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  • Writer's pictureJyoti Pande

How Curofy, started up by three IIT grads, is focused on connecting the medical community

Saturday, 1 August 2015

Talk to anyone associated with public health, and they will tell you about the miasma of antibiotic resistance sweeping the world. The World Health Organization's first report on the global state for antibiotic-resistant bacteria recently warned that the world is entering a “post-antibiotic era,” in which even the most powerful antibiotics available are becoming ineffecive against infections so easily treated in the past.

Closer home, a newspaper story last month highlighted a study that tracks infants in India born with bacterial infections that are resistant to most known antibiotics which said that 58,000 of the 800,000 infants who die annually, die due to multi-drug resistance. “Evidence is now overwhelming that a significant share of the bacteria present in India — in its water, sewage, animals, soil and even its mothers — are immune to nearly all antibiotics,” The New York Times report datelined Amravati, India, said.

Even if some feel that that is a generalised overstatement, the fact remains that India's public health infrastructure is poor and the country hasn't managed to bring down background rates of infections in any significant manner. In such situations, doctors end up prescribing antibiotics preventively and more liberally – in some cases to treat viral diseases that antibiotics can't even cure. Inappropriate use of antibiotics can worsen the situation by increasing multi-drug resistance. It is a classic paradox where effectiveness is diminished by use and increased accessibility and consumption of antibiotic often leads to increased resistance.

Add to this, the growing overuse of antibiotics in livestock to keep them disease-free and stimulate growth, as industrial scale farming spreads, with increasingly more animals packed into tinier amounts of space – and you have the perfect storm.

“Antibiotic consumption in India has increased 70% between 2000 and 2010,” says

Dr Ramanan Laxminarayan, Vice President, Research and Policy at the Public Health Foundation of India.

An even more dangerous subset of antibiotic-resistance is hospital-acquired infections – ask any doctor worth his stethoscope and he will tell you that, counter-intuitively, infection rates in Indian intensive care units are almost 40% higher than in general wards. An Indian Intensive Care Case Mix and Practice Patterns study recently found that one out of every eight patients in India die from infections contracted in ICUs. To begin with, ICU patients are more prone to catching even the slightest infections, as they are more immune-compromised since they are on heavy doses of antibiotics - and pathogens in the ICU are more resistant to these antibiotics, explain doctors. Recently, U. (Mandolin) Srinivas survived a liver transplant – but not the hospital acquired infection that followed.

Antibiotic infections are tough, sometimes impossible, to treat and the most likely reason for longer hospital stays and increased treatment costs. “Hospital acquired infections should be the highest public health priority in India,” Dr Laxminarayan says.

In a September 2014 Science magazine publication, Dr Laxminarayan said antibiotic effectiveness is a natural societal resource that is diminished by antibiotic use. “As with other such assets, keeping it available requires both conservation and innovation.” Conservation makes best use of antibiotic effectiveness by reducing demand through vaccination, infection control, diagnostics, public education, incentives for clinicians to prescribe fewer antibiotics, and restrictions on

access to newer, last-resort antibiotics. Innovation includes improving the efficacy of current drugs and replenishing effectiveness by developing new drugs, he said.

In most countries, but especially India, none of this is happening, say physicians.

The Centers for Disease Control and Prevention has already warned of potentially catastrophic consequences unless immediate action is taken to reduce overuse, track and prevent the spread of resistance and develop new drugs. Significantly, three months ago, the Obama administration finally outlined a national strategy to tackle the growing threat of antibiotic resistance that includes incentives for new drug discovery and development, tighter stewardship of existing antibiotics and improvements in tracking their use and that of microbes resistant to them.

Overall, across geographies, big pharmaceutical companies seem to have stepped back from responsibilty on R&D for new drug discovery in this field – simply because it is so much more profitable to find new drugs that focus on lifestyle and other diseases where efficacy isn't diminished by use. But in an interesting development, a couple of new startups in India have recently entered the field of drug discovery - Bugworks in Bangalore, co-founded by Anand Anandkumar, Janaki Venkatraman and Santanu Datta, and Vitas in Hyderabad, co-founded by Radha Rangarajan and Rajinder Kumar. The latter recently pitched to the Indian Angel Network for funding of Rs 3 crore and got fully subscribed within minutes. The deal was led by four IAN members, including well-known angels such as Jerry Rao and Hemant Kanakia.

Vitas Pharma started in 2011 as a drug discovery and development company, involved in identifying and developing next-generation antibiotics to treat multi-drug resistant hospital acquired infections. Its two co-founders, (Dr Rajinder Kumar also serves as the chief medical officer of the company) have invested almost $1 million of their own funds as well as grants to bring the company up to the product development stage. The money raised from IAN will be used primarily for completing the safety, pharmacology and toxicology package and filing an investigational new drug and clinical trail application for one programme, the founders said. The next round of funding will be initiated in 12 months to raise Rs. 20 crore.

"Vitas is going after an area of drug discovery that is very important for humanity. We're currently facing a perfect storm of superbugs which are resistant to most existing antibiotics – and India has become an epicenter because of over-prescription of antibiotics by Indian doctors for even minor ailments,” said Hemant Kanakia in an email from the U.S. “The reluctance of major pharma companies to engage in sustained R&D effort to develop new antibiotics makes it especially important to support startups like Vitas. Plus, Radha's clear exposition and factual command of her business proposition impressed us. She came across as someone with a very good sense of the business as well as the sciences aspect of her startup,” Kanakia added.

Rangarajan has received her Bachelor's degree from Stanford University and PhD from Rockefeller University. Before starting Vitas, she was a postdoctoral fellow at the Harvard School of Public Health in Infectious diseases and a scientist in the drug discovery division of Dr Reddy's Laboratories. “The WHO now cites antimicrobial resistance as one of three greatest threats to human health. Given the current levels of drug resistance and their widespread occurrence globally, drugs that overcome resistance and offer significant clinical benefit are urgently needed,” Rangarajan, who is also CEO, Vitas, said in a phone interview from Hyderabad.

The Vitas portfolio currently includes compounds for bacterial infections such as hospital acquired pneumonia, blood stream infections, complicated skin and soft tissue infections and complicated urinary tract infections.

"We have filed three patents till date. These compounds target vital metabolic functions in the cell and are novel, thus overcoming drug resistance. The most advanced project is at a lead optimized stage and is intended for the treatment of complicated skin infections and hospital acquired pneumonia caused by Methicillin-Resistant Staphylococcus Aureus (MRSA). The other three projects are at different stages of preclinical development from hit to lead," says Rangarajn.

"Our operational model is based heavily on the public-private partnership model. Vitas was incubated in the University of Hyderabad and the IKP Knowledge Park. We work with academic institutions and public hospitals," Rangarajan said.

At the moment, Vitas Pharma is collaborating with both academia and industry. "We have an ongoing collaboration with, Dr Harinath Chakrapani at Indian Institute of Science Education and Research, Pune; Dr Sharon Peacock, University of Cambridge, Dr V Lakshmi, Nizam's Institute of Medical Sciences, Dr D.Balasubramanian L. V. Prasad Eye Institute, and Syngene (a Biocon group company). We've also had past collaborations with the faculty at the University of Hyderabad," Dr Radha says.

"We are a research and development-driven product company. Our business model is to out-license our molecules after achieving proof-of-concept in the target population,” she added. This makes Vitas's “customers” mid-to-large pharmaceutical companies with expertise in clinical development and regulatory practices, with sales and marketing capabilities in the major markets. At present, the company has filed for 3 patent applications, two international and one in India and has four key programs in its portfolio, one of which is a collaboration in which Kiran Majumdar Shaw has invested.

The Vitas team consists of scientists with Master's or PhD degrees, in chemistry or biology, with relevant industry or academic experience. "In the field of new drug discovery for antibiotics, there are only a handful of companies worldwide. We have the distinction of being one of them," Rangarajan says. However, she feels that the appetite of Indian private investors for investment in R&D driven biotech companies is very low – they are very risk averse. “This is in contrast to other parts of the world such as the Silicon Valley or Boston, where investment in biotechnology is considered an essential component of the growth story," she says.

With that contrast in mind, she emphasizes that, in India the government needs to take the role in creating an ecosystem for R&D driven companies to thrive. "This includes creating capital for start-ups, establishing incubators, accelerators and putting in place policies that are small-company-friendly and tax incentives to promote private investment in R&D," she says.

Rangarajan sees Vitas entering the clinical development phase with its assets, and successfully out-licensing and building partnerships with other pharmaceutical companies. "Our focus will remain on infectious diseases, although we may expand our scope to include anti-virals and anti-parasitics in the future. Pain and inflammation is another area that we might venture into,” she says. In the long term, Vitas wants to establish itself as a world class pharmaceutical company, with secured finances and ongoing clinical development programmes for antibacterial indications and diagnostics.

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