Introducing Lab Rats: A Mint series on India’s biotech startups

Mumbai: On 10 October, Hyderabad-based biotech startup PopVax announced a new milestone—its broad-spectrum, fridge-stable covid-19 mRNA (messenger ribonucleic acid) had entered human trials. This is especially significant for easing distribution in developing countries with limited cold-chain infrastructure, especially in the event of another outbreak, which would require prompt deployment.

Many mRNA vaccines, which are now being developed for several diseases including cancer, require ultracold storage—in the range of -20 to -80 degrees Celsius. PopVax’s candidate, which is being tested for safety in patients, can be stored in refrigerators (2-8 degrees Celsius) for over nine months.

The startup hopes to advance its platform for other infectious diseases as well as cancers, according to chief executive officer (CEO) and founder Soham Sankaran.

PopVax plans to make its covid-19 drug candidate open source for researchers and producers after completing Phase 1 trials—“our gift to the world,” said Sankaran.

Improving the temperature stability of mRNA vaccines is a crucial requirement, but one that few are trying to address. The research, though sparse, is largely happening in academic settings or in developing countries. Researchers at the Massachusetts Institute of Technology (MIT) are trying to tweak formulations to be heat-resistant and have demonstrated promising results in mice. Thailand’s first mRNA shot, ChulaCov19, remains stable at fridge temperatures for three months and has successfully completed phase 1 trials.

This is where Indian biotech stands today—on the precipice of groundbreaking development for a global patient pool, addressing access and availability, while staying abreast of global competitors.

These are, of course, still few and far. India’s total R&D (research and development) pipeline for novel drug research is currently pegged at roughly 225 molecules. This would be about a tenth of China’s total pipeline, according to Vikash Agarwalla, India leader, healthcare practice, BCG.

What is notable, says Agarwalla, is that roughly 17% of the molecules in India’s R&D pipeline are first-in-class, meaning a completely new drug or mechanism to treat a disease. This compares to China’s 24%, demonstrating the quality of innovation happening in India.

China, which has already surpassed the US for the largest number of clinical trials globally, is targeting 25% of global first-in-class drugs now, as part of its five-year-plan to cement itself as a global centre of biotech innovation.

What is a drug really?

To understand a drug, you must understand a disease. And to understand many diseases, you must understand proteins.

Proteins are essential to almost every biological process. They send messages, catalyse chemical reactions, regulate cell growth, build structures such as collagen, and recognise foreign or abnormal molecules. Your DNA holds the instructions for making proteins.

Many diseases involve proteins gone wrong—too much, too little, in the wrong place, altered by mutations, or acting abnormally. Developing treatments can therefore mean finding a way to interact with a disease-related protein, either directly or by altering the processes that regulate it. That is where the challenge lies, because proteins aren’t simple switches—they are three-dimensional, constantly moving molecules whose shapes and interactions influence how they work.

A drug must find a suitable target and interact with it to get the desired result without causing harm to the body. This lies at the heart of much modern drug discovery.

In this series, we highlight a few such promising startups. This is by no means an exhaustive list. Rather, it is a sample size designed to capture the depth and breadth of the country’s biotech ecosystem.

There are a host of challenges to overcome: Sankaran of PopVax outlines the slow trial timelines and how to attract the right talent to India; Parul Ganju of Ahammune talks about initial sparse funding and how the startup advanced its drug targeting vitiligo; the three founders of Helex Inc. explain how they are trying to make a cutting-edge therapy truly affordable; the scientist-engineer founders at Peptris speak on how they are trying to build a globally competitive artificial intelligence-based drug discovery platform in a crowded market; and Kavitha Iyer Rodrigues of Zumutor underscores the ultimate biotech challenge of giving back returns to patient capital investors.

Spin round the block?

India’s drug industry—known as the ‘pharmacy of the world’ for supplying 20% of the global generics medicines and 60% of vaccines—hasn’t always stayed away from innovation.

The 1990s saw a concerted effort to pursue innovation, with Dr Reddy’s, Ranbaxy, Torrent, Sun Pharma and Zydus all launching programmes. However, two decades of small-molecule R&D had led to only one drug entirely discovered and developed by an Indian company getting approved by the Indian regulator (Saroglitazar was developed by Zydus for diabetic dyslipidemia and hypertriglyceridemia; the Drug Controller General of India approved it in 2013).

By the mid-2010s, several Indian drugmakers had either shuttered or shrunk their discovery programs. Some, like Glenmark and Wockhardt, stuck to it doggedly, much to the ire of public markets, but have been vindicated in recent years—as evidenced by Glenmark’s landmark $700 million AbbVie deal.

Startups, however, are a new story in this ecosystem. Dr Ratnesh Jain, founder of the Mumbai Biocluster and a professor at the Institute of Chemical Technology, pointed out that about 95% of innovative therapies originate from either early-stage startups or academia-linked innovators, which are typically licensed by larger firms.

Indian startups are working with much tighter funding than their peers in the US and Europe, he admitted. But they can still hold their own against larger firms, given that the playing field may not be entirely defined by funding, but rather by the science.

“In Big Pharma, one has 100 problems to solve. For a startup, there’s only one problem to solve. In this case, the entire attention and energy goes to that particular problem,” Jain said.

Recent policy efforts are instrumental in shaping India’s fledgling biotech ecosystem.

Take, for example, the Promotion of Research and Innovation in Pharma MedTech Sector (PRIP) scheme, which approved ₹1,600 crore across 41 projects recently in its first tranche, or the ₹1 trillion Research, Development and Innovation (RDI) Fund and ₹10,000 crore Biopharma Shakti scheme announced in this year’s budget. A simultaneous increase in venture capital interest too has helped.

However, core innovation requires a knowledge base in R&D, which comes from research institutions, argued Dr Manish Diwan, head of the BIRAC-RDI fund, which falls under the RDI scheme. “If our research institutions reach the next orbit of their research which is cutting edge… that’s when we can attain the scale [required] for first-in-class innovation,” he said. BIRAC is short for Biotechnology Industry Research Assistance Council, a not-for-profit set up under the Department of Biotechnology.

Biotech research and innovation hubs and incubators, like the Centre for Cellular and Molecular Platforms (C-CAMP) in Bengaluru or the Centre for Cellular and Molecular Biology and ASPIRE-BioNEST in Hyderabad can help early-stage work.

Earlier this month, C-CAMP was selected as one of five focused research organizations under the RDI fund with a funding commitment of ₹500 crore.

However, these are nascent efforts and the quantum of innovation still needs to be built. Indian startups have not yet had their ‘AbbVie’ moment, but a few early wins and successful deals could set the tone.