Bangalore: Nearly two years after Supreet Deshpande spun off NovaLead Pharma Pvt. Ltd from its parent company VLife Technologies, which was started to bring the discipline of technology to the celebrated serendipity of drug discovery, he has managed to sell his story to the investors, raising $8 million (Rs39 crore) from two private equity (PE) funds based in Mumbai.

Illustration: Jayachandran / Mint

Deshpande claims that one of the most promising drugs in his company’s pipeline of 11 drugs is an existing intravenous drug that his suite of software, and later animal studies, has found to be effective as an ointment in healing diabetic foot ulcer. The next two molecules in advanced stages are for colon and pancreatic cancer.

“Globally, some 280 million people are affected by diabetes, and going by the medical data, 15% of them will develop diabetic foot ulcer of which 25% will lead to amputation," says Deshpande. He doesn’t want to name the PE funds, one of which is an existing fund; another, part of an industrial house, is a new entrant. Today, hardly any medication exists for diabetic foot ulcers. So, Deshpande is convinced he has an assured market when his drug hits the market two years later.

A mechanical engineer by training, Deshpande came to the pharmaceutical business with the aim of repositioning existing drugs to new indications, also called repurposing. By definition, repurposing is not a new phenomenon; pharmaceutical companies have been doing this for years, but more by serendipity than by hard-nosed science. What small information technology- and biology-driven companies are trying to do now is by design—a systematic uncovering of many activities that existing or abandoned drugs are involved in. This also leads to significant cost reduction in drug development vis-a-vis de novo drug development as safety parameters are already proven and clinical runs are much shorter.

Some noted examples of accidental repurposing are: Viagra, originally developed for hypertension, but later found to be effective in erectile dysfunction; Wellbutrin, a drug first developed to treat depression, but later found another indication in smoking cessation (and is now marketed as Zyban by GlaxoSmithKline Plc). This week, scientists from Stanford University School of Medicine report in PNAS (Proceedings of the National Academy of Sciences of the United States of America) that the inexpensive hypertension drug lisinopril may be effective against multiple-sclerosis, a chronic autoimmune disease.

“Repurposing is a way to making cheaper therapeutics, which is driven not by serendipity, but by hypothesis and a rational approach," says Suri Venkatachalam, founder of Connexios Life Sciences Pvt. Ltd, a drug discovery company which is working with several generic drug molecules and testing them on the “network model of disease" that his company has built. This is not like a traditional predictive model, but generates what-if scenarios and “helps us examine if we can impact multiple targets by one or a combination of molecules and vice versa," he says.

Connexios is testing a combination of two molecules, which have been co-prescribed for other indications but now work synergistically to lower triglyceride levels and significantly lower body weight. While this could be an anti-obesity therapy or manage cardiovascular risk as well just like fibrates (a class of cholesterol-lowering drugs) Venkatachalam adds that his company is testing it thoroughly in animals and analysing the data. Globally, a few start-ups have the headstart, cashing in on the spurt in computational tools, gene expression databases, drug annotation technologies and overall declining productivity of traditional pharmaceutical research. Big pharma has traditionally done this, which has been notoriously called “ever-greening of patents" by many, says Sanjiv Kaul, managing director at ChrysCapital Investment Advisors in New Delhi. But the industry as a whole is now looking at using computational tools to screen its existing library of discarded molecules or late stage-clinical failures for new indications.

Experts say “repositioning" can lead to new business models for Indian companies. They can look for new indications themselves and validate them through animal and proof-of-concept human studies and then license them out to pharma companies.

Alternatively, start-ups can tell big pharma, “lets look at your chemistry" and mine their molecule repository, says Venkatachalam. For instance, Bangalore-based Cellworks Group Inc., which raised $10 million in PE investment in March, announced last week it has signed a pact with ISP Personal Care, a global provider of advanced personal care ingredients, to use its computer modelling to screen biomolecules for skincare products. Cellworks’ chief executive Taher Abbasi says the company plans to design therapy and license it out since its technology allows it to look at biological targets across cell systems for different disease areas. In another business model, says Kaul, Indian companies can in-licence molecules from big pharma, screen them, validate them and then license back to the parent companies for development. In all these cases, intellectual property is safe as patents are sought and given for new indications as well as for new formulations, which Deshpande and Venkatachalam are hedging on. But it appears repurposing is possible in another crucial phase of drug development—post-marketing surveillance or pharmacovigilance, which essentially identifies adverse side effects of drugs. Experts say “repurposed" pharmacovigilance would look for and understand beneficial side effects of drugs that may surface during their development or use.

Mark S. Boguski, former vice-president of Novartis Institute of Biomedical Research, who is now at the Harvard Medical School and has founded Resounding Health Inc., a medical search and discovery engine, says social networking communities could be used to report the beneficial side effects of drugs. “Resounding Health has novel algorithms to crowdsource medical information from consumers and to organize and analyse the data relative to existing knowledge," he said in an email.

Boguski thinks neither the regulatory agencies nor the big pharma will be able to accomplish the “disruptive" changes necessary for this new model. If big pharma gets involved, it will be by acquiring the early movers which invariably are the start-ups. “But it’s just as likely, I think, that the first movers could be acquired by other industries seeking to expand beyond their core businesses. Both Microsoft and Google, for example, have made major commitments to moving into health care and this is one way for them to do this in a novel way." Resounding Health is pursuing both direct-to-consumer and business-to-business strategies. It is free to consumers but also offers a professional version. “We are currently in discussions with one Indian firm on a joint venture but cannot say anything further at this time," said Boguski.