SGLT1

Post hoc analysis evaluated sotagliflozin in patients with diabetic kidney disease (DKD) THE WOODLANDS, Texas, Oct. 23, 2024 (GLOBE NEWSWIRE) -- Lexicon Pharmaceuticals, Inc. (Nasdaq: LXRX) today announced a new analysis of its Phase 3 SCORED clinical trial demonstrating the protective effects of sotagliflozin in patients with diabetic kidney disease (DKD). Data will be presented at Kidney Week 2024, the annual meeting of the American Society of Nephrology in San Diego, California. Previous analyses of the SCORED trial have shown that sotagliflozin, a dual SGLT1 & 2 inhibitor, reduced the risk of kidney and cardiorenal composite endpoints in patients with type 2 diabetes (T2D) and diabetic kidney disease (DKD). The objective of this new post hoc analysis of SCORED was to evaluate the effect of sotagliflozin versus placebo on Estimated Glomerular Filtration Rate (eGFR) slope, and the impact of baseline kidney function and glycemia. The eGFR slope assessment is widely used as a surrogate endpoint in cardiovascular and chronic kidney disease trials. Details for the presentation are as follows: “ Effect of sotagliflozin on eGFR slope by baseline kidney function and glycemic control ” – a moderated poster presentation, Friday, October 25, 10:00a.m.PT, 4:00-5:00p.m, Exhibit Hall, San Diego Convention Center, presented by Vikas S. Sridhar, M.D., University of Toronto, Ontario Within the entire cohort of 10,574 participants, a placebo-adjusted acute decline in eGFR of -2.59 ml/min/1.73m2/year (95% CI -2.88, -2.30; p<0.0001) was observed. The total placebo-adjusted slope was -0.08 ml/min/1.73m2/year (95% CI -0.43, 0.27; p=0.67). Compared to placebo, sotagliflozin had a greater benefit on chronic slope with increasing baseline albuminuria (P-interaction=0.023). Full study results will be discussed during the moderated poster and can be accessed here on the Kidney Week website. “Researchers observed positive renal protection with sotagliflozin across a spectrum of baseline kidney function and glycemic control. This study makes an important contribution to understanding the clinical benefits of sotagliflozin for people with diabetic kidney disease,” said Craig Granowitz, M.D., Ph.D., Lexicon’s senior vice president and chief medical officer. About sotagliflozin Discovered using Lexicon’s unique approach to gene science, sotagliflozin is an oral inhibitor of two proteins responsible for glucose regulation known as sodium-glucose cotransporter types 2 and 1 (SGLT2 and SGLT1). SGLT2 is responsible for glucose and sodium reabsorption by the kidney and SGLT1 is responsible for glucose and sodium absorption in the gastrointestinal tract. Sotagliflozin has been studied in multiple patient populations encompassing heart failure, diabetes, and chronic kidney disease in clinical studies involving approximately 20,000 patients. About Lexicon Pharmaceuticals Lexicon is a biopharmaceutical company with a mission of pioneering medicines that transform patients’ lives. Through the Genome5000™ program, Lexicon’s unique genomics target discovery platform, Lexicon scientists studied the role and function of nearly 5,000 genes and identified more than 100 protein targets with significant therapeutic potential in a range of diseases. Through the precise targeting of these proteins, Lexicon is pioneering the discovery and development of innovative medicines to treat disease safely and effectively. Lexicon has commercially launched one of these medicines, INPEFA® (sotagliflozin) in the United States, and has a pipeline of other promising drug candidates in discovery and clinical and preclinical development in neuropathic pain, diabetes and metabolism and other indications. For additional information, please visit Safe Harbor Statement This press release contains “forward-looking statements,” including statements relating to Lexicon’s financial position and long-term outlook on its business, including the commercialization of its approved products and the clinical development of, regulatory filings for, and potential therapeutic and commercial potential of its other drug candidates. In addition, this press release also contains forward looking statements relating to Lexicon’s growth and future operating results, discovery, development and commercialization of products, strategic alliances and intellectual property, as well as other matters that are not historical facts or information. All forward-looking statements are based on management’s current assumptions and expectations and involve risks, uncertainties and other important factors, specifically including Lexicon’s ability to meet its capital requirements, successfully commercialize its approved products, successfully conduct preclinical and clinical development and obtain necessary regulatory approvals of its other drug candidates on its anticipated timelines, achieve its operational objectives, obtain patent protection for its discoveries and establish strategic alliances, as well as additional factors relating to manufacturing, intellectual property rights, and the therapeutic or commercial value of its approved products and other drug candidates. Any of these risks, uncertainties and other factors may cause Lexicon’s actual results to be materially different from any future results expressed or implied by such forward-looking statements. Information identifying such important factors is contained under “Risk Factors” in Lexicon’s annual report on Form 10-K for the year ended December 31, 2023, as filed with the Securities and Exchange Commission. Lexicon undertakes no obligation to update or revise any such forward-looking statements, whether as a result of new information, future events or otherwise. For Investor and Media Inquiries : Lisa DeFrancesco Lexicon Pharmaceuticals, Inc. lexinvest@lexpharma.com

Insight 数据库「医药交易」模块显示，本周全球范围内共发生 13 项医药交易（截至 10 月 18 日），涉及辉瑞、诺华、赛诺菲、百裕制药、灵北制药、晖致医药等公司。 其中： 大额交易中，有灵北制药约 25 亿美元收购罕见病公司获得癫痫新药，辉瑞超 15 亿美元布局分子胶降解剂； 在中国创新药出海方面，百裕制药开发的一款小分子抗肿瘤药以 11.7 亿美元的价格授予诺华； 另外，还有赛诺菲、灵北制药、晖致医药等公司达成新合作，涉及放射性配体疗法、SGLT-1/2 双效抑制剂、5-HT2C 受体激动剂、YKL-40 抑制剂等创新产品。 下面，Insight 数据库将节选部分备受关注的交易案例做介绍，仅供读者参阅。 跨国药企竞相布局新疗法   辉瑞超 15 亿美元布局分子胶 TRIANA Biomedicines 与辉瑞达成合作，以发现包括肿瘤学在内多个疾病领域多个靶点的新型分子胶降解剂。为此，前者将获得 4900 万美元预付款，并有资格获得超过 15 亿美元的潜在未来里程碑以及分层特许权使用费。 根据协议，TRIANA 公司将利用其分子胶发现平台，领导发现和确定潜在的开发候选管线。而辉瑞将拥有独家许可选择权，以进一步推进临床前和临床开发。   诺华约 11.7 亿美元引进百裕制药小分子抗肿瘤药 诺华与百裕制药签订独家许可协议，获得百裕制药一款在研抗肿瘤小分子药物的全球独家开发及商业化权利。根据协议，百裕制药将收到 7000 万美元首付款，及可达 11 亿美元的开发、注册、商业化等里程碑付款和相应特许权使用费。 百裕制药专注银杏核心药效成分研究二十余年，聚焦肿瘤及自身免疫疾病领域。此次授权的产品正是该公司创新药团队发现的一款治疗恶性肿瘤小分子创新药。   赛诺菲 3 亿欧元股权投资 Orano Med 赛诺菲与 Orano Med 签署协议，加速下一代放射性配体药物的开发。根据协议，赛诺菲将向 Orano Med 进行 3 亿欧元的股权投资。基于 Orano Med 的专业知识及其放射性配体药物研发管线，双方将共同专注于基于铅-212 同位素的α粒子放射性配体疗法的发现、设计和临床开发。 上个月，赛诺菲已与 RadioMedix 和 Orano Med 达成总额约 3.2 亿欧元合作，以共同开发基于同位素铅的放射性配体疗法（RLT）用于癌症治疗。该合作则主要聚焦于后期临床项目 AlphaMedix，用于治疗进展性生长抑素受体表达神经内分泌肿瘤（NET）成年患者。 其它授权合作   灵北制药收购公司获得癫痫新药 灵北制药（Lundbeck）和 Longboard Pharmaceuticals 达成协议，灵北制药将收购 Longboard 公司并获得潜在「best-in-class」产品 bexicaserin（LP352）。该交易预计将于 2024 年第四季度完成，总交易价值约为 26 亿美元股权价值和 25 亿美元现金净额。 Bexicaserin 是一款高选择性、口服、新型 5-HT2C 受体激动剂，正在开发用于治疗与发育性癫痫性脑病（DEE）相关的癫痫发作，包括 Dravet 综合征、Lennox-Gastaut 综合征和其他罕见癫痫。目前，该产品用于治疗 Dravet 综合征相关癫痫发作的全球 3 期试验正在进行中。   晖致医药 2500 万美元引进 SGLT-1/2 双效抑制剂 晖致医药（Viatris）获得 Lexicon Pharmaceutical 独家许可，可在美国和欧洲以外的所有适应症中商业化 SGLT-1/2 双效抑制剂 Sotagliflozin，Lexicon 保留了该药在美国和欧洲所有适应症的独家商业化权利。为此，Lexicon 公司将获得 2500 万美元的预付款及潜在监管和商业里程碑付款。 Sotagliflozin 已于 2023 年 5 月获得美国 FDA 批准，用于降低成人患者的心血管死亡、因心力衰竭而住院或接受急救的风险。这些患者患有心力衰竭或 2 型糖尿病、慢性肾病，并携带其它心血管疾病风险因子。   Molecure 与 Ocean Biomedical 达成合作 Molecure 公司与 Ocean Biomedical 签署了一项独家许可协议，后者获得了在全球范围内进一步研究、开发、制造和商业化 Molecure 公司 OAT-3912 和其他选择性 YKL-40 抑制剂的独家权利。根据协议，Molecure 公司将获得 60 万美元的现金和股票作为初始补偿，并有望获得潜在里程碑付款，协议最高价值约为 3200 万美元。 该协议涵盖了「first-in-class」的小分子 YKL-40 抑制剂，包括先导分子 OAT-3912，它在各种癌症及炎症和纤维化疾病的临床前模型中显示出潜在治疗益处。   Orasis 公司 1800 万美元授出滴眼液韩国权益 Orasis Pharmaceuticals 授予 Optus pharmaceutical 在韩国商业化、进口和销售 0.4% Qlosi（盐酸匹罗卡品滴眼液）的权利，这是一种治疗成人老视的新型矫正滴眼液。 根据协议，这项合作其他条款包括预付款和关键里程碑的付款，共计 1800 万美元，此外还有韩国市场销售额的两位数特许权使用费。Optus 公司计划率先在韩国市场推出一种新的老视治疗药物，并计划在获得监管批准和销售批准后，于 2026 年在韩国推出 Qlosi。 除了上述案例，本周还有一些其它公司也达成了不同类型的合作，限于篇幅，此处不再一一介绍。欲了解本周更多授权合作信息，可点击阅读原文前往 Insight 数据库「医药交易」模块查看。 封面来源：站酷海洛 Plus 免责声明：本文仅作信息分享，不代表 Insight 立场和观点，也不作治疗方案推荐和介绍。如有需求，请咨询和联系正规医疗机构。 编辑：馨药 PR 稿对接：微信 insightxb 投稿：微信 insightxb；邮箱 insight@dxy.cn 多样化功能、可溯源数据…… Insight 数据库网页版等你体验 点击阅读原文，立刻解锁！

-Lexicon to receive an upfront payment of $25 million and the potential for contingent regulatory and commercial milestone paymentsTHE WOODLANDS, Texas, Oct. 16, 2024 (GLOBE NEWSWIRE) -- Lexicon Pharmaceuticals, Inc. (Nasdaq: LXRX) today announced that Viatris Inc. (Nasdaq: VTRS) has obtained an exclusive license from Lexicon to commercialize sotagliflozin outside of the United States and Europe in all indications. Lexicon retains sole commercialization rights for sotagliflozin in all indications in the United States and Europe. Sotagliflozin was approved by the U.S. Food and Drug Administration in May 2023 to reduce the risk of cardiovascular death, hospitalization for heart failure, and urgent heart failure visit in adults with heart failure or type 2 diabetes mellitus, chronic kidney disease, and other cardiovascular risk factors. “We are pleased to be working with Viatris, a company with strong cardiometabolic expertise, global commercial capabilities and a successful track record of launching medicines in new territories. We are confident that this agreement will expand the reach of sotagliflozin to more patients in need,” said Dr. Mike Exton, Ph.D., chief executive officer and director of Lexicon. “Partnering with high quality companies to support commercialization of our medicines globally is a critical pillar of our Lead to Succeed strategy at Lexicon. We plan to continue to evaluate strategic partnerships for additional assets, territories and indications to augment Lexicon’s development and commercial capabilities, advance our pipeline and expand access of our medicines to more patients around the world.” Viatris chief commercial officer Corinne Le Goff said: “This licensing agreement with Lexicon adds another asset to our expanding innovative portfolio in cardiovascular diseases which gives us the opportunity to further drive accelerated and durable revenue growth in the future. We believe we will be able to leverage our strong foundation in cardiovascular diseases and our unique infrastructure to execute on the potential of sotagliflozin. We look forward to working with Lexicon to make a real difference and expand access for patients.” Under the terms of the agreement, Viatris has acquired rights to sotagliflozin in all global markets outside of the U.S. and Europe in exchange for an upfront payment to Lexicon of $25 million, and the potential for contingent regulatory and sales milestone payments and tiered royalties ranging from low-double-digit to upper-teens on annual net sales. Viatris will be responsible for all regulatory and commercialization activities for sotagliflozin in the licensed territories. Lexicon will be responsible for providing clinical and commercial supply of sotagliflozin to Viatris at an agreed upon transfer price. About Lexicon Pharmaceuticals Lexicon is a biopharmaceutical company with a mission of pioneering medicines that transform patients’ lives. Through its Genome5000™ program, Lexicon scientists studied the role and function of nearly 5,000 genes and identified more than 100 protein targets with significant therapeutic potential in a range of diseases. Through the precise targeting of these proteins, Lexicon is pioneering the discovery and development of innovative medicines to safely and effectively treat disease. Lexicon is commercially launching one of these medicines, INPEFA® (sotagliflozin) in the United States, and has a pipeline of other promising drug candidates in discovery and clinical and preclinical development in neuropathic pain, diabetes and metabolism and other indications. For additional information, please visit www.lexpharma.com. About ViatrisViatris Inc. (Nasdaq: VTRS) is a global healthcare company uniquely positioned to bridge the traditional divide between generics and brands, combining the best of both to more holistically address healthcare needs globally. With a mission to empower people worldwide to live healthier at every stage of life, Viatris provides access at scale, currently supplying high-quality medicines to approximately 1 billion patients around the world annually and touching all of life’s moments, from birth to the end of life, acute conditions to chronic diseases. With its exceptionally extensive and diverse portfolio of medicines, a one-of-a-kind global supply chain designed to reach more people when and where they need them, and the scientific expertise to address some of the world’s most enduring health challenges, access takes on deep meaning at Viatris. Viatris is headquartered in the U.S., with global centers in Pittsburgh, Shanghai and Hyderabad, India. Learn more at viatris.com and investor.viatris.com, and connect with Viatris on LinkedIn, Instagram, YouTube and X (formerly Twitter). About SotagliflozinDiscovered using Lexicon’s unique approach to gene science, sotagliflozin is an oral inhibitor of two proteins responsible for glucose regulation known as sodium-glucose cotransporter types 2 and 1 (SGLT2 and SGLT1). SGLT2 is responsible for glucose and sodium reabsorption by the kidney and SGLT1 is responsible for glucose and sodium absorption in the gastrointestinal tract. Sotagliflozin has been studied in multiple patient populations encompassing heart failure, diabetes, and chronic kidney disease in clinical studies involving approximately 20,000 patients. INDICATION INPEFA is indicated to reduce the risk of cardiovascular death, hospitalization for heart failure, and urgent heart failure visit in adults with:  heart failure or  type 2 diabetes mellitus, chronic kidney disease, and other cardiovascular risk factors  IMPORTANT SAFETY INFORMATION  Dosing: Assess renal function and volume status and, if necessary, correct volume depletion prior to initiation of INPEFA.  INPEFA dosing for patients with decompensated heart failure may begin when patients are hemodynamically stable, including when hospitalized or immediately upon discharge.  Contraindications: INPEFA is contraindicated in patients with hypersensitivity to INPEFA or any of its components.  Ketoacidosis: INPEFA increases the risk of ketoacidosis in patients with type 1 diabetes mellitus (T1DM).  Type 2 diabetes Mellitus (T2DM) and pancreatic disorders are also risk factors.  The risk of ketoacidosis may be greater with higher doses.  There have been postmarketing reports of fatal events of ketoacidosis in patients with type 2 diabetes using sodium glucose transporter 2 (SGLT2) inhibitors.  Before initiating INPEFA, assess risk factors for ketoacidosis. Consider ketone monitoring in patients with T1DM and consider ketone monitoring in others at risk for ketoacidosis and educate patients on the signs/symptoms of ketoacidosis.  Patients receiving INPEFA may require monitoring and temporary discontinuation of therapy in clinical situations known to predispose to ketoacidosis.  INPEFA is not indicated for glycemic control.  Assess patients who present with signs and symptoms of metabolic acidosis or ketoacidosis, regardless of blood glucose level.  If suspected, discontinue INPEFA, evaluate, and treat promptly.  Monitor patients for resolution of ketoacidosis before restarting INPEFA.  Volume Depletion: INPEFA can cause intravascular volume depletion which may sometimes manifest as symptomatic hypotension or acute transient changes in creatinine.  There have been post-marketing reports of acute kidney injury, some requiring hospitalization and dialysis, in patients with type 2 diabetes mellitus receiving SGLT2 inhibitors.  Patients with impaired renal function (eGFR < 60 mL/min/1.73 m2), elderly patients, or patients on loop diuretics may be at increased risk for volume depletion or hypotension.  Before initiating INPEFA in patients with one or more of these characteristics, assess volume status and renal function, and monitor for signs and symptoms of hypotension during therapy.  Urosepsis and Pyelonephritis: Treatment with SGLT2 inhibitors, including INPEFA, increases the risk for urinary tract infections.  Serious urinary tract infections including urosepsis and pyelonephritis requiring hospitalization have been reported. Evaluate patients for signs and symptoms of urinary tract infections and treat promptly.  Hypoglycemia with Concomitant Use with Insulin and Insulin Secretagogues: Insulin and insulin secretagogues are known to cause hypoglycemia.  INPEFA may increase the risk of hypoglycemia when combined with insulin or an insulin secretagogue.  Therefore, a lower dose of insulin or insulin secretagogue may be required to minimize the risk of hypoglycemia when used with INPEFA. Necrotizing Fasciitis of the Perineum (Fournier’s Gangrene): Reports of Fournier’s Gangrene, a rare but serious and life-threatening necrotizing infection requiring urgent surgical intervention, have been identified in post-marketing surveillance in patients with diabetes mellitus receiving SGLT2 inhibitors.  Assess patients who present with pain, tenderness, erythema, or swelling in the genital or perineal area, along with fever or malaise. If suspected, start treatment immediately with broad-spectrum antibiotics and, if necessary, surgical debridement.  Discontinue INPEFA, closely monitor patient signs and symptoms, and provide appropriate alternative therapy for heart failure.  Genital Mycotic Infections: INPEFA increases the risk of genital mycotic infections.  Monitor and treat as appropriate.  Urinary Glucose Test and 1,5-anhydroglucitol (1,5-AG) Assay: these are not reliable for patients taking SGLT2 inhibitors.  Use alternative testing methods to monitor glucose levels.   Common Adverse Reactions: the most commonly reported adverse reactions (incidence ≥ 5%) were urinary tract infection, volume depletion, diarrhea, and hypoglycemia.  Drug Interactions:  Digoxin: Monitor patients appropriately as there is an increase in the exposure of digoxin when coadministered with INPEFA 400 mg. Uridine 5'-diphospho-glucuronosyltransferase (UGT) Inducer: The coadministration of rifampicin, an inducer of UGTs, with sotagliflozin resulted in a decrease in the exposure of sotagliflozin.   Lithium: Concomitant use of an SGLT2 inhibitor with lithium may decrease serum lithium concentrations.  Monitor serum lithium concentration more frequently during INPEFA initiation and with dosage changes.  Use in Specific Populations:  Pregnancy and Lactation: INPEFA is not recommended during the second and third trimesters of pregnancy, nor while breastfeeding.  Geriatric Use: No INPEFA dosage change is recommended based on age.  No overall differences in efficacy were detected between these patients and younger patients, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.  Elderly patients may be at increased risk for volume depletion adverse reactions, including hypotension.Renal Impairment: INPEFA was evaluated in patients with chronic kidney disease (eGFR 25 to 60 mL/min/1.73 m2) and in patients with heart failure with eGFR < 60 mL/min/1.73 m2.  The safety profile of INPEFA across eGFR subgroups in these studies was consistent with the known safety profile.  There was an increase in volume-related adverse events (e.g., hypotension, dizziness) in patients with eGFR < 30 mL/min/1.73m2 relative to the overall safety population.  Efficacy and safety studies with INPEFA did not enroll patients with an eGFR less than 25 mL/min/1.73 m2 or on dialysis.  After starting therapy in the studies, patients were discontinued if eGFR fell below 15 mL/min/1.73 m2 or were initiated on chronic dialysis.Hepatic Impairment: INPEFA is not recommended in patients with moderate or severe hepatic impairment. Click here for full Prescribing Information. https://www.lexpharma.com/inpefa-US-PI.pdf Safe Harbor Statement This press release contains “forward-looking statements,” including statements relating to Lexicon’s financial position and long-term outlook on its business, growth and future operating results, discovery and development of products, strategic alliances and intellectual property, as well as other matters that are not historical facts or information. All forward-looking statements are based on management’s current assumptions and expectations and involve risks, uncertainties and other important factors, specifically including Lexicon’s ability to meet its capital requirements, successfully commercialize INPEFA in heart failure on the timeline and/or at the prices currently contemplated or at all, conduct preclinical and clinical development and obtain necessary regulatory approvals of sotagliflozin (in other indications), LX9211, LX9851 and its other drug candidates on its anticipated timelines, achieve its operational objectives, obtain patent protection for its discoveries and establish strategic alliances, as well as additional factors relating to manufacturing, intellectual property rights, and the therapeutic or commercial value of its drug candidates. Any of these risks, uncertainties and other factors may cause Lexicon’s actual results to be materially different from any future results expressed or implied by such forward-looking statements. Information identifying such important factors is contained under “Risk Factors” in Lexicon’s annual report on Form 10-K for the year ended December 31, 2023 and other subsequent disclosure documents 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. For Media and Investor Inquiries: Lisa DeFrancescoLexicon Pharmaceuticals, Inc.lexinvest@lexpharma.com