2017 Archived Content
Cambridge Healthtech Institute’s Fourth Annual
Antibacterial Discovery and Development
October 18-19, 2017 | Omni Parker House | Boston, MA
New discovery platforms, novel screens and approaches are vital for the discovery of new antibacterials and for ceasing the dangerous trends of multidrug microbial resistance. The Antibacterial Discovery and Development track will focus
on the general, strategic issues and solutions that would allow new antibacterial development to move forward. The conference will be held October 18-19 in Boston as part of the Fourth Annual Re-Entering Antibacterial Discovery and Development Summit and it will be followed by Targeting Gram-Negative Pathogens on October 19-20.
Scientific Advisers:
Lynn Silver, Ph.D., Silver Consulting, LLC
Joyce Sutcliffe, Ph.D., Former Senior Vice President, Biology, Tetraphase Pharmaceuticals, Inc.
Final Agenda
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Wednesday, October 18
7:30 am Registration and Morning Coffee
8:30 Chairperson’s Opening Remarks
Katherine Young, MS, Senior Principal Scientist, Richard T. Clark Fellow for Global Health, Infectious Diseases, Merck
8:35 To Kill a Bacterium You Need to Think Like a Bacterium
Eric Brown, Ph.D., Professor, Biochemistry and Biomedical Sciences, McMaster University
Antibiotic drug resistance has reached crisis proportions, principally because modern industrial drug discovery efforts have failed to provide new antibiotics. In the Brown lab, we are investigating enigmatic processes that are essential for the survival
of bacterial pathogens and are working to understand these processes in the context of complex cell systems. The Brown research group is also developing creative chemical-biology platforms to enable the discovery and characterization of new chemical
probes with utility as tool compounds in exploring complex biology. Efforts to date have resulted in new knowledge, platforms, chemical probes and lead compounds for antibacterial research. The ultimate goal of these studies is to contribute fresh
directions for new antibacterial therapies.
9:05 Platforms for Natural Product Discovery
Kim Lewis, Ph.D., University Distinguished Professor, Biology; Director of Antimicrobial Discovery
Center, Biology, Northeastern University
Screening soil microorganisms for antimicrobials produced most antibiotics currently in use. This Waxman platform was overmined by the 60s, precipitating the current antimicrobial resistance crisis. Compounds developed since come from ad hoc projects
that are not backed up by a discovery platform, resulting in a large probability of program failure. Two platforms in development can produce novel natural product antibiotics – growing previously uncultured bacteria; and turning on
silent operons.
9:35 Development of Microbiome Drugs for Preventing Infections by Multidrug Resistant Bacteria
David N. Cook, Ph.D., Executive Vice President of R&D, CSO, Seres Therapeutics, Inc.
A benefit to the host of an intact microbiome is the ability to resist colonization by exogenous pathogens in the gut. Antibiotics can disrupt the gut microbiome and cause dysbiosis that enables bacterial infections. Seres Therapeutics is developing
multiple Ecobiotic drug candidates to reduce gut colonization and prevent infection in at-risk patients, including immunocompromised and neutropenic patients. Progress in these programs will be reviewed.
10:05 Antibiotic Collaborative Drug Discovery Secure Data Sharing
Janice Kranz, Ph.D., Research Scientist, Assay Informatics Collaborative Drug Discovery
Inc.
With the resurgence of interest in the Antibiotic Drug Discovery field, it is critical that we learn from the past. Not just at the conceptual level, but at the detailed data level too. Towards that end, CDD has curated antibiotic data from
Challenges of Antibacterial Discovery. Conceptually, by collaborating together we mimic with ideas and data, the processes bacteria use to transfer genomic and mechanistic information.
10:35 Coffee Break
11:05 The Changing Environment and Challenges in Infections by Antibiotic-Resistant Pathogens
Yoav Golan, M.D., MS FIDSA, Attending Physician, Infectious Diseases, Tufts Medical Center
Advanced age, diabetes, and obesity, among other factors, fuel the emergence of hard to treat, polymicrobial and antibiotic resistant infections. Typical polymicrobial infections include Intra-abdominal and wound infections. These may require
repeated courses of combination antibiotics, which lead to antibiotic resistance and can increases toxicity, intolerability and drug-drug interactions. Improved infection prevention, better supportive care, and the development of novel
broad-spectrum and safe antibiotics are required.
11:35 Affinity Selection–Mass Spectrometry Identifies Antibacterial Agents with Novel Mechanisms of Action from Whole Cell Active Compound Libraries
Katherine Young, MS, Senior Principal Scientist, Richard T. Clark
Fellow for Global Health, Infectious Diseases, Merck
The discovery of new antibacterial agents is directly linked to new screening technologies, particularly technologies that can help to eliminate the rediscovery of known or toxic compounds. Affinity Selection–Mass Spectrometry (ALIS)
has proven to be a useful tool for identifying target/hit pairs, particularly when used with compound libraries pre-selected for whole cell inhibition. Novel antibacterial RNA polymerase inhibitor and DHFR anti-Mycobacterium tuberculosis
compounds discovered via ALIS will be presented.
12:05 pm The Epitranscriptome as a Source of Targets for Antimicrobial Drug Development
Peter Dedon, Ph.D., Professor, Biological Engineering, Massachusetts Institute
of Technology
All forms of RNA in all organisms, including parasites, bacteria and viruses, are post-transcriptionally modified with dozens of chemical structures, all of which have important functions in microbial physiology. In pathogenic bacteria,
ribosomal RNA modifications are associated with antibiotic resistance, while recent discoveries in parasites and bacteria reveal the critical role of transfer RNA modifications in survival during infection. This point is illustrated
with novel RNA modification targets in mycobacteria.
12:35 Enjoy Lunch on Your Own
1:05 Session Break
2:10 Chairperson’s Remarks
Joyce Sutcliffe, Ph.D., Former Senior Vice President, Biology, Tetraphase Pharmaceuticals, Inc.
2:20 Cyclic Boronic Acid BLIs: Novel Class with Untapped Potential
Olga Lomovskaya, Ph.D., Vice President, Infectious Diseases, The Medicines
Company
Vaborbactam is a cyclic boronic acid inhibitor of class A and class C beta-lactamases. It is now in clinical development in combination with meropenem. Biochemical and structural studies demonstrated significant mechanistic differences
between vaborbactam and diazabicyclooctanes such as avibactam. The follow-on programs have been initiated that are based on the recent discovery of a new series of potent cyclic boronic acid BLIs capable of inhibiting both serine and
metallo carbapenemases.
2:55 Fighting Back against MBL Mediated CREs: Development of Metallo-Beta-Lactamase Inhibitors for Use in Combination with Carbapenems
Martin Everett, Ph.D., CSO, Antabio
MBL-mediated CRE are already endemic in many countries and rapidly spreading world-wide. Antabio have identified a potent and selective lead series with excellent drug-like properties which it is moving into development. Lead compounds
show broad spectrum potentiation of meropenem against clinical CRE isolates and demonstrate efficacy in animal models of infection.
3:30 Refreshment Break in the Exhibit Hall with Poster Viewing
4:00 De-Risking Antimicrobial Development
George L. Drusano, M.D., Professor, Director, Institute for Therapeutic
Innovation, University of Florida
Dose and schedule choice are the single most important factors in successfully registering a new antimicrobial. Preclinical PK/PD model evaluation to identify exposure targets for effect and toxicity can be employed along with Monte Carlo
simulation with human pharmacokinetics to identify doses and schedules that are highly likely to be successful in the Phase II/III environment. This is extremely important for the development of narrow spectrum agents.
4:30 PANEL DISCUSSION: Considerations for the Discovery Scientist
Joyce Sutcliffe, Ph.D., Former Senior Vice President, Biology, Tetraphase Pharmaceuticals, Inc.
- What makes a good hit? What makes a good lead?
- How do you build a screening paradigm?
- How important is a target product profile? When should it be developed?
- What clinical development aspects should be considered in the discovery process? When should they be incorporated?
Panelists: Olga Lomovskaya, Ph.D., Vice President, Infectious Diseases, The Medicines Company
Eric Brown, Ph.D., Professor, Biochemistry and Biomedical Sciences, McMaster University
Yoav Golan, M.D., MS FIDSA, Attending Physician, Infectious Diseases, Tufts Medical Center
Kim Lewis, Ph.D., University Distinguished Professor, Biology; Director of Antimicrobial Discovery Center, Biology, Northeastern University
5:00 Welcome Reception in the Exhibit Hall with Poster Viewing
6:00 Close of Day
6:00 Dinner Short Course Registration*
*(Separate Registration required)
6:15 Dinner Short Course
Day 1 | Day 2 | Download Brochure
Thursday, October 19
7:50 am Interactive Breakout Discussion Groups with Continental Breakfast
This session features various discussion groups that are led by a moderator/s who ensures focused conversations around the key issues listed. Attendees choose to join a specific group and the small, informal setting facilitates sharing
of ideas and active networking. Continental breakfast is available for all participants. Details on the topics and moderators are available on the conference website.
Topic: β-Lactam/β-Lactamase Inhibitors
Moderator: Olga Lomovskaya, Ph.D., Vice President, Infectious Diseases, The Medicines Company
- β -Lactamase Inhibitor Combinations (e.g. piperacillin-tazobactam, ceftolozane-tazobactam and ceftazidime-avibactam)
- Gram-negative pathogens
- Future Directions
Topic: Driving Innovation by Delinking Investment in Antibiotic R&D from Sales Revenues
Moderator: Tyler Merkeley, (Acting) Chief of Staff, Head, Special Projects & Portfolio Management, Biomedical Advanced Research and Development Authority (BARDA)
- Delinkage: how do we design this new incentive mechanism that will support innovation?
- Global access: how can we secure access to new products when resistance renders treatments ineffective?
- New business models: how can we drive antibiotic development in an era of antibiotic resistance?
Topic: Antibacterial Discovery Platforms
Moderator: Eric Brown, Ph.D., Professor, Biochemistry and Biomedical Sciences, McMaster University
- Innovative platforms
- Development of synthetic antibiotics
- Designing species-specific antibiotics
- Where do we go from here?
8:50 Chairperson’s Remarks
Chris Stevens, M.D., CMO, Arsanis, Inc.
9:00 Monoclonal Antibodies for the Prevention of Infectious Disease: Development Program Targeting Staphylococcus aureus
Chris Stevens, M.D., CMO, Arsanis, Inc.
Present an overview of the discovery and development of ASN100, a pair of monoclonal antibodies, targeting six S. aureus toxins. Phase I data includes the demonstration of ASN100 penetration into the epithelial lining
fluid supporting the target of S. aureus pneumonia prevention. Overview of an ongoing Phase II S. aureus pneumonia prevention study in mechanically ventilated patients including assumptions for study design
and sample size calculations.
9:30 Design and Synthesis of S-ribosylhomocysteine Analogues
Christiane Chbib, Pharm.D., Ph.D., Assistant Professor, College
of Pharmacy, Larkin Health Science Institute
Three novel classes of S-ribosylhomocysteine (SRH) analogues as potential inhibitors of S-ribosylhomocysteinase (LuxS enzyme) and AI-2 modulators of quorum sensing were developed.
10:00 Antivirulents: Can Bacterial Infections Be Cleared without Antibiotics?
Menachem Shoham, Ph.D., Associate Professor, Biochemistry, Case
Western Reserve University
Antivirulents represent an attractive alternative to antibiotics. These agents disarm pathogens of disease-causing toxins without killing them, thereby eliminating survival pressure to develop resistance. Small-molecule F19 is a broad-spectrum
antivirulent that inhibits toxin formation in gram-positive pathogens by blocking transcription factor AgrA from binding to its cognate promoter DNA.
10:30 Coffee Break in the Exhibit Hall with Poster Viewing
11:00 Chairperson’s Remarks
Melissa Stundick, Ph.D., Head of Strategic Alliances, Spero Therapeutics
11:15 Series of Brief Presentations
Driving Re-Investment in Antibiotics: Update from Europe’s DRIVE-AB
Kevin Outterson, Professor of Law, Boston University & Executive
Director, CARB-X
DRIVE-AB has spent three years evaluating economic incentives to rekindle antibiotic R&D (www.drive-ab.eu), funded by the European Union with matching contributions from EFPIA companies. Final results and recommendations from DRIVE-AB
will be presented.
Venture Capitalists: What Are Investors Looking For?
Vikas Goyal, Associate, SR One
CARB-X: What Does It Mean to be Powered by CARB-X?
Tyler Merkeley, CARB-X Co-Founder, BARDA’s CARB-X Program Manager,
U.S. Department of Health and Human Services (HHS), Biomedical Advanced Research and Development Authority (BARDA)
CARB-X is a global innovation fund to support antibacterial product development supported by the Biomedical Advanced Research and Development Authority (BARDA), National Institute of Allergy and Infectious Diseases and Wellcome Trust,
the UK-based global charitable foundation dedicated to improving health. Co-founder, Tyler Merkeley, will share BARDA’s continued vision for CARB-X as the “Global Innovation Fund” to address antibiotic resistant
infections, highlight the Powered by CARB-X portfolio, and discuss future partnerships and funding opportunities.
Update on Pathways & Policies to Facilitate Antibiotic Development
Nicole Mahoney, Director, Global Policy, Merck
Antibiotic resistance continues to be a focus for policy makers determined to ensure the continued availability of effective treatments for patients with serious infections. This talk will provide an update on recent discussions with
an emphasis on regulatory developments.
12:15 pm PANEL DISCUSSION:Non-Scientific Solutions to Advance Antimicrobial Pipeline
Moderator:
Melissa Stundick, Ph.D., Head of Strategic
Alliances, Spero Therapeutics
Panelists: Speakers of the Session
1:00 Close of Conference
Day 1 | Day 2 | Download Brochure