Epigenetics isn’t new. But so far, the growing scientific understanding of gene regulation has largely been used to make cancer drugs. What if you could use the same concept to reprogram neurons to combat neurological disorders? This is the plan that Atlas Venture has shaped for its new startup, Rodin Therapeutics.
Named after Auguste Rodin, the French sculptor who fashioned “The Thinker,” Cambridge, MA-based Rodin is built on the idea of converging the concepts of epigenetics—the idea of switching genes on or off without altering the underlying DNA—with neurology. The company was founded earlier this summer with the help of an unspecified amount of seed funding from Atlas, Johnson & Johnson Development Corp., and Germany-based Proteros Biostructures. It was also one of the two first startup investments announced by Johnson & Johnson when it opened the Boston Innovation Center on June 27.
“The vision here is to be a real leader in the field of epigenetics and neurology,” says Bruce Booth, Rodin’s acting CEO and a partner at Atlas.
Booth says he’s been intently following that field since mid-2007, when published research in the area really began heating up, and has tried to start a company in the framework of Rodin “multiple times” since then. The challenge, however, has been finding a way to make a drug that only hits specific enzymes in the epigenetic process, rather than several at a time, which can lead to side effects.
“In cancer you can accept a higher side effect profile than you can in other areas,” he says. “But in the field of neurology and in frail Alzheimer’s patients, or post-traumatic stress disorder patients, you really need a significant safety margin so you’re able to get an effective dose that is clean of adverse side effects and can be used chronically.”
Booth concluded that the field wasn’t ready for a Rodin in 2008 or even 2010. But recently, after looking through a number of different approaches, Atlas began a partnership with Proteros, a company with expertise in structural biology that has collaborations with more than 80 biotech and agricultural companies. Booth says Proteros’ discovery platform has allowed Atlas to identify, at the very least, “a path” towards achieving its goal of developing epigenetic drugs with the specificity it needs.
So Atlas and Proteros joined together to create Rodin in a way that represents both a financial and strategic partnership.
While Atlas is the largest equity holder and Proteros is also a “core” stockholder, Booth says that a project team that includes Proteros scientists is “part of the fabric” of Rodin. Initially, the core wet lab work will be done at Proteros before new drug candidates are ready to be tested somewhere else, according to Booth. Ultimately, Rodin will get exclusive rights to the drugs that come out of that work.
Booth is the company’s acting CEO, but chief scientific officer Martin Jefson, Pfizer’s former head of Neuroscience Research, and chief business officer Ankit Mahadevia, a former Genentech executive and an Atlas venture partner, are really running the company on a day-to-day basis, he says.
Then there’s J&J. The pharma conglomerate made an equity investment in Rodin in June as part of the opening of its Boston Innovation Center, which is meant to serve as a conduit for J&J to gain access to early-stage innovation projects. As part of it, Marian Nakada, the vice president of Johnson & Johnson Development Corp., joined Rodin’s board of directors. And Jeffrey Nye, the central nervous system (CNS) therapeutics lead for the Boston Innovation Center, is a core member of Rodin’s scientific advisory board. Nye and Nakada have also been actively involved in helping Rodin both structure its initial seed financing and develop the company’s drug discovery plan and business approach.
“They moved quick, they were nimble, and they shared our entrepreneurial view of how to build a company,” Booth says.
The financing Rodin has secured, meanwhile, is structured as a set of tranches that get the company from early drug discovery to an investigational new drug application—which will likely take a few years. The first tranche gives Rodin about 12 months of financial leeway, at which point it hopes to hit an unspecified drug discovery milestone and have enough momentum to recruit a full-time CEO. The second tranche would then kick in, and help Rodin get to the point of having a molecule ready for clinical development.
Once Rodin’s first drug candidate is ready to hit the clinic, Booth expects that there would be a Series B round that would get the compound through a Phase 2 human proof-of-concept study. Rodin is considering a range of potential disease targets for that drug, such as cognitive impairment from Alzheimer’s or schizophrenia. The first drug would be a “nucleating program” to give the company enough juice to start up other programs and build a pipeline, Booth says.
Of course, those are all projections as this point—Rodin is in its infancy. It’s only in the discovery phase, and essentially consists of a team of Rodin executives and Proteros and J&J scientists. The company at this stage is essentially all about testing a series of concepts, so it can figure out which ones are best to prove. One big concept Rodin seeks to test is about whether epigenetic approaches can be used to reprogram a neuron to regain some of its ability to function and do things such as form new synapses.
“Those are parts of the CNS biology that can be affected through epigenetic mechanisms,” Booth says. “Frankly, a lot of the neurotransmitter-based mechanisms are unlikely to do [that].”
In Alzheimer’s, Rodin has some quite unorthodox strategies in mind. It doesn’t plan to try to fight off the buildup of amyloid plaques, or changed levels of Tau in cerebrospinal fluid—two popular methods of Alzheimer’s research that target what are believed to be major contributors to the disease. Rather, it hopes to create a drug that gives patients “an extra five or 10 years of functionally normal cognitive levels,” Booth says.
“It’s not just about holding their cognition flat—we’d like to see improvements in cognition, and that’s our aspiration,” Booth says. “In preclinical models, these types of mechanisms have shown that, where you can take animals who have functional cognitive impairment and by treating them with these types of approaches, you can actually improve their cognitive performance.”
This type of goal in Alzheimer’s brings to mind Watertown, MA-based startup Envivo Pharmaceuticals. Envivo is developing EVP-6124, a so-called alpha 7 nicotinic agonist that is supposed to boost transmission between synapses in the brain and thus, improve cognition. Booth says the epigenetic drug Rodin envisions could be used in combination with that type of drug, or palliative treatments like Pfizer and Eisai Pharmaceuticals’ donepezil (Aricept), since it uses a different mechanism to try to help rewire neurons to improve memory.
For Atlas, meanwhile, Rodin represents a bet on neurology at a time when Big Pharma, stung by failure, is shying away. Atlas recently started up Providence, RI-based Mnemosyne Pharmaceuticals, and has two other companies that it is currently in the process of seeding. One is named Ataxion, and the other, unnamed as of yet, is targeting Parkinson’s.
“A lot of Big Pharma have deprioritized CNS, and in some ways that creates a great opportunity,” Booth says. “We should be starting [these companies] early now so that in four to five years, we can have interesting clinical data at a time when larger pharmaceutical companies may be wanting to come back into the space.”
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