Targeting Key Antibacterial R&D Challenges - Day 1



2014 Targeting Key Antibacterial R&D Challenges 

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MONDAY, OCTOBER 27

7:15am Registration and Morning Coffee

8:15 Welcome Remarks from the Conference Director

Marina Filshtinsky, M.D., Cambridge Healthtech Institute

KEYNOTE SESSION  

8:20 Chairperson’s Opening Remarks

Joyce A. Sutcliffe, Ph.D., Senior Vice President, Biology, Tetraphase Pharmaceuticals, Inc. 

 8:30 Keynote Presentation: The Bacterial Resistance Portfolio – The Challenge of Microbial Ingenuity

DavidHooperDavid C. Hooper, M.D., Professor of Medicine, Harvard Medical School; Chief, Infection Control Unit, Associate Chief, Division of Infectious Diseases, Massachusetts General Hospital

Antimicrobials have contributed importantly to human health, but bacterial resistance has recently surpassed the development of new agents to deal with it. Resistance to natural product antibiotics has been primed by longstanding selective pressures in Nature and augmented for all antimicrobials by their use in humans and animals. Microbial ingenuity drawing on the adaptive capabilities of gene acquisition and mutational plasticity has employed alterations in drug targets, altered access of drug to its targets, and drug modification mechanisms alone or in combination to generate multidrug-resistant pathogens for which unmet medical need is increasing.

9:00 The Critical Role of PK-PD in Support of Antibacterial Drug Development

JohnRexJohn Rex, M.D., Vice President and Head, Infection, Global Medicines Development, AstraZeneca

As placebo (or knowing allocation to a therapy unlikely to be active) is unethical in development of antibacterial agents and also because of the importance of developing novel antibacterial agents in advance of epidemic spread of highly resistant bacterial strains, recently developed approaches to the registration of novel antibacterial agents depend heavily on the preclinical PK-PD insights. Exposure-response relationships demonstrated in preclinical in vivo models have been shown repeatedly to be predictive of response in man, thus making it possible for such preclinical insights to provide compelling direct experimental proof of causality that can be used to support interpretation of the limited (and sometimes pathogen-focused) clinical datasets that can be developed in a realistic timeframe (Rex et al., The Lancet ID 13:269-75, 2013).   

9:30 Busting Myths about Mechanisms of Antibiotic Action

MankinAlexanderAlexander Mankin, Ph.D., Professor, Center for Pharmaceutical Biotechnology, Department of Medicinal Chemistry & Pharmacognosy, University of Illinois at Chicago

What we think we know about the mechanisms of action of many antibiotics comes from the studies which are half a century old. New experimental approaches show that many textbook 'facts' about the mechanisms of action of a number of antibiotics are incomplete, or even plainly wrong. Some of the recent findins reveal principally new aspects of action of a variety of commonly used 'old' and 'new' ribosomal antibiotics - from erythromycin to linezolid. Understanding the true mechanisms is critical for the knowledge-based development of better drugs.

GRAM NEGATIVES AT THE TOP OF THE UNMET NEEDS LIST  

Polyphor10:00 Discovery of Novel Protein Epitope Mimetic (PEM) Antibiotics, A New Class Active Against Gram-Negative Pathogens 

Dan_Obrecht_PolyphorDaniel Obrecht, Ph.D., CSO, Polyphor Ltd, Switzerland

Polyphor Ltd has developed a novel class of antibiotics derived from its proprietary Protein Epitope Mimetic (PEM) technology platform, active against Gram-negative ESKAPE pathogens including MDR isolates. POL7080, a  PEM antibiotic selective against Pseudomonas is currently in Phase II clinical trials (in collaboration with Roche). Furthermore, PEM antibiotics have been identified with excellent, complementary, and broad spectrum activity against a wide range of Gram-negative pathogens.

10:30 Coffee Break in the Exhibit Hall with Poster Viewing

11:00 Developing New Antibacterial Agents for Multi-Drug Resistant (MDR) Gram-Negative Bacteria

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

CDC has identified carbapenamase-producing Enterobacteriaceae (CRE) as a major antimicrobial resistance threat. This resistance threatens the usefulness of the entire beta-lactam class of antimicrobials. A new class of cyclic boronate beta-lactamase inhibitors has been discovered that restores the activity of beta-lactam antibiotics againts gram-negative pathoegens. CarbavanceTM is the first agent from this class that is entering into patient trials in combination with a carbapenem.

11:30 Tetraphase Platform is Answering the Alarm to Combat Lethal, Multi-Drug-Resistant Bacteria

JoyceSutcliffeJoyce A. Sutcliffe, Ph.D., Senior Vice President, Biology, Tetraphase Pharmaceuticals, Inc.

Tetraphase has a proprietary technology platform to discover novel antibiotics with the potential to improve the treatment of infections caused by multidrug-resistant Gram-negative and Gram-positive aerobic and anaerobic bacteria, including carbapenem-resistant pathogens. Its lead compound eravacycline is in global Phase 3 clinical trials for the intravenous (IV) treatment of complicated intra-abdominal infections and IV to oral transition therapy for the treatment of complicated urinary tract infections. Eravacycline has MIC50/90 values of 0.5/1.0 µg/ml and 0.5/2.0 µg/ml against carbapenem-resistant Enterobacteriaceae and carbapenem-resistant Acinetobacter baumannii, respectively.

BasileaLogo12:00 pm Overcoming Resistance with Beta-Lactams

MarkJonesMark 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.

Lakewood Amedex12:15 Bisphosphocins™: A Novel Class of Broad Spectrum Antimicrobials

Paul_DiTullioPaul DiTullio, Vice President, Product Development, Lakewood-Amedex Inc.

Lakewood Amedex has discovered an exciting new class of broad spectrum antimicrobials, termed bisphosphocins™,  that have the potential to change how serious bacterial infections are treated.  Bisphosphocins™ have been shown effective both in vitro and in vivo against some of the most problematic bacterial strains, posses a unique mechanism of action, and are directly bactericidal even against biofilm encased bacteria.  This novel class of compounds is being developed to treat a wide range of serious chronic and acute bacterial infections.

12:30 Luncheon Presentation

Speaker to be Announced

 



ANTIBACTERIAL BIOLOGICS  

1:55 Chairperson’s Remarks

Mark T. Esser, Ph.D., Director, Translational Medicine, Infectious Diseases and Vaccines, MedImmune

2:00 Antibody-Antibiotic-Conjugates (AACs): a novel therapeutic platform to treat invasive S. aureus infections

SanjeevMariathasanSanjeev Mariathasan, Ph.D., Scientist, Infectious Diseases Department, Genentech

Although S. aureus is generally thought to be an extracellular pathogen, investigations have revealed its ability to infect and survive in various types of host cells. This facultative intracellular persistence enables long-term colonization of the host, and is likely a reason for clinical failures of, and relapses after, conventional antibiotic therapy. Therefore, a more successful anti-staphylococcal therapy should include the elimination of intracellular bacteria. Towards this aim, we have developed a novel therapeutic approach that effectively kills intracellular S. aureus.

2:30 A Novel Synthetic Antimicrobial Peptide: A New Weapon for Multi-Drug-Resistant Bacteria?

AlessandroPiniAlessandro Pini, Ph.D., Professor, Department of Medical Biotechnology, University of Siena

An artificial antimicrobial peptide in branched form will be presented. It will be shown the peptide strong activity against multi-resistant pathogens including clinical isolates of P. aeruginosa, A. baumanii, K. pneumonia and others, without relevant toxicity for eukaryotic cells. Its potent antibacterial and anti-inflammatory activity in vivo, in models of sepsis, lung and skin infections will be also illustrated. Currently, this molecule is under preclinical development and it is expected to enter clinical trials within two years.

3:00 Cyclic Lipopeptides: Promising Lead Candidates for New Antibiotics Discovery

Predrag Cudic, Ph.D., Assistant Member, Drug Discovery, Torrey Pines Institute for Molecular Studies

Due to their unique structure and high potency fusaricidin or the LI-F class of natural products isolated for Paenibacillus sp. emerge as attractive lead structures for the discovery and development of new antibacterial agents capable of treating complicated infections caused by multidrug-resistant bacteria. Using rational synthetic and combinatorial chemistry approaches we have modified these natural products and discovered novel cyclic lipopeptides of this class with potent in vivo activity against MDR bacteria, including bacterial biofilms, and low nonspecific toxicity.

3:30 Refreshment Break in the Exhibit Hall with Poster Viewing

TECHNOLOGY TO SERVE ANTIBACTERIAL R&D  

4:00 A “GoogleMAP”-Type Molecular View of Microbes - From Culture to People

PieterDorresteinPieter Dorrestein, Ph.D., Director, Therapeutic Discovery Mass Spectrometry Center, Co-Director, Institute for Metabolomics Medicine, University of California - San Diego

In this lecture, I will discuss real-time and 3D mass spectrometric methods to capture microbial molecules from microbes in culture and directly from surfaces such as people as well as the creation of a social network and crowd source annotation of molecules that are detected by mass spectrometry.

4:30 Applications of in vivo Imaging in the Evaluation of the Pathophysiology of Bacterial Infections and in the Development of Countermeasures to BSL3/4 Pathogens

ThomasBocanThomas M. Bocan, Ph.D., Molecular and Translational Sciences Division, US Army Medical Research Institute of Infectious Diseases

Imaging has the potential when applied preclinically to the development of countermeasures against BSL3/4 threat agents to address: 1) presence, biodistribution and timecourse of infection +/- drug; 2) binding of the therapeutic to the target; and 3) expression of a pharmacologic effect either related to drug mechanism, efficacy or safety. Preclinical imaging could potentially provide real-time, dynamic tools to characterize the pathogen, animal model and for developing countermeasures under the U.S. FDA Animal Rule provision with high confidence of success and clinical benefit.

5:00 Rapid Diagnostics to Enable Pathogen-Specific Drug Development

MarkEsserMark T. Esser, Ph.D., Director, Translational Medicine, Infectious Diseases and Vaccines, MedImmune

This presentation will discuss how MedImmune is using rapid molecular diagnostics, biomarkers and next-generation sequencing in clinical trials to develop novel monoclonal antibodies for the prevention of Pseudomonas aeruginosa and Staphylococcus aureus nosocomial infections.

5:30 Welcome Reception in the Exhibit Hall with Poster Viewing

6:30 Close of Day

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