Hypertrophy, Left Ventricular

Commercial launch of INPEFA® (sotagliflozin) continues to progress. with increasing demand across the cardiology community and improving payer access Patient enrollment underway in PROGRESS, a Phase 2b study of LX9211 in Diabetic Peripheral Neuropathic Pain; topline data anticipated Q2 2025 Preparations underway for Phase 3 study of sotagliflozin in Hypertrophic Cardiomyopathy and resubmission of NDA for sotagliflozin in Type 1 Diabetes Recent Successful Capital Raise Supports Company Initiatives for Growth and Expansion Company to Present at the Leerink Partners Global Biopharma Conference Tuesday, March 12th at 3:40 p.m. ET THE WOODLANDS, Texas, March 11, 2024 (GLOBE NEWSWIRE) -- Lexicon Pharmaceuticals, Inc. (Nasdaq: LXRX), today reported financial results for the three months ended December 31, 2023 and provided an update on key corporate milestones. “2023 was a pivotal year for Lexicon,” said Lonnel Coats, Lexicon’s chief executive officer. “We launched INPEFA within weeks of receiving U.S. FDA approval with a broad label for heart failure, while in parallel continuing the advancement of our innovative research and development pipeline.” “In the fourth quarter, we saw continued progress on the launch of INPEFA and began to see increased prescriber demand and important formulary wins, which we expect to accelerate in the first half of 2024. We advanced LX9211 into late-stage development for diabetic peripheral neuropathic pain (DPNP), with the potential to become the first new, non-opioid drug approved for neuropathic pain in over two decades.” “We are preparing for Phase 3 development of sotagliflozin in hypertrophic cardiomyopathy (HCM), an area of high unmet need with very few treatments in development. And following recent feedback from FDA, we are preparing to resubmit our New Drug Application (NDA) for sotagliflozin as an adjunct to insulin therapy in patients with type 1 diabetes and chronic kidney disease. Our research and development engine also continues to produce, and we are conducting preclinical development on an oral small molecule compound for obesity and weight management. With these opportunities and the support from shareholders in our recent successful financing, Lexicon is well positioned for growth and expansion in 2024 and beyond.” Fourth Quarter Highlights INPEFA® (sotagliflozin) Launch Progress INPEFA was placed on the formularies of multiple important Medicare and commercial plans during the fourth quarter, including Express Scripts’ Premier Access and Premier Performance national formularies for Medicare patients and Basic and High Performance formularies for commercially insured patients. Publications and Data On October 4, Craig Granowitz, M.D., Ph.D., Lexicon’s senior vice president and chief medical officer, conducted an oral presentation entitled Temporal shift in heart failure medications prescribed to hospitalised patients with and without diabetes in a large US integrated health system at the 59th Annual Meeting of European Association for the Study of Diabetes (EASD) in Hamburg, Germany and online. On October 8, Michael J. Davies, Ph.D., Lexicon’s executive director of clinical development, presented a new analysis of clinical trial data for sotagliflozin entitled Sotagliflozin Reduces the Risk of Cardiovascular Events In Patients With Left Ventricular Hypertrophy Without Hypertension: A Post Hoc Analysis From SCORED at the Heart Failure Society of America (HFSA) Annual Scientific Meeting in Cleveland, Ohio. On November 12, 2023, Lexicon had a significant presence and conducted multiple presentations related to INPEFA at the American Heart Association Scientific Sessions 2023, including one oral presentation highlighting the early clinical benefit of INPEFA for heart failure and atherosclerotic events and another focusing on cost-effectiveness metrics associated with the use of INPEFA. LX9211 In December, patient enrollment began in the PROGRESS Phase 2b dose optimization study and is progressing well. The PROGRESS study marks initiation of the late-stage development program for AAK1 inhibitor LX9211, with potential to become the first new, non-opioid drug therapy approved in neuropathic pain in more than 20 years. Topline data from the PROGRESS study is anticipated in 2Q 2025. Data relating to LX9211 were shared at various global congresses during the fourth quarter, including the 33rd Annual Meeting of the Diabetic Neuropathy Study Group (NeuroDiab), held September 28-October 1 in Thessaloniki, Greece; the 59th Annual Meeting of the European Association for the Study of Diabetes (EASD), held October 2-6 in Hamburg, Germany and online; the 17th Annual Pain Therapeutics Summit (Arrowhead Conference), held October 19-20 in San Diego, California; and the 2nd World Brain Disorders and Neuroscience Summit (BDNS), held November 9-11 in Singapore and online. Additional Pipeline Opportunities Preparations are underway for Phase 3 development of sotagliflozin in HCM. Following recent feedback from FDA, preparations are underway to resubmit Lexicon’s NDA for sotagliflozin as an adjunct to insulin therapy in patients with type 1 diabetes and chronic kidney disease. As part of Lexicon’s ongoing discovery efforts, the company is advancing preclinical development of a novel oral compound for obesity and weight management. Fourth Quarter 2023 Financial Highlights Unless otherwise stated, all comparisons are for the fourth quarter and full year of 2023 compared to the fourth quarter and full year of 2022. Revenues: Revenues for the fourth quarter and full year of 2023 were $0.7 million and $1.2 million, respectively, primarily from the commercialization of INPEFA. Research and Development (R&D) Expenses: Research and development expenses for the fourth quarter of 2023 increased to $14.8 million from $14.0 million for the corresponding period in 2022. Full-year research and development expenses increased to $58.9 million in 2023 from $52.8 million for the corresponding period in 2022, primarily due to higher manufacturing costs, partially offset by lower professional and consulting fees related to the prior year NDA resubmission for heart failure. Selling, General and Administrative (SG&A) Expenses: Selling, general and administrative expenses for the fourth quarter of 2023 increased to $32.6 million from $16.3 million in 2022 and for the full-year 2023 increased to $114.0 million from $48.1 million in 2022. The increase in 2023 is primarily due to the significant investment in the commercial launch of INPEFA, including higher salaries and benefits of the new sales force and other increased headcount, higher travel, and higher marketing costs. Net Loss: Net loss for the fourth quarter of 2023 was $48.2 million, or $0.20 per share, as compared to a net loss of $30.5 million, or $0.16 per share, in the corresponding period in 2022. For the fourth quarters of 2023 and 2022, net loss included non-cash, stock-based compensation expense of $3.2 million and $3.3 million, respectively. Net loss for the full year was $175.6 million, or $0.79 per share, in 2023 as compared to a net loss of $101.9 million, or $0.62 per share, in the corresponding period in 2022. For the full years of 2023 and 2022, net loss included non-cash, stock-based compensation expense of $14.3 million and $11.5 million, respectively. Cash and Investments: As of December 31, 2023, Lexicon had $170.0 million in cash and investments, as compared to $138.4 million as of December 31, 2022. Lexicon 2024 Investor Day – April 22, 2024 In lieu of a year-end earnings conference call, Lexicon plans to hold an Investor Day on April 22, 2024. The event will be webcast live on Lexicon’s website at . The agenda will include a business and regulatory update, with participation from multiple physician experts in the areas of cardiometabolic disorders, HCM, type 1 diabetes and diabetic peripheral neuropathic pain. For Lexicon’s latest investor presentation, please visit . Planned Participation in Upcoming Investor Conferences: Leerink Partners Global Biopharma Conference March 12 Needham 23rd Annual Virtual Healthcare Conference on April 8-11 Piper Sandler Virtual Cardiovascular Day on April 10 Piper Sandler Spring Biopharma Symposium on April 16-17 These events will be webcast live on Lexicon’s website at . About INPEFA® (sotagliflozin) Discovered using Lexicon’s unique approach to gene science, INPEFA® (sotagliflozin) is an oral inhibitor of two proteins responsible for glucose regulation known as sodium-glucose cotransporter types 2 and 1 (SGLT2 and SGLT1). SGLT2 is responsible for glucose and sodium reabsorption by the kidney and SGLT1 is responsible for glucose and sodium absorption in the gastrointestinal tract. Sotagliflozin has been studied in multiple patient populations encompassing heart failure, diabetes, and chronic kidney disease in clinical studies involving approximately 20,000 patients. INDICATION INPEFA is indicated to reduce the risk of cardiovascular death, hospitalization for heart failure, and urgent heart failure visit in adults with: heart failure or type 2 diabetes mellitus, chronic kidney disease, and other cardiovascular risk factors IMPORTANT SAFETY INFORMATION Dosing: Assess renal function and volume status and, if necessary, correct volume depletion prior to initiation of INPEFA. INPEFA dosing for patients with decompensated heart failure may begin when patients are hemodynamically stable, including when hospitalized or immediately upon discharge. Contraindications: INPEFA is contraindicated in patients with hypersensitivity to INPEFA or any of its components. Ketoacidosis: INPEFA increases the risk of ketoacidosis in patients with type 1 diabetes mellitus (T1DM). Type 2 diabetes Mellitus (T2DM) and pancreatic disorders are also risk factors. The risk of ketoacidosis may be greater with higher doses. There have been postmarketing reports of fatal events of ketoacidosis in patients with type 2 diabetes using sodium glucose transporter 2 (SGLT2) inhibitors. Before initiating INPEFA, assess risk factors for ketoacidosis. Consider ketone monitoring in patients with T1DM and consider ketone monitoring in others at risk for ketoacidosis and educate patients on the signs/symptoms of ketoacidosis. Patients receiving INPEFA may require monitoring and temporary discontinuation of therapy in clinical situations known to predispose to ketoacidosis. INPEFA is not indicated for glycemic control. Assess patients who present with signs and symptoms of metabolic acidosis or ketoacidosis, regardless of blood glucose level. If suspected, discontinue INPEFA, evaluate, and treat promptly. Monitor patients for resolution of ketoacidosis before restarting INPEFA. Volume Depletion: INPEFA can cause intravascular volume depletion which may sometimes manifest as symptomatic hypotension or acute transient changes in creatinine. There have been post-marketing reports of acute kidney injury, some requiring hospitalization and dialysis, in patients with type 2 diabetes mellitus receiving SGLT2 inhibitors. Patients with impaired renal function (eGFR < 60 mL/min/1.73 m2), elderly patients, or patients on loop diuretics may be at increased risk for volume depletion or hypotension. Before initiating INPEFA in patients with one or more of these characteristics, assess volume status and renal function, and monitor for signs and symptoms of hypotension during therapy. Urosepsis and Pyelonephritis: Treatment with SGLT2 inhibitors, including INPEFA, increases the risk for urinary tract infections. Serious urinary tract infections including urosepsis and pyelonephritis requiring hospitalization have been reported. Evaluate patients for signs and symptoms of urinary tract infections and treat promptly. Hypoglycemia with Concomitant Use with Insulin and Insulin Secretagogues: Insulin and insulin secretagogues are known to cause hypoglycemia. INPEFA may increase the risk of hypoglycemia when combined with insulin or an insulin secretagogue. Therefore, a lower dose of insulin or insulin secretagogue may be required to minimize the risk of hypoglycemia when used with INPEFA. Necrotizing Fasciitis of the Perineum (Fournier’s Gangrene): Reports of Fournier’s Gangrene, a rare but serious and life-threatening necrotizing infection requiring urgent surgical intervention, have been identified in post-marketing surveillance in patients with diabetes mellitus receiving SGLT2 inhibitors. Assess patients who present with pain, tenderness, erythema, or swelling in the genital or perineal area, along with fever or malaise. If suspected, start treatment immediately with broad-spectrum antibiotics and, if necessary, surgical debridement. Discontinue INPEFA, closely monitor patient signs and symptoms, and provide appropriate alternative therapy for heart failure. Genital Mycotic Infections: INPEFA increases the risk of genital mycotic infections. Monitor and treat as appropriate. Urinary Glucose Test and 1,5-anhydroglucitol (1,5-AG) Assay: these are not reliable for patients taking SGLT2 inhibitors. Use alternative testing methods to monitor glucose levels. Common Adverse Reactions: the most commonly reported adverse reactions (incidence ≥ 5%) were urinary tract infection, volume depletion, diarrhea, and hypoglycemia. Drug Interactions: Digoxin: Monitor patients appropriately as there is an increase in the exposure of digoxin when coadministered with INPEFA 400 mg. Uridine 5'-diphospho-glucuronosyltransferase (UGT) Inducer: The coadministration of rifampicin, an inducer of UGTs, with sotagliflozin resulted in a decrease in the exposure of sotagliflozin. Lithium: Concomitant use of an SGLT2 inhibitor with lithium may decrease serum lithium concentrations. Monitor serum lithium concentration more frequently during INPEFA initiation and with dosage changes. Use in Specific Populations: Pregnancy and Lactation: INPEFA is not recommended during the second and third trimesters of pregnancy, nor while breastfeeding. Geriatric Use: No INPEFA dosage change is recommended based on age. No overall differences in efficacy were detected between these patients and younger patients, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. Elderly patients may be at increased risk for volume depletion adverse reactions, including hypotension. Renal Impairment: INPEFA was evaluated in patients with chronic kidney disease (eGFR 25 to 60 mL/min/1.73 m2) and in patients with heart failure with eGFR < 60 mL/min/1.73 m2. The safety pro INPEFA across eGFR subgroups in these studies was consistent with the known safety profile. There was an increase in volume-related adverse events (e.g., hypotension, dizziness) in patients with eGFR < 30 mL/min/1.73m2 relative to the overall safety population. Efficacy and safety studies with INPEFA did not enroll patients with an eGFR less than 25 mL/min/1.73 m2 or on dialysis. After starting therapy in the studies, patients were discontinued if eGFR fell below 15 mL/min/1.73 m2 or were initiated on chronic dialysis. Hepatic Impairment: INPEFA is not recommended in patients with moderate or severe hepatic impairment. Click here for full Prescribing Information. About Lexicon Pharmaceuticals Lexicon is a biopharmaceutical company with a mission of pioneering medicines that transform patients’ lives. Through its Genome5000™ program, Lexicon scientists studied the role and function of nearly 5,000 genes and identified more than 100 protein targets with significant therapeutic potential in a range of diseases. Through the precise targeting of these proteins, Lexicon is pioneering the discovery and development of innovative medicines to safely and effectively treat disease. Lexicon has advanced multiple medicines to market and has a pipeline of promising drug candidates in discovery and clinical and preclinical development in heart failure, neuropathic pain, diabetes and metabolism and other indications. For additional information, please visit . Safe Harbor Statement This press release contains “forward-looking statements,” including statements relating to Lexicon’s financial position and long-term outlook on its business, including the commercialization of its approved products and the clinical development of, regulatory filings for, and potential therapeutic and commercial potential of its other drug candidates. In addition, this press release also contains forward looking statements relating to Lexicon’s growth and future operating results, discovery, development and commercialization of products, strategic alliances and intellectual property, as well as other matters that are not historical facts or information. All forward-looking statements are based on management’s current assumptions and expectations and involve risks, uncertainties and other important factors, specifically including Lexicon’s ability to meet its capital requirements, successfully commercialize its approved products, successfully conduct preclinical and clinical development and obtain necessary regulatory approvals of its other drug candidates on its anticipated timelines, achieve its operational objectives, obtain patent protection for its discoveries and establish strategic alliances, as well as additional factors relating to manufacturing, intellectual property rights, and the therapeutic or commercial value of its approved products and other drug candidates. Any of these risks, uncertainties and other factors may cause Lexicon’s actual results to be materially different from any future results expressed or implied by such forward-looking statements. Information identifying such important factors is contained under “Risk Factors” in Lexicon’s annual report on Form 10-K for the year ended December 31, 2022, as filed with the Securities and Exchange Commission. Lexicon undertakes no obligation to update or revise any such forward-looking statements, whether as a result of new information, future events or otherwise. Lexicon Pharmaceuticals, Inc. Selected Financial Data Consolidated Statements of Operations Data Three Months Ended December 31, Years Ended December 31, (In thousands, except per share data) 2023 2022 2023 2022 (Unaudited) (Unaudited) Revenues: Net product revenue $ 672 $ - $ 1,110 $ - Royalties and other revenue 30 28 94 139 Total revenues 702 28 1,204 139 Operating expenses: Cost of sales 70 - 85 - Research and development, including stock-based compensation of $1,297, $1,184, $5,139 and $4,253, respectively 14,762 13,977 58,887 52,816 Selling, general and administrative, including stock-based compensation of $1,915, $2,084, $9,201, and $7,267, respectively 32,607 16,329 113,982 48,083 Total operating expenses 47,439 30,306 172,954 100,899 Loss from operations (46,737 ) (30,278 ) (171,750 ) (100,760 ) Interest expense (3,909 ) (1,103 ) (11,589 ) (2,780 ) Interest and other income, net 2,402 887 7,732 1,596 Net loss $ (48,244 ) $ (30,494 ) $ (175,607 ) $ (101,944 ) Net loss per common share, basic and diluted $ (0.20 ) $ (0.16 ) $ (0.79 ) $ (0.62 ) Shares used in computing net loss per common share, basic and diluted 244,925 188,726 221,130 165,733 As of As of Consolidated Balance Sheet Data December 31, 2023 December 31, 2022 (In thousands) Cash and investments $ 170,026 $ 138,357 Property and equipment, net 1,987 2,071 Goodwill 44,543 44,543 Total assets 229,429 194,299 Long-term debt, net 99,508 48,579 Accumulated deficit (1,765,327 ) (1,589,720 ) Total stockholders' equity 94,622 117,124 For Investor Inquiries: Lisa DeFrancesco Lexicon Pharmaceuticals, Inc. lexinvest@lexpharma.com For Media Inquiries: Alina Cocuzza Lexicon Pharmaceuticals, Inc. acocuzza@lexpharma.com

SOUTH SAN FRANCISCO, Calif., Jan. 25, 2024 (GLOBE NEWSWIRE) -- Cytokinetics, Inc. (Nasdaq: CYTK) today announced new data at CMR 2024 demonstrating favorable effects on cardiac structure, function and fibrosis related to treatment with aficamten in FOREST-HCM (Follow-up, Open-Label, Research Evaluation of Sustained Treatment with Aficamten in HCM), the open label extension clinical trial of aficamten in patients with hypertrophic cardiomyopathy (HCM). In many patients with HCM, the left ventricular hypertrophy that characterizes the disease results in elevated cardiac mass, and left ventricular outflow tract (LVOT) obstruction is often accompanied by mitral valve regurgitation. Patients with HCM may also present with myocardial fibrosis, a strong predictor of abnormal cardiac rhythm and sudden death, and other cardiac structural abnormalities such as increased left atrial volume. Previously presented data from FOREST-HCM showed that prolonged treatment with aficamten was associated with sustained reductions in LVOT gradients with no treatment interruptions for low left ventricular ejection fraction (LVEF) due to aficamten, as well as sustained reductions in cardiac biomarkers and improved symptoms. New data presented today from the cardiac magnetic resonance (CMR) sub-study in FOREST-HCM show that treatment with aficamten for 48 weeks resulted in favorable cardiac structural remodeling, improvements in cardiac function, and stabilization of myocardial fibrosis. At the time of this analysis, 16 patients in FOREST-HCM had completed a CMR at baseline and at Week 48. Baseline characteristics of the CMR cohort were comparable to the overall patient population in FOREST-HCM. In this trial, treatment with aficamten for 48 weeks resulted in statistically significant improvements in measures of cardiac structure and function including left ventricular mass index (-11.4 g/m2 ±19.4, p=0.03), maximum left ventricular septal wall thickness (-1.3 mm ±1.8, p=0.02), left atrial volume (-16.3 ml/m2 ±26.4, p=0.05), and mitral regurgitant volume (-12.9 ml ±15.1, p=0.01) and fraction (-9.5% ± 15.1, p=0.05). Additionally, treatment with aficamten stabilized interstitial and replacement myocardial fibrosis, with no increase in the fibrosis mass, as measured by absolute mass of late gadolinium enhancement (-0.6 g ± 5.0, p=0.64). “These are the first long-term CMR data to emerge from FOREST-HCM, and they demonstrate potential disease modifying effects of aficamten in patients with obstructive HCM,” said Fady I. Malik, M.D., Ph.D., Cytokinetics’ Executive Vice President of Research & Development. “Added to the existing body of evidence from both FOREST-HCM and SEQUOIA-HCM, the pivotal Phase 3 clinical trial of aficamten in oHCM, these data further support the pro aficamten as a potential next-in-class cardiac myosin inhibitor that is not only associated with statistically significant and clinically meaningful improvements to hemodynamics and symptoms, but that improves the architecture of the heart. We look forward to expanding on these data in the future.” About 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. About the Broad Phase 3 Clinical Trials Program for Aficamten 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. SEQUOIA-HCM (Safety, Efficacy, and Quantitative Understanding of Obstruction Impact of Aficamten in HCM), was the pivotal Phase 3 clinical trial in patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM). The results from SEQUOIA-HCM show that treatment with aficamten significantly improved exercise capacity compared to placebo, increasing peak oxygen uptake (pVO2) measured by cardiopulmonary exercise testing (CPET) by a least square mean difference (95% CI) of 1.74 (1.04 - 2.44) mL/kg/min (p=0.000002). The treatment effect with aficamten was consistent across all prespecified subgroups reflective of patient baseline characteristics and treatment strategies, including patients receiving or not receiving background beta-blocker therapy. Statistically significant (p<0.0001) and clinically meaningful improvements were also observed in all 10 prespecified secondary endpoints. Aficamten was well-tolerated with an adverse event pro to placebo. Treatment emergent serious adverse events occurred in 8 (5.6%) and 13 (9.3%) patients on aficamten and placebo, respectively. Core echocardiographic left ventricular ejection fraction (LVEF) was observed to be <50% in 5 patients (3.5%) on aficamten compared to 1 patient (0.7%) on placebo. There were no instances of worsening heart failure or treatment interruptions due to low LVEF. Aficamten is currently the subject of two ongoing Phase 3 clinical trials: MAPLE-HCM (Metoprolol vs Aficamten in Patients with LVOT Obstruction on Exercise Capacity in HCM), evaluating aficamten as monotherapy compared to metoprolol as monotherapy in patients with obstructive HCM, and ACACIA-HCM (Assessment Comparing Aficamten to Placebo on Cardiac Endpoints In Adults with Non-Obstructive HCM), evaluating aficamten in patients with symptomatic non-obstructive 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. About Hypertrophic Cardiomyopathy Hypertrophic cardiomyopathy (HCM) is a disease in which the heart muscle (myocardium) becomes abnormally thick (hypertrophied). The thickening of cardiac muscle leads to the inside of the left ventricle becoming smaller and stiffer, and thus the ventricle becomes less able to relax and fill with blood. This ultimately limits the heart’s pumping function, resulting in reduced exercise capacity and symptoms including chest pain, dizziness, shortness of breath, or fainting during physical activity. HCM is the most common monogenic inherited cardiovascular disorder, with approximately 280,000 patients diagnosed in the U.S., however, there are an estimated 400,000-800,000 additional patients who remain undiagnosed.1,2,3 Two-thirds of patients with HCM have obstructive HCM (oHCM), where the thickening of the cardiac muscle leads to left ventricular outflow tract (LVOT) obstruction, while one-third have non-obstructive HCM (nHCM), where blood flow isn’t impacted, but the heart muscle is still thickened. People with HCM are at high risk of also developing cardiovascular complications including atrial fibrillation, stroke and mitral valve disease.4 People with HCM are at risk for potentially fatal ventricular arrhythmias and it is one of the leading causes of sudden cardiac death in younger people or athletes.5 A subset of patients with HCM are at high risk of progressive disease leading to dilated cardiomyopathy and heart failure necessitating cardiac transplantation. About Cytokinetics Cytokinetics is a late-stage, specialty cardiovascular biopharmaceutical company focused on discovering, developing and commercializing first-in-class muscle activators and next-in-class muscle inhibitors 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 interactions 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. Aficamten is also currently being evaluated in two ongoing Phase 3 clinical trials: MAPLE-HCM, evaluating aficamten as monotherapy compared to metoprolol as monotherapy in patients with obstructive HCM and ACACIA-HCM, evaluating aficamten in patients with non-obstructive HCM. Cytokinetics is also developing omecamtiv mecarbil, a cardiac muscle activator, in patients with heart failure. Additionally, Cytokinetics is developing CK-136, a cardiac troponin activator for the potential treatment HFrEF and other types of heart failure, such as right ventricular failure, resulting from impaired cardiac contractility, and 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 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 disclaims any intent or obligation to update these forward-looking statements and claims the protection of the Act’s Safe Harbor for forward-looking statements. Examples of such statements include, but are not limited to, statements express or implied relating to the properties or potential benefits of aficamten or any of our other drug candidates and our ability to obtain regulatory approval for aficamten for the treatment of obstructive hypertrophic cardiomyopathy or any other indication from FDA or any other regulatory body in the United States or abroad. 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 the risks related to Cytokinetics’ business outlines in Cytokinetics’ filings with the Securities and Exchange Commission. 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 Weiser Senior Vice President, Corporate Communications, Investor Relations (415) 290-7757 References: CVrg: Heart Failure 2020-2029, p 44; Maron et al. 2013 DOI: 10.1016/S0140-6736(12)60397-3; Maron et al 2018 10.1056/NEJMra1710575 Symphony Health 2016-2021 Patient Claims Data DoF; Maron MS, Hellawell JL, Lucove JC, Farzaneh-Far R, Olivotto I. Occurrence of Clinically Diagnosed Hypertrophic Cardiomyopathy in the United States. Am J Cardiol. 2016; 15;117(10):1651-1654. Gersh, B.J., Maron, B.J., Bonow, R.O., Dearani, J.A., Fifer, M.A., Link, M.S., et al. 2011 ACCF/AHA guidelines for the diagnosis and treatment of hypertrophic cardiomyopathy. A report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Journal of the American College of Cardiology and Circulation, 58, e212-260. Hong Y, Su WW, Li X. Risk factors of sudden cardiac death in hypertrophic cardiomyopathy. Current Opinion in Cardiology. 2022 Jan 1;37(1):15-21

Commercial launch of INPEFA® (sotagliflozin) as a differentiated, new treatment option for heart failure patients shows meaningful progress in Q3 with increasing demand across the cardiology community Significant formulary inclusions effective in Q4 opening the opportunity for further commercial acceleration into 2024 and beyond LX9211 moving into late-stage development for the treatment of diabetic peripheral neuropathic pain Conference Call and Webcast at 8:00 am Eastern Time THE WOODLANDS, Texas, Nov. 08, 2023 (GLOBE NEWSWIRE) -- Lexicon Pharmaceuticals, Inc. (Nasdaq: LXRX), today reported financial results for the three months ended September 30th, 2023 and provided an update on key corporate milestones. “We achieved important milestones this quarter in commercially launching INPEFA (sotagliflozin) in the U.S. for the treatment of heart failure while simultaneously advancing LX9211 into late-stage development for diabetic peripheral neuropathic pain,” said Lonnel Coats, Lexicon’s chief executive officer. “We saw increasing prescription demand and clinical utilization for INPEFA throughout the third quarter notwithstanding limited access, and are now beginning to see important formulary wins, with some of the more notable becoming effective on November 1st. With additional formulary wins expected, coupled with increasing uptake from a broadening base of priority physicians, we are confident the momentum behind INPEFA will continue to accelerate as we enter 2024.” “We remain focused on showcasing the growing breadth of INPEFA’s clinical evidence and strengthening value proposition at major medical meetings, further demonstrating its differentiated profile for heart failure patients.” “We are also continuing to present data regarding LX9211, for which we have commenced late-stage development in diabetic peripheral neuropathic pain, with patient enrollment expected to begin this quarter in a Phase 2b clinical trial. We remain excited about the clinical profile of LX9211 and believe it could become the first new, non-opioid drug for neuropathic pain in over two decades – an area where new treatment options are urgently needed. Our continued progress with the launch of INPEFA coupled with the advancement of LX9211 into late-stage development are both major milestones in Lexicon’s path to fulfilling its mission of pioneering medicines that transform patients’ lives.” Third Quarter Highlights INPEFA® (sotagliflozin) Launch Progress On June 26, Lexicon commenced the U.S. commercial launch of INPEFA (sotagliflozin) for the treatment of heart failure, with product made available in pharmacies and sales representatives deployed across the U.S.On October 9, Lexicon announced that Express Scripts, the pharmacy benefits management (PBM) business of The Cigna Group's Evernorth, determined that it would place INPEFA on its Premier Access and Premier Performance national formularies for Medicare patients on November 1, 2023. On November 1, Lexicon announced that Express Scripts had also determined that it would place INPEFA on its Basic and High Performance formularies for commercially insured patients on that date. These placements provide access to INPEFA for Express Scripts Medicare and commercial patients in plans that utilize these formularies and who meet the parameters of INPEFA’s FDA-approved indication. Publications and Data On August 8, Lexicon announced that a post hoc analysis of data from the SOLOIST-WHF Phase 3 outcomes study of sotagliflozin was published by the Journal of the American College of Cardiology (JACC): Heart Failure. The main endpoint of the analysis was first occurrence of cardiovascular death or heart failure-related event (hospitalizations or urgent care visits for heart failure) within 30 and 90 days after hospital discharge (not randomization) in the subgroup of patients who began study treatment on or before discharge. Treatment with sotagliflozin resulted in significant relative risk reductions of approximately 50% for readmission for non-fatal heart failure events and for the composite of cardiovascular death and readmission for heart failure at 30- or 90-days following hospital discharge versus placebo.On August 26, two analyses of clinical study results relating to sotagliflozin and Lexicon-supported data were presented during the European Society of Cardiology (ESC) Congress 2023 in Amsterdam, the Netherlands. Bertram Pitt, M.D., FACC, professor of medicine emeritus at the University of Michigan, School of Medicine, Ann Arbor, MI conducted an oral presentation entitled Mediators of the benefit of sotagliflozin in patients with worsening heart failure in SOLOIST-WHF. In addition, Marc Bonaca, M.D., M.P.H., University of Colorado Anschutz Medical Campus, Aurora, CO presented a moderated ePoster entitled Temporal shift in heart failure diagnoses among hospitalized patients within a large US integrated health system.On October 4, Craig Granowitz, M.D., Ph.D., Lexicon’s senior vice president and chief medical officer, conducted an oral presentation entitled Temporal shift in heart failure medications prescribed to hospitalised patients with and without diabetes in a large US integrated health system at the 59th Annual Meeting of European Association for the Study of Diabetes (EASD) in Hamburg, Germany and online. On October 8, Michael J. Davies, Ph.D., Lexicon’s executive director of clinical development, presented a new analysis of clinical trial data for sotagliflozin entitled Sotagliflozin Reduces the Risk of Cardiovascular Events In Patients With Left Ventricular Hypertrophy Without Hypertension: A Post Hoc Analysis From SCORED was presented at the Heart Failure Society of America (HFSA) Annual Scientific Meeting in Cleveland, Ohio. LX9211 In June, Lexicon announced the planned advancement of AAK1-inhibitor LX9211 into late-stage development in diabetic peripheral neuropathic pain. During Q3, our teams have continued the preparations for the Phase 2b dose optimization study, with the first patient expected to be enrolled in early December 2023. On September 7, Lexicon announced a series of presentations relating to LX9211 occurring throughout the third and fourth quarters. Data were or will be shared in four oral presentations and one poster presentation at various global congresses, including NeuPSIG 2023 International Congress on Neuropathic Pain, held September 7-9 in Lisbon, Portugal; 33rd Annual Meeting of the Diabetic Neuropathy Study Group (NeuroDiab), held September 28-October 1 in Thessaloniki, Greece; 59th Annual Meeting of the European Association for the Study of Diabetes (EASD), held October 2-6 in Hamburg, Germany and online; 17th Annual Pain Therapeutics Summit (Arrowhead Conference), held October 19-20 in San Diego, California; and 2nd World Brain Disorders and Neuroscience Summit (BDNS), being held November 9-11 in Singapore and online. Third Quarter 2023 Financial Highlights Revenues: Revenues for the third quarter of 2023 were $0.2 million, primarily from the recent commercial launch of INPEFA. INPEFA net product revenues from launch (late June) through September 30, 2023 total $0.4 million. Research and Development (R&D) Expenses: Research and development expenses for the third quarter of 2023 increased to $17.6 million from $10.6 million for the corresponding period in 2022, primarily due to higher manufacturing costs and higher external research and development expenses related to the LX9211 program, partially offset by lower professional and consulting fees. Selling, General and Administrative (SG&A) Expenses: Selling, general and administrative expenses for the third quarter of 2023 increased to $32.2 million from $12.6 million for the corresponding period in 2022, primarily due to increases in salaries and benefits, professional and consulting costs and marketing costs relating to preparations for the commercial launch of INPEFA. Net Loss: Net loss for the third quarter of 2023 was $50.5 million, or $0.21 per share, as compared to a net loss of $23.4 million, or $0.13 per share, in the corresponding period in 2022. For the third quarters of 2023 and 2022, net loss included non-cash, stock-based compensation expense of $3.9 million and $2.6 million, respectively. Cash and Investments: As of September 30, 2023, Lexicon had $218.4 million in cash and investments, as compared to $138.4 million as of December 31, 2022. Conference Call and Webcast Information Lexicon management will hold a live conference call and webcast today at 8:00 am ET / 7:00 am CT to review its financial and operating results and to provide a general business update. The dial-in number for the conference call is 888-317-6003 and the conference ID for all callers is 2598226. The live webcast and replay may be accessed by visiting Lexicon’s website at www.lexpharma.com/events. An archived version of the webcast will be available on the website for 14 days. About INPEFA® (sotagliflozin) Discovered using Lexicon’s unique approach to gene science, INPEFA® (sotagliflozin) is an oral inhibitor of two proteins responsible for glucose regulation known as sodium-glucose cotransporter types 2 and 1 (SGLT2 and SGLT1). SGLT2 is responsible for glucose and sodium reabsorption by the kidney and SGLT1 is responsible for glucose and sodium absorption in the gastrointestinal tract. Sotagliflozin has been studied in multiple patient populations encompassing heart failure, diabetes, and chronic kidney disease in clinical studies involving approximately 20,000 patients. INDICATION INPEFA is indicated to reduce the risk of cardiovascular death, hospitalization for heart failure, and urgent heart failure visit in adults with: heart failure ortype 2 diabetes mellitus, chronic kidney disease, and other cardiovascular risk factors IMPORTANT SAFETY INFORMATION Dosing: Assess renal function and volume status and, if necessary, correct volume depletion prior to initiation of INPEFA. INPEFA dosing for patients with decompensated heart failure may begin when patients are hemodynamically stable, including when hospitalized or immediately upon discharge. Contraindications: INPEFA is contraindicated in patients with hypersensitivity to INPEFA or any of its components. Ketoacidosis: INPEFA increases the risk of ketoacidosis in patients with type 1 diabetes mellitus (T1DM). Type 2 diabetes Mellitus (T2DM) and pancreatic disorders are also risk factors. The risk of ketoacidosis may be greater with higher doses. There have been postmarketing reports of fatal events of ketoacidosis in patients with type 2 diabetes using sodium glucose transporter 2 (SGLT2) inhibitors. Before initiating INPEFA, assess risk factors for ketoacidosis. Consider ketone monitoring in patients with T1DM and consider ketone monitoring in others at risk for ketoacidosis and educate patients on the signs/symptoms of ketoacidosis. Patients receiving INPEFA may require monitoring and temporary discontinuation of therapy in clinical situations known to predispose to ketoacidosis. INPEFA is not indicated for glycemic control. Assess patients who present with signs and symptoms of metabolic acidosis or ketoacidosis, regardless of blood glucose level. If suspected, discontinue INPEFA, evaluate, and treat promptly. Monitor patients for resolution of ketoacidosis before restarting INPEFA. Volume Depletion: INPEFA can cause intravascular volume depletion which may sometimes manifest as symptomatic hypotension or acute transient changes in creatinine. There have been post-marketing reports of acute kidney injury, some requiring hospitalization and dialysis, in patients with type 2 diabetes mellitus receiving SGLT2 inhibitors. Patients with impaired renal function (eGFR < 60 mL/min/1.73 m2), elderly patients, or patients on loop diuretics may be at increased risk for volume depletion or hypotension. Before initiating INPEFA in patients with one or more of these characteristics, assess volume status and renal function, and monitor for signs and symptoms of hypotension during therapy. Urosepsis and Pyelonephritis: Treatment with SGLT2 inhibitors, including INPEFA, increases the risk for urinary tract infections. Serious urinary tract infections including urosepsis and pyelonephritis requiring hospitalization have been reported. Evaluate patients for signs and symptoms of urinary tract infections and treat promptly. Hypoglycemia with Concomitant Use with Insulin and Insulin Secretagogues: Insulin and insulin secretagogues are known to cause hypoglycemia. INPEFA may increase the risk of hypoglycemia when combined with insulin or an insulin secretagogue. Therefore, a lower dose of insulin or insulin secretagogue may be required to minimize the risk of hypoglycemia when used with INPEFA. Necrotizing Fasciitis of the Perineum (Fournier’s Gangrene): Reports of Fournier’s Gangrene, a rare but serious and life-threatening necrotizing infection requiring urgent surgical intervention, have been identified in post-marketing surveillance in patients with diabetes mellitus receiving SGLT2 inhibitors. Assess patients who present with pain, tenderness, erythema, or swelling in the genital or perineal area, along with fever or malaise. If suspected, start treatment immediately with broad-spectrum antibiotics and, if necessary, surgical debridement. Discontinue INPEFA, closely monitor patient signs and symptoms, and provide appropriate alternative therapy for heart failure. Genital Mycotic Infections: INPEFA increases the risk of genital mycotic infections. Monitor and treat as appropriate. Urinary Glucose Test and 1,5-anhydroglucitol (1,5-AG) Assay: these are not reliable for patients taking SGLT2 inhibitors. Use alternative testing methods to monitor glucose levels. Common Adverse Reactions: the most commonly reported adverse reactions (incidence ≥ 5%) were urinary tract infection, volume depletion, diarrhea, and hypoglycemia. Drug Interactions: Digoxin: Monitor patients appropriately as there is an increase in the exposure of digoxin when coadministered with INPEFA 400 mg.Uridine 5'-diphospho-glucuronosyltransferase (UGT) Inducer: The coadministration of rifampicin, an inducer of UGTs, with sotagliflozin resulted in a decrease in the exposure of sotagliflozin.Lithium: Concomitant use of an SGLT2 inhibitor with lithium may decrease serum lithium concentrations. Monitor serum lithium concentration more frequently during INPEFA initiation and with dosage changes. Use in Specific Populations: Pregnancy and Lactation: INPEFA is not recommended during the second and third trimesters of pregnancy, nor while breastfeeding.Geriatric Use: No INPEFA dosage change is recommended based on age. No overall differences in efficacy were detected between these patients and younger patients, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. Elderly patients may be at increased risk for volume depletion adverse reactions, including hypotension.Renal Impairment: INPEFA was evaluated in patients with chronic kidney disease (eGFR 25 to 60 mL/min/1.73 m2) and in patients with heart failure with eGFR < 60 mL/min/1.73 m2. The safety profile of INPEFA across eGFR subgroups in these studies was consistent with the known safety profile. There was an increase in volume-related adverse events (e.g., hypotension, dizziness) in patients with eGFR < 30 mL/min/1.73m2 relative to the overall safety population. Efficacy and safety studies with INPEFA did not enroll patients with an eGFR less than 25 mL/min/1.73 m2 or on dialysis. After starting therapy in the studies, patients were discontinued if eGFR fell below 15 mL/min/1.73 m2 or were initiated on chronic dialysis.Hepatic Impairment: INPEFA is not recommended in patients with moderate or severe hepatic impairment. Click here for full Prescribing Information. About Lexicon Pharmaceuticals Lexicon is a biopharmaceutical company with a mission of pioneering medicines that transform patients’ lives. Through its Genome5000™ program, Lexicon scientists studied the role and function of nearly 5,000 genes and identified more than 100 protein targets with significant therapeutic potential in a range of diseases. Through the precise targeting of these proteins, Lexicon is pioneering the discovery and development of innovative medicines to safely and effectively treat disease. Lexicon has advanced multiple medicines to market and has a pipeline of promising drug candidates in discovery and clinical and preclinical development in heart failure, neuropathic pain, diabetes and metabolism and other indications. For additional information, please visit www.lexpharma.com. Safe Harbor Statement This press release contains “forward-looking statements,” including statements relating to Lexicon’s financial position and long-term outlook on its business, including the commercialization of its approved products and the clinical development of, regulatory filings for, and potential therapeutic and commercial potential of its other drug candidates. In addition, this press release also contains forward looking statements relating to Lexicon’s growth and future operating results, discovery, development and commercialization of products, strategic alliances and intellectual property, as well as other matters that are not historical facts or information. All forward-looking statements are based on management’s current assumptions and expectations and involve risks, uncertainties and other important factors, specifically including Lexicon’s ability to meet its capital requirements, successfully commercialize its approved products, successfully conduct preclinical and clinical development and obtain necessary regulatory approvals of its other drug candidates on its anticipated timelines, achieve its operational objectives, obtain patent protection for its discoveries and establish strategic alliances, as well as additional factors relating to manufacturing, intellectual property rights, and the therapeutic or commercial value of its approved products and other drug candidates. Any of these risks, uncertainties and other factors may cause Lexicon’s actual results to be materially different from any future results expressed or implied by such forward-looking statements. Information identifying such important factors is contained under “Risk Factors” in Lexicon’s annual report on Form 10-K for the year ended December 31, 2022, as filed with the Securities and Exchange Commission. Lexicon undertakes no obligation to update or revise any such forward-looking statements, whether as a result of new information, future events or otherwise. Lexicon Pharmaceuticals, Inc.Selected Financial Data Consolidated Statements of Operations Data Three Months Ended September 30, Nine Months Ended September 30,(In thousands, except per share data) 2023 2022 2023 2022 (Unaudited) (Unaudited)Revenues: Net product revenue $148 $- $438 $- Royalties and other revenue 14 39 64 111 Total revenues 162 39 502 111 Operating expenses: Cost of Sales 7 - 15 - Research and development, including stock-based compensation of $1,337, $939, $3,842 and $3,069, respectively 17,558 10,557 44,125 38,839 Selling, general and administrative, including stock-based compensation of $2,561, $1,709, $7,286, and $5,183, respectively 32,228 12,577 81,375 31,754 Total operating expenses 49,793 23,134 125,515 70,593 Loss from operations (49,631) (23,095) (125,013) (70,482)Interest expense (3,899) (864) (7,680) (1,677)Interest and other income, net 3,005 572 5,330 709 Net loss $(50,525) $(23,387) $(127,363) $(71,450) Net loss per common share, basic and diluted $(0.21) $(0.13) $(0.60) $(0.45) Shares used in computing net loss per common share, basic and diluted 244,925 174,904 213,112 157,984 As of As of Consolidated Balance Sheet Data September 30, 2023 December 31, 2022 (In thousands) Cash and investments $218,427 $138,357 Property and equipment, net 2,134 2,071 Goodwill 44,543 44,543 Total assets 276,479 194,299 Long-term debt, net of issuance costs 99,265 48,579 Accumulated deficit (1,717,083) (1,589,720) Total stockholders' equity 139,510 117,124 For Investor Inquiries: Lexicon Investor RelationsLexicon Pharmaceuticals, Inc.lexinvest@lexpharma.com For Media Inquiries: Alina KolomeyerLexicon Pharmaceuticals, Inc.akolomeyer@lexpharma.com