The drug industry is pouring billions into R&D against Alzheimer’s disease. Yet many people in the business will tell you not nearly enough is known about the underlying biology—what causes Alzheimer’s, what combination of factors drives it and how to slow it down or halt its relentless progression. Only one out of 244 Alzheimer’s drugs tested in clinical trials from 2002 through 2012 reached the market, as Meg Tirrell and I discussed in a recent podcast.
The quest for more relevant knowledge to guide drug development has led some major drugmakers and investors to bet on a Cambridge, Mass.-based startup, Yumanity Therapeutics. Yumanity is announcing today it has raised $45 million in a Series A venture financing. Fidelity Management & Research Company, the giant investment firm, led the round. It was joined by Redmile Group, Alexandria Venture Investments, Biogen, Sanofi-Genzyme BioVentures and Dolby Family Ventures, a family office run by the heirs of billionaire audio pioneer Ray Dolby, who suffered from Alzheimer’s. (For more on the rise of wealthy family offices investing in biotech, subscribers can see this December article in Timmerman Report).
“I’d characterize the group as smart money, and money that understands the science behind what we’re trying to accomplish,” said Tony Coles, the founding chairman and CEO of Yumanity. “One of the biggest challenges of the industry is we just don’t understand the biology of Alzheimer’s and Parkinson’s very well. We’ve got some basic work to do on the basic mechanisms, and then we can train our guns of drug discovery on those mechanisms.”
Yumanity is still in the early days of its R&D. The company is built on research from Susan Lindquist’s lab at the Whitehead Institute for Biomedical Research. Her studies have concentrated on protein misfolding, which happens sometimes when DNA gets transcribed into amino acids that don’t fold into the proper shape needed for the protein to do its job. That basic molecular dysfunction plays over time in neurodegenerative diseases such as Alzheimer’s, Parkinson’s and Lou Gehrig’s disease (amyotrophic lateral sclerosis). As people live longer, cells undergo more divisions, more misfolded proteins accumulate, and neurodegeneration gets worse. Alzheimer's Disease International estimated in its 2010 report that there were 35.6 million people with Alzheimer’s disease worldwide, and the number will grow to 115.4 million people by 2050.
The startup came to public attention in late 2014 partly because of its edgy science, its urgent mission and its high-profile cofounders. Yumanity is led by Coles, a well-known pharmaceutical executive who sold his last company, Onyx Pharmaceuticals, to
The main job at Yumanity, before raising the big Series A financing, was to show it could put together the critical pieces of a drug discovery engine. The company uses a yeast-based system to identify promising molecular pathways that appear to go awry in neurodegeneration. Another essential tool--induced pluripotent stem cell technologies--enable Yumanity to make human neurons in the lab dish. Those cells are important because they are human, and because they can verify findings from the initial yeast-based platform that’s fast and cheap. Other tools to assess genes and protein variations are supposed to help Yumanity narrow down the patient populations most likely to benefit from a genetically tailored approach. Altogether, the knowledge of the biological pathways that go awry in protein misfolding is supposed to set the table for Yumanity to do high-throughput screens of small-molecule chemical compounds that might bind with a molecular target well enough to become viable new drug candidates.
Getting the first 20 people working together, and working out processes with a couple of contract vendors that help with aspects of the biology and chemistry, have been the main achievements of the first year. After its big first wave of publicity, the company collected 900 resumes of people seeking to come work there. Hiring so many of “the best and brightest,” as Coles put it, helped put Yumanity in position to collect such a big Series A round.
Bernard Davitian, a managing director with Sanofi-Genzyme Bioventures, said his firm chose to invest because it generally looks for breakthrough science, big medical needs and top-notch investors and management teams.
“Clearly, Yumanity Therapeutics fits this description and Tony (Coles) is an outstanding leader,” Davitian said. “We are excited by Yumanity’s new paradigm to transform drug discovery in this area.”
Jeffery Kelly, a expert in protein folding at the Scripps Research Institute in San Diego and a Yumanity board member, said the company stands out because of the unusual pieces it has put together. Yumanity represents the first time someone has put these particular technology pieces together for neuroscience drug discovery. The technology "removes a major obstacle" in taking initial drug screen "hits" from the discovery stage through further development, he said.
Even if the drug discovery technologies are firmly in place, there’s an immense amount of work to do. Yumanity doesn’t yet have a lead drug candidate, or anything ready yet for thorough animal testing. Coles declined to give a timeline for when that might occur, or when Yumanity might be ready for the more meaningful proving ground of human clinical trials. Alzheimer’s is still somewhat a mystery, as scientists debate the role of beta-amyloid plaque buildup, tau tangles, faulty cell-trafficking and even the role of inflammation. “Several things may be going awry,” Coles said. “We may need combo therapies attacking each of these aspects, and maybe different drugs at different stages of disease.”
That’s the kind of drug development plan that will take a lot of time, money and hard work. Earlier in his career, Coles concentrated on drugs further along in the R&D continuum, seeing them all the way through to FDA approval. He knows how much remains ahead, and that Yumanity has essentially run a solid first mile out of a marathon. “We’ve made an enormous amount of progress,” Coles said. “We’re off to the races.”
