Company: Medusa Pharmaceuticals
Location: London, Oxford and Cambridge
Founded: 2021
Founders: Dr James Duboff and Professor Peter Sarkies
Written by: Megan Thomas
Edited by: Caroline Babisz & Natasha Barrow
Professor Peter Sarkies, Co-Founder of Medusa Pharmaceuticals, returned to his lab at Imperial College London expecting to see an antibiotic-resistant strain of Escherichia coli growing on an antibiotic-containing agar plate. Instead he saw nothing. Frustrated, he repeated the experiment in which he was adding an alkylating agent to E.coli to investigate how it may impact its genetic evolution. He found the same outcome each time: the resistant E. coli's growth was being significantly impaired by the contents of the plate, when the bacteria should have been growing. After more investigation, he realised he may have found a way to reinvigorate the antibiotic that was being used on the plate, so it was now able to kill the resistant E.coli it was once ineffective against. Essentially, Peter had discovered that the alkylating agent and the antibiotic were working together to kill the resistant E.coli – like Perseus using the head of Medusa to turn his enemies to stone.1
This serendipitous discovery led to the founding of Medusa Pharmaceuticals. Medusa’s method works in a specific class of antibiotics called aminoglycosides, which act by disrupting bacterial protein synthesis2. Co-Founder of Medusa, Dr James Duboff explained: “what we have is a very specific synergy between two entire classes of compounds. So the entire family of alkylating agents and the entire class of aminoglycoside antibiotics exhibit this synergistic interaction which overcomes resistance.” Aminoglycoside antibiotics are a critical aspect of the treatment regime in people with cystic fibrosis and non-cystic fibrosis bronchiectasis, as they prevent and manage lower respiratory airway infections2,3. These antibiotics may be taken repeatedly and for extended periods of time, increasing the risk of antibiotic resistance as well as toxicity4,5. Medusa’s main area of focus so far has been cystic fibrosis.
Cystic fibrosis is a genetic condition that affects many organs in the body6. People with this condition develop a build-up of sticky mucus in their lungs which can lead to serious infections4. One of the most concerning infections is with the bacteria Pseudomonas aeruginosa, an opportunistic pulmonary pathogen responsible for significant morbidity and mortality in people with cystic fibrosis3,4. These infections can be very difficult to clear and can become chronic. The treatment for such an infection is usually inhaled doses of an aminoglycoside, such as tobramycin2,3,4,7. In some cases, the inhaled antibiotic is used over very long periods of time to suppress chronic infections.7 However, as with all antibiotic treatments, there is a risk that P. aeruginosa may develop resistance to the aminoglycoside. Another concern is toxicity. High doses of aminoglycosides have well documented side effects, such as ototoxicity (hearing loss) and nephrotoxicity (kidney damage)4.
With Medusa’s approach, they could provide a treatment against antibiotic-resistant strains of P. aeruginosa and also be able to drop the concentration of the aminoglycoside needed, thanks to the synergy of their drug combination. So far, Medusa have successfully demonstrated the synergy and efficacy of their method on clinical isolates of P. aeruginosa obtained from people with cystic fibrosis. They have also found that there is no increase in toxicity to human cells when the aminoglycoside is combined with the alkylating agent in in vitro testing. The next step to progress this technology towards clinical use is in vivo testing.
This success is promising at a time of global concern about rising rates of antimicrobial resistance (AMR)8. The advent of antibiotics was seen as a medical miracle in the fight against bacterial infections. But, since Fleming discovered penicillin in 1928, we have been in an evolutionary arms race against the bacteria we aim to eradicate. As a result of this man-made selection pressure, bacteria had to find new ways of adapting and surviving9,10. These resilient bacteria can then multiply and spread, leading to the emergence of antibiotic-resistant strains of bacteria, or ‘superbugs’ like the notorious methicillin-resistant staphylococcus aureus (MRSA)10.
The last new class of antibiotics was discovered and brought to market in the 1980s10. With the repeated use, overuse and mis-use of the same classes of antibiotics worldwide, bacteria have countless opportunities to develop resistance10. We are now hurtling towards a future where there are no options left to treat antibiotic-resistant infections. This bleak prophecy has been dubbed the ‘post-antibiotic era’ and is projected to kill 10 million people each year by 205011. Medusa are a promising part of the movement trying to stop this future from becoming a reality.
However, this is not an easy arena to be in as a startup company. In fact, even large pharmaceutical companies are hesitant to invest in the sector due to a plethora of financial, regulatory and technical barriers when it comes to developing new antibiotics10, 12. From a commercial perspective, new antibiotics are extremely time consuming and expensive to make, reaching costs of over $1Bn and taking 10–15 years to bring to market12.
Moreover, any novel antibiotic should not be widely distributed to avoid the risks of antibiotic resistance, leading to a catch 22 situation. James explained: “if you make an entirely new antibiotic, it should be considered a golden bullet that you want to leave in a safe, hidden away from society, because the second it's launched, the second it's in a person or an animal or in the environment, bacteria will, no matter how hard we try, start to evolve resistance to that. And it might take one hundred years, it might take a week. We don't know, because they can just evolve sporadically.” This makes antibiotics an unattractive investment for pharmaceutical companies and venture capital firms, as well as a daunting area for startups to step into.
Medusa may have found a solution to the key barriers startups in this sector face, by breathing life into already existing antibiotics and combining them with existing drugs that are already approved for use in humans. “We've essentially reshaped the paradigm in a way, because rather than trying to make a new drug, we are developing a brand new approach” said James. With their approach, Medusa can leverage the decades of existing research, manufacturing processes and distribution systems of existing drugs to significantly lower research and development costs and facilitate market adoption. The main aim for Medusa going forwards is to “find the perfect combinations and concentrations of these synergistic drugs to combat AMR infections and save lives, all around the world”.
As well as having implications in the management of cystic fibrosis, Medusa are actively looking into how their research could help to treat tuberculosis, Clostridium difficile infections, malaria and other eukaryotic infections. To date, they have been funded through government and charity grants including prestigious awards from InnovateUK and the Cystic Fibrosis Trust. They are now entering a seed funding round aiming to raise £2M to progress their core technology and continue to establish this new approach to overcome AMR. Reach out to james@medusapharma.com with any queries.
Medusa Pharmaceuticals were one of eight groundbreaking startups graduating from the SEC's in-house accelerator programme, the Innovators Club. Find out more about the Innovators Club here.
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