Ji Xing Pharmaceuticals Co., Ltd.

Primary endpoint was met with 74% of participants dosed with LNZ100 achieving three-lines or greater improvement at 3 hours post treatment，and maintaining their optimal distance visual acuity (i.e., not losing 5 or more letters). The difference in efficacy was statistically significant in the LNZ100 treatment group compared to the vehicle group (p<0.0001) Rapid onset and long duration shown with 69% of participants achieving three-lines or greater improvement at 30 minutes and 30% at 10 hours 91% of participants indicated they noticed an improvement in their near vision LNZ100 could potentially be the best-in-class non-invasive treatment for presbyopia SHANGHAI, China and SAN DIEGO, Oct. 27, 2024 (GLOBE NEWSWIRE) -- Corxel Pharmaceuticals (CORXEL) and LENZ Therapeutics (Nasdaq: LENZ) today announced positive topline data from the Phase 3 JX07001 clinical trial of LNZ100 in patients with presbyopia in China. CORXEL is a leading biotech company committed to bringing innovative science and medicines to underserved patients with serious and life-threatening diseases. LENZ Therapeutics is a pre-commercial biopharmaceutical company focused on developing the first and only aceclidine-based eye drop to improve near vision in people with presbyopia. In this China Phase 3 safety and efficacy trial, LNZ100 (1.75% aceclidine HCl) achieved the primary endpoint and key secondary endpoints, with statistically significant three-lines or greater improvement in Best Corrected Distance Visual Acuity (BCDVA) at near, and maintaining their optimal distance visual acuity (i.e., not losing 5 or more letters). More results showed (all p<0.0001): Rapid onset: 84% and 69% achieved two-lines and three-lines or greater improvement at 30 minutes respectively.3 hours post treatment: 88% and 74% achieved two-lines and three-lines or greater improvement at 3 hours respectively，and maintained their optimal distance visual acuity (i.e., not losing 5 or more letters).Long duration: 61% and 30% achieved two-lines and three-lines or greater improvement at 10 hours respectively. LNZ100 was well-tolerated with no serious treatment-related adverse events observed in the trial. The study was a Phase 3, multicenter, randomized, double-blind, vehicle-controlled study, including a 4-week efficacy study followed by a 5-month extension safety study, designed to evaluate the efficacy and safety of LNZ100 (an aceclidine-based ophthalmic solution) in participants with presbyopia. The objectives were to assess the potential of LNZ100 to improve near vision among Chinese presbyopia patients and to evaluate the efficacy and safety profiles.  The trial has enrolled 300 participants, with a broad enrollment criteria of between 45 and 75 years of age with a refractive range of -4.0D SE to +1.0D SE, including those who had undergone laser-assisted cornea refractive surgery/monofocal IOL implantation. Professor Jia Qu, Principal Investigator and Co-Principal Investigator，Vice Chairman of Ophthalmology Branch, Chinese Medical Association, Director of optometry department, Wenzhou Medical University said: “we are very pleased with the results of the LNZ100 trial, particularly the significant efficacy and favorable safety profile of LNZ100 in patients with presbyopia, demonstrating an important advance in the field of presbyopia treatment in China. Currently, patients mainly rely on wearing eyeglasses as treatment for presbyopia. There is a large unmet need for non-invasive and reversible treatments. We expect that LNZ100 will fill this vacuum and become an innovative force in the treatment of presbyopia in China, providing more patients with the hope of clear vision." Professor Fan Lyu, Principal Investigator and Co-Principal Investigator，Head of optometry working-group under Ophthalmology Branch, Chinese Medical Association, Director of National Clinical Medical Research Centre for Eye Diseases said: "The main active ingredient of LNZ100, aceclidine, causes temporary pupil constriction, resulting in an optical effect that significantly extends the depth of focus and improves the quality of vision. The statistically significant data and clinically meaningful outcomes observed in the trials provide strong support for the efficacy and safety of LNZ100. We anticipate that LNZ100 will be a practical treatment option for a wide spectrum of patients and will have a favorable impact on paradigm shift of helping improve near-vision in the Chinese presbyopia population. “We are especially grateful to all the hard-working and dedicated researchers, partner organizations and all the volunteers who participated in the study,” Sandy Mou, Board Executive Director and Chief Executive Officer of CORXEL, said. “The common goal is to benefit hundreds of millions of people around the world, to set an international leading research benchmark, and to introduce novel treatment concepts and potentially optimal products to China first, providing a safe and convenient treatment option for the vast number of presbyopia patients. Looking ahead, we will actively communicate and cooperate with drug regulatory authorities to expedite the submission and approval of LNZ100. We believe that LNZ100 will not only significantly improve patients' vision and quality of life, but will also have a profound impact on the field of presbyopia treatment and research in China.” “We would like to first congratulate the team at CORXEL for their effort in their Phase 3 clinical study in China. We are pleased with the impressive and consistent performance demonstrated by LNZ100 in our collective studies, further validating the vision of targeting an ‘all eyes, all day’ solution,” said Eef Schimmelpennink, President and Chief Executive Officer of LENZ Therapeutics. “With this data, we believe LNZ100 has further enhanced its potential as a global therapy and is further on its path towards providing access to the estimated 400 million people with presbyopia in China. This data signifies a tremendous joint effort between the CORXEL and LENZ teams and comes in rapid succession to the recent FDA acceptance of our New Drug Application for LNZ100 in the United States.” About PresbyopiaPresbyopia is a physiological phenomenon associated with aging that results in a progressively worsening ability to see nearby objects clearly. It is caused by the gradual hardening of the lens. This results in a decline of the eye's adjustment function, and the inability to focus the image of nearby objects on the retina, leading to a decline in near vision. Studies have shown that the onset of presbyopia typically occurs around the age of 38, reaching a prevalence rate of nearly 100 percent at the age of 52 in China. It is estimated that more than 400 million people in China suffer from presbyopia.  Currently, the treatment options for presbyopia are very limited. Wearing glasses requires frequent removal and insertion, causing many inconveniences in work and life. Surgery, as an irreversible invasive operation, has a very limited acceptance. There are no approved drugs for the treatment of presbyopia in China and the medical need for non-invasive, safe, efficient and reversible treatments for presbyopia remains unsolved.  About LNZ100LNZ100 (aceclidine) eye drops are being developed by LENZ Therapeutics and CORXEL acquired the Greater China rights for the development and commercialization in April 2022. LNZ100 is formulated with aceclidine, a miotic, and designed to achieve optimal pupil diameter without impacting distance vision, a key limitation of other miotics. Miotics are compounds that cause pupil constriction, or miosis, creating a pinhole effect that enables better focus of incoming light from near objects onto the retina. Research has shown that a pupil diameter below two millimeters (2 mm) is optimal for presbyopia treatment and results in clinically meaningful improvement in near vision. Unlike other miotics such as pilocarpine and carbachol, aceclidine’s mechanism of action is pupil-selective, meaning it can activate the iris sphincter muscle and cause miosis of the pupil to a diameter below 2 mm without overstimulating the ciliary muscles that can cause a myopic shift and impair distance vision. As a result, aceclidine does not require any remaining accommodation to improve near vision, broadening its benefits to older presbyopes whose lens has lost this capacity. Therefore, we expect that users may be able to benefit from treatment even as they age from mid-40s to well into their mid-70s and across a broad range of refractive errors, as demonstrated in clinical testing to date. About CORXELCORXEL, formerly named Ji Xing Pharmaceuticals, is a leading biotech company headquartered in US and China committed to bringing innovative science and medicines to underserved patients with serious and life-threatening cardiometabolic diseases. Backed by RTW Investments, CORXEL was founded in 2019 to develop and commercialize novel, innovative therapeutics to treat unmet medical needs in diseases. With a strong and further developing asset pipeline, industry leading talent, and patient-centric focus, CORXEL is dedicated to deliver a meaningful and lasting impact on patients. The full portfolio of CORXEL consists of 2 assets with global rights and 4 assets with Greater China rights in late-stage clinical development. The portfolio with global rights are JX09 for hypertension and JX10 for acute ischemic stroke (AIS), while the portfolio with Greater China rights include aficamten, etripamil, varenicline solution nasal spray/US brand name TYRVAYA®, and LNZ100. For further information about CORXEL, please visit www.corxelbio.com.   About LENZ TherapeuticsLENZ Therapeutics is a pre-commercial biopharmaceutical company focused on the development and commercialization of the first and only aceclidine-based eye drop to improve near vision in patients with presbyopia. LENZ’s product candidate, LNZ100 is a preservative-free, single-use, once-daily eye drop containing aceclidine. LNZ100 was evaluated in the registration-enabling Phase 3 CLARITY study as a potential therapy for the treatment of presbyopia, a condition impacting an estimated 1.8 billion people globally and 128 million people in the United States. The U.S. Food and Drug Administration (FDA) has assigned a Prescription Drug User Fee Act (PDUFA) target action date of August 8, 2025 for LNZ100. LENZ is committed to commercializing an ideal pharmaceutical presbyopia solution that enhances vision for “all eyes, all day”. LENZ is headquartered in San Diego, California. For more information, visit: LENZ-Tx.com. Forward-Looking StatementsThis press release contains forward-looking statements within the meaning of United States federal securities laws. You can identify forward-looking statements by words such as “may,” “will,” “could,” “can,” “would,” “should,” “expect,” “intend,” “plan,” “anticipate,” “believe,” “estimate,” “predict,” “project,” “potential,” “poised,” “continue,” “ongoing” or the negative of these terms or other comparable terminology, but not all forward-looking statements will contain these words. Forward-looking statements in this press release include, but are not limited to, statements regarding the potential of LNZ100 to have best-in-class performance and LNZ100 as a global therapy; the size of the addressable population for LNZ100; expectations regarding the commercial opportunity and beneficial characteristics of LNZ100; and plans and expectations regarding commercialization of LNZ100, if approved. These statements are based on numerous assumptions concerning the development of LENZ’s products and target markets and involve substantial risks, uncertainties and other factors that may cause actual results, levels of activity, performance or achievement to be materially different from the information expressed or implied by these forward-looking statements, including those risk factors described in the section titled “Risk Factors” in LENZ’s Quarterly Report on Form 10-Q filed for the quarter ended June 30, 2024 and in LENZ’s subsequent filings with the SEC. LENZ cannot assure you that the forward-looking statements in this press release or the assumptions upon which they are based will prove to be accurate. The forward-looking statements in this press release are as of the date of this press release. Except as otherwise required by applicable law, LENZ disclaims any duty to update any forward-looking statements. You should, therefore, not rely on these forward-looking statements as representing our views as of any date subsequent to the date of this press release. LENZ Therapeutics Contact: Dan Chevallard IR@LENZ-Tx.com

Sept. 06, 2024 -- Milestone® Pharmaceuticals Inc. (Nasdaq: MIST), a biopharmaceutical company focused on the development and commercialization of innovative cardiovascular medicines, today announced its licensing partner, Ji Xing Pharmaceuticals Ltd, released positive topline results from a multi-center, randomized, double-blind, placebo-controlled trial in China evaluating the efficacy and safety of etripamil nasal spray in paroxysmal supraventricular tachycardia (PSVT). The trial design closely matched the RAPID Phase 3 Study of etripamil in PSVT conducted by Milestone in North America and Europe. The 500-patient Phase 3 trial (JX02002) met its primary endpoint, with a Kaplan Meier analysis shows a statistically significantly greater proportion of patients who self-administered etripamil converted from PSVT to sinus rhythm within 30 minutes compared to placebo (40.5% vs. 15.9%, respectively; hazard ratio [HR] = 3.00; 95% CI 1.58-5.71; p<0.001). Statistically significant (p<0.05) results were also shown for the secondary efficacy endpoints for percent of patients’ PSVT converted to sinus rhythm by 10, 15, 45, and 60 minutes after self-administration of study drug. Ji Xing further reported that, overall, treatment emergent adverse events were comparable between treatment groups, and there were no reported serious adverse events related to etripamil. The safety and tolerability data from the JX02002 trial were consistent with previous clinical studies. This important study further expands the etripamil global development program to more than 2,000 unique patients treated with etripamil. "Congratulations to Ji Xing and all the clinical investigators on the successful completion of this large Phase 3 study of etripamil in PSVT," said Joseph Oliveto, President and Chief Executive Officer of Milestone Pharmaceuticals. "We are proud to partner with our colleagues at Ji Xing as they advance etripamil toward regulatory approval in China, with the potential to help millions of patients struggling with PSVT." Under the terms of the license agreement announced on May 21, 2021, Milestone granted Ji Xing an exclusive license to develop and, if regulatory approval is obtained, commercialize etripamil in patients with PSVT in Greater China. Milestone received an upfront cash payment consisting of $15 million along with a $5 million equity investment by RTW Investments, LP. In addition, Milestone remains eligible to receive up to $107.5 million in milestone payments and royalties on future sales of etripamil in Greater China (including Mainland China, Hong Kong, Macau & Taiwan). Milestone supplies etripamil and delivery devices to Ji Xing. Ji Xing is responsible for development and commercialization costs in Greater China. An estimated two million people in the United States are currently diagnosed with PSVT which is a type of arrhythmia or abnormal heart rhythm. PSVT is characterized by episodes of sudden-onset rapid heartbeats often exceeding 150 to 200 beats per minute. The heart rate spike is unpredictable and may last several hours. The rapid heart rate often causes disabling severe palpitations, shortness of breath, chest discomfort, dizziness or lightheadedness, and distress, forcing patients to limit their daily activities. The uncertainty of when an episode of PSVT will strike or how long it will persist can provoke anxiety in patients and negatively impact their day-to-day life between episodes. The impact and morbidity from an attack can be especially detrimental in patients with underlying cardiovascular or medical conditions, such as heart failure, obstructive coronary disease, or dehydration. Many health care providers are dissatisfied with the lack of effective treatment options with patients often requiring prolonged, burdensome, and costly trips to the emergency department or even invasive cardiac ablation procedures. Etripamil is Milestone's lead investigational product. It is a novel calcium channel blocker nasal spray under clinical development for frequent and often highly symptomatic episodes of PSVT and atrial fibrillation with rapid ventricular rate (AFib-RVR). It is designed as a self-administered rapid response therapy for patients thereby bypassing the need for immediate medical oversight. If approved, etripamil is intended to provide health care providers with a new treatment option to enable on-demand care and patient self-management. This portable, self-administered treatment may provide patients with active management and a greater sense of control over their condition. CARDAMYST™ (etripamil) nasal spray, the conditionally approved brand name for etripamil nasal spray, is well studied with a robust clinical trial program that includes a completed Phase 3 clinical-stage program for the treatment of PSVT and Phase 2 trial for the treatment of patients with AFib-RVR. Milestone Pharmaceuticals Inc. (Nasdaq: MIST) is a biopharmaceutical company developing and commercializing innovative cardiovascular solutions to improve the lives of people living with complex and life-altering heart conditions. The Company’s focus on understanding unmet patient needs and improving the patient experience has led us to develop new treatment approaches that provide patients with an active role in self-managing their care. Milestone’s lead investigational product is etripamil, a novel calcium channel blocker nasal spray that is being studied for patients to self-administer without medical supervision to treat symptomatic episodic attacks associated with PSVT and AFib-RVR. 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Type B Meeting Held with FDA Related to Potential Risk Mitigation Strategies for Aficamten;Company Has Initiated Rolling NDA Submission FDA Cleared Protocol Amendment for FOREST-HCM Reducing Frequency ofEchocardiographic Monitoring Required During Maintenance Treatment ~$1.4 Billion in Cash, Cash Equivalents and Investments as of June 30, 2024 SOUTH SAN FRANCISCO, Calif., Aug. 08, 2024 (GLOBE NEWSWIRE) -- Cytokinetics, Incorporated (Nasdaq: CYTK) reported a management update and financial results for the second quarter of 2024. “Cytokinetics made substantial progress during the second quarter across our pipeline and aligned to near-term goals as well as our longer-term vision to build a sustainable specialty cardiology business. In May, we secured contingent access to more than $1 billion in funding to support the potential global launch of aficamten as well as to continue conduct of label-expanding clinical trials of aficamten worldwide and to advance our later-stage pipeline including omecamtiv mecarbil and CK-586,” said Robert I. Blum, Cytokinetics’ President and Chief Executive Officer. “These three programs, anchored in our pioneering science of myosin modulation, provide synergistic opportunities in adjacent specialty cardiology indications that we believe will unlock shareholder value while making good on our promise to patients.” Q2 and Recent Highlights Cardiac Muscle Programs aficamten (cardiac myosin inhibitor) Presented primary results from SEQUOIA-HCM (Safety, Efficacy, and Quantitative Understanding of Obstruction Impact of Aficamten in HCM) at the European Society of Cardiology Heart Failure 2024 Congress, demonstrating statistically significant and clinically meaningful improvements in the primary efficacy endpoint of peak oxygen uptake (pVO2) and all secondary endpoints with results consistent across all prespecified subgroups. Additional results presented from SEQUOIA-HCM showed that treatment with aficamten resulted in predictable dosing with no dose interruptions or associated heart failure due to left ventricular ejection fraction (LVEF) <50% and improved a novel integrated exercise performance metric. Improvements in pVO2 were shown to be highly correlated with improvements in cardiac structure and function. Participated in a Type B meeting with the U.S. Food and Drug Administration (FDA) to discuss potential strategies related to safety monitoring and risk mitigation for aficamten and included a review of how results from SEQUOIA-HCM and intrinsic properties of aficamten may inform risk mitigation. The Company expects to propose a distinct risk mitigation approach specific to aficamten with the New Drug Application (NDA) for which the rolling submission is underway. The Company is on track to complete the rolling NDA submission for aficamten in Q3 2024.The FDA recently cleared a protocol amendment for FOREST-HCM (Follow-up, Open-Label, Research Evaluation of Sustained Treatment with Aficamten in HCM) reducing the frequency of echocardiographic monitoring for patients with obstructive HCM to every 6 months during maintenance treatment for patients with LVEF >55%. Participated in meetings with the European Medicines Agency (EMA) and National Agencies in the EU during which the company confirmed plans to submit a Marketing Authorization Application (MAA) for aficamten in Q4 2024 and discussed the content of the expected filing. Coordinated with Ji Xing Pharmaceuticals to support the planned submission of an NDA for aficamten to the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) in China in 2H 2024.Continued commercial readiness activities for aficamten including refining our market development campaign, designing the treatment experience inclusive of distribution and patient support programs, advancing key market research, and finalizing the structure for the field-based sales team. Began pre-approval information exchange activities to proactively share health care economic and scientific information with payers and initiated development of U.S. and global value dossiers. Initiated a Phase 1 study evaluating the pharmacokinetics, safety and tolerability of aficamten in healthy Japanese and Caucasian participants. We expect to continue enrollment throughout 2024.Opened enrollment to CEDAR-HCM (Clinical Evaluation of Dosing with Aficamten to Reduce Obstruction in a Pediatric Population in HCM), a clinical trial of aficamten in a pediatric population with symptomatic obstructive HCM. We expect to continue enrollment in CEDAR-HCM throughout 2024.Continued enrolling patients in MAPLE-HCM (Metoprolol vs Aficamten in Patients with LVOT Obstruction on Exercise Capacity in HCM), the Phase 3 clinical trial comparing aficamten as monotherapy to metoprolol as monotherapy in patients with symptomatic obstructive HCM. We expect to complete enrollment in MAPLE-HCM in Q3 2024.Continued enrolling patients in ACACIA-HCM (Assessment Comparing Aficamten to Placebo on Cardiac Endpoints In Adults with Non-Obstructive HCM), the pivotal Phase 3 clinical trial of aficamten in patients with non-obstructive HCM. We expect to continue enrollment in ACACIA-HCM throughout 2024 and complete enrollment in 2025.Published the following manuscripts: “Aficamten for Symptomatic Obstructive Hypertrophic Cardiomyopathy” in the New England Journal of Medicine.“The Prognostic Value of Peak Oxygen Uptake in Obstructive Hypertrophic Cardiomyopathy: A Literature Review to Inform Economic Model Development” in the Journal of Medical Economics.“Safety and Efficacy of Aficamten in Patients with Non-Obstructive Hypertrophic Cardiomyopathy: A 36-Week Analysis from FOREST-HCM” in the European Journal of Heart Failure.“Aficamten is a Small-Molecule Cardiac Myosin Inhibitor Designed to Treat Hypertrophic Cardiomyopathy” in Nature Cardiovascular Research.“Dosing and Safety Profile of Aficamten in Symptomatic Obstructive Hypertrophic Cardiomyopathy: Results From SEQUOIA-HCM” in the Journal of the American Heart Association. omecamtiv mecarbil (cardiac myosin activator) Participated in a Type C meeting with the FDA that addressed design features of a confirmatory Phase 3 clinical trial of omecamtiv mecarbil with discussion of patient population, endpoints, as well as several additional pragmatic elements related to clinical trial conduct.Advanced preparations to conduct a confirmatory Phase 3 clinical trial of omecamtiv mecarbil in patients with heart failure with reduced ejection fraction (HFrEF) expected to start in Q4 2024. CK-4021586 (CK-586, cardiac myosin inhibitor) Announced topline data from the Phase 1 study of CK-586 and expect to present primary data in Q3 2024. Data from the Phase 1 study support progression to a Phase 2a clinical trial in patients with heart failure with preserved ejection fraction (HFpEF) which we expect to start in Q4 2024. CK-3828136 (CK-136, cardiac troponin activator) Completed analyses of the Phase 1 study of CK-136, which met its primary objective to assess the safety, tolerability and pharmacokinetics of single and multiple doses of CK-136 in healthy participants. Due to the Company’s strategic prioritization of its other clinical trial programs, further development of CK-136 has been discontinued. Pre-Clinical Development and Ongoing Research Continued pre-clinical development and research activities directed to additional muscle biology focused programs. In 2024, we expect to initiate Phase 1 clinical development of a fast skeletal troponin activator with potential therapeutic application to a specific type of muscular dystrophy. Corporate Hosted the inaugural CLIMB Research Symposium: Contemporary Landscapes In Muscle Biology, a one-day research symposium that brought scientists, researchers and emerging professionals together to share innovative research in the field of muscle biology. Second Quarter 2024 Financial Results Cash, Cash Equivalents and Investments As of June 30, 2024, the company had approximately $1.4 billion in cash, cash equivalents and investments compared to $634.3 million at March 31, 2024. In the second quarter, the company completed a public offering of 11,274,510 shares of its common stock which included the underwriters’ exercise in full of their option to purchase additional shares, raising approximately $563.2 million in net proceeds, after deducting underwriting discounts and commissions. On May 22, 2024, the company entered into a strategic funding collaboration with Royalty Pharma totaling up to $575 million to support the commercialization of aficamten and to advance the company’s expanding cardiovascular pipeline as the company advances its muscle biology-directed specialty cardiology business. The company received $250 million upon execution, including $100 million to fund a confirmatory Phase 3 trial of omecamtiv mecarbil, $50 million to fund a proof-of-concept Phase 2a clinical trial for CK-586, $50 million term loan to support the potential commercial launch of aficamten in obstructive HCM, and $50 million from the purchase of Cytokinetics’ common stock in a private placement. Under the terms of the collaboration, the company, at its option, can borrow up to $175 million upon satisfaction of certain conditions and receive up to $150 million investment in a Phase 3 clinical trial of CK-586 subject to Royalty Pharma exercising its option to participate in the funding of such a trial in exchange for an additional revenue interest in the net sales of CK-586. Revenues Total revenues for the second quarter of 2024 were $0.2 million compared to $0.9 million for the same period in 2023. Research and Development (R&D) Expenses R&D expenses for the second quarter of 2024 were $79.6 million which included $11.5 million of non-cash stock-based compensation expense, compared to $83.2 million for the same period in 2023 which included $8.2 million of non-cash stock-based compensation expense. The decrease was primarily driven by the timing of clinical trial activities and wind down activities for COURAGE-ALS which ended in the first quarter of 2023. General and Administrative (G&A) Expenses G&A expenses for the second quarter of 2024 were $50.8 million which included $13.1 million of non-cash stock-based compensation expense, compared to $39.7 million for the same period in 2023 which included $10.5 million in non-cash stock-based compensation expense. The increase was primarily driven by investments toward commercial readiness and personnel related expenses. Net Income (Loss) Net loss for the second quarter of 2024 was $143.3 million, or $(1.31) per share, basic and diluted, compared to a net loss of $128.6 million, or $(1.34) per share, basic and diluted, for the same period in 2023. 2024 Financial Guidance The company is updating its full year 2024 financial guidance: Current GuidancePrevious GuidanceGAAP Operating Expense[1]$555m to $575m$535m to $555mNon-cash Expense[2] Included in GAAP Operating Expense$110m to $105m$115m to $105mNon-GAAP Operating Expense[3]$445m to $470m$420m to $450mNet Cash Utilization[4]$400m to $420m$390m to $420m The financial guidance does not include the effect of GAAP adjustments caused by events that may occur subsequent to the publication of this guidance including but not limited to business development activities. [1]GAAP operating expense comprised of R&D and G&A expenses.[2]Non-cash operating expense comprised of stock-based compensation and depreciation.[3]Non-GAAP operating expense comprised of R&D and G&A expenses but excludes non-cash operating expense.[4]Net cash utilization is a non-GAAP financial measure that we define as our ending 2023 cash, cash equivalents, and investments balance of $655 million plus the net proceeds of $707 million received from the sale of common stock (through the at-the-market facility, public offerings, and stock purchase agreement with Royalty Pharma) plus proceeds of $200 million received from the structured financing agreement with Royalty Pharma announced on May 22, 2024 minus our projected ending 2024 cash, cash equivalents, and investments balance of between $1,142 million and $1,162 million. Conference Call and Webcast Information Members of Cytokinetics’ senior management team will review the company’s second quarter 2024 results on a conference call today at 4:30 PM Eastern Time. The conference call will be simultaneously webcast and can be accessed from the Investors & Media section of Cytokinetics’ website at www.cytokinetics.com. The live audio of the conference call can also be accessed by telephone by registering in advance at the following link: Cytokinetics Q2 2024 Earnings Conference Call. Upon registration, participants will receive a dial-in number and a unique passcode to access the call. An archived replay of the webcast will be available via Cytokinetics’ website for twelve months. About Cytokinetics Cytokinetics is a late-stage, specialty cardiovascular biopharmaceutical company focused on discovering, developing and commercializing muscle biology directed drug candidates as potential treatments for debilitating diseases in which cardiac muscle performance is compromised. As a leader in muscle biology and the mechanics of muscle performance, the company is developing small molecule drug candidates specifically engineered to impact myocardial muscle function and contractility. Cytokinetics is preparing for regulatory submissions for aficamten, its next-in-class cardiac myosin inhibitor, following positive results from SEQUOIA-HCM, the pivotal Phase 3 clinical trial in obstructive hypertrophic cardiomyopathy which were published in the New England Journal of Medicine. Aficamten is also currently being evaluated in MAPLE-HCM, a Phase 3 clinical trial of aficamten as monotherapy compared to metoprolol as monotherapy in patients with obstructive HCM, ACACIA-HCM, a Phase 3 clinical trial of aficamten in patients with non-obstructive HCM, CEDAR-HCM, a clinical trial of aficamten in a pediatric population with obstructive HCM, and FOREST-HCM, an open-label extension clinical study of aficamten in patients with HCM. Cytokinetics is also developing omecamtiv mecarbil, a cardiac muscle activator, in patients with heart failure. Additionally, Cytokinetics is developing CK-586, a cardiac myosin inhibitor with a mechanism of action distinct from aficamten for the potential treatment of HFpEF. For additional information about Cytokinetics, visit www.cytokinetics.com and follow us on X, LinkedIn, Facebook and YouTube. Forward-Looking Statements This press release contains forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995 (the “Act”). Cytokinetics claims the protection of the Act’s Safe Harbor for forward-looking statements. Examples of such statements include, but not limited to, statements, express or implied, relating to our or our partners’ research and development and commercial readiness activities, including the initiation, conduct, design, enrollment, progress, continuation, completion, timing and results of any of our clinical trials, or more specifically, our ability to file a new drug application for aficamten in the United States in the third quarter of 2024 or a marketing authorisation application for aficamten in the European Union in the fourth quarter of 2024, our ability to complete enrollment of MAPLE-HCM in the third quarter of 2024, our ability to complete enrollment of ACACIA-HCM in 2025, our ability to start a new Phase 3 confirmatory trial of omecamtiv mecarbil in the fourth quarter of 2024, and to commence a Phase 2a study of CK-586, if ever, the timing of interactions with FDA or any other regulatory authorities in connection to any of our drug candidates and the outcomes of such interactions; statements relating to the potential patient population who could benefit from aficamten, omecamtiv mecarbil, CK-586, CK-136 or any of our other drug candidates; statements relating to our ability to receive additional capital or other funding, including, but not limited to, our ability to meet any of the conditions relating to or to otherwise secure additional loan disbursements under any of our agreements with entities affiliated with Royalty Pharma or additional milestone payments from Ji Xing; statements relating to our operating expenses or cash utilization for the remainder of 2024, and statements relating to our cash balance at year-end 2024 or any other particular date or the amount of cash runway such cash balances represent at any particular time. Such statements are based on management's current expectations, but actual results may differ materially due to various risks and uncertainties, including, but not limited to Cytokinetics’ need for additional funding and such additional funding may not be available on acceptable terms, if at all; potential difficulties or delays in the development, testing, regulatory approvals for trial commencement, progression or product sale or manufacturing, or production of Cytokinetics’ drug candidates that could slow or prevent clinical development or product approval; patient enrollment for or conduct of clinical trials may be difficult or delayed; the FDA or foreign regulatory agencies may delay or limit Cytokinetics’ or its partners’ ability to conduct clinical trials; Cytokinetics may incur unanticipated research and development and other costs; standards of care may change, rendering Cytokinetics’ drug candidates obsolete; and competitive products or alternative therapies may be developed by others for the treatment of indications Cytokinetics’ drug candidates and potential drug candidates may target. For further information regarding these and other risks related to Cytokinetics’ business, investors should consult Cytokinetics’ filings with the Securities and Exchange Commission, particularly under the caption “Risk Factors” in Cytokinetics’ Annual Report on Form 10-K for the year 2023. Forward-looking statements are not guarantees of future performance, and Cytokinetics’ actual results of operations, financial condition and liquidity, and the development of the industry in which it operates, may differ materially from the forward-looking statements contained in this press release. Any forward-looking statements that Cytokinetics makes in this press release speak only as of the date of this press release. Cytokinetics assumes no obligation to update its forward-looking statements whether as a result of new information, future events or otherwise, after the date of this press release. CYTOKINETICS® and the CYTOKINETICS and C-shaped logo are registered trademarks of Cytokinetics in the U.S. and certain other countries. Contact:Cytokinetics Diane WeiserSenior Vice President, Corporate Affairs(415) 290-7757 Cytokinetics, IncorporatedCondensed Consolidated Balance Sheets(in thousands) June 30, 2024 December 31, 2023 (unaudited) ASSETS Current assets: Cash and short term investments $1,056,775 $614,824 Other current assets 11,035 13,227 Total current assets 1,067,810 628,051 Long-term investments 305,361 40,534 Property and equipment, net 65,689 68,748 Operating lease right-of-use assets 77,249 78,987 Other assets 7,679 7,996 Total assets $1,523,788 $824,316 LIABILITIES AND STOCKHOLDERS’ EQUITY (DEFICIT) Current liabilities: Accounts payable and accrued liabilities $49,283 $64,148 Short-term operating lease liabilities 18,507 17,891 Current portion of long-term debt 11,520 10,080 Derivative liabilities measured at fair value 13,200 — Other current liabilities 10,267 10,559 Total current liabilities 102,777 102,678 Term loan, net 92,831 58,384 Convertible notes, net 550,600 548,989 Liabilities related to revenue participation right purchase agreements, net 435,112 379,975 Long-term operating lease liabilities 116,718 120,427 Liabilities related to RPI Transactions measured at fair value 117,200 — Other non-current liabilities — 186 Total liabilities 1,415,238 1,210,639 Commitments and contingencies Stockholders’ equity (deficit): Common stock 117 102 Additional paid-in capital 2,500,654 1,725,823 Accumulated other comprehensive loss (1,022) (10)Accumulated deficit (2,391,199) (2,112,238)Total stockholders’ equity (deficit) 108,550 (386,323)Total liabilities and stockholders’ equity (deficit) $1,523,788 $824,316 Cytokinetics, IncorporatedCondensed Consolidated Statements of Operations(in thousands except per share data)(unaudited) Three Months Ended June 30, 2024 June 30, 2023Revenues: Research and development revenues $249 $867 Milestone revenues — — Total revenues 249 867 Operating expenses: Research and development 79,597 83,194 General and administrative 50,824 39,722 Total operating expenses 130,421 122,916 Operating loss (130,172) (122,049)Interest expense (12,732) (7,045)Non-cash interest expense on liabilities related to revenue participation right purchase agreements (11,567) (6,322)Interest and other income, net 11,553 6,779 Change in fair value of derivative liabilities (600) — Change in fair value of liabilities related to RPI Transactions 200 — Net loss $(143,318) $(128,637)Net loss per share — basic and diluted $(1.31) $(1.34)Weighted-average number of shares used in computing net loss per share — basic and diluted 109,240 95,755