Actelion Presents REPAIR Study Interim Analysis at the American College of Cardiology's 68th Annual Scientific Session

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1 Interim Analysis Shwed Treatment with OPSUMIT (macitentan) Assciated with Significant Imprvement in Right Ventricular (RV) Functin and Pulmnary Vascular Resistance (PVR) in Patients with Pulmnary Arterial Hypertensin (PAH) Actelin Presents REPAIR Study Interim Analysis at the American Cllege f Cardilgy's 68th Annual Scientific Sessin SOUTH SAN FRANCISCO, Calif. and ALLSCHWIL, Switzerland, March 15, 2019 /PRNewswire/ - - Actelin Pharmaceuticals US, Inc., ne f the Janssen Pharmaceutical Cmpanies f Jhnsn & Jhnsn, annunced tday an interim analysis frm the Right ventricular Remdeling in Pulmnary ArterIal hypertensin (REPAIR) study f OPSUMIT (macitentan) that shws treatment with OPSUMIT in patients with pulmnary arterial hypertensin (PAH) was assciated with significant imprvements in right ventricular (RV) functin including reversal f RV remdeling and reduced pulmnary vascular resistance (PVR). The data are being presented at the American Cllege f Cardilgy's 68th Annual Scientific Sessin. "The REPAIR study is the first multicenter study in PAH t use a primary endpint measured by cardiac MRI," said Stephan Rsenkranz, MD, Head f Pulmnary Hypertensin Center and Head f Clgne Cardivascular Research Center (CCRC), University f Clgne, Divisin f Cardilgy. "These results ffer clinicians wh treat this severe and prgressive disease a better understanding f the effects that macitentan can have n RV remdeling and functin in patients with PAH." The REPAIR study is a 52-week, pen-label, multicenter study evaluating the effect f OPSUMIT n RV remdeling and functin as determined by cardiac magnetic resnance imaging (MRI) and right heart catheterizatin. OPSUMIT was initiated as mntherapy r sequential cmbinatin therapy with a phsphdiesterase-type 5 (PDE-5) inhibitr r as initial cmbinatin therapy with a PDE-5 inhibitr. The pre-specified interim analysis including 42 patients with PAH shwed significant imprvements in bth primary endpints including a 15.2 ml mean increase (p<0.0001) in RV strke vlume (RVSV) and a 37% reductin (p<0.0001) in PVR frm baseline at Week 26. RVSV was determined by pulmnary artery flw MRI and PVR was measured by right heart catheterizatin. A full evaluatin, with fcus n RV, was als perfrmed using MRI. "Measurement f RV functin in patients with PAH is very helpful in mnitring respnse t treatment," said Richard N. Channick, MD, Prfessr f Medicine and Directr, Acute and Chrnic Thrmbemblic Disease Prgram at UCLA Medical Center. "The REPAIR study shws us that RV functin, as determined by MRI, is a relevant endpint in studying treatment efficacy in PAH." Pulmnary arterial hypertensin is a prgressive disease in which bld vessels in the lungs becme restricted. This frces the right heart t wrk harder t pump bld t the lungs, and RV functin is impaired. The results frm the REPAIR interim analysis suggest that treatment with OPSUMIT is assciated with significantly imprved RV functin as determined by MRI in patients with PAH. In the REPAIR study, the safety prfile f OPSUMIT was cnsistent with previus clinical trial data.these results add t the grwing bdy f research int understanding OPSUMIT in PAH.

2 "We are very pleased with these interim results frm the REPAIR study and we will wrk diligently t reprt the full study results in the near future," said Alessandr Maresta, MD, VP and Head f Glbal Medical Affairs at Actelin Pharmaceuticals Ltd. "We are cmmitted t nging research and t advancing therapies fr peple with PAH and are prud t make a difference in patients' lives." *Drs. Rsenkranz and Channick have received research supprt frm Actelin and have served as paid cnsultants t the cmpany. Ntes t the Editr ABOUT PULMONARY ARTERIAL HYPERTENSION (PAH) Pulmnary arterial hypertensin (PAH) is a chrnic, life-threatening disrder characterized by abnrmally high bld pressure in the arteries between the heart and lungs f an affected individual. The symptms f PAH are nn-specific and can range frm mild breathlessness and fatigue during nrmal daily activity t symptms f right heart failure and severe restrictins n exercise capacity and ultimately reduced life expectancy. PAH is ne grup within the classificatin f pulmnary hypertensin (PH). This grup includes idipathic PAH, heritable PAH and PAH caused by factrs which include cnnective tissue disease, HIV infectin and cngenital heart disease. The last decade has seen significant advances in the understanding f the pathphysilgy f PAH, which has been paralleled with develpments f treatment guidelines and new therapies. Drugs targeting the three pathways that have been established in the pathgenesis f PAH are endthelin receptr antagnists (ERAs), prstacyclin analgs and phsphdiesterase-5 inhibitrs. PAH treatments have transfrmed the prgnsis fr PAH patients frm symptmatic imprvements in exercise tlerance 10 years ag t delayed disease prgressin tday. Imprved disease awareness and evidence-based guidelines develped frm randmized cntrlled clinical trial data have highlighted the need fr early interventin, gal-riented treatment and cmbinatin therapy. ABOUT THE REPAIR STUDY The Right ventricular Remdeling in Pulmnary ArterIal hypertensin (REPAIR) study is a 52-week, pen-label, multicenter study evaluating the effect f OPSUMIT n right ventricular (RV) remdeling and functin as determined by cardiac MRI and right heart catheterizatin. REPAIR is the first multicenter study in PAH t use a primary endpint measured by MRI enabling clinicians t further understand the direct effects f OPSUMIT n RV remdeling and functin in patients with PAH. In the REPAIR study, OPSUMIT was initiated as mntherapy r sequential cmbinatin therapy with a phsphdiesterase-type 5 (PDE-5) inhibitr r as initial cmbinatin therapy with a PDE-5 inhibitr. The tw primary endpints were (1) change in RVSV frm baseline t Week 26, determined by pulmnary artery flw MRI, and (2) change in PVR frm baseline t Week 26 measured by right heart catheterizatin. In the pre-specified interim analysis including the first 42 patients enrlled, RVSV was significantly increased (mean change 15.2 ml, 96% CI [9.3; 21.0], p<0.0001) and PVR was significantly decreased (37%, 99% CI [26; 46], p<0.0001) at Week 26. The study was declared psitive and enrllment was stpped. All enrlled patients remain in the study up t their 52-week assessments, and a supprtive final analysis will be presented when the results becme available. The REPAIR study shwed that treatment with OPSUMIT was assciated with significant imprvement in RV functin in patients with PAH. What is OPSUMIT (macitentan)? OPSUMIT is a prescriptin medicine used t treat pulmnary arterial hypertensin (PAH, WHO Grup 1). PAH is high bld pressure in the arteries f yur lungs. OPSUMIT can:

3 Imprve yur ability t exercise as measured by the 6-minute walk distance (6MWD). In a clinical study f mainly WHO FC II-III patients, thse taking OPSUMIT walked, n average, 22 meters farther at Mnth 6 than patients nt taking it Imprve sme f yur symptms Help slw dwn the prgressin f yur disease Lwer yur chance f being hspitalized fr PAH It is nt knwn if OPSUMIT is safe and effective in children. The mst imprtant infrmatin abut OPSUMIT (macitentan) D nt take OPSUMIT if yu are pregnant r trying t get pregnant. OPSUMIT can cause serius birth defects if taken while pregnant. Wmen wh are able t get pregnant must have negative pregnancy tests: Befre starting OPSUMIT Each mnth while taking OPSUMIT Fr 1 mnth after stpping OPSUMIT Yur dctr will decide when yu shuld take pregnancy tests. Yu are medically able t get pregnant if yu are a wman wh fits all f the fllwing guidelines: has started puberty, even if yu have nt had a menstrual perid yet has a uterus has nt gne thrugh menpause (menpause means yu have nt had a menstrual perid fr at least 12 mnths fr natural reasns, r have had yur varies remved) Yu are nt medically able t get pregnant if yu are a wman wh fits at least 1 f the fllwing guidelines: has nt started puberty des nt have a uterus has gne thrugh menpause (yu have nt had a menstrual perid fr at least 12 mnths fr natural reasns, r have had yur varies remved) is infertile fr ther medical reasns and this infertility is permanent and cannt be reversed While taking OPSUMIT, and fr 1 mnth after stpping OPSUMIT, wmen wh are able t get pregnant must use 2 acceptable frms f birth cntrl. Wmen wh have had a tubal sterilizatin, a prgesterne implant, r have an IUD (intrauterine device) d nt need a secnd frm f birth cntrl. Talk t yur dctr r gyneclgist abut which birth cntrl t use while n OPSUMIT. If yu decide t change yur frm f birth cntrl, talk with yur dctr r gyneclgist. This way yu can be sure t chse anther acceptable frm f birth cntrl. Als review the Medicatin Guide fr acceptable birth cntrl ptins. It's imprtant nt t have unprtected sex while taking OPSUMIT. Tell yur dctr right away if yu have unprtected sex, think yur birth cntrl has failed, miss a menstrual perid, r think yu may be pregnant. He r she may recmmend using a frm f emergency birth cntrl. If yu are the parent r caregiver f a female child wh started taking OPSUMIT befre reaching puberty, check with yur child regularly fr any signs f puberty. Yur child may reach puberty befre having

4 her first menstrual perid. Talk t yur dctr if yu think yur child is shwing signs f puberty r if yu have any questins abut the signs f puberty. Befre starting OPSUMIT, wmen must enrll in a prgram called the OPSUMIT Risk Evaluatin and Mitigatin Strategy (REMS). If yu are a wman wh is able t get pregnant, yu must talk t yur dctr t learn the benefits and risks f OPSUMIT. Yu must als agree t all f the instructins in the prgram. Men wh are prescribed OPSUMIT d nt need t enrll in this prgram. Wh shuld nt take OPSUMIT? D nt take OPSUMIT if yu are pregnant, plan t becme pregnant, r becme pregnant during treatment with OPSUMIT. OPSUMIT can cause serius birth defects. See "The mst imprtant infrmatin abut OPSUMIT." Talk t yur dctr abut all yur medical cnditins, as well as all the medicines, vitamins, and supplements yu take. OPSUMIT and ther medicines may affect each ther causing side effects. Tell yur dctr right away if yu take an HIV medicine. D nt start any new medicine until yu check with yur dctr. What shuld I avid while taking OPSUMIT? D nt get pregnant. OPSUMIT can cause serius birth defects. See "The mst imprtant infrmatin abut OPSUMIT." If yu miss a menstrual perid r think yu may be pregnant, call yur dctr right away Yu shuld nt breastfeed if yu take OPSUMIT. It is nt knwn if OPSUMIT passes int yur breast milk. Talk t yur dctr abut the best way t feed yur baby What are the pssible side effects f OPSUMIT? OPSUMIT can cause serius side effects, including: Serius birth defects. See "The mst imprtant infrmatin abut OPSUMIT" Sme medicines that are like OPSUMIT can cause liver prblems. Yur dctr shuld d bld tests t check yur liver befre yu start OPSUMIT. Tell yur dctr if yu have any f these symptms, which culd be a sign f liver prblems while n OPSUMIT: Nausea r vmiting Pain in the upper right stmach Feeling tired Lss f appetite Yur skin r the whites f yur eyes turn yellw Dark urine Fever Itching Fluid retentin culd happen during the first weeks after starting OPSUMIT. Tell yur dctr right away if yu ntice unusual weight gain r swelling in yur ankles r legs. Yur dctr will lk fr the cause Lw red bld cell levels (anemia) can happen while taking OPSUMIT, usually during the first weeks after starting OPSUMIT. In sme cases a bld transfusin may be needed, but this is nt cmmn. Yur dctr will d bld tests t check fr anemia befre yu start OPSUMIT. Yu may als need t d these bld tests while taking OPSUMIT Decreased sperm cunts. OPSUMIT, and ther medicines like OPSUMIT, may cause decreased sperm cunts in men wh take these medicines. If fathering a child is imprtant t yu, tell yur dctr

5 The mst cmmn side effects are: Stuffy nse r sre thrat Irritatin f the airways (brnchitis) Headache Flu Urinary tract infectin Talk t yur dctr if yu have a side effect that bthers yu r des nt g away. These are nt all the pssible side effects f OPSUMIT. Fr mre infrmatin, ask yur dctr r pharmacist. Yu may reprt side effects t FDA at FDA-1088 r Please see full Prescribing Infrmatin and Medicatin Guide, including an Imprtant Warning abut Serius Birth Defects at ABOUT ACTELION Actelin, a leader in Pulmnary Arterial Hypertensin, became part f the Janssen Pharmaceutical Cmpanies f Jhnsn & Jhnsn fllwing its acquisitin in June Actelin's medicines have helped t expand and strengthen Janssen's prtfli with leading, differentiated in-market medicines and prmising late-stage cmpunds. Janssen has added Pulmnary Hypertensin as a therapeutic area f fcus t maintain the leadership psitin Actelin has built within this rare disease area. Learn mre at Fllw us ABOUT THE JANSSEN PHARMACEUTICAL COMPANIES OF JOHNSON & JOHNSON At Janssen, we're creating a future where disease is a thing f the past. We're the Pharmaceutical Cmpanies f Jhnsn & Jhnsn, wrking tirelessly t make that future a reality fr patients everywhere by fighting sickness with science, imprving access with ingenuity, and healing hpelessness with heart. We fcus n areas f medicine where we can make the biggest difference: Cardivascular & Metablism, Immunlgy, Infectius Diseases & Vaccines, Neurscience, Onclgy, and Pulmnary Hypertensin. Learn mre at Fllw us at and Actelin Pharmaceuticals US, Inc. is ne f the Janssen Pharmaceutical Cmpanies f Jhnsn & Jhnsn. Cautins Cncerning Frward-Lking Statements This press release cntains "frward-lking statements" as defined in the Private Securities Litigatin Refrm Act f 1995 regarding the develpment f OPSUMIT (macitentan). The reader is cautined nt t rely n these frward-lking statements. These statements are based n current expectatins f future events. If underlying assumptins prve inaccurate r knwn r unknwn risks r uncertainties materialize, actual results culd vary materially frm the expectatins and prjectins f Actelin Pharmaceuticals US, Inc., any f the ther Janssen Pharmaceutical Cmpanies and/r Jhnsn & Jhnsn. Risks and uncertainties include, but are nt limited t: challenges and uncertainties inherent in prduct research and develpment, including the uncertainty f clinical success and f btaining regulatry apprvals; uncertainty f cmmercial success; manufacturing difficulties and delays; cmpetitin, including technlgical advances, new prducts and patents attained by cmpetitrs; challenges t patents; prduct efficacy r safety cncerns resulting in prduct recalls r regulatry actin; changes in behavir and spending patterns f purchasers f health care prducts and services; changes t applicable laws and regulatins, including glbal health care refrms; and trends tward health care cst cntainment. A further list and descriptins f these risks, uncertainties and ther factrs can be fund in Jhnsn & Jhnsn's Annual Reprt n Frm 10-K fr the fiscal year ended December 30, 2018, including in the sectins captined "Cautinary Nte Regarding Frward-Lking Statements" and "Item 1A. Risk Factrs," and in the cmpany's mst recently filed Quarterly Reprt n Frm 10-Q, and the

6 cmpany's subsequent filings with the Securities and Exchange Cmmissin. Cpies f these filings are available nline at r n request frm Jhnsn & Jhnsn. Nne f the Janssen Pharmaceutical Cmpanies nr Jhnsn & Jhnsn undertakes t update any frward-lking statement as a result f new infrmatin r future events r develpments. REFERENCES 1. Rsenkranz S et al. Effects f Macitentan n Right Ventricular Remdeling in Pulmnary Arterial Hypertensin: Results Frm the REPAIR Study Interim Analysis. Prceedings frm the American Cllege f Cardilgy; March 16-18, 2019; New Orleans, LA. Abstract OPSUMIT (macitentan) Summary f Prduct Characteristics. Actelin Pharmaceuticals Ltd. September OPSUMIT (macitentan) full Prescribing Infrmatin. Actelin Pharmaceuticals US, Inc. Octber SERAPHIN Trial (Pulid et al. NEJM 2013). 5. Pulid T et al. Macitentan and Mrbidity and Mrtality in Pulmnary Arterial Hypertensin. N Engl J Med 2013;369: Blli MH et al. The Discvery f N-[5-(4-Brmphenyl)-6-[2-[(5-brm-2-pyrimidinyl)xy]ethxy]-4- pyrimidinyl]-n'-prpylsulfamide (Macitentan), an Orally Active, Ptent Dual Endthelin Receptr Antagnist. J Med Chem. 2012; 55: Iglarz M. et al. Pharmaclgy f macitentan, an rally active tissue targeting dual endthelin receptr antagnist. J Pharmacl Exp Ther. 2008;327(3): Media Cntact Media Cntact Investr Cntact Investr Cntact Carline Pavis David Kewn Lesley Fishman Christpher DelOrefice Office: Office: Office: Office: CPavis@its.jnj.cm DKewn@its.jnj.cm LFishma@its.jnj.cm CDelref@its.jnj.cm