afgen Presents Positive Safety and Efficacy Data From Phase 2 Trial of Beloranib in Severe Obesity and Proof of Concept Trial in Prader-Willi Syndrome

Zafgen, Inc.

, a biopharmaceutical company dedicated to significantly improving the health and well-being of patients affected by obesity and complex metabolic disorders, today announced positive efficacy and safety data from its ZAF-201 Phase 2 trial of beloranib, a MetAP2 inhibitor, in obese patients. The Company also announced efficacy and safety data from ZAF-211, a proof of concept study of beloranib in patients with Prader-Willi syndrome (PWS). These findings, presented at the 22nd European Congress on Obesity (ECO) on May 7-8, 2015 in Prague, Czech Republic, demonstrated meaningful weight loss and improvement in cardiometabolic biomarkers. "We are very pleased to present these results to the European obesity research community from our trials in patients with severe obesity and PWS, which demonstrated that treatment with beloranib is not only safe, but also showed meaningful improvements in body weight in obese patients," said Thomas Hughes, Ph.D., Chief Executive Officer of Zafgen. "In both trials, beloranib treatment also improved a variety of biomarkers associated with cardiovascular disease risk and inflammation, supporting its potential to improve common co-morbid conditions affecting patients with obesity and PWS." Beloranib is a novel, first-in-class injectable small molecule therapy with a unique mechanism of action that reduces drive to eat while stimulating the use of stored fat as an energy source. Severe Obesity Results (ZAF-201) ZAF-201, a Phase 2 randomized, double-blind, placebo-controlled trial evaluated the efficacy, safety and tolerability of beloranib 0.6 mg, 1.2 mg or 2.4 mg administered as twice-weekly subcutaneous injections for 12 weeks in patients with severe obesity. The trial enrolled 147 men and women, of which 117 completed the study. The mean age of patients was 48.4 years, and body mass index (BMI) and body weight (BW) was consistent with Class 2 obesity (approximately 38 kg/m2 and 100 kg, respectively). Patients were not counseled to adhere to any diet or exercise regimens as part of the trial. Results from this trial showed that 12 weeks of treatment with beloranib led to sustained, progressive, and dose-dependent weight loss of up to ~11 kg from baseline. Additionally, beloranib treatment significantly reduced sense of hunger and prospective food intake, and known markers of beloranib response, including major cardiovascular risk factors and markers of inflammation, were also improved at 12 weeks. Significant reductions in total and LDL cholesterol and triglyceride levels and an increase in HDL cholesterol were noted in the beloranib 2.4 mg group. A significant increase in HDL cholesterol and decrease in triglyceride levels was observed with beloranib 1.2 mg. Consistent with reduced fat mass and improved adipose tissue function and inflammation, significant (p<0.001) changes in adiponectin, leptin, and hs-CRP were observed with beloranib. PWS Results (ZAF-211) PWS is the most common known genetic cause of life-threatening obesity and results in constant and unrelenting hunger that drives patients with PWS to engage in problematic hunger-related behaviors and gain excessive weight. As a result, many of those affected become morbidly obese and suffer significant mortality. The proof of concept study with beloranib enrolled adult patients with PWS and started with a two-week, single-blind, placebo lead-in period followed by a four-week, double-blind, randomized, treatment period of beloranib 1.2 mg, 1.8 mg, or placebo administered as twice-weekly subcutaneous injections. An optional four-week, open-label extension phase was also offered to patients. The trial enrolled 17 patients with confirmed PWS, all of whom completed the study, with a mean age of 33.5 years, mean BMI of 31.4 kg/m2 and mean BW of 71.8 kg. The study design allowed for a 50% increase in calorie intake for the duration of the study to account for stringent calorie restriction being enforced at the group home where these patients were housed. Results from this trial showed that beloranib appeared safe and well-tolerated, and led to dose-dependent body and total fat mass reductions despite 50% increase in total daily calorie intake. Treatment with beloranib also reduced hyperphagia-related behaviors typical of patients with PWS, and improved biomarkers associated with cardiovascular disease risk and adipose tissue function. The effects of beloranib treatment on body mass and total fat mass in this trial were similar to those seen in non-PWS obese patients, indicating that beloranib effects are evident in PWS as well. "The results of this proof of concept study are important, as treatment with beloranib reduced hyperphagia-related (compulsive overeating) problem behaviors typical of PWS," said Dennis Kim, M.D., Chief Medical Officer at Zafgen. "Beloranib continues to demonstrate promising results, and this study supports its potential as a safe and effective treatment option for this unique patient population. Based on these study results, Zafgen has moved forth with the program in PWS and is currently conducting a Phase 3 clinical trial in the United States that we refer to as the bestPWS trial." Safety and Tolerability In both trials, there were no reports of severe adverse events (SAEs) or AEs leading to early study withdrawal in patients receiving beloranib; the most common AE was injection site bruising of mild intensity comparable between beloranib and placebo groups. In the Phase 2 trial of beloranib in severe obesity, the most common cause for early study withdrawal was sleep-related, mainly a delay of onset of sleep. Other commonly reported AEs included nausea, diarrhea and headache. These AEs were generally mild and transient in nature. In addition, no clinically significant abnormal laboratory measures, vital signs, or electrocardiography (ECG) findings were observed in either trial.