Alector Closes $133 Million to Expand Alzheimer’s Programs

South San Francisco-based Alector closed on a Series E financing worth $133 million. Participating companies were Deerfield Management, AbbVie Ventures, Federated Kaufmann Fund, Section 32, Euclidean Capital, Foresite Capital, Lilly Asia Ventures, New Leaf Venture Partners, Perceptive Advisors, Casdin Capital, Polaris Partners, OrbiMed, MRL Ventures, GV, the Dementia Discovery Fund, Mission Bay Capital, Amgen Ventures, and others.

It’s an interesting and broad set of investors, with the venture arms of several biopharma companies—AbbVie, Eli Lilly, and Amgen—involved, as well as Google’s GV, and Section 32, which is run by Bill Maris, who originally founded Google Ventures. The Dementia Discovery Fund is the largest venture fund focused solely on discovering and developing novel therapies for dementia, and recently completed a $350 million fundraiser of its own, which was met with a $60 million investment from the U.S. AARP.

The money will be used to advance the company’s clinical programs and expand its discovery platform. It also announced its three lead programs. They are AL001, for the treatment of frontotemporal dementia (FTD), which targets the protein linked to FTD; AL002, which targets a triggering receptor expressed on myeloid cells 2 (TREM2), linked to Alzheimer’s and other neurodegenerative diseases; and AL003, which targets SIGLEC-3, a transmembrane receptor expressed on cells of myeloid lineage, a risk factor for Alzheimer’s.

“There has been a lack of new approaches to treat the underlying causes of devastating neurodegenerative diseases such as frontotemporal dementia (FTD) and Alzheimer’s disease,” said Sabah Oney, Alector’s chief business officer, in a statement. “At Alector, we are focused on the advancement of innovative, first-in-class medicines to treat these serious diseases. We are thrilled to have strong support from industry-leading investors, and this financing ensures sufficient resources for the continued development of our novel drug pipeline.”

Two of the drugs target immune system receptors in the brain, TREM2 and SIGLEC-3. Part of the company’s theory is that problems in patients’ immune system are linked to higher risk of Alzheimer’s and FTD. The approach to immuno-neurology is similar to that currently being used in immuno-oncology, where some compounds boost the immune system while others dampen its effects.

“We are going to test both drugs as standalone modalities and in combination,” Amon Rosenthal, Alector’s chief executive officer, told FierceBiotech. “You may need to both press the accelerator and release the brake for the car to move. So we are testing both to find the most optimal approach.”

Alector hopes to begin those clinical trials by the end of this year. It plans to use a suite of liquid and imaging biomarkers to evaluate the compounds’ activity against Alzheimer’s early in the trials. The third compound will likely give faster results because frontotemporal dementia has a faster progression than Alzheimer’s.

According to Rosenthal, in preclinical research, patients whose TREM2 gene showed no functionality developed dementia by the age of 40 and died within a few years. Also, patients whose TREM2 gene has lower activity had triple the risk of Alzheimer’s disease. Patients whose TREM2 genes had mutations causing overexpression had less risk than the general population.

Rosenthal also believes that the compounds, if they prove out, could complement other therapies being developed in the Alzheimer’s and dementia spaces. This refers to various antibodies that attack beta-amyloid. He told FierceBiotech, “But if the microglia are not functioning, this approach is not going to work well. We think that our drug would be beneficial whether or not there is a beta-amyloid therapy on the market. If there is, our drug will synergize with this therapy.”