Fighting Superbugs - A partnership for the future of anti-infectives

Though the discovery of antibiotics transformed patient outcomes, saving millions of lives since the creation of Penicillin in 1928, it also started a clock. By their nature, bacteria and other infection-causing micro-organisms continually adapt to antimicrobial treatments, reducing their effectiveness and becoming more resistant to treatment over time.

For much of the 20th century this was combatted by the development of new classes of antibiotics to which disease-causing microbes had not been previously exposed. However, the most recent class of antibiotics in use today is based on a discovery made 33 years ago or earlier [1]. As a result, the world faces a growing threat from the rise of antimicrobial resistance (AMR).

It is estimated that over 700,000 people die annually as a result of AMR infections [2]. This number is expected to grow to 10,000,000 by 2050[3] if new ways of combating microbes that are becoming AMR— or “superbugs” [4]—are not found. Canada has recognized this urgent need for action, and in 2017 the Public Health Agency of Canada released its Pan-Canadian Framework for Tackling Antimicrobial Resistance and Antimicrobial Use based on input from concerned experts in academia, government, and industry.

One team working to fight these superbugs is the partnership between Fedora Pharmaceuticals Inc. (Fedora)—a biotech in Edmonton dedicated to the discovery and development of novel antimicrobial drug candidates that challenge AMR—and the laboratory of Dr. Carlos Velazquez-Martinez, Associate Professor in the Faculty of Pharmacy and Pharmaceutical Sciences. Spurred by a grant from Alberta Innovates, and implemented by API, the partnership between Fedora and the faculty is focused on developing a new pipeline of antibiotic drugs that will be effective against multi-drug resistant pathogens.

“This is an exciting and timely field of research considering the significant amount of evidence reported worldwide on the increasing incidence of chemoresistance, and the challenges associated to the hunt for new antibiotics,”[5] says Velazquez-Martinez.

Fedora is no stranger to anti-infectives or to the faculty. Its CEO, Chris Micetich and his team have over 120 years of cumulative experience in the area. Chris’ father, Dr. Ron Micetich, a former faculty member, created the beta-lactamase inhibitor Tazobactam in partnership with Japan’s Taiho Pharmaceutical Company, which is now a blockbuster drug with over one billion US dollar sales annually.

“We are proud to continue the longstanding relationship with the faculty. This partnership will serve as a model for all university-industry interactions across the country, resulting in highly skilled and educated candidates being sought after to enter the work force. As a team, we’re working closely together to bridge the transition gap between academia and industry,” says Chris.

The partnership between Fedora and the faculty is a pilot project in applied learning and one of the first collaborations facilitated by API since its launch. Working in the lab of Velazquez-Martinez, post-doctoral students, Dr. Myron Wilde and Dr. Yasin Tabatabaei, funded by Alberta Innovates, are taking part in a once in a lifetime project. With Fedora, they are working on the chemical synthesis of a series of drug molecules with potential antibacterial activity, specifically against gram-negative strains resistant to current antimicrobial treatments that, if successful, will go on to save countless lives. In the process, they will receive direct industry experience and be positioned to start meaningful careers in the pharmaceutical industry, continuing on to contribute to this critical area for the future of health care worldwide.

“This educational model is expected to provide postdoctoral fellows with a high-level vision not only on technical aspects related to synthetic organic chemistry, but also the approach followed by entrepreneurs in the high-risk drug development business,” says Velaquez-Martinez.

Beyond the training opportunity, he says that their goal is the production of at least one lead molecule with a potent, selective and safe profile for its potential use as an antibacterial agent.

“For the first time since I started my research career at the University of Alberta, my group will have the opportunity to learn the wide variety of translational considerations guiding the design and development of new drug candidates,” says Velazquez-Martinez. “We consider this an exciting opportunity to work with industry, and at the same time, bring funds to carry out research from sources other than traditional granting agencies. This model has the added benefit of a commercial partner willing to help us with the much needed translational jump, moving ideas to high-value products that save lives.”

1 Daptomycin, which was discovered in 1984.

2, 3, 4 The Review on Antimicrobial Resistance. Tackling drug-resistant infections globally, 2016. Available: amr-review.org

5 Chemical & Engineering News, volume 96, issue 49. The hunt for new antibiotics grows harder as resistance builds, 2018. Available: https://pubs.acs.org/toc/cgeabj/96/49