Each year, around 60,000 deaths are caused by antibiotic-resistant bacteria in Europe and the U.S., and this number is growing.
In addition, antibiotic-resistant bacteria causes prolonged treatments and extended hospital stays for numerous other patients, resulting in increased healthcare costs.
Finnish company Northern Antibiotics is working on a new antibiotic molecule, a derivative of polymyxin, that has significant potential to become one of the few last-resort weapons against bacteria resistant to all antibiotics now in use.
Currently the company, led by Professor Martti Vaara, is scouting for a commercial partner as the development requires additional funding. With the help of additional resources and a commercial partner, the Northern Antibiotics’, antibiotic molecule could be ready for hospital use in mid-2020’s.
Based on pre-clinical research, the polymyxin derivative, which belongs to the so-called peptide antibiotics, is effective against bacteria that are resistant to carbapenem antibiotics.
Until now, carbapenem antibiotics have been used to treat serious infections caused by the so-called super bacteria resistant to any other antibiotics. Carbapenems work in the same fashion as penicillin and cephalosporin but are still effective against bacteria that are resistant, amongst others, to these common antibiotics. However, now bugs are turning resistant to carbapenems, too, and this is the most likely reason why we are in danger of losing the race against the deadly super bacteria. In future, just as an example, a urinary tract infection could lead to death.
At the end of the 1960’s, the extensive use of the old polymyxin was terminated because the antibiotic was found to be too toxic to kidneys and because better-tolerated drugs belonging to other antibiotic classes were discovered. Now polymyxins have resurged as the last-resort drugs against extremely multi-resistant strains, even though their nephrotoxicity forces clinicians to administer them at doses that are lower than those required for optimal efficacy.
In the preclinical studies, the polymyxin derivative developed by Northern Antibiotics has been found to be less nephrotoxic than the old polymyxin. In addition, high levels of the derivative are excreted into urine which, as compared to the old polymyxin, increases the efficacy and makes it possible to use significantly lower doses in the treatment of urinary tract infections. Thus, also the risks of side-effects decrease in the same proportion.
The hospital use of Northern Antibiotics’ antibiotic derivative is possible already during 2020’s as its development has proceeded to a late preclinical stage. External funding, on top of the company’s own capital, would take the new antibiotic to a point of start of the first human clinical trials.
In 2015, Northern Antibiotics licensed another polymyxin derivative of its to an American antibiotic company Spero Therapeutics. This molecule is inactive alone but it does enhance the activity of other antibiotics, and it has already passed the first phase of human clinical trials.
Media Q&As
Q: Polymyxin is highly poisonous. Are you going to give it to humans?
A: Actually, the old polymyxin is today still used when the pathogen is resistant to other antibiotics. However, due to nephrotoxicity, low doses have to be used, and this does compromise the efficacy. Based on tests in animals, the polymyxin derivative developed by Northern Antibiotics is less nephrotoxic than the old polymyxin. In addition, high levels of the derivative are excreted into urine which, as compared to the old polymyxin, makes it possible to use significantly lower doses in the treatment of urinary tract infections. Thus, also the risks of side-effects decrease in the same proportion.
Q: The innovation is not new. Why hasn’t the drug been commercialized yet?
A: The development process of medicines is slow and most innovations fail during various stages of the process. We have progressed to the late preclinical stage. Now we need further studies to file an Investigational New Drug (IND) application to obtain permission to start human clinical trials. We are so far that we anticipate that, if everything goes right, the hospital use of our antibiotic molecule is possible already in the 2020’s. Antibiotic-resistant super bacteria are getting more common day by day. So, the need for new antibiotics like ours is there.
Q: Why NA’s innovation is better than other options under development?
A: The polymyxin derivative developed by NA has a significant potential to become one of the few new weapons against bacteria that have become resistant to all antibiotics now in use. One could say that we need an armature of around 3 to 5 last-resort antibiotics in order to fight against antibiotic-resistant bacteria. The innovation of Northern Antibiotics is based on polymyxin the good and bad characteristics of which are already known. For this reason, the outcome of the development work is safer to predict than that of the development of a completely new antibiotic family.
Q: What does NA want? What do you need to get the product to the markets?
A: In addition to our own capital, we need some three million euros in order to take the new antibiotic to a point of start of the first human clinical trials.
Virtual screening yields small molecules to enhance cancer immunotherapy