Superbugs are rising. India’s scientists are fighting back

At the same time, in the same city, Bugworks, a biotech firm, was taking shape. A group of scientists and executives from AstraZeneca came on board, embarking on drug research around infectious diseases.

Founded by Anand Anandkumar, Balasubramanian V., Santanu Datta and Shahul Hameed, the company set its sights on a growing global crisis—antimicrobial resistance. There is a dire need for new antibiotics as existing drugs are losing efficacy. Bacteria evolve to grow immune to medicines meant to kill them.

The company has raised close to $43 million in funding since inception and has two novel antibiotic drug candidates in the pipeline—one in phase 1 trials and the second at the preclinical stage. A drug candidate is a molecule which has passed initial discovery and is being further studied.

The biotech’s genesis exemplifies a larger story. As Big Pharma started vacating infectious diseases research to chase more lucrative segments like oncology and diabetes, it left behind a gaping void. A handful of plucky innovators in India, the world’s generic pharmacy, are addressing the gap, weathering financial storms and scientific uncertainty to give the world much-needed new antibiotics.

In early 2024, Chennai-based Orchid Pharma’s molecule, Enmetazobactam, became the first new chemical entity discovered in India to be approved by the US Food and Drug Administration (FDA). Drugmaker Wockhardt has over five novel antibiotics in its pipeline, with two already rolled out in India.

While developing a new drug is in itself a considerable feat—roughly one in 10 drug candidates that have made it to phase 1 trials further make it to the regulatory approval point—doing this in India is a gargantuan achievement. Innovators have to navigate not just scientific challenges, but a tough funding landscape.

Estimates on the cost of developing a new drug vary across the board. A Deloitte report analysing the R&D costs of 20 big pharma companies stated that it cost an average $2.23 billion to develop a drug in 2024. A 2024 study, published in JAMA Network Open Journal, suggested far lower expenses. Analysing data between 2000 and 2018, it stated that the cost of developing a new drug was $172.7 million, but the figure rose to $879.3 million when cost of capital and drug development failures were included.

“Today, a new drug costs $4-5 billion. We developed five to six products at a cost of $500-600 million…but compared to our financial resources, it’s a very significant, sustained, long-term commitment,” said Habil Khorakiwala, Wockhardt’s chairman.

The Mumbai-based drugmaker started its drug discovery programme 25 years ago, and is reaping the benefits only now.

A private equity investor working in the healthcare sector, who didn’t want to be identified, said that a founder has to take an “existential risk” to embark on a drug discovery journey. “Even at scale, you have to bet,” the investor said.

Attack and kill

There are over 30 classes of antibiotics. The last new class of antibiotics to reach the market was discovered in 1987—Daptomycin (Lipopeptides).

Antibiotics are classified based on factors like their chemical structure and mechanism of action. New drugs being commercialised since then have been within existing classes, even as bacteria evolve to fight these known mechanisms. Bacterial antimicrobial resistance was associated with 4.71 million global deaths in 2021, according to a Lancet study. This could increase to 39 million by 2050.

“Microbes are far superior to us. They know significantly more than the human mind and they find ways and means to circumvent our methods to exist,” Maneesh Paul. S, microbiologist and the lead co-inventor of Orchid Pharma’s Enmetazobactam, told Mint.

Microbes know significantly more than the human mind and they find ways to circumvent our methods to exist.
— Maneesh Paul. S

According to WHO’s 2024 report on antibacterial agents, there were 97 such agents in various phases of clinical development globally, as of 31 December 2023. Of these, 32 “traditional” agents address WHO’s bacterial priority pathogens, a list of resistant pathogens classified into three priority levels—critical, high, and medium.

Discovering an antibiotic is a challenging process. Indeed, one of the first ones was serendipitous. Almost a century ago, Alexander Fleming returned from holiday to find that a mold growing in petri dishes had killed the bacteria inside. He named the substance Penicillin.

There are several challenges in the scientific process of antibiotic discovery itself. First and foremost is finding a compound that will kill the pathogen without being toxic to the human body. Antibiotic doses are higher than other drugs, measured in grams rather than milligrams.

The second challenge lies in bacterial biology itself. There are several target species that evolve over time to become resistant. The antibiotic must target these in different parts of the body, a flexibility that is not required of many other therapies like hypertension or diabetes.

Penetrating the cell membrane of Gram-negative bacteria, which can cause infections such as pneumonia, urinary tract infections, as well as hospital-acquired infections at surgical sites or in the bloodstream, is another key challenge.

Gram-negative and Gram-positive refers to bacteria with differing cell wall structures. Gram-negative bacteria have a protective outer membrane—this double-membrane, and other factors, makes them particularly resistant to many antibiotics.

Scientists have discovered different methods to attack the bacteria. For instance, there are beta-lactamase inhibitors, which work by inactivating bacterial enzymes which would otherwise attack and kill antibiotics like penicillins and cephalosporins. Even then, scientists have to consider which bacterial enzymes will be the bigger threat in five years, as resistance develops.

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They screen thousands of potential compounds to find promising antimicrobial activity. These compounds are then tested on infectious pathogens in a lab, and refined or improved upon. In other cases, researchers modify existing antibiotics to make them stronger or figure out ways to bypass bacterial resistance.

Breakthroughs come when the innovators figure out a way to circumvent the bacteria’s bolstered defences.

The prayer

Maneesh Paul of Orchid Pharma joined the company in 2006 as a senior research scientist. Previously, he was a researcher at John Hopkins and had also worked for the US FDA.

It took the company two years to discover the new molecule, Enmetazobactam, which was later approved for use in the treatment of complicated urinary tract infections, hospital-acquired pneumonia and ventilator-associated pneumonia, he said.

Scientists at the company looked at existing drugs that were losing efficacy, and sought to find ways to structurally modify the molecules to improve it. They zeroed in on a drug called Tazobactam, which is used in combination with other antibiotics like penicillins and cephalosporins.

“We found a space in the patent and we said this is where we will crack that,” said Paul, referring to how the team found a way to structurally modify the molecule to invent Enmetazobactam. “I used to pray everyday—Lord grant me wisdom and open the eyes of my heart and mind to see the beauty of your creation, which I can’t see with my knowledge.”

The molecule initially got labelled as inactive in pre-clinical in vivo testing (studies done on living organisms). Paul’s team cracked it in 2008 by developing a novel animal testing model. But that was just the start of the story. Once a potential molecule is found, the real journey begins—it has to be developed, tested and its mettle proved.

Chemist Senthilkumar U.P. is the other lead co-inventor at Orchid. Along with Paul, he led the way. It took 18 years for the drug to get US FDA approved.

During this time, the company went through corporate debt restructuring, saw its ownership change hands, and even lost the global rights to its drug to Allecra Therapeutics. In a big win, last month, it bought back the global rights by acquiring Allecra.

Khorakiwala’s 5X

The journey from discovery to development is long and arduous; it needs an entrepreneur with grit to back it up.

Habil Khorakiwala bet on antibiotics research 25 years ago when he set up Wockhardt’s new drug discovery programme under chief scientific officer Mahesh Patel. The company, then an Indian pharma giant in the generics space, had big ambitions. “Why can’t an Indian company be a global leader in antibiotics after 10 or 20 years?” Khorakiwala asked.

While the discovery programme took off, Wockhardt faced its share of financial struggles that eroded its market position. A spree of rapid acquisitions in the early 2000s swelled debt, which peaked at ₹4,000 crore in 2008. Losses from complex currency derivative hedging further weakened its financial position, forcing it into corporate debt restructuring. In 2013-14, the US FDA imposed import alerts on two of its Indian plants, resulting in substantial revenue losses from the US market.

But Khorakiwala held on to his discovery promise. “We’ve spent about 12% (of revenue) on R&D through the years, in spite of my financial problems,” he told Mint.

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When he had doubts, he revisited the company’s goals, and said that the conviction with which they had started out didn’t change. He also tried to understand the science behind their discoveries. The 83-year-old started attending the company’s annual meetings and scientific conferences, engaged with key opinion leaders from the scientific community, and showcased the company’s product pipeline.

The perseverance paid off. Wockhardt, thus far, has launched two antibiotics in India. A third is ready for launch.

In 2020, the company launched Emrok, an intravenous antibiotic, and its oral counterpart, Emrok O, for acute bacterial infections. While the company has not shared any sales number, the antibiotic has been used to treat over 100,000 patients as of May 2025, Wockhardt claimed.

Miqnaf (Nafithromycin), an oral antibiotic, was launched in May this year. The drug is approved for treating community acquired bacterial pneumonia.

In an interview with CNBC-TV18, in January 2025, Khorakiwala projected sales of ₹200-300 crore over the next two years for the drug. The addressable market opportunity is over a billion dollars— ₹10,800 crore—according to an investor presentation by the company.

Wockhardt says it has three more drugs in the pipeline and will continue to work on novel antibiotic development as these drugs are bound to face bacterial resistance as well.

After significant volatility over the last two decades, the company’s stock has taken off on the back of its R&D pipeline, gaining almost fivefold in the last two years. Its shares closed ₹1,461.30 on 8 September.

Discovery of BWC0977

Bugworks, meanwhile, is working on a ‘broad-spectrum’ drug which could target a wide range of bacteria, including both Gram-negative and Gram-positive types.

“Bacteria come in different colours, shapes and sizes. Each one needs a different drug to address it,” said Vasan Sambandamurthy, the company’s senior vice president for global strategy. Mint spoke to him in April this year.

The company discovered BWC0977, a novel, broad-spectrum drug candidate capable of targeting all major pathogenic bacteria. The drug candidate was discovered with funding, ecosystem and expertise help from the CARB-X, a global non-profit that supports the fight against antimicrobial resistance.

BWC0977 is being developed as two products—an intravenous infusion for treating serious bacterial infections and an oral dosage for treating community acquired infections.

“We have gone through a lot of failures…In pharma discovery, you start by saying that this will fail. The sooner it fails, the cheaper, better,” Sambandamurthy said.

BWC0977 is being developed as two products—an intravenous infusion for treating serious bacterial infections and an oral dosage for treating community acquired infections.

The company hit its first roadblock when it was about to enter phase-1 trials in Australia—the covid-19 pandemic hit and all operations came to a standstill.

Once work resumed in 2021, Bugworks hit another scientific hurdle. During the phase-1 trials, the drug candidate is tested in humans in different doses to establish safety, tolerability and pharmacokinetics. While it was being tested for multiple ascending doses (where subjects are given the same drug multiple times over a period of time), the drug started causing irritation and inflammation at the injection site, commonly known as infusion site reactions.

The company had to go back to the drawing board. Now, it is set to head back to the clinic again, in partnership with CARB-X and GARDP, another non-profit organization developing new treatments for drug-resistant infections.

Bugworks, meanwhile, decided to de-risk. In the last few years, it has expanded its research focus to oncology and has developed two drug candidates that are in preclinical stages.

Small pie, big cut

Antibiotic research has not elicited much interest in the past few decades because the market is not particularly large. Drug courses are short—three, seven, fourteen days. Compare these to drugs for non-communicable diseases, like hypertension or diabetes, taken for a lifetime, or highly priced cancer medicines, taken for months, if not years. Plus, these drugs cannot be sold over the counter, because of the fear of growing resistance.

Since the 2000s, Big Pharma has been quietly exiting anti-infectives research. Bristol-Myers Squibb, once a leader in antibiotics, pivoted away from infectious disease research in the 2000s, followed by the likes of Eli Lilly and Sanofi. GlaxoSmithKline (GSK) and Pfizer, major leaders in the space, have significantly reduced antibiotic research.

Among the recently launched antibiotics, Pfizer’s Zavicefta is the only one to have clocked around $700 million to $1 billion in global sales, according to estimates by industry analysts.

For global drug giants, clocking sales over $25-30 billion annually for drugs like Keytruda (immuno-oncology) and Wegovy/Ozempic (weight loss), these are meagre numbers. Overall, the antibiotic market was worth $50-55 billion in 2024, according to Grand View Research.

But for smaller Indian companies, an antibiotic drug can change their fortunes. For instance, Wockhardt’s upcoming drug Zaynich, for use in critical care patients, could be a multi-billion dollar opportunity. It has an addressable patient pool of over two million, across the US, Europe, China and India. The market is worth ₹17,000 crore in India and $7 billion in US and Europe, combined.

For Orchid Pharma, which recently bought back global rights to its drug, Enmetazobactam, from Allecra, the focus is on planning a US entry.

“Globally, the product has already been licensed in Europe, the Middle East and North African markets, and we are in advanced discussions for several other geographies,” Manish Dhanuka, the company’s managing director, told investors during its first quarter earnings call. The company’s whole time director, Mridul Dhanuka, had previously indicated that the drug could reach $2 billion in peak sales until it reaches patent expiration in 2031-32.

Bugworks, meanwhile, says it is seeing interest from larger pharma companies for a licensing deal, but any further action hinges on successful phase 1 trials.

For Indian innovators, the story so far has been one of conviction, resilience and a deep commitment to science in a tough landscape. But this is only the beginning. The country’s drug industry is seeing a slow but sure pivot towards more innovation—both from incumbents as well as from small but ambitious biotechs. The wait is for the next big breakthrough.