Antibiotic resistance: the small Indian biotech hoping to solve a big problem 

A technician at the Bugworks lab in India
A researcher at the Bugworks lab in India Credit: Samyukta Lakshmi /Bloomberg

When a former Conservative Treasury minister calls for an industry to be nationalised it’s a clear sign that the sector must be fundamentally broken.

Lord Jim O’Neill, former Treasury minister for both David Cameron and Theresa May and chair of a review into antibiotic resistance in 2016, told an event at the Wellcome Trust last month that the failure of the pharmaceutical sector to develop new antibiotics meant that it was time for the industry to be turned into some kind of "government funded utility".

No new antibiotic has emerged on the market in the last 40 years – a major concern when dire warnings about growing antibiotic resistance seem to come out almost daily. 

A recent United Nations report warned that unless urgent action is taken AMR will have devastating consequences, including causing 10 million deaths a year by 2050 and damage to the global economy similar to the 2008-09 financial crisis.

Simple infections may become untreatable and routine operations and chemotherapy might become impossible because there will be no drugs to treat the infections that often come afterwards.

While combating antibiotic resistance requires a multi-pronged approach, developing new drugs is a vital component. Big pharma is pulling out of the antibiotic industry in big numbers – just eight of the largest global companies are still developing antibiotics.

And earlier this month Achaogen, which developed an antibiotic to treat drug-resistant urinary tract infections, collapsed – one of the most “significant and worrying corporate failures of this decade”, warned Wellcome’s director Jeremy Farrar.

The problem is an economic one, says Tim Jinks, Wellcome’s head of drug-resistant programmes.

“We want antibiotics to be inexpensive but we also want them to be kept in reserve so they don’t get overused. This makes it very difficult to recoup the cost of product development. The business case just doesn’t add up,” he says.

But while it may seem doom and gloom in the antibiotic development arena – there is some light.

“The small biotechs have been the engines in this space,” says Dr Jinks.

One of these is Bugworks, a company headquartered in the United States but which carries out its research and development in Bangalore – the Silicon Valley of India.

Bugworks is funded by Carb-X, a partnership including the UK, US and German governments and the Wellcome Trust, whose aim is to kick-start the development of new antibiotics.

Its founder, Anand Anandkumar, is a serial tech entrepreneur who launched two successful electronics start-ups and then a cancer start-up called Cellworks before turning his attention to AMR.

Bugworks has developed a novel broad-spectrum antibiotic to kill multi-drug resistant Gram-negative bacteria – a drug that has the potential to be used on anything from urinary tract infections to nasty stomach bugs.

Dr Anandkumar – who talks at 100 miles an hour and is fizzing with energy – says: “If you look at the bad boys, Gram negative is really really bad. The negatives are bad because they have an extra external cell wall – it’s like they have an impregnable fortress around them.

Staff of Burgworks in India with founder Anand Anandkumar standing fourth from the right
Staff of Bugworks in India with founder Anand Anandkumar standing fourth from the right Credit: Burgworks

“They also have pumps inside them – they’re very smart. So when they see an antibiotic coming in they kick it out,” he says.

What Bugworks has managed to do is break through the cell wall, avoid the pumps – “which are like bouncers” – and have figured out a novel target to hit, thus making it as resistance-proof as possible.

India is an ideal place to do research on superbugs, says Dr Anandkumar, because it is a country where AMR is a huge problem. Antibiotics are taken without prescription and lax agriculture rules mean that livestock are pumped full of drugs as a way of fattening them up.

“We do have enough rules in place but we don’t have enough enforcement. It’s a mindset change. We take antibiotics for everything – for a cold, for a cough, feeling low, feeling high. That’s going to take a generation to change,” says Dr Anandkumar.

But this proliferation of superbugs gives Bugworks the edge. “We test out compounds on really nasty bugs very early on in the process which you can’t find in Birmingham or Boston. We have the talent, the access to the hospital ecosystem and, importantly, the superbugs,” says Dr Anandkumar.

The antibiotic is in the pre-clinical stage – that is, it has not gone through all three phases of clinical trials which mean it is safe and effective. But Dr Anandkumar hopes it will be ready for phase one by the end of this year.

Carb-X has given Bugworks an initial grant of $2.6m with potential for that to go up to $3.6m. It sounds like a lot of money but to bring an antibiotic through all the clinical trials requires around $150m, he says.

“Carb-X takes it to phase one and then they hope and pray that someone will take it to phase two and phase three. Phase two costs about $25m and phase three about $150m,” he says.

There is no shortage of companies like his, working at the early research stage – Carb-X is working with more than 20 small biotechs to help them to phase one, although Bugworks is one of the most advanced.

But it’s getting a drug to the next stage so it’s ready to be manufactured at a large scale which is difficult and expensive, with the whole process thought to cost in the region of £1 billion.

Professor Dame Sally Davies, England's chief medical officer calls this the "pull through" – the small biotechs provide the initial push but it's the large pharmaceutical firms that pull the drug through to market.

The UK government has made tentative steps to address the problem with an announcement earlier this year that pharmaceutical companies will be paid upfront for antibiotics based on their value to the NHS, rather than on the volumes consumed.

Dr Jinks of Wellcome is cautiously optimistic about this.

“This could help solve the issue but it’s going to take two years before any decision emerges. That’s concerning as it means there will be further delay,” he says.

Meanwhile Dr Anandkumar is spending a lot of time using his considerable reserves of energy to drum up interest in his product among private and public donors.

“I’m banking on the fact our science is so good and, like Carb-X, some public fund will come and help us get it to the next stage. And I’ll go to Richard Branson and say 'you can save the world',” he says.

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