Alector Snags $133M to Activate Immune Cells Against Neurodegeneration

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Xconomy
San Francisco
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Pharmaceutical companies have been working for years to find a drug that could break up the toxic clusters of proteins associated with Alzheimer’s disease and other neurodegenerative disorders. Many of those companies have suffered disappointing failures by targeting those clusters head-on. Now a Bay Area biotechnology company, Alector, is ready to try tackling the problem from a different angle— energizing immune system cells, the body’s natural clean-up crew, to clear away the debris.

South San Francisco-based Alector announced today that it raised $133 million in a Series E fundraising round, and unveiled the first three immune system-modulating antibodies in its pipeline that will be tested in clinical trials. The company, founded in 2013, expects to move its drug development program into the clinic later this year, and the new capital will help fund that effort.

Alector, whose fundraising total now adds up to $415 million, has raised capital from a group of investors that ranges from drug company venture funding arms to GV, the venture capital arm of Google parent company Alphabet (NASDAQ: GOOGL).

With its immune system approach to therapies for neurodegeneration, Alector is riding a tailwind from the promising results from some of the new immunotherapies developed to treat cancer. In fact, Alector says cancer is also a target for its drug development program.

But for now, its lead drug candidates are centered on neurodegenerative disease, and rely on the growing body of research about the role of the aging or malfunctioning immune system in Alzheimer’s disease and other disorders of the brain. All three of the experimental drugs Alector plans to test first in human beings are antibodies that can cross the blood-brain barrier.

Two of them, AL002 and AL003, are potential treatments for Alzheimer’s disease. Both of those have been chosen for co-development by AbbVie (NYSE: ABBV), says Alector’s chief medical officer Robert Paul. Drug giant AbbVie announced a collaboration with Alector in October, under which it gained the option for global development and commercial rights to two of Alector’s targets. Under the deal, the two companies will co-fund the programs and share global profits equally. AbbVie paid Alector $205 million upfront, and may make a later $20 million equity investment in the smaller company.

AL001 in frontotemporal dementia

The remaining antibody, AL001, was developed as a possible treatment for another neurodegenerative disease, frontotemporal dementia (FTD), a term that describes a group of disorders involving the shrinkage of the frontal and temporal lobes of the brain, as the Mayo Clinic describes it. The disease affects behavior, emotions, thinking, and the use of language. Symptoms vary, but they worsen over time. In a subset of people with a rapidly progressing form of the disorder, FTD has been linked to a genetic mutation that hampers their production of a beneficial protein called progranulin, or PGRN.

AL001 was designed to increase therapeutic brain levels of progranulin (PGRN), which sustains the survival of neurons and also moderates the potentially harmful inflammatory responses of certain immune system cells, the myeloid cells called microglia, Paul says.

AL001 blocks the breakdown of PGRN by binding to receptors on the surface of both microglia and neurons that facilitate PGRN degradation. The intended result: higher available PGRN levels, neurons protected from injury, and less of the inflammation that threatens brain health, Paul says.

Alector counts an estimated 200,000 people afflicted with frontotemporal dementia, but the company will choose participants in the first clinical trials for AL001 from among the patients whose frontotemporal dementia is traced to their genetic make-up through diagnostic testing, Paul says.

This small subset of FTD sufferers have only one functioning gene to direct the production of PGRN, so their levels of the health-promoting protein can be less than half of that in people with the normal complement of two functioning genes, according to Alector. Life expectancy is low in this population, the company says.

This patient group is an ideal one to start testing the efficacy of elevating PGRN levels, Paul says, because the cause of their disorder seems to be clearly established as the lack of sufficient PGRN, and not to other causes. Paul says Alector should be able to run a smaller-than-usual clinical trial of AL001 in these patients because the antibody is so precisely targeted to address their form of the disease. This patient group is considered the most likely to show a high rate of response to the treatment compared with other FTD patients, he says.

If AL001 gains regulatory approval for the treatment of genetically caused FTD, these patients would need to take the antibody preparation throughout their lives to sustain their PGRN levels, Paul says.

And if AL001 is successful in that initial trial group, Alector plans to explore the potential of elevating PGRN in the broader population of people with FTD, which can develop due to causes other than genetic mutations. Other target diseases for AL001 are Alzheimer’s disease and Parkinson’s disease.

Two Alector drugs ready for Alzheimer’s trials

Both of Alector’s drug candidates for Alzheimer’s disease are designed to activate the immune cells called microglia to clean away various kinds of molecular debris that can harm nerve cells in the brain. This garbage includes fragments of neurons that have died, as well as the harmful conglomerations of molecules associated with Alzheimer’s disease—beta-amyloid aggregates and tangles of tau.

AL002 is designed to restore function to … Next Page »





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