SGLT1

Lexicon Pharmaceuticals' original Zynquista FDA rejection was in 2019. Since then, the company has persisted in its regulatory efforts. Ever since its first FDA rejection five years ago, Lexicon Pharmaceuticals hasn’t given up hope on its Type 1 diabetes prospect sotagliflozin. Now, the company’s approval dreams could be coming into focus as the drugmaker prepares to refile its application. After hearing recent regulatory feedback from the agency, Lexicon said it plans to submit the drug by the middle of the year, the company said in a press release. “We have remained steadfast in our support of sotagliflozin in type 1 diabetes and have worked diligently to identify a regulatory path forward for what we believe will be an important new therapy,” CEO Lonnel Coats noted in the release. Lexicon is hoping for an approval that clears the drug to be used as an add-on to insulin therapy for adults with Type 1 diabetes mellitus and chronic kidney disease, the company said in its fourth-quarter and full-year earnings presentation (PDF). If approved, the drug will be branded as Zynquista. Lexicon hit the first bump on its regulatory road in 2019, when the FDA rejected its bid with a safety-related complete response letter following a 8-8 vote from an advisory committee. At the time, Sanofi was partnered on the drug, but the French pharma jumped ship after the rejection and subsequent trial flops in Type 2 diabetes. In the rejection, the FDA cited concerns about the risk of diabetic ketoacidosis for patients taking insulin plus Zynquista. However, Lexicon maintains that the risk can be managed and may be outweighed by patients' unmet needs. Despite the FDA rejection, Zynquista was approved in Europe in 2019. Lexicon has a trove of phase 3 data proving Zynquista’s worth in diabetes with chronic kidney disease when paired with insulin, the company has said. The long-awaited nod would be highly beneficial to Lexicon, which took home $1.2 million in total 2023 revenues. Net losses for the year came out to $175.6 million. At one point, some analysts had blockbuster-level expectations for the drug. Meanwhile, the drugmaker has been able to take sotaglifozin into another indication. The med scored approval for heart failure last year—branded as Inpefa—and launched weeks later, marking the first SGLT1/SGLT2 inhibitor to hit the U.S. market. The company is also testing the drug in hypertrophic cardiomyopathy.

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

-INPEFA® Launch Positioned for Acceleration in 2024- -Clinical Data and FDA Feedback Support INPEFA Life Cycle Management Opportunity in Hypertrophic Cardiomyopathy- -LX9211 Late-Stage Development Underway, with Potential to Be First New Non-Opioid Drug for Diabetic Peripheral Neuropathic Pain in Over Two Decades- -Company Presentation January 11, 2024 at 10:30am PST (1:30pm ET)- THE WOODLANDS, Texas, Jan. 08, 2024 (GLOBE NEWSWIRE) -- Lexicon Pharmaceuticals, Inc. (Nasdaq: LXRX), a biopharmaceutical company with a mission of pioneering medicines that transform patients’ lives, today announced a business and pipeline update at the 42nd Annual J.P. Morgan Healthcare Conference taking place January 8-12, 2024. “Lexicon achieved major advancements in 2023 in its business and pipeline of pharmaceutical innovations,” said Lonnel Coats, chief executive officer and director of Lexicon. “We gained FDA approval in heart failure for INPEFA® (sotagliflozin), an important new drug created from our own discovery efforts, and we advanced neuropathic pain drug candidate LX9211 into late-stage development. We are working diligently to build on this success in 2024 as we focus on accelerating the launch of INPEFA, leveraging its differentiated profile and recently-adopted guidelines in the large, fast-growing and under-penetrated heart failure market, and advancing the clinical program for LX9211 in diabetic peripheral neuropathic pain (DPNP), where it has the potential to become the first, new, non-opioid drug in over two decades. We are also evaluating additional opportunities for partnership and growth including life-cycle management potential for INPEFA in hypertrophic cardiomyopathy (HCM).” INPEFA Launch Positioned for Acceleration in 2024 Lexicon continues to focus on accelerating the launch of INPEFA, having recently strengthened and evolved its commercial organization to be better placed for success with recent leadership additions and a sales force in place of approximately 150 cardiovascular specialty representatives focused on high-volume prescribers and institutions. The company’s sales force has succeeded in driving demand well ahead of filled prescriptions in 2023 pending continuing progress in establishing broader market access and reimbursement. Further improving and expanding market access and reimbursement is a key area of focus in 2024, together with driving further prescription and prescriber growth and achieving favorable formulary decisions among integrated delivery networks (IDNs). Lexicon aims to significantly increase market access coverage in the first half of 2024 and expects continued prescription and net sales growth throughout the year, accelerating in the second half of 2024. The company will also focus on ensuring a strong ongoing awareness of INPEFA in the medical community through medical publications and congress presence. Clinical Data and FDA Feedback Support INPEFA Life Cycle Management Opportunity in HCMClinical data from INPEFA’s heart failure studies and its unique mechanism of inhibiting SGLT1 and SGLT2 support a life-cycle management opportunity in HCM, a condition of high unmet need that affects approximately one million people in the U.S. In discussions with the FDA, Lexicon has aligned on a protocol for a single Phase 3 study that could support a supplemental New Drug Application (sNDA) for an INPEFA label expansion encompassing patients with both obstructive and non-obstructive HCM. Exploration of Potential Path Forward in Type 1 Diabetes Lexicon and the FDA agreed to pause the pending proceedings relating to Lexicon’s request for an administrative hearing on whether there were grounds for the FDA’s previous denial of the NDA for sotagliflozin in type 1 diabetes in order to engage in discussions, now underway, regarding a potential path forward for the approval of sotagliflozin in type 1 diabetes. LX9211 Late-Stage Development Underway, with Potential to Be First New Non-Opioid Drug for DPNP in Over Two DecadesAn estimated 20 million patients in the U.S. experience neuropathic pain, and approximately 5 million patients experience DPNP, with the current standard of care often inadequate and involving undesirable side effects. LX9211 has the potential to be the first non-opioid approach with a novel mechanism in over two decades in this large, underserved market. LX9211 is distinguished in having established clinical success versus placebo in its Phase 2 proof-of-concept study, an important achievement enabling progression into late-stage development and pivotal studies. LX9211 is further distinguished in having achieved clinical success in a study, aligned with how new DPNP drugs are likely to be used in practice, in which patients were permitted to maintain one stable-dose DPNP therapy (gabapentin, pregabalin or duloxetine) without being forced to withdraw from therapies that, although inadequate, may be providing benefit. Patient enrollment in the PROGRESS Phase 2b study is now underway, with data anticipated in Q2 2025. Company to Present at J.P. Morgan Healthcare Conference Thursday, January 11, 2024 at 10:30am PST (1:30pm ET)Lonnel Coats, Lexicon’s chief executive officer, will make a company presentation. Jeff Wade, Lexicon’s president and chief financial officer, Tom Garner, Lexicon’s senior vice president and chief commercial officer, and Craig Granowitz, M.D., Ph.D., Lexicon’s senior vice president and chief medical officer, will also participate. A simultaneous webcast will be available in the “Events” section of the Lexicon website at www.lexpharma.com/events, and a recording of the webcast will be available for two weeks following the original on-demand date. INDICATIONINPEFA® 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 INFORMATIONDosing: 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 a history of serious hypersensitivity reaction to INPEFA.Warnings and Precautions: 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. 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 is commercially launching one of these medicines, INPEFA® (sotagliflozin) in the United States, and has a pipeline of other promising drug candidates in discovery and clinical and preclinical development in 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, growth and future operating results, discovery and development 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 INPEFA in heart failure on the timeline and/or at the prices currently contemplated or at all, conduct preclinical and clinical development and obtain necessary regulatory approvals of INPEFA (in other indications), LX9211 and 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 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 and other subsequent disclosure documents 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. For Investor Inquiries: Lisa DeFrancesco Lexicon Pharmaceuticals, Inc.lexinvest@lexpharma.com For Media Inquiries: Alina CocuzzaLexicon Pharmaceuticals, Inc.acocuzza@lexpharma.com