1Q 201 1Q 2018 8 UPD UPDATE TE May 10, 2018 SAFE SAFE HARBOR - PowerPoint PPT Presentation

1Q 201 1Q 2018 8 UPD UPDATE TE May 10, 2018

SAFE SAFE HARBOR HARBOR ST STATE TEME MENT NT This presentation and any statements made for and during any presentation or meeting contain forward-looking statements related to Synergy Pharmaceuticals Inc. under the safe harbor provisions of Section 21E of the Private Securities Litigation Reform Act of 1995 and are subject to risks and uncertainties that could cause actual results to differ materially from those projected. These statements may be identified by the use of forward-looking words such as "anticipate," "planned," "believe," "forecast," "estimated," "expected," and "intend," among others. There are a number of factors that could cause actual events to differ materially from those indicated by such forward-looking statements. These factors include, but are not limited to, the development, launch, introduction and commercial potential of TRULANCE™; growth and oppo rtunity, including peak sales and the potential demand for TRULANCE, as well as its potential impact on applicable markets; market size; substantial competition; our ability to continue as a going concern; our need for additional financing; uncertainties of patent protection and litigation; uncertainties of government or third party payer reimbursement; dependence upon third parties; our financial performance and results, including the risk that we are unable to manage our operating expenses or cash use for operations, or are unable to commercialize our products, within the guided ranges or otherwise as expected; and risks related to failure to obtain FDA clearances or approvals and noncompliance with FDA regulations. As with any pharmaceutical under development, there are significant risks in the development, regulatory approval and commercialization of new products. There are no guarantees that future clinical trials discussed in this presentation will be completed or successful or that any product will receive regulatory approval for any indication or prove to be commercially successful. Investors should read the risk factors set forth in our most recent periodic reports filed with the Securities and Exchange Commission, including our Form 10-K for the year ended December 31, 2017. While the list of factors presented here is considered representative, no such list should be considered to be a complete statement of all potential risks and uncertainties. Unlisted factors may present significant additional obstacles to the realization of forward-looking statements. Forward-looking statements included herein are made as of the date hereof, and we do not undertake any obligation to update publicly such statements to reflect subsequent events or circumstances except as required by law. The information in this presentation is not targeted at the residents of any particular country or jurisdiction and is not intended for distribution to, or use by, any person in any jurisdiction or country where such distribution or use would be contrary to local law or regulation. 2 1Q 2018 Update I May 10, 2018

IN INTR TROD ODUC UCTION TION Troy Hamilton Chief Executive Officer

20 2018 18 KEY KEY BUSINE USINESS SS PRI PRIORITI ORITIES ES OPTIMIZIN G D R I V E the value of Trulance VAL U E F O R PAT I E N T S , EN SU R IN G C U S TO M E R S & a strong financial foundation S H AR E H O L D E R S EXPLOR IN G all strategic & business development opportunities 4 1Q 2018 Update I May 10, 2018

OPT OPTIMIZ IMIZING ING THE THE VAL ALUE UE OF TR OF TRULAN ULANCE CE • Trulance 1Q’18 net sales up 18% vs. 4Q’17 adjusted net sales • Continuing to drive market share, prescription volume and expanding prescriber base • Only CIC/IBS-C Rx brand to show positive growth quarter-over-quarter • Pulling through formulary wins and expanding coverage 5 1Q 2018 Update I May 10, 2018

TR TRUL ULANCE ANCE ACHIEVE CHIEVED D HIG HIGHEST HEST TOTAL AL MONTHL MONTHLY Y NORMALIZED NORMALIZED PRE PRESCR SCRIPT PTIO IONS NS IN IN MAR MARCH CH 20 2018 18 Normalized TRx 20,000 17143 18,000 Started promoting 16,000 IBS-C in late 14,000 February 2018 Normalized TRX 12,000 10,000 8,000 6,000 4,000 2,000 0 Mar-17 Apr-17 May-17 Jun-17 Jul-17 Aug-17 Sep-17 Oct-17 Nov-17 Dec-17 Jan-18 Feb-18 Mar-18 6 Source: IQVIA XPT, Mar 2017 – Mar 2018 1Q 2018 Update I May 10, 2018

TRULANCE ONLY Rx BRAND TO SHOW POSITIVE GROWTH DESPITE TYPICAL 1Q CHALLENGES % Normalized TRx Volume Change 1Q 2018 vs. 4Q 2017 Other Branded Rx Trulance 6.0% 3.8% 4.0% 2.0% 0.0% -2.0% -4.0% -5.3% -6.0% 7 Source: IQVIA - NPA 1Q 2018 Update I May 10, 2018

TR TRULAN ULANCE CE OUT OUTGR GROWING WING THE THE COMP COMPET ETITIO ITION % Normalized TRx Volume Change 9-weeks ending 2/23/18 vs. 9-weeks ending 4/27/18 Other Branded Rx Trulance 24% 25.0% 20.0% 15.0% 10.0% 4.7% 5.0% 0.0% 8 Source: IQVIA - NPA 1Q 2018 Update I May 10, 2018

TRULANCE PRESCRIBER BASE GREW OVER 20% IN 1Q’18 11,755 12,000 10,920 10,295 9,644 10,000 8,868 Total TRULANCE Prescribers 7,974 8,000 7,043 6,121 6,000 4,949 3,768 4,000 2,427 2,000 1,145 257 0 9 Source: IQVIA XPT, Mar 2017 – Mar 2018 1Q 2018 Update I May 10, 2018

2018 20 18 MARKE MARKET T ACCE CCESS SS FOCU FOCUS S AND AND PRI PRIORITI ORITIES ES EXPANDING COVERAGE FOR TRULANCE Maximize Current Improve National Expand Regional Coverage Coverage Coverage • • • Pull-through Commercial Regional Payers formulary wins • • Medicare Part D State Medicaid • Push-through prior • Managed Medicaid authorization obstacles 10 1Q 2018 Update I May 10, 2018

1Q 20 1Q 2018 18 FIN FINANC ANCIAL IAL SUMMA SUMMARY Gary Gemignani Chief Financial Officer

1Q 20 1Q 2018 18 FIN FINANCIAL ANCIAL SUM SUMMAR MARY Select finan Select financial cial mea measur sures es (no (non-GAA GAAP) P) (Unaudited, $ in thousands) Three Months Ended Three Months Ended March 31, 2018 December 31, 2017 Adj. Net sales $ 8,586 $ 7,343 $ 2,721 $ 1,474 Adj. R&D expenses Adj. SG&A expenses $ 37,857 $ 39,662 Adj. Operating expenses $ 40,578 $ 41,136 12 1Q 2018 Update I May 10, 2018

ENS ENSURING URING A A ST STRONG ONG FIN FINANCIAL ANCIAL FOU FOUND NDATI TION ON • PRIORITIZED KEY INVESTMENTS IN AREAS OF HIGH-RETURN - Essential market access initiatives - Sales force and high-return marketing programs • ACHIEVED COST EFFICIENCIES / MAINTAINED DISCIPLINED EXPENSE MANAGEMENT - Lowering projected full year 2018 total adjusted OPEX to be in $165M - $175M range • SECURED CONTINUED ACCESS TO CAPITAL AND FINANCIAL FLEXIBILITY - Ability to access up to an additional $100M via amended CRG debt facility in 2018 13 1Q 2018 Update I May 10, 2018

EXP EXPLORING ORING ALL ALL ST STRA RATE TEGIC GIC & & BUSINE USINESS SS DEV DEVEL ELOPM OPMENT ENT OPP OPPOR ORTUN TUNITIES ITIES • Executed on Trulance Canadian licensing deal • Initiated partnership with NIH to advance dolcanatide development • Engaged in ongoing process to review and evaluate a broad range of strategic opportunities to enhance shareholder value 14 1Q 2018 Update I May 10, 2018

OPP OPPOR ORTUNI TUNITY TY TO B O BUILD SHAREHOLDER UILD SHAREHOLDER VAL ALUE UE THR THROUGH OUGH ONGO ONGOIN ING B G BUS USIN INES ESS S DEVE DEVELOP OPMENT MENT EF EFFOR FORTS TS • TRULANCE/SYNERGY in US - Partnering to extend reach and promotion in primary care market - In-license or partner with an additional asset, leveraging commercial infrastructure & GI expertise • TRULANCE Ex-US - Pursue ex-US licensing deals where commercial dynamics allow for value creation • CORPORATE DEVELOPMENT - Enhance pipeline with strategic partnering opportunities - M&A and other strategic options that may accelerate profitability and create shareholder value 15 1Q 2018 Update I May 10, 2018

20 2018 18 KEY KEY BUSINE USINESS SS PRI PRIORITI ORITIES ES OPTIMIZIN G D R I V E the value of Trulance VAL U E F O R PAT I E N T S , EN SU R IN G C U S TO M E R S & a strong financial foundation S H AR E H O L D E R S EXPLOR IN G all strategic & business development opportunities 16 1Q 2018 Update I May 10, 2018

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