Another Viagra? One Israeli startup is streamlining drug discovery

ReThink Pharmaceuticals Co-Founder Dmitry Shvartsman (left), CEO Etty Amir and COO Guy Seemann. (Photo credit: courtesy)

Viagra was a happy accident. Initially developed to reduce high blood pressure, the drug was ‘repositioned’ to treat erectile dysfunction when researchers noted that patients in clinical trials experienced certain beneficial side effects.

Drug repositioning is often achieved by trial and error, but ReThink Pharmaceuticals wants to make those happy accidents a regular occurrence. The year old company has found a way to identify ‘failed’ drugs that could be repositioned to treat other diseases. ‘And it’s validated,’ boasts CEO Etty Amir, a former Teva executive.

Rethink’s technology, developed by the company’s Chief Scientist Dr Yuval Tabach, cherry-picks chemical compounds that have alternative applications, which Rethink then verifies in the medical literature and in their own clinical trials. The company ‘offers an array of drug discovery options [using] a unique system that can simultaneously compute the possibilities for thousands of drugs,’ says Amir, who joined the company earlier this year. Until that point, Co-Founder and now COO Guy Seemann had been running the company without taking a salary from it.

Dr Yuval Tabach in his lab: namely a computer and thousands of DNA data sets. (Credit: courtesy)

Based on bioinformatics research that Tabach did while he was at Harvard Medical School, Rethink’s technology is able to understand and predict gene interactions by grouping genes that share a similar function. Known as genes clusters, these groupings have been used by evolutionary biologists to better understand how genetic mutations caused species to diverge from each other. Yet Tabach realised that gene clusters could also aid the process of drug discovery.

Gene clusters highlight the relationship between genes and gene groupings. (Credit: courtesy)

Instead of mapping the genome as a linear sequence of approximately 20,000 genes, he visualised gene clusters on a connectivity map that presents the genome as a network of direct and indirect relations. This ‘genetic road map’ is what enables the drug developers to see alternative directions for existing or ‘failed’ drugs, usually molecules that have passed initial safety screenings, but lack effectiveness.

It’s no secret that drug development is a long and costly process. On average, a new molecular entity takes between 10 – 15 years to develop and gain approval, and the costs range from $500 million to $2 billion. ‘Pharmaceutical companies will do whatever it takes to mitigate risk and reduce costs,’ explains Amir. During her 12 year tenure at Teva, she saw many drugs scrapped six or seven years into development, and can relate to the frustrations of researchers and sales executives when a drug is shelved during Phase III, the most extensive and expensive part of a clinical trial. ‘You can’t win back the time and money spent.’ Just last year, Merck terminated its 16 year development of Tecemotide, a therapeutic cancer vaccine intended to treat advanced Non-Small Cell Lung Cancer on the grounds that the drug did not improve overall survival. Researchers are still assessing whether the therapy is effective in other cancers.

Developing successful methods to treat cancer has been one of the greatest concerns of the pharma industry, and Rethink is dedicating particular focus to it. Now at Hebrew University’s Medical School in Ein Karem, Tabach has been gathering genetic data on about 450 species that are resistant to cancer. ‘Some of the major challenges in medicine, like increasing lifespan and reducing cancer have already been solved by nature, multiple times,’ says Tabach. ‘Many species have evolved genetic mechanisms that make them resistant to cancer and some also show significantly long life span. Other species have developed extraordinary traits, such as resistance to hypoxia, ability to hibernate, regeneration of lost tissue or adaptation to extreme environments.’

Naked mole rats are resistant to cancer and have comparatively longer life spans than other rat species. (Photo credit: Buffenstein/Barshop Institute/UTHSCSA)

For example, the naked mole rat, a rather unsightly creature, is resistant to cancer, tolerant to hypoxia and has an extremely long lifespan. Its relative, the blind mole rat, a native to the Golan Heights, also self-destroys cancer cells by what researchers believe to be a different method than that of its cousin. Other examples include wood frogs that are tolerant to freezing and tardigrades which have survived in outer space without protection. ‘Using comparative genomics we can identify the genes that suppress cancer, have a role in aging and protect the organism under extreme environment,’ explains Tabach.

ReThink’s proposition comes at a time when pharmaceutical pipelines are running dry and industry giants, like Novartis, Pfizer and GlaxoKlineSmith are eagerly buying and selling in-house R&D units to strategically position themselves. They are also snapping up smaller, more specialised biomedical outfits. While acquisitions refuel their pipelines and have the potential to generate long term returns, they are also costly. Last year, the Irish drugmaker Actavis acquired Allergan, a company widely known for its botox products, for a record $72.7 billion, and just last week, Teva purchased Allergan’s generic drug business for $40.5 billion.

Precisely because of these high price tags, ReThink maintains that their platform and the wider use of data analytics will have a profound impact on the pharma industry as a whole. Similarly, the management consultancy firm McKinsey estimates that applying big-data strategies to pharma R&D could generate up to $100 billion in value annually across the US health-care system. Intel and GE have been quick to seize the opportunity by developing data analytic tools specifically for life science analytics, as well as IBM, ReThink’s partner for systems development.

Now part of the Boston-based accelerator, MassChallenge, ReThink is looking for initial investment to expand the capacity of their platform so that it may handle multiple operations at once. Meanwhile, the company is in advanced negotiations with a German Medical Institution in order to run their first pilot program with patients. The team has also engaged in discussions with pharmaceutical companies that have shown interest in ReThink’s ability to identify new applications for old drugs.

Such enthusiasm from a traditionally risk averse, conservative industry is telling. Drug repositioning could save drugmakers billions of dollars, but more importantly, it could lead to the release of hundreds of drugs stalled in pharma pipelines.