Zafgen Reports First Quarter 2019 Operating and Financial Results Recently announced positive results for second cohort of Phase 2 clinical trial of ZGN-1061 Company is currently in the formal regulatory process related

Zafgen Reports First Quarter 2019 Operating and Financial Results

Recently announced positive results for second cohort of Phase 2 clinical trial of ZGN-1061

Company is currently in the formal regulatory process related to the clinical hold for ZGN-1061;

Update still anticipated in Q2 2019

PATH for PWS study continues enrollment with strong support from PWS community

Boston, Mass., May 9, 2019 Zafgen, Inc. (Nasdaq:ZFGN), a clinical-stage biopharmaceutical company leveraging its

proprietary knowledge of MetAP2 systems biology to develop novel therapies for patients affected by a range of metabolic diseases, today reported its first quarter 2019 operating and financial results.

Since our last update, we have continued to concentrate on addressing the FDA s comments on the ZGN-1061

IND clinical hold. The team has generated a substantial amount of new data since ZGN-1061 was placed on clinical hold, which we believe support a constructive dialogue with the FDA, said Jeffrey

Hatfield, Chief Executive Officer. We still expect to update investors on ZGN-1061 in the second quarter of 2019.

First Quarter 2019 Financial

Cash, Cash Equivalents and Marketable Securities

As of March 31, 2019, the Company had cash, cash equivalents, and marketable securities totaling $104.7 million.

The Company reported a net loss for the

first quarter of 2019 of $13.1 million, or $0.35 per share, compared to a net loss of $16.0 million, or $0.58 per share, for the first quarter of 2018.

The weighted average common shares (basic and diluted) outstanding used to compute net loss per share were 37,313,947 for the first quarter of 2019 compared

to 27,541,594 for the same quarter of 2018.

Research and Development Expenses

Research and development expenses for the first quarter of 2019 were $9.6 million compared to $12.4 million for the first quarter of 2018. The

decrease in research and development expenses compared to the prior year period was primarily due to decreased clinical costs related to ZGN-1061 as the results of the second cohort of the Phase 2 clinical

trial in type 2 diabetes were reported in January 2019. There was also a decrease in the ZGN-1258 program costs due to the suspension of the program during the first quarter of 2019. There were also decreases

in discovery and screening costs and non-cash stock-based compensation expense in the first quarter of 2019 as compared to the first quarter of 2018. These decreases in research and development costs were

partially offset by an increase in costs related to the ZGN-1345 program as the program advances as a development stage candidate.

General and Administrative Expenses

General and administrative expenses for the first quarter of 2019 were $3.6 million, compared to $3.3 million for the first quarter of 2018. The

increase in general and administrative expenses as compared to the prior year period was primarily due to an increase in personnel related costs and non-cash stock-based compensation expense.

Zafgen (Nasdaq:ZFGN) is a

clinical-stage biopharmaceutical company leveraging its proprietary MetAP2 biology platform to develop novel therapies for patients affected by complex metabolic diseases. Zafgen has pioneered the study of MetAP2 inhibitors in both common and rare

metabolic disorders. Learn more at www.zafgen.com.

Safe Harbor Statement

Various statements in this release concerning Zafgen s future expectations, plans and prospects, including without limitation, Zafgen s expectations

regarding the development and use of ZGN-1258, ZGN-1061, ZGN-1345 and other second-generation MetAP2 inhibitors as treatments for

metabolic diseases including Prader-Willi syndrome, type 2 diabetes, liver diseases and obesity, the collection of medical history and medical events from PATH for PWS participants to inform development for potential treatments for Prader-Willi

syndrome and Zafgen s expectations with respect to the timing and success of its ability to collect and analyze PATH for PWS data for development and clinical trial design and with respect to its nonclinical studies and clinical trials of ZGN-1258, ZGN-1061, ZGN-1345 and its other product candidates, Zafgen s expected cash, cash equivalents and marketable securities

balance as of March 31, 2019, and Zafgen s expectations regarding the length of its cash runway, may constitute forward-looking statements for the purposes of the safe harbor provisions of The Private Securities Litigation Reform Act of

1995 and other federal securities laws. Forward-looking statements can be identified by terminology such as anticipate, believe, could, could increase the likelihood, estimate,

expect, intend, is planned, may, should, will, will enable, would be expected, look forward, may provide, would or

similar terms, variations of such terms or the negative of those terms. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including, without limitation,

Zafgen s ability to successfully demonstrate the efficacy and safety of ZGN-1258, ZGN-1061, ZGN-1345 and its other product

candidates and to differentiate them from first generation MetAP2 inhibitors, such as beloranib, the nonclinical and clinical results for ZGN-1258, ZGN-1061, ZGN-1345 and its other product candidates, which may not support further development and marketing approval, actions of regulatory agencies, which may affect the initiation, timing and progress of nonclinical

studies and clinical trials of its product candidates, Zafgen s ability to successfully engage with the FDA concerning the clinical hold on a clinical trial of ZGN-1061 and to design and conduct a

nonclinical study or clinical trial demonstrating sufficient data to exclude cardiovascular risk to an acceptable degree, Zafgen s ability to overcome the full clinical hold place on ZGN-1061 by the FDA

and obtain regulatory approval, Zafgen s ability to continue to evaluate ZGN-1258 and to advance the program in nonclinical and clinical development, Zafgen s ability to obtain, maintain and protect

intellectual property, Zafgen s ability to enforce its patents against infringers and defend its patent portfolio against challenges from third parties, competition from others

developing products for similar uses, Zafgen s ability to manage operating expenses, Zafgen s ability to obtain additional funding to support its business activities and establish and maintain strategic business alliances and new

business initiatives when needed, Zafgen s ability to attract and retain personnel, Zafgen s dependence on third parties for development, manufacture, marketing, sales and distribution of product candidates, and unexpected

expenditures, as well as those risks more fully discussed in the section entitled Risk Factors in Zafgen s most recent Annual Report on Form 10-K filed with the Securities and

Exchange Commission, as well as discussions of potential risks, uncertainties, and other important factors in Zafgen s subsequent filings with the Securities and Exchange Commission, including without limitation Zafgen s

Quarterly Reports on Form 10-Q. In addition, any forward-looking statements represent Zafgen s views only as of today and should not be relied upon as representing its views as of any subsequent

date. Zafgen explicitly disclaims any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise.

Media/Investor Relations Contacts:

Chief Financial Officer

Ten Bridge Communications

CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS

(In thousands, except share and per share data)

CONDENSED CONSOLIDATED BALANCE SHEETS

(In thousands, except share and per share data)