- Phase 1 healthy volunteer portion of the AL001 study successfully met its primary objective of safety and demonstrated proof-of-mechanism in the central nervous system (CNS)
- Phase 1b study of AL001 enrolling frontotemporal dementia (FTD) patients with a mutation in the progranulin gene will assess safety and pharmacodynamics, and will monitor target specific biomarkers
SOUTH SAN FRANCISCO, Calif., April 17, 2019 (GLOBE NEWSWIRE) -- Alector, Inc. (ALEC), a clinical-stage biotechnology company pioneering immuno-neurology, a novel therapeutic approach for the treatment of neurodegeneration, today announced dosing of the first frontotemporal dementia (FTD) patient in the Phase 1b portion of the INFRONT clinical study of AL001 after successful completion of the healthy volunteer single ascending dose escalation portion of the study.
“AL001 was generally well tolerated, with no drug-related serious adverse events in healthy volunteers, achieving the study’s primary objective. Moreover, AL001 successfully demonstrated proof of mechanism in healthy volunteers by showing a dose dependent increase in progranulin levels, a disease specific biomarker, in plasma and in cerebrospinal fluid,” said Robert Paul, M.D., Ph.D., chief medical officer.
In a subset of FTD patients, mutations in a single copy of the progranulin gene lead to a 50% or greater decrease in the level of progranulin, which in turn leads to development of FTD with greater than 90% penetrance. This subset of patients is known as FTD-GRN. Alector aims to deploy AL001 to increase the level of progranulin in FTD-GRN patients, by inhibiting a progranulin degradation mechanism.
“We are proceeding with the Phase 1b study which will assess the safety of multiple doses of AL001 as a primary objective. AL001’s therapeutic approach is conceptually similar to enzyme replacement therapy and as such AL001 is designed to increase the level of progranulin in these FTD-GRN patients. In addition to the safety, we will also measure the levels of progranulin in plasma and in cerebrospinal fluid to demonstrate proof of mechanism in FTD-GRN patients by increasing the levels of this critical factor,” said Omer Siddiqui, vice president of development operations. “These data will inform future clinical studies, including rational dose selection in potential registrational studies.”
About Frontotemporal Dementia (FTD)
FTD is a rapidly progressing and severe form of dementia found most frequently in individuals less than 65 years old at time of diagnosis. It affects 50,000 to 60,000 individuals in the United States and roughly 110,000 individuals in the European Union, with potentially higher prevalence in Asia and Latin America. There is currently no approved treatment available for FTD patients.
There are multiple heritable forms of FTD, such as FTD-GRN, which represent 5% to 10% of all patients with FTD, and approximately 22% of heritable FTD cases. Mutations in a single copy of progranulin lead to a 50% or greater decrease in the level of progranulin and lead to development of FTD with greater than 90% penetrance. To date researchers have identified over 70 inherited loss of function mutations in progranulin that lead to FTD.
Patients with FTD exhibit a range of symptoms including personality changes, compulsive behavior, lack of restraint, apathy, and anxiety as well as language and behavioral problems. FTD symptoms have an insidious onset with clinical symptoms usually appearing between 45 to 65 years of age at an average age of 58. Average life expectancy in FTD patients is seven to ten years after the start of symptoms. The rate of disease progression in FTD is faster than in Alzheimer’s disease, adding to the severity of the disease and unmet medical need in patients.
AL001 is Alector’s wholly-owned human monoclonal antibody designed to modulate progranulin, a regulator of immune activity in the brain with genetic links to multiple neurodegenerative disorders, including FTD, Alzheimer’s disease, and Parkinson’s disease. It aims to increase the level of progranulin in humans by inhibiting a progranulin degradation mechanism. AL001 was discovered and engineered in collaborative effort between Alector and Adimab, LLC.
AL001 was granted Orphan Drug designation by the U.S. Food and Drug Administration for the treatment of FTD in June 2018.
Alector is a clinical stage biotechnology company pioneering immuno-neurology, a novel therapeutic approach for the treatment of neurodegenerative diseases. Immuno-neurology targets immune dysfunction as a root cause of multiple pathologies that are drivers of degenerative brain disorders. Alector is developing a broad portfolio of programs designed to functionally repair genetic mutations that cause dysfunction of the brain’s immune system and enable the rejuvenated immune cells to counteract emerging brain pathologies. The Company’s product candidates are supported by biomarkers and target genetically defined patient populations in frontotemporal dementia and Alzheimer’s disease. Alector is headquartered in South San Francisco, California. For additional information, please visit www.alector.com.
Cautionary Note Regarding Forward-Looking Statements
This press release contains “forward-looking” statements within the meaning of The Private Securities Litigation Reform Act of 1995. Such forward-looking statements are based on our beliefs and assumptions and on information currently available to us on the date of this press release. Forward-looking statements may involve known and unknown risks, uncertainties and other factors that may cause our actual results, performance or achievements to be materially different from those expressed or implied by the forward-looking statements. These statements include but are not limited to statements regarding the Company’s plans for and anticipated benefits and mechanism of the Company’s product candidates, the timing and objectives of the clinical studies and anticipated regulatory and development milestones. Except as required by law, we assume no obligation to update these forward-looking statements publicly, or to update the reasons actual results could differ materially from those anticipated in the forward-looking statements, even if new information becomes available in the future. Important factors that could cause our actual results to differ materially are detailed from time to time in the reports Alector files with the Securities and Exchange Commission, including in our annual report on Form 10-K that is filed with the Securities and Exchange Commission (“SEC”). Copies of reports filed with the SEC are posted on Alector’s website and are available from Alector without charge.
Source: Alector, Inc.