April 10, 2018 Welcome and Introduction Kimberly Lee, D.O. Head of Investor Relations and Corporate Strategy Precision Science. Pioneering Medicine. Patient Driven. 0 ©Precision 2018 Lexicon Pharmaceuticals, Science. Inc. Pioneering Medicine. Patient Driven. Forward-looking Statements This presentation, including any oral presentation accompanying it, contains “forward- looking statements,” including statements about Lexicon’s strategy and operating performance and events or developments that we expect or anticipate will occur in the future, such as projections of our future results of operations or of our financial condition, the level of market acceptance and commercial success of XERMELO®, the results of and expected timing of the completion of our ongoing and future clinical trials, the expected timing and outcome of discussions with regulatory authorities regarding such trials, the expected timing of initiation of our other planned clinical trials, the expected enrollment in our ongoing and future clinical trials, our other research and development efforts, the status of activities performed under our collaborative agreements and the anticipated trends in our business. These forward-looking statements are based on management’s current assumptions and expectations and involve risks, uncertainties and other important factors that 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 in our most recent annual report on Form 10-K and quarterly reports on Form 10-Q, including the sections entitled “Risk Factors,” as well as our current reports on Form 8-K, in each case 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. 1 © 2018 Lexicon Pharmaceuticals, Inc. April 10, 2018 Opening Remarks Lonnel Coats President and Chief Executive Officer Precision Science. Pioneering Medicine. Patient Driven. 2 ©Precision 2018 Lexicon Pharmaceuticals, Science. Inc. Pioneering Medicine. Patient Driven. R&D Day Agenda and Speakers Time Topic Speaker 8:30 – 8:35 Introduction Lonnel Coats 8:35 - 8:40 XERMELO market opportunity Alex Santini 8:40 – 8:50 XERMELO life cycle management introduction Praveen Tyle, Ph.D. 8:50 – 9:15 Preclinical evidence for and clinical development of XERMELO in cancer Ranuka Iyer, M.D. 9:15 – 9:30 Q&A Session #1 9:30 – 9:40 Coffee break 9:40 – 9:45 Sotagliflozin – introduction Pablo Lapuerta, M.D. 9:45 – 10:00 Sotagliflozin mechanism of action David Powell, M.D. 10:00 – 10:20 Sotagliflozin Phase 3 program Pablo Lapuerta, M.D. 10:30 – 10:45 Unmet need in type 1 diabetes and management of risk/benefit Jake Kushner, M.D. 10:45 – 11:05 Pipeline progress – LX2761 and LX9211updates Praveen Tyle, Ph.D. 11:05 – 11:10 Finance overview Jeffrey L. Wade, J.D. 11:10 – 11:25 Q&A Session #2 11:25 – 11:30 Closing remarks Lonnel Coats 3 © 2018 Lexicon Pharmaceuticals, Inc. Speaker Biographies Lonnel Coats, President and Chief Executive Officer and Director Mr. Coats has been our president and chief executive officer and a director since July 2014. From 1996 through June 2014, Mr. Coats served in a series of leadership positions at Eisai Inc. and Eisai Corporation of North America, most recently as chief executive officer from 2010 to June 2014 and president and chief operating officer from 2004 to 2010. Prior to joining Eisai, Mr. Coats spent eight years with Janssen Pharmaceuticals, Inc., a division of Johnson & Johnson, where he held a variety of management and sales positions. Mr. Coats received his B.P.A. from Oakland University. Alex Santini, Executive Vice President and Chief Commercial Officer Alexander A. Santini has been our executive vice president and chief commercial officer since November 2016 and previously served as vice president, market access and head of market access and channel management since joining our company in April 2015. Mr. Santini served in a series of leadership positions at Bayer Healthcare Pharmaceuticals from 2006 to October 2014, most recently as vice president of market access and executive member, where he had executive responsibility for market access, pricing, trade and channel management and payer account management. Prior to 2006, Mr. Santini held executive leadership roles of increasing responsibility at Berlex Laboratories, where he worked for 22 years before joining Bayer. Mr. Santini served as a non-commissioned officer in the United States Air Force, where he completed the Radiologic Technology Program at the United States Air Force School of Health Care Science and an AAS in business marketing from Westchester Community College. 4 © 2018 Lexicon Pharmaceuticals, Inc. Speaker Biographies Praveen Tyle, Ph.D., Executive Vice President of Research and Development Dr. Tyle has been our executive vice president of research and development since May 2016. Dr. Tyle was previously a member of the executive management team at Osmotic Pharmaceutical Corp., serving as president and chief executive officer from January 2013 through April 2016 and as executive vice president and chief scientific officer from August 2012 to December 2012. Prior to his service at Osmotica, Dr. Tyle held a series of leadership positions within the pharmaceutical industry, including executive vice president and chief science officer for the United States Pharmacopeia, senior vice president and global head of research and development and business development and licensing at Novartis OTC, corporate senior vice president of global research and development and chief scientific officer at Bausch & Lomb Incorporated and vice president and global head of pharmaceutical sciences at Pharmacia Corporation. Dr. Tyle received his B.Pharm. from the Indian Institute of Technology, Banaras Hindu University and his Ph.D. in pharmaceutics and pharmaceutical chemistry from the Ohio State University. Renuka Iyer, M.D., Section Chief, GI Medical Oncology, Co-Director Liver and Pancreas Tumor Center, Roswell Park Cancer Center Dr. Renuka Iyer is a Professor of Oncology and Co-Director of the Liver and Pancreas Tumor Program and Section Chief for Gastrointestinal Oncology for Roswell Park Comprehensive Cancer Center in Buffalo, NY. Her clinical and research focus is hepatocellular cancer, biliary cancer and neuroendocrine cancer and she does clinical and lab research in these diseases. Dr. Iyer received her MD at the University of Mumbai, Grant Medical College. She completed her residency at Lincoln Medical and Mental Health Center, Cornell University and her fellowship at Roswell Park before joining the faculty at Roswell Park where she has been for the last 14 years. She serves as co-chair of the regional meetings planning committee for NANETs and on the Medical and Nursing Advisory Board of the Cholangiocarcinoma Foundation. She is a member of the Alliance hepatobiliary clinical trials working group and a panelist on the NCCN hepatobiliary guidelines panel. 5 © 2018 Lexicon Pharmaceuticals, Inc. Speaker Biographies Pablo Lapuerta, M.D., Executive Vice President and Chief Medical Officer Dr. Lapuerta is our executive vice president and chief medical officer and previously served in a number of other roles since joining Lexicon in 2011, including executive vice president, safety, pharmacovigilance and medical affairs and executive vice president, clinical development. Prior to joining Lexicon, Dr. Lapuerta was a vice president at Bristol-Myers Squibb Company with responsibility for global development of an Alzheimer’s disease drug candidate. He also served as senior vice president, clinical strategy and chief medical officer for Cogentus Pharmaceuticals, Inc. He holds a B.A. in biology from Harvard College and an M.D. from Harvard Medical School. David Powell, M.D., Senior Vice President, Metabolism Research Dr. Powell received a B.A. from Rutgers University and an M.D. from UMDNJ – New Jersey Medical School. After pursuing postgraduate pediatric fellowship training in nephrology at the University of California – San Francisco and endocrinology research at Stanford University Medical School, Dr. Powell joined the Baylor College of Medicine Pediatrics faculty in 1986 where he practiced medicine as a nephrologist and ran an NIH-supported research program focusing on the action of insulin and other hormones. In 2000, Dr. Powell joined Lexicon to lead our metabolism research program. To date, this program has identified telotristat ethyl, an approved treatment for carcinoid syndrome diarrhea in combination with SSA therapy in adults inadequately controlled by SSA therapy, and both sotagliflozin and LX2761, investigational drugs for individuals with diabetes. 6 © 2018 Lexicon Pharmaceuticals, Inc. Speaker Biographies Jake Kushner, M.D., McNair Medical Institute Scholar and Associate Professor at the Baylor College of Medicine Dr. Jake Kushner is a McNair Medical Institute Scholar and an Associate Professor at the Baylor College of Medicine. For 6 years he served as Chief of Pediatric Diabetes and Endocrinology at the Baylor College of Medicine and Texas Children’s Hospital. A graduate of the University of California at Berkeley, Dr. Kushner earned his medical doctorate from Albany Medical College followed by pediatrics residency at Brown, pediatric endocrinology fellowship at Children’s Hospital Boston, and a 5-year research fellowship at