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© 2018 Lexicon Pharmaceuticals, Inc. 0 Precision Science. Pioneering Medicine. Patient Driven.
Welcome and Introduction
Precision Science. Pioneering Medicine. Patient Driven.
Kimberly Lee, D.O.Head of Investor Relations and Corporate Strategy
April 10, 2018
© 2018 Lexicon Pharmaceuticals, Inc. 1
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.
Forward-looking Statements
© 2018 Lexicon Pharmaceuticals, Inc. 2 Precision Science. Pioneering Medicine. Patient Driven.
Opening Remarks
Precision Science. Pioneering Medicine. Patient Driven.
Lonnel CoatsPresident and Chief Executive Officer
April 10, 2018
© 2018 Lexicon Pharmaceuticals, Inc. 3
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
© 2018 Lexicon Pharmaceuticals, Inc. 4
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.
© 2018 Lexicon Pharmaceuticals, Inc. 5
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.
© 2018 Lexicon Pharmaceuticals, Inc. 6
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 CogentusPharmaceuticals, 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.
© 2018 Lexicon Pharmaceuticals, Inc. 7
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 the Joslin Diabetes Center (both of Harvard Medical School). Dr. Kushner has received numerous national honors, including a Basil O’Connor award from the March of Dimes and elected membership to the American Society of Clinical Investigation. He has also served as president of the Society for Pediatric Research. His research has been supported by the National Institutes of Health, the Juvenile Diabetes Research Foundation, and other sources. Dr. Kushner serves as an advisor to Lexicon Pharmaceuticals, Virta Health Inc., and the T1D Exchange. He is the current chair of DDK-B, an NIH study section that reviews training applications in diabetes research. Dr. Kushner’s clinical interests center around the care of children, adolescents, and young adults with type 1 diabetes.
Jeffrey L. Wade, J.D., Executive Vice President, Corporate and Administrative Affairs and Chief Financial Officer
Mr. Wade is our executive vice president, corporate and administrative affairs and chief financial officer. Mr. Wade has been with Lexicon since 1999 and has served in a number of roles, including executive vice president, corporate development and chief financial officer and executive vice president and general counsel. Prior to joining Lexicon, he was a corporate securities and finance attorney with the law firm of Andrews & Kurth L.L.P., most recently as a partner, where he represented companies in the biotechnology, information technology and energy industries. Mr. Wade is a member of the board of directors of the Texas Healthcare and Bioscience Institute. He received his B.A. and J.D. from the University of Texas.
© 2018 Lexicon Pharmaceuticals, Inc. 8 Precision Science. Pioneering Medicine. Patient Driven.
XERMELO Market Opportunity
Precision Science. Pioneering Medicine. Patient Driven.
Alex SantiniExecutive Vice President and Chief Commercial Officer
April 10, 2018
© 2018 Lexicon Pharmaceuticals, Inc. 9
XERMELO® (telotristat ethyl) - First and Only Oral Treatment Approved for Carcinoid Syndrome Diarrhea
• Reduces serotonin production
• Reduces frequency of carcinoid syndrome diarrheaN o v e l , o r a l t r y p t op h a n
h y d r o x y l a s e ( T P H ) i n h i b i t o r
• U.S. approval February 28, 2017
• U.S. launch March 1, 2017
• EU approval September 19, 2017
© 2018 Lexicon Pharmaceuticals, Inc. 10
Carcinoid Syndrome Diarrhea – Meaningful Market Opportunity
D E S C R I P T I O N P A T I E N T P O P U L A T I O N *
Includes:
• Frequent, debilitating diarrhea
• Facial flushing
• Abdominal pain
• Fatigue
• Heart valve damage over time
Carcino id syndrome resu l ts f rom metas tat ic neuroendocr ine tumors (mNETs ) that produce la rge amounts o f serotonin , a key med iator o f gas tro intest ina l mot i l i ty , pa in and inf lammat ion
D I S E A S E B U R D E N
~14,000 Patients in U.S.
~98% On SSA therapy in U.S.
*EPI Research, NET Claims data from IMS, Lexicon-sponsored market research with 50 oncologists, August 2014; Yao et al. J Clin Onc. 26:3063-3072, 2008.
WAC for SSA therapies ~ $6,111-$7,249/month~11% CAGR in WAC over past 2 years
© 2018 Lexicon Pharmaceuticals, Inc. 11
Perception Study – Physicians’ vs. Patients’ View of Symptom Control
Source: Primary research with 80 oncologists and 24 patients (May 2015)
45% Uncontrolled
80%
20% Controlled
80% Uncontrolled
55% Controlled
Physicians’ View Patients’ View
There remains a significant difference between patients’ and physicians’ attitudes toward how well controlled the disease is
© 2018 Lexicon Pharmaceuticals, Inc. 12 Precision Science. Pioneering Medicine. Patient Driven.
XERMELO Life Cycle Management –Introduction
Precision Science. Pioneering Medicine. Patient Driven.
Praveen Tyle, Ph.D.Executive Vice President, Research & Development
April 10, 2018
© 2018 Lexicon Pharmaceuticals, Inc. 13
XERMELO® (telotristat ethyl) Life Cycle Management
Compound Indication Preclinical Phase 1 Phase 2 Phase 3 Registration Marketed
Carcinoid syndrome diarrhea
Carcinoid syndrome diarrhea
Telotristat EthylNeuro-endocrine tumor (NET)
Telotristat EthylBiliary tract cancer(BTC)
Telotristat EthylInvestigator-Initiated studies
Telotristat Ethyl/other TPH inhibitors
Other indications
FDA approval Feb 28, 2017; US launch Mar 01, 2017
EMA approval Sept 19, 2017; EU launch ongoing
Initiating Phase 2 in 2018
Initiating Phase 2 in 2018
In discussion
© 2018 Lexicon Pharmaceuticals, Inc. 14
XERMELO (telotristat ethyl) and Somatostatin Analogs (SSAs) Have Different and Complementary Mechanisms of Action
Tryptophan
5-hydroxytryptophan (5-HTP)
Serotonin (5-HT)
Tryptophan hydroxylase
(TPH)
Neuroendocrine tumor (NET) cell
SSASSTR
Telotristatethyl
Graphic adapted from: Kronenberg H, et al, eds. Williams Textbook of Endocrinology. 11th ed. 2008:1823-1824 and Van der Horst-Schrivers A, et al. Neuroendocrinology. 2004;80(suppl 1):28-32.
1XERMELO [prescribing information]. The Woodlands, TX: Lexicon Pharmaceuticals, Inc.; February 2017.2Sandostatin LAR Depot [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; July 2016. 3Molina-Cerrillo J, et al. Oncologist. 2016;21(6):701-707. 4Appetecchia M, Baldelli R. J Exp Clin Cancer Res. 2010;29:19.
Inside the Cell• Telotristat ethyl
inhibits TPH 1,3
• Telotristat ethyl decreases serotonin overproduction 1
Outside the Cell• SSA blocks the release
of serotonin 2,4
© 2018 Lexicon Pharmaceuticals, Inc. 15
XERMELO (telotristat ethyl) Life Cycle Management –
Anti-tumor Activity Driven by Mechanism of Action
➢Clinical studies have established anti-tumor activity of SSAs in patients with NETs▪ Multiple pathways are involved, one of which relates to inhibition
of serotonin release
➢Preclinical data show that inhibiting TPH and serotonin synthesis reduces cancer cell growth in cholangiocarcinoma and gallbladder cancer (biliary tract cancers – BTC)
➢Suggest an opportunity for XERMELO
➢ Initiating Phase 2 studies
Preclinical evidence for and
clinical development of
XERMELO in cancer
Renuka Iyer, M.D.,
Roswell Park Comprehensive Cancer Center
Name/ Topic Company Role
Renuka Iyer, MD
Novartis;
Ipsen Biopharmaceuticals, Inc.
Merck;
Ipsen Biopharmaceuticals, Inc.
Eisai Oncology, Bayer
Consulting / Speaking / Teaching
Grant / Research Support
Advisory Committee / Review Panel
Relevant Disclosure and Resolution
In accordance with the ACCME® standards for Commercial Support these relationships were reviewed
Under Accreditation Council for Continuing Medical Education, guidelines disclosure must be made regarding relevant financial
relationships with commercial interests within the last 12 months.
Overview
• Role of serotonin in solid tumors
• 5HT blockade slows tumor growth
• Neuroendocrine Tumor (NET) Overview- NET Space
• Where Xermelo may fit (Rationale: 5HT+ mTOR/ 5HIAA)
• Biliary Tract Cancer (BTC) Overview - BTC Space
• Preclinical studies in BTC models
• Chronic inflammation and Immunity - BTC and Tryptophan
• Where Xermelo may fit
• Takeaways
Serotonin in Solid Tumors
• Serotonin is a mitotic factor
• Serotonin growth stimulatory
effect also seen on several types
of carcinoma and carcinoid cell
lines
• Inhibition of cancer cell growth
occurs in some cases through
serotonin receptor antagonists
• Current evidence suggests
inhibiting serotonin production via
TPH1 could inhibit proliferation of
cancer cells
Adapted from Sarrouilhe D, et al. Curr Mol Med. 2015;15:62-77. * Christensen DK 2016 Oncotarget
/ NETs
Anti-5HT inhibits tumor growth - Synergy
with mTOR
• Anti-5HT therapy showed slower growth rate (A,
B) (CHEMOPREVENTIVE EFFECT)
• 4/12 mice developed tumors (33%) less
incidence (C/D) in wild type and no tumors in
TPH deleted 0/11
Growth with rapamycin + SB 204 (antagonist of
5HT)1
In presence of fetal calf serum (control) rapa
did not inhibit proliferation but SB204 did
1 Soll C, Hepatology, 51(4) 2010: 1244-1254
SB 204 + rapa
SB 204
Rapa
SB 204
SB 204 + rapa
Rapa
Neuroendocrine Tumors – Overview
• Neuroendocrine tumors (NETs), a relatively rare and heterogeneous tumor type, affect approximately 171,321 people in the United States1
• Cause debilitating symptoms and potentially life-threatening issues2, many from dense fibrosis
• Classified by embryonic origin (foregut, midgut,
and hindgut)3,4
• Diagnosis is complex, may remain asymptomatic for a long time and is often misdiagnosed due to non-specific symptoms5,6
• First-line systemic treatment of GEP-NETs is long-acting SSAs7,8
• Second-line systemic treatments include everolimus, chemotherapy, PRRTs and liver-directed therapies7,8
1 Dasari A JAMA Oncol. 2017 Oct 1;3(10):1335-1342. 2 Hallet J, et al. Cancer. 2015;121:589-597. 3 Lawrence B, et al. Endocrinol
Metab Clin North Am. 2011;40:1-18. 4 Friling A, et al. Endocr Relat Cancer. 2012;19:R163-R185. 5 Mamikunian G, et al, eds.
Neuroendocrine Tumors: A Comprehensive Guide to Diagnosis and Management. 4th ed. Inglewood, CA: Inter Science Institute;
2009. 6 Öberg K. Ann Oncol. 2010;21(suppl 7):vii72-vii80. 7 Kunz P. J Clin Oncol. 2015;33:1855-1863. 8NCCN clinical practice
guidelines in oncology (NCCN Guidelines®): neuroendocrine tumors. V.3.2017.
http://www.nccn.org/professionals/physician_gls/pdf/neuroendocrine.pdf. Accessed 10/12/2017
NET Space: New Antitumor Agents
Needed
• SSA: Anti-proliferative effects (PROMID 13 months, CLARINET 29 months NR) control arm placebo
First line untreated, GEPNETs. Not lung.
• Everolimus: RR ~7-9%, PFS 11 months RADIANT 4 control arm placebo 3.9 months.
After SSA, progressed within last 6 months. All NETs, ECOG 0,1
• PRRT: RR 18%, PFS 25-40 months. Control arm Sandostatin 60 mg,
Benefit varies.
Pancreas > GI NETs > Unknown primary NETs. Only
for SSR positive disease, restricted to tertiary sites, good kidney
function.
Correlation Between u5-HIAA Levels and
Outcome in NETs
• TELESTAR study, Xermelo treatment associated with weight gain- unexplained-
Was it due to stable disease?
• PFS or QOL, or SD is the best response even in effective therapies in NETS:
PROMID (66%), CLARINET (NR), RADIANT 4 (73%) AND NETTER- 1 (NR) in
this disease
1 Van der Horst-Schrivers A, et al. Eur J Cancer. 2007;43:2651-2657. 2 Bartholomew T, et al. Poster. ENETS. 2014 (abstr H2).3 Kulke MH et al, J Clin Oncol. 2017 ;35(1):14-23. 4 Yao J GI asco 2012 J ournal of Clinical Oncology 2012 30:15_suppl, 4014-4014
Re-analysis of RADIANT 2:
Everolimus + Octreotide vs
OctreotideMedian PFS was significantly longer
for pts with baseline 5-HIAA
<median vs >median at baseline.
5-HIAA< median 17months vs 11
months > median; p<.001)
Everolimus was more
effective in low 5HIAA, put
another way less effective in
high 5HIAA4
High 5HIAA correlated
with reduced survival in
retrospective studies of
NETs 1,2
Telotristat effectiveness
strongly correlated with
5HIAA reduction3
NET Proof-of-Concept (POC) Study
Design
• Efficacy and safety of everolimus plus Xermelo will be
studied in patients with well differentiated NETs of midgut
origin
• Single arm, open label study
• Primary endpoint will be the rate of progression-free survival
at 12 months
– Historical control 12-month PFS from RADIANT-4 study is 44%
Biliary Tract Cancers – Overview
• Approximately 10,000 cases per year were diagnosed as
aggressive malignancies with poor prognosis1, but
intrahepatic cholangiocarcinoma is increasing2
• Multiple molecular signatures identified in different biliary tract
cancer types3
• Palliative first-line chemotherapy – cisplatin/gemcitabine 3-4
• No standard second-line palliative chemotherapy4
• Folfox or fluoropyrimidine based chemo is used
1 Marks & Yee. World J Gastroenterol. (2016); 22(4): 1335-1347. 2Goral V. Asian Pacific J. Cancer Prev.
(2017); 18(6): 1469-73 3 Zhao & Lim. J. Gastrointestinal Oncol. (2017); 8(3): 430-40; 4 NCCN Clinical
Practice Guidelines in Oncology. Hepatobiliary Cancers. Guidelines Version 3. 2017, August 15, 2017.
https://www.nccn.org/professionals/physician_gls/PDF/hepatobiliary.pdf. Accessed on 10/04/17.
Only One Approved Therapy -
Urgent Need in Biliary Cancer• GEM CIS (approved): versus gem alone, 12 weeks (stop or continue).
11.7 mo OS vs 8.1 with gem and PFS 8.0 vs 5.0 with gem alone. RR 20%.1
ABC-02 - Phase 3 study of advanced biliary cancer accrued 410 pts in 28
months.
• FOLFOX (off-label): PFS 3.6 months, less if no response to prior therapy2
• Gem cape, Gem abraxane cis, VERY few trials
Comprehensive exome and transcriptome analysis
of intrahepatic, perihilar and distal
cholangiocarcinomas and gallbladder cancers in
Japanese patients. IDH1, IDH2, FGFR family,
HER 2 main actionable 3
1 Valle J, Wassan H, Palmer Dh et al N Engl J Med. 2010. 362(14):1273-81. 2 Lamarca A et al Annals of Oncol 25: 2328-2338,20143 Razumilava N, Gores G. Nat Genet. 2015. 47(9):967-8.
Evidence Supporting Serotonin’s Role in
BTC Preclinical Models• Dysregulation of serotonin may
be associated with progression
of BTC1
• TPH1 is upregulated1 and
monoamine oxidase-A is
markedly decreased in BTC2
• Increased serotonin secretion in
BTC cell lines and bile of BTC
patients1
• Inhibition of serotonin synthesis
by a TPH Inhibitor (pCPA)
resulted in decreased cell
proliferation in vitro and in vivo1
• Cholangiocarcinoma (CCA)
shown to express similar
markers as NETs1
1 Alpini G et al, Cancer Res. 68:9184-9193, 2008 2 Huang L et al, Lab Invest. 92:1451-1460, 2012
TPH
inhibitor
Vehicle
NET markers
pCPA: p-chlorophenylalanine
Chronic Inflammation and Immune Dysfunction are Drivers
in BTC Progression - Tryptophan Plays a Role in
Regulation of Both
1 Romani L, Fallarino F, De Luca A et al Nature 2008. 451(7175):211-5 2 Li L et al, Front Immunol. 2012; 3:109. 3 https://www.cancer.gov/types/liver/patient/bile-duct-treatment-pdq 4 Goeppert B et al Br J Cancer 2013:109:2665–2674
Tryptophan is a key factor
in chronic inflammation
and cancer1
Tryptophan plays a role
in immunomodulation2
• Bile duct stones
• Liver fluke infections
• Chronic HBV and HCV infection
BTC is caused by inflammation3
Tumor infiltrating lymphocytes
are prognostic in BTC4
• Immune targeting is of great
interest in BTC- Several
ongoing trials
BTC POC Study Design
• Efficacy and safety of Xermelo in combination with
standard 1st-line chemotherapy (gemcitabine plus
cisplatin) will be studied in patients with advanced BTC
• Single arm, open label study
• Primary endpoint will be the rate of progression-free
survival at 6 months
– Historical control 6-month PFS from ABC-02 study is 59.3%
Takeaways• Serotonin is overproduced in many cancers and has a role in cancer
progression
• Significant need exists in NETs and BTC, orphan diseases, but rising
in incidence
• In NETs, in combination with everolimus, especially in elevated 5HIAA
where everolimus doesn’t work as well, Xermelo lowers 5HIAA and
may improve patient outcomes
• In BTC, survival is under one year with gemcitabine and cisplatin in
first line. In addition, patients don’t tolerate cisplatin after 6 months.
Adding Xermelo may maintain benefit from gemcitabine and improve
quality of life.
• Xermelo has potential in second line or alone, to slow progression,
and demonstrate efficacy in clinical or lab biomarkers
• Ongoing preclinical work and collaborations may help develop more
indications
THANK YOU!
Precision Science. Pioneering Medicine. Patient Driven.
XERMELO Life Cycle Management –Opportunities for XERMELO
Precision Science. Pioneering Medicine. Patient Driven.
Praveen Tyle, Ph.D.Executive Vice President, Research & Development
April 10, 2018
© 2018 Lexicon Pharmaceuticals, Inc. 33
Estimated Number of U.S. Patients Eligible for XERMELO by Indication, if Approved, By 2025
US prevalence for NETs based on Dasari 2017. US growth rate to 2025 assumes the last 5-year (2007-2011) growth rate will continue to 2025.US prevalence for CSD assumes that 52% of NET patients have mid-gut tumors, of which 20% will experience Carcinoid Syndrome and of those, 84% will experience CSD (source: Mamikunian G, et al, eds. Neuroendocrine Tumors: A Comprehensive Guide to Diagnosis and Management. 4th ed. Inglewood, CA: Inter Science Institute; 2009. 2. DeVita V, et al, eds. Cancer: Principles and Practice of Oncology. 7th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2000).Overlap between the two NET-related indications represents tumor progressive patients who are on everolimus.Cholangiocarcinoma incidence assumed to be 1.6 per 100K in the US according to Kirstein et el. 75% are metastatic due to late/difficult diagnosis, and prevalence rate assumes a survival curve according to DeOliverira et al. Gallbladder cancer incidence assume to be 1.1 per 100K in the US according to Henley et al. 45% are metastatic, and prevalence is calculated by the survival rate based on hundal et. Al.NET patient eligible for XERMELO assumes 52% of all NET patients will have a midgut tumor (source: Dasari, 2017), and of those, 20% of the patients are on everolimus(Lexicon market research, Jan 2018).All CSD patients assumed to be XERMLEO eligible, even though penetration rate may differ depending on symptoms.90% of BTC patients are on Gem/Cis and are deemed eligible for XERMELO.
+20,000
Progressing
Mid-Gut NETs
18,000
Carcinoid
Syndrome
Diarrhea
10,000
Biliary Tract Cancers
Precision Science. Pioneering Medicine. Patient Driven.
Q&A Session #1
Precision Science. Pioneering Medicine. Patient Driven.
April 10, 2018
© 2018 Lexicon Pharmaceuticals, Inc. 35 Precision Science. Pioneering Medicine. Patient Driven.
Sotagliflozin Discovery and Differentiation
Pablo Lapuerta, M.D.Executive Vice President and Chief Medical Officer
April 10, 2018
© 2018 Lexicon Pharmaceuticals, Inc. 36
Sotagliflozin Development and Differentiation
• Genetic technology guided a discovery biology program that differentiated sotagliflozin
- First company to develop a dual SGLT1/2 inhibitor
• A profile with robust efficacy and potential opportunities in safety has guided sotagliflozin clinical research
• Unmet needs in type 1 diabetes indicate opportunity for sotagliflozin to improve outcomes
- Therapeutic innovation in type 1 diabetes has mostly been limited tovariations on insulin and its delivery
- Insulin has a narrow therapeutic window, with hypoglycemia being asignificant challenge to intensive glucose management
• In type 2 diabetes sotagliflozin has an important opportunity for those with renal impairment
- Selective SGLT2 inhibitors are less effective and, in some cases, contraindicated in patients with chronic kidney disease
© 2018 Lexicon Pharmaceuticals, Inc. 37 Precision Science. Pioneering Medicine. Patient Driven.
Mechanism of Action of Sotagliflozin
Precision Science. Pioneering Medicine. Patient Driven.
David Powell, M.D.Senior Vice President, Metabolism
April 10, 2018
© 2018 Lexicon Pharmaceuticals, Inc. 38
Sotagliflozin - First-in-Class Dual SGLT1/SGLT2 Inhibitor for Diabetes
SGLT2 SGLT2 reabsorbs 90% of filtered glucose in the kidney
Inhibiting SGLT2 in the kidneyincreases glucose excretion in the urine
Results in reduced glucosereabsorbed into the body
Mechanism is independent of insulin
Effect diminishes with declining renal function
© 2018 Lexicon Pharmaceuticals, Inc. 39
SGLT2 reabsorbs 90% of filtered glucose in the kidney
Inhibiting SGLT2 in the kidneyincreases glucose excretion in the urine
Results in reduced glucosereabsorbed into the body
Mechanism is independent of insulin
Effect diminishes with declining renal function
Sotagliflozin - First-in-Class Dual SGLT1/SGLT2 Inhibitor for Diabetes
SGLT2 SGLT1 is the primary transporterfor glucose/galactose in the GI tract
Inhibiting SGLT1 in the GI tractreduces glucose absorption after a meal
Results in elevated GI hormones (GLP-1, PYY) and reduced peak blood glucose
Mechanism is independent of insulin
Effect does not diminish with declining renal function
SGLT1
© 2018 Lexicon Pharmaceuticals, Inc. 40 Precision Science. Pioneering Medicine. Patient Driven.
Mechanism of Action (MOA):Preclinical Data
© 2018 Lexicon Pharmaceuticals, Inc. 41
SGLT2 Knockout (KO) Mice: Increased Urinary Glucose Excretion (MOA) Improved Glucose Tolerance
WT 4 KO 4
Oral Glucose Tolerance Test
Recent pooled WT
WT KO
WT 4 KO 4
Recent pooled WT
Oral Glucose Tolerance Test
t0 t30 t60
Time in Minutes
t90G
lucose A
rea U
nd
er
the C
urv
e
Initial Screen: SGLT2 KO Mouse Data
Source: Powell DR et al 2013 Am J Physiol Endocrinol Metab
© 2018 Lexicon Pharmaceuticals, Inc. 42
SGLT1 KO Mice: Reduced Glucose Absorption (MOA) Profoundly Improved Glucose Tolerance
WT 4 KO 6
Recent pooled WT
t0 t30 t60
Time in Minutes
WT 4 KO 6
Recent pooled WT
WT KO
Initial Screen: SGLT1 KO Mouse Data
Glu
cose A
rea U
nd
er
the C
urv
e
Oral Glucose Tolerance Test Oral Glucose Tolerance Test
Source: Powell DR et al 2013 Am J Physiol Endocrinol Metab
© 2018 Lexicon Pharmaceuticals, Inc. 43
0
100
200
300
400
500
0.4 0.6 0.8 1.0 1.2 1.4 1.6
Nu
mb
er
of
KO
Lin
es
KO / WT Glucose Excursion AUC
Glucose Tolerance: Improved Normal Impaired
SGLT2
DPP4
SGLT1
Lexicon Screen of Gene Knockouts Identified SGLT1 and SGLT2 as Top Anti-Diabetic Targets
Source: Powell DR et al 2013 Am J Physiol Endocrinol Metab
© 2018 Lexicon Pharmaceuticals, Inc. 44
Plasma GLP-1 Levels Increase in SGLT1 KO Mice after a Glucose Challenge
Meal challenge provided at hr 0
N = 4-5 mice for each data point
Cecal Glucose Cecal pH Plasma Total GLP-1
Source: Powell DR et al 2013 J Pharmacol Exp Ther
© 2018 Lexicon Pharmaceuticals, Inc. 45
Plasma GLP-1 Levels Do Not Increase in SGLT2 KO Mice after a Glucose Challenge
Meal challenge provided at hr 0
N = 4-5 mice for each data point
Plasma Total GLP-1Cecal Glucose Cecal pH
Source: Powell DR et al 2013 J Pharmacol Exp Ther
© 2018 Lexicon Pharmaceuticals, Inc. 46
Sotagliflozin Improved Glycemic Control and Increased GLP-1 in a Preclinical Model of Type 2 Diabetes
Improved Glucose Tolerance Lower A1C
• Data from KKAy mouse model of T2D (n = 15 mice/group)
• Favorable preclinical safety profile; no evidence of gastrointestinal side effects
Increased GLP-1
Source: Powell DR et al 2014 J Pharmacol Exp Ther
© 2018 Lexicon Pharmaceuticals, Inc. 47
Combination of Sotagliflozin and Sitagliptin Synergistically Increased Active GLP-1 Levels
Meal challenge provided at hr 0
N = 5 mice for each data point
Measures taken after 14 days of combination dosing in mice
Source: Zambrowicz et al 2013 Clin Ther
© 2018 Lexicon Pharmaceuticals, Inc. 48
Sotagliflozin Lowered Blood Glucose While Avoiding Hypoglycemia in Preclinical Model of Type 1 Diabetes
Frequency of hypoglycemia(Number of samples):
< 70 mg/dL <50 mg/dL 0.05U insulin/vehicle: 0/100 0/100
0.2U insulin/vehicle: 13/100 5/1000.05U insulin/2 mg/kg sotagliflozin: 0/100 0/100
0.05U insulin/30 mg/kg sotagliflozin: 1/90 0/90
Study performed in NOD Mouse model of T1D (n = 9-10 mice/group)
* ** *
** **
*
*Different from other groups, p < 0.05
Source: Powell DR et al 2015 Diabetes Metab Syndr Obes
© 2018 Lexicon Pharmaceuticals, Inc. 49 Precision Science. Pioneering Medicine. Patient Driven.
Mechanism of Action: Clinical Data
© 2018 Lexicon Pharmaceuticals, Inc. 50
Postprandial Glucose Reduction is Characteristic of SGLT1 Inhibition in Subjects with T2D
p < 0.001, placebo AUC vs AUC of 150 mg or 300 mg
Blood Glucose Above Fasting Level (from Randomized, Placebo-controlled Phase 2a Study of Sotagliflozin; n=12/group)
Source: Zambrowicz et al 2012 Clin Pharmacol Ther
© 2018 Lexicon Pharmaceuticals, Inc. 51
Glucose Absorption and Reabsorption in Individuals with Type 2 Diabetes (T2D)
No Urinary Glucose
Source: Zambrowicz et al 2012 Clin Pharmacol Ther
Meal
SGLT1 Glucose
Absorption
Glucose Filtration
SGLT2Glucose
Reabsorption
Blood Glucose
Tissues
Post-meal Glucose Levels,
T2D
© 2018 Lexicon Pharmaceuticals, Inc. 52
Increased Urinary Glucose
Excretion
Glucose Absorption and Reabsorption in Patients with T2D on an SGLT2 Inhibitor
Post-meal Glucose Levels,
T2D
Sources: Zambrowicz et al 2012 Clin Pharmacol TherNishimura et al 2015 Cardiovasc Diabetol
Meal
SGLT1 Glucose
Absorption
Glucose Filtration
SGLT2Glucose
Reabsorption
Blood Glucose
Tissues
X
© 2018 Lexicon Pharmaceuticals, Inc. 53
Meal
SGLT1 Glucose
Absorption
Glucose Filtration
Blood Glucose
Moderately Increased
Urinary Glucose Excretion
X
Glucose Absorption and Reabsorption in Patients with T2D on a Dual SGLT1/SGLT2 Inhibitor
X
Post-meal Glucose Levels,
T2D
Sources: Zambrowicz et al 2012 Clin Pharmacol TherNishimura et al 2015 Cardiovasc Diabetol
Tissues
SGLT2Glucose
Reabsorption
© 2018 Lexicon Pharmaceuticals, Inc. 54
Single Dose of Sotagliflozin Elevates GLP-1 Over the Course of the Day in Subjects with Type 2 Diabetes
Randomized, cross-over study of subjects with T2D (n = 12) treated with single oral doses of different sotagliflozin formulations. A 5-day washout period separated formulation dosing days. Sotagliflozin data were compared to baseline values.
Baseline 2x150 mg Tablet 300 mg Liquid
Source: Zambrowicz et al 2012 Clin Pharmacol Ther
© 2018 Lexicon Pharmaceuticals, Inc. 55
Combining Sotagliflozin & Sitagliptin in Subjects with T2D Increases Active GLP-1 Compared to Either Agent Alone
Randomized, cross-over study of subjects with T2D (n = 18) treated with single oral doses of sotagliflozin, sitagliptin or the sotagliflozin/sitagliptin combination. 7-day washout periods separated compound dosing days.
*
*
* p < 0.001
vs combination
Source: Zambrowicz et al 2013 Clin Ther
© 2018 Lexicon Pharmaceuticals, Inc. 56 Precision Science. Pioneering Medicine. Patient Driven.
Sotagliflozin Clinical Differentiation
Precision Science. Pioneering Medicine. Patient Driven.
Pablo Lapuerta, M.D.Executive Vice President and Chief Medical Officer
April 10, 2018
© 2018 Lexicon Pharmaceuticals, Inc. 57
Sotagliflozin Differentiation - Dual Inhibition of SGLT1 and SGLT2
• Potential for more robust efficacy than SGLT2 inhibition alone- Greater post-prandial glucose reduction- GLP-1 elevation after meals- Consistent A1C reduction- Efficacy in the setting of renal impairment
• Potential for differentiation in safety- Less urinary glucose excretion
• May be relevant to volume depletion, genitourinary infections, and DKA
- Potentially less hypoglycemia than standard of care with insulin
The vision of dual inhibition has guided clinical development
© 2018 Lexicon Pharmaceuticals, Inc. 58
Sotagliflozin - Modest Urinary Glucose Excretion (UGE)
24 hour UGE (g)
Sotagliflozin400 mg
Canagliflozin300 mg
Empagliflozin25 mg
Dapagliflozin10 mg
Ertugliflozin15 mg
Healthy Volunteers
24 hour UGE (g)1 36-44 70 56 40 58
Type 2 Diabetes
24 hour UGE (g)2 54 >100 80 68 >69-80
Type 1 Diabetes
24 hour UGE (g)3 70 NA* 134 88 NA*
1Lapuerta et al. Diabetes & Vascular Disease Research 2015;12(2) :101–110, and FDA Clin. Pharm. Reviews obtained at www.fda.gov2Rosenstock et al. Diabetes Care 2015;38:431–438. Sha et al. PLoS One 2014;9(9):e110069, Heise et al. Diabetes Ther (2013) 4:331–345, List et al., Diabetes Care 32:650–657, 2009, Amin et al. Diab Obes Metab17: 591–598, 2015 3Lexicon data on file, study LX4211.206. Perkins et al. Diabetes Care 2014;37:1480–1483, Henry et al. Diabetes Care 2015;38:412–419*No published data on UGE in T1DM
© 2018 Lexicon Pharmaceuticals, Inc. 59
Urinary Glucose Excretion from SGLT2 Inhibition -Function of Plasma Glucose
Example - Canagliflozin urinary glucose excretion after a meal is elevated for about 3 hours while glucose levels are high
Source: Diabetes Care 36:2154–2161, 2013
Reductions in post-prandial glucose from gastrointestinal
SGLT1 inhibition may limit UGE
– Canagliflozin– Placebo
© 2018 Lexicon Pharmaceuticals, Inc. 60
Sotagliflozin Phase 2 Results in Type 2 Diabetes -Large Reductions in Postprandial Glucose
Green: Placebo, Blue: Sota 150 mg, Red: Sota 300 mg
Source: Lapuerta, P et al. Diabetes & Vascular Disease Research 2015, Vol. 12(2) 101–110
© 2018 Lexicon Pharmaceuticals, Inc. 61
Sotagliflozin Differentiation - Long Half-life Supports Gastrointestinal SGLT1 Inhibition
Sotagliflozin400 mg
Canagliflozin300 mg
Empagliflozin25 mg
Dapagliflozin10 mg
Ertugliflozin15 mg
Half-life (hours)1
29 13.1 12 3* 15.3
Reductions in post-prandial glucose have been shown with sotagliflozin even 24 hours after the
last dose2
*half-life estimation may have been affected by limits of assay
1Lapuerta et al. Diabetes & Vascular Disease Research 2015;12(2): 101–110 and FDA Clinical Pharmacology Biopharmaceutics Reviews2Lexicon data on file, study LX4211.202
© 2018 Lexicon Pharmaceuticals, Inc. 62
Sotagliflozin in Renal Impairment- Reduction in Postprandial Glucose
100
120
140
160
180
200
220
240
-1 0 1 2 3 4
Day -1 Day 7
100
120
140
160
180
200
220
240
-1 0 1 2 3 4
Day -1 Day 7
Sotagliflozinn=16
Placebon=15
Hours Hours
Glu
cose (m
g/dl)
Glu
cose (m
g/dl)
Mean 24-hour Urinary Glucose Excretion: 34 g on sotagliflozin 400 mg
Source: Zambrowicz et al. Clin Ther. 2015 Jan 1;37(1):71-82
© 2018 Lexicon Pharmaceuticals, Inc. 63
Sotagliflozin in Renal Impairment - Elevation in Total GLP-1
Sotagliflozinn=16
Placebon=15
Hours Hours
Tota
l G
LP-1
, p
mol/
L
Tota
l G
LP-1
, p
mol/
L5
10
15
20
-1 0 1 2 3 4
Day -1 Day 7
5
10
15
20
-1 0 1 2 3 4
Day -1 Day 7
Source: Zambrowicz et al. Clin Ther. 2015 Jan 1;37(1):71-82
© 2018 Lexicon Pharmaceuticals, Inc. 64
Advancing Sotagliflozin into Type 1 Diabetes -Reducing Glycemic Variability
Sensor Glucose (mg/dL)
0
50
100
150
200
250
300
350
400
Time
0:00:00 4:00:00 8:00:00 12:00:00 16:00:00 20:00:00 24:00:00
Figure 1: Continuous Glucose Monitoring (CGM) Data by Study day and TimeLX4211 - 203 Study --- Pioneer Group
Subject ID=102_001 Study Day=-1 Subject Status=INPATIENT BASELINE
B L D
B=Breakfast L=Lunch D=Dinner
Insulin Only
3 2 3.75 0 0.7 0
Sensor Glucose (mg/dL)
0
50
100
150
200
250
300
350
400
Time
0:00:00 4:00:00 8:00:00 12:00:00 16:00:00 20:00:00 24:00:00
Figure 1: Continuous Glucose Monitoring (CGM) Data by Study day and TimeLX4211 - 203 Study --- Pioneer Group
Subject ID=102_001 Study Day=1 Subject Status=INPATIENT ON TREATMENT
B L D
Start Sotagliflozinwith No Bolus Insulin
0 0.7 0
Insulin Bolus: Units
Source: Lapuerta et al. Diabetes & Vascular Disease Research 2015;12(2): 101–110
Baseline (Day -1)Insulin without Sotagliflozin
Day 1No insulin at breakfast
+ Sotagliflozin
© 2018 Lexicon Pharmaceuticals, Inc. 65
Sotagliflozin Dapagliflozin
Optimizing insulin as robustly as possible ✓
Enrolling patients with A1C < 7.0% ✓
Enrolling patients with A1C >10.5% ✓
Enrolling patients with eGFR < 60 mg/dL ✓
Including a study in patients at risk for DKA ✓
Including a large pragmatic trial ✓
Conducting the largest program of its kind ✓
Type 1 Diabetes- Key Development Choices
The Vision:Robust efficacy with potential differentiation in safety
© 2018 Lexicon Pharmaceuticals, Inc. 66
Sotagliflozin – Largest Phase 3 Program for an Oral Anti-Diabetic Agent in Broad Range of T1DM Patients
Phase 3 Studies in T1DM Patient Size/Dose
Primary Endpoint
Top-LineResults
StudyCompletion
inTandem1
• 750 patients
• Placebo, 200mg, 400mg once-daily
Reduction of A1C vs. placebo on optimized insulin (24 weeks)
Met primaryendpoint of efficacy and
favorable safety
Completed
(52-week total study duration)
inTandem2
• 750 patients
• Placebo, 200mg, 400mg once-daily
Reduction of A1C vs. placebo on optimized insulin (24 weeks)
Met primary endpoint of efficacy and
favorable safety
Completed
(52-week total study duration)
inTandem3
• 1,400 patients
• Placebo, 400mg once-daily
Proportion with A1C < 7.0% and no SH and no DKA (24 weeks)
Met primary endpoint of efficacy and
favorable safety
Completed
(24-week total study duration)
U.S. and EU regulatory filings for T1DM submitted in 1Q 2018
© 2018 Lexicon Pharmaceuticals, Inc. 67
Sotagliflozin – Significant A1C Reductions on Top of Optimized Insulin in Patients with T1DM
-0.37%-0.39%
-0.03%
400mg dose 200mg dose Placebo
inTandem1 (n=793)A1C reduction (%) after24 weeks
-0.49%
-0.43%
-0.08%
400mg dose 200mg dose Placebo
inTandem2 (n=782)A1C reduction (%) after24 weeks
© 2018 Lexicon Pharmaceuticals, Inc. 68
inTandem3 Phase 3 Clinical Trial – NEJM Publication in Sept 2017 Validates Need for New T1DM Therapy
© 2018 Lexicon Pharmaceuticals, Inc. 69
inTandem3 Data from the NEJM – Primary Endpoint and All Secondary Endpoints Achieved
inTandem3 (n=1,405)
PlaceboSotagliflozin
400 mg P-Value
Net benefit 15.2% 28.6% p<0.001
A1C (%) -0.33 -0.79 p<0.001
Body weight (kg) +0.8 -2.2 p<0.001
Blood pressure (mmHg)* -5.7 -9.2 p=0.002
Bolus insulin -1.1 IU/day -3.9 IU/day p<0.001
*16 weeks in patients with SBP>130 mm Hg
© 2018 Lexicon Pharmaceuticals, Inc. 70
Continuous Glucose Monitoring Data - SotagliflozinImproved Time in Range by Up to 3 Hours/day
• Positive pooled continuous glucose monitoring (CGM) data from the pivotal inTandem1 and inTandem2 studies announced recently
- Sotagliflozin significantly increased the time in target glucose range of 70-180 mg/dL and decreased glucose variability
Sotagliflozin 200 mg additional 1.3 hours per day in target glucose range
Sotagliflozin 400 mg additional 2.8 hours per day in target glucose range
© 2018 Lexicon Pharmaceuticals, Inc. 71
inTandem3 Weight Data – Body Weight Significantly Reduced
© 2018 Lexicon Pharmaceuticals, Inc. 72
Safety – Largest and Most Comprehensive Safety Database, Lower Hypoglycemia and Manageable DKA in High-Risk Patients
Severe Hypoglycemia DKA
• Hypoglycemia profile is relevant to patients- inTandem3: sotagliflozin vs. placebo; 11.8 vs. 15.4 events of glucose
≤55mg/dL per person-year (p<0.001)• Diabetic ketoacidosis (DKA) incidence low in setting of education and monitoring
24 week data Overall Rate Discontinuation Rate Overall Rate Discontinuation Rate
inTandem1 (n=793)• Placebo• Sotagliflozin 200 mg• Sotagliflozin 400 mg
6.7%4.2%4.6%
0.4%0.0%0.0%
0.0%1.1%3.1%
0.0%0.4%0.8%
inTandem2 (n=782)• Placebo• Sotagliflozin 200 mg• Sotagliflozin 400 mg
2.7%3.8%2.3%
0.0%0.0%0.0%
0.0%0.4%1.1%
0.0%0.0%0.8%
inTandem3 (n=1,405)• Placebo• Sotagliflozin 400 mg
2.4%3.0%
0.1%0.3%
0.6%3.0%
0.1%1.6%
© 2018 Lexicon Pharmaceuticals, Inc. 73
Sotagliflozin and SGLT Inhibition – Incremental DKA Risk that Can Be Managed with Proper Care Instructions
Placebo-Adjusted Proportion of Patients with DKA Event2 Low Dose High Dose
inTandem Program 0.6% 2.4%
DEPICT-13 1.7% 2.5%
• Background rate of DKA in people with type 1 diabetes ranges between 5-8% annually1
• Sotagliflozin’s inTandem program and dapagliflozin DEPICT-1 have demonstrated manageable incremental DKA risk over placebo that can be mitigated with appropriate care instructions and monitoring
1 Beck et al, The T1D Exchange Clinic Registry, J Clin Endocrinol Metab 97: 4383-4389, 2012; Weinstock et al, Severe Hypoglycemia and Diabetic Ketoacidosis in Adults with Type 1 Diabetes: Results from the T1D Exchange Clinic Registry, J Clin Endocrinol Metab 98: 3411-3419, 2013 (proportion of patients reporting at least one DKA event in the previous 12 months).2 Proportion of patients with DKA event classified as either definite or probable/possible through 24 weeks of treatment;3 Dandona et al., Efficacy and safety of dapagliflozin in patients with inadequately controlled type 1 diabetes (DEPICT-1): 24 week results from a multicentre, double-blind, phase 3, randomised controlled trial, Lancet Diabetes Endocrinol 2017 (published online).
© 2018 Lexicon Pharmaceuticals, Inc.
A1C distribution created from population data from T1D ExchangeT1D population based on company research.
Type 1 Diabetes Mellitus (T1DM) – Large Market Opportunity
• 1.55 million adults are estimated to be living with type 1 diabetes in the United States in 2018 and has grown at 3.5%/year over the last 5 years
• 75% of adults living with type 1 have an A1C > 7.0%
• WAC of SGLT2i class is $14.35/day ($5,238/year)
• 12.7% CAGR in WAC over the last two years
1.55 Million Adults Living With T1D in the U.S.
1.55 M100%
© 2018 Lexicon Pharmaceuticals, Inc.
0.88 M57%
0.67 M43%
1.55 Million Adults Living With T1D in the U.S.
A1C distribution created from population data from T1D ExchangeT1D population based on company research.
Type 1 Diabetes Mellitus (T1DM) – Large Market Opportunity
DEPICT-1 excluded about 43% of the population (672K)
Only 57% of the T1D Community Studied
• 1.55 million adults are estimated to be living with type 1 diabetes in the United States in 2018 and has grown at 3.5%/year over the last 5 years
• 75% of adults living with type 1 have an A1C > 7.0%
DEPICT-1 removed all patients who did not
have an A1C after run-in between 7.5%-10.5%
© 2018 Lexicon Pharmaceuticals, Inc.
Type 1 Diabetes Mellitus (T1DM) – Large Market Opportunity
57% of the T1D Community Studied99+% of the T1D Community Studied
0.88 M57%
0.67 M43%
1.5 M99%
0.02 M1%
Dapagliflozin was restricted to 57% of the populationSotagliflozin is the most comprehensively studied SGLT in T1D
Sotagliflozin did not restrict patients:
• Included participants with an A1C after run-in between 5.6%-15.4%
• Included patients with an eGFR < 60 (5.3% of participants)
• Studied all adults – including those over 75 years old
A1C distribution created from population data from T1D ExchangeT1D population based on company research.
• 1.55 million adults are estimated to be living with type 1 diabetes in the United States in 2018 and has grown at 3.5%/year over the last 5 years
• 75% of adults living with type 1 have an A1C > 7.0%
We have submitted to the FDA the 1st application for approval of an oral adjunct to insulin
Unmet needs in type 1 diabetes
Jake A. Kushner, M.D.
jake.kushner@mac.com
@JakeKushnerMD
Disclosure: consultant for Lexicon, Virta
Health, KNOW foods, and Sanofi
Michael Bliss, The Discovery of Insulin,
University of Chicago Press, 1982, 2007
Was insulin a “cure” for type 1 diabetes?
The Cumulative Incidence of Long-
Term Sequelae of Juvenile Diabetes,
by Duration of Diabetes, Joslin Clinic,
1898-1956.
Insulin-treated T1D patients began to suffer from
unforeseen complications
Insulin-treated T1D patients had high rates of mortality,
even into the 1990s
Does improved glycemic control reduce
complications?
Diabetes Control Complication Trial (DCCT):
1441 T1D patients, 1-5 years duration, ages 13-39
“intensive therapy” vs. “conventional therapy”
Improved glucose control Intensive glucose control for ~6.5 years in DCCT
Decreased retinopathy with
intensive T1D treatment!
for only 10 yearsIntensive glucose control for ~10 years in DCCT
Decreased cardiovascular disease with intensive T1D
treatment!
Decreased mortality with intensive T1D treatment!
• Injected insulin is the only available
therapy
• High burden of illness: Very challenging
to keep blood sugars in normal range
• Risk of weight gain & hypoglycemia
with increased insulin
• Frequent hypoglycemia (typically 1-2
episodes per week)
• Severe hypoglycemia risk: ~10% per
year
• Pramlintide is the only FDA approved
T1D adjuvant therapy, associated with
hypoglycemia, and infrequently
prescribed
Millions of people have type 1 diabetes
Most with T1D fail to achieve A1c target
A1c target: <7 in adults
Most with T1D fail to achieve A1c target
18 y old, T1D for
>10 yrs
(High carb diet)
Adverse consequences in typically treated T1D?
Typically treated T1D results in
excess risk of cardiovascular
death
Weight gain is associated with cardiovascular
disease in intensive T1D treatment
Sotagliflozin Results
inTandem3
inTandem3
Placebo
Sotagliflozin
400 mg P-Value
Net benefit (A1c<7.0% without
severe hypo or DKA)15.2% 28.6% p<0.001
A1C (%) change at 24 weeks -0.33 -0.79 p<0.001
Body weight (kg) +0.8 -2.2 p<0.001
Blood pressure (mmHg)* -5.7 -9.2 p=0.002
Bolus insulin -1.1 IU/day -3.9 IU/day p<0.001
Hypoglycemia (glucose ≤ 55
mg/dL) episodes per person-year15.4 11.8 p<0.001
*16 weeks in patients with SBP>130 mm Hg.
• DKA education by healthcare providers
• Ketone monitoring recommended
• 3% DKA on sotagliflozin 400 mg at 24 weeks
Garg SK and Strumph P. N Engl J Med 2018; 378:966-968
(In 52 week studies, incidences of DKA on sotagliflozin were ~2-4%)
Sotagliflozin Clinical Trial
Safety Experience
Access provided by
CORRESPONDENCE
Effects of Sotagliflozin Added to Insulin in Type 1Diabetes
March 8, 2018
N Engl J Med 2018; 378:966-968
DOI: 10.1056/NEJMc1800394
Metrics
TO THE EDITOR
Garg et al. (Dec. 14 issue) report the superiority of adding sotagliflozin, an oral inhibitor of sodium–
glucose cotransporters 1 and 2 (SGLT1/2), to insulin in patients with type 1 diabetes, as compared with
placebo, in the inTandem3 trial. They used a unique primary end point that assesses both risk and benefit
simultaneously: a glycated hemoglobin of less than 7% without severe hypoglycemia or diabetic
ketoacidosis at week 24 (i.e., benefit without harm).
According to our calculations of the number needed to treat that are based on data provided in the article,
the number of patients who would need to be treated to show unqualified success (a situation in which
benefit is achieved without harm ) is 8, which is very close to 7, the number of patients who would need
to be treated for one patient to show benefit. During a 24-week period, the numbers of patients who
would need to be treated to show harm from at least one episode of severe hypoglycemia, diabetic
ketoacidosis, volume depletion, or genital mycotic infection with sotagliflozin, as compared with placebo,
are 167, 40, 64, and 23, respectively, with P values of 0.60, <0.001, 0.009, and <0.001. (P values for the
between-group differences in adverse events were not provided in the article.) The corresponding
numbers of patients who had a likelihood of being either helped or harmed are 24, 6, 9, and 3. Given the
short duration of the trial and the likely worsening of numbers with respect to the likelihood of harm or
benefit in the real world, a continuous risk–benefit assessment of sotagliflozin is warranted.
1
2
3
Access provided by
CORRESPONDENCE
Effects of Sotagliflozin Added to Insulin in Type 1Diabetes
March 8, 2018
N Engl J Med 2018; 378:966-968
DOI: 10.1056/NEJMc1800394
Metrics
TO THE EDITOR
Garg et al. (Dec. 14 issue) report the superiority of adding sotagliflozin, an oral inhibitor of sodium–
glucose cotransporters 1 and 2 (SGLT1/2), to insulin in patients with type 1 diabetes, as compared with
placebo, in the inTandem3 trial. They used a unique primary end point that assesses both risk and benefit
simultaneously: a glycated hemoglobin of less than 7% without severe hypoglycemia or diabetic
ketoacidosis at week 24 (i.e., benefit without harm).
According to our calculations of the number needed to treat that are based on data provided in the article,
the number of patients who would need to be treated to show unqualified success (a situation in which
benefit is achieved without harm ) is 8, which is very close to 7, the number of patients who would need
to be treated for one patient to show benefit. During a 24-week period, the numbers of patients who
would need to be treated to show harm from at least one episode of severe hypoglycemia, diabetic
ketoacidosis, volume depletion, or genital mycotic infection with sotagliflozin, as compared with placebo,
are 167, 40, 64, and 23, respectively, with P values of 0.60, <0.001, 0.009, and <0.001. (P values for the
between-group differences in adverse events were not provided in the article.) The corresponding
numbers of patients who had a likelihood of being either helped or harmed are 24, 6, 9, and 3. Given the
short duration of the trial and the likely worsening of numbers with respect to the likelihood of harm or
benefit in the real world, a continuous risk–benefit assessment of sotagliflozin is warranted.
1
2
3
Patient Education and Monitoring for DKA
• Recognize potential symptoms of ketosis or DKA, even when glucose is
normal or only mildly elevated
- Nausea, vomiting, or stomach pain
- Constantly feeling tired, general malaise
- Thirst, frequent urination, or very dry mouth
• Check ketones If these symptoms are present, or in situations at risk for
DKA, including
- Acute illness
- Prolonged fasting
- Significant reductions or interruptions in insulin dosing
• Contact a healthcare provider if ketones are positive, or if the condition
does not improve
- If in doubt, stop sotagliflozin until contacting the provider
- It is important to know that both carbohydrate and insulin are
necessary for ketosis to resolve
Sotagliflozin: Patient Perspective
• Short-term
– A1c reduction
– Greater time in range
• Less hyperglycemia and
hypoglycemia
– Weight loss
– Treatment satisfaction
• Long-term
– Potential to address risks of
nephropathy, neuropathy,
retinopathy, and
cardiovascular disease
• Recognize the potential for DKA
– Potentially 2% to 4%
incidence at 1 year
• Monitor ketones to mitigate risk of
DKA, with advice to stay in close
contact with health care provider
when ill
Potential Benefits Patient commitment
© 2018 Lexicon Pharmaceuticals, Inc. 100Precision Science. Pioneering Medicine. Patient Driven.
Sotagliflozin Program Summary
Precision Science. Pioneering Medicine. Patient Driven.
Pablo Lapuerta, M.D.Executive Vice President and Chief Medical Officer
April 10, 2018
© 2018 Lexicon Pharmaceuticals, Inc. 101
Phase 3 Program in T1DM – Summary
• inTandem program has the largest efficacy and safety database of an oral anti-diabetic agent for T1DM
• Sotagliflozin profile- Robust A1C efficacy on top of insulin- Improved glucose time in range- Robust weight reduction- Lower rate of hypoglycemic episodes with glucose ≤ 55 mg/dL- Incremental incidence of positively-adjudicated DKA was low at
52 weeks• DKA can be managed with education and monitoring
© 2018 Lexicon Pharmaceuticals, Inc. 102
T2DM Phase 3 Program – Ten Ongoing Studies Targeting Over 15,000 Patients with More to Come This Year
Metformin Study
500patients
Severe renal impairment
(SOTA-CKD4) Study
276patients
Combination Study with
sulfonylurea or metformin
500patients
Monotherapy Study
400patients
Moderate renal
impairment (SOTA-CKD3)
Study
780patients
(NCT03242018)(NCT03242252)
(NCT02926950)(NCT02926950)(NCT02926937)
Uncontrolled on basal insulin or
OADs (SOTA-INS) Study
560 patients
(NCT03285594)
CV and Renal Events
(SCORED) Study
10,500patients
(NCT03315143)
Empagliflozin (SOTA-EMPA)
on DPP4 background
700patients
(NCT03351478)
Glimepiride (SOTA-GLIM)
Study
930patients
(NCT03332771)
Efficacy and Bone Safety
(SOTA-BONE) Study
360 patients
(NCT03386344)
© 2018 Lexicon Pharmaceuticals, Inc. 103
Sotagliflozin Program – Summary
• Type 1 diabetes- NDA and MAA filings submitted in 1Q 2018
• Type 2 diabetes- Data for majority of the Phase 3 studies expected in 2019- MAA filing planned for 2H19- NDA filing planned for early 2020
© 2018 Lexicon Pharmaceuticals, Inc. 104Precision Science. Pioneering Medicine. Patient Driven.
Pipeline Progress – LX2761 (diabetes) and LX9211 (neuropathic pain)
Precision Science. Pioneering Medicine. Patient Driven.
Praveen Tyle, Ph.D.Executive Vice President, Research & Development
April 10, 2018
© 2018 Lexicon Pharmaceuticals, Inc. 105
Lexicon’s Scientific Platform Has Produced a Commercial Product and a Pipeline of Innovative Drug Candidates
Compound Partner Target Indication Preclinical Phase 1 Phase 2 Phase 3 Registration Marketed
Whollyowned (U.S./ Japan)
TPH1Carcinoid syndrome diarrhea
Ipsen(ex-U.S./ ex-Japan)
TPH1Carcinoid syndrome diarrhea
SotagliflozinSanofi (WW, ex-Japan)
SGLT1/SGLT2
Type 1 diabetes (T1DM)
SotagliflozinSanofi (WW, ex-Japan)
SGLT1/SGLT2
Type 2 diabetes (T2DM)
Whollyowned (U.S./ Japan)
TPH1Neuroendocrine tumors (NETs)
Whollyowned (U.S./ Japan)
TPH1Biliary tract cancer (BTC)
LX2761Wholly owned
SGLT1 (GI tract)
Diabetes
LX9211Wholly owned
AAK1Neuropathic pain
NDA / MAA filed March, 2018
FDA approval Feb 28, 2017; US launch Mar 01, 2017
EMA approval Sept 19, 2017; EU launch ongoing
Phase 3 ongoing
Phase 1b ongoing
Phase 1a ongoing
Initiating Phase 2
Initiating Phase 2
© 2018 Lexicon Pharmaceuticals, Inc. 106Precision Science. Pioneering Medicine. Patient Driven.
LX2761 - Diabetes
© 2018 Lexicon Pharmaceuticals, Inc. 107
SGLT2 reabsorbs 90% of filtered glucose in the kidney
Inhibiting SGLT2 in the kidneyincreases glucose excretion in the urine
Results in reduced glucosereabsorbed into the body
Mechanism is independent of insulin
Effect diminishes with declining renal function
LX2761 – Locally-acting SGLT1 Inhibitor for Diabetes
SGLT2 SGLT1 is the primary transporterfor glucose/galactose in the GI tract
Inhibiting SGLT1 in the GI tract delays &reduces glucose absorption after a meal
Results in elevated GI hormones (GLP-1) and reduced peak blood glucose
Mechanism is independent of insulin
Mechanism is independent of renal function
SGLT1
© 2018 Lexicon Pharmaceuticals, Inc. 108
LX2761 - Drug Candidate for Diabetes Focused on SGLT1 in GI Tract
➢ Potent, orally-delivered small molecule strategically designed to maximize SGLT1 inhibition locally in the gastrointestinal tract with no urinary glucose excretion➢ Ability to minimize PPG excursions➢ Ability to maximize GLP-1 release➢ Minimal systemic exposure
➢ Phase 1a clinical trials completed
➢ Phase 1b clinical trials ongoing
➢ Lexicon has granted Sanofi certain rights of first negotiation
© 2018 Lexicon Pharmaceuticals, Inc. 109
LX2761 - Designed to Remain in the Intestine After Oral Delivery to Inhibit Local SGLT1
Oral delivery of LX2761 results in very low systemic exposure in mice
Source: Goodwin NC et al 2017 J Med Chem
© 2018 Lexicon Pharmaceuticals, Inc. 110
LX2761 - No Increase in Urinary Glucose Excretion
24-hour urine glucose on day 1 and day 2 after oral delivery with a
single dose in mice
Source: Goodwin NC et al 2017 J Med Chem
© 2018 Lexicon Pharmaceuticals, Inc. 111
LX2761 Blunted Glucose Excursions in Preclinical Testing
Data from oral glucose tolerance tests in rats
Source: Powell DR et al 2017 J Pharmacol Exp Ther
© 2018 Lexicon Pharmaceuticals, Inc. 112
Decreased Glucose Excursions When Oral Glucose was Administered 15 Hours After the Last Dose of LX2761
Note: The adult male C57 mice studied were fed ad lib between the last oral dose of LX2761 and the OGTT
Source: Powell DR et al 2017 J Pharmacol Exp Ther
© 2018 Lexicon Pharmaceuticals, Inc. 113
➢ Adult male mice received vehicle, LX2761 and/or sitagliptin by oral delivery
➢ Each mouse received 4 g/kg glucose by oral delivery
LX2761 and DPP-4 Inhibitor Sitagliptin Synergistically Increase Postprandial GLP-1 Levels in Preclinical Testing
Source: Powell DR et al 2017 J Pharmacol Exp Ther
© 2018 Lexicon Pharmaceuticals, Inc. 114
LX2761 – Key Takeaways
➢Potent, oral, locally-acting SGLT1 inhibitor
➢Robust preclinical efficacy and good safety profile ▪ Reduces PPG▪ No increase in UGE, consistent with local action▪ Synergy with DDP-4 inhibitor in preserving active GLP-1
➢ Phase 1a clinical trials completed in healthy subjects and patients with type 2 diabetes
➢ Phase 1b clinical trials in patients with type 2 diabetes ongoing, with data expected mid-2018
© 2018 Lexicon Pharmaceuticals, Inc. 115Precision Science. Pioneering Medicine. Patient Driven.
LX9211 - Neuropathic Pain
Discovering Breakthrough Treatments for Human Disease
April 10, 2018
© 2018 Lexicon Pharmaceuticals, Inc. 116
R&D in the Pain Market – Overview
Source: Bio Industry Analysis: The State of Innovation in Highly Prevalent Chronic Diseases Volume II: Pain and Addiction Therapeutics
2 approved NCEs for pain in a decade
(milnacipran and tapentadol)
87% are
non-opioid
receptors
Only 125
NCEs
220 clinical
programs
In contrast, oncology has >2,000 clinical programs (1,700 NCEs)
Most approved pain products since 2007 have been reformulations or have pre-2007 market history
© 2018 Lexicon Pharmaceuticals, Inc. 117
LX9211- A Novel Therapeutic Approach for Neuropathic Pain: Adaptor Associated Kinase-1 (AAK1) Inhibitor
➢ Discovered in Lexicon’s neuroscience drug discovery alliance with Bristol-Myers Squibb
➢ Lexicon has acquired exclusive development and commercialization rights
➢ Potent, highly-selective, oral small molecule inhibitor of target discovered and extensively characterized in alliance. Robust efficacy in preclinical models
➢ IND filed; Phase 1 clinical trial underway
Substantial need for new therapies with improved efficacy and tolerability for neuropathic pain and for new therapies for pain without
addictive potential
© 2018 Lexicon Pharmaceuticals, Inc. 118
Diabetic Neuropathic Pain Disease - Overview
➢A late-stage complication in patients with diabetes mellitus, affects approximately 15% of patients.
➢Complicates diabetes treatment by limiting the patient’s ability to exercise, which improves glucose management
➢Severely interferes with sleep, which can also negatively impact glycemic control
➢Symptoms differ in clinical course, distribution, fiber involvement and pathophysiology
© 2018 Lexicon Pharmaceuticals, Inc. 119
Lexicon’s Genome 5000 Program - AAK1 Knockout Mice Have Anti-Nociceptive Phenotype
Mouse Spinal Nerve Ligation Model
Source: Kostich et al 2016, J Pharmacol Exp Ther
© 2018 Lexicon Pharmaceuticals, Inc. 120
AAK1 Inhibitor LX9211 Reduces Streptozotocin-induced Diabetic Neuropathic Pain in Rats
-10
0
10
20
30
40
50
60
70
80
90
100
110
120
130
140
150
0 1.5 3.5 5.5Inhib
itio
n o
f M
echa
nic
al A
llodynia
(%
)
Time After Treatment (h)
Vehicle in Non-diabetic Animals LX9211 (0.3 mg/kg)
Vehicle in Diabetic Animals LX9211 (1 mg/kg)
LX9211 (0.1 mg/kg) LX9211 (3 mg/kg)
****
********
****
****
****
*P<0.05, ****P=0.0001 compared to vehicle in diabetic animals
**** **** **** ****
Source: Unpublished data from Lexicon
**
© 2018 Lexicon Pharmaceuticals, Inc. 121
LX9211 Does Not Impair Motoric Coordination in the Rat
- Rotarod Performance Test
0
100
200
300
1 3 5
Rid
ing T
Ime (
s)
Time After Treatment (h)
Vehicle LX9211 (3 mg/kg) LX9211 (30 mg/kg) Gabapentin (100 mg/kg)
*P<0.05, **P<0.01, ****P=0.0001 compared to vehicle
*
******
Source: Unpublished data from Lexicon
© 2018 Lexicon Pharmaceuticals, Inc. 122
AAK1 Inhibitors - Mechanisms of Action
➢ Mechanism involves α2 adrenergic pathway
➢ Mechanism thought to involve GABAergic pathway
➢ Target does not have the same motor side effects seen with gabapentinoids
➢ Spinal dorsal horn key site of action (central nervous system target)
➢ Mechanism does not involve opioids
© 2018 Lexicon Pharmaceuticals, Inc. 123
LX9211- A Potent and Selective AAK1 Inhibitor for Neuropathic Pain: Key Takeaways
➢ High potency and specificity for AAK1 inhibition
➢ Robust target engagement and efficacy
➢ Superior profile to the current standard of care
➢ Excellent brain penetration
➢ Opioid target sparing
➢ Phase 1a clinical study ongoing
➢ Market opportunity for safe and effective medications
© 2018 Lexicon Pharmaceuticals, Inc. 124Precision Science. Pioneering Medicine. Patient Driven.
Financial Overview
Precision Science. Pioneering Medicine. Patient Driven.
Jeffrey L. Wade, J.D.Executive Vice President, Corporate and Administrative Affairs and Chief Financial Officer
April 10, 2018
© 2018 Lexicon Pharmaceuticals, Inc. 125
2017 Financials
Selected Income Sheet Data: 2017 2016
Revenue $90.3M1 $83.3M
Operating Expenses2
R&D $156.8M $178.2M
SG&A $66.2M $43.0M
Total Operating Expenses $227.0M $220.5M
Net Loss $(129.1)M $(141.4)M
Net Loss Per Common Share $(1.23) $(1.36)
Selected Balance Sheet Data: As of Dec 31, 2017
Cash & Investments $310.8 million
Total Assets $436.5 million
Total Debt $245.7 million
Common Shares Outstanding 105.7 million
1Includes $15.9M in net product revenue
2Includes stock-based compensation expenses
© 2018 Lexicon Pharmaceuticals, Inc. 126
2018 Financial Guidance
Selected Income Sheet Data:2018 Financial
Guidance
Revenue
Revenue from collaborations $30-$40M
Net product revenueAt least double year-
over-year
Operating Expenses1
R&D $125-$135M
SG&A $80-$90M
Total Operating Expenses $205-$225M
Non-Cash Expenses ~$17M
Net Cash Used in Operations $190-$205M
1Includes stock-based compensation expenses
© 2018 Lexicon Pharmaceuticals, Inc. 127
2018 Marks a Year of Transition - Sotagliflozin
Investments in sotagliflozin through 2018 may begin to yield returns in 2019 and 2020
Regulatory
Milestones
•$220M –
Milestones linked to
first commercial sale
after regulatory
approval for T1D
and T2D in U.S. and
Europe
Development
Milestones
•$110M –Milestones linked to
Phase 3 study
results in T2D
•$100M – Milestone
linked to success in
either of two T2D
outcomes studies
Sales Milestones
and Royalties
•$990M – Sales
milestones
•Royalties on net
sales
$430M
© 2018 Lexicon Pharmaceuticals, Inc. 128
Investment in the Future – Commercial and R&D
• Commercialization- Investments in XERMELO commercialization and medical affairs
activities, with a view towards achieving positive cash flow on the brand in the next 12-24 months
- Initiation of investments in sotagliflozin U.S. T1D commercialization and medical affairs activities, shared with Sanofi
• Research and development- Significant wind-down in R&D expenses for sotagliflozin
• Phase 3 program in T1D complete, with Q1 2018 global filings• Lexicon’s share of T2D development costs to be fully satisfied in 2018
- Investment in XERMELO clinical studies in biliary tract cancers and neuroendocrine tumors (NETs)
- Continued investment in earlier-stage R&D programs (including LX2761, LX9211 and additional research)
© 2018 Lexicon Pharmaceuticals, Inc. 129Precision Science. Pioneering Medicine. Patient Driven.
Q&A Session #2
Precision Science. Pioneering Medicine. Patient Driven.
April 10, 2018
© 2018 Lexicon Pharmaceuticals, Inc. 130Precision Science. Pioneering Medicine. Patient Driven.
Closing Remarks
Precision Science. Pioneering Medicine. Patient Driven.
Lonnel CoatsPresident and Chief Executive Officer
April 10, 2018
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