Researchers around the world have explored the ties between the immune system and devastating neurodegenerative diseases such as Alzheimer’s. San Francisco biotech Alector wants to exploit those ties to make drugs, and today it announced $32 million in venture funding—with another round likely coming by year’s end—to continue that work.
Alector was founded two years ago by bioengineering specialist and Dartmouth College professor Tillman Gerngross, former Genentech scientist Arnon Rosenthal, and Columbia University professor Asa Abeliovich. The aim is to go after neurodegeneration by stimulating the innate immune system—cells such as macrophages and microglia. Those cells, in turn, would work harder to prevent the misfolded proteins, often ending in clumps or tangles in patients’ brains, that are the hallmark of Alzheimer’s and other diseases.
I asked Rosenthal, the CEO, if there are lessons to be drawn from the red-hot field of cancer immunotherapy, which also aims to unleash the power of the immune system to fight disease. One branch of the field is developing antibodies that help “unmask” tumors that otherwise hide from the immune system’s T cells. These so-called checkpoint inhibitors have had success knocking down some severe skin cancers and a type of lung cancer, but as solo therapies they’re facing limitations, and companies are scrambling to test combinations of checkpoint antibodies and other drugs.
Alector is developing antibodies, too. The targets Alector is going after—proteins on the surfaces of innate immune cells in the brain—are different than cancer immunotherapy’s targets, but “the cell biology is similar,” says Rosenthal.
One big difference, he says, is that T cells are part of the adaptive immune system—a rapid response network that can mount a vicious counterattack when unleashed against an invading microbe or growing tumor. Developers working either with immunotherapies that stimulate T cells, or directly with engineered T cells, have to be extra careful not to point the T cells toward healthy tissue. They also have to monitor patients closely for an overheated immune response, which can lead to serious, even deadly side effects.
But Rosenthal says studies show that innate immune stimulation poses less risk of what he calls “overactivity.” He also says Alector is working to engineer antibodies that reduce the risk.
“There’s always some level of risk of over enhancing the immune system, but the way we design drug leads and focus on innate immune decreases the risk,” Rosenthal said. His hypothesis is that the immune cells will only become active in the presence of pathological agents, such as the abnormal proteins that are hallmarks of many brain diseases. If one of Alector’s antibodies were given to a healthy person, the immune system would be on alert, “more vigilant in looking for pathologies, but we don’t think it would be activated indiscriminately,” said Rosenthal.
The company will need to do key experiments before testing that hypothesis in people. Alector has identified about a dozen targets and is currently working to hone the right antibodies for six of those targets. Rosenthal declined to name the targets, but he did say they are associated with “risk genes,” those that, when mutated, put people at higher risk of developing a particular disease. Having two copies of a mutation of the apolipoprotein E called ApoE4, for example, boosts a person’s risk of Alzheimer’s by roughly ten-fold, perhaps more. The first patients Alector will test will probably have such mutations, as a way to show Alector’s approach is on the right track, but ultimately Alector’s drugs will be applicable to everyone with a disease, Rosenthal said.
If all breaks right for Alector, it could start clinical trials in one or two diseases in 12 to 24 months, Rosenthal said. He wouldn’t commit to Alzheimer’s as the lead indication, saying the company still needs “more concrete data” from animal tests.
Alector chairman Gerngross said Alector set out to raise $10 million but within two months had rounded up $32 million, with MRL Ventures, the venture arm of drug giant Merck (NYSE: MRK), taking the lead. It’s strictly financial; Merck has no rights or ties to Alector’s work.
The cash isn’t contingent upon Alector hitting milestones, as venture rounds often are. A new “significant” investment is likely before the end of the year, Gerngross said.
One of Gerngross’s other startups, Adimab of Lebanon, NH, where he is CEO, is working with Alector to refine its antibodies. The companies also share an unusual investor, Google Ventures, which infrequently invests in biopharmaceutical companies. Google joined Alector’s Series C round, as did Mission Bay Capital and Topspin Partners. Previous investors OrbiMed Advisors and Polaris Partners also pitched in. Gerngross said Google Ventures has cashed out of its Adimab investment, which it first made in 2009.
Image of the brain courtesy of Allan Ajifo under a Creative Commons license.