Archived Content
Cambridge Healthtech Institute’s Sixth Annual
Antibacterial Drug Development
Integrating Chemistry and Biology
April 17-18
Day 1 | Day 2Download Drug Discovery Chemistry Brochure or Antibacterial Brochure
WEDNESDAY, APRIL 18
7:45 am Continental Breakfast Breakout Discussions
In this interactive session, several topics will be offered for discussions and delegates are invited to choose a breakout topic of interest and join the moderated discussion at hand. In this informal setting, participants are encouraged to share examples from their work, vet ideas with peers and be part of a group problem-solving endeavor. We emphasize that this discussion is an informal exchange amongst scientists and is not meant to be, in any way, a product discussion.
Topic 1: Targeting Gram-Negative Pathogens
Moderator: Ian Critchley, Ph.D., Vice President, Microbiology, Cerexa, Inc.
Topic 2: Structure-Assisted Lead Optimization
Moderator: Jim Palmer, Ph.D., Director, Drug Discovery, Research, Biota Holdings, Ltd.
• Tackling non-target related resistance mechanisms such as bacterial efflux pumps: how can structural biology help?
• How can we translate "This is nice technology to have" into "Here's a preclinical candidate" better?
Topic 3: Targeting Drug-Resistant Pathogens – Challenges and Approaches
Moderator: Jutta Heim, Ph.D., Professor, Biotechnology; CSO, Discovery, Evolva SA
How close is the “Andromeda” strain?
Is FDA willing to accept single pathogen NDAs?
What are compounds on horizon and possibly alternative approaches?
8:55 Chairperson’s Opening Remarks
9:00 Development of Novel Antibiotic Candidates: Redesigning Tetracyclines by Convergent Assembly of Building Blocks
Joyce Sutcliffe, Ph.D., Senior Vice President, Biology, Tetraphase Pharmaceuticals, Inc.
The ability to deliver clinical candidates from any antibacterial program is challenging, especially in the face of multidrug-resistant pathogens. Tetracycline represented an early, broad-spectrum antibiotic and a valuable addition to the medical arma-mentarium. New molecules with desirable IV/oral pharmacokinetics that retain activity against all mechanisms of tetracycline resistance, and are potent against contemporary multidrug-resistant pathogens can be fashioned from convergent synthesis. TP-434, a compound in phase 2, and TP-2758, a compound in phase 1, were synthesized and are being developed as potential IV/oral broad-spectrum antibiotics, especially targeting multidrug-resistant gram-negative bacteria. A preclinical program that extends the spectrum to include Pseudomonas aeruginosa while retaining activity against other important gram-negative bacteria will also be described.
9:30 Gaining Insights into Molecular Targets of ß-Lactam Antibiotics in Gram-Negative Pathogens
Seungil Han, Ph.D., Senior Principal Scientist, Pfizer, Inc.
Multidrug-resistant (MDR) Gram-negative organisms such as Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli, and Acinetobacter baumannii are emerging as significant pathogens. ß-lactam antibiotics disrupt cell-wall synthesis in Gram-negative bacteria by covalently inactivating members of a family of enzymes known as penicillin-binding proteins (PBPs). MC-1, a Trojan Horse agent combining a siderophore mimic with a monocyclic ß-lactam antibiotic showed promising antibacterial activity against MDR Gram-negative microorganisms. Structural, biochemical, and computational studies provide a molecular basis for recognition of PBPs and potential strategies in medicinal chemistry to improve the potency of this class of agents.
10:00 Networking Coffee Break in the Exhibit Hall with Poster Viewing
10:45 POL7080 – A Novel Pseudomonas Specific Antibiotic for Treatment of Severe Infections
Klaus Dembowsky, M.D., Ph.D., Head, Drug Discovery and Development, CMO, Polyphor Ltd.
POL7080 is a novel, narrow spectrum intravenous antibiotic based on Protein Epitope Mimetics (PEM) Technology. POL7080 is highly active against a broad panel of Pseudomonas strains, including MDR strains. It has a novel mode of action interfering with the synthesis and transport of LPS. In a Phase I study, POL7080 was well tolerated and safe and had a favorable pharmacokinetic profile in humans. The further clinical path could include Phase II studies in pneumonia and/or urinary tract infections caused by Pseudomonas and would be favorably supported by the use of rapid microbiological diagnostic tools.
11:15 CRS3123, a Novel Agent for Treatment of Clostridium Difficile Infection
Thale Jarvis, Ph.D., Vice President, R&D, Crestone, Inc.
Emergence of hypervirulent and drug-resistant strains of Clostridium difficile has resulted in an alarming increase in incidence of Clostridium difficile Infection (CDI) in the past decade, especially among elderly patients. CRS3123 is a promising narrow spectrum agent that demonstrates selective growth inhibition of Clostridium difficile as well as inhibition of toxin production and spore formation. In a hamster model of CDI, oral CRS3123 shows sustained efficacy with virtually no tendency for recurrence, in marked contrast to existing CDI therapy with vancomycin. CRS3123 shows no cross-resistance to existing antibiotics and is active against all C. difficile strains tested, including the epidemic fluoroquinolone-resistant NAP1/BI/027 strain. CRS3123 is currently entering clinical development as a novel mechanism of action agent for treatment of CDI.
11:45 pm End of Conference
Day 1 | Day 2Download Drug Discovery Chemistry Brochure or Antibacterial Brochure