Pipeline Development - Pilavapadin (LX9211) Phase 2b PROGRESS study identified the 10 mg dose as the most clinically meaningful for DPNP[13], with post-hoc analysis showing statistically significant pain reduction compared to placebo (p = 0.04) in combined 10 mg dosing arms[16] - The PROGRESS study enrolled 496 patients[12], and the 10 mg dose had a completion rate of 87.8%[18], similar to the placebo group's 87.9%[18] - LX9851 IND-enabling studies are underway for obesity and related metabolic disorders[6], showing potential for weight loss maintenance after semaglutide discontinuation in preclinical studies[34] - SONATA-HCM Phase 3 trial is enrolling globally to evaluate sotagliflozin in both obstructive and non-obstructive HCM patients[21, 29] Sotagliflozin & INPEFA - Sotagliflozin has shown a 0.77 hazard ratio (95% CI 0.65-0.91, p=0.0020) for reduced major adverse cardiovascular events (MACE) in patients with T2D, CKD, and high CV risk[23] - Approximately 1.1 million people in the U.S. have HCM[26, 27], presenting a significant market opportunity for sotagliflozin[26] - Viatris is undertaking ex-US, ex-EU registration and regional development of sotagliflozin[21] Market Opportunity & Partnerships - Approximately 9 million U.S. patients have progressive DPNP[20], with 60% experiencing moderate-to-severe pain and low satisfaction with current treatments[20] - Lexicon entered an exclusive licensing agreement with Novo Nordisk for LX9851, receiving $75 million in upfront and near-term milestones, with potential for up to $1 billion in aggregate payments[40] - Lexicon entered an exclusive licensing agreement with Viatris for sotagliflozin outside the U.S. and Europe, receiving $25 million upfront, with potential for almost $200 million in milestone payments[40]

Business Highlights - Lexicon entered an exclusive worldwide licensing agreement with Novo Nordisk for LX9851[5, 21] - Pilavapadin (LX9211) PROGRESS readout identified a de-risked dose of 10mg to move into Phase 3 trials[5] - The company reduced debt and strengthened its financial position[5] - Pilavapadin 10 mg has consistently delivered clinically meaningful pain reduction[7] Market Opportunity - Approximately 9 million people in the U S living with diabetes suffer from DPNP[10] - It is projected that there will be 13 million DPNP patients in the U S by 2035[10] - Approximately 70% of patients with neuropathic pain do not achieve partial pain management[10] - Approximately 11 million people in the U S have either obstructive or non-obstructive HCM[14] Financial Overview - As of March 31, 2025, Lexicon had $1948 million in cash, cash equivalents, and short-term investments[26] - Total debt was $586 million as of March 31, 2025[26] - Total revenues for Q1 2025 were $13 million compared to $11 million in Q1 2024[26] - The company expects total 2025 operating expenses to be between $135 million and $145 million[29]

The ADA emphasizes that hypoglycemia remains an important patient management issue in T1D. Its Standards of Care in Diabetes -- 2025 clinical update states, "Health care professionals should be vigilant in preventing hypoglycemia." In addition, severe hypoglycemia accounts for 5% of T1D hospitalizations and up to 10% of T1D deaths. Chronic kidney disease (CKD) is an important, independent risk factor for hypoglycemia in people with T1D. Approximately 20% to 40% of people with T1D develop CKD. Treatment with ...

Core Insights - Lexicon Pharmaceuticals is set to present data on sotagliflozin's ability to reduce hypoglycemic events in type 1 diabetes patients at the 85th Scientific Sessions of the American Diabetes Association on June 22, 2025 [1][3] - The company will also present topline data from the PROGRESS Phase 2b study on pilavapadin (LX9211) for diabetic peripheral neuropathic pain during the same event [1][3] Sotagliflozin Presentation - The presentation titled "Sotagliflozin Added to Insulin Reduces the Risk of Clinically Important Hypoglycemic Events in Adults with Type 1 Diabetes Regardless of Kidney Function" will take place on June 22, 2025, from 4:00-4:15 p.m. CT [3] - Clinical efficacy data for sotagliflozin will be segmented by kidney function subgroups based on Estimated Glomerular Filtration Rate (eGFR) [2] PROGRESS Study Overview - The PROGRESS study began in December 2023, enrolling 496 adult patients with diabetes and moderate to severe diabetic peripheral neuropathic pain [6] - The study is placebo-controlled, focusing on changes in pain levels over an 8-week period with various dosages of pilavapadin [6][7] About Sotagliflozin - Sotagliflozin is an oral inhibitor targeting SGLT2 and SGLT1 proteins, which are involved in glucose regulation [5] - The drug has been studied in approximately 20,000 patients across various conditions, including heart failure and chronic kidney disease [5] About Diabetic Peripheral Neuropathic Pain (DPNP) - DPNP is a chronic complication of diabetes affecting around 9 million patients in the U.S., causing symptoms like burning pain and numbness [8]

Summary of Lexicon Pharmaceuticals Conference Call Company Overview - **Company**: Lexicon Pharmaceuticals - **Industry**: Biopharmaceuticals, focusing on cardiometabolic and associated disorders - **Key Products**: LX9851 (obesity treatment), pilovapitan (neuropathic pain), sotagliflozin (hypertrophic cardiomyopathy) Core Points and Arguments 1. **Licensing Agreement**: Lexicon signed an exclusive worldwide license for LX9851 with Novo Nordisk, providing significant financial terms and flexibility on the balance sheet for a preclinical asset [3][4] 2. **Pilovapitan Development**: The Phase 2b study for pilovapitan in diabetic peripheral neuropathic pain (DPNP) showed a significant reduction in pain scores compared to placebo, with a 1.5 to nearly 2-point drop from baseline within 6 to 8 weeks [4][14] 3. **Sotagliflozin Progress**: Enrollment for sotagliflozin in hypertrophic cardiomyopathy (HCM) is progressing well, with data readouts expected in 2027. The drug is positioned to target both obstructive and non-obstructive HCM [4][34] 4. **FDA Engagement**: Lexicon is preparing to meet with the FDA for pilovapitan's Phase 3 study, expecting to submit a complete data package by late Q3 to early Q4 [18][19] 5. **Partnerships**: The partnership with Viatris is validating for sotagliflozin, with plans to file in challenging markets like Canada and Australia [10][34] 6. **Financial Position**: Lexicon ended Q1 with approximately $195 million in cash, sufficient to fund ongoing projects, but the Phase 3 program will be funded in partnership [28][29] 7. **Market Positioning**: Sotagliflozin is expected to be prescribed widely due to its known safety profile and ease of use, potentially becoming the first indicated new medicine in non-obstructive HCM [34][35] Additional Important Insights 1. **Clinical Need**: There is a significant need for non-opioid medications for chronic neuropathic pain, as current options are inadequate [12] 2. **Trial Design**: The Phase 3 trial for pilovapitan will have a single active dose versus placebo design to minimize placebo effects [22][23] 3. **Market Dynamics**: The ability to charge a higher price for sotagliflozin in HCM is contingent on being the first approved medicine for that indication, similar to previous experiences with Zynquista [36][37] 4. **Milestone Payments**: Lexicon expects to receive $30 million in near-term milestone payments from the Novo partnership, with the first being the submission of the IND [46][48] This summary encapsulates the key points discussed during the conference call, highlighting Lexicon's strategic direction, product pipeline, and market positioning.

Group 1 - Lexicon Pharmaceuticals will participate in a fireside chat at the 2025 Jefferies Global Healthcare Conference on June 5 at 12:50 p.m. ET [1] - The event will be accessible live and as a replay on the Company's website [1] Group 2 - Lexicon Pharmaceuticals is a biopharmaceutical company focused on pioneering medicines that transform patients' lives [2] - The Genome5000™ program has enabled Lexicon to study nearly 5,000 genes, identifying over 100 protein targets with significant therapeutic potential [2] - The company has advanced multiple medicines to market and has a pipeline of drug candidates in various stages of development for conditions such as heart failure, neuropathic pain, obesity, cardiology, and diabetes [2]

Financial Data and Key Metrics Changes - The company reported approximately $195 million in cash and investments as of the end of March [3] - In Q1, the company generated about $1.4 million in sales for its heart failure drug, Impefa, maintaining sales levels from previous quarters despite a scaled-down commercial footprint [20] Business Line Data and Key Metrics Changes - The Phase 2b PROGRESS study for pilovaparin demonstrated that the 10 mg daily dose outperformed the 20 mg dose, supporting its efficacy for diabetic peripheral neuropathic pain [12] - The company has seen no sales growth for Impefa this year but expects to maintain sales in the U.S. while pursuing regulatory approvals in other countries [20][21] Market Data and Key Metrics Changes - There are approximately 9 million people in the U.S. diagnosed with diabetic peripheral neuropathic pain, indicating a significant market opportunity for new treatments [5] - The company is actively pursuing regulatory approvals in the UAE, Saudi Arabia, and Canada for Impefa, which could lead to meaningful sales growth outside the U.S. [21] Company Strategy and Development Direction - The company is focusing on partnerships to enhance the development and commercialization of its assets, particularly pilovaparin, which has potential for multiple indications [17] - The company aims to maintain its presence in the market for Impefa while building evidence for its efficacy through ongoing studies [22] Management's Comments on Operating Environment and Future Outlook - Management highlighted the desperate need for new non-opioid treatments in the context of the opioid crisis, particularly for diabetic peripheral neuropathic pain [6] - The company is optimistic about the upcoming catalysts, including data presentations and regulatory meetings, which are expected to drive value for its development pipeline [45] Other Important Information - The company has entered into a partnership with Novo Nordisk for its obesity asset, receiving $75 million in upfront payments and potential future milestones totaling up to $1 billion [38] - The SONata HCM clinical trial for sotagliflozin is designed to include both obstructive and nonobstructive hypertrophic cardiomyopathy, with regulatory approvals obtained in 20 countries [33][34] Q&A Session Summary Question: Can you provide insights on pilovaparin's next regulatory steps? - The company plans to present data from the Phase 2b study at major medical meetings and will have an end-of-Phase 2 meeting with the FDA to finalize Phase 3 designs [14][15] Question: What are the commercial prospects for soragliflozin? - The company has maintained sales of Impefa in the U.S. and is pursuing regulatory approvals in other countries, expecting meaningful sales growth as these approvals are granted [20][21] Question: What is the rationale for evaluating sotagliflozin in both forms of HCM? - The underlying pathophysiology of HCM is similar in both obstructive and nonobstructive forms, making sotagliflozin a promising candidate for treatment [24][25] Question: How is the partnership with Novo Nordisk structured? - The partnership allows Novo to take over the IND submission process after Lexicon completes the IND enabling studies, which are expected to be finished this year [41][42]

Core Insights - Lexicon Pharmaceuticals is conducting a pivotal Phase 3 clinical trial named SONATA-HCM to evaluate the safety and efficacy of sotagliflozin in patients with both obstructive and non-obstructive hypertrophic cardiomyopathy (HCM) [1][2] - The study aims to enroll 500 patients globally, with a primary efficacy endpoint focused on symptom improvement as measured by the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score [3][4] - The trial is expected to support a supplemental new drug application for sotagliflozin, addressing a significant unmet need in the treatment of non-obstructive HCM [2][4] Study Design and Objectives - SONATA-HCM is a randomized, double-blind, placebo-controlled multicenter trial [3] - The study will include 250 patients with obstructive HCM and 250 with non-obstructive HCM [3] - The primary endpoint is the change in symptoms from baseline to week 26, assessed through the KCCQ CSS survey [3] Clinical Significance - There is a notable lack of approved therapies for non-obstructive HCM, highlighting the importance of this study [4] - Sotagliflozin has shown potential benefits in heart failure patients, which may extend to HCM patients if proven effective [4] - The drug's dual inhibition of SGLT1 and SGLT2 is associated with reduced risk of major adverse cardiovascular events, as noted in recent publications [4] Company Overview - Lexicon Pharmaceuticals focuses on pioneering medicines that transform patients' lives, utilizing a unique genomics target discovery platform [7][8] - The company has a pipeline of drug candidates in various stages of development, including treatments for HCM, neuropathic pain, obesity, and metabolic disorders [8]

Financial Performance - Revenues for Q1 2025 were approximately $1.3 million, up from $1.1 million in Q1 2024, primarily from sales of INPEFA[79]. - Research and development expenses increased by 6% to $15.3 million in Q1 2025 from $14.4 million in Q1 2024, driven by a 12% rise in third-party services[81]. - Selling, general and administrative expenses decreased by 64% to $11.6 million in Q1 2025 from $32.1 million in Q1 2024[82]. - Net loss for Q1 2025 was $25.3 million, or $0.07 per share, compared to a net loss of $48.4 million, or $0.20 per share, in Q1 2024[86]. - The company had an accumulated deficit of approximately $2.0 billion as of March 31, 2025[77]. Cash and Investments - Cash, cash equivalents, and short-term investments totaled $194.8 million as of March 31, 2025, down from $238.0 million at the end of 2024[90]. - Current unrestricted cash and investments amount to approximately $194.8 million as of March 31, 2025, sufficient to fund operations for at least the next 12 months[101]. - The company has approximately $194.8 million in cash and cash equivalents, with limited market and credit risk exposure[104]. Debt and Financing - The company entered into an Open Market Sale Agreement with Jefferies LLC for the potential sale of up to $75 million in common stock[91]. - A seventh amendment to the loan agreement with Oxford included a prepayment of $45 million and modifications to financial covenants[92]. - The company repaid $45 million to Oxford in April 2025, with additional payments of $20.2 million, $30.2 million, and $11.6 million due in the fiscal years ending December 31, 2027, 2028, and 2029 respectively[93]. - As of March 31, 2025, the company maintained a minimum cash balance of $29 million in a blocked account, in compliance with its debt covenants[94]. - The outstanding Oxford Term Loans bear interest at a floating rate tied to the 1-month CME Term SOFR rate, maturing by March 2029[105]. - If liquidity needs arise, the company may seek additional financing through collaborations or selling equity, which could dilute stockholder value[102]. Regulatory and Collaboration Updates - The company received Fast Track designation from the FDA for pilavapadin in diabetic peripheral neuropathic pain[74]. - The company is pursuing regulatory approval for ZYNQUISTA (sotagliflozin) for type 1 diabetes, with ongoing proceedings related to its NDA[70]. - The company entered into an exclusive license agreement with Novo Nordisk A/S in March 2025, receiving an upfront payment of $45 million and potential milestone payments totaling up to $960 million[95]. - An exclusive license agreement with Viatris for the development of sotagliflozin resulted in an upfront payment of $25 million in October 2024[96]. - Upon regulatory approval of sotagliflozin, the company will make royalty payments totaling $4.5 million in three annual installments of $1.5 million[97]. Future Outlook - The company expects substantial future capital requirements, influenced by ongoing R&D success and new collaborations[100].

Group 1 - Lexicon Pharmaceuticals reported a quarterly loss of $0.07 per share, better than the Zacks Consensus Estimate of a loss of $0.10, and an improvement from a loss of $0.20 per share a year ago, resulting in an earnings surprise of 30% [1] - The company posted revenues of $1.26 million for the quarter ended March 2025, missing the Zacks Consensus Estimate by 23.52%, compared to year-ago revenues of $1.13 million [2] - Lexicon shares have declined approximately 8.8% since the beginning of the year, while the S&P 500 has seen a decline of -0.6% [3] Group 2 - The current consensus EPS estimate for the upcoming quarter is -$0.09 on revenues of $2.37 million, and for the current fiscal year, it is -$0.37 on revenues of $15.43 million [7] - The Zacks Industry Rank for Medical - Biomedical and Genetics is in the top 35% of over 250 Zacks industries, indicating a favorable outlook for the industry [8] - Lexicon has a Zacks Rank of 2 (Buy), suggesting that the stock is expected to outperform the market in the near future [6]