-first century marks a perfect storm of patent expirations, contracting western economies, and increasing demands from “payers” that pharmaceuticals demonstrate cost effectiveness of their drugs. The result is the shrinking of “big pharma” right before our eyes and nowhere has the impact been felt more than in infectious disease research at large pharmaceutical companies. All the while bacterial resistance to antibiotics is increasing even as the number of new drugs being developed to treat bacterial infections is at its lowest point since the drawn of the antibiotic era. This surfeit of new agents implies that the “traditional” approaches to drug discovery and development have run their course and novel (entrepreneurial, opportunistic) approaches for the treatment and prevention of microbial infections (and forestalling the emergence of resistance) are required. Against that background we are have seen an increasingly convoluted regulatory regime with indications being parsed finer and finer yet with larger numbers of patients required to reach arbitrary (but often clinically meaningless) statistical endpoints. To date there has been some modest biologics drug discovery efforts to discover novel antibacterial agents for the prevention and/or treatment of Staphylococcal and Pseudomonal infections but these efforts now appear to be picking up speed and are progressing in the clinic. Is there hope?

1:30 End of Targeting Key Antibacterial R&D Challenges

 

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