Pathogens for antimicrobial resistance may still be a bit off peoples’ radar, but the lessons from unpreparedness of COVID-19 are in the mind of Qpex.
Qpex is focusing on ways to combat Antimicrobial Resistance.
For San Diego-based Qpex Biopharma, which is focused on developing new treatments unhindered by antimicrobial resistance (AMR), 2021 has been a busy year. Over the past nine months, the company has seen two new assets move into human trials, joining a third that began clinical testing in late 2020.
The World Health Organization regards antimicrobial resistance as one of the greatest threats across the globe. It is estimated that more than 700,000 people die each year from infections that are resistant to most, or all antibiotics. In 2019, the U.S. Center for Disease Control and Prevention (CDC) estimated that over 2.8 million antibiotic-resistant infections occur every year. By the year 2050, it has been estimated that the antimicrobial threat will eclipse cancer-related deaths. Because of this threat, novel approaches developed by Qpex are in urgent need.
The Qpex pipeline targets pathogens that pose some of the most serious and urgent threats, including carbapenem-resistant Acinetobacter, Pseudomonas and Enterobacteriaceae (CRE). Notably, CRE is found in the community as well as the hospital setting, and there are no oral antibiotics targeting this pathogen.
Mike Dudley, PharmD, president and chief executive officer of Qpex, noted that over the past 20 months, with the hazards of an ongoing global pandemic, the world has come to more clearly understand the enormity of infectious disease threats. Antimicrobial-resistant pathogens may still be a bit off peoples’ radar, but the hard lessons learned from lack of preparation for the COVID-19 pandemic are clearly in the sights of Qpex.
“[The] COVID pandemic reminded us that infectious diseases have no borders. The Delta variant underscored how mutations in pathogens can quickly unwind progress,” Dudley said.
Antimicrobial resistance is not one single big problem, but a series of smaller ones. Likening the AMR landscape to climate change, Dudley said many discrete problems in smaller patient populations and settings have come together, raising significant concern. While there have been anxieties about the overuse of antibiotics by prescribing physicians that are contributing to AMR, Dudley reminds us that appropriate use also leads to resistance among key pathogens.
“We have to keep innovating and making new drugs to keep ahead of this. It’s not just about using less antibiotics. You have to understand the resistance landscape and how the pathogens are becoming more resistant,” he said.
Innovations in Antimicrobial Resistance
The innovations in antimicrobial resistance (AMR) are largely coming from smaller, more nimble companies like Qpex, which was spun out of The Medicines Company in 2018. That company divested its early-stage infectious disease products into Qpex, including proprietary beta-lactamase inhibitor technology and a new chemical class of drugs based on a boron pharmacophore that has demonstrated unique pharmacological properties. Dudley shared that Qpex currently has three clinical-stage products that are potentially best-in-class.
Two of the products in the clinic are beta-lactamase inhibitors. They are not antibiotics themselves but are used in combination with beta-lactam antibiotics to restore their potency by targeting a class-specific mechanism. Dudley noted that in the resistance landscape, there are two types of resistance, one that affects a specific drug class, and the other involves resistance mechanisms that affect multiple classes of drugs. Innovation needs to keep BOTH mechanisms in mind. The first of these is ORAvance, an oral, ultra-broad spectrum beta-lactamase inhibitor for use in combination with beta-lactam antibiotics for drug-resistant gram-negative bacterial infections in settings where intravenous therapy is not possible or desirable.
The second is an intravenous (IV) formulation of QPX7728. The IV product, which Qpex is calling OMNIvance, is also used in combination with a beta-lactamase antibiotic against pathogens, including carbapenem-resistant Acinetobacter, Enterobacteriaceae and Pseudomonas, he said. QPX7728 entered the clinic in December 2020.
Dudley said this asset has broad efficacy against pathogens and works with multiple drugs, which he noted is important in this treatment landscape. “This can be an important option for critically ill patients.”
The third product is QPX9003, a next-generation IV-administered synthetic rationally designed polymyxin for infections caused by drug-resistant gram-negative pathogens, including Acinetobacter and Pseudomonas aeruginosa, which the CDC has listed as serious antimicrobial resistance threats. While currently marketed polymyxins discovered in the 1950s are mixtures of a natural product, QPX9003 was developed in conjunction with researchers in Australia who were able to engineer a new form of polymyxin that has less toxicity concerns than the original formulation.
“Now that resistance to newer drugs has emerged, clinicians retreated to older drug classes like polymyxin that have poor clinical efficacy and toxicity. We’ve been really excited about the discovery of the improved version of this drug, which has a lot of advantages over the older form,” Dudley said.
These assets are currently in Phase I with readouts expected in 2022. The investigational products are likely to skip Phase II and move directly into Phase III due to a complete Phase I study combined with preclinical research. Dudley said the information gleaned from those studies can be combined with animal data in order to inform proper dosing levels for Phase III.
Qpex scientists have a strong record of working with public-private partnerships, and Qpex has a strategic partnership with BARDA, the Biomedical Advanced Research Authority, a division of the U.S. Department of Health and Human Services. The partnership with BARDA provides the potential for up to $132 million to support the development of a portfolio of new antibiotics to fight drug-resistant, gram-negative infections. The initial award in 2016 was for $32 million, and Qpex has secured additional awards from the achievement of milestones in each of the programs.
The company has forged a partnership with Raleigh-Durham and Beijing-based Brii Biosciences, which will participate in Qpex’s global development plans for its portfolio with the hopes of bringing the Qpex-developed assets to market in its home country. Dudley said the antimicrobial resistance problems his company is addressing are serious and frequent problems in China. Because of that, Qpex began early on to seek a partner like Brii to provide a pathway to the market in China.
“The last nine months have been a great run for Qpex and it’s something we’re excited to continue,” Dudley said.
