The Challenge of Antibacterial Drug Development

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7:00 am Registration and Morning Coffee

8:00 Chairperson’s Opening Remarks

Lynn L. Silver, Ph.D., Silver Consulting, LLC

8:10 Opening Presentation:
Multi-Targeting in Antibacterial Discovery

Lynn L. Silver, Ph.D., Silver Consulting, LLC

Successful systemic monotherapeutic antibacterials are multi-targeted. It has been hypothesized that this is due to their low potential for rapid target-based resistance development. Possibilities for new multi-targeted agents will be discussed.

Targeting MRSA

8:50 NVC-422, a Novel Topical Antimicrobial Effective against MRSA in Impetigo

Mark Anderson, Ph.D., CSO, R&D, NovaBay Pharmaceuticals

Impetigo is a contagious skin infection caused by S. aureus, including MRSA, and S. pyogenes. We completed a Phase 2a clinical study of 129 impetigo patients where NVC-422 demonstrated 80-90% clinical and microbiological success. Response rates for MRSA infections were 100% across all treatment groups, whether MRSA was the sole organism or in a mixed infection. In laboratory studies no resistant mutants of Gram-positive or Gram-negative bacteria were generated following serial passage in sub-lethal concentrations of NVC-422.

9:20 Torezolid:  The Next Generation

Karen Joy Shaw, Ph.D., Senior Vice President, Biology, Trius Therapeutics, Inc.

Torezolid phosphate (TR-701) is an IV and orally administered second generation oxazolidinone for the treatment of serious gram-positive infections, including methicillin-resistance Staphylococcus aureus (MRSA).  Trius is currently conducting a Phase 3 clinical trial in acute bacterial skin and skin structure infections.

As a second generation oxazolidinone, torezolid phosphate (TR-701) is chemically differentiated from, and designed for improved potency, resistance and spectrum of activity over the first generation of clinically developed oxazolidinones.

We believe torezolid phosphate (TR-701) offers a number of important potential advantages over linezolid, including greater potency, once daily dosing, predictable drug exposure, a shorter course of therapy, in vivo bactericidal activity, lower frequency of resistance, activity against linezolid-resistant bacterial strains, and an improved safety profile.

9:50 Networking Coffee Break in the Exhibit Hall with Poster Viewing

10:15 Discovery of Anti-Virulence Agents against MRSA

Menachem Shoham, Ph.D., Associate Professor, Biochemistry, Case Western Reserve University

MRSA is a growing public health problem because it is increasingly resistant to antibiotics. Thus, there is a dire need for alternative treatments. This work describes the discovery of potential antipathogenic drugs that inhibit toxin production, thus rendering the bacteria harmless without affecting growth. Underlying this approach is the hypothesis that targeting the AgrA transcription factor with a specific inhibitor can suppress toxin biosynthesis in Staphylococci. Since homologs of AgrA exist in many bacterial species, it might be possible to develop a broad-spectrum antipathogenic agent. 

Trends and Challenges

10:45 Artilysins – Novel Targeted Antibacterials

Stefan Miller, Ph.D., CEO, Lisando GmbH

ARTILYSIN´s, specific enzymes, are designed to efficiently disrupt the cell surfaces of gram negative or gram positive bacteria. By addressing conserved structures, defined target bacteria are selectively destroyed. ARTILYSIN do not only suppress the formation of biofilm, but destroy as well multiresistant, pathogenic bacteria, as for example Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa.

Sponsored by
Cubist logo
11:15 Emerging Trends and Future Prospects for Novel Antibacterials R&D

Steven C. Gilman, Ph.D., Executive Vice President of Research and Development and CSO, Cubist Pharmaceuticals, Inc.

The rate of resistance to current antibiotics is increasing such that some bacterial infections are essentially untreatable by the current armamentarium of available treatment options. Despite this high unmet medical need, investment by large and small pharma in new antibacterials has declined and no new classes of antibacterials have been discovered in recent years. In addition, regulatory uncertainty and increasing requirements around FDA guidelines have led to concerns about the approval risk for novel antibacterials. This presentation will discuss the key scientific, business and regulatory factors limiting the discovery and development of novel antibacterials and potential solutions to this dilemma.

11:30 PK/PD in the Drug Development Process – Learning from Mistakes

Ursula Theuretzbacher, Ph.D., Founder, Center for Anti-Infective Agents (CEFAIA)

The pre-clinical and early clinical PK assessment as well as PD studies provide the input for in vitro and in vivo PK/PD models that evaluate exposure-effect relationships. Such PK/PD models are powerful tools for human dose selection, for determining susceptibility breakpoints as well as strategies to mitigate resistance development. Recent late stage clinical failures illustrate the importance of understanding the impact of PKs such as protein binding and concentrations at infection sites and incorporating them early into adequate PK/PD evaluations.

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


Case Studies and Lessons Learned

1:25 Chairperson’s Remarks

Menachem Shoham, Ph.D., Associate Professor, Biochemistry, Case Western Reserve University

1:30 Blueprints for Broad Spectrum Antibacterial Agent Discovery

Lance Stewart, Ph.D., CEO, Emerald Biostructures; Co-PI for Seattle Structural Genomics Center for Infectious Disease

Our Seattle Structural Genomics Center for Infectious Disease is funded by NIAID produce 100s of X-ray crystal structures of infectious disease protein targets, establishing a “blueprint for structure guided drug design”. We have established a network of investigators and resources to pursue cost effective collaborative discovery or new small molecule antibiotic candidates with broad spectrum activity. Importantly, we are taking innovative tech transfer measures so that co-invented IP is protected in an enabling fashion in order to ensure a clear path from lead discovery to partnership for development and marketing.

2:00 Discovery of MK-7655, a Beta-Lactamase Inhibitor for Combination with Imipinem

Timothy A. Blizzard, Ph.D., Distinguished Senior Investigator, Medicinal Chemistry, Merck Research Labs

2:30 The Activity of the Monosulfactam BAL30072 against Carbapenem-Resistant Gram-Negative Bacteria

Eric Desarbre, Ph.D., Scientist, Research, Basilea Pharmaceutica International

Covered are the growing resistance to carbapenems among Enterobacteriaceae and the non-fermentors such as P. aeruginosa and A. baumannii, the properties of BAL30072 and its activity against MDR Gram-negative bacteria.

3:00 Solithromycin: A well Tolerated Fluroketolide with Broad Spectrum, Potent Activity

Prabha Fernandes, Ph.D., CEO, Cempra Pharmaceuticals, Inc.

3:15 Networking Refreshment Break in the Exhibit Hall with Poster Viewing


Targeting Resistance

4:00 An Antibiotics Franchise to Treat Drug-Resistant Bacterial Infections

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

Since its inception four years ago, Tetraphase has developed a strong pipeline with a lead broad spectrum candidate in Phase 2 clinical trials, and two other differentiated candidates poised to enter the clinic in 2011. Our portfolio consists of TP-434, a broad-spectrum antibiotic for use as IV/oral step-down treatment of serious hospital infections. This compound is currently in Phase 2 studies for treatment community-acquired complicated intra-abdominal infections. TP-2758 is a novel tetracycline with IV/oral promise of targeting complicated urinary tract infections with emphasis on multidrug-resistant gram-negative infections and is scheduled for Phase 1 oral studies in first half of 2011. TP-834 is a compound in preclinical development with IV/oral potential targeting empiric monotherapy of community-acquired bacterial pneumonia. All three candidates were discovered at Tetraphase using our unparalleled chemistry platform allowing new tetracyclic derivatives to be designed by total synthesis. Each of these compounds are structurally unique and each offers significant differentiation from drugs that are currently on the market or in development by other companies.

4:30 Novel Siderophore-Conjugated Monocarbam Diols Circumvent Clinically-Relevant Resistance Mechanisms in Multi-Drug Resistant Gram-Negative Pathogens

Andrew Tomaras, Ph.D., Principle Scientist, Pfizer

5:00 Tackling Microbial Resistance: Novel Targets Accessed by Boron Antibacterials

M.R.K. Alley, Ph.D., Head, Discovery Biology, Anacor Pharmaceuticals, Inc.

5:30 Networking Cocktail Reception in the Exhibit Hall with Poster Viewing

6:30 End of Day

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