Original Publication Date: 6 April, 2017
Publication / Source: Infectious Diseases Hub
Authors: Ruth Neale (Community for Open Antimicrobial Drug Discovery, Brisbane, Australia)
Well, SDRI 2017 is officially over. And what a final day it was.
The day began with antibiotic drug discovery expert John Rex. Rex, a physician and drug developer, has an impressive background with ~30 years of development and policy experience focused on antimicrobial agents. Currently Chief Strategy Officer for CARB-X and working for the Wellcome Trust (London, UK), Rex spoke about the successes and failures of those navigating the antibiotic drug discovery pipeline.
“Antibiotics are the fire extinguishers of medicine,” he commented.
“Fire extinguishers have two roles – they put out fires, and will be on hand to put out fires – which keeps everybody safe. Antibiotics have two uses – they treat infections and we know that you could be treated – again, keeps everybody safe.”
He gave his perspective on giving new therapies the best chance. His key points include – seek novelty that addresses unmet need; get it registered – and he emphasized the need to justify the dose by lots of pre-clinical pharmacokinetic-pharmacodynamic (PK-PD) data; and in short – keep it simple!
“Effective antibiotics underpin all of healthcare and it is critical that the global pipeline be vibrant and robust. Substantial resources are available for antibiotic research and development but successfully developing a new antibiotic requires discipline & focus,” Rex explained.
His last slide emphasized the need to grab every opportunity to share and learn through events/workshops like SDRI (thanks Rex!).
The first session of the final day explored new drug targets, chaired by Vicky Avery of Griffith Institute for Drug Discovery (Brisbane, Australia). In order to rationally develop novel antimicrobials, new drug targets specific for the pathogen of interest must first be identified. While this approach has shown limited success in the past, a number of new promising targets have been identified in recent years.
Alita Miller from Entasis Therapeutics (MA, USA; start-up funded by AstraZeneca) began the session discussing the company’s pathogen-directed strategies. Antibacterial regulatory guidelines have been recently updated to allow for more streamlined development of narrow-spectrum, precision therapies to treat highly problematic, multidrug-resistant bacterial infections. Accordingly, various strategies are being pursued to develop candidate agents for narrower-than-usual or specific pathogen-directed indications.
Entasis Therapeutics has embraced this new paradigm as exemplified by its two current clinical programs: (1) zoliflodacin, a novel oral antibiotic for the treatment of uncomplicated gonorrhea that recently successfully completed Phase II and (2) sulbactam-ETX2514, a novel combination agent targeting carbapenem-resistant Acinetobacter baumannii which is currently in Phase I testing. Details around the discovery and development of each of these candidates were presented.
Next up was drug discovery expert Ian Gilbert from Dundee (UK) focusing on neglected diseases. The Drug Discovery Unit (DDU) was set up at the University of Dundee in 2006. It is a fully integrated drug discovery unit, combining hit discovery, medicinal and computational chemistry, drug metabolism and pharmacokinetics. The key aims of the unit are to tackle unmet medical need. Gilbert outlined some of the work that DDU have carried out on drug discovery for neglected infectious diseases. He focused on the development of a potential new compound for the treatment of malaria that works by a novel mechanism of action.
Tania de Koning-Ward, Deakin University (Melbourne, Australia), closed the session explaining strategies to target host-cell remodeling pathways of the malaria parasite. Tania revealed using reverse genetics, biochemical and proteomic approaches, which steps in this complex pathway provide new opportunities for drug targeting.
The final session of SDRI 2017 was vector control and vaccines, chaired by microbiologist Paul Young at The University of Queensland (UQ; Brisbane, Australia). The session assessed several different approaches to prevent and reduce drug-resistant infections. Reducing the carriers of pathogens via vector control, or preventing infections by utilizing vaccines, can be strikingly effective at reducing the number of cases requiring antimicrobial therapy.
Heidi Drummer from Burnet Institute (Melbourne, Australia) began the session by describing her research on meeting the challenge of eliminating hepatitis C. Drummer explained her work into combining direct acting antivirals with prophylactic vaccines. Significant cost savings to healthcare systems can be achieved through the combined use of highly effective non-toxic direct acting antivirals and vaccines to achieve elimination targets faster.
The next talk focused on imaging the dengue virus infection and treatment response by Subhash Vasudevan, Duke-National University Singapore. Vasudevan explained that the development of antiviral drugs and biotherapeutics for acute viral diseases like dengue fever require reliable and robust biomarkers.
Greg Devine from QIMR Berghofer (Brisbane, Australia) closed the session with his talk on new defenses against mosquito-vectors of disease, explaining progress and prognoses.
Another rapid fire session took place before afternoon tea break. Abodiun D Ogunniyi, from the University of Adelaide (Australia), spoke on a bioluminescent model of bacterial infection for pre-clinical efficacy trials of novel drug classes. Lynn Miesel from Eurofins Panlabs in WA, USA focused on efficacy of a novel anti-fungal, echinocandin. Finally Zyta M Ziora, from UQ, described her research into complexing metal cations to antibiotics to improve biopotency.
The overall goal for SDRI 2017 was to set three priorities and guide research efforts towards global solutions for drug resistance research. To close the meeting we invited Jason Gale, Bloomberg news (Sydney, Australia), to lead a concerted discussion to help set these priorities. Panel members included Sally Davies (CMO, Public Health England, London, UK), Jennifer Leeds (Novartis, USA), Zuoyu Xu (NIH, MD, USA), John Rex (CARB-X and Wellcome Trust, London, UK), Ramanan Laxminarayan (CDDEP and PHFI) and scientific committee members Matthew Cooper (UQ, Australia) and Liz Harry (UTS, Australia).
The lively discussion covered funding models, outreach and education, and the important issue of how to bridge the gap between industry and academia.
The following key priorities were voted on by the delegates:
- Antimicrobial resistance surveillance and monitoring
- Novel antimicrobial drug discovery
- Improvements to existing anti-infective agents and repurposing old drugs
- New drug targets
- Alternate therapies
- Preventing infections – vector control and vaccines
- Education, outreach and awareness of drug-resistant infections
- New funding models
Talented Sue Pillans joined us for the panel discussion and visually recorded and captured the discussion. After the vote, the three priorities that came out on top included novel antibiotic drug discovery, new funding models and finally education, outreach and awareness of drug-resistant infections.
Throughout the conference antibiotic drug discovery experts in industry were referred to as “endangered species”. As big pharma continuously exit the field, these experts will be lost and unable to train the next generation of AMR researchers. Rex, ex-AstraZeneca, and Jennifer Leeds, Norvatis, were described as the “rhino of the AMR world” and “the gorilla of the AMR world” respectively.
The meeting concluded with co-chairs Matthew Cooper and Jian Li thanking the delegates and encouraging the younger generation of scientists in the room to not give up!
Congratulations to Amy Cain (Liverpool, UK) who came out on top with the best poster prize awarded by ACS Infectious Disease and Kathy Andrews (Brisbane, Australia) who won the best 5 minute rapid fire talk.
Hosting global AMR health experts Ramanan Laxminarayan and Sally Davies in Brisbane for SDRI 2017 has been an extremely memorable time in my career, which I will never forget.
Now for some well-earned rest.
About the author
I am the Outreach Program Coordinator for a global open-access antibiotic drug discovery initiative called the Community for Open Antimicrobial Drug Discovery (CO-ADD). We launched in February 2015 to uncover significant and rich chemical diversity held outside of corporate compound collections. CO-ADD has developed a collaborative pipeline of new antibiotic candidates through the provision of free and timely antimicrobial screening to academic researchers around the world. CO-ADD tests compounds against five of the top pathogens listed on the WHO priority list for Research and Development of new antibiotics, as well as two fungi. CO-ADD is based at The University of Queensland (UQ) Institute for Molecular Bioscience.