Royalty Pharma and Cytokinetics Announce Expanded Strategic Funding Collaboration Totaling Up to $575 Million to Support Commercial Launch of Aficamten and to Advance R&D Pipeline
Royalty Pharma and Cytokinetics Announce Expanded Strategic Funding Collaboration Totaling Up to $575 Million to Support Commercial Launch of Aficamten and to Advance R&D Pipeline
Deal provides Cytokinetics with diversified access to capital as company advances its specialty cardiology franchise
隨着公司推進其專業心臟病學特許經營權，該協議爲Cytokinetics提供了多元化的資本渠道
NEW YORK and SOUTH SAN FRANCISCO, Calif., May 22, 2024 (GLOBE NEWSWIRE) -- Royalty Pharma plc (Nasdaq: RPRX) and Cytokinetics, Incorporated (Nasdaq: CYTK) today announced they have entered into a strategic funding collaboration providing capital to support the commercialization of aficamten and advance the company's expanding cardiovascular pipeline while diversifying access to capital as the company advances its muscle biology-directed specialty cardiology business.
紐約和加利福尼亞州南舊金山，2024年5月22日（GLOBE NEWSWIRE）——Royalty Pharma plc（納斯達克股票代碼：RPRX）和Cytokinetics, Incorporated（納斯達克股票代碼：CYTK）今天宣佈，他們已達成戰略融資合作，提供資金以支持aficamten的商業化並推進公司不斷擴大的心血管產品線，同時隨着公司推進其肌肉生物學導向心臟專業的發展，實現資本渠道的多樣化學業務。
"We are excited to support Cytokinetics as the company advances towards commercialization of aficamten," said Pablo Legorreta, Royalty Pharma's founder and Chief Executive Officer. "This is our third transaction with Cytokinetics and highlights our ability to structure creative, win-win funding solutions and underscores the breadth of our funding capabilities. Aficamten has demonstrated an impressive clinical profile in its pivotal Phase 3 study, and we believe it has the potential to significantly improve the lives of patients with HCM, if approved by the FDA."
Royalty Pharma創始人兼首席執行官巴勃羅·萊戈雷塔表示：“隨着公司向aficamten商業化邁進，我們很高興能夠支持Cytokinetics。”“這是我們與Cytokinetics的第三筆交易，凸顯了我們構建創新、雙贏融資解決方案的能力，也凸顯了我們融資能力的廣度。Aficamten在其關鍵的3期研究中表現出了令人印象深刻的臨床特徵，我們相信，如果獲得美國食品藥品管理局的批准，它有可能顯著改善HCM患者的生活。”
"We have enjoyed a longstanding relationship with Royalty Pharma and this expanded strategic collaboration reinforces our shared conviction in the value of our cardiac myosin focused pipeline of drug candidates," said Robert I. Blum, Cytokinetics' President and Chief Executive Officer. "This diversified access to capital from a trusted partner supports our launch of aficamten while also fortifying our capital structure and lowering our cost of capital as we become a sustainable company. We believe this deal delivers on stated objectives of advancing our later-stage portfolio of potential medicines alongside our goal of increasing shareholder value."
Cytokinetics總裁兼首席執行官羅伯特·布魯姆表示：“我們與Royalty Pharma有着長期的合作關係，這種擴大的戰略合作增強了我們對以心肌球蛋白爲重點的候選藥物產品線價值的共同信念。”“這種從值得信賴的合作伙伴那裏獲得資金的多樣化渠道支持了我們推出aficamten，同時也鞏固了我們的資本結構，降低了我們的資本成本，使我們成爲一家可持續發展的公司。我們認爲，這筆交易實現了既定目標，即推進我們後期潛在藥物的產品組合，同時實現增加股東價值的目標。”
"Both omecamtiv mecarbil and CK-586 represent strategic opportunities to expand our specialty cardiology pipeline in adjacent cardiovascular indications and help underserved patients," said Fady I. Malik, M.D., Ph.D., Cytokinetics' Executive Vice President of Research & Development. "Building on feedback from the FDA and EMA, we have designed a confirmatory Phase 3 clinical trial intended to replicate treatment effects previously observed with omecamtiv mecarbil among higher risk patients with heart failure with reduced ejection fraction. In addition, we look forward to advancing CK-586 to Phase 2 to further assess the pharmacology of cardiac myosin inhibition in sicker patients with heart failure with preserved ejection fraction."
細胞動力學研究與開發執行副總裁法迪·馬利克醫學博士說：“omecamtiv mecarbil和 CK-586 都代表了擴大我們在鄰近心血管適應症中的專業心臟病學產品線並幫助得不到充分服務的患者的戰略機遇。”“根據美國食品藥品管理局和歐洲藥品管理局的反饋，我們設計了一項確認性的3期臨床試驗，旨在複製先前使用omecamtiv mecarbil在射血分數降低的高風險心力衰竭患者中觀察到的治療效果。此外，我們期待將 CK-586 推進到第 2 階段，以進一步評估射血分數保持不變的病情較重的心力衰竭患者心肌球蛋白抑制的藥理學。”
The transaction includes funding for planned commercialization, development funding, royalty restructuring and revenue sharing, and the purchase of Cytokinetics equity, together, affording Cytokinetics $250 million on closing and up to a total of $575 million to support the company's further maturation and corporate development.
該交易包括計劃商業化融資、開發融資、特許權使用費重組和收益分成，以及收購Cytokinetics股權，在收盤時共向Cytokinetics提供2.5億美元，總額爲5.75億美元，以支持公司的進一步成熟和企業發展。
The key components of this strategic funding collaboration include:
此次戰略籌資合作的關鍵組成部分包括：
1. Commercial launch funding: Cytokinetics to receive $50 million and is eligible to draw an additional $175 million within 12 months of approval of aficamten in oHCM; the capital will be repayable over 10 years in quarterly installments (totaling 1.9x).
1。商業啓動資金：Cytokinetics將獲得5000萬美元，並有資格在OHCM批准aficamten後的12個月內再提取1.75億美元；這筆資金將在10年內按季度分期償還（總額爲1.9倍）。
2. Royalty restructuring: Royalty Pharma's royalty on aficamten was restructured so that Royalty Pharma will now receive 4.5% up to $5.0 billion of annual net sales of aficamten and 1% above $5.0 billion of annual net sales compared to the prior 4.5% up to $1.0 billion of annual net sales and 3.5% above $1.0 billion of annual net sales.
2。特許權使用費重組：Royalty Pharma對aficamten的特許權使用費進行了重組，因此Royalty Pharma現在將獲得4.5％至50億美元的aficamten年淨銷售額，超過50億美元的年淨銷售額爲1％，而之前的年淨銷售額爲4.5％，高於10億美元。
3. Development funding: Cytokinetics will receive $100 million in upfront capital to fund a confirmatory Phase 3 clinical trial of omecamtiv mecarbil in patients with heart failure and reduced ejection fraction. If the Phase 3 clinical trial is positive and FDA approval is received within specified time frames, Royalty Pharma will receive fixed payments totaling $100 million following approval, as well as an incremental 2.0% royalty on annual net sales and/or fixed quarterly payments. If the Phase 3 trial is not successful or does not lead to FDA approval, Cytokinetics will repay Royalty Pharma up to $237.5 million over eighteen or twenty-two quarters, in fixed quarterly payments.
3.開發資金：Cytokinetics將獲得1億美元的前期資金，用於資助一項針對心力衰竭和射血分數降低患者的omecamtiv mecarbil的3期確認性臨床試驗。如果3期臨床試驗呈陽性並且在規定的時間範圍內獲得FDA的批准，則Royalty Pharma將在批准後獲得總額爲1億美元的固定付款，以及每年淨銷售額的2.0％增量特許權使用費和/或固定的季度付款。如果第三階段試驗不成功或未獲得美國食品藥品管理局的批准，Cytokinetics將在十八或二十二個季度內以固定的季度付款方式向特許權使用費製藥公司償還高達2.375億美元的款項。
Development funding: Cytokinetics to receive $50 million in upfront capital to fund a proof-of-concept Phase 2 clinical trial for CK-586 in patients with heart failure and preserved ejection fraction and Royalty Pharma will have an option to invest up to an additional $150 million to fund Phase 3 development of CK-586, for which it would be eligible to receive a $150 million milestone payment upon FDA approval and a 4.5% royalty on annual net sales of CK-586.
開發資金：Cytokinetics將獲得5000萬美元的前期資金，用於資助一項針對心力衰竭和射血分數保留患者的 CK-586 的概念驗證二期臨床試驗，Royalty Pharma將可以選擇額外投資高達1.5億美元來資助 CK-586 的第三階段開發，經美國食品藥品管理局批准，它將有資格獲得1.5億美元的里程碑式付款，以及CK-586 年淨銷售額4.5％的特許權使用費。
If Royalty Pharma does not opt-in to fund Phase 3 development, Royalty Pharma will receive a 1.0% royalty on annual net sales of CK-586.
如果Royalty Pharma不選擇爲第三階段的開發提供資金，則Royalty Pharma將獲得 CK-586 年淨銷售額的1.0％的特許權使用費。
4. Equity Purchase: Royalty Pharma will purchase $50 million of Cytokinetics' common stock in a private placement that will be concurrent with the underwritten public offering that Cytokinetics plans to launch today.
4。股權收購：Royalty Pharma將通過私募方式購買Cytokinetics的5000萬美元普通股，該配股將與Cytokinetics計劃於今天啓動的承銷公開發行同時進行。
From these transactions, Cytokinetics anticipates receipt of up to $250 million in nearer-term funding. Together with its proforma cash at the end of the first quarter of 2024, this funding from Royalty Pharma enables Cytokinetics extended cash runway based on expected 2024 expenditures, inclusive of planned commercialization activities and expanded pipeline development programs.
從這些交易中，Cytokinetics預計將獲得高達2.5億美元的近期融資。加上2024年第一季度末的預計現金，來自Royalty Pharma的這筆資金使Cytokinetics能夠根據2024年的預期支出（包括計劃中的商業化活動和擴大的管道開發計劃）延長現金流。
Advisors
顧問
Goodwin Procter LLP, Fenwick & West LLP, Maiwald GmbH, and Wolf, Greenfield & Sacks, P.C., acted as legal advisors to Royalty Pharma. Cooley LLP and Morrison & Foerster LLP acted as legal advisors to Cytokinetics on the transactions. Evercore served as a financial advisor to Cytokinetics on the transactions.
古德溫·寶潔律師事務所、芬威克和西部律師事務所、Maiwald GmbH和Wolf、Greenfield & Sacks, P.C. 擔任Royalty Pharma的法律顧問。Cooley LLP和Morrison & Foerster LLP擔任了Cytokinetics的交易法律顧問。Evercore曾擔任Cytokinetics的財務顧問，負責這些交易。
About Aficamten
關於 Aficamten
Aficamten is an investigational selective, small molecule cardiac myosin inhibitor discovered following an extensive chemical optimization program that was conducted with careful attention to therapeutic index and pharmacokinetic properties and as may translate into next-in-class potential in clinical development. Aficamten was designed to reduce the number of active actin-myosin cross bridges during each cardiac cycle and consequently suppress the myocardial hypercontractility that is associated with hypertrophic cardiomyopathy (HCM). In preclinical models, aficamten reduced myocardial contractility by binding directly to cardiac myosin at a distinct and selective allosteric binding site, thereby preventing myosin from entering a force producing state.
Aficamten是一種在研的選擇性小分子心肌球蛋白抑制劑，是經過廣泛的化學優化計劃後發現的，該計劃在仔細關注治療指數和藥代動力學特性後發現，這可能會轉化爲臨床開發中的下一代潛力。Aficamten旨在減少每個心臟週期中活性肌動蛋白-肌球蛋白交叉橋的數量，從而抑制與肥厚型心肌病（HCM）相關的心肌收縮過度。在臨床前模型中，aficamten通過在不同的選擇性變構結合位點直接與心肌球蛋白結合來降低心肌收縮力，從而防止肌球蛋白進入力產生狀態。
The development program for aficamten is assessing its potential as a treatment that improves exercise capacity and relieves symptoms in patients with HCM as well as its potential long-term effects on cardiac structure and function.
aficamten的開發計劃正在評估其作爲一種治療方法的潛力，可以改善HCM患者的運動能力和緩解症狀，以及其對心臟結構和功能的潛在長期影響。
Aficamten was evaluated in SEQUOIA-HCM (Safety, Efficacy, and Quantitative Understanding of Obstruction Impact of Aficamten in HCM), a positive pivotal Phase 3 clinical trial in patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM). Aficamten received Breakthrough Therapy Designation for the treatment of symptomatic obstructive HCM from the U.S. Food & Drug Administration (FDA) as well as the National Medical Products Administration (NMPA) in China. Cytokinetics expects to submit a New Drug Application (NDA) to the FDA in Q3 2024 and a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) in Q4 2024.
SEQUOIA-HCM（對Aficamten對HCM的梗阻影響的定量理解）對Aficamten進行了評估，這是一項針對症狀性梗阻性肥厚型心肌病（HCM）患者的積極的關鍵性3期臨床試驗。Aficamten獲得了美國食品藥品監督管理局（FDA）和中國國家藥品監督管理局（NMPA）頒發的用於治療有症狀阻塞性HCM的突破性療法稱號。Cytokinetics預計將在2024年第三季度向美國食品藥品管理局提交新藥申請（NDA），並在2024年第四季度向歐洲藥品管理局（EMA）提交上市許可申請（MAA）。
About Omecamtiv Mecarbil
關於 Omecamtiv Mecarbil
Omecamtiv mecarbil is an investigational, selective, small molecule cardiac myosin activator, the first of a novel class of myotropes1 designed to directly target the contractile mechanisms of the heart, binding to and recruiting more cardiac myosin heads to interact with actin during systole. Omecamtiv mecarbil is designed to increase the number of active actin-myosin cross bridges during each cardiac cycle and consequently augment the impaired contractility that is associated with heart failure with reduced ejection fraction (HFrEF). Preclinical research has shown that omecamtiv mecarbil increases cardiac contractility without increasing intracellular myocyte calcium concentrations or myocardial oxygen consumption.2-4
Omecamtiv mecarbil 是一種在研的選擇性小分子心肌球蛋白激活劑，是新一類新型 myotropes1 中的第一種，旨在直接靶向心髒的收縮機制，結合並招募更多的心肌球蛋白頭在收縮期期間與肌動蛋白相互作用。Omecamtiv mecarbil 旨在增加每個心臟週期中活性肌動蛋白-肌球蛋白交叉橋的數量，從而通過降低射血分數 (HFref) 來增強與心力衰竭相關的收縮力受損。臨床前研究表明，omecamtiv mecarbil 可在不增加細胞內肌細胞鈣濃度或心肌耗氧量的情況下增加心臟收縮力。2-4
The development program for omecamtiv mecarbil assessed its potential for the treatment of HFrEF. Positive results from GALACTIC-HF demonstrated a statistically significant effect of treatment with omecamtiv mecarbil to reduce risk of the primary composite endpoint of cardiovascular (CV) death or heart failure events (heart failure hospitalization and other urgent treatment for heart failure) compared to placebo in patients treated with standard of care Adverse events and treatment discontinuation of study drug were balanced between the treatment arms.
omecamtiv mecarbil的開發計劃評估了其治療HFref的潛力。GALACTIC-HF的陽性結果表明，與安慰劑相比，使用omecamtiv mecarbil治療對降低心血管（CV）死亡或心力衰竭事件（心力衰竭住院和其他心力衰竭緊急治療）的主要複合終點風險具有統計學上的顯著效果。治療組之間平衡了研究藥物的不良事件和停藥情況。
In February 2023, the U.S. Food and Drug Administration (FDA) issued a Complete Response Letter (CRL) regarding the New Drug Application (NDA) for omecamtiv mecarbil, stating that GALACTIC-HF was not sufficiently persuasive to establish substantial evidence of effectiveness for reducing the risk of heart failure events and cardiovascular death in adults with chronic heart failure with reduced ejection fraction, in lieu of evidence from at least two adequate and well-controlled clinical investigations. In May 2024, Cytokinetics withdrew the Marketing Authorization Application (MAA) from the European Medicines Agency (EMA) for omecamtiv mecarbil based on feedback from the Committee for Medicinal Products for Human Use (CHMP) indicating that the Committee would not be able to conclude that the benefits outweigh the risks on the basis of the results from GALACTIC-HF alone. Cytokinetics is planning to start an additional Phase 3 trial of omecamtiv mecarbil in Q4 2024 in advanced HFrEF patients with objective to confirm and elaborate on positive results previously observed in GALACTIC-HF.
2023年2月，美國食品藥品監督管理局（FDA）發佈了關於omecamtiv mecarbil新藥申請（NDA）的完整回覆信（CRL），稱GALACTIC-HF的說服力不足以確立實質性證據，證明射血分數降低的慢性心力衰竭的成年人發生心力衰竭和心血管死亡的風險是有效的，而不是來自至少兩個足夠和控制良好的臨床研究。2024年5月，Cytokinetics撤回了歐洲藥品管理局（EMA）對omecamtiv mecarbil的上市許可申請（MAA），理由是人用藥品委員會（CHMP）的反饋表明，該委員會無法僅憑GALACTIC-HF的結果得出收益大於風險的結論。Cytokinetics計劃在2024年第四季度啓動一項針對晚期HFreF患者的Omecamtiv mecarbil的額外3期試驗，目的是確認和詳細說明先前在GALACTIC-HF中觀察到的陽性結果。
About CK-4021586 (CK-586)
關於 CK-4021586 (CK-586)
CK-4021586 (CK-586) is a novel, selective, oral, small molecule cardiac myosin inhibitor designed to reduce the hypercontractility associated with heart failure with preserved ejection fraction (HFpEF). In preclinical models, CK-586 reduced cardiac hypercontractility by decreasing the number of active myosin cross-bridges during cardiac contraction thereby reducing the contractile force, without effect on calcium transients. In some patients, HFpEF is a condition that resembles non-obstructive hypertrophic cardiomyopathy (HCM) in that the patients have higher ejection fractions, thickened walls of their heart, elevated biomarkers, and symptoms of heart failure. In a Phase 2 clinical trial in patients with non-obstructive HCM, aficamten, a cardiac myosin inhibitor also developed by the Company, was well tolerated, improved patient reported outcomes (Kansas City Cardiomyopathy Questionnaire (KCCQ) and New York Heart Association (NYHA) Functional Class) and biomarkers, measures that are also relevant to HFpEF, lending support for this mechanism of action in HFpEF.
CK-4021586（CK-586）是一種新型的選擇性口服小分子心肌球蛋白抑制劑，旨在通過保留射血分數（HfpEF）來降低與心力衰竭相關的過度收縮力。在臨床前模型中，CK-586 通過減少心臟收縮期間活性肌球蛋白交叉橋的數量來降低心臟過度收縮力，從而降低收縮力，而不會影響鈣瞬變。在某些患者中，HfpEF是一種類似於非阻塞性肥厚型心肌病（HCM）的疾病，因爲患者的射血分數更高，心壁變厚，生物標誌物升高，並且有心力衰竭的症狀。在一項針對非阻塞性HCM患者的2期臨床試驗中，同樣由該公司開發的心肌球蛋白抑制劑aficamten的耐受性良好，患者報告的預後（堪薩斯城心肌病問卷（KCCQ）和紐約心臟協會（NYHA）功能類別）和生物標誌物，這些指標也與HFPEF有關，爲HFPEF中的這種作用機制提供了支持 F。
The Phase 1 study of CK-586 met its primary endpoint and secondary objectives, demonstrating that CK-586 was safe and well-tolerated in healthy participants with linear pharmacokinetics. These data are supportive of advancing CK-586 to a Phase 2 clinical trial in patients with HFpEF which is expected to begin in Q4 2024.
CK-586 的 1 期研究達到了其主要終點和次要目標，表明 CK-586 對具有線性藥代動力學的健康參與者是安全且耐受性良好。這些數據支持將 CK-586 推進到針對HfpEF患者的2期臨床試驗，該試驗預計將於2024年第四季度開始。
References:
參考文獻：
Psotka MA, Gottlieb SS, Francis GS et al. Cardiac Calcitropes, Myotropes, and Mitotropes. JACC. 2019; 73:2345-53.
Planelles-Herrero VJ, Hartman JJ, Robert-Paganin J. et al. Mechanistic and structural basis for activation of cardiac myosin force production by omecamtiv mecarbil. Nat Commun. 2017;8:190.
Shen YT, Malik FI, Zhao X, et al. Improvement of cardiac function by a cardiac myosin activator in conscious dogs with systolic heart failure. Circ Heart Fail. 2010; 3: 522-27.
Malik FI, Hartman JJ, Elias KA, Morgan BP, Rodriguez H, Brejc K, Anderson RL, Sueoka SH, Lee KH, Finer JT, Sakowicz R. Cardiac myosin activation: a potential therapeutic approach for systolic heart failure. Science. 2011 Mar 18;331(6023):1439-43.
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Planelles-Herrero VJ、Hartman JJ.、Robert-Paganin J. 等omecamtiv mecarbil 激活心肌球蛋白產生的機制和結構基礎。Nat Commun. 2017；8:190。
Shen YT、Malik FI、Zhao X 等通過心肌球激活劑改善有收縮期心力衰竭的有意識的狗的心臟功能。Circ Heart Fail. 2010; 3:522-27。
Malik FI、Hartman JJ、Elias KA、Morgan BP、Rodriguez H、Brejc K、安德森 RL、Sueoka SH、Lee KH、Finer JT、Sakowicz R. 心臟肌球蛋白激活：收縮期心力衰竭的潛在治療方法。科學。2011 年 3 月 18 日；331 (6023): 1439-43。
譯文內容由第三人軟體翻譯。