Lexicon Pharmaceuticals (NASDAQ:LXRX) outlined progress across three late-stage programs and reported sharply lower operating expenses during its fourth-quarter and full-year 2025 earnings call held March 5, 2026. Management emphasized near-term regulatory and clinical milestones for sotagliflozin in type 1 diabetes and hypertrophic cardiomyopathy (HCM), continued partnering efforts for the chronic pain candidate pilavapadin, and milestone-driven progress for the obesity program LX9851 under its license with Novo Nordisk.
Pipeline priorities and 2026 milestones
Chief Executive Officer Dr. Mike Exton said the company is advancing three “strong novel late-stage programs” spanning cardiometabolic disease and chronic pain: sotagliflozin in HCM and type 1 diabetes (T1D), pilavapadin for diabetic peripheral neuropathic pain (DPNP), and LX9851 in obesity (being developed by Novo Nordisk).
- SONATA-HCM Phase III trial: Enrollment is “enrolling well,” and the company expects to complete enrollment by mid-year 2026.
- Zynquista (sotagliflozin) in T1D: Lexicon plans to resubmit its NDA in 2026, citing FDA feedback that third-party Steno-1 data may support resubmission if patient exposure and safety requirements are met.
- Pilavapadin in DPNP: Lexicon is seeking a partner to support Phase III development following an end-of-Phase II FDA meeting.
Exton also said Lexicon entered 2026 with “significant momentum,” pointing to a successful FDA end-of-Phase II meeting for pilavapadin, continued SONATA-HCM enrollment that surpassed 50% earlier in the quarter, and progress toward a potential Zynquista resubmission.
Sotagliflozin: HCM trial enrollment and supporting studies
Chief Medical Officer Dr. Craig Granowitz reviewed sotagliflozin’s dual SGLT1/SGLT2 mechanism and argued that SGLT1 inhibition—particularly in the GI tract and heart—may contribute to postprandial glycemic control in T1D and potential myocardial effects relevant to HCM. He noted SGLT1 is upregulated in certain ischemic heart conditions and in patients with HCM.
For HCM, Granowitz said Lexicon’s Phase III SONATA-HCM registrational trial includes both obstructive and non-obstructive patients and uses a Kansas City Cardiomyopathy Questionnaire (KCCQ) endpoint aimed at supporting a regulatory filing and a broad label. The company has initiated 130+ sites across roughly 20 countries, including the U.S., Europe, Israel, and Latin America. Top-line results are expected in the first quarter of 2027.
In Q&A, Granowitz said the trial is now in the “steep part” of the enrollment curve with all sites open, and enrollment has been consistent with or ahead of projections. He added that while the study stratifies obstructive and non-obstructive patients, enrollment is “stratified but not capped,” and he said the company is seeing strong inflow from the non-obstructive cohort.
Granowitz also cited two investigator-initiated efforts as complementary to SONATA-HCM:
- SOTA-CARDIA: Presented at the American Heart Association meeting in November, this study evaluated sotagliflozin in HFpEF patients without diabetes and reported improvements in measures including KCCQ score, six-minute walk test, left ventricular mass, and left atrial filling pressure, which Granowitz said support rationale for use in non-obstructive HCM.
- SOTA-CROSS: An ongoing 12-week crossover study in symptomatic non-obstructive HCM with a readout expected in 2027, measuring cardiac function, symptoms, and biomarkers.
Management also referenced upcoming data presentations at the American College of Cardiology’s 75th Annual Scientific Sessions and additional HCM-focused medical meetings in the second half of 2026.
Zynquista in type 1 diabetes: FDA feedback and Steno-1 metrics
Granowitz said the FDA confirmed in late 2025 discussions that the Steno-1 investigator-initiated trial may be sufficient to support review of an NDA resubmission for Zynquista in T1D. Based on enrollment estimates and safety data received to date, Lexicon is planning for an NDA resubmission and “potential regulatory approval” in 2026.
In response to a question about diabetic ketoacidosis (DKA) safety data and review timing, Exton said the company expects a six-month review and reiterated an expectation of submission in 2026 with a potential approval before the end of 2026.
Granowitz provided additional detail on the FDA’s criteria discussed with Lexicon. He said the agency and the company pre-agreed on two key criteria for resubmission: total exposure and DKA rate. He added the FDA was looking for a DKA rate “at or below” what was achieved with the 400 mg dose arm in the inTANDEM program, describing it as a number needed to harm of about 26, corresponding to roughly 3.5 cases per 100 patient-years. Granowitz said Lexicon is tracking in a way—on both exposure and DKA rates—that gives the company “a high degree of confidence” in its submission and approval timelines, while noting the Steno-1 trial is not run by Lexicon.
LX9851 and pilavapadin: milestones and partnering path
Lexicon’s obesity candidate LX9851 is now fully handed off to Novo Nordisk after completion of IND-enabling activities, Granowitz said. Progress triggered a $10 million milestone payment in February under Lexicon’s license agreement, and he noted the potential for another $20 million in additional milestones in 2026. Management also pointed to a recent Journal of the Endocrine Society publication on ACSL5 inhibition, described as a featured article, as providing preclinical insight into the target and candidate.
On pilavapadin, Granowitz said Lexicon accumulated data from more than 600 treated patients and characterized the safety and tolerability profile as well-understood and acceptable. Following an end-of-Phase II FDA meeting, he said the agency raised no objections to advancing into Phase III for DPNP. The Phase III program would include two placebo-controlled, 12-week, two-arm registrational studies comparing a 10 mg daily dose to placebo, with a primary endpoint of placebo-controlled change in average daily pain score from baseline to week 12. He added FDA confirmed no additional preclinical studies would be required that would complicate or delay progression into Phase III.
In Q&A, Exton said the end-of-Phase II outcome allowed partnering conversations to become “a little more specific” and helped reduce regulatory risk, which he said has been “incredibly well-received.” He also said Lexicon is not planning to commit capital to initiate Phase III on its own, noting the company is prioritizing spending on the cardiometabolic opportunities in T1D and HCM.
Financial results: lower expenses and updated 2026 outlook
Chief Financial Officer Scott Coiante reported total revenue of $5.5 million for the fourth quarter of 2025 and $49.8 million for the full year. Fourth-quarter revenue included $4.3 million of licensing revenue recognized from the Novo Nordisk agreement and $1.1 million in net sales of INPEFA. For full-year 2025, revenue included $45 million of licensing revenue from Novo Nordisk and $4.6 million of INPEFA net sales.
Research and development expense fell to $11.3 million in Q4 2025 from $26.7 million in Q4 2024. Full-year R&D expense declined to $61.1 million from $84.5 million, primarily due to lower external research expenses from the PROGRESS Phase II trial, partially offset by increased investment in the SONATA Phase III study.
Selling, general and administrative expense declined to $8.8 million in Q4 2025 from $32.3 million in Q4 2024. Full-year SG&A expense decreased to $37.3 million from $143.1 million, which Coiante attributed to the company’s strategic repositioning in late 2024 and significantly reduced marketing and promotional efforts for INPEFA in 2025.
Net loss for Q4 2025 was $15.5 million, or $0.04 per share, compared to a net loss of $33.8 million, or $0.09 per share, in Q4 2024. Full-year 2025 net loss was $50.3 million, or $0.14 per share, versus $200.4 million, or $0.63 per share, in 2024.
Lexicon ended 2025 with $125.2 million in cash, investments, and restricted cash, compared with $238 million at the end of 2024. Coiante said that subsequent to year-end the company strengthened its cash position by more than $100 million from net proceeds of common and preferred stock sales and a Novo Nordisk milestone payment. He also noted Lexicon reduced total debt by approximately $46.3 million in 2025, primarily using proceeds from the Novo Nordisk upfront payment.
For 2026, Coiante guided to total operating expenses of $100 million to $110 million, including R&D expense of $63 million to $68 million (excluding Phase III pilavapadin costs, which Lexicon aims to fund via a partner) and SG&A expense of $37 million to $42 million.
About Lexicon Pharmaceuticals (NASDAQ:LXRX)
Lexicon Pharmaceuticals, Inc is a biopharmaceutical company focused on the discovery and development of novel medicines through its proprietary genome biology platform. By leveraging large-scale gene knockout libraries, the company identifies potential therapeutic targets and advances them through preclinical and clinical development. Lexicon’s approach emphasizes the translation of genetic insights into targeted therapies for a range of human diseases.
The company’s most advanced product is telotristat ethyl (sold under the brand name XERMELO), an oral treatment approved for the management of carcinoid syndrome diarrhea in patients inadequately controlled by somatostatin analog therapy.
