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Definitive QT Study Completed • Required study, part of cardiovascular safety profile • 64 healthy volunteers randomized to single doses of LX4211 400
mg, 2000 mg, placebo, or moxifloxacin in crossover fashion • Study results met FDA guidance for supporting CV safety
Additional Multiple Ascending Dose Study Completed • Phase 1 study evaluating safety and tolerability of 800 mg dose • 25 subjects randomized 2:2:1 to 10 days of treatment with LX4211
400 mg, LX4211 800 mg, or placebo • Study results showed adequate safety and pharmacokinetic data to
support use of LX4211 400 mg in Phase 3 clinical development
Type 1 Diabetes: An Area of High Unmet Medical Need
• Substantial and growing patient population ‒ More than one million patients in the U.S. ‒ Incidence rate in children, where most T1DM is first diagnosed, is
growing at 3% annually
• Key area of unmet medical need: Therapies that achieve euglycemia ‒ Reduction of glucose variability ‒ More effective and less difficult management of glucose control
• Substantial majority of T1DM patients are not achieving HbA1c
targets ‒ More than 50% have HbA1c >8% ‒ Up to 80% of T1DM patients in some age cohorts are above target
• Significant percentage of T1DM patients experience severe
hypoglycemic events ‒ Increases with age and duration of diabetes
• Open-label Pioneer Group of 3 subjects on insulin pump to allow for initial assessment of safety and establishment of initial insulin dose reduction for Expansion Group
• Expansion Group of approximately 30 subjects on either
• Adult subjects 18 to 55 years old (inclusive) with T1DM, currently on either continuous subcutaneous insulin infusion (CSII, insulin pump) or multiple dose insulin injection (MDI)
• Screening with the following laboratory values: - HbA1c value ≥7.0% to ≤9.0% - FPG ≤270 mg/dL - Body mass index (BMI) ≤32 kg/m2 - Fasting C-peptide ≤0.7 ng/L - Triglycerides ≤1000 mg/dL
• Primary goal: to establish safety and mechanistic proof-of-concept - First co-administration of LX4211 with insulin
• Primary Endpoint
- To assess the effect of LX4211 on the total amount of bolus insulin required
• Secondary Objectives (partial list)
- To assess multiple parameters of glycemic control - To assess the effect of LX4211 on basal and total insulin use - To assess other metabolic, pharmacodynamic and
LX4211 Achieved Positive Proof-of-Concept in Type 1 Diabetes, Progressing into Late-Stage Development
• LX4211 met primary endpoint by lowering bolus insulin by 32%
• LX4211 improved glycemic control:
- Lowered A1C by 0.55% in four weeks - Less hyperglycemia, CGM time > 180 mg/dL range - More CGM time in 70-180mg/dL range - No increase in hypoglycemia - Less glycemic variability by multiple measures
• LX4211 decreased body weight
• LX4211 was well tolerated
• Lexicon is committed to progressing LX4211 into Phase 3
LX4211 Strategy for Late Stage Development and Commercialization
• Unique dual mechanism of action through inhibition of both SGLT1 and SGLT2 with favorable safety profile
• Phase 3 program in broad population of patients with diabetes - Alone or in combination other agents to treat type 2 diabetes - Diabetics with renal impairment - Type 1 diabetes
• Mechanistic synergy with DPP-4 inhibitors with potential for
Assessment of U.S. Carcinoid Market and Telotristat Etiprate’s Opportunity
U.S. Carcinoid Treatment Flow
Market Assessment
Treated with Octreotide (13.4K, 98%)
Octreotide Adequately Controlled (7.4K, 55%)
Octreotide Not Adequately Controlled
(6.0K, 45%)
Carcinoid Functioning Tumors
(13.7K, 22%)
Carcinoid Non Functioning Tumors
(47.8K, 78%)
New Patients – Treatment Naive (Incidence)
1.6K
Sources: EPI Research, NET Claims data from IMS, primary research with 45 oncologists, August 2013
Note: Segment sizes in 2012
Telotristat etiprate blocks the
production of serotonin and is planned to be positioned as an essential add-on therapy to somatostatin analogs (SSA) during a patient’s journey with a functioning carcinoid tumor
Serotonin is a key
driver of functioning carcinoid tumors, and its overproduction results in the consequences of carcinoid syndrome
Most Carcinoid Patients are Eventually Not Adequately Controlled on Octreotide
% controlled % not controlled
79% of patients are eventually not adequately controlled on
octreotide
Octreotide fails to adequately control carcinoid syndrome within
36 months for 71% of patients
The current treatment paradigm for these patients includes: • Titration to higher doses of octreotide beyond label recommendations • Increase in frequency of immediate release octreotide injections
0 to 6
14%
6 to 12
12%
12 to 24
24% 24 to 36
21%
> 36
29%
No new therapy options exist for patients not adequately controlled
Note: values above represent time in months
Source: Primary research with 45 oncologists, August 2013
Telotristat Etiprate Phase 3 Study Overview: TELESTAR
• Phase 3, randomized, placebo-controlled, double-blind study
• Sample size: 105 subjects (at minimum)
• Double-blind treatment period: 12 weeks
• Open-label extension and follow-up period: 36 weeks
Objectives
• Primary: To confirm that at least 1 or more doses of telotristat etiprate compared to placebo is effective in reducing the change from baseline in the number of daily bowel movements (BMs) over the 12-week double-blind portion (treatment period) of the trial in patients inadequately controlled on somatostatin analog therapy
• Telotristat etiprate (LX1032) for carcinoid syndrome - Pivotal Phase 3 study TELESTAR enrolling well - Companion study TELECAST in progress - Commercial preparations underway
• LX4211 for diabetes
- Phase 3-ready in type 2 diabetes - Phase 3 planning underway for type 1 diabetes