Rodin Therapeutics started up last year with a plan to treat neurological disorders like Alzheimer’s by enhancing cognition, rather than trying to wipe out the plaques that build up in the brain. Roughly a year later, the Cambridge, MA-based startup has come far enough to warrant a big round of venture dollars.
Rodin is announcing today that it’s closed a $12.9 million round led by founding investor Atlas Venture, and Johnson & Johnson Development Corp., the venture subsidiary of New Brunswick, NJ-based Johnson & Johnson NYSE: JNJ). Rodin will use the cash to refine and select its first drug prospect and get it into its first clinical trial, according to chief business officer (and Atlas venture partner) Ankit Mahadevia. Using the relatively new field of epigenetics–switching genes on or off without affecting the underlying DNA—Rodin aims to treat neurological diseases like Alzheimer’s, or potentially post-traumatic stress disorder (PTSD).
As I wrote last year, Rodin was formed in March 2013 through a strategic partnership with Germany-based drug discovery company Proteros Biostructures. Proteros is a stockholder in the company, and it is hosting the core wet lab work for Rodin’s prospective drug discovery efforts.
The general idea behind Rodin is to discover epigenetic drugs that can be used to reprogram neurons to regain some of their ability to function, potentially improving cognition. In theory, this could help curb the neurodegenerative effects of diseases like Alzheimer’s, PTSD, or frontotemporal dementia.
Rodin doesn’t want to reverse the course of these disorders—it’s not going to pursue yet another approach to fight off amyloid plaques, for example, which are a hallmark of Alzheimer’s. Rather, the startup wants to develop a drug that can, say, add years of quality life to an Alzheimer’s patient by helping boost that patient’s cognitive abilities, either as an alternative to palliative treatments like donepezil (Aricept) or in combination with them.
The cognitive enhancement approach is similar to the one Forum Pharmaceuticals (formerly known EnVivo Pharmaceuticals) is taking with Alzheimer’s. And Mahadevia says that we’re still a few years away from knowing whether other Alzheimer’s drug approaches, such as beta secretase inhibitors, really work, leaving room for treatments like this to have an impact.
Mahadevia adds that the approved cognitive enhancement drugs “don’t work all that well” and carry a “large” side effect profile. Donepezil, for instance, is associated with headaches, fatigue, vomiting, and more serious things like seizures and fainting.
“There’s a large gap and there’s a huge need for something that’s better that current symptomatic therapies, so that’s the big opportunity for us,” he says.
Rodin hasn’t yet specified which particular cognitive disorder it wants to tackle initially, but it wants to develop a compound that targets a specific histone deacetylase (HDAC) isoenzyme, which Mahadevia says is implicated in the generation of new synapses and improved associative learning.
The big challenge is to come up with a drug that hits that specific enzyme rather than several enzymes at a time, which could lead to side effects. Many of the early HDAC-inhibiting cancer drugs hit more than one enzyme, leading to things like fatigue, nausea, and potentially even brain hemorrhages.
But the bar for side effects is lower in advanced cancer patients. Rodin doesn’t have nearly as much leeway with a drug meant to be taken chronically by, for instance, frail Alzheimer’s patients.
“You just need a safer drug,” Mahadevia says.
A number of groups have tried to improve HDAC inhibitors and make them more specific, says Mahadevia. (Acetylon Pharmaceuticals, for one, is developing selective HDAC inhibitors for blood cancers.) But they’re not, as of yet, “selective down to the isoenzyme,” he says, and the literature suggests that level of selectivity is necessary to safely address central nervous system disorders like Alzheimer’s.
Mahadevia says that Rodin has shown enough proof over the past 12 months to convince Atlas and J&J to shell out the Series A cash. Rodin has developed selective enzyme inhibitors that meet “at least the preliminary specs” of what’s needed to move forward, such as specificity and potential drug-like properties.
To be clear, there’s a long way to go. But the company owns two different families of compounds—each based on two separate types of chemistry—with potential. Rodin will use the cash to refine and develop two sets of chemical compounds, which it declined to describe, except to say that one set came from Proteros, the other via a license from the Broad Institute of MIT and Harvard, which has an equity stake in Rodin.
“We have some more work to do of course, but for us it was really proof that the idea holds some merit and has been able to advance interesting drug matter forward.” Mahadevia says.
Rodin has also added names to its ranks. Pfizer and Satori Pharmaceuticals veteran Barbara Tate has been hired as Rodin’s head of biology, joining acting CEO and Atlas partner Bruce Booth, chief scientific officer Martin Jefson (Pfizer’s former head of neuroscience research), and Mahadevia (who is also CEO of another recent Atlas startup, Spero Therapeutics).
MIT professor Li-Huei Tsai now chairs Rodin’s scientific advisory board, which also includes Jeffrey Nye, the central nervous system therapeutics lead for J&J’s Boston Innovation Center; Marcelo Wood of UC Irvine; Lisa Monteggia of the University of Texas Southwestern; Andre Fischer of the University of Gottingen; Ed Holson of the Broad Institute, and Stephen Haggarty of Massachusetts General Hospital.