FORUM Pharmaceuticals Inc. Initiates Phase 2a Clinical Trial of FRM-0334 in Frontotemporal Dementia with GRN Mutation

Genetically-targeted Therapy in Development to Address Ultra-orphan Neurological Disease

WATERTOWN, MA, USA I February 10, 2015 I FORUM Pharmaceuticals Inc., a biopharmaceutical company singularly focused on the development and delivery of innovative medicines to treat serious brain diseases, today announced dosing of the first patient in a Phase 2a proof of mechanism clinical trial to evaluate FORUM’s investigational therapy FRM-0334 in patients with the ultra-orphan rare disease frontotemporal dementia with granulin mutation (FTD-GRN). FTD-GRN is a rare, early-onset and rapidly progressive neurodegenerative brain disorder that can affect behavior, cognition, language and motor skills. FTD-GRN results from genetic mutations in the granulin (GRN) gene that lead to less progranulin protein, which is believed to play an important role in neuron survival. FRM-0334 may have therapeutic potential to partially reverse the loss of protein function in FTD-GRN.

“As a company at the forefront in developing innovative therapies for serious brain disease, we are excited to advance our genetically-targeted candidate, FRM-0334, into this Phase 2 clinical trial,” said Deborah Dunsire, M.D., President and Chief Executive Officer of FORUM Pharmaceuticals. “Part of FORUM’s strategy is to incorporate precision medicines into our robust pipeline, and FRM-0334 complements our ongoing Phase 3 development of encenicline for schizophrenia and Alzheimer’s disease. We are hopeful that FRM-0334 may address the urgent needs of granulin-associated FTD patients and their families who are affected by this rare disease.”

The randomized, double-blind, placebo-controlled, dose-escalating Phase 2a clinical trial will evaluate the safety, tolerability and pharmacodynamic effects of two doses of FRM-0334 in subjects with prodromal to moderate FTD-GRN. Primary endpoints will assess the safety and tolerability of FRM-0334 in subjects with the FTD-GRN genotype, as well as effects of FRM-0334 on plasma and cerebrospinal fluid progranulin concentrations. FORUM anticipates enrolling subjects at multiple sites in the United States and Western Europe for the trial. The Company has previously completed a Phase 1 study of FRM-0334 in Europe, where it was found to be well tolerated at all doses tested.

“Granulin-associated FTD is a rare form of rapidly progressing and ultimately fatal dementia for which no therapies currently exist,” said Prof. Dr. John van Swieten, Erasmus Medical Center Depart of Neurology, Rotterdam, The Netherlands. “As a young-onset dementia that generally affects patients between the ages of 45 to 65, FTD strikes adults who may be in the prime of life. The functional impairment resulting from FTD can leave the patient unable to continue working, and also significantly compromise his or her ability to carry out activities of daily life.”

“In addition to safety and tolerability, this Phase 2a trial is designed to investigate the possible effect of FRM-0334 on progranulin levels in patients with the FTD-GRN genotype,” said Gerhard Koenig, Ph.D., Senior Vice President, Research and Chief Scientific Officer at FORUM. “Loss of the granulin protein is believed to be detrimental to neuronal survival, and patients with granulin-associated FTD have significantly less granulin protein due to a mutation in one of the two copies of the GRN gene. FRM-0334 is a histone deacetylase inhibitor that enhances gene transcription of the remaining healthy GRN gene, and we believe that this genetically targeted therapy may have the promise to raise granulin levels and positively affect neuronal survival.”

About FRM-0334

FORUM Pharmaceuticals is developing FRM-0334, an orally bioavailable, small molecule inhibitor of histone deacetylase (HDAC) enzymes, for the potential treatment of patients with frontotemporal dementia (FTD) associated with genetic mutation of the granulin (GRN) gene, known as FTD-GRN. In FTD-GRN, mutation renders one of the granulin alleles incapable of producing normal levels of the precursor protein progranulin. Low production of progranulin is associated with the neurodegeneration that arises in FTD-GRN. By activating the remaining healthy gene allele, FRM-0334 may have therapeutic potential to partially reverse the loss of protein function in granulin-associated FTD.

FORUM has completed a Phase 1 clinical study of FRM-0334 in healthy volunteers in Europe, where it was found to be well tolerated at all doses tested.

About Frontotemporal Dementia (FTD)

Frontotemporal dementia (FTD), part of the frontotemporal lobar degeneration (FTLD) syndrome, is a rare but rapidly progressing degenerative syndrome having several subtypes, and is characterized by changes in personality, cognition, language and behavior. FTD has an early onset, often occurring in people 45 to 65 years of age, and is usually fatal less than 10 years from onset. FTD affects an estimated 50,000 to 60,000 in the United States and an estimated 4 to 15 people per 100,000 in the United States and Europe. A specific subtype of FTD, FTD-GRN, results from genetic mutations in the granulin (GRN) gene that lead to less progranulin protein, which is believed to play an important role in neuron survival. This form of FTD affects an estimated 3 to 15 people per 100,000 people and accounts for 5 to 10 percent of all cases of FTD.

About FORUM Pharmaceuticals Inc.

FORUM Pharmaceuticals Inc. (“FORUM Pharmaceuticals” or “FORUM”) is dedicated to developing groundbreaking medicines in support of all those who are affected by or caring for people with serious brain disease, to help them live fuller, more enriching lives. The Company’s robust and diverse pipeline is focused on discovering and developing new treatments for important neurodegenerative diseases that explore novel mechanisms of action to potentially alter the progression of brain disease and provide improvement in cognitive and overall function. FORUM’s lead compound, encenicline (EVP-6124), is currently being evaluated in separate ongoing Phase 3 clinical trial programs: COGNITIV SZ, which looks to improve cognitive impairment in patients with schizophrenia, and COGNITIV AD, which aims to improve cognition in patients with Alzheimer’s disease. The Company is also developing genetically-targeted therapies, including FRM-0334 for the potential treatment of frontotemporal dementia. Privately owned, FORUM Pharmaceuticals is based in Watertown, Mass. For more information about FORUM, visit

SOURCE: Forum Pharmaceuticals

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