Lysosomal Therapeutics of Cambridge, MA, has closed a $20 million Series A round to push forward a drug for Parkinson’s disease that exploits the link between neurodegeneration and a family of rare genetic disorders.
LTI raised a $5 million seed round last year. When it found a compound to develop as its lead Parkinson’s candidate, as Xconomy reported last month, its previous backers, led by Atlas Venture, ponied up for the much larger Series A.
The rare disease connection is no coincidence. Former Genzyme CEO Henri Termeer and other Genzyme alumni were cofounders. Genzyme pioneered enzyme replacement therapy that has extended the lives of patients with Gaucher, a hereditary disease caused by a deficiency in the enzyme glucocerebrosidase (GCase). As Gaucher patients began to live longer, their doctors started noticing that they had a greater than normal incidence of Parkinson’s.
Those observations led to more formal studies of the link between GCase and alpha-synuclein, the a protein that misfolds and clumps up in the brains of Parkinson’s patients. LTI scientific founder Dmitri Krainc of the Feinberg School of Medicine at Northwestern University is a leader in the field.
LTI licensed a group of compounds from the National Institutes of Health, and Krainc studied them in neurons derived from an extremely rare group of Parkinson’s patients. Those neurons produced an overabundance of alpha-synuclein, but the compound LTI is moving forward showed it could knock down alpha-synuclein levels while boosting GCase.
LTI CEO Kees Been (pictured) explained the correlation between the two proteins when we spoke last month. “You can have lower and lower levels of GCase without having disease,” said Been. “But only until you hit a particular level does the level of synuclein come up. It’s an interesting phenomenon.”
LTI is betting the reverse will be true: Boost healthy GCase with a drug, and Parkinson’s patients will benefit as synuclein clears out. LTI has competition. Amicus Therapeutics (NASDAQ: FOLD), of Cranbury, NJ, is working on the problem, and its research in the area is under license to Cambridge-based Biogen Idec (NASDAQ: BIIB).
Researchers at the University of California, Los Angeles, recently found that an Amicus drug being tested against Gaucher has shown promise for Parkinson’s—albeit only in mice so far.
There’s still a ways to go before human testing, however. First, chemical modifications are required to “optimize” the lead compound—make it behave more like a drug. While LTI is doing that, it will also run experiments to see if the amount of GCase in a Parkinson patient’s peripheral blood cells makes a good biomarker—that is, a stand-in for the disease to help LTI choose people for their trials who are more likely to respond to a GCase-boosting drug.
The Michael J. Fox Foundation for Parkinson’s Research has helped fund LTI’s biomarker research.
Ultimately, LTI will need to find a larger partner to carry a Parkinson’s drug through advanced clinical trials, Been told Xconomy last month. A Phase 3 trial in Parkinson’s could cost $150 million, he said.
Joining Atlas Venture in the A round were other existing investors Hatteras Venture Partners, Lilly Ventures, Sanofi-Genzyme BioVentures, Roche Venture Fund, and Partners Innovation Fund, as well as Orion Equity Partners, and the former Genzyme execs Termeer and Bob Carpenter.