According to the World Health Organization (WHO), antimicrobial resistance (AMR) is one of the biggest threats to global health, food security, and development today. If this trend is not slowed or reversed, it could jeopardize many, if not most, of our medical advancements to date. Antimicrobials are essential for the prevention and treatment of infections, which affect the success of a multitude of medical procedures including organ transplantation, cancer chemotherapy, and any type of major surgery.
Despite billions of dollars of investment and sustained efforts over decades, very little progress has been made in the discovery and development of new antimicrobial treatments. For instance, no new class of antibiotic for Gram-negative infections has obtained approval in over 40 years. Various Gram-positive bacterial infections including Methicillin-resistant staphylococcus aureus (MRSA) and Vancomycin-resistant Enterococci (VRE) have been termed ‘superbugs’ due to their significant resistance to most of the existing antibiotics, with high resistance rates particularly in hospitals. Globally, approximately 240,000 people died from multidrug-resistant tuberculosis in 2016.
From a scientific and technical standpoint, all the low-hanging fruit [in antibiotics] have already been taken so it is more difficult to find a breakthrough
While many Chinese biotechs have set their sights on developing cancer therapeutics, two enterprising CEOs have decided to go down the uncommon path of microbial research. Zhenkun Ma, the founder and CEO TenNor Therapeutics did this with his eyes wide open, having previously worked with different entities in this space, including nine years as Head of Research and subsequently chief scientific office at the Global Alliance for TB Drug Development (the TB Alliance). He outlines the major challenges within this space. “firstly, from a scientific and technical standpoint, all the low-hanging fruit have already been taken so it is more difficult to find a breakthrough. Secondly, the market situation for antibiotics can be challenging for companies. There are many generic drugs available in this space and the current insurance reimbursement system – in both mature and emerging markets – is not set up well to promote innovation.”
For this reason, he established TenNor Therapeutics with the decision to “developing differentiated candidates for clear unmet medical needs that can be used as first-line treatment instead of being reserved as second- or third-line therapies – to ensure that our business model is sustainable.”
TenNor currently has three clinical programs targeting biofilm infections associated with medical implants or devices; gastrointestinal (GI) tract-associated diseases like cirrhosis hepatic encephalopathy (HE); and anaerobic bacterial infections like H. pylori and bacterial vaginosis. The needs are significant – for H. pylori for instance, it is estimated that an estimated 50 percent of the population carries this infection, which is associated with gastric ulcer, as well as gastric cancer, while in bacterial vaginosis, the resistance rate for the main pathogen to first-line treatment metronidazole is extremely high, estimated between 70 to 90 percent in China and 30 to 40 percent in the U.S.
The urgency has escalated due to a spate of recent exits by Big Pharma players from this space. Giants like Novartis, Sanofi, BMS, AstraZeneca and Eli Lilly have all pulled out from funding programs within the antimicrobial space in the past couple of years. But MicuRx Pharmaceuticals is in it for the long haul. Established in 2007 by long-time colleagues President & CEO Dr Zhengyu Yuan and Mikhail Gordeev (EVP and CSO), MicuRx is actually their second biotech focusing on antimicrobial resistance (AMR). Their first, Versicor, founded in 1996, took two drugs to US NDA before being acquired by Pfizer for USD 1.9 billion in 2005. With that stellar track record, they decided to continue exploring this space, this time shifting their center of operations to China, with a focus on developing next-generation antimicrobial drugs.
Their flagship candidate, contezolid, has already finished Phase III pivotal trials in China and Phase II trials in the US (contezolid has also been granted QIDP designation and Fast Track status by the US FDA) and expects to file for approval in China soon.
Dr Yuan explains the importance of this compound. “Contezolid is a drug belonging to the oxazolidinone class of molecules. Within this class, there is an existing blockbuster drug on the market, linezolid. Compared with another older drug vancomycin, linezolid is available both intravenously and orally with very good tissue distribution, and very effective against multi-drug resistant (MDR) Gram-positive bacterial infections, without the nephrotoxicity commonly seen in vancomycin.” However, Yuan continues, “linezolid has some problems with bone marrow toxicity, which limits its use to a large extent clinically. For infections with no alternatives, for example, drug-resistant tuberculosis, it is still prescribed but around 70 percent of patients will eventually develop bone marrow toxicity related side effects and around 30 percent will develop neuropathy, sometimes even losing their eyesight.” Meanwhile, contezolid is as efficacious as linezolid but without the bone marrow toxicity.
Estimates suggest that by 2050, AMR could be responsible for 10 million deaths globally and cost the world up to USD 100 trillion. With so much at stake, all efforts to combat this global scourge are certainly welcome.