Pyelonephritis

On track for topline data from SPR720 Phase 2a proof-of-concept trial in treatment-naive and treatment-experienced non-refractory NTM-PD patients, expected in 2H 2024Initiated enrollment in PIVOT-PO, a pivotal Phase 3 clinical trial of oral Tebipenem HBr in cUTI Submitted IND for SPR206 and received FDA clearance to proceed with Phase 2 clinical trialReiterate expected cash runway into late 2025Conference call and webcast at 4:30pm ET today CAMBRIDGE, Mass., March 13, 2024 (GLOBE NEWSWIRE) -- Spero Therapeutics, Inc. (Nasdaq: SPRO), a multi-asset clinical-stage biopharmaceutical company, focused on identifying and developing novel treatments for rare diseases and multi-drug resistant (MDR) bacterial infections, today announced financial results for the fourth quarter and full year ended December 31, 2023, and provided a business update. “2023 was a productive year for Spero and we have been focused on execution across our programs,” said Sath Shukla, President, and Chief Executive Officer of Spero. “We are well poised to unveil top-line data for SPR720 Phase 2a, which is expected in 2H 2024, and our excitement is fueled by the hope it may bring for the rare disease community grappling with nontuberculous mycobacterial pulmonary disease (NTM-PD). On tebipenem HBr, engaging with the FDA and in collaboration with our partner, GSK, we are actively enrolling patients globally in our Phase 3 PIVOT-PO clinical trial. Positioned as the first oral broad-spectrum carbapenem in the United States for cUTI, we believe this product has the potential to change the treatment paradigm for these patients and underscores Spero’s commitment to innovation. We reiterate our expected cash runway into late 2025 based on our year-end cash balance, along with tebipenem HBr development milestone payments from GSK and our disciplined capital allocation.” Pipeline Update SPR720 SPR720 is an investigational novel, oral, first-line treatment for NTM-PD. Top-line data from the Phase 2a proof-of-concept clinical trial in treatment-naive and treatment-experienced non-refractory NTM-PD patients is expected in 2H 2024. The trial is expected to enroll treatment-naïve or treatment-experienced participants with non-refractory NTM-PD due to Mycobacterium avium complex. The primary endpoint evaluates changes in bacterial load in sputum samples from baseline to the end of the 56-day treatment period. Key secondary endpoints include assessments of clinical response, quality of life, pharmacokinetics, and safety and tolerability. For more information on the trial, see ClinicalTrials.gov identifier NCT05496374.A paper Efficacy of SPR720 in murine models of non-tuberculous mycobacterial pulmonary infection (Nicole Cotroneo et al) was published in Journal of Antimicrobial Chemotherapy in February 2024.A paper Nontuberculous mycobacterial pulmonary disease and the potential role of SPR720 (Kevin Winthrop et al) was published in Expert Review of Anti-infective Therapy in October 2023. Tebipenem HBr Tebipenem HBr is an investigational oral carbapenem antibiotic being developed for the treatment of complicated urinary tract infection (cUTI) including acute pyelonephritis (AP) to help patients avoid hospitalizations or reduce duration of in-patient therapy. Spero commenced enrollment in PIVOT-PO, a global, randomized, double-blind, Phase 3 clinical trial of tebipenem HBr in patients with cUTI, including AP in December 2023. The trial compares oral tebipenem HBr with intravenous imipenem cilastatin, in hospitalized adult patients with cUTI/AP. The primary endpoint is the number of patients with overall response (a combination of clinical cure and favorable microbiological response) at the Test-of-Cure (TOC) visit. The trial is expected to enroll approximately 2,648 patients, with enrollment completion anticipated in 2H 2025. For more information on PIVOT-PO, refer to ClinicalTrials.gov ID NCT06059846. In July 2023, Spero received written agreement from the U.S. Food and Drug Administration (FDA), under a Special Protocol Assessment (SPA), on the design and size of PIVOT-PO. The FDA has indicated that positive and persuasive results from PIVOT-PO, supported with confirmatory evidence of efficacy, could be sufficient to support approval of tebipenem HBr as a treatment for cUTI, including pyelonephritis, for a limited use indication. Under the terms of its license agreement with GSK, in December 2023, upon dosing the first patient, Spero earned $95 million in development milestones payable in four equal installments over two years. Spero also received a $30 million development milestone payment following the SPA. Further details on the agreement with GSK can be found here. SPR206 SPR206 is an innovative, investigational IV-administered direct-acting next generation polymyxin that has shown antibiotic activity against MDR Gram-negative pathogens, including carbapenem-resistant Enterobacteriaceae, Acinetobacter baumannii and Pseudomonas aeruginosa in preclinical studies. An Investigational New Drug (IND) application has been cleared by the FDA to advance SPR206, to treat MDR Gram-negative bacterial infections, into a Phase 2 clinical trial in participants with hospital-acquired or ventilator-associated bacterial pneumonia.The results from the Phase 1 bronchoalveolar lavage (BAL) study of SPR206 were published in a paper Pharmacokinetics of SPR206 in Plasma, Pulmonary Epithelial Lining Fluid, and Alveolar Macrophages following Intravenous Administration to Healthy Adult Subjects (Keith Rodvold et al) in Antimicrobials and Chemotherapy in July 2023. A paper Safety and pharmacokinetics of SPR206 in subjects with varying degrees of renal impairment (Jon B. Bruss et al) was published in Antimicrobials and Chemotherapy in October 2023. Corporate Highlights Satyavrat “Sath” Shukla successfully transitioned to President and Chief Executive Officer (CEO) of the company, and a member of the Board of Directors in August 2023. Mr. Shukla had previously been Chief Financial Officer and Treasurer of the company. Mr. Shukla succeeded Spero’s prior CEO and President, Ankit Mahadevia, M.D., who became Chair of the Board of Directors in August 2023.Esther Rajavelu was appointed as Chief Financial Officer, Chief Business Officer, and Treasurer in November 2023. Ms. Rajavelu brings over 20 years of experience working in the biotech and financial sectors focused on growth strategy, M&A, and financing. Fourth Quarter and Full Year 2023 Financial Results Spero reported net income of $51.2 million for the fourth quarter and an overall net income of $22.8 million, for the year ended December 31, 2023, or a diluted net income per share of common stock of $0.96 and $0.43, respectively. Net income for the fourth quarter and net loss for the year ended December 31, 2022, was $26.8 million and $(46.4) million, or $0.55 and $(1.23) per share of common stock, respectively.Total revenue for the fourth quarter of 2023 was $73.5 million, compared with total revenue of $47.4 million for the fourth quarter of 2022. The revenue increase for the fourth quarter of 2023 was primarily due to $71.8 million in collaboration revenue related to our agreements with GSK and Pfizer. Total revenue for the year ended December 31, 2023 was $103.8 million, compared to $53.5 million for the year ended December 31, 2022. The revenue increase for the year ended December 31, 2023, was primarily due to the aforementioned collaboration revenue related to our agreements with GSK and Pfizer.Research and development expenses for the fourth quarter of 2023 were $16.6 million, compared to $15.1 million of research and development expenses for the same period in 2022. Research and development expenses for the year ended December 31, 2023 were $51.4 million, compared to $47.6 million for the year ended December 31, 2022. The increase in research and development expenses year-over-year was primarily due to increased clinical activity during the period related to the ongoing Phase 2a clinical trial of SPR720, offset by personnel-related costs.General and administrative expenses for the fourth quarter of 2023 were $6.4 million, compared to $6.5 million of general and administrative expenses for the same period in 2022. This year-over-year decrease was primarily due to changes in personnel-related costs, offset by increased professional and consulting fees. General and administrative expenses for the year ended December 31, 2023, were $25.6 million, compared to $36.5 million for the year ended December 31, 2022, with lower expenses in 2023 compared to 2022 primarily due to decreases in both personnel-related costs and professional and consulting fees.As of December 31, 2023, Spero had cash and cash equivalents of $76.3 million. Since the year-end closing of financials, the company received $23.8 million, the first tranche of the $95.0 million in development milestones from GSK. Based on its current operating plans, Spero expects that its cash and cash equivalents, together with other non-dilutive funding commitments, will be sufficient to fund its operating expenses and capital expenditure requirements into late 2025. For further details on Spero’s financials, refer to Spero’s Annual Report on Form 10-K, filed with the U.S. Securities and Exchange Commission (SEC) today. Conference Call and Live Webcast Today at 4:30 pm EST Spero will host a conference call and webcast today at 4:30 p.m. ET. To access the call, please dial 1-877-704-4453 (domestic) or 1-201-389-0920 (international) and refer to conference ID 13744458 or click on this Link and request a return call. The conference call will also be webcast live and can be accessed through this website link, and on Spero's website at www.sperotherapeutics.com on the "Events and Presentations" page under the "Connect" tab. An archived webcast will be available on Spero's website for 30 days following the presentation. Tebipenem HBr Research SupportSelect tebipenem HBr studies have been funded in part with federal funds from the Department of Health and Human Services; Administration for Strategic Preparedness and Response; Biomedical Advanced Research and Development Authority, under contract number HHSO100201800015C. Government Agency Research Support The views expressed in this press release are those of the authors and may not reflect the official policy or position of the Department of the Army, Department of Defense, or the U.S. Government. Department of Defense Select SPR206 studies are supported by the Office of the Assistant Secretary of Defense for Health Affairs, through the Joint Warfighter Medical Research Program under Award No. W81XWH 19 1 0295. Opinions, interpretations, conclusions, and recommendations are those of the author and are not necessarily endorsed by the Department of Defense. National Institute of Allergy and Infectious Disease Select SPR206 studies have been funded in whole or in part with Federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under Contract No. 75N93021C00022. About Spero TherapeuticsSpero Therapeutics, headquartered in Cambridge, Massachusetts, is a multi-asset clinical-stage biopharmaceutical company focused on identifying and developing novel treatments for rare diseases and MDR bacterial infections with high unmet need. For more information, visit www.sperotherapeutics.com. Forward Looking Statements This press release may contain forward-looking statements. These statements include, but are not limited to, statements about the design, initiation, timing, progress and results of Spero's preclinical studies and clinical trials and its research and development programs, as well as the regulatory path forward for tebipenem HBr and potential FDA approval, the potential commercialization of tebipenem HBr, the potential receipt under the GSK license agreement of milestone payments and royalties on future sales of tebipenem HBr, and Spero’s cash runway. In some cases, forward-looking statements can be identified by terms such as "may," "will," "should," "expect," "plan," "aim," "anticipate," "could," "intent," "target," "project," "contemplate," "believe," "estimate," "predict," "potential" or "continue" or the negative of these terms or other similar expressions. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including whether tebipenem HBr, SPR720 and SPR206 will advance through the clinical trial process on a timely basis, or at all, taking into account the effects of possible regulatory delays, slower than anticipated patient enrollment, manufacturing challenges, clinical trial design and clinical outcomes; whether the results of such trials will warrant submission for approval from the FDA or equivalent foreign regulatory agencies; whether the FDA will ultimately approve tebipenem HBr and, if so, the timing of any such approval; whether the FDA will require any additional clinical data or place labeling restrictions on the use of tebipenem HBr that would delay approval and/or reduce the commercial prospects of tebipenem HBr; whether a successful commercial launch can be achieved and market acceptance of tebipenem HBr can be established; whether results obtained in preclinical studies and clinical trials will be indicative of results obtained in future clinical trials; Spero's reliance on third parties to manufacture, develop, and commercialize its product candidates, if approved; Spero’s need for additional funding; the ability to commercialize Spero's product candidates, if approved; Spero's ability to retain key personnel; Spero’s ongoing leadership transitions; whether Spero's cash resources will be sufficient to fund its continuing operations for the periods and/or trials anticipated; and other factors discussed in the "Risk Factors" set forth in filings that Spero periodically makes with the SEC. The forward-looking statements included in this press release represent Spero's views as of the date of this press release. Spero anticipates that subsequent events and developments will cause its views to change. However, while Spero may elect to update these forward-looking statements at some point in the future, it specifically disclaims any obligation to do so. These forward-looking statements should not be relied upon as representing Spero's views as of any date subsequent to the date of this press release. Investor Relations Contact:Ashley R. RobinsonManaging Director, LifeSci Advisors, LLCarr@lifesciadvisors.com(617) 775-5956 Media Inquiries: media@sperotherapeutics.com Spero Therapeutics, Inc.Condensed Consolidated Balance Sheet Data(in thousands)(Unaudited) December 31, December 31, 2023 2022 ChangeCash, cash equivalents and marketable securities $76,333 $109,107 $(32,774)Other assets 106,057 15,695 90,362 Total assets $ 182,390 $ 124,802 $ 57,588 Total liabilities $75,496 $48,868 $26,628 Total stockholder's equity 106,894 75,934 30,960 Total liabilities and stockholders' equity $ 182,390 $ 124,802 $ 57,588 Spero Therapeutics, Inc.Condensed Consolidated Statements of Operations(in thousands, except share and per share data)(unaudited) Three Months Ended December 31, Year Ended December 31, 2023 2022 2023 2022 Revenues: Grant revenue $1,698 $1,087 $7,046 $4,930 Collaboration revenue - related party 71,603 46,076 95,802 46,076 Collaboration revenue 223 278 933 2,503 Total revenues 73,524 47,441 103,781 53,509 Operating expenses: Research and development 16,558 15,089 51,440 47,593 General and administrative 6,433 6,495 25,554 36,483 Impairment of long-term asset — — 5,306 — Restructuring — (67) — 11,630 Total operating expenses 22,991 21,517 82,300 95,706 Loss from operations 50,533 25,924 21,481 (42,197)Other income (expense) 1,046 847 3,923 (4,218)Net income (loss) before income taxes 51,579 26,771 25,404 (46,415)Income tax expense (387) — (2,598) — Net income (loss) attributable to common shareholders of Spero Therapeutics, Inc. $51,192 $26,771 $22,806 $(46,415) Net loss per share attributable to common shareholders per share, basic $0.97 $0.55 $0.43 $(1.23)Net loss per share attributable to common shareholders per share, diluted $0.96 $0.55 $0.43 $(1.23) Weighted average shares outstanding, basic: 52,999,491 48,715,409 52,703,467 37,585,075 Weighted average shares outstanding, diluted: 53,108,270 48,942,616 52,989,030 37,585,075

Key Hires in CMC/Technical Operations, Business Development, and Finance MALVERN, Pa.--(BUSINESS WIRE)-- Venatorx Pharmaceuticals, a private, pre-commercial pharmaceutical company focused on improving health outcomes for patients with multidrug-resistant bacterial infections and hard-to-treat viral infections, announced expansion of its leadership team with three key industry veterans: Jason Burdette joining as Senior Vice President, CMC and Technical Operations: Armand Girard as Chief Business Officer; and Tamra Adams, and Chief Financial Officer. These appointments come as the Company expands its remit from pure R&D to encompass support of commercialization. "Jason, Armand and Tamra bring a breadth of experience that will be instrumental to Venatorx as we continue to advance our portfolio and maximize the value of our assets," said Christopher J. Burns, Ph.D., President and CEO of Venatorx. "These additions to our senior leadership team are critical to ensure we are prepared for our NDA resubmission and are strategically positioned for continued success." Jason Burdette – Senior Vice President, CMC and Technical Operations – Burdette started at Venatorx in late 2023 and is an experienced leader with more than 30 years in the pharmaceutical industry across process chemistry, formulation and process development, manufacturing, supply chain management, and technical operations. He joined Venatorx from Aimmune/Nestle Health Science where he was a Senior Vice President and Head of Technical Operations. At Aimmune/Nestle Health Science, Burdette was responsible for formulation and process development, analytical development, CMC, manufacturing science and technology, quality control, quality assurance, supply chain, and product distribution. Before this, he was the Senior Vice President of Technical Operations with Paratek Pharmaceuticals and over the years has worked at Eagle Pharmaceuticals, Shire with aaiPharma, Elan Pharmaceuticals, Sandoz, and Mylan Pharmaceuticals. Burdette earned a bachelor's degree in chemistry and an MBA from West Virginia University. Armand Girard – Chief Business Officer – Girard is a seasoned biopharmaceutical executive with multiple product approvals and launches over his 25 years of experience in strategic planning, corporate development, clinical development, and business development. He has extensive partnering experience having completed collaborations, licenses, acquisitions, and spinouts by and between leading pharmaceutical and biotech companies. Girard joined Venatorx from GlycoMimetics where he was the Chief Business Officer. At GlycoMimetics, he was responsible for corporate strategy, partnering, and managing the company's corporate and institutional alliances supporting the development of uproleselan. Previously, he was Vice President, Technical Assessment and Senior Director for Business Development at Shire Pharmaceuticals to build the product pipeline and support Shire's strategic venture arm through investments. He received his undergraduate degree from Lehigh University and an MBA from St Joseph's Haub School of Business Executive Pharmaceutical Marketing Program. Tamra Adams – Chief Financial Officer – Adams has over 25 years of financial management experience. Most recently, she was CFO at Antios Therapeutics, a clinical-stage biopharmaceutical company that was developing innovative therapies to treat and cure HBV. Adams helped lead a $107 million financing and was responsible for IPO readiness, including filing the S-1. Before joining Antios, she founded Accounting Concepts, Inc., a firm that provided CFO, accounting, and financial services to emerging growth companies in the biopharmaceutical and information technology industries. Before that, Adams was the Senior Financial Executive at Silverstorm Technologies and began her career at Ernst & Young, followed by Goldman Sachs. She received her undergraduate degree from the State University of New York at Albany and received her CPA license in New York State. About Venatorx Pharmaceuticals, Inc. Venatorx is a private, late-stage clinical pharmaceutical company focused on improving health outcomes for patients with multidrug-resistant bacterial infections and hard-to-treat viral infections. Venatorx’s lead program, cefepime-taniborbactam, is a clinical-stage antibiotic that successfully completed a Phase 3 study in adults with complicated urinary tract infections (cUTI), including pyelonephritis. In October 2022, BARDA awarded a contract of up to $318M for development and procurement of cefepime-taniborbactam for the treatment of melioidosis and multi-drug resistant infections. Venatorx is also developing an oral antibacterial, ceftibuten-ledaborbactam (formerly known as VNRX-7145), for the treatment of cUTI, including pyelonephritis, caused by certain bacteria in adult patients with limited treatment options; this product is completing Phase 1 and will advance directly to a global Phase 3 cUTI clinical trial. For more information about Venatorx and its anti-infectives portfolio, please visit . Forward Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including without limitation statements regarding the potential, safety, efficacy, and regulatory and clinical development of Venatorx Pharmaceuticals’ product candidates.

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