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Beloranib programme suspended

Zafgen suspends Beloranib to focus on ZGN-1061

ZGN-1061 in Phase I development for severe and complicated obesity indications

Zafgen is refocusing its resources on development of a differentiated second-generation MetAP2 inhibitor, ZGN-1061, in severe and complicated obesity, following a comprehensive review of its assets and clinical programs, as well as feedback from regulatory authorities. As a result, the company is suspending further development of beloranib.

"As the leader of the MetAP2 inhibitor field, we have spent many years validating the tremendous potential of this pathway for the treatment of complicated obesity with beloranib, which in multiple clinical trials demonstrated robust reductions in body weight, improvements in glycaemic control, and other benefits related to cardiovascular disease risk," said Dr Thomas Hughes, President and CEO of Zafgen. "However, given the heightened complexity and future cost of beloranib development, balanced against the emerging product profile of ZGN-1061, we believe that the long-term opportunity for ZGN-1061 is more robust than for beloranib. Given our deep knowledge of this new and exciting drug class, and our strong cash position, we believe we are well-positioned to advance ZGN-1061 as a potential new treatment for prevalent obesity-related indications."

The beloranib Investigational New Drug (IND) application was placed on full clinical hold in December 2015 by the FDA. To address the clinical hold, Zafgen recently held a Type A meeting with the FDA to discuss the clinical and preclinical data for beloranib as well as a proposed risk mitigation strategy for beloranib in Prader-Willi syndrome (PWS). Following its discussions with the FDA and review of other considerations, Zafgen has determined that the obstacles, costs and development timelines to obtain marketing approval for beloranib are too great to justify additional investment in the programme, particularly given the promising emerging profile of ZGN-1061.

ZGN-1061, like beloranib, is a fumagillin-class MetAP2 inhibitor that was discovered by Zafgen's researchers as part of a multi-year campaign to identify novel compounds that avoided limiting pre-clinical safety concerns observed with beloranib, including teratogenicity and effects on testicular function. The compound has similar efficacy, potency, and range of activity in animal models of obesity as beloranib, but displays highly differentiated properties and a reduced potential to impact thrombosis, supporting the value of the compound as a more highly optimised MetAP2 inhibitor.

ZGN-1061 modulates the activity of key cellular processes that control the body's ability to make and store fat, and utilise fat and glucose as an energy source. ZGN-1061 is also anticipated to help reduce hunger and restore balance to fat metabolism, enabling calories to once again be used as a productive energy source, leading to weight loss and improved metabolic control.

Zafgen is currently screening patients to initiate a Phase 1 clinical trial evaluating ZGN-1061 for safety, tolerability, and weight loss efficacy over four weeks of treatment, and currently expects Phase 1 clinical data by the end of the first quarter of 2017. Based on the clinical data demonstrating beloranib's significant effect on body weight and glycaemic control in patients with severe obesity complicated by type 2 diabetes, Zafgen plans to focus later-stage development of ZGN-1061 in severe and complicated obesity.

As part of the strategic restructuring, the company plans to reorganise its operations to align with its new priorities focused on ZGN-1061 development. Zafgen's workforce is being reduced by approximately 34%, to a total of 31 employees, by December 2016. Zafgen expects the restructuring to result in approximately US$4.8 million in reduced annualised workforce expenses once the plan is fully implemented. It also expects to incur a non-recurring charge of approximately US$2.4 million in the third quarter of 2016 related to the restructuring.

"We would also like to express our deepest gratitude to the investigators, patients and families who participated in our beloranib trials,” said Hughes. While we are disappointed that we could not see beloranib through to approval, we are excited about the potential of ZGN-1061, and look forward to advancing this high-value candidate in the clinic."      

The company believes that its current cash balance is sufficient to fund operations through the end of 2018, at which time it expects to have completed a Phase 2a clinical trial for ZGN-1061.

Zafgen holds exclusive worldwide rights for the development and commercialisation of ZGN-1061.

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