Presentation

BUSINESS UPDATE CALL September 7, 2017

INTRODUCTION Gem Hopkins VP, Investor Relations & Corporate Communications

SAFE HARBOR STATEMENT 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 opportunity, 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, 2016. 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.

3 Business Update I September 7, 2017

AGENDA • Business Overview – Gary S. Jacob • Financial Update – Gary Gemignani • Launch Update – Troy Hamilton • Closing Remarks – Gary Jacob • Q&A Portion


OVERVIEW Gary S. Jacob, PhD Chairman & CEO

RECENT HIGHLIGHTS • Completed first full quarter of launch of Trulance in CIC •

More than 12,600 prescriptions, $2.3M net revenues, for 2Q17

• Trulance sNDA for IBS-C accepted for FDA review •

January 24, 2018 PDUFA date

• Secured $300 million debt financing


KEY BUSINESS PRIORITIES • Optimize the value of Trulance •

Continue to grow market share in CIC

•

Expand utility in IBS-C – January 24, 2018 PDUFA date

• Ensure a strong financial foundation •

Continue to evaluate opportunities to improve expense management

•

Transition Company to cash flow positive

• Maximize long-term shareholder value


FINANCIAL UPDATE Gary Gemignani EVP, Chief Financial Officer

ENSURING A STRONG FINANCIAL FOUNDATION • Secured $300 million debt financing •

Funds will be used primarily to support the commercial launch of Trulance

•

Non-dilutive source of capital that enhances cash position

• Continue to evaluate opportunities to improve operating efficiency and expense management


TRULANCE LAUNCH UPDATE Troy Hamilton EVP, Chief Commercial Officer

SYNERGY AND TRULANCE: WELL POSITIONED FOR SUCCESS

RIGHT

MARKET

RIGHT

PRODUCT

RIGHT

STRATEGY

RIGHT

TEAM


KEY CUSTOMERS AND LAUNCH STRATEGIES Launch Strategies

HCPs

PATIENTS

Drive Awareness of Trulance and Stimulate Trial and Adoption

Activate and Support the Rx Ready Patient

Ensure Access PAYERS 12 Business Update I September 7, 2017

LESS THAN 20% OF PRESCRIBERS ARE WRITING 70% OF THE TOTAL BRANDED PRESCRIPTIONS

Decile 10 9 8 7 6 5 4 3 2 1 Total 4-10

Rx Mean 460 245 163 113 78 54 36 24 14 4

# of Doctors 753 1,411 2,120 3,057 4,440 6,448 9,484 14,549 25,109 94,563 161,934 27,713

Branded Rx Combined % of Doctors # of Prescriptions 0.5% 346,054 0.9% 346,028 1.3% 346,114 1.9% 346,196 2.7% 346,134 4.0% 346,132 5.9% 346,141 9.0% 346,145 15.5% 346,109 58.4% 346,071 100% 3,461,124 17% 2,422,799

% of Prescriptions 10.0% 10.0% 10.0% 10.0% 10.0% 10.0% 10.0% 10.0% 10.0% 10.0% 100% 70%

27,713 HCPs = 70% of Rx’s • ~ 45% primary care physicians • ~ 30% gastroenterologists • ~ 18% nurse practitioners or physician assistants Decile 3: 2 Rx’s per month Decile 2: ~ 1 Rx per month Decile 1: = 1 Rx every 3 months

Source: QuintilesIMS Xponent - March 2017; excluding non-called on specialties (peds, pain, hem/onc)

Business Update I September 7, 2017

13

TARGETED COMMERCIAL STRATEGY FOCUSED ON A CONCENTRATED PRESCRIBER BASE Branded Rx Market 134,221 Prescribers

27,713 Prescribers

1.0MM TRx (30%)

2.4MM TRx (~70%)

Key Points: • The ~27K prescribers are within 15K group practices/offices • Reaching the 27K prescribers with an experienced sales force and surround sound of promotional efforts

Source: QuintilesIMS Xponent - March 2017; excluding non-called on specialties (peds, pain, hem/onc)`


14

KEY LAUNCH STRATEGIES AND ACTIVITIES

ü Sales force of ~ 250 educating ~ 27,000 prescribers HCPs

ü Over 360,000 sample packs distributed to field to date

• Drive Awareness of Trulance and Stimulate Trial / Adoption

ü ~ 430 peer-to-peer speaker programs, > 6000 attendees

• Activate and Support the Rx Ready Patient

ü Launched comprehensive HCP media plan

• Ensure Access

ü DDW 2017 – significant promotional presence; 6 abstracts (two posters of distinction, one oral presentation)

Source: Company Data


15

KEY LAUNCH STRATEGIES AND ACTIVITIES ü Trulance Campaign: PATIENTS • Drive Awareness of Trulance and Stimulate Trial / Adoption

▬ Point of Care Promotion: ~ 20,000 offices ▬ Web Sponsorships/Display Ads: > 245,000,000 impressions ▬ Search Engine Marketing: > 403,000 clicks ▬ Trulance.com visits: > 615,000 for consumer site

ü Confront Constipation Campaign: • Activate and Support the Rx Ready Patient • Ensure Access

▬ Disease awareness initiative ▬ 33 original media placements ▬ > 310,000,000 media impressions ▬ > 95,000 Emoji App downloads



16

KEY LAUNCH STRATEGIES AND ACTIVITIES

ü Removing barriers and gaining commercial open access PAYERS • Drive Awareness of Trulance and Stimulate Trial / Adoption • Activate and Support the Rx Ready Patient • Ensure Access

ü > 67% of patients with commercial insurance currently have unrestricted access; 2018 discussions ongoing ü Trulance Access Support Services Program ▬

“Savings-to-Go” program: copay of $25/Rx for > 95% of patients with commercial insurance

▬

Prior authorization support

ü Medicare Part D and Medicaid Discussions Ongoing



17

KEY PERFORMANCE METRICS

TRULANCE TOTAL MONTHLY PRESCRIPTION VOLUME HAS INCREASED OVER 140% ON AVERAGE MONTH-OVER-MONTH Trulance Monthly Total Prescriptions 8,000

Cumulative Trulance Monthly Total Prescriptions 25,000

7186

7,000

19834

6262

20,000

TRx Volume

5,000

4149

4,000

12648

6386

1843

2,000

5,000

394

2237 394 Jul-17

Jun-17

May-17

Apr-17

Jul-17

Jun-17

May-17

0 Apr-17

0

Mar-17

1,000

15,000

10,000

3,000

Mar-17

TRx Volume

6,000

Source: QuintilesIMS


19

4/7/17

8/25/17

8/18/17

8/11/17

8/4/17

7/28/17

7/21/17

7/14/17

0

Business Update I September 7, 2017 Source: QuintilesIMS

27024

25018

23095

21194

30,000

8/25/17

8/18/17

8/11/17

19327

17491

15749

25,000

8/4/17

7/28/17

7/21/17

13995

12647

11023

20,000

7/14/17

7/7/17

6/30/17

9447

8120

6868

5866

15,000

6/23/17

6/16/17

6/9/17

6/2/17

4751

3799

2943

10,000

5/26/17

5/19/17

5/12/17

5/5/17

2213

1585 4/28/17

4/21/17

5,000

1096

674

4/7/17

Trulance Weekly TRx Volume

4/14/17

392

3/31/17

0

148

2,500

3/24/17

TRx Volume

2006

1923

1901

1867

1836

1,742

1,754

Holiday Week

1,624

1,576 1,348

1,327

1,252

Holiday Week

2,000

7/7/17

6/30/17

6/23/17

6/16/17

6/9/17

1,115 1,002

952

856

1,500

6/2/17

5/26/17

5/19/17

5/12/17

730

628

489

422

282

1,000

5/5/17

4/28/17

4/21/17

4/14/17

244

124

500

3/31/17

3/24/17

TRx Volume

TRULANCE TOTAL WEEKLY PRESCRIPTION VOLUME SHOWING CONSISTENT GROWTH Cumulative Trulance Weekly TRx Volume

20

TRULANCE NEW-TO-BRAND PRESCRIPTION MARKET SHARE AT 13.3% AMONG GASTROENTEROLOGISTS NBRx Market Share Among Gastroenterologists 80% 66.9%

70%

65.7%

60%

40% 31.8%

30%

21.0%

20%

13.3% 12.9%

Jul-17

Jun-17

May-17

Apr-17

Mar-17

Feb-17

Jan-17

Dec-16

Nov-16

Oct-16

Sep-16

Aug-16

Jul-16

Jun-16

May-16

Apr-16

Mar-16

0%

Feb-16

10%

Jan-16

NBRx Market Share

50%

LAUNCH

LAUNCH

Amitiza Brand

Linzess Brand

Linzess 72mcg

Trulance 3mg Source: QuintilesIMS


21

TRULANCE PRESCRIBERS HAVE INCREASED AN AVERAGE OF 136% MONTH-OVER-MONTH SINCE LAUNCH 4,949

5,000

3,768

Cumulative Trulance Prescribers

4,000

3,000

2,427

2,000 1,145 1,000 257 0 March

April

May

June

July Source: QI XPT, Mar – Jul 2017


22

MAJORITY OF TRULANCE GROWTH COMING FROM PATIENTS NEW TO BRANDED RX TREATMENTS Trulance NRx Breakdown Add on 6%

New Therapy Starts 51%

Switch To 43%

•

51% of Trulance NRx were new branded Rx therapy starts

•

43% of Trulance patients have converted from other Rx treatments

Source: Weeks ending 3/17 – 6/30, QIMS XPD


23

OPTIMIZING THE VALUE OF TRULANCE • Positive early launch results • Early prescriber and patient experience appears promising • Continue to execute on our launch plan • Opportunity to “broaden the base” and build off of successful Trulance launch •

DTC development

•

Prepare for IBS-C launch


CONCLUSION Gary S. Jacob, PhD Chairman & CEO

RECAP OF OUR KEY BUSINESS PRIORITIES •

Optimize the value of Trulance

•

Ensure a strong financial foundation

•

Maximize long-term shareholder value


Q&A SESSION September 7, 2017