New Data at 2026 American Heart Association Scientific Sessions Highlight Cardiovascular Effects of Sotagliflozin on Thrombus Formation and in Hypertrophic Cardiomyopathy

The laboratory findings precede an expected Q1 2027 Phase 3 readout in symptomatic obstructive and non-obstructive HCM.

Rhea-AI Summary

Lexicon Pharmaceuticals (Nasdaq: LXRX) announced two studies showing sotagliflozin reduced laboratory clot formation and work performed by human heart tissue. In a four-week, randomized, open-label crossover study of 15 healthy adults, clot formation fell from baseline by 11.9% under arterial-like flow (p=0.043) and 15.6% under venous-like flow (p=0.012). Empagliflozin reductions did not reach statistical significance.

In living heart-tissue slices, both drugs directly reduced heart-muscle work; sotagliflozin showed greater potency at higher pressures, mimicking hypertrophic cardiomyopathy (HCM). These were laboratory findings, not HCM patient-treatment outcomes. The tissue findings were also published in JACC: Basic to Translational Science. Lexicon expects Phase 3 SONATA-HCM topline results in Q1 2027 for symptomatic obstructive and non-obstructive HCM.

3 points · 0 major

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Rhea-AI gives every point it takes from this document a weight. Minor counts 1, Moderate 3 and Major 9, so one Major point outweighs several Minor ones. The bar adds up the weights on each side, and when neither side holds more than 65% of the total the balance reads Mixed.

It reads the document as published, with the same rules for every company, and it does not look at what the market expected or at how the stock traded, so a point can be objectively good on a day the stock falls.

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0 major · 2 points

Hollow bars mark forward-looking points. How the balance works

Positive

• Moderate point. Forward-looking: it has not happened yet and may not happen.Lexicon expects Phase 3 SONATA-HCM topline results in Q1 2027 for symptomatic obstructive and non-obstructive HCM.
• Minor pointSotagliflozin reduced laboratory clot formation from baseline by 11.9% arterial-like and 15.6% venous-like, both statistically significant.
• Minor pointHuman heart-tissue testing showed directly reduced muscle work, with greater potency than empagliflozin at higher pressures.

Negative

• Minor pointClot findings came from an open-label study of 15 healthy adults using laboratory blood testing.
• Minor pointDirect heart-muscle findings reflect short-term exposure in removed tissue, rather than treatment outcomes in HCM patients.

Key Figures

Arterial-like clot reduction: 11.9%; p=0.043 Venous-like clot reduction: 15.6%; p=0.012 Study participants: 15 healthy adults +4 more

Arterial-like clot reduction

11.9%; p=0.043

From baseline under arterial-like flow conditions

Venous-like clot reduction

15.6%; p=0.012

From baseline under venous-like flow conditions

Study participants

15 healthy adults

Randomized, open-label crossover study

Study duration

4 weeks

Randomized, open-label crossover study

Sotagliflozin dose

400 mg once daily

Crossover study treatment

Empagliflozin dose

10 mg once daily

Crossover study comparator

SONATA-HCM topline timing

Q1 2027

Expected results from ongoing Phase 3 trial

Historical Context

1 past event · Latest: Oct 21

1 event

1. Oct 21

   mechanistic study findings

   24h Move

   -1.3%

   Earlier preclinical studies reported reduced HCM cardiac dysfunction and clot formation with sotagliflozin.

24h Move is the share-price change in the day after each event; other market factors may also have contributed.

Key Terms

ex vivo, randomized crossover study, hypertrophic cardiomyopathy, septal myectomy, +1 more

5 terms

ex vivo technical

"reduced ex vivo thrombus formation from baseline"

Ex vivo describes tests or treatments performed on living cells, tissues, or organs that have been removed from the body and studied in an external environment. For investors, ex vivo work sits between basic lab dish tests and whole‑animal or human studies, offering a more realistic preview of how a therapy or diagnostic might behave in real tissue — like running an engine on a test stand before putting it back into a car — which can reduce scientific risk and inform development milestones.

randomized crossover study technical

"In the 4-week, randomized, open-label crossover study"

A randomized crossover study is a clinical trial design where participants are randomly assigned to receive two or more treatments in different sequences, so each person acts as their own comparison over time—like trying two recipes in random order to judge which tastes better. For investors, it matters because this design can give clearer, more efficient comparisons of effectiveness or safety with fewer subjects, but results can be affected if one treatment's effects carry over into the next period.

hypertrophic cardiomyopathy medical

"heart muscle affected by HCM"

Hypertrophic cardiomyopathy is a genetic heart condition in which the heart muscle becomes abnormally thick, making it harder for the heart to pump and for electrical signals to travel normally; think of a pump whose walls have thickened so it moves less efficiently. Investors care because the condition drives demand for diagnostics, drugs and devices, affects workforce and insurance costs, and can influence clinical trial results, regulatory approvals and liability exposure in healthcare-related companies.

septal myectomy medical

"during septal myectomy, a surgery to relieve obstruction"

A septal myectomy is an open-heart surgical procedure that removes a portion of the thickened interventricular septum (the wall between the heart’s left and right ventricles) to widen the left ventricular outflow tract and relieve obstruction caused by hypertrophic cardiomyopathy. The surgeon accesses the heart, usually through the aorta, and excises the obstructing muscle while the patient is on cardiopulmonary bypass; it is a definitive, invasive treatment typically performed at specialized centers and is distinct from less invasive alternatives such as alcohol septal ablation. It carries the risks and recovery needs of major cardiac surgery and is intended for patients whose symptoms or obstruction are not controlled by medication.

afterloads medical

"afterloads, or the pressures the heart pumps against"

A fee charged when an investor sells or redeems shares of a fund, paid out of the redemption proceeds rather than when the shares were bought. Afterloads—also called back-end loads or contingent deferred sales charges (CDSCs)—are usually calculated as a percentage of the redemption amount and often follow a declining schedule so the charge falls to zero if the investor holds the shares long enough; they are distinct from front-end loads (paid on purchase) and ongoing management or 12b-1 fees (recurring annual charges).

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-- In a randomized crossover study, sotagliflozin significantly reduced ex vivo thrombus formation from baseline under both arterial and venous flow conditions --

-- Study in living human heart tissue indicate sotagliflozin acutely and directly reduces myocardial work in hypertrophic cardiomyopathy (HCM) --

-- Findings add mechanistic insight into sotagliflozin's dual SGLT1/SGLT2 inhibition ahead of SONATA-HCM topline results in Q1 2027 --

THE WOODLANDS, Texas, Nov. 09, 2026 (GLOBE NEWSWIRE) -- Lexicon Pharmaceuticals, Inc. (Nasdaq: LXRX), a leading cardiometabolic biopharmaceutical company, today announced new data highlighting the cardiovascular effects of its dual SGLT1/2 inhibitor, sotagliflozin, which were shared in two poster presentations at the American Heart Association (AHA) Scientific Sessions 2026. The investigator-initiated studies were sponsored by Lexicon and conducted by investigators at the Ichan School of Medicine at Mount Sinai and Penn Cardiovascular Institute.

In the first presentation, "Zafar et al. Effects of Sotagliflozin and Empagliflozin on Thrombus Formation in Healthy Volunteers: A Randomized Crossover Trial", researchers from the Ichan School of Medicine examined whether sotagliflozin reduces the blood's tendency to form clots, which are the leading cause of heart attacks and strokes.

In the 4-week, randomized, open-label crossover study, 15 healthy adults received once-daily sotagliflozin 400 mg and the selective SGLT2 inhibitor empagliflozin 10 mg in random order. Researchers measured clot formation in participants' blood before and after each treatment, using an ex vivo laboratory model in which blood is drawn over a system that mimics a damaged artery and at speeds that replicate arterial and venous blood flow. Sotagliflozin significantly reduced clot formation from baseline under both arterial-like (11.9%; p=0.043) and venous-like (15.6%; p=0.012) conditions. Reductions with empagliflozin did not reach statistical significance.

The second presentation, "Taichman et al. Load-Dependent Effects of Sodium Glucose Co-Transporter Inhibitors on Work in Human Hypertrophic Cardiomyopathy Living Myocardial Slices," examined whether sotagliflozin acts directly on human heart muscle affected by HCM.

Researchers at Penn Cardiovascular Institute used heart tissue removed from patients with HCM during septal myectomy, a surgery to relieve obstruction, along with tissue from non-failing donor hearts. In an ex vivo model using living myocardial slices, myocardial work was studied across a physiologic range of afterloads, or the pressures the heart pumps against. Short-term exposure to sotagliflozin and empagliflozin directly reduced the work performed by the heart muscle. Sotagliflozin showed increased potency versus empagliflozin at higher afterloads, which mimics the HCM condition. The findings indicate that sotagliflozin can act directly on the heart, independent of its effects on the kidneys and metabolism. The findings were simultaneously published in JACC: Basic to Translational Science.

"A growing body of research continues to suggest that adding SGLT1 inhibition may contribute to cardiovascular effects beyond those seen with SGLT2 inhibition alone," said Craig Granowitz, M.D., Ph.D., senior vice president and chief medical officer of Lexicon. "The thrombosis data point to a potential mechanism behind the reductions in heart attack and stroke seen in SCORED, while the human tissue findings show a direct effect of sotagliflozin on the hypercontractile heart muscle that characterizes HCM. Together, these new datasets strengthen the scientific rationale for sotagliflozin in HCM and reinforce our excitement for the pivotal readout of our SONATA-HCM study."

The ongoing Phase 3 SONATA-HCM trial is evaluating sotagliflozin as a potential treatment option for patients with symptomatic obstructive and non-obstructive HCM. Topline results are expected in the first quarter of 2027.

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 and the heart. Sotagliflozin has been studied in multiple patient populations encompassing heart failure, diabetes, and chronic kidney disease in clinical studies involving approximately 20,000 patients. Sotagliflozin is also currently under investigation for hypertrophic cardiomyopathy (HCM).

About Lexicon Pharmaceuticals
Lexicon Pharmaceuticals is a biopharmaceutical company pursuing novel medicines for patients with serious cardiometabolic diseases. Building on a proven legacy in genetic target discovery, Lexicon is advancing a clinical pipeline in areas of significant and often underserved need, with programs in hypertrophic cardiomyopathy (HCM), type 1 diabetes (T1D), obesity and other related metabolic conditions. Lexicon is committed to developing differentiated therapies that can be integrated broadly into clinical practice, with the goal of expanding treatment options for patients. Its capabilities extend from early-stage target discovery through clinical development and commercialization, strategically paired with high-impact collaborations to maximize the global reach of its medicines. For additional information, please visit www.lexpharma.com.

Safe Harbor Statement
This press release contains "forward-looking statements," including statements relating to the research, development and therapeutic and commercial potential of sotagliflozin, including in hypertrophic cardiomyopathy. In addition, this press release may also contain forward-looking 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, 2025, 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 Media Inquiries:
Dave Belian
Lexicon Pharmaceuticals, Inc.
lexinvest@lexpharma.com

For Investor Inquiries:
Lisa DeFrancesco
Lexicon Pharmaceuticals, Inc.
lexinvest@lexpharma.com

FAQ

AI-generated questions and answers. How Rhea-AI works. Not financial advice.

What did Lexicon's sotagliflozin clot-formation study show?

Sotagliflozin significantly reduced laboratory clot formation from baseline by 11.9% under arterial-like flow (p=0.043) and 15.6% under venous-like flow (p=0.012). Reductions with empagliflozin did not reach statistical significance; this does not establish a statistically significant difference between the drugs.

When does Lexicon expect SONATA-HCM results for sotagliflozin?

Lexicon expects topline results in the first quarter of 2027. The ongoing Phase 3 SONATA-HCM trial is evaluating sotagliflozin as a potential treatment for patients with symptomatic obstructive and non-obstructive hypertrophic cardiomyopathy.

What doses were tested in Lexicon's sotagliflozin clot-formation study?

The 15 healthy adults received once-daily sotagliflozin 400 mg and empagliflozin 10 mg in random order. Researchers measured clot formation before and after each treatment during the four-week, randomized, open-label crossover study.