16 of the roughly 600 total assets Cydan has looked at, and killed off ten of those programs. For the ones that turn into startups, Cydan’s principals—as in, Adams, McArthur and the rest of its team—get some equity for their efforts. Cydan’s backers then step in with the investment cash, as they did with Imara, and get lion’s share of the stock.
Cydan finds these assets from a variety of places. With Vtesse, for instance, VTS-270 was already being tested in a National Institutes of Health-sponsored Phase 1 study (here’s more on that from the Wall Street Journal); Vtesse had licensed the experimental drug from the NIH. Other times, as with Imara, Cydan advances “assets on paper,” Adams says. That is, molecules that have been synthesized by a drug maker, but haven’t been tested yet.
Danish pharma firm H. Lundbeck A/S had synthesized hundreds of different molecules that inhibit an enzyme called phosphodiesterase 9 (PDE9). Lundbeck had thinking about these drugs as potential treatments for neurological diseases like Alzheimer’s (as have others, including Pfizer), but recent research (such as this 2014 paper from the journal Blood) has suggested they might be useful as a treatment for sickle cell, in which the bone marrow produces abnormal “sickle” shaped red blood cells that can get stuck in the bloodstream and block blood flow.
Since Lundbeck is a neurology-focused company, it has no interest in sickle cell. It gauged Cydan’s interest in developing a treatment for the blood disorder, and offered a list of “literally four sheets of PDE9 inhibitors” to choose from, McArthur says. Cydan took eight, began synthesizing them, and whittled the numbers down until it came up with what’s being called IMR-687. Imara has full rights to the drug, a pill that is meant to prevent the “sickling” of blood cells and the resulting outbreaks of pain that occur they clog up blood vessels. Lundbeck would get milestones and royalty payments if the drug progresses.
This is just one of several sickle cell treatments in development, along with a gene therapy from Cambridge-based Bluebird Bio (NASDAQ: [[ticker:BLUE]]), and drugs from the San Francisco Bay Area’s Global Blood Therapeutics (NASDAQ: [[ticker:GBT]]) and San Diego-based Mast Therapeutics (NASDAQ: [[ticker:MSTX]]). Gene editing approaches with CRISPR-Cas9 are advancing as well, as my colleague Alex Lash reported last year.
Pfizer even has a rival PDE9-blocking drug for sickle cell in Phase 1 testing though McArthur contends that Imara’s drug has an advantage. The Pfizer drug, PF-04447943, gets into the brain, and Imara’s IMR-687 doesn’t. Pfizer’s drug was originally tested in Alzheimer’s—where diffusion into the brain would be an asset—but it failed a Phase 2 trial. A sickle cell treatment should be different, McArthur says.
“Do you really want to be inhibiting PDE9 in the brain of kids and babies and young adults? Probably not,” McArthur says. “[That’s why] we specifically selected a drug that could not get into the brain.”
Still, given all the competition, Cydan faces an uphill battle to show it’s made the right bet with Imara. If it can, it could be easier for Cydan to go back to its investors to fund its next round, and create its next batch of startups. Adams notes that Cydan itself has enough cash to get to mid-2017, but discussions are already underway about what’ll come next, and what the next iteration of Cydan will look like.
“The first time we raised money, this was a white space,” he said. “Now we have a track record, a pipeline, and a knowledge base.”
