April 15, 2014 (Vol. 34, No. 8)

Gail Dutton

A More Fitting Name, an Abiding Commitment to Fighting Neuropsychiatric Disorders

The brain is, perhaps, the ultimate medical frontier. There is a high unmet need for new therapies that address cognition and prevent disease from robbing individuals of their very essence.

Forum Pharmaceuticals, which was known as EnVivo Pharmaceuticals until April 2, is committed to addressing that need. “We focus singularly in this space. We are a purpose-built company,” says Deborah Dunsire, M.D., Forum’s new president and CEO. Prior to joining Forum, Dr. Dunsire was president and CEO of Millennium: The Takeda Oncology Company.

The issue of cognition among Alzheimer’s patients is urgent, and becomes more so in light of the world’s aging population. “Some 16 million people have the early, prodromal symptoms of Alzheimer’s disease, and people are living longer. If all those people develop Alzheimer’s disease, the consequences are dire. This is a disease we have to solve,” Dr. Dunsire insists.

Cognition, a key area of Alzheimer’s disease, also affects schizophrenia, although this is under-recognized. “Patients may be treated for hallucinations with an antipsychotic, but after the first episode of psychosis, they are not at the same cognitive level as before. This changes their lives,” Dr. Dunsire contends. “We believe therapeutics could address the symptoms that prevent people from moving on with their lives, yet there have been no new classes of therapies for schizophrenia for over a decade.”


Forum Pharmaceuticals’ pipeline includes alpha-7, histone deacetylase inhibition, gamma secretase modulation, and phosphodiesterase inhibitor programs. The compounds in these programs are intended to treat neuropsychiatric conditions for which currently available therapies are insufficient and leave profound unmet needs.

Clinical Trials

Forum Pharmaceuticals is evaluating encenicline-hydrochloride (EVP-6124), a novel alpha-7 (α7) potentiator. The compound, which is administered orally, is thought to penetrate the blood/brain barrier to function as a co-agonist with naturally occurring acetylcholine to improve neural processing and cognitive performance for memory and executive function.

In-licensed before it reached the clinical-development stage, encenicline is in a Phase III trial in approximately 200 centers globally to assess its ability to improve cognition in patients with Alzheimer’s disease and in patients with schizophrenia. Phase II results indicated clinically significant improvements in cognition when encenicline was administered. “So far, it’s very well-tolerated,” Dr. Dunsire points out.

The 26-week Phase III trial for Alzheimer’s disease launched in January 2014. It plans to enroll 1,600 patients. A similar trial for schizophrenia began one year earlier, in February 2013.

“The trial is conducted under a Special Protocol Assessment with the FDA, so if it meets the endpoints, that would be a sufficient basis for the FDA to consider approval, although not a guarantee,” she explains. The trial design was developed with very close interaction with the FDA. The company already has a licensing agreement with Mitsubishi Tanabe Pharma to develop and commercialize encenicline in Japan and other parts of Asia.

While encenicline has advanced furthest in Forum’s pipeline, another program targeting Alzheimer’s disease is in Phase II trials. It uses gamma secretase modulation (GSM) rather than inhibition as a novel means of reducing production of the 42-amino-acid form of beta amyloid (Abeta42) and increasing production of shorter, nonamyloidogenic Abeta peptides and, therefore, reduce the brain’s ability to produce the plaque. EVP-0962 shows anti-amyloid activity and is likely to have an improved safety profile when compared to gamma secretase inhibitors.

For schizophrenia, EVP-6308 addresses psychosis and cognition in one pill. The compound, a highly selective phosphodiesterase (PDE) inhibitor, is in Phase I trials. The company says this represents a new approach “to treat positive, negative, and cognitive symptoms in patients with acute and chronic schizophrenia.”

Forum also is investigating histone deacetylase (HDAC) inhibition to normalize and increase gene transcription in a rare variant of dementia. EVP-0334, a first-in-class drug, has completed Phase I trials and is expected to enter Phase II trials later this year.

In addition to its own development programs, Forum also works closely with the Dominantly Inherited Alzheimer Network (DIAN), an international research partnership dedicated to understanding a rare form of Alzheimer’s disease caused by genetic mutation. Along with other DIAN Pharma Consortium members, Forum shares its expertise in designing and implementing clinical trials.

“Everything seems to be coming together now,” Dr. Dunsire remarks, and Forum is expanding. While partnering with a contract research organization to conduct clinical trials, it also is building its internal capabilities, hiring people who have experience with shepherding drugs through trials, the NDA approval process, and commercialization. Dr. Dunsire expects Forum’s staff of 160 to expand to approximately 230 by year’s end.


Rebranding

Forum’s discovery research, which is aimed at identifying new targets and molecules, is conducted in-house and with partners in academia. The company’s clinical research is conducted in medical institutions throughout the world. To these research tasks, remarks Dr. Dunsire, “We bring an understanding of the compound and the biology.”

The company’s name change, which took effect April 2, reflects an attempt at rebranding. “The name ‘EnVivo’ caused confusion,” Dr. Dunsire admits. “With a program in Phase III and outreach work with the medical community to build awareness around cognition, we realized we had reached an inflection point. We wanted to go forward with a name that differentiates and communicates who we are.”

In rebranding the company as Forum Pharmaceuticals, the company combines the historic function of a forum with its aspirations. “A forum is a place where people come together and share ideas,” Dr. Dunsire says. “It’s a place where innovation can happen.”

“Science and ideas can be debated and, through that, turned into new medications to transform medicine,” Dr Dunsire continues. “To make headway on the formerly intractable problems of dementia, schizophrenia, and Alzheimer’s disease, we need to connect and collaborate with communities of patients, scientists, and regulators. Only then can we conquer these diseases. The name change represents this connected, collaborative approach.”


Forum Pharmaceuticals

Location: 500 Arsenal Street, Watertown, MA 02472

Phone: (617) 225-4250

Website: www.envivopharma.com

Principal: Deborah Dunsire, M.D., President and CEO

Number of Employees: 160

Focus: Forum Pharmaceuticals focuses on discovering and developing therapeutics to improve the function and course of disease in patients with neuropsychiatric diseases. Its multitarget approach addresses the cognitive elements of Alzheimer’s disease and schizophrenia.