Emerging Entrepreneurs

Developing next-gen drugs to fight superbugs

N Ramakrishnan | Updated on February 04, 2020 Published on February 03, 2020

V. Balasubramanian (left), COO, and Anand Anandkumar, CEO, Bugworks Research India   -  N. Ramakrishnan

Drug discovery start-up Bugworks Research working on a broad spectrum antibiotic

A constant thread that runs through a conversation with V Balasubramanian, Director, and Anand Anandkumar, Chief Executive Officer, Bugworks Research India Pvt Ltd, is the huge opportunity that is also a challenge that the Bengaluru-based drug discovery start-up has, and the innovative approach it has adopted to develop a class of next-generation antibiotics to help fight global superbugs.

As Balasubramanian explains, consider these facts: the last new antibiotic class was discovered in the 1960s. Resistance to drugs had started globally and the problem of bacterial resistance was stark. Equally important, Big Pharma was pulling out of antibiotics research. These two issues – the growing problem of anti-microbial resistance (AMR) and Big Pharma exiting pharma R&D – were not just challenges, but opportunities too. Balasubramanian, Anand and Santanu Datta, ex-AstraZeneca, teamed up to form Bugworks to work on discovering a new generation of drugs to fight superbugs.

Anand refers to the magnitude of the problem they are dealing with – almost a million deaths a year due to AMR, with 30-40 per cent of the global mortality happening here.

A lot of people had left AstraZeneca India owing to site closure. “We picked the cream and we re-stitched this team. We are all coming with 20 plus years each of drug discovery experience. We were tuned in to the emerging problem of the resistance as well as the fact that all the big players were getting out. We looked at it as a fantastic opportunity to capitalise and build on,” says Balasubramanian.

 

According to him, they realised that one of the problems of bacterial infection is being able to generate new chemical leads as the starting point for drugs. This was a challenge because bacteria have evolved to have a bunch of garbage disposal units on their outer surface called efflux pumps. Anything you put in to kill, the bacteria throws it out. Successful antibiotics have evolved to bypass the pumps and they have been able to get in. Balasubramanian describes dealing with the efflux pump as being similar to dealing with a 100-headed demon, where you chop one pump, the next one takes over.

“We took a different way. We said let us not try to hit the pump. Let us design chemicals which will not be seen by the pump. We designed a stealth strategy. That has been the secret for the success,” says Balasubramanian. Rather than trying to hit the pump, Bugworks, he says, decided to avoid the pump altogether.

The big challenge

When Big Pharma was quitting this area, what gave them the confidence that they would be able to succeed? Balasubramanian explains that return on investment was a big challenge for Big Pharma. For Bugworks, the cost base was low. “Being a small company and doing it much more efficiently, keeps the costs significantly down. The Big Pharma philosophy carried massive costs with it,” he adds. Also, being able to take quick decisions was another big plus for the six-year-old start-up. Most of the R&D now happens in the small and medium enterprises, while Big Pharma has become more of search and development. That is, they leave the discovery to the small players that are able to take higher risks, turn around faster, have a low cost base and then come to a point where they have proof of concept. Big Pharma is good at scaling up. The discovery engine has moved to SMEs, says Balasubramanian.

Anand adds that any search on antibiotics will show that is difficult in terms of economics. It takes 10-12 years to get a drug out. What also helped Bugworks was that governments across the world realised the magnitude of the problem posed by super bugs and were prepared to pump in huge sums of money in the form of competitive global grants to help fight them. “These governments are coming together, supporting innovative engines like Bugworks to at least go through the R&D costs,” says Anand.

Another change that is happening, according to Anand, is that new pricing policies being put in place globally. “Governments are changing the dynamics of how they are going to pay for antibiotics, because they realise that novel antibiotics is not a volume game and needs to be compensated on value to society,” he adds.

These market rewards – pull incentives – will happen in the next 12-24 months. “We believe our timing is perfect. Had we started the company eight years ago we would have had a product ready for the market but nowhere to go,” says Anand.

Clinical trials

Bugworks, they say, is working on a broad spectrum antibiotic and the company will shortly enter Phase I clinical trials. If the human safety data is good, they feel there is a good chance that the product will be a blockbuster because they have figured out how to take on a broad spectrum of bacteria. Bugworks has managed to keep costs low by engaging with contract research organisations in different countries. It has more than 25 partners across the world. Thanks to this strategy, Bugworks’ infrastructure cost is almost nothing. It gives the company the option to pick the best available. There is an inherent robustness in their model.

“Our data integrity is so good because it is coming from 20 different players who don’t speak to each other; I am the only one speaking. It has given us phenomenal benefit. It has kept the cost base low. It has given us access to the best where it is available. The most important collateral was the data integrity that came out,” says Balasubramanian.

According to him, Bugworks is just finishing regulatory studies and hopes to start Phase I clinical trials around April. And, if all goes well across the different stages – and they feel there is no reason why it shouldn’t – they should have a drug out in 3-5 years. There is a paradigm shift happening in the regulatory environment to allow clinical trials to happen in countries such as India and the developed countries accepting the data, because this is where a majority of the problem lies. If this happens, they will be able to crunch the time for phase 3 of the clinical trials – which is looking at whether the drug is safe and efficacious.

GYROX platform

According to Anand, Bugworks has created a platform called GYROX, which has the potential to come up with multiple products from the same family. This would be the first time since the 1960s that a major antibiotic is coming out.

Thanks to their strategy, Anand feels that Bugworks will not need to raise huge sums of money that drug discovery companies typically need. The company is going through a funding round and is in discussions with global investors.

 

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Published on February 03, 2020
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