What changed in this filing

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Item 1. Business

2026-03-05 compared with 2025-03-07 · 117 added, 105 removed, 353 unchanged (39% of the section changed)

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We are devoting most of our resources to the research and development of our most advanced drug candidates and the commercialization of our approved drug, INPEFA ® (sotagliflozin):

• We are developing pilavapadin (LX 9211), an orally-delivered small molecule drug candidate, as a treatment for neuropathic pain.

We have completed three Phase 2 clinical trials ev aluating the safety and tolerability of pilavapadin and its effects on DPNP and neuropathic pain.

We have reported top-line results from our Phase 2b clinical trial of pilavapadin in diabetic peripheral neuropathic pain, or DPNP, which demonstrated clear evidence of effect at the 10 mg dose and have received Fast Track designation from the U.S.

Food and Drug Administration, or FDA, for development of pilavapadin in that indication.

We have also reported positive results from a Phase 2a clinical trial of pilavapadin in DPNP and results from a separate Phase 2a clinical trial of pilavapadin in post-herpetic neuralgia which also demonstrated evidence of effect.

• We are developing LX9851, an orally-delivered small molecule drug candidate, as a treatment for obesity and associated cardiometabolic disorders and are conducting preclinical development of LX9851 in preparation for filing an investigational new drug application, or IND, with the FDA.

• We are commercializing INPEFA (sotagliflozin), an orally-delivered small molecule drug, in the United States to reduce the risk of cardiovascular death, hospitalization for heart failure, and urgent heart failure visits in adults with heart failure or type 2 diabetes mellitus, chronic kidney disease, or CKD, and other cardiovascular risk factors.

We are also developing sotagliflozin as a treatment for hypertrophic cardiomyopathy, or HCM, and are conducting a Phase 3 clinical trial of sotagliflozin in that indication.

• We are developing sotagliflozin, an orally-delivered small molecule drug candidate, as a treatment for hypertrophic cardiomyopathy, or HCM, and are conducting the SONATA-HCM pivotal Phase 3 clinical trial of sotagliflozin in that indication.

• We are separately pursuing regulatory approval of ZYNQUISTA ® (sotagliflozin) as a treatment for type 1 diabetes.

The FDA issued a complete response letter regarding our New Drug Application, or NDA, for sotagliflozin in type 1 diabetes in March 2019 and an additional complete response letter in December 2024 regarding our NDA for sotagliflozin as an adjunct to insulin therapy for glycemic control in adults with type 1 diabetes and CKD.

Food and Drug Administration, or FDA, issued complete response letters regarding our New Drug Application, or NDA, for ZYNQUISTA in type 1 diabetes in March 2019 and December 2024.

At our request, the FDA has issued a public Notice of Opportunity for Hearing, or NOOH, on whether there are grounds for denying approval of our NDA and those proceedings are ongoing.

The FDA has separately provided feedback that a third-party-funded, investigator-initiated study of sotagliflozin appears to be of adequate design and employs sufficient data collection methods to provide viable evidence of the incidence of diabetic ketoacidosis, or DKA, with adequate safety data, prior to its completion, to support review of a resubmission of the NDA.

We are preparing to potentially resubmit the NDA for ZYNQUISTA in type 1 diabetes if supported by patient exposure and safety data from such study.

• We are developing pilavapadin, an orally-delivered small molecule drug candidate, as a treatment for neuropathic pain.

We have completed two Phase 2 clinical trials evaluating the safety and tolerability of pilavapadin and its effects on diabetic peripheral neuropathic pain, or DPNP.

We have reported results from our PROGRESS Phase 2b clinical trial of pilavapadin in DPNP, which demonstrated clear evidence of effect at the 10 mg dose, and positive results from our RELIEF-DPN-1 Phase 2a clinical trial of pilavapadin in DPNP.

We have received Fast Track designation from the FDA for development of pilavapadin in that indication and are currently advancing third party collaboration discussions for its further development and commercialization.

• We have developed LX9851, an orally-delivered small molecule drug candidate, as a treatment for obesity and associated cardiometabolic disorders.

We have granted Novo Nordisk an exclusive, worldwide, royalty-bearing license to develop, manufacture and commercialize LX9851 and have completed preclinical development of LX9851 in preparation for the filing of an investigational new drug application, or IND, with the FDA and commencement of clinical development by Novo Nordisk.

• We continue to make INPEFA (sotagliflozin) commercially available in the United States.

INPEFA is approved to reduce the risk of cardiovascular death, hospitalization for heart failure, and urgent heart failure visits in adults with heart failure or type 2 diabetes mellitus, chronic kidney disease, or CKD, and other cardiovascular risk factors.

• We are conducting preclinical research and development of compounds from a number of additional drug programs originating from our internal drug discovery efforts.

Pilavapadin originated from our collaborative neuroscience drug discovery efforts with Bristol-Myers Squibb and LX9851, sotagliflozin and compounds from a number of additional drug programs originated from our own internal drug discovery efforts.

Sotagliflozin, LX9851 and compounds from a number of additional drug programs originated from our own internal drug discovery efforts and pilavapadin originated from our collaborative neuroscience drug discovery efforts with Bristol-Myers Squibb.

Our efforts were driven by a systematic, target biology-driven approach in which we used gene knockout technologies and an integrated platform of advanced medical technologies to systematically study the physiological and behavioral functions of almost 5,000 genes in mice and assessed the utility of the proteins encoded by the corresponding human genes as potential drug targets.

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We seek to retain exclusive or co-exclusive rights to the benefits of certain research and development programs by developing and commercializing drug candidates from those programs internally, particularly in the United States for indications treated by specialist physicians.

We seek to collaborate with other pharmaceutical and biotechnology companies with respect to the research, development and commercialization of certain of our drug candidates, particularly with respect to commercialization in territories outside the United States or commercialization in the United States for indications treated by primary care physicians, or when the collaboration may otherwise provide us with access to expertise and resources that we do not possess internally or are complementary to our own.

We were incorporated in Delaware in July 1995, commenced operations in September 1995 and were listed on The Nasdaq Global Select Market in April 2000.

commercialization in the United States for indications treated by primary care physicians, or when the collaboration may otherwise provide us with access to expertise and resources that we do not possess internally or are complementary to our own.

We were incorporated in Delaware in July 1995, commenced operations in September 1995 and were listed on The Nasdaq Capital Market in April 2000.

Our corporate headquarters are located at 2445 Technology Forest Blvd., 11th Floor, The Woodlands, Texas 77381, and our telephone number is (281) 863-3000.

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Drugs and Drug Candidates

We are devoting most of our resources to the research and development of pilavapadin, LX9851 and sotagliflozin and the commercialization of INPEFA.

We are devoting most of our resources to the research and development of sotagliflozin, pilavapadin, LX9851 and the commercialization of INPEFA.

We have also advanced a number of additional compounds into various stages of preclinical research and development.

Sotagliflozin

Sotagliflozin is an orally-delivered small molecule compound that we are developing for HCM and type 1 diabetes and commercializing for heart failure.

Our scientists identified the targets of sotagliflozin, sodium-glucose cotransporter type 1, or SGLT1, and sodium-glucose cotransporter type 2, or SGLT2, in our target discovery efforts based on their discovery that mice lacking SGLT1, SGLT2 or both exhibited favorable phenotypes across multiple measures of metabolism and glucose control in preclinical models.

Preclinical studies of sotagliflozin demonstrated that compounds inhibiting both targets had a favorable preclinical profile relative to compounds selective for SGLT2.

We use “sotagliflozin” when referring to our development for HCM, “ZYNQUISTA” when referring to our development for type 1 diabetes and “INPEFA” when referring to our FDA-approved drug.

Hypertrophic Cardiomyopathy

We are conducting a Phase 3 clinical trial, SONATA-HCM, evaluating the efficacy and safety of sotagliflozin and its effects on HCM.

The trial is expected to enroll approximately 500 patients experiencing obstructive or non-obstructive HCM in a randomized, double-blind, placebo-controlled study of a 400mg once daily dose of sotagliflozin over a 26-week treatment period.

Doses for patients not tolerating treatment may be reduced to 200mg beginning at week 4.

The primary efficacy endpoint under evaluation will be change from baseline in the patient-reported Kansas City Cardiomyopathy Questionnaire, or KCCQ, clinical summary score at 26 weeks, with secondary endpoints including change in KCCQ total symptom score and New York Heart Association class improvement at 26 weeks.

Type 1 Diabetes

The FDA issued a complete response letter in March 2019 regarding our NDA for ZYNQUISTA in type 1 diabetes and confirmed that position in denying two appeals of the complete response letter in November 2019 and March 2020.

The FDA issued an additional complete response letter in December 2024 regarding our NDA for ZYNQUISTA as an adjunct to insulin therapy for glycemic control in adults with type 1 diabetes and CKD.

At our request, the FDA has issued a public NOOH on whether there are grounds for denying approval of our NDA and those proceedings are ongoing.

The FDA has separately provided feedback that STENO1, a third-party-funded, investigator-initiated study of sotagliflozin being conducted by the STENO Diabetes Centers in Denmark, appears to be of adequate design and employs sufficient data collection methods to provide viable evidence of the incidence of DKA, with adequate safety data, prior to its completion, to support review of a resubmission of the NDA.

We are preparing to potentially resubmit the NDA for ZYNQUISTA as an adjunct to insulin for glycemic control in adults with type 1 diabetes if the patient exposure and safety data requirements identified by the FDA for STENO1 are achieved.

Heart Failure

We commercially launched INPEFA, a once-daily oral tablet, following regulatory approval in the United States 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, CKD, and other cardiovascular risk factors.

We continue to manufacture and make INPEFA available to patients and prescribers.

We maintain a small virtual contract sales force for INPEFA.

Our internal medical affairs function maintains responsibility for responding to external clinical-related inquiries regarding the appropriate use of INPEFA with regularly updated and well-substantiated scientific and medical information.

We principally sell INPEFA to a limited number of major wholesalers, as well as selected regional wholesalers, most of whom in turn resell INPEFA to retail pharmacies, hospitals, government agencies and other institutions for subsequent resale and dispensing to patients and healthcare providers.

We also utilize a mail order pharmacy to dispense INPEFA.

Pilavapadin (LX9211)

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We have received Fast Track designation from the FDA for development of pilavapadin in DPNP.

Our scientists identified the target of pilavapadin, adapter-associated kinase 1, or AAK1, in our target discovery efforts based on their discovery that mice lacking AAK1 exhibited increased resistance to induced neuropathic pain in preclinical models.

Our scientists identified the target of pilavapadin, adapter-associated kinase 1, or AAK1, in our target discovery efforts based on their discovery that mice lacking the AAK1 gene exhibited increased resistance to induced neuropathic pain in preclinical models.

Pilavapadin and another development candidate were discovered by scientists working within our drug discovery alliance with Bristol-Myers Squibb from which we hold exclusive development and commercialization rights.

Preclinical studies of pilavapadin demonstrated central nervous system penetration and reduction in pain behavior in models of neuropathic pain without affecting opiate pathways.

We have completed three Phase 2 clinical trials evaluating the safety and tolerability of pilavapadin and its effects on DPNP and neuropathic pain.

We have completed three Phase 2 clinical trials evaluating the safety and tolerability of pilavapadin and its effects on neuropathic pain.

Our PROGRESS Phase 2b clinical trial enrolled 496 patients with type 1 or type 2 diabetes and experiencing moderate to severe DPNP in a randomized, double-blind, placebo-controlled study evaluating three treatment groups receiving once daily pilavapadin doses of 10mg, 20mg or 20mg for seven days followed by 10mg thereafter.

The effects of pilavapadin were assessed over a 16-week evaluation period, which included a screening period of two weeks and a blinded evaluation period of 14 weeks.

The primary efficacy endpoint under evaluation in the study was the reduction in an average daily pain score, or ADPS, from baseline to Week 8 as compared to placebo, with secondary endpoints including reduction in burning pain and reduction in pain interference on sleep at 8 weeks.

The primary efficacy endpoint under evaluation in the study was the change in an average daily pain score, or ADPS, from baseline to Week 8 as compared to placebo, with secondary endpoints including change in burning pain and change in pain interference on sleep from baseline to week 8.

Certain patient-reported outcome measures were also assessed.

Topline data from the study showed a reduction in ADPS from baseline to week 8 with the 10 mg, 20 mg/10 mg and 20 mg dose arms achieving reductions of 1.74, 1.70 and 1.38 respectively, compared to 1.31 in the placebo arm.

Data from the study showed a reduction in ADPS from baseline to week 8 with the 10 mg, 20 mg/10 mg and 20 mg dose arms achieving LS mean reductions of 1.74, 1.70 and 1.37 respectively, compared to 1.31 in the placebo arm.

The study’s statistical analysis plan was designed to detect a dose-response signal based on a prespecified model that assumed separation of all treatment arms from placebo when measuring the primary endpoint.

As a result of the lack of separation in ADPS reduction between the 20 mg dose arm and placebo, the study results did not reach statistical significance on the primary endpoint (p=0.11).

However, the 10 mg dose arm demonstrated clear evidence of effect by achieving early and clinically meaningful separation from placebo on ADPS that was maintained throughout the study duration.

However, the 10 mg dose arm demonstrated clear evidence of effect by achieving early and clinically meaningful separation from placebo on ADPS that was maintained throughout the study duration and post hoc analyses of the primary efficacy endpoint, excluding the the 20 mg treatment group, were nominally significant (p<0.05).

Adverse events were more frequent in the pilavapadin treatment arms, but were significantly improved from the RELIEF-DPN-1 study across all doses.

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Adverse events were most prominent at the 20 mg dose and pilavapadin was generally well-tolerated at the 10 mg dose.

Dizziness and nausea were the most commonly reported adverse events and the most frequently associated with patient discontinuations from the study, which occurred most predominantly in the 20 mg dose.

No drug related serious adverse events or deaths were reported in the study.

Dizziness, nausea and constipation were the most commonly reported adverse events.

and the most frequently associated with patient discontinuations from the study, which occurred most predominantly in the 20 mg dose.

Two drug-related serious adverse events, toxic encephalopathy and urinary tract infection, and no drug-related deaths were reported in the study.

Our RELIEF-DPN-1 Phase 2 clinical trial enrolled 319 patients experiencing DPNP in a randomized, double-blind, placebo-controlled study of pilavapadin evaluating three treatment groups receiving an initial loading dose of 100mg or 200mg of pilavapadin or placebo, followed by once daily doses of 10mg or 20mg of pilavapadin or placebo, respectively.

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Consistent and statistically significant benefits in burning pain, pain interference with sleep and other measures of particular importance in DPNP were also observed in both pilavapadin treatment arms as compared to placebo during the initial 6-week treatment period.

During the blinded 5-week placebo run-off period, there was a gradual tapering of efficacy in both treatment arms with no evidence of rebound pain or withdrawal symptoms.

During the blinded 5-week placebo run-off period,

there was a gradual tapering of efficacy in both treatment arms with no evidence of rebound pain or withdrawal symptoms.

Adverse events were more frequent in the pilavapadin treatment arms and at the higher dose during the initial 6-week treatment period, with the most common being dizziness, headache and nausea and nearly all being reported as mild or moderate.

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The primary efficacy endpoint under evaluation in the study was the change from baseline to week 6 in ADPS based on the 11-point numerical rating scale in patients treated with pilavapadin compared with placebo.

Topline data from the study showed a reduction from baseline to week 6 in ADPS of 2.42 points in the pilavapadin arm, compared to a reduction of 1.62 points in the placebo arm (p=0.120 versus placebo), missing statistical significance in the study’s primary endpoint but demonstrating evidence of effect.

Data from the study showed a reduction from baseline to week 6 in ADPS of 2.42 points in the pilavapadin arm, compared to a reduction of 1.62 points in the placebo arm (p=0.120 versus placebo), missing statistical significance in the study’s primary endpoint but demonstrating evidence of effect.

Separation of pilavapadin from placebo on ADPS was observed at week 1 and maintained consistently thereafter, with an average placebo-adjusted reduction over the 6-week treatment period of 0.80 points (p=0.031 versus placebo).

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No drug-related serious adverse events or deaths were reported in the study.

We are developing LX9851, an orally-delivered small molecule drug candidate, for the treatment of obesity and as a tool for weight management.

We are conducting IND-enabling studies of the compound and its associated back-up molecules in preparation for filing an IND.

Our scientists identified the target of LX9851 in our target discovery efforts based on their discovery that mice lacking such target exhibited favorable phenotypes across multiple measures of metabolic syndrome in preclinical models, including resistance to diet-induced obesity and improved body composition.

Sotagliflozin

Sotagliflozin is an orally-delivered small molecule compound that we are commercializing for heart failure and developing for HCM and type 1 diabetes.

Preclinical studies of sotagliflozin demonstrated that compounds inhibiting both targets had a favorable preclinical profile relative to compounds selective for SGLT2.

We use “INPEFA” when referring to our FDA-approved drug, “sotagliflozin” when referring to our development for HCM and “ZYNQUISTA” when referring to our development for type 1 diabetes.

Heart Failure

In November 2024, we restructured and significantly reduced our commercial operations for INPEFA, but we continue to manufacture and make INPEFA available to patients and prescribers.

We do not maintain a sales force for INPEFA.

Our internal medical affairs function maintains responsibility for responding to external inquiries regarding the appropriate use of INPEFA with regularly updated and well-substantiated scientific and medical information.

Hypertrophic Cardiomyopathy

We are conducting a Phase 3 clinical trial, SONATA HCM, evaluating the efficacy and safety of sotagliflozin and its effects on HCM.

Doses for patients not tolerating treatment may be reduced to 200mg beginning at week 4.

The primary efficacy endpoint under evaluation will be change from baseline in the patient-reported Kansas City Cardiomyopathy Questionnaire, or

KCCQ, clinical summary score at 26 weeks, with secondary endpoints including change in KCCQ total symptom score and New York Heart Association class improvement at 26 weeks.

Type 1 Diabetes

The FDA issued an additional complete response letter in December 2024 regarding our NDA for ZYNQUISTA as an adjunct to insulin therapy for glycemic control in adults with type 1 diabetes and CKD.

At our request, the FDA has issued a public NOOH on whether there are grounds for denying approval of our NDA and those proceedings are ongoing.

The FDA has raised no objections to the advancement of pilavapadin into Phase 3 development for DPNP and we are currently advancing third party collaboration discussions for its further development and commercialization.

We have developed LX9851, an orally-delivered small molecule drug candidate, for the treatment of obesity and associated cardiometabolic disorders.

We have granted Novo Nordisk an exclusive, worldwide, royalty-bearing license to develop, manufacture and commercialize LX9851 and have completed IND-enabling studies of the compound and its associated back-up molecules in preparation for the filing of an IND with the FDA and commencement of clinical development by Novo Nordisk.

Our scientists identified the target of LX9851, acyl-CoA synthetase long-chain family member 5, or ACSL5, in our target discovery efforts based on their discovery that mice lacking such target exhibited favorable phenotypes across multiple measures of metabolic syndrome in preclinical models, including resistance to diet-induced obesity and improved body composition.

Additional Research and Development Programs

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We also seek to collaborate with other pharmaceutical and biotechnology companies, research institutes and academic institutions to capitalize on our drug target discoveries.

We entered into an exclusive license agreement with Novo Nordisk A/S in March 2025 under which we granted Novo

Nordisk an exclusive, worldwide, royalty-bearing right and license to develop, manufacture and commercialize LX9851.

We have received a $45 million upfront payment and a $10 million milestone payment under the agreement and are eligible to receive up to an aggregate of $475 million upon the achievement of additional specified regulatory and commercial launch milestones, up to an aggregate of $475 million upon achievement of specified sales milestones and tiered, escalating royalties ranging from single-digit to low-double-digit percentages of annual net sales of LX9851.

Novo Nordisk is responsible for all regulatory, development and commercialization activities for LX9851.

responsible for providing clinical supply of LX9851 to Novo Nordisk at an agreed upon transfer price for a specified time

period, following which Novo Nordisk will be responsible for all manufacturing and supply activities for LX9851.

We entered into an exclusive license agreement with Viatris Inc.

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Viatris is responsible for all regulatory and commercialization activities for sotagliflozin in the licensed territory as well as conducting any additional clinical trials required to obtain such regulatory approvals.

We and Viatris have agreed to enter into a manufacturing and supply agreement pursuant to which we will supply Viatris’ development and commercial requirements of sotagliflozin and Viatris will pay an agreed upon transfer price for such supply.

Viatris obtained regulatory approval for the marketing and sale of sotagliflozin for heart failure in the United Arab Emirates (UAE) and has submitted applications for the regulatory approval of sotagliflozin for heart failure in several other countries in the licensed territory, including Canada, Australia and New Zealand.

We and Viatris have entered into a manufacturing and supply agreement pursuant to which we supply Viatris’ development and commercial requirements of sotagliflozin and Viatris pays an agreed upon transfer price for such supply.

Bristol-Myers Squibb

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We received $86 million in upfront payments and research funding under the agreement during the target discovery portion of the alliance, which expired in October 2009.

In addition, we are entitled to receive clinical and regulatory milestone payments ranging, depending on the timing and extent of our efforts in

the alliance, up to $76 million for each drug developed by Bristol-Myers Squibb under the alliance.

In addition, we are entitled to receive clinical and regulatory milestone payments ranging, depending on the timing and extent of our efforts in the alliance, up to $76 million for each drug developed by Bristol-Myers Squibb under the alliance.

We will also earn royalties on sales of drugs commercialized by Bristol-Myers Squibb under the alliance.

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Manufacturing and Product Supply

We do not own or operate manufacturing or distribution facilities or resources for commercial production and distribution of INPEFA or clinical production and distribution of pilavapadin, LX9851, sotagliflozin or our other drug candidates.

We do not own or operate manufacturing or distribution facilities or resources for commercial production and distribution of INPEFA or clinical production and distribution of sotagliflozin, pilavapadin, LX9851 or our other drug candidates.

Instead, we have multiple contractual agreements in place with third-party contract manufacturing organizations, or CMOs, who, on our behalf, manufacture commercial supplies of INPEFA and clinical supplies of our drug candidates, and will continue to do so for the foreseeable future.

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Third-party API contract manufacturers in Asia and Europe stock sufficient quantities of these materials to ensure they can manufacture quantities of API sufficient to meet our commercial and clinical requirements.

We store API at third-party facilities in North America and Asia, and provide appropriate amounts to third-party drug product contract manufacturers in North America and Asia who then manufacture, package and label our specified quantities of finished commercial goods for INPEFA and clinical goods for our drug candidates.

We store API at third-party facilities in North America and Asia, and provide appropriate amounts to third-party drug product contract manufacturers in North America who then manufacture, package and label our specified quantities of finished commercial goods for INPEFA and clinical goods for our drug candidates.

Our third-party contract manufacturers also need to obtain materials such as excipients, components and reagents to manufacture our API and finished drug products.

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In addition, our competitors may develop products that are more effective than those we develop or commercialize products more effectively and profitably than we do.

Similarly, our collaborators face similar competition from other competitors who may succeed in developing products

more quickly, developing products that are more effective than those developed by our collaborators or commercialize products more effectively and profitably than our collaborators.

Similarly, our collaborators face similar competition from other competitors who may succeed in developing products more quickly, developing products that are more effective than those developed by our collaborators or commercialize products more effectively and profitably than our collaborators.

The competition for our drugs and drug candidates includes both marketed products and drug candidates that are being developed by others, including pharmaceutical products that are currently in a more advanced stage of commercialization or clinical development than are our own drugs and drug candidates.

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• the availability of substantial capital resources to fund commercialization and development activities.

We expect that our principal competition for sotagliflozin in the treatment of hypertrophic cardiomyopathy would include generic beta blockers, selective SGLT2 inhibitors prescribed off-label and calcium channel blockers and cardiac myosin inhibitors, such as mavacamten marketed by Bristol Myers Squibb and aficamten marketed by Cytokinetics.

We expect that our principal competition for ZYNQUISTA in the treatment of type 1 diabetes would include established insulin therapies, and potentially, to some extent, selective SGLT2 inhibitors currently being prescribed off-label.

Such selective SGLT2 inhibitors include dapagliflozin and empagliflozin, currently marketed for the treatment of type 2 diabetes by AstraZeneca and through an alliance between Boehringer Ingelheim and Eli Lilly, respectively.

We expect that our principal competition for pilavapadin for the treatment of DPNP would include duloxetine and pregabalin, which are currently marketed for the treatment of DPNP by Eli Lilly and Pfizer, respectively, and are also available as generics.

We may also experience competition from suzetrigine, which is currently being developed for DPNP by Vertex.

We may also experience competition from suzetrigine, which is currently being marketed for the treatment of moderate to severe acute pain in adults by Vertex.

We also expect that we would experience competition from gabapentin, which is available as a generic and is frequently prescribed off-label for the treatment of DPNP.

We expect that our principal competition for LX9851 would include drugs approved for weight loss, including GLP-1 analogs and similar drugs.

We expect that our and Novo Nordisk’s principal competition for LX9851 would include drugs approved for weight loss, including GLP-1 analogs and similar drugs.

Our principal competition for INPEFA for the treatment of heart failure includes dapagliflozin and empagliflozin, currently marketed for the treatment of heart failure by AstraZeneca and through an alliance between Boehringer Ingelheim and Eli Lilly, respectively.

Such competition also includes, to some extent, other classes of drugs used in the treatment of heart failure, such as the combination drug sacubitril/valsartan, currently marketed for the treatment of heart failure by Novartis, and vericiguat, currently marketed for the treatment of heart failure by Merck.

We expect that our principal competition for sotagliflozin in the treatment of hypertrophic cardiomyopathy would include generic beta blockers and calcium channel blockers and cardiac myosin inhibitors, such as mavacamten marketed by Bristol Myers Squibb and aficamten in development by Cytokinetics.

We expect that our principal competition for sotagliflozin in the treatment of type 1 diabetes would include established insulin therapies, and potentially, to some extent, selective SGLT2 inhibitors currently being prescribed off-label.

Such selective SGLT2 inhibitors include dapagliflozin, empagliflozin and canagliflozin, currently marketed for the treatment of type 2 diabetes by AstraZeneca, through an alliance between Boehringer Ingelheim and Eli Lilly, and by Janssen (a subsidiary of Johnson & Johnson), respectively.

Such competition also includes, to some extent, other classes of drugs used in the treatment of heart failure, such as the combination drug sacubitril/valsartan, currently marketed for the treatment of heart failure by Novartis, vericiguat, currently marketed for the treatment of heart failure by Merck, and older generic medications such as beta-blockers and diuretics.

Government Regulation

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• preclinical laboratory and animal tests performed under current good laboratory practices, or cGLP;

• submission of an Investigational New Drug application, or IND, which must become effective before human clinical trials may commence;

• submission of an IND, which must become effective before human clinical trials may commence;

• adequate and well-controlled human clinical trials to establish the safety and efficacy of the drug candidate for its intended use;

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Once issued, the FDA may withdraw product approval if ongoing regulatory standards are not met or if safety problems occur after the product reaches the market.

In addition, the FDA may require testing and surveillance programs to monitor the effect of approved products which have been commercialized, and the FDA has the power to prevent or limit further marketing of a product based on the results of these post-marketing programs.

In addition, the FDA may require testing and surveillance programs to monitor the effect of

approved products which have been commercialized, and the FDA has the power to prevent or limit further marketing of a product based on the results of these post-marketing programs.

In addition to obtaining FDA approval for each product, each drug manufacturing establishment must be inspected and approved by the FDA.

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The FDA closely regulates the marketing and promotion of drugs, including restricting the promotion of uses for which a drug is not approved by the agency.

Not only must a company have appropriate substantiation to support claims made about a drug, under the FDA’s current interpretation of relevant laws, a company can make only those claims relating to safety and efficacy that are for indications for which the FDA has approved the drug and are otherwise consistent with the FDA-

approved label for the drug.

Failure to comply with these requirements can result in adverse publicity, warning letters, corrective advertising and potential civil and criminal penalties.

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Upon FDA receipt of orphan drug designation, the sponsor is eligible for tax credits of up to 25% for qualified clinical trial expenses, the ability to apply for annual grant funding and waiver of PDUFA application fee.

In addition, upon marketing approval, an orphan-designated drug could be eligible for seven years of market exclusivity for the approved orphan-designated indication.

In addition, upon marketing approval, an orphan-designated drug could be eligible for seven years

of market exclusivity for the approved orphan-designated indication.

Such orphan drug exclusivity, if awarded, would only block the approval of any drug considered the same drug for the same orphan indication.

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In addition to regulations in the United States, we are subject to the regulations of other countries governing clinical trials and the manufacturing, commercial sales and distribution of our products outside of the United States.

Whether or not we obtain FDA approval for a product, we must obtain approval by the comparable regulatory authorities of countries outside of the United States before we can commence clinical trials in such countries and approval of the regulators of such countries or economic areas, such as the European Union, before we may market products in those countries or areas.

economic areas, such as the European Union, before we may market products in those countries or areas.

The approval process and requirements governing the conduct of clinical trials, product licensing, pricing and reimbursement vary greatly from place to place, and the time may be longer or shorter than that required for FDA approval.

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As in the United States, we may apply for designation of a product as an Orphan drug for the treatment of a specific indication in the European Union before the application for marketing authorization is made.

in the community and when, without incentives, it is unlikely that sales of the drug in the European Union would be sufficient to justify the necessary investment in developing the medicinal product.

In the European Union, orphan designation is available for products in development which are either intended for the diagnosis, prevention or treatment of life-threatening or chronically debilitating conditions affecting not more than 5 in 10,000 persons in the European Union, or intended for the diagnosis, prevention or treatment of a life-threatening, seriously debilitating or serious and chronic condition in the community and when, without incentives, it is unlikely that sales of the drug in the European Union would be sufficient to justify the necessary investment in developing the medicinal product.

Additionally, the sponsor of an application for orphan drug designation must establish that there exists no satisfactory authorized method of diagnosis, prevention, or treatment of the condition or even if such treatment exists, the product will be of significant benefit to those affected by that condition.

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and federal civil and criminal false claims laws and civil monetary penalty laws, which prohibit, among other things, individuals or entities from knowingly presenting, or causing to be presented, claims for payment from Medicare, Medicaid, or other third-party payers that are false or fraudulent.

Additionally, we are subject to state law equivalents of each of the above federal laws, which may be broader in scope and apply regardless of whether the payer is a federal healthcare program, and many of which differ from each other in significant ways and may not have the same effect, further complicate compliance efforts.

Additionally, we are subject to state law equivalents of each of the above federal laws, which may be

broader in scope and apply regardless of whether the payer is a federal healthcare program, and many of which differ from each other in significant ways and may not have the same effect, further complicate compliance efforts.

Numerous federal and state laws, including state security breach notification laws, state health information privacy laws and federal and state consumer protection laws, govern the collection, use and disclosure of personal information.

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These programs require submission of pricing data and calculation of discounts and rebates pursuant to complex statutory formulas, as well as the entry into government procurement contracts governed by the Federal Acquisition Regulations, and the guidance governing such calculations is not always clear.

Compliance with such requirements can require

significant investment in personnel, systems and resources, but failure to properly calculate our prices, or offer required discounts or rebates could subject us to substantial penalties.

Compliance with such requirements can require significant investment in personnel, systems and resources, but failure to properly calculate our prices, or offer required discounts or rebates could subject us to substantial penalties.

Healthcare Reform

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With regard to biopharmaceutical products, the ACA, among other things, addressed a new methodology by which rebates owed by manufacturers under the Medicaid Drug Rebate Program are calculated for drugs that are inhaled, infused, instilled, implanted or injected, increased the minimum Medicaid rebates owed by manufacturers under the Medicaid Drug Rebate Program and extended the rebate program to individuals enrolled in Medicaid managed care organizations, established annual fees on manufacturers of certain branded prescription drugs, and created a new Medicare Part D coverage gap discount program.

Additionally, the Creating and Restoring Equal Access to Equivalent Samples Act of 2019, or the CREATES Act, aimed to address the concern articulated by both the FDA and others in the industry that some brand manufacturers have improperly restricted the distribution of their products, including by invoking the existence of a risk evaluation and mitigation strategies, or REMS, program for certain products, to deny generic product developers access to samples of brand products.

REMS, program for certain products, to deny generic product developers access to samples of brand products.

Because generic product developers need samples to conduct certain comparative testing required by the FDA, some have attributed the inability to timely obtain samples as a cause of delay in the entry of generic products.

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DHHS has solicited feedback on some of various measures intended to lower drug prices and reduce the out of pocket costs of drugs and implemented others under its existing authority.

Congress and the executive branch have each indicated that it will

continue to seek new legislative and/or administrative measures to control drug costs, making this area subject to ongoing uncertainty.

Congress and the executive branch have each indicated that it will continue to seek new legislative and/or administrative measures to control drug costs, making this area subject to ongoing uncertainty.

Individual states in the United States have also increasingly passed legislation and implemented regulations designed to control pharmaceutical product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing.

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These and other laws and their implementing regulations govern our manufacture, use, storage, handling, transport and disposal of various biological, chemical, radioactive and other hazardous substances used in our operations and the wastes generated by those activities.

We cannot eliminate the risk of accidental contamination or discharge and any resultant injury from these substances.

We cannot eliminate the risk of accidental contamination or discharge

and any resultant injury from these substances.

We may face liability for any injury or contamination that results from our use or the use by third parties of those substances, and such liability may exceed our insurance coverage and our total assets.

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We own or exclusively license patents and patent applications throughout the world that claim our drugs and drug candidates, including:

• issued patents and pending patent applications in Europe, the United States, and other countries throughout the world, including Australia, Brazil, Canada, China, Europe, India, Israel, Japan, Mexico, New Zealand, South Africa, and South Korea, that claim pilavapadin, crystalline forms of pilavapadin, pharmaceutical compositions comprising pilavapadin, and methods of its manufacture and use;

• pending United States and Patent Cooperation Treaty (PCT) patent applications that claim LX9851, pharmaceutical compositions comprising it, and methods of its manufacture and use;

• issued patents and pending patent applications in Europe, the United States, and other countries throughout the world, including Australia, Argentina, Brazil, Canada, China, Europe, India, Israel, Japan, Mexico, New Zealand, South Africa, and South Korea, that claim sotagliflozin, crystalline forms of sotagliflozin, pharmaceutical compositions comprising sotagliflozin, and methods of its manufacture and use.

• issued patents and pending patent applications in Europe, the United States, and other countries including Australia, Argentina, Brazil, Canada, China, Europe, India, Israel, Japan, Mexico, New Zealand, South Africa, and South Korea, that claim sotagliflozin, crystalline forms of sotagliflozin, pharmaceutical compositions comprising sotagliflozin, and methods of its manufacture and use;

• issued patents and pending patent applications in Europe, the United States, and other countries including Australia, Brazil, Canada, China, Europe, India, Israel, Japan, Mexico, New Zealand, South Africa, and South Korea, that claim pilavapadin, crystalline forms of pilavapadin, pharmaceutical compositions comprising pilavapadin, and methods of its manufacture and use;

• pending international Patent Cooperation Treaty (PCT) patent applications that claim LX9851, pharmaceutical compositions comprising LX9851, and methods of its manufacture and use;

The normal life of a patent depends primarily on when it was filed.

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We have filed patent applications and hold issued patents covering each of our drugs and drug candidates.

The earliest normal expiration date of our United States patents that claim sotagliflozin is 2028, but the FDA granted a five-year extension to the term of the patent claiming the composition of matter of sotagliflozin, moving its expiration date to 2033.

None of our United States patents that claim pilavapadin has a normal expiration date earlier than 2035.

The earliest normal expiration date for any patent that issues from our applications claiming LX9851 is February 15, 2045.

The earliest normal expiration date of our United States patents that claim sotagliflozin is 2028.

However, we have applied for an extension of patent term based on the FDA’s

approval of the drug and expect that upon acceptance of that application, an additional five years will be added to the term of a patent that claims sotagiflozin, pushing its expiration date out to 2033.

The earliest normal expiration date for any patent that issues from our applications claiming LX9851 is 2045.

All of our employees, consultants and advisors are required to execute a proprietary information agreement upon the commencement of employment or consultation.

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Coiante 59 Senior Vice President and Chief Financial Officer

Corrigan 41 Senior Vice President, Regulatory and Quality Assurance

Crum 53 Senior Vice President and General Counsel

DeFrancesco 47 Senior Vice President, Investor Relations and Corporate Communications

Suma Gopinathan, M.S., Ph.D.

53 Senior Vice President, Discovery

Granowitz, M.D., Ph.D.

61 Senior Vice President and Chief Medical Officer

71 Executive Vice President, Innovation and Chemical Sciences

Martens 42 Senior Vice President, Partnerships and Corporate Strategy

McDermott 55 Senior Vice President, Human Resources

Alexander 57 Vice President, Finance and Accounting

has been our chief executive officer and a director since July 2024.

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from Villanova University.

Corrigan has been our senior vice president, regulatory affairs and quality assurance since August 2024.

Corrigan previously served as executive vice president, regulatory policy at Greenleaf Health, Inc.

Prior to joining Greenleaf Health, Mr.

Corrigan held a variety of senior government affairs and public policy positions with Vertex Pharmaceuticals, Inc.

and Astellas Pharma US, Inc.

Corrigan received his B.A.

from Boston College and J.D.

from George Mason University School of Law.

Crum has been our senior vice president and general counsel since October 2021 and previously served in a series of legal leadership positions since joining our company in 2001.

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from Seton Hall University.

S uma Gopinathan, M.S., Ph.D.

has been our senior vice president, discovery since August 2025 and previously served in a series of scientific leadership positions since joining our company in 2002.

Gopinathan has also served as a consultant to multiple biotechnology and pharmaceutical companies in various preclinical and clinical development areas, including pharmacology, pharmacokinetics and formulation development.

Gopinathan received her B.Pharm.

from Bangalore University, her M.Pharm.

from Kakatiya University and her Ph.D.

from the University of Houston.

Granowitz, M.D., Ph.D.

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from Columbia University.

has been our executive vice president of innovation and chemical sciences since September 2020 and previously served in a series of manufacturing and scientific leadership positions since joining our company in 2001.

Main was president and chief executive officer of Coelacanth Corporation, a leader in using proprietary chemistry technologies to rapidly discover new chemical entities for drug development, until our acquisition of Coelacanth in 2001.

Main was formerly senior vice president, U.S.

Research at Novartis Pharmaceuticals Corporation, where he worked for 20 years before joining Coelacanth.

Main holds a B.S.

from the University of Aberdeen, Scotland and a Ph.D.

in organic chemistry from the University of Liverpool, England and completed postdoctoral studies at the Woodward Research Institute.

Martens has been our senior vice president, partnerships and corporate strategy since February 2026 and previously served in a series of business development and corporate strategy leadership positions since joining our company in

September 2024.

Martens previously served as executive vice president, commercial solutions and corporate strategy for One Drop from 2019 to September 2024.

Prior to joining One Drop, Ms.

Martens held various commercialization leadership roles during nine years at Sanofi and served for four years as an investment banking analyst at BMO Capital Markets.

Martens received her B.A.

from Brown University and her M.B.A.

from Columbia Business School.

McDermott has been our senior vice president, human resources since August 2024 and previously served as our vice president, human resources since January 2022.

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from State University of New York at Plattsburgh.

Alexander has been our vice president of finance and accounting and principal accounting officer since September 2021 and previously served as controller since joining our company in 2017.

Alexander previously served as controller of Johnson Specialty Tools, LLC and in a variety of finance and accounting management positions for Trican Well Services, L.P., Nabors Industries Ltd.

and Ernst & Young, LLP.

Alexander is a certified public accountant and received her B.B.A.

from the University of Oklahoma.

Significant Shareholders

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Invus currently owns approximately 48.3% of the outstanding shares of our common stock.

An affiliate of Invus, L.P.

also owns shares of our Series B Convertible Preferred Stock, which are automatically convertible into shares of our common stock upon the satisfaction of certain conditions.

Following such conversion, Invus will own approximately 50.6% of the outstanding shares of our common stock.

Human Capital Resources

As of February 28, 2025, we employed 103 persons, of whom 19 hold M.D.

As of March 2, 2026, we employed 81 persons, of whom 15 hold M.D.

degrees and another 22 hold other advanced degrees.

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Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-K

Item 1. Business