Lead drug ZGN-433 is designed to restore sensitivity of fat tissue to hormonal control mechanisms.

Obesity therapeutics firm Zafgen raised $33 million in a Series C financing round led by its existing investor syndicate including Atlas Venture and Third Rock Ventures. The company says the funds will be used to progress its pipeline and move its lead methionine aminopeptidase 2 (MetAP2) inhibitor ZGN-433 (beloranib hemioxalate) into Phase II trials for the treatment of severe obesity, within the next 6–12 months.

Zafgen’s anti-obesity approach is focused on restoring the sensitivity of the fat tissue in obese individuals to natural hormonal control mechanisms, which essentially then drives fat loss. ZGN-433 is being developed as a twice-weekly subcutaneous injection, but Zafgen says it is also working on second-generation compounds that would potentially be suitable for oral administration and for use in other indications.

Beloranib hemioxalate was originally developed by CKD Pharmaceuticals and proflied as a potential treatment for solid tumors. The drug is licensed exclusively to Zafgen worldwide excluding Korea.

In June the firm reported new data from a Phase Ib study evaluating ZGN-433 in severely obese individuals. The data showed treatment with ZGN-433 was associated with rapid and significant improvements in cardiovascular risk markers including LDL cholesterol, triglycerides, and C-reactive protein with no evidence of major tolerability or safety issues. The results in addition confirmed preclinical findings that MetAP2 inhibition leads to changes in fat metabolism and levels of leptin and adiponectin.

Positive topline results from the study had been reported back in January and showed ZGN-433 therapy met its primary weight loss endpoint, with treated patients demonstrating median weight loss of 1 kg per week. Changes in lipid parameters associated with treatment included a 38% reduction in triglyceride levels and a 23% reduction in LDL levels.

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