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Prader-Willi Syndrome trial

Zafgen completes enrolment of Phase 3 PWS trial

The company expects to report the first data from this trial early in the first quarter of 2016

Zafgen has completed enrollment of ZAF-311, also known as the Beloranib Efficacy Safety and Tolerability in Prader-Willi syndrome (bestPWS) study, a Phase 3 clinical trial of beloranib for the treatment of patients with Prader-Willi syndrome (PWS). The objective of the study is to evaluate the efficacy and safety of beloranib in PWS patients over six months of randomised treatment, followed by a six-month open label extension. The trial includes 108 patients with PWS enrolled across 15 sites in the US; the planned enrolment target number was 102 patients.

"We're pleased to announce that we have met and ultimately exceeded our enrolment target for this important Phase 3 trial of beloranib in patients with Prader-Willi syndrome," said Dr Thomas Hughes, Chief Executive Officer of Zafgen. "We remain committed to advancing beloranib and further exploring its potential as an effective treatment option for patients and families living with this challenging condition. We expect the first data readout from this trial early in the first quarter next year."

PWS is the most common known genetic cause of life-threatening obesity, results in constant and unrelenting hunger that drives patients with PWS to engage in problematic hunger-related behaviours and gain excessive weight. As a result, many of those affected become morbidly obese and suffer significant mortality. There is currently no cure for this disease. Although the cause is complex, it results from a deletion or loss of function of a cluster of genes on the 15th chromosome.

PWS typically causes low muscle mass and function, short stature, incomplete sexual development, and a chronic feeling of hunger that, coupled with a metabolism that utilizes drastically fewer calories than normal, can lead to excessive eating and life-threatening obesity. PWS occurs in males and females equally and in all races, with the same incidence around the world. Prevalence estimates have ranged from 1:8,000 to 1:50,000.

BestPWS is a six-month trial consisting of randomized, double-blind, placebo controlled, twice-weekly subcutaneous injections of 1.8mg or 2.4mg of beloranib or placebo in 108 patients with PWS. The primary efficacy endpoints for this trial are hyperphagia-related behaviors and body weight. Secondary endpoints include changes in total body fat mass, LDL-c, HDL-c, C-reactive protein (CRP) which is a marker of systemic inflammation, among others, and quality of life.

At the time of screening, patients enrolled in the trial are, on average 20 years old, morbidly obese (BMI40 kg/m2), roughly equal number of males and females, and have a hyperphagia total score consistent with moderate to severe hyperphagia. Thus, the enrolled population is representative of the general PWS population and what was intended for this Phase 3 clinical trial.

"BestPWS is the first of two pivotal clinical trials of beloranib in PWS patients," said Dr Dennis Kim, Chief Medical Officer of Zafgen. "Patients with PWS and their families are in need of a novel and effective treatment option, and beloranib has the potential to be the first therapy to help improve hyperphagia and body weight, improving the lives of patients, families and caretakers alike. This is the first time that a double-blind, randomised placebo controlled Phase 3 clinical trial in PWS has been conducted."

Beloranib is a novel, first-in-class injectable small molecule therapy with a unique mechanism of action that reduces hunger while stimulating the use of stored fat as an energy source. Beloranib is a potent inhibitor of methionine aminopeptidase 2 (MetAP2), an enzyme that modulates the activity of key cellular processes that control metabolism. MetAP2 inhibitors work, at least in part, by directing MetAP2 binding to cellular stress mediators, and, thus, reducing the tone of signals that drive lipid synthesis by the liver and fat storage throughout the body. In this manner, MetAP2 inhibition increases metabolism of fat as an energy source.

The company is also developing ZGN-839, a liver-targeted MetAP2 inhibitor, for the treatment of nonalcoholic steatohepatitis (NASH), and abdominal obesity. Zafgen aspires to improve the lives of patients through targeted treatments and has assembled a team accomplished in bringing therapies to patients with both rare and prevalent metabolic diseases.

Zafgen holds exclusive worldwide rights (exclusive of South Korea) for the development and commercialization of beloranib. Zafgen exclusively licensed beloranib from Chong Kun Dang (CKD) Pharmaceutical Corp. of South Korea.

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