Postpericardiotomy Syndrome

Sept. 16, 2022 12:03 UTC FDA Also Approves and Closes RECOVER III Post-Approval Study DANVERS, Mass.--(BUSINESS WIRE)--Abiomed (Nasdaq: ABMD) announces two approvals from the U.S. Food and Drug Administration (FDA) related to clinical research of Impella heart pumps in acute myocardial infarction (AMI) cardiogenic shock patients. This press release features multimedia. View the full release here: RECOVER IV is an on-label, two-arm RCT that is designed to provide the clinical evidence needed to achieve a Class I guideline recommendation for Impella use in AMI cardiogenic shock. (Graphic: Business Wire) The FDA has approved the on-label RECOVER IV randomized controlled trial (RCT) for AMI cardiogenic shock patients. RECOVER IV is a two-arm trial that will assess whether percutaneous coronary intervention (PCI), with Impella support initiated prior to the PCI, is superior to PCI without Impella support. “This landmark trial will be the culmination of over 20 years of research in the interventional therapy of AMI and will apply all the clinical advancements we have made to improve survival and heart recovery for AMI patients with cardiogenic shock as demonstrated in multiple prospective studies,” said William O’Neill, MD, medical director of the Center for Structural Heart Disease at Henry Ford Health and a RECOVER IV national co-principal investigator. The primary endpoint of RECOVER IV is all-cause mortality at 30 days. Secondary endpoints include major adverse cardiovascular and cerebrovascular events (MACCE) at 30 days, days alive out of the hospital at six months, recovery of left ventricular (LV) function, need for durable ventricular assist device (VAD) or heart transplant, and health-related quality of life as measured by responses to the Kansas City Cardiomyopathy Questionnaire (KCCQ) at one year. Abiomed’s goal in conducting the trial is to achieve a global AMI cardiogenic shock Class I guideline recommendation for Impella and related best practice protocols, including Impella implantation pre-PCI (see figure 1). “I am optimistic that RECOVER IV will further demonstrate the benefits of hemodynamic support and best practice protocols. These benefits include ventricular unloading using Impella pre-PCI, reduced LV wall stress, reduced pulmonary congestion, increased collateral coronary blood flow, and enhanced cardio protection so that more AMI cardiogenic shock patients can survive and achieve native heart recovery. The heart team and field have evolved and understand how important myocardial recovery is for both AMI and AMI cardiogenic shock to reduce the growing epidemic of heart failure,” said Navin K. Kapur, MD, executive director of the Cardiovascular Center for Research and Innovation (CVCRI) at Tufts Medical Center and a national co-principal investigator for RECOVER IV. FDA Approves and Closes RECOVER III Post-Approval Study Additionally, the FDA has approved and closed Impella’s prospective AMI cardiogenic shock post-approval study (PAS), RECOVER III. This study gathered real-world evidence on AMI cardiogenic shock patients treated with Impella between 2017–2019, collecting detailed data including stages of cardiogenic shock, cardiac output and timing of implantation. RECOVER III fulfills Abiomed’s PAS requirement and the FDA’s approval and closure of RECOVER III further validates Impella as a safe and effective therapy for AMI cardiogenic shock. Impella remains the only mechanical circulatory support (MCS) device that has received the FDA’s highest level of pre-market approval (PMA) and PAS regulatory approval for AMI cardiogenic shock. Based on RECOVER III, Impella’s label for AMI cardiogenic shock will be updated to reflect data for up to one-year post-procedure. AMI Cardiogenic Shock Clinical History AMI cardiogenic shock has one of the highest mortality rates in the field of medicine. The survival rate has remained approximately 50% for cardiogenic shock patients in SCAI stages D and E without Impella support and associated best practices. Survival alone in cardiogenic shock is no longer the gold standard. Multiple Impella best practice studies demonstrate greater than 70% survival with greater than 90% native heart recovery (see figure 2). Impella best practices, such as pre-PCI implantation (see figure 3), have been developed by the recognized physician experts in the field of circulatory support and published over the last decade in multiple clinical studies from the U.S., Germany, Italy and Japan. Heart recovery after AMI cardiogenic shock improves patient quality of life and makes Impella one of the most cost-effective therapies in the CMS Medicare population and in private insurance. In the U.S. alone, more than 200,000 patients are admitted to the hospital every year in cardiogenic shock. FDA Regulatory History of AMI Cardiogenic Shock Impella is the most studied heart pump in the history of the FDA (see figures 4 & 5) and has exclusive FDA PMA as a safe and effective therapy for cardiogenic shock, high-risk PCI and right heart failure. Since 2004, more than 1,200 peer-reviewed studies, including real-world evidence analyses, prospective clinical studies and RCTs have published about the clinical benefits of Impella. Impella has been used to treat more than 235,000 patients globally and is included in 13 clinical society guidelines. In 2021, the European Society of Cardiology upgraded Impella to a Class IIa recommendation for the treatment of cardiogenic shock. The intra-aortic balloon (IAB) is currently Class III (harmful) for routine use in cardiogenic shock in Europe and Japan based on the IABP-SHOCK II RCT, which demonstrated IAB compared to inotropic therapy provided no benefit to survival or hemodynamic augmentation. In 2020, IAB became Class III (harmful) in the U.S. guideline recommendations for post-cardiotomy cardiogenic shock. All MCS and ventricular assist devices (VADs) since 1992 were approved with single-arm studies compared to historical survival rates judged on objective performance criteria (OPC) due to the ethical and logistical challenges of randomizing critically ill patients requiring immediate hemodynamic augmentation. In 2008 and 2009, Abiomed attempted the FDA RECOVER II RCT, which compared Impella to IAB in AMI cardiogenic shock. RECOVER II enrolled only 1 patient in 15 months at more than 30 sites before being halted for logistical and ethical consent challenges and lack of enrollment. The FDA granted Impella 510(k) clearance in 2008 and after multiple FDA and prospective physician-initiated studies, the FDA approved high-risk PCI in 2015, AMI cardiogenic shock in 2016 (see figure 6), and other forms of heart failure with cardiogenic shock in 2018. With the fulfillment of RECOVER III and approval of RECOVER IV RCT, Abiomed is pursuing an on-label study to strengthen the global guidelines and improve outcomes for patients. Abiomed has sponsored and funded several AMI cardiogenic shock studies since 2006 (see figure 7), including the only FDA studies in this space. The difficulty randomizing AMI cardiogenic shock patients in execution has been demonstrated in multiple studies including IMPRESS in STEMI (n=18), IMPRESS in Cardiac Arrest (n=48), Seyfarth, et al. (n=26) and the Abiomed-sponsored FDA RECOVER II RCT (n=1). All these studies failed to randomize and were halted early for failure to enroll their designated numbers based on logistical and ethical consent challenges. Recent FDA Regulatory Changes for Exception from Informed Consent (EFIC) Randomizing patients in AMICS has been challenging because they require emergent care and are too sick to provide traditional informed consent to enroll in a trial. In 1996, the FDA created the exception from informed consent (EFIC) pathway for emergency clinical research. This pathway allows investigators to broadly educate a community about a trial, then enroll patients without consent from patients, their family or their legally authorized representatives. In 2022, after engaging with the FDA on the RECOVER IV RCT study design, the FDA approved the RECOVER IV RCT study protocol, which includes the use of EFIC. This community awareness process is rare and only used when the patients being studied are experiencing a life-threatening medical condition causing serious deficiency of mental function. This is a significant milestone for the field and physician leaders. The next steps include local hospital Institutional Review Board (IRB) approvals and a commitment from physicians to randomize. “This pivotal randomized trial is historic as the first to use EFIC community consent to enroll cardiogenic shock patients. I applaud the FDA for its partnership to help solve the consent challenges in cardiogenic shock RCTs and call on the physician community to enroll and randomize patients in RECOVER IV,” said Gregg W. Stone, MD, professor of medicine and director of academic affairs for the Mount Sinai Heart Health System in New York and study chair for RECOVER IV. For more information on current best practices in treating AMI cardiogenic shock patients please click here. For more information on the RECOVER IV RCT study please click here. ABOUT IMPELLA HEART PUMPS Impella 2.5® and Impella CP® with SmartAssist® are U.S. FDA approved to treat certain advanced heart failure patients undergoing elective and urgent percutaneous coronary interventions (PCI), such as stenting or balloon angioplasty, to reopen blocked coronary arteries. Impella 2.5, Impella CP, Impella CP with SmartAssist®, Impella 5.0®, Impella LD®, and Impella 5.5® with SmartAssist® are U.S. FDA approved to treat heart attack or cardiomyopathy patients in cardiogenic shock and have the unique ability to enable native heart recovery, allowing patients to return home with their own heart. ABOUT ABIOMED Based in Danvers, Massachusetts, U.S.A., Abiomed is a leading provider of medical technology that provides circulatory support and oxygenation. Our products are designed to enable the heart to rest by improving blood flow and/or provide sufficient oxygenation to those in respiratory failure. For additional information, please visit: . FORWARD-LOOKING STATEMENTS Any forward-looking statements are subject to risks and uncertainties such as those described in Abiomed's periodic reports on the Securities and Exchange Commission. Actual results may differ materially from anticipated results.

- Rapid resolution of both reported pain and inflammation as well as improvement in quality of life scores - - Tapering and discontinuation of corticosteroids without pericarditis recurrence - - Markedly lower annualized incidence of pericarditis episodes while on treatment - - Pivotal Phase 3 trial of rilonacept in recurrent pericarditis (RHAPSODY) enrolling; data expected in 2H 2020 - HAMILTON, Bermuda, Nov. 16, 2019 (GLOBE NEWSWIRE) -- Kiniksa Pharmaceuticals, Ltd. (Nasdaq: KNSA) (“Kiniksa”), a biopharmaceutical company focused on discovering, acquiring, developing and commercializing therapeutic medicines for patients with significant unmet medical need, reported final data from an open-label Phase 2 clinical trial of rilonacept, a weekly, subcutaneously-injected, recombinant fusion protein that blocks IL-1α and IL-1β signaling. The data were included in a poster presentation at the American Heart Association (AHA) Scientific Sessions 2019. “The final Phase 2 data showed the potential for rilonacept to improve clinically meaningful outcomes associated with unmet need in recurrent pericarditis,” said Sanj K. Patel, Chief Executive Officer and Chairman of the Board of Kiniksa. “Rilonacept treatment in the Phase 2 trial led to a rapid resolution of recurrent pericarditis episodes that was sustained throughout the 6-month study as well as an improvement in overall quality of life scores. Treatment with rilonacept also led to a decrease in the annualized incidence of pericarditis episodes and importantly supported the discontinuation of corticosteroids without pericarditis recurrence. These data further confirm our confidence in the design of RHAPSODY, our pivotal Phase 3 trial of rilonacept in recurrent pericarditis, for which we expect top-line data in the second half of 2020.” Dr. Allan Klein, MD, of Cleveland Clinic and co-principal investigator for the trial, presented Efficacy and Safety of Rilonacept in Recurrent Pericarditis: A Multicenter Phase 2 Clinical Trial. The materials are available through the Science section of Kiniksa’s website (www.kiniksa.com). The Phase 2 trial evaluated the treatment response to rilonacept in a range of pericarditis populations and was divided into five parts across two cohorts. Symptomatic recurrent pericarditis patients: Part 1: Symptomatic patients with recurrent pericarditis and C-reactive protein (CRP) > 1 mg/dL; Part 2: Symptomatic patients with recurrent pericarditis and CRP ≤ 1 mg/dL but pericardial inflammation confirmed by magnetic resonance imaging (MRI); and Part 4: Symptomatic patients with post-pericardiotomy syndrome (PPS) and CRP > 1 mg/dL. Corticosteroid-dependent recurrent pericarditis patients: Part 3: Asymptomatic patients with recurrent pericarditis who were dependent upon or unable to wean off corticosteroids; and Part 5: Asymptomatic patients with PPS who were dependent upon or unable to wean off corticosteroids. In this study, all patients received a loading dose of rilonacept 320 mg subcutaneously (SC) followed by 160 mg SC weekly maintenance on top of any combination of co-administered nonsteroidal anti-inflammatory drugs (NSAIDs) and/or colchicine and/or corticosteroids during a 6-week base treatment period. There was an optional 18-week extension treatment period, during which physicians were given the option to wean patients off concomitant NSAIDs, colchicine, and/or corticosteroids. The assessed efficacy outcomes measures included an 11-point pain Numerical Rating Scale (NRS), CRP, electrocardiogram, and size of pericardial effusion. The co-principal investigators were Dr. Allan Klein of Cleveland Clinic and Dr. David Lin of Minneapolis Heart Institute Foundation. 25 unique patients enrolled in the 6-week base treatment period across Parts 1 through 5 of the Phase 2 trial, and 23 patients continued into the optional 18-week extension treatment period and completed 24 weeks of treatment. The Phase 2 data provided first evidence that rilonacept treatment improved clinically meaningful outcomes associated with the unmet medical need in recurrent pericarditis. Resolution of Pericarditis Episodes Symptomatic recurrent pericarditis patients with CRP > 1mg/dL (Parts 1 and 4; n = 13), who were failing standard of care management with NSAIDs, colchicine, and/or corticosteroids, are expected to be most relevant to the enrollment population for the ongoing Phase 3 clinical trial (RHAPSODY). There was a rapid reduction in both reported pain and inflammation after the first dose as well as a persistent and clinically meaningful response throughout the study for these patients. Mean patient-reported pericardial pain on an 11-point NRS decreased from 4.5 at baseline to 0.5 at 24 weeks; mean CRP decreased from 4.6 mg/dL at baseline to 0.2 mg/dL at 24 weeks; mean time to CRP normalization was 9 days; and pericardial signs resolved or improved in all patients, including pericardial effusion (6/7 patients), PR depression (2/3 patients), widespread ST elevation (2/2 patients) and pericardial rub (2/2 patients). Symptomatic recurrent pericarditis patients with CRP ≤ 1mg/dL (Part 2; n = 3), who were failing standard of care management with NSAIDs, colchicine, and/or corticosteroids, showed a reduction in both reported pain and inflammation after the first dose as well as a persistent and clinically meaningful response throughout the study. Mean patient-reported pericardial pain on an 11-point NRS decreased from 4.7 at baseline to 0.0 at 24 weeks; and mean CRP decreased from 0.46 mg/dL at baseline to 0.32 mg/dL at 24 weeks. Tapering and Discontinuation of Corticosteroids without Pericarditis Recurrence 15 recurrent pericarditis patients on corticosteroids at baseline enrolled in the 6-week base treatment period, and 13 continued into the optional 18-week extension treatment period and completed 24 weeks of treatment. During the optional 18-week extension treatment period, investigators were given the option to wean patients from concomitant medications while continuing weekly rilonacept treatment. All patients on corticosteroids stopped or tapered corticosteroids during this part of the study without experiencing a recurrent pericarditis episode. 11 recurrent pericarditis patients discontinued corticosteroids completely: 4 symptomatic patients across Parts 1 and 2 as well as 7 corticosteroid-dependent patients across Parts 3 and 5. The corticosteroid dose was successfully tapered in the 2 remaining recurrent pericarditis patients by the end of the 24-week study period: 1 symptomatic patient in Part 2 and 1 corticosteroid-dependent patient in Part 3. Reduction in Recurrences of Pericarditis Episodes A comparison of the annualized incidence of pericarditis episodes during the study while receiving rilonacept versus patients’ own natural history in the period prior to the study demonstrated a decrease in annualized incidence of pericarditis episodes across all parts from 3.9 episodes/year prior to the study to <0.18 episodes/year. Improved Quality of Life Scores Rilonacept treatment resulted in improvement of Patient Reported Outcomes Measurement Information System (PROMIS) Global Health scores for Physical and Mental Global Health (U.S. mean score = 50.0; standard deviation = 10). In symptomatic recurrent pericarditis patients (Parts 1, 2, and 4), the mean Physical and Mental Global Health baseline scores were 39.9 and 44.5, respectively, and improved to 51.3 and 50.5, respectively, at 24 weeks. In corticosteroid-dependent recurrent pericarditis patients (Parts 3 and 5), the mean Physical and Mental Global Health baseline scores were 43.3 and 46.5, respectively, and improved to 46.8 and 50.7, respectively, at 24 weeks. Safety Rilonacept was generally well-tolerated in the study, with adverse events consistent with the U.S. Food and Drug Administration (FDA)-approved label for the treatment of Cryopyrin-Associated Periodic Syndromes (CAPS), including Familial Cold Autoinflammatory Syndrome and Muckle-Wells Syndrome. The most common adverse events were mild, transient injection site reactions that did not cause discontinuation. There was one treatment-related serious adverse event which resulted in discontinuation: a skin abscess which responded to medical treatment. Infections are reported in the rilonacept label for CAPS. “Recurrent pericarditis is a debilitating autoinflammatory disease with a clear unmet need,” said Dr. Allan Klein, MD, of Cleveland Clinic. “The final Phase 2 data show a sustained clinical response over 6 months of treatment, supporting tapering of corticosteroids while on treatment and affirming the efficacy of the interim analysis reported at the American College of Cardiology’s (ACC) Annual Scientific Sessions in March 2018. I look forward to further investigation of rilonacept in the ongoing Phase 3 trial, RHAPSODY.” Kiniksa is enrolling RHAPSODY, a global, randomized withdrawal (RW) design, pivotal Phase 3 clinical trial in the U.S., Australia, Israel, and Italy. The primary efficacy endpoint is time-to-first pericarditis-recurrence in the RW period. The Clinical Endpoint Committee will adjudicate all suspected pericarditis recurrences for inclusion in the primary efficacy endpoint analysis. Top-line data are expected in the second half of 2020. About RHAPSODY RHAPSODY is the ongoing, pivotal Phase 3 clinical trial in recurrent pericarditis utilizing rilonacept. The company expects that at least 50 patients will be randomized into the RW period. Eligible patients must present at screening with at least a third pericarditis episode, defined as at least 1 day with pericarditis pain of ≥ 4 on the 11-point NRS and a CRP value ≥ 1 mg/dL within the 7-day period prior to first study drug administration. Patients included in the study may be receiving concomitant NSAIDs and/or colchicine and/or oral corticosteroid treatment in any combination. The study is comprised of 5 periods: a screening period; a single-blind run-in period during which patients receive a loading dose of rilonacept 320 mg injected SC followed by 160 mg SC weekly while background pericarditis medications are tapered and discontinued; a double-blind, placebo-controlled 24-week RW period during which clinical responders to rilonacept are randomized 1:1 and receive 160 mg SC weekly rilonacept or placebo for at least 24 weeks; a long-term extension treatment period after trial completion during which all patients completing the RW period have the option to receive up to 24 weeks of open-label rilonacept 160 mg SC weekly; and a long-term extension follow-up period during which all patients in the long-term extension period will be followed for 24 weeks for safety and pericarditis recurrences. The co-principal investigators are Dr. Allan Klein of Cleveland Clinic and Dr. Massimo Imazio of the University of Torino, Italy. About Rilonacept Rilonacept is a weekly, subcutaneously-injected, recombinant fusion protein that blocks inflammatory cytokines interleukin-1α (IL-1α) and interleukin 1β (IL-1β) signaling. Rilonacept was discovered and developed by Regeneron Pharmaceuticals, Inc. (Regeneron) and is approved by the FDA under the brand name ARCALYST® for the treatment of Cryopyrin-Associated Periodic Syndromes (CAPS), which includes Familial Cold Autoinflammatory Syndrome and Muckle-Wells Syndrome. IL-1 blockade may interfere with immune response to infections. Serious, life-threatening infections have been reported in patients taking ARCALYST. ARCALYST should be discontinued if a patient develops a serious infection. Taking ARCALYST with TNF inhibitors is not recommended because this may increase the risk of serious infections. Kiniksa exclusively licensed rilonacept from Regeneron for recurrent pericarditis and certain other indications. Rilonacept in recurrent pericarditis is an investigational drug. About Kiniksa Kiniksa is a biopharmaceutical company focused on discovering, acquiring, developing and commercializing therapeutic medicines for patients suffering from debilitating diseases with significant unmet medical need. Kiniksa has a pipeline of product candidates across various stages of development, focused on autoinflammatory and autoimmune conditions. For more information, please visit www.kiniksa.com. Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. In some cases, you can identify forward looking statements by terms such as “may,” “will,” “should,” “expect,” “plan,” “anticipate,” “could,” “intend,” “target,” “project,” “contemplate,” “believe,” “estimate,” “predict,” “potential” or “continue” or the negative of these terms or other similar expressions, although not all forward‑looking statements contain these identifying words. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including without limitation, statements regarding: the potential relevance of final data presented at AHA from our Phase 2 clinical trial in recurrent pericarditis, including its potential support for discontinuation of corticosteroids and our Phase 3 clinical trial design as well as its potential impact on unmet medical need; statements regarding the expected number of patients randomized in the RW period and objectives of the design of our Phase 3 clinical trial for rilonacept; and timing of potential data from the Phase 3 clinical trial. These forward-looking statements are based on management’s current expectations. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including without limitation, the following: changes between final data from our Phase 2 clinical trial presented at AHA or otherwise and any additional data or research disclosed by us or others with respect to recurrent pericarditis; our potential inability to replicate in later clinical trials, including our Phase 3 clinical trial, the positive final data from our Phase 2 and earlier clinical trials and other studies; delays or difficulty in activating sites or enrolling patients in our global Phase 3 clinical trial; patients failing to complete the clinical trial; patients failing to experience pre-specified events during the clinical trial within an expected time-frame, if at all; potential complications in coordinating among requirements, regulations and guidelines of regulatory authorities across a number of jurisdictions for our global Phase 3 clinical trial; impact of additional data from us or other companies; potential undesirable side effects caused by rilonacept; our potential inability to demonstrate safety and efficacy to the satisfaction of applicable regulatory authorities; our reliance on Regeneron to manufacture rilonacept; drug substance and/or drug product shortages; and our reliance on third parties to conduct research, clinical trials, and/or certain regulatory activities for rilonacept. These and other important factors discussed under the caption “Risk Factors” in our Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (“SEC”) on November 5, 2019 and our other reports filed with the SEC could cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. Any such forward-looking statements represent management’s estimates as of the date of this press release. While we may elect to update such forward-looking statements at some point in the future, we disclaim any obligation to do so, even if subsequent events cause our views to change. These forward-looking statements should not be relied upon as representing our views as of any date subsequent to the date of this press release. ARCALYST® is a registered trademark of Regeneron Pharmaceuticals, Inc. Every Second Counts!™ Kiniksa Investor and Media Contact Mark Ragosa (781) 430-8289 mragosa@kiniksa.com Source: Kiniksa Pharmaceuticals, Ltd.

–First patient dosed in Phase 2a trial of KPL-716 in prurigo nodularis – Upcoming presentations at SID, ISPOR and EULAR scientific conferences on KPL-716, rilonacept and mavrilimumab, respectively – Acquisition of KPL-404 (anti-CD40) complete; IND filing with FDA anticipated in 2H 2019 HAMILTON, Bermuda, May 02, 2019 (GLOBE NEWSWIRE) -- Kiniksa Pharmaceuticals, Ltd. (Nasdaq: KNSA) (“Kiniksa”), a biopharmaceutical company focused on discovering, acquiring, developing and commercializing therapeutic medicines for patients with significant unmet medical need, today reported first quarter 2019 financial results and highlighted recent corporate and pipeline activity. “The first quarter of 2019 was marked by the advancement of our clinical-stage pipeline,” said Sanj K. Patel, Chief Executive Officer and Chairman of the Board of Kiniksa. “Progress included the initiation of our Phase 2a trial for KPL-716 in prurigo nodularis as well as the continued enrollment of our pivotal Phase 3 trial for rilonacept in recurrent pericarditis and our global Phase 2 trial for mavrilimumab in giant cell arteritis. Going forward, we expect to build upon this momentum with focused investment behind our product candidates, including commercial readiness activities for rilonacept, and continued execution.” Clinical-Stage Pipeline Activity Rilonacept (IL-1α and IL-1β cytokine trap) Kiniksa is advancing rilonacept for the potential treatment of recurrent pericarditis, a painful autoinflammatory cardiovascular disease with an estimated U.S. prevalent population of approximately 40,000 patients seeking and receiving medical treatment. Kiniksa is enrolling RHAPSODY, a global, randomized-withdrawal (RW) design, pivotal Phase 3 clinical trial of rilonacept in subjects with recurrent pericarditis. The primary efficacy endpoint is time-to-first-adjudicated pericarditis-recurrence in the RW period. Top-line data are expected in the second half of 2020. In March 2019, Kiniksa presented interim data from an open-label Phase 2 clinical trial of rilonacept in subjects with recurrent pericarditis at the American College of Cardiology’s (ACC) 68th Annual Scientific Session. As of the January 2019 data cutoff date, all symptomatic recurrent pericarditis and post-pericardiotomy syndrome (PPS) subjects showed reductions in both C-reactive protein (CRP) and reported pain as well as improvement in quality of life scores. Additionally, CRP and reported pain remained low for all asymptomatic recurrent pericarditis and PPS subjects. Rilonacept has been generally well-tolerated in the study, with adverse events (AEs) consistent with the U.S. Food and Drug Administration (FDA)-approved label of rilonacept for the treatment of Cryopyrin-Associated Periodic Syndromes (CAPS). The most common AEs were injection site reactions. There was one treatment-related serious AE which resulted in discontinuation: a skin abscess that responded to medical treatment. Enrollment has closed and Kiniksa expects to complete the trial in the second half of 2019. Kiniksa is advancing its commercial readiness activities for rilonacept, including the expansion of its commercial and medical affairs teams and raising awareness of unmet need through payer, physician and patient engagement. Kiniksa plans to present new data from a systematic literature review highlighting the economic and humanistic burden of recurrent pericarditis at the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) in May 2019. Kiniksa is enrolling RHAPSODY, a global, randomized-withdrawal (RW) design, pivotal Phase 3 clinical trial of rilonacept in subjects with recurrent pericarditis. The primary efficacy endpoint is time-to-first-adjudicated pericarditis-recurrence in the RW period. Top-line data are expected in the second half of 2020. In March 2019, Kiniksa presented interim data from an open-label Phase 2 clinical trial of rilonacept in subjects with recurrent pericarditis at the American College of Cardiology’s (ACC) 68th Annual Scientific Session. As of the January 2019 data cutoff date, all symptomatic recurrent pericarditis and post-pericardiotomy syndrome (PPS) subjects showed reductions in both C-reactive protein (CRP) and reported pain as well as improvement in quality of life scores. Additionally, CRP and reported pain remained low for all asymptomatic recurrent pericarditis and PPS subjects. Rilonacept has been generally well-tolerated in the study, with adverse events (AEs) consistent with the U.S. Food and Drug Administration (FDA)-approved label of rilonacept for the treatment of Cryopyrin-Associated Periodic Syndromes (CAPS). The most common AEs were injection site reactions. There was one treatment-related serious AE which resulted in discontinuation: a skin abscess that responded to medical treatment. Enrollment has closed and Kiniksa expects to complete the trial in the second half of 2019. Mavrilimumab (monoclonal antibody inhibitor targeting GM-CSFRα) Kiniksa is advancing mavrilimumab for the potential treatment of giant cell arteritis (GCA), a chronic inflammatory disease of medium-large blood vessels with an estimated U.S. prevalence of approximately 75,000 to 150,000 patients. Kiniksa is enrolling a global Phase 2 proof-of-concept clinical trial of mavrilimumab in subjects with GCA. The primary efficacy endpoint is time-to-first-flare. Top-line data are expected in the second half of 2020. In April 2019, Kiniksa presented the design of the global Phase 2 clinical trial of mavrilimumab in GCA at the 19thInternational Vasculitis Workshop. Kiniksa plans to present preclinical data on the granulocyte macrophage colony stimulating factor (GM-CSF) and Type 1 T helper (TH1) signaling pathways in temporal arteries of GCA patients at the European League Against Rheumatism’s (EULAR) European Congress of Rheumatology in June 2019. Kiniksa is enrolling a global Phase 2 proof-of-concept clinical trial of mavrilimumab in subjects with GCA. The primary efficacy endpoint is time-to-first-flare. Top-line data are expected in the second half of 2020. KPL-716 (monoclonal antibody inhibitor of signaling through OSMRβ) Kiniksa is advancing KPL-716 for the potential treatment of a variety of pruritic diseases, including prurigo nodularis, a chronic inflammatory skin condition with an estimated U.S. prevalence of approximately 300,000 patients. Kiniksa is enrolling a Phase 2a clinical trial of KPL-716 in subjects with prurigo nodularis. The primary efficacy endpoint is percent change from baseline in weekly average Worst-Itch Numeric Rating Scale (WI-NRS). Top-line data are expected in the first half of 2020. Kiniksa plans to initiate an exploratory Phase 2 clinical trial in diseases characterized by chronic pruritus in the first half of 2019. The trial is designed to identify chronic pruritic conditions where interleukin-31 (IL-31) and/or oncostatin M (OSM) may be playing a role and to investigate the efficacy, safety and tolerability of KPL-716 in reducing the moderate-to-severe pruritus experienced by these subjects. Top-line data are expected in the second half of 2020. Kiniksa completed enrollment in a repeated-single-dose Phase 1b clinical trial of KPL-716 in subjects with moderate-to-severe atopic dermatitis experiencing moderate-to-severe pruritus. The study is designed to provide safety and exploratory data on both pruritus and inflammation disease response markers. Top-line data are expected in the second half of 2019. In April 2019, Kiniksa presented encore KPL-716 Phase 1a/1b clinical data at Revolutionizing Atopic Dermatitis (RAD). Kiniksa plans to present clinical and preclinical data from KPL-716 at the Society for Investigational Dermatology (SID) in May 2019. The data provides further scientific rationale for targeting oncostatin M receptor beta (OSMRβ) and dual pathway inhibition of IL-31 and OSM via KPL-716 for the potential treatment of chronic pruritic diseases. Kiniksa is enrolling a Phase 2a clinical trial of KPL-716 in subjects with prurigo nodularis. The primary efficacy endpoint is percent change from baseline in weekly average Worst-Itch Numeric Rating Scale (WI-NRS). Top-line data are expected in the first half of 2020. Kiniksa plans to initiate an exploratory Phase 2 clinical trial in diseases characterized by chronic pruritus in the first half of 2019. The trial is designed to identify chronic pruritic conditions where interleukin-31 (IL-31) and/or oncostatin M (OSM) may be playing a role and to investigate the efficacy, safety and tolerability of KPL-716 in reducing the moderate-to-severe pruritus experienced by these subjects. Top-line data are expected in the second half of 2020. Kiniksa completed enrollment in a repeated-single-dose Phase 1b clinical trial of KPL-716 in subjects with moderate-to-severe atopic dermatitis experiencing moderate-to-severe pruritus. The study is designed to provide safety and exploratory data on both pruritus and inflammation disease response markers. Top-line data are expected in the second half of 2019. Preclinical Pipeline Activity Kiniksa is progressing its preclinical activities with KPL-404, a monoclonal antibody inhibitor of the CD40 co-stimulatory receptor, in T-cell-dependent, B-cell-mediated disorders. Kiniksa expects to file an investigational new drug (IND) application with the FDA in the second half of 2019 and initiate a Phase 1 clinical trial in the first half of 2020. In April 2019, Kiniksa presented preclinical KPL-404 data at the Keystone Symposia, Antibodies as Drugs: New Horizons in the Therapeutic Use of Engineered Antibodies. The data showed favorable pharmacokinetic and pharmacodynamic profiles, including engagement of CD40 target and block of antigen-specific primary and secondary antibody responses in a T-cell dependent antibody response cynomolgus monkey model. In March 2019, Kiniksa closed the acquisition of Primatope Therapeutics, Inc. (“Primatope”), the company that owned or controlled the intellectual property related to KPL-404. Kiniksa is evaluating the progression of KPL-045, a monoclonal antibody inhibitor of the CD30 ligand co-stimulatory molecule, pending preclinical data from the program in the context of the company’s portfolio. In April 2019, Kiniksa presented preclinical KPL-404 data at the Keystone Symposia, Antibodies as Drugs: New Horizons in the Therapeutic Use of Engineered Antibodies. The data showed favorable pharmacokinetic and pharmacodynamic profiles, including engagement of CD40 target and block of antigen-specific primary and secondary antibody responses in a T-cell dependent antibody response cynomolgus monkey model. In March 2019, Kiniksa closed the acquisition of Primatope Therapeutics, Inc. (“Primatope”), the company that owned or controlled the intellectual property related to KPL-404. Financial Results and Recent Corporate Activity In the first quarter of 2019, Kiniksa completed a public offering of 2,816,110 Class A common shares (inclusive of the underwriters’ overallotment option exercise) at a public offering price of $18.26 per share and a concurrent private placement of 2,000,000 Class A1 common shares, at the same offering price per share. Aggregate net proceeds to Kiniksa were approximately $83.0 million. For the first quarter of 2019, Kiniksa reported a net loss of $65.8 million, compared to a net loss of $16.0 million for the first quarter of 2018. Total operating expenses for the first quarter of 2019 totaled $67.6 million compared to $16.3 million for the first quarter of 2018. Non-cash share-based compensation expense totaled $2.9 million for the first quarter of 2019, compared to $0.6 million for the first quarter of 2018. Total operating expenses for the first quarter of 2019 included $18.0 million related to the acquisition of Primatope and $10.0 million related to the first patient dosed in the Phase 2a clinical trial of KPL-716 in subjects with prurigo nodularis. As of March 31, 2019, the company had cash, cash equivalents and short-term investments of $326.5 million and no outstanding debt. Total operating expenses for the first quarter of 2019 included $18.0 million related to the acquisition of Primatope and $10.0 million related to the first patient dosed in the Phase 2a clinical trial of KPL-716 in subjects with prurigo nodularis. Financial Guidance Kiniksa expects that its cash, cash equivalents and short-investments will fund its current operating plan into 2021. About Kiniksa Kiniksa is a biopharmaceutical company focused on discovering, acquiring, developing and commercializing therapeutic medicines for patients suffering from debilitating diseases with significant unmet medical need. Kiniksa has a pipeline of product candidates across various stages of development, focused on autoinflammatory and autoimmune conditions. For more information, please visit www.kiniksa.com. About Rilonacept Rilonacept is a weekly, subcutaneously-injected, recombinant fusion protein that blocks interleukin-1α (IL-1α) and interleukin 1β (IL-1β) signaling. Rilonacept was discovered and developed by Regeneron Pharmaceuticals, Inc. and is approved by the FDA under the brand name ARCALYST® for the treatment of CAPS, which includes Familial Cold Autoinflammatory Syndrome and Muckle-Wells Syndrome. IL-1 blockade may interfere with immune response to infections. Serious, life-threatening infections have been reported in patients taking ARCALYST. ARCALYST should be discontinued if a patient develops a serious infection. Taking ARCALYST with TNF inhibitors is not recommended because this may increase the risk of serious infections. Kiniksa exclusively licensed rilonacept from Regeneron for recurrent pericarditis and certain other indications. Rilonacept in recurrent pericarditis is an investigational drug. About Mavrilimumab Mavrilimumab is an investigational fully-human monoclonal antibody that is designed to antagonize GM-CSF signaling by binding to the alpha subunit of the GM-CSF receptor. Kiniksa’s lead indication for mavrilimumab is giant cell arteritis, an inflammatory disease of blood vessels. About KPL-716 KPL-716 is an investigational fully-human monoclonal antibody that targets OSMRβ, which mediates signaling of IL-31 and OSM, two key cytokines implicated in pruritus, inflammation and fibrosis. Kiniksa believes KPL-716 to be the only monoclonal antibody in development that targets both pathways simultaneously. About KPL-404 KPL-404 is an investigational humanized monoclonal antibody that is designed to inhibit the CD40-CD40-ligand interaction, a key T-cell co-stimulatory signal critical for B-cell maturation and immunoglobulin class switching. Dysregulation of the CD40-CD40L pathway has been implicated in multiple autoimmune disease pathologies such as Systemic Lupus Erythematosus, Rheumatoid Arthritis, Sjogren’s Syndrome and Grave’s Disease. About KPL-045 KPL-045 is an investigational fully-human monoclonal antibody that is designed to inhibit the CD30-CD30 ligand interaction, a co-stimulatory signal involved in activating and sustaining memory T-cells. Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. In some cases, you can identify forward looking statements by terms such as “may,” “will,” “should,” “expect,” “plan,” “anticipate,” “could,” “intend,” “target,” “project,” “contemplate,” “believe,” “estimate,” “predict,” “potential” or “continue” or the negative of these terms or other similar expressions, although not all forward‑looking statements contain these identifying words. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including without limitation, statements regarding: our execution, pre-commercial activities and investment focus, and potential results therefrom; expected timeframe for funding our operating plan with current cash, cash equivalents and short-term investments; plans and timing for completion of clinical trials; proposed indications for the investigation of our product candidates; estimated disease prevalence; plans and timing to report or present top-line clinical trial, pre-clinical and other data; plans and timing for the submission of investigational new drug and other applications and submissions to regulatory authorities; and plans and timing to advance additional pipeline programs into clinical trials. These forward-looking statements are based on management’s current expectations. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including without limitation, the following: potential delays or difficulty in enrollment of patients in, and activation of sites for, our clinical trials; potential complications in coordinating among requirements, regulations and guidelines of regulatory authorities across a number of jurisdictions for our global clinical trials; potential delays or difficulty in completing our clinical trials; potential undesirable side effects caused by our product candidates; our potential inability to demonstrate safety and efficacy to the satisfaction of applicable regulatory authorities; potential for changes between final data and any interim “top-line” and preliminary data we announce; impact of additional data from us or other companies; our potential inability to replicate in later clinical trials positive results from our earlier clinical trials; our ability to manufacture drug substance for Phase 1 clinical trials using our facilities; drug substance and/or drug product shortages caused by issues at our third-party manufacturers’ facilities; our reliance on certain third parties as the sole source of supply of the drug substance and drug products used in our product candidates; our reliance on third parties to conduct our research, pre-clinical studies, clinical trials, and other trials for our product candidates; we face substantial competition; and our ability to attract and retain qualified personnel. These and other important factors discussed under the caption “Risk Factors” in our Annual Report on Form 10-K filed with the Securities and Exchange Commission (“SEC”) on March 12, 2019 and our other reports filed with the SEC could cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. Any such forward-looking statements represent management’s estimates as of the date of this press release. While we may elect to update such forward-looking statements at some point in the future, we disclaim any obligation to do so, even if subsequent events cause our views to change. These forward-looking statements should not be relied upon as representing our views as of any date subsequent to the date of this press release. ARCALYST® is a registered trademark of Regeneron Pharmaceuticals, Inc. Every Second Counts!™ Kiniksa Investor and Media Contact Mark Ragosa (781) 430-8289 mragosa@kiniksa.com Source: Kiniksa Pharmaceuticals, Ltd.