From Beer To Bispecifics And Beyond

India’s biotech scene is buzzing, with over 600 companies and 2,800 startups which collectively contributed approximately US$12 billion to the country’s economy in 2017. But amid the thousands of hopefuls trying to make it big in India, one name stands out: Bangalore-headquartered Biocon, arguably the country’s biggest biotech success story.

Founded in 1978 with just US$140 in capital, Biocon closed its first day of trading in 2004 a billion-dollar company. Since then, the company has become a global powerhouse, producing everything from biosimilars to bispecific antibodies.

We caught up with Biocon’s founder, Ms. Kiran Mazumdar-Shaw, at the 2019 Forbes Global CEO Conference to find out what’s next for the company and why she feels that biotech’s center of gravity is shifting to Asia.

Biocon’s first product, launched in 1979, was an enzyme used to make beer less cloudy. While the company has always been interested in innovation and developing its own proprietary enzymes, it made a conscious strategic shift to pharmaceuticals in the 1990s, Mazumdar-Shaw shared with Asian Scientist Magazine.

Even then, some twenty years after Biocon was founded, Indian biotech companies were few and far between, with many of them focused on producing generic drugs rather than developing new drugs of their own. This approach has been controversial—on one hand, it has helped India become the ‘pharmacy of the world’ as the largest supplier of generic drugs; on the other hand, it has been criticized as a violation of intellectual property rights and a stifling of innovation.

But as a pioneer and key player in India’s biotech industry, Mazumdar-Shaw has witnessed a sea change in recent years.

“In the past, research was always very imitative; today, there’s a lot of innovation going on. For the first time, I’m seeing research focused on absolutely new concepts at research institutes and pharma companies alike.”

At Biocon, for example, there has been a big push towards biologics like monoclonal antibodies. The company is behind BIOMAb-EGFR, India’s first indigenously-developed novel monoclonal antibody, and ALZUMAb, the first therapeutic antibody targeting CD6, a T-cell transmembrane glycoprotein, to treat autoimmune diseases.

“I am very proud of those two antibodies because we didn’t start with a pre-existing product,” Mazumdar-Shaw said. “The data and knowledge we acquired during our initial years of developing absolutely novel antibodies in India gave us the confidence to start developing biosimilars as well.”

“Today, if you ask me what are the most exciting things happening in Biocon, [I would say that] we have started a very serious effort in bispecific fusion antibodies. We’re really looking forward to making a big success of that on top of our pipeline of molecules.”

Unlike typical monoclonal antibodies which recognize a single target, bispecific antibodies can simultaneously bind to two different targets, a property that makes them particularly interesting for immune checkpoint inhibitors.

“Because our immune system is very complex, it takes a multiplexing of antibodies to really do something efficacious,” Mazumdar-Shaw explained. “We have started developing fusion bispecific antibodies combining a T-cell trap with a receptor targeting arm. The idea is to latch on to the tumor antigen and then get the T-cells to start attacking the tumor microenvironment.”

Outside of her role in Biocon, Mazumdar-Shaw has been busy leading the way for innovative cancer therapies, most notably in making chimeric antigen receptor T-cell (CAR-T) technology more affordable for patients in India through her spinoff company, Immuneel.

A joint venture between Mazumdar-Shaw, oncologist Siddhartha Mukherjee and venture capitalist Kush Parmar, Immuneel aims to bring the cutting-edge—and prohibitively expensive—CAR-T cancer therapy down to a fraction of its current cost, to make it more affordable for patients in India. How much more affordable? Their goal is reduce the price of CAR-T therapy to US$50,000, making it 20 to 40 times less than what it would cost in the United States.

CAR-T therapy involves taking a patient’s own immune cells and genetically modifying them to hunt down and destroy cancer cells. This tailor-made approach tends to drive up costs, as with any bespoke product. But Mazumdar-Shaw believes that the key to making the treatment more affordable is by streamlining the supply process.

“If you look at it, a large part of the cost is really the supply chain cost of delivering CAR-Ts to patients,” she pointed out. “We believe that by working on every step of the supply chain, making it like a hub-and-spoke model where you’re working with centers and hospitals rather than taking it to a central lab, we can cut down costs.”

The company, which was formed this year, aims to be able to dose their first patient by the third quarter of 2020, Mazumdar-Shaw said.

One of the reasons that India is an attractive place to launch a startup like Immuneel is that it has a growing middle class and a well-educated talent pool. “The other thing is that in India we expect to be using CAR-T therapy not just on end-stage patients but earlier on, where we hope to get better remission and a lower relapse rate,” Mazumdar-Shaw said.

The main draw of India and Asia as a whole, however, is the simple fact that it is home to the majority of the world’s population, making it where the patents are.

“I have always believed as an entrepreneur and as a scientist, that to prove your science and make a success of your science, you need to deliver the benefit of that science to patients,” Mazumdar-Shaw said. “And if most of the patients reside in Asia, then why not look at Asia as an important part of what you’re doing?”

Beyond serving Asia’s patient population, conducting research in Asia and for Asia is a great need, she continued, because most of the clinical trials to date have only been conducted on Caucasian populations.

“We know that there are genetic and ethnic differences in the way we respond to drugs and in the way drug doses are arrived at,” Mazumdar-Shaw said. “I think people now recognize that this [research on Asian populations] is valuable data. If you really want to build value through innovation, then this kind of differentiated data is going to be very powerful.”

Over half of the world’s population is in Asia. It’s well known that different diseases hit certain races or ethnicities harder than others. I’ve got a hand ligament contracture that dominantly it’s Northern Europeans. I cannot fault her one bit for her valid observation:

“We know that there are genetic and ethnic differences in the way we respond to drugs and in the way drug doses are arrived at. I think people now recognize that this [research on Asian populations] is valuable data. If you really want to build value through innovation, then this kind of differentiated data is going to be very powerful.”

It is not a “dig” against Caucasians.

Indians and middle easterners are Caucasians, so I am not sure where that came from. I know India is in Asia, but it is super hard to group it with Asian countries such as China, Japan, Tibet, etc. They aren’t the same race.

“Caucasians” are the instant market. The most profitable. That’s why trials are directed towards them.

And, as another said, Indians are not distinct from Caucasians. Though perhaps more representative of the Asian population.

An interesting path.

“Mazumdar hoped to go to medical school, but could not obtain a scholarship.[20]

Her father, Rasendra Mazumdar, was the head brewmaster at United Breweries. He suggested that she study fermentation science, and train to be a brewmaster, a very non-traditional field for women. Mazumdar went to Federation University (formerly University of Ballarat) in Australia to study malting and brewing. In 1974, she was the only woman enrolled in the brewing course and topped in her class. She earned the degree of master brewer in 1975?”

From Wiki

All you have to do is read some of those articles I linked to to see that there are indeed diseases unique to the Indian subcontinent. Yes, the Indians are seeing big increases is cardiovascular disease and diabetes because of adoption of the western diet. But you will find a lot of them are genetic problems caused by inbreeding due to social customs.

I don’t know why you would declare this “silly.”

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