September 10, 2015
By Mark Terry, BioSpace.com Breaking News Staff
Ember Therapeutics and its relationship with Third Rock Ventures is being held up as an example of the risks of investing in biotech companies.
Ember Therapeutics was based on research conducted by Harvard researcher Bruce Spiegelman and the discovery of a hormone that was involved in exercise and fat metabolism. The hormone, dubbed irisin, seemed to help convert white fat, the unhealthy kind of fat, into so-called brown fat, which is considered “good” fat.
Scientists — and investors — speculated that if the processes involved with irisin and fat metabolism could be identified and turned into a drug, they would be sitting on a blockbuster weight-loss drug.
Third Rock Ventures, based in Boston, committed $34 million and helped create Ember Therapeutics in December 2011. It bought the rights for irisin and other molecules. Spiegelman was brought on as a scientific founder. Hopes were high that Ember would come up with a product to test in humans in two years or so.
In March 2015, Ember merged with New York-based Mariel Therapeutics. Mariel focuses on targeted therapies for osteoarthritis and kidney fibrosis using Bone Morphogenetic Protein (BMP)-7. The two companies had a clinical pipeline of four drugs in development, one that had just completed Phase II clinical trials in osteoarthritis and three others that were wrapping up preclinical development and were expected to enter Phase I.
What wasn’t specified in the companies’ press release in March was that Mariel didn’t acquire the rights for irisin, which were returned to Harvard University, reports Bloomberg. In a statement to Bloomberg, Kevin Starr, a partner with Third Rock, said, “It would take a longer time horizon than anticipated to sort through the complex biology and pathways of brown fat.”
According to the Pharmaceutical Research and Manufacturers of America, it can take longer than an average of 10 years to research and develop a new drug. In the case of Ember Therapeutics, it was given about three years.
Perhaps other factors include some ambiguity around irisin. In March 2015, Scientific Reports published an article, “Irisin — a myth rather than an exercise-inducible myokine,” by Alke Albrecht, Harold Erickson and others. The premise of the article revolved around the laboratory techniques used by Spiegelman and others to identify irisin circulating in the blood, essentially a technique called ELISA. ELISA, which stands for enzyme linked immunosorbent assay, is a very sensitive test. An alternate technique, called Western blotting, is used to detect specific proteins in a sample. Albrecht and others looked for irisin using Western blotting, and didn’t find the expected size molecules in the sample, calling into question all the previous studies of irisin.
In an interview with Bloomberg, Erickson said, “Many research labs around the world are spending serious money on these studies, and we wanted to get their attention.” His conclusion was that there was “no credible evidence that irisin exists in the blood of any animal.”
Spiegelman performed more research and published a paper in the journal Cell Metabolism last month. In this work, Spiegelman utilized mass spectrometry to isolate irisin in human blood. Erickson then agreed that irisin probably actually exists, but indicated to Bloomberg that Spiegelman hasn’t proven that the molecule can actually stimulate white fat to act like brown fat.
That sort of technical uncertainty, along with a lengthy and unpredictable timeline, can create the kind of volatile environment that makes investors nervous, particularly with the high burn rate of biotech investment dollars.
Most recently, Ember announced on Aug. 6, 2015 that Montreal-based Knight Therapeutics had extended a secure loan of $1 million (U.S.) and additional equity commitments to Ember valued up to $5 million. Knigh also inked an exclusive distribution agreement with Ember to commercialize its Bone Morphogenetic Protein-7 (BMP-7) pipeline in Canada and various international markets. Ember appears to have moved out of the sexy area of fat reduction to bone and cartilage regeneration for osteoarthritis.
