LXRX Lexicon Pharmaceuticals Inc

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 or
• type 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