8-K

UNITED STATES
SECURITIES AND EXCHANGE COMMISSION

Washington, DC 20549

FORM 8-K

CURRENT REPORT

Pursuant to Section 13 or 15(d) of
The Securities Exchange Act of 1934

Date of Report (Date of earliest event reported): January 31, 2019

United Therapeutics Corporation

(Exact name of registrant as specified in its charter)

Delaware	000-26301	52-1984749
(State or other jurisdiction of	(Commission File Number)	(IRS Employer
incorporation)		Identification No.)

1040 Spring Street
Silver Spring, MD 20910
(Address of principal executive offices, including zip code)

(301) 608-9292
(Registrant’s telephone number, including area code)

N/A
(Former name or former address, if changed since last report)

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:

o Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

o Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

o Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

o Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§ 230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§ 240.12b-2 of this chapter).

Emerging growth company o

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. o

Item 7.01.Regulation FD.

On January 31, 2019, United Therapeutics Corporation (the “Company”) issued a press release disclosing data from its FREEDOM-EV clinical study of Orenitram® (treprostinil) Extended-Release Tablets, including data shared during an oral presentation at the Pulmonary Vascular Research Institute (“PVRI”) Annual World Congress on Pulmonary Vascular Disease in Barcelona, Spain. A copy of the press release, as well as a copy of the slides presented at the PVRI presentation, are being furnished as Exhibit 99.1 and Exhibit 99.2 hereto, respectively, and are incorporated herein by reference.

The information in this Item 7.01 and the related Item 9.01, including Exhibit 99.1 and Exhibit 99.2 attached hereto, are being furnished and shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act as amended, regardless of any general incorporation language in such filing.

Item 9.01.Financial Statements and Exhibits.

(d) Exhibits

Exhibit No.	Description of Document
99.1	Press release dated January 31, 2019.
99.2	Slide presentation entitled “Treatment with Oral Treprostinil is Associated with Improved Survival in Pulmonary Arterial Hypertension Participants from the FREEDOM-EV Study”, presented at the Pulmonary Vascular Research Institute Annual World Congress on Pulmonary Vascular Disease in Barcelona, Spain on January 31, 2019.

SIGNATURES

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.

	UNITED THERAPEUTICS CORPORATION
	By:	/s/ Paul A. Mahon
Date: January 31, 2019	Name:	Paul A. Mahon
	Title:	General Counsel

2

EX-99.1

Exhibit 99.1

Contact: James Edgemond

Phone: (301) 608-9292

E-mail: jedgemond@unither.com

SURVIVAL DATA FROM FREEDOM-EV STUDY OF ORENITRAM
PRESENTED AT THE PULMONARY VASCULAR RESEARCH INSTITUTE
ANNUAL WORLD CONGRESS

Silver Spring, MD and Research Triangle Park, NC, January 31, 2019: United Therapeutics Corporation (Nasdaq: UTHR) today announced that key data from the FREEDOM-EV study of Orenitram® (treprostinil) extended-release tablets were shared during an oral presentation at the Pulmonary Vascular Research Institute Annual World Congress on Pulmonary Vascular Disease in Barcelona, Spain. The presentation was given by R. James White, M.D., Ph.D., Professor of Medicine, Pharmacology & Physiology in the Division of Pulmonary & Critical Care Medicine at the University of Rochester Medical Center and steering committee member for the FREEDOM-EV study.

Presentation Highlights

The primary endpoint of this pivotal, double-blind, placebo-controlled, event-driven trial in patients with pulmonary arterial hypertension (PAH) was met. Orenitram decreased the risk of adjudicated clinical worsening events by 26% compared to placebo (p=0.0391). These results were largely driven by delay in disease progression; Orenitram decreased the risk of disease progression by 61% compared with placebo (p=0.0002). Mortality was similar between Orenitram and placebo groups at the end of randomized treatment. However, in participants for which data are available (89%), Orenitram was associated with a 37% decreased risk of mortality compared with placebo (p=0.0324) at study closure (which includes additional data accrued in the open-label extension study).

“We are thrilled that the FREEDOM-EV study has shown that not only does Orenitram delay disease progression but is the first and only oral prostacyclin-class therapy to indicate a positive impact on survival at study closure,” said Martine Rothblatt, Ph.D., Chairman and Chief Executive Officer of United Therapeutics. “These data build off the foundation of the FREEDOM-M study and will bolster Orenitram’s perceived value for payors and prescribers, opening the door for more patients to benefit from this medicine.”

“I am very excited to share the complete FREEDOM-EV data package at meetings over the next months,” said Dr. White. “Orenitram provided clear benefits in the study, and the indication that those assigned to Orenitram treatment had a survival advantage should make prescribers think very differently about the oral form of treprostinil.”

United Therapeutics has submitted the FREEDOM-EV study results to the U.S. Food and Drug Administration in support of a potential label amendment for Orenitram and is evaluating whether the results could support marketing applications outside the United States.

Baseline Characteristics

FREEDOM-EV participants were predominantly of lower risk at baseline: World Health Organization (WHO) functional class II (63%). In addition, FREEDOM-EV participants had a median six-minute walk distance (6MWD) of 405 meters, and a median time since PAH diagnosis of 0.54 years at baseline.

Dosing in FREEDOM-EV

Participants received single PAH background therapy of phosphodiesterase type 5 inhibitor/soluble guanylate cyclase stimulator (72%) or endothelin receptor antagonist (28%). Median time on PAH background therapy at baseline was 23.4 weeks. A median Orenitram dose of 2.5 mg and 3.5625 mg three times daily (TID) was achieved at 12 and 24 weeks, respectively.

Safety and Tolerability

Treatment with Orenitram in the FREEDOM-EV study was generally well tolerated and the safety profile was consistent with previous studies and known prostacyclin-related adverse events (see the discussion of adverse events below under “About Orenitram”). Over the course of the long-term study (median exposure of 60.6 and 55.4 weeks for Orenitram and placebo participants, respectively), 19% of Orenitram and 4% of placebo participants discontinued treatment due to adverse events.

Secondary Endpoints

Secondary endpoints are summarized below and will be discussed in detail at upcoming scientific conferences. These include: changes from baseline in 6MWD, Borg dyspnea score (shortness of breath test) and functional class, NT-proBNP levels, and combined 6MWD and Borg dyspnea score:

·Change in 6MWD:   The median 6MWD trended toward improvement at week 24 (Hodges-Lehmann treatment estimate: 7 meters; p=0.0913). Median 6MWD improved with Orenitram at weeks 36 (13 meters; p=0.0094) and 48 (21 meters; p=0.0008) compared to placebo.

·Change in Borg dyspnea score and WHO functional class: When classified categorically as ‘improved’, ‘no change’, or ‘deteriorated’, participants in the Orenitram group exhibited a positive shift in Borg dyspnea score and WHO functional class compared to placebo at weeks 24, 36, and 48 (p<0.05, all).

·Change in NT-proBNP levels:  NT-proBNP levels were significantly improved with Orenitram at weeks 24 and 36 (p<0.0001, both).

·Change in combined 6MWD and Borg dyspnea score:  Combined 6MWD and Borg dyspnea score was significantly improved with Orenitram when assessed at week 24 compared to placebo (p=0.0057).

Additional Information

The complete presentation of FREEDOM-EV data has been filed by United Therapeutics with the SEC as Exhibit 99.2 to its Current Report on Form 8-K filed with the U.S. Securities and Exchange Commission on January 31, 2019.

Additional detailed data from the FREEDOM-EV study will be made available through oral presentations at the upcoming International Society for Heart and Lung Transplantation (Apr. 3-6, 2019; Orlando, FL) and American Thoracic Society (May 17-22, 2019; Dallas, TX) conferences and through scientific publications.

About FREEDOM-EV

FREEDOM-EV was a phase 3, international, multi-center, randomized, double-blind, placebo-controlled, event-driven clinical worsening study of oral treprostinil in patients with PAH receiving background oral monotherapy (a phosphodiesterase type 5 inhibitor, an endothelin receptor antagonist or a soluble guanylate cyclase stimulator). Global enrollment was completed in December 2017 with a total of 690 patients. Patients were randomized 1:1 to receive three daily doses of Orenitram or placebo. This event-driven study was conducted in 152 centers from 23 countries in North and Latin America, Europe, and Asia-Pacific, with 214 patients having an adjudicated clinical worsening (morbidity or mortality) event: death, hospitalization due to worsening of PAH, initiation of inhaled or infused prostacyclin treatment for PAH, disease progression, or unsatisfactory long-term clinical response. Disease progression was defined as a decrease in 6MWD by >15% and an increase in functional class or the appearance or worsening of right-heart failure. Dosing in FREEDOM-EV was initiated at 0.125 mg TID and increased to a maximum of 12 mg TID. This event-driven study was designed to demonstrate a prolongation of time to the first adjudicated clinical worsening event for patients treated with Orenitram compared with placebo and to further establish the safety of Orenitram in PAH patients. Investigator-reported clinical worsening events were adjudicated by an independent committee blinded to study treatment. Mortality was analyzed at the end of randomized treatment and study closure, which included open-label treatment. Vital status was assessed at six-month intervals for consenting individuals who discontinued participation.

About Orenitram

Indication

Orenitram is a prostacyclin vasodilator indicated for treatment of PAH (WHO Group 1) to improve exercise capacity. The study that established effectiveness included predominately patients with WHO functional class II-III symptoms and etiologies of idiopathic or heritable PAH (75%) or PAH associated with connective tissue disease (19%).

When used as the sole vasodilator, the effect of Orenitram on exercise is about 10% of the deficit, and the effect, if any, on a background of another vasodilator is probably less than this.

Important Safety Information for Orenitram

CONTRAINDICATIONS

·Orenitram is contraindicated in patients with severe hepatic impairment (Child Pugh Class C)

WARNINGS AND PRECAUTIONS

·Abrupt discontinuation or sudden large reductions in dosage of Orenitram may result in worsening of PAH symptoms

·Orenitram inhibits platelet aggregation and increases the risk of bleeding

·The Orenitram tablet shell does not dissolve. In patients with diverticulosis, Orenitram tablets can lodge in a diverticulum

DRUG INTERACTIONS / SPECIFIC POPULATIONS

·Concomitant administration of Orenitram with diuretics, antihypertensive agents, or other vasodilators increases the risk of symptomatic hypotension

·Orenitram inhibits platelet aggregation; there is an increased risk of bleeding, particularly among patients receiving anticoagulants

·Co-administration of Orenitram and the CYP2C8 enzyme inhibitor gemfibrozil increases exposure to treprostinil; therefore, Orenitram dosage reduction may be necessary in these patients

·Pregnancy Category C. Animal reproductive studies with Orenitram have shown an adverse effect on the fetus. There are no adequate and well-controlled studies in humans

·It is not known whether treprostinil is excreted in human milk or absorbed systemically after ingestion. Because many drugs are excreted in human milk, choose Orenitram or breastfeeding

·Safety and effectiveness in patients under 18 years of age have not been established

·There is a marked increase in the systemic exposure to treprostinil in hepatically impaired patients

ADVERSE REACTIONS

·In the 12-week placebo-controlled monotherapy study, adverse reactions that occurred at rates at least 5% higher on Orenitram than on placebo included headache, diarrhea, nausea, flushing, pain in jaw, pain in extremity, hypokalemia, and abdominal discomfort.

Please see Full Prescribing Information and Patient Information for Orenitram. For additional information about Orenitram, visit www.orenitram.com or call 1-877-UNITHER (1-877-864-8437).

About United Therapeutics

United Therapeutics Corporation focuses on the strength of a balanced, value-creating biotechnology model. We are confident in our future thanks to our fundamental attributes, namely our obsession with quality and innovation, the power of our brands, our entrepreneurial

culture and our bioinformatics leadership. We also believe that our determination to be responsible citizens — having a positive impact on patients, the environment and society — will sustain our success in the long term.

Through our wholly-owned subsidiary, Lung Biotechnology PBC, we are focused on addressing the acute national shortage of transplantable lungs and other organs with a variety of technologies that either delay the need for such organs or expand the supply. Lung Biotechnology is the first public benefit corporation subsidiary of a public biotechnology or pharmaceutical company. [uthr-g]

Forward-looking Statements

Statements included in this press release that are not historical in nature are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements include, among others, statements regarding the impact of the FREEDOM-EV results on physicians, payers and patients, our pending application to the FDA to include the FREEDOM-EV results in the Orenitram label, and the potential for the FREEDOM-EV results to support marketing applications for Orenitram outside the U.S. These forward-looking statements are subject to certain risks and uncertainties, such as those described in our periodic and other reports filed with the Securities and Exchange Commission that could cause actual results to differ materially from anticipated results. The forward-looking statements in this press release are qualified by the cautionary statements, cautionary language and risk factors set forth in our periodic reports and documents filed with the Securities and Exchange Commission, including our most recent Annual Report on Form 10-K, Quarterly Reports on Form 10-Q and Current Reports on Form 8-K. We claim the protection of the safe harbor contained in the Private Securities Litigation Reform Act of 1995 for forward-looking statements. We are providing this information as of January 31, 2019 and assume no obligation to update or revise the information contained in this press release whether as a result of new information, future events or any other reason.

ORENITRAM is a registered trademark of United Therapeutics Corporation.

EX-99.2

Exhibit 99.2

Treatment with Oral Treprostinil is Associated with Improved Survival in Pulmonary Arterial Hypertension Participants from the FREEDOM-EV Study R. J. White 1; C. Jerjes-Sanchez 2; G. Meyer 3; T. Pulido 4; P. Sepulveda 5; K.Y. Wang 6; C. Q. Deng 7; R. Grover 7; V. F. Tapson 8 on behalf of FREEDOM-EV investigators 1University of Rochester Medical Center, Rochester, NY; 2Unidad De Inv Clinica En Medicina, Monterrey, Mexico; 3Complexo Hospitalar Santa Casa de Porto Alegre, Porto Alegre, Brazil; 4Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico; 5Hospital San Juan De Dios, University of Chile, Santiago, Chile; 6Taichung Veterans General Hospital, Taichung, Taiwan; 7United Therapeutics, Research Triangle Park, NC; 8Cedars Sinai, Los Angeles, CA Presented at the 13th PVRI World Congress January 30 – February 05, 2019 Barcelona, Spain Disclosure: This study was sponsored by United Therapeutics Corporation. 1

The University of Rochester does research with and provides consulting service to United Therapeutics, with all funds to institution. RJW has no personal financial interest in FREEDOM-EV results or United Therapeutics. Presented at the 13th PVRI World Congress January 30 – February 05, 2019 Barcelona, Spain Disclosure: This study was sponsored by United Therapeutics Corporation. 2 Disclosures

Presented at the 13th PVRI World Congress January 30 – February 05, 2019 Barcelona, Spain Disclosure: This study was sponsored by United Therapeutics Corporation. 3 FREEDOM-EV Study Design Primary Efficacy Endpoint Time to the first clinical worsening event NCT01560624 TDE-PH-310 Randomize 1:1 Double-blind N=690 Subjects with PAH receiving background oral monotherapy 152 Centers from 23 Countries Treatment period continued until the 205th adjudicated CW event ORAL TREPROSTINIL (UT-15C) TID PLACEBO TID

Presented at the 13th PVRI World Congress January 30 – February 05, 2019 Barcelona, Spain Disclosure: This study was sponsored by United Therapeutics Corporation. 4 Primary Endpoint Definition Key Clinical Assessments Primary Endpoint Clinical Worsening Event (blindly adjudicated) Death (all causes) Hospitalization due to worsening PAH Initiation of an inhaled or infused prostacyclin Disease progression Decrease in 6MWD >15% and increase in WHO FC Decrease in 6MWD >15% and appearance or worsening of symptoms of right heart failure Unsatisfactory long-term clinical response Decrease in 6MWD at week 24 and beyond Sustained WHO FC III/IV symptoms for at least 24 weeks

Presented at the 13th PVRI World Congress January 30 – February 05, 2019 Barcelona, Spain Disclosure: This study was sponsored by United Therapeutics Corporation. 5 Secondary Endpoint Definition Key Clinical Assessments Change from baseline to week 24: 6MWD NT-proBNP Combined 6MWD and Borg dyspnea score Other Exercise capacity, as measured by 6MWD at each visit up to week 48 (other than week 24) Borg dyspnea score WHO FC Risk assessment Safety Vital status Secondary Endpoints

Presented at the 13th PVRI World Congress January 30 – February 05, 2019 Barcelona, Spain Disclosure: This study was sponsored by United Therapeutics Corporation. 6 Demographic & Baseline Characteristics AGE 85% < 65 YRS OLD 79% 15% >65 YRS OLD 21% 47% ASIA & PACIFIC 25.5% SOUTH & LATIN AMERICA GEOGRAPHIC REGION 13.5% NORTH AMERICA PAH 63% IDIOPATHIC OR HERITABLE 3% OTHER 26% CONNECTIVE TISSUE DISEASE 1% HIV INFECTION 7% CONGENITAL HEART DEFECT SEX MEAN ± SD AGE: 45 ± 16 YRS MEDIAN (RANGE) AGE: 43 (18-76) YRS 14% EUROPE

Presented at the 13th PVRI World Congress January 30 – February 05, 2019 Barcelona, Spain Disclosure: This study was sponsored by United Therapeutics Corporation. 7 Demographic & Baseline Characteristics TIME SINCE DIAGNOSIS BACKGROUND PAH THERAPY 72% PDE-5I OR sGC 28% ERA 6MWD 63% FC II WHO FC 3% FC I 34% FC III 0.1% FC IV MEDIAN (IQR): 405 (342, 461) M MEDIAN (IQR): 0.5 (0.2, 1.1) YRS Distance (m) Years MEDIAN (IQR) TIME ON BACKGROUND: 23 (10, 46) WEEKS

Presented at the 13th PVRI World Congress January 30 – February 05, 2019 Barcelona, Spain Disclosure: This study was sponsored by United Therapeutics Corporation. 8 Median Dose by Visit 2.5 (0.125, 10.625) mg 3.5625 (0.125, 12) mg 0 1 2 3 4 5 6 W0 W4 W8 W12 W24 W36 W48 W60 W72 W84 W96 VISIT Oral Treprostinil Dose (mg) TID

Presented at the 13th PVRI World Congress January 30 – February 05, 2019 Barcelona, Spain Disclosure: This study was sponsored by United Therapeutics Corporation. 9 Adjudicated Clinical Worsening Events ORAL TREPROSTINIL PLACEBO a Hazard ratio, 95% CI, and P value are calculated with proportional hazard model with treatment, background PAH therapy and baseline 6MWD as explanatory variables. N=346 % N=344 % Clinical worsening event category as the first event n (%) All events 90 26% 124 36% Death (all causes) 15 4.3% 14 4.1% Hospitalization due to PAH 35 10.1% 35 10.2% Initiation of inhaled or infused prostacyclin 2 0.6% 5 1.5% Disease progression 19 5.5% 50 14.5% Unsatisfactory long-term clinical response 19 5.5% 20 5.8% Hazard Ratio (95% Cl) (Oral treprostinil - Placebo)a 0.74 (0.56, 0.97) P=0.0275

Presented at the 13th PVRI World Congress January 30 – February 05, 2019 Barcelona, Spain Disclosure: This study was sponsored by United Therapeutics Corporation. 10 Time to Adjudicated Clinical Worsening (Weeks) Kaplan–Meier Estimates PATIENTS WITHOUT AN EVENT (%) p= 0.0391a HR: 0.74 (95% CI: 0.56-0.97), p= 0.0275b ORAL TREPROSTINIL PLACEBO Population: ITT WEEKS a p value is calculated with log rank test stratified by background PAH therapy and baseline 6MWD category. b Hazard ratio, 95% CI, and p value are calculated with proportional hazard model with treatment, background PAH therapy and baseline 6MWD as explanatory variables. No. at risk Oral treprostinil 346 283 187 152 116 81 Placebo 344 276 197 153 121 91

Presented at the 13th PVRI World Congress January 30 – February 05, 2019 Barcelona, Spain Disclosure: This study was sponsored by United Therapeutics Corporation. 11 Most Commonly Reported Adverse Events (By Preferred Term) ORAL TREPROSTINIL N = 346 PLACEBO N = 344 n(%) n(%) Preferred term Any event 342 (98.8%) 328 (95.3%) Headache 259 (74.9%) 120 (34.9%) Diarrhea 240 (69.4%) 98 (28.5%) Flushing 154 (44.5%) 27 (7.8%) Nausea 139 (40.2%) 78 (22.7%) Vomiting 123 (35.5%) 35 (10.2 %) Dizziness 81 (23.4%) 75 (21.8%) Upper respiratory tract infection 73 (21.1%) 82 (23.8%) Discontinuations due to AEs: 18.8% oral treprostinil versus 4.1% placebo

Presented at the 13th PVRI World Congress January 30 – February 05, 2019 Barcelona, Spain Disclosure: This study was sponsored by United Therapeutics Corporation. 12 Summary of Subject Disposition at Study Closure Entered Study TDE-PH-310 n=690 Discontinued from Study TDE-PH-310 or -311 n=106 Participated in vital status sub-study (n=80) Alive at closure of TDE-PH-310 (n=57) Death (n=18) Unable to contact (n=5) Did not participate in vital status sub-study (n=26) Site closed before amendment/did not participate (n=2) Participant did not consent (n=24) Transitioned to Study TDE-PH-311 n=213 Alive at closure of TDE-PH-310 (n=180) Death (n=13) Discontinued (n=20) Placebo n=344 Transitioned to TDE-PH-311 (n=258) Death (n=18) Discontinued (n=68) Transitioned to Study TDE-PH-311 n=258 Alive at closure of TDE-PH-310 (n=196) Death (n=24) Discontinued (n=38) Oral Treprostinil n=346 Transitioned to TDE-PH-311 (n=213) Death (n=17) Discontinued (n=116) Discontinued from Study TDE-PH-310 or -311 n=136 Participated in vital status sub-study (n=98) Alive at closure of TDE-PH-310 (n=85) Death (n=8) Unable to contact (n=5) Did not participate in vital status sub-study (n=38) Site closed before amendment/did not participate (n=6) Participant did not consent (n=32)

Presented at the 13th PVRI World Congress January 30 – February 05, 2019 Barcelona, Spain Disclosure: This study was sponsored by United Therapeutics Corporation. 13 Summary of Deaths (All Causes) at Study Closure ORAL TREPROSTINIL PLACEBO a Vital status was collected at closure of Study TDE-PH-310 for all subjects, including subjects who rolled over to extension study (TDE-PH-311) and who discontinued early from the study. For subjects whose vital status was not available at study closure, their time to death was censored at the subjects’ last known date to be alive. Subjects who were alive at the study closure have their time to death censored at the last contact date. b p value is calculated with Logrank test stratified by background PAH therapy and baseline 6MWD category. c Hazard ratio, 95% CI, and p value are calculated with proportional hazard model with treatment, background PAH therapy and baseline 6MWD as explanatory variables. Deaths at study closurea N=346 % N=344 % p value 38 11% 60 17.4% 0.0324b Hazard Ratio (95% CI) (Oral treprostinil – Placebo)c 0.63 (0.42, 0.95) 0.0259 Vital status confirmed for 89% of initial participants, unknown for 43 oral treprostinil and 31 placebo

Presented at the 13th PVRI World Congress January 30 – February 05, 2019 Barcelona, Spain Disclosure: This study was sponsored by United Therapeutics Corporation. 14 Summary of Deaths (All Causes) ORAL TREPROSTINIL PLACEBO a Vital status was collected at closure of Study TDE-PH-310 for all subjects, including subjects who rolled over to extension study (TDE-PH-311) and who discontinued early from the study. For subjects whose vital status was not available at study closure, their time to death was censored at the subjects’ last known date to be alive. Subjects who were alive at the study closure have their time to death censored at the last contact date. b Hazard ratio, 95% CI, and p value are calculated with proportional hazard model with treatment, background PAH therapy and baseline 6MWD as explanatory variables. c p value is calculated with Logrank test stratified by background PAH therapy and baseline 6MWD category. Timepoint N=346 % N=344 % Hazard Ratio (95% CI), p value (Oral treprostinil – Placebo)b p valuec Deaths at end of randomized treatment 17 4.9% 18 5.2% 1 (0.52, 1.95), 0.9917 0.9781 Deaths at end of open-label extension 30 8.7% 41 11.9% 0.78 (0.49, 1.25), 0.3064 0.3747 Deaths at study closurea 38 11% 60 17.4% 0.63 (0.42, 0.95), 0.0259 0.0324 Vital status confirmed for 89% of initial participants, unknown for 43 oral treprostinil and 31 placebo

Presented at the 13th PVRI World Congress January 30 – February 05, 2019 Barcelona, Spain Disclosure: This study was sponsored by United Therapeutics Corporation. 15 Summary of Risk Stratification at Baseline Population: ITT 32.9% 17.7% 28.1% 21.3% 33.2% 25.2% 30.3% 11.3% NUMBER OF LOW-RISK CATEGORIES MET Placebo N=334 Oral Treprostinil N=337 p = 0.0017 3 Low-risk factors 2 Low-risk factors 1 Low-risk factors 0 Low-risk factors

Presented at the 13th PVRI World Congress January 30 – February 05, 2019 Barcelona, Spain Disclosure: This study was sponsored by United Therapeutics Corporation. 16 Summary of Deaths (All Causes) Adjusted by Baseline Risk Stratification a Vital status was collected at closure of Study TDE-PH-310 for all subjects, including subjects who rolled over to extension study (TDE-PH-311) and who discontinued early from the study. For subjects whose vital status was not available at study closure, their time to death was censored at the subjects’ last known date to be alive. Subjects who were alive at the study closure have their time to death censored at the last contact date. b Hazard ratio, 95% CI, and p value are calculated with proportional hazard model with treatment and baseline risk criteria as explanatory variables. c p value is calculated with Logrank test stratified by number of low-risk criteria at baseline. Timepoint Hazard Ratio (95% CI), p value (Oral treprostinil – Placebo)b p valuec Death at end of randomized treatment 0.87 (0.44,1.71); 0.6811 0.7212 Death at end of open-label extension 0.69 (0.43,1.12); 0.1369 0.1364 Death at study closurea 0.58 (0.38,0.89), 0.0116 0.0104 Vital status confirmed for 89% of initial participants, unknown for 43 oral treprostinil and 31 placebo

The primary efficacy endpoint of delayed time to first clinical worsening was met Disease progression is driving the treatment difference Safety profile was similar to the previous studies and was common to prostacyclin class of therapies Oral treprostinil added on to background PAH monotherapy significantly reduced the risk of a clinical worsening event at end of treatment and was associated with improved survival at study closure Presented at the 13th PVRI World Congress January 30 – February 05, 2019 Barcelona, Spain Disclosure: This study was sponsored by United Therapeutics Corporation. 17 Summary

Presented at the 13th PVRI World Congress January 30 – February 05, 2019 Barcelona, Spain Disclosure: This study was sponsored by United Therapeutics Corporation. 18 FREEDOM-EV Investigators Investigator Institution Linda Cadaret Sif Hansdottir (Previous Investigator) University of Iowa Hospitals and Clinics Ronald Jack Oudiz Harbor UCLA Medical Center David B. Badesch University of Colorado Denver Michael Mathier UPMC Presbyterian Hospital John Swiston Vancouver General Hospital, The Lung Centre Robert Schilz University Hospitals Case Medical Center Tomas Rene Pulido Zamudio Instituto Nacional de Cardiologia Ignacio Chavez Nicholas Hill Tufts Medical Center Aaron Waxman Brigham and Women’s Hospital Catherine J. Markin Legacy Medical Group – Pulmonary and Sleep Clinic Dianne Lynn Zwicke Aurora St. Luke’s Medical Center Micah Fisher Emory University School of Medicine, The Emory Clinic Veronica Franco Namita Sood (Previous Investigator) The Ohio State University, Wexner Medical Center Myung H. Park University of Maryland Hospital Naushad Hirani Peter Lougheed Centre Roblee Allen University of California Davis Medical Center Jeremy P. Feldman Arizona Pulmonary Specialists, Ltd Sanjay Mehta London Health Sciences Centre – Victoria Hospital Carlos Jerjes Sanchez Diaz Unidad de Investigacion Clinica en Medicina S.C. Vijay Balasubramanian Community Regional Medical Centers – CRMC/UCSF Fresno Vandana Kavita Seeram Abubakr Bajwa (Previous Investigator) University of Florida College of Medicine Austin B. Thompson III University of Nebraska Medical Center Christina Migliore Barnabas Health Newark Beth Israel Medical Center Jean Elwing University of Cincinnati/UC Health John W. McConnell Kentuckiana Pulmonary Research Center Jinesh P. Mehta Franck Farzad Rahaghi (Previous Investigator) Cleveland Clinic Florida J. Eduardo Rame Hospital of the University of Pennsylvania Akram Khan Oregon Health and Science University Bela Patel University of Texas Medical School Investigator Institution Evangelos Michelakis Mazankowski Heart Institute, University of Alberta Hospital Ron M. Oren HeartCare Midwest James R. Klinger Rhode Island Hospital Hassan Alnuaimat University of Florida Clinical Research Center Jens Erik Nielsen-Kudsk Aarhus University Hospital, Skejby John Fitzgerald Eelke Feenstra Fiona Dawn Kermeen (Previous Investigator) The Prince Charles Hospital Anne Margaret Keogh St Vincent’s Hospital Trevor John Williams The Alfred Hospital Mordechai Reuben Kramer Rabin Medical Center, Beilinson Campus Michael Jonathan Segel Issahar Ben-Dov (Previous Investigator) The Chaim Sheba Medical Center Neville Berkman Hadassah-Hebrew University Hospital Hadassah Medical Organization Bozena Sobkowicz Uniwersytecki Szpital Kliniczny w Bialymstoku Tatiana Mularek-Kubzdela Szpital Kliniczny Przemienienia Panskiego Irene M. Lang Medical University of Vienna Anko Boonstra Vrije Universiteit Medisch Centrum Adam Torbicki Europejskie Centrum Zdrowia Otwock John Gerard Coghlan Royal Free London NHS Foundation Trust David Gerard Kiely Sheffield Teaching Hospitals NHS Foundation Trust Royal Hallamshire Hospital Madelon Clementina Vonk Radbound University Nijmegen Medical Center Joanna Wanda Pepke-Zaba Papworth Hospital Piotr Podolec Krakowski Szpital Specjalistyczny im. Jana Pawla II Arnaud Bourdin CHU de Montpellier, Hopital Arnaud de Villeneuve Pr Eric Hachulla CHRU de Lille – Hopital Claude Huriez Michele D’Alto Azienda Ospedaliera Specialistica dei Colli- Ospedale Monaldi Carmine Dario Vizza Universita di Roma “Sapienza”- Policlinico Umberto I Hans Klose Universitatsklinikum Hamburg-Eppendorf Michael Halank Gert Hoffken (Previous Investigator) Universitatsklinikum Carl Gustav Carus Dresden

Presented at the 13th PVRI World Congress January 30 – February 05, 2019 Barcelona, Spain Disclosure: This study was sponsored by United Therapeutics Corporation. 19 FREEDOM-EV Investigators, Cont. Investigator Institution Ralf Ewert Universitatsmedizin Greifswald Klinik und Poliklinik fur Innere Medizin B Stephan Rosenkranz Universitatsklinikum Koln Ekkehard Grunig Thoraxklinik Heidelberg gGmbH Mordechai Yigla Rambam Health Care Campus Yochai Adir The Lady Davis Carmel Medical Center Shirish Hiremath Ruby Hall Clinic, Grant Medical Foundation Prafulla Gopinath Kerkar King Edward Memorial VII Hospital & Seth Gordhandas Sunderdas Medical College Pujar Venkateshacharya Suresh Narayana Health – Narayana Institute of Cardiac Sciences Hemang Ashwinkumar Baxi Care Institute of Medical Sciences Abraham Oomman Apollo Hospitals Rajpal Kanaklal Abhaichand G Kupppuswamy Naidu Memorial Hospital Claire Dromer Hopital Haut Leveque, Centre Francois Magendie Jinming Liu Shanghai Pulmonary Hospital Zhang Shuyang Peking Union Medical College Hospital Lei Pan Beijing Shijitan Hospital Samuel Allen Beaumont Health Pulmonary Hypertension Center William Harvey Indiana University Health North Hospital Michael S. Eggert Sentara Pulmonary & Critical Care Specialists, Sentara Heart Hospital Antoine Hage Cedars-Sinai Medical Center Chad E. Miller Piedmont Healthcare Pulmonary & Critical Care Research Rana Lee Adawi Awdish Hector Cajigas (Previous Investigator) Henry Ford Health System Paraskevi Argyropoulou-Pataka General Hospital of Thesaloniki ‘G. Papanikolaou’ Stylianos Orfanos University General Hospital ‘Attikon’’ Pr Ari Chaouat Hopital Brabois Wei-chun Huang Chin-Chang Cheng (Previous Investigator) Kaohsiung Veterans General Hospital Chih-Hsin Hsu National Cheng Kung University Hospital Hsao-Hsun Hsu National Taiwan University Hospital Kuo-Yang Wang Taichung Veterans General Hospital Hyuk-Jae Chang Severance Hospital, Yonsei University Health System Investigator Institution Hyung-Kwan Kim Jun-Bean Park (Previous Investigator) Hyung-Kwan Kim (Previous Investigator) Seoul National University Hospital Sung-A Chang Duk-Kyung Kim (Previous Investigator) Sung-A Chang (Previous Investigator) Samsung Medical Center Peter Paul Yousseff Royal Prince Alfred Hospital Jaquelina Sonoe Ota Arakaki Universidade Federal de Sao Paulo – Unifesp/EPM Padma Kumar Edla Arjun Maxcure Mediciti Hospitals Frederico Thadeu Assis Figueiredo Campos Instituto das Pequenas Missionarias de Maria Imaculada- Hospital Madre Teresa Vijay Chopra Rahul Mehrotra (Previous Investigator) Vijay Chopra (Previous Investigator) Medanta, The Medicity Ricardo de Amorim Correa Hospital das Clinicas da Universidade Federal de Minas Gerais James Laurence Lordan Paul Anthony Corris (Previous Investigator) Freeman Hospital Rogerio de Souza HC da FMUSP Instituto do Coracao INCOR Sao Paulo Laura Scelsi Fondazione IRCCS Policlinico San Matteo di Pavia Gisela Martina Bohns Meyer Irmandade da Santa Casa de Misericordia de Porto Alegre - ISCMPA Maria Auxiliadora Carmo Moreira Hospital das Clinicas da UFG Rajeev Kumar Rajput Indraprastha Apollo Hospitals Jitendra Pal Singh Sawhney Sir Ganga Ram Hospital Subir Bimalendu Ghosh Kamal Harishchandra Sharma (Previous Investigator) Apollo Hospitals International Limited Patrizio Vitulo Instituto Mediterraneo Trapianti Terapie Alta Specializzazione ISMETT di Palmero Benjamin Joh-Han Ng Nepean Hospital Hugo Hyung Bok Yoo Universidade Estadual Paulista Julio de Mesquita Filho- Campus de Botucatu- Faculdade de Medicina Martine Reynaud-Gauber Centre Hospitalier Universitaire Nord

Presented at the 13th PVRI World Congress January 30 – February 05, 2019 Barcelona, Spain Disclosure: This study was sponsored by United Therapeutics Corporation. 20 FREEDOM-EV Investigators, Cont. Investigator Institution Daniel Grinnan Virginia Commonwealth University Medical Center Benjamin Howard Trichon Asheville Cardiology Associates Cheng Zhaozhong The Affiliated Hospital of Qingdao University Yuanhua Yang Beijing Chao-Yang Hospital, CMU Zhou Daxin Zhongshan Hospital Fudan University Shen Jieyan Renji Hospital Shanghai Jiaotong University School of Medicine Wook-Jin-Chung Gachon University Gil Medical Center Jong-Min Song Assan Medical Center Clara Hjalmarsson Bengt Rundqvist (Previous Investigator) Sahlgrenska University Hospital Clark McDonough Augusta University Martin Russell Brown Macquarie University Pablo Andres Sepulveda Varela Hospital San Juan de Dios Monica Maria Zagolin Blancaire Asesoria e Investigaciones Medicas TASOL Ltda. Graciela Noemi Svetliza Hospital Italiano de Buenos Aires Adrian Jose Lescano Sanatorio San Jose Guillermo Roberto Bortman Sanatorio de la Trinidad Mitre Fabian Antonio Diez Hospital Italiano Garibaldi Cristian Edgardo Botta Hospital Provincial Jose Maria Cullen R. James White Mary M. Parkes Center Franz Rischard University of Arizona Clinical and Translational Science (CATS) Research Center Investigator Institution Martine Reynaud-Gauber Centre Hospitalier Universitaire Nord Marie-France Seronde Centre Hospitalier Regional Universitaire de Besancon – Hopital Jean Minjoz Bhagavathula Kutumba Srinivasa Sastry Care Hospitals Bao Chunde Renji Hospital Shanghai Jiaotong University School of Medicine Yi Qun West China Hospital of Sichuan University Cheng Xiaoshu The Second Affiliated Hospital of Nanchang Medical University Yu Zaixin Xiangya Hospital of Central South University Xinli Li The First Affiliated Hospital of Nanjing Medical University Yao Hua Guangdong General Hospital Zhang Gangcheng Wuhan Asia Heart Hospital Xianyang Zhu The General Hospital of Shenyang Military Region Yundai Chen Chinese PLA General Hospital David McNaughton Smallwood Royal Melbourne Hospital Monica Silveira Lapa Hospital Alemao Oswaldo Cruz Ulrich Kruger Herzzentrum Duisberg Nathan Brent Dwyer Royal Hobart Hospital Lim Soo Teik National Heart Centre Singapore Regina Steringer-Mascherbauer Krankenhaus der Elisabethined Linz GmbH Juliane Kronsbein Barbara Monika Hauptmeier (Previous Investigator) Andrea Koch (Previous Investigator) Berufsgenossenschaftliches Universitätsklinikum Bergmannsheil GmbH Matthias Held Klinikum Wurzburg Mitte gGmbH Tobias Johannes Lange Universitatsklinikum Regensburg Claus Neurohr University of Munich – Klinikum Großhadern Heinrike Wilkens Universitatsklinikum des Saarlandes Hubert Rolf Wilhelm Wirtz Universitatsklinikum Leipzig AoR Stavros Konstantinides Universitatsmedizin der Johannes Gutenberg-Universitat Mainz Magnus Nisell Karolinska University Hospital, Solna Jorn Carlsen Rigshospitalet, Copenhagen University Hospital Yip Wei Luen James National University Hospital Daniel Grinnan Virginia Commonwealth University Medical Center

Additional Slides Presented at the 13th PVRI World Congress January 30 – February 05, 2019 Barcelona, Spain Disclosure: This study was sponsored by United Therapeutics Corporation. 21

Presented at the 13th PVRI World Congress January 30 – February 05, 2019 Barcelona, Spain Disclosure: This study was sponsored by United Therapeutics Corporation. 22 Time to Death at Study Closure Kaplan–Meier Estimates a P value is calculated with log rank test stratified by background PAH therapy and baseline 6MWD category. b Hazard ratio, 95% CI, and P value are calculated with proportional hazard model with treatment, background PAH therapy and baseline 6MWD as explanatory variables. PATIENTS WITHOUT AN EVENT (%) P= 0.0324a HR: 0.63 (95% CI: 0.42-0.95), P= 0.0259b WEEKS ORAL TREPROSTINIL PLACEBO No. at risk Oral treprostinil 346 323 275 246 214 182 143 117 88 56 27 4 1 Placebo 344 326 288 255 229 192 147 111 80 52 27 6 0 Population: ITT

Summary and Analysis of Disease Progression 23 ORAL TREPROSTINIL PLACEBO N=346 % N=344 % Number and percentage of subject disease progression All Events 19 5.5% 50 14.5% Decrease in 6MWD >15% and increase in WHO Functional Class 9 2.6% 28 8.1% Decrease in 6MWD >15% and appearance or worsening of symptoms of right heart failure 10 2.9% 22 6.4% Hazard Ratio (95% CI) (Oral Treprostinil – Placebo)a 0.39 (0.23, 0.66) P=0.0004 a Hazard ratio, 95% CI, and P value are calculated with proportional hazard model with treatment, background PAH therapy and baseline 6MWD as explanatory variables. Presented at the 13th PVRI World Congress January 30 – February 05, 2019 Barcelona, Spain Disclosure: This study was sponsored by United Therapeutics Corporation.

Time to Disease Progression (Weeks) Kaplan–Meier Estimates 24 a P value is calculated with log rank test stratified by background PAH therapy and baseline 6MWD category. b Hazard ratio, 95% CI, and P value are calculated with proportional hazard model with treatment, background PAH therapy and baseline 6MWD as explanatory variables. PATIENTS WITHOUT AN EVENT (%) P= 0.0002a HR: 0.39 (95% Cl: 0.23-0.66), P=0.0004b WEEKS ORAL TREPROSTINIL PLACEBO No. at risk Oral treprostinil 346 286 191 154 116 82 Placebo 344 278 199 154 122 91 Presented at the 13th PVRI World Congress January 30 – February 05, 2019 Barcelona, Spain Disclosure: This study was sponsored by United Therapeutics Corporation. Population: ITT