Our Science & Approach

Zafgen has undertaken years of research to characterize the MetAP2 pathway and its effects in various bodily systems. We are focused on leveraging our proprietary understanding of this pathway to develop transformative therapeutics that treat the underlying biological mechanisms of a variety of metabolic diseases. Our approach has the potential to significantly improve the health and well-being of patients affected by a range of both rare and more prevalent metabolic disorders where MetAP2 plays a central role.

The Science & Promise of MetAP2 Inhibition


Zafgen’s approach builds off a growing body of scientific evidence showing that patients affected by complex metabolic diseases metabolize fat very differently from healthy people.

With our proprietary MetAP2 development platform, advanced chemistry insights and understanding of the unique characteristics of rare and more common complex metabolic disorders, Zafgen has developed several MetAP2 inhibitors, which modulate the cellular mechanisms that control the body’s ability to make and store fat and to use fat and glucose as an energy source.

The second-generation MetAP2 inhibitors now in our pipeline have each been optimized to preferentially target specific tissue systems relevant to the disease being pursued and to minimize exposure elsewhere in the body, which we anticipate will result in clinically differentiated efficacy and safety.

ZGN-1061 for type 2 diabetes

ZGN-1061 is being developed for patients with type 2 diabetes. We have reported positive full 12-week results for both cohorts of our Phase 2 proof-of-concept trial, including the 1.8 mg dose cohort of the trial.

The  FDA has placed a clinical hold on the Investigational New Drug Application (IND) for the company’s first U.S. clinical trial of ZGN-1061.

ZGN-1258 for Prader-Willi syndrome

Zafgen has suspended plans to file an investigational new drug (IND) application for ZGN-1258, the Company’s candidate for rare metabolic disorders including Prader-Willi syndrome (PWS).

ZGN-1258 is designed to change the way the body metabolizes fat, reduce fat mass, and decrease hyperphagia. There are currently no approved medications to aid in controlling hyperphagia.


ZGN-1345, an orally dosed MetAP2 inhibitor specifically targeting the liver, has been formally advanced to development candidate stage as a differentiated third asset within the Company’s pipeline. Nonclinical models have shown positive preliminary results in multiple liver disease indications.


Prader-Willi Syndrome

The Novel MetAP2 inhibitor, ZGN-1258, Reduces Body Weight and Food Intake in Mouse Models of Obesity Foundation for Prader-Willi Research 2018 Symposium & Family Conference, October 2018
ZGN-1258: A Novel Potent MetAP2 Inhibitor With Reduced Risk of Coagulopathy Foundation for Prader-Willi Research 2018 Symposium & Family Conference, October 2018
VIEW All Prader-Willi Syndrome Publications & Posters

Liver-directed Candidate

Methionine Aminopeptidase 2 Inhibition Attenuates Liver Pathology in Mouse Model of NASH American Association for The Study of Liver Diseases, October 2017, Poster 2054
VIEW All Liver-directed Candidate Publications & Posters

General MetAP2

Pharmacologic Inhibition of MetAP2 Increases Mitochondrial Number and Activity in Skeletal Muscle Keystone Symposia on Mitochondrial Biology in Heart and Skeletal Muscle, January 2019, Poster 2032
VIEW All General MetAP2 Publications & Posters

Patient Stories

Patients and their families inspire our work.

Learn more about our patient resources