The goal of this clinical trial is to compare a one-week course of diazoxide (2 mg/kg per dose x 14 doses) and placebo in people with obesity and insulin resistance (IR) with metabolic dysfunction-associated steatotic liver disease (MASLD). The main question it aims to answer are how mitigation of compensatory hyperinsulinemia with diazoxide affects hepatic de novo lipogenesis, a major contributor to MASLD pathophysiology.
Participants will:
* Take 14 doses of placebo over 7 days, followed 4-12 weeks later by either 14 doses of diazoxide (at 2 mg per kg of body weight per dose [mpk]) or another 14 doses of placebo, over 7 days
* Take 18 doses of heavy (deuterated) water (50 mL each) over 7 days, twice
* Have blood drawn and saliva collected after an overnight fast on four mornings over the course of the study
* Undergo insulin suppression tests (IST) to assess the degree of insulin resistance at the end of each 1-week study period
* Consume their total calculated daily caloric needs as divided into three meals per day
Researchers will compare blood tests at the beginning and end of each 1-week study period in participants randomized (like the flip of a coin) to receive either placebo followed by diazoxide or placebo followed by placebo, to see how the drug treatment affects de novo lipogenesis, serum insulin, plasma glucose, and other serum lipid parameters (triglycerides, free fatty acids), among others.

Start Date01 Apr 2026

Sponsor / Collaborator

Columbia University

[+2]

NCT06606327

/ RecruitingPhase 1IIT

Human Models of Primary Hyperinsulinemia: Diazoxide Suppression Test (DzST) Pilot & Feasibility Study

The goal of this study is to learn about how the hormone insulin controls blood sugar. The main question it aims to answer is about how much insulin the body actually needs to maintain a normal blood sugar level. People with obesity and high insulin levels will receive eight doses of diazoxide, a drug that suppresses the pancreas's production of insulin, and will have their fasting blood sugar and insulin levels checked daily while taking the drug.

Start Date23 Oct 2024

Sponsor / Collaborator

Columbia University

[+2]

NCT06308107

/ CompletedPhase 1IIT

Safety and Feasibility of Hyperkalemic Cardioplegia With Diazoxide in Cardiac Surgery (CPG-DZX) Trial

This study aims to confirm the safety and efficacy of diazoxide as an additive to hyperkalemic cardioplegia in patients undergoing cardiac surgery with cardiopulmonary bypass. The investigators hypothesize that diazoxide combined with hyperkalemic cardioplegia provides superior myocardial protection and reduced myocardial stunning compared with standard cardioplegia alone. Thirty patients will receive treatment. Safety will be assessed by comparing mean arterial blood pressure measurements, glucose levels and incidence of adverse events between the two groups. Efficacy will be assessed by comparing right and left ventricular function in pre-operative vs post-operative transesophageal echocardiograms, need for mechanical circulatory support, ease of separation from bypass and Vasoactive Inotrope Score (VIS) between the two groups. The information gained could pave the way for the use of Katp (Potassium-atp) channel openers to prevent stunning, improve patient outcomes, and reduce health care costs related to myocardial stunning that requires inotropic and mechanical support following cardiac surgery.

Start Date08 Jul 2024

Sponsor / Collaborator

The Johns Hopkins University

100 Clinical Results associated with Diazoxide

100 Translational Medicine associated with Diazoxide

100 Patents (Medical) associated with Diazoxide

3,762

Literatures (Medical) associated with Diazoxide

01 Mar 2026·CLINICAL ENDOCRINOLOGY

Genetic and Clinical Characterisation of Congenital Hyperinsulinism: Identification of a Novel ABCC8 Variant

Article

Author: Ganie, Mohd Ashraf ; Ganie, Shahid Ahmad ; Sofi, Javid Ahmad ; Radha, Venkatesan ; Shah, Idrees A. ; Qadir, Ajaz ; Mir, Mohd Rafi ; Mohan, Viswanathan

ABSTRACT:

Background:

Congenital hyperinsulinism (CHI) is a rare but significant cause of persistent hypoglycemia in neonates and infants. Mutations in several genes, including ABCC8 and KCNJ11 , are known to cause CHI. However, data on CHI from our region remain limited.

Purpose:

To assess the genetic spectrum, clinical characteristics, and outcomes of patients with CHI.

Methods:

This was a single‐centre observational study conducted in the Department of Endocrinology and the Multidisciplinary Research Unit at Sher‐i‐Kashmir Institute of Medical Sciences, Srinagar, involving six unrelated patients with clinically suspected CHI who underwent detailed clinical evaluation and targeted genetic testing using a 19‐gene panel associated with CHI, including hyperinsulinism–hyperammonaemia syndrome. Genetic analysis was performed using Sanger sequencing, followed by parental segregation analysis to determine the inheritance patterns.

Results:

The mean age at presentation was 24.2 days. Parental consanguinity was present in 3/6 cases. Three patients (50%) presented with hypoglycemic seizures, while the remaining presented with feeding refusal and lethargy. Likely pathogenic variants were identified in three patients (50%). The most commonly affected gene was ABCC8 ( n = 2), followed by KCNJ11 ( n = 1). Detected ABCC8 variants included a likely novel pathogenic splice variant (c.1009_1011 + 11del) and a frameshift variant (c.453del), whereas the KCNJ11 missense variant identified was c.107 T > A. The likely pathogenic homozygous novel variant, c.1009_1011 + 11del, resulted in a 14 base pair deletion in the intron six and exon six junction of the gene. The mutation affected the invariant GT donor splice site downstream of exon 6 (5 splice). Clinically, two patients responded to diazoxide therapy, while four were classified as diazoxide‐unresponsive. Partial pancreatectomy was performed in two of the diazoxide‐unresponsive cases. The mean duration of follow‐up was 22 months (range: 2–42 months).

Conclusion:

This study documents a likely novel ABCC8 pathogenic variant from a region with limited prior data on CHI, enhancing global understanding of its genetic diversity. Our findings emphasize the importance of integrating genetic testing into standard diagnostic protocols for timely and tailored interventions. The main limitations of this study include the use of Sanger sequencing as the sole genetic testing approach and the absence of functional validation of the identified variants.

01 Feb 2026·JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY

Sphingosine-1-phosphate activates I in ventricular myocytes via mitochondrial reactive oxygen production

Article

Author: Mauro, Adolfo G ; Baumgarten, Clive M ; Raucci, Frank J ; Lesnefsky, Edward J

AIMS:

We previously demonstrated that bacterial sphingomyelinase (SMase), which converts plasmalemmal sphingomyelin to long-chain ceramides, activates the swelling-activated chloride current (I_Cl,swell) in rabbit ventricular myocytes in a reactive oxygen (ROS)-dependent manner under isosmotic conditions. Ceramides can be converted to sphingosine by ceramidase and, in turn, phosphorylated by sphingosine kinase to yield sphingosine-1-phosphate (S1P), which binds to multiple cytoplasmic targets and activates S1P receptors via inside-out transport. This study was designed to determine the cellular source of ROS production elicited by SMase, the sphingolipid species responsible, and thereby, the mechanism of activation of I_Cl,swell by sphingolipids.

METHODS AND RESULTS:

Whole-cell patch clamp experiments were conducted using freshly isolated rabbit ventricular myocytes. Inhibition of ceramidase with D-erythro-MAPP, which increases the concentration of endogenous ceramides in the cell membrane, prevented activation of I_Cl,swell upon exposure to SMase. Similarly, inhibition of sphingosine kinase with DL-threo-dihydrosphingosine to prevent SIP formation by phosphorylation of sphingosine also completely inhibited SMase-induced Cl^- current. In contrast, addition of S1P to the bath solution elicited I_Cl,swell. ROS generated by both NADPH oxidase 2 (NOX2) and mitochondria previously were implicated in triggering I_Cl,swell. SMase-induced I_Cl,swell activation was abrogated by blocking mitochondrial electron transport at Complex I with rotenone but was insensitive to blockade of NOX2 with either apocynin or gp91ds-tat. Moreover, diazoxide, which augments mitochondrial ROS production, evoked I_Cl,swell, and 5-HD, an inhibitor of this pathway, reversed the SMase and diazoxide-induced currents. Flow cytometry using C-H₂DCFDA-AM to assess cytoplasmic ROS in HL-1 myocytes confirmed the effects of the interventions on ROS production.

CONCLUSIONS:

Taken together, these data suggest S1P is the sphingolipid that triggers I_Cl,swell in cardiomyocyte, and activation of I_Cl,swell by SMase and S1P is due to ROS produced by mitochondria and appears independent of NOX2.

TRANSLATIONAL PERSPECTIVE:

I_Cl,swell modulates apoptosis, cell volume, action potential duration, and participation in mechanoelectrical feedback in cardiomyocytes. Persistent activation of I_Cl,swell is seen in several forms of cardiac disease, including dilated cardiomyopathy [1] and models of heart failure [2]. Additionally, it has been implicated in metabolic syndrome and subsequent development of type 2 diabetes (DM2) [3]. This implies a complex relationship, in which there may be both direct effects on damaged cardiomyocytes and indirect effects on the cardiovascular system in general leading to chronic cellular stress such as that seen in DM2. This report demonstrates, for the first time, that S1P augments I_Cl,swell activation in cardiomyocytes via disruption of the mitochondrial respiratory chain resulting in ROS release. This presents potential therapeutic targets for the treatment of cardiovascular diseases, such as dilated cardiomyopathy or metabolic syndrome, characterized by alterations in sphingolipid metabolism.

01 Feb 2026·DIABETOLOGIA

Modelling the effects of human SUR1 R1420H variation on insulin secretory function using isogenic iPSC-derived pancreatic islets

Article

Author: Baier, Leslie J ; Bogardus, Clifton ; Barkho, Katiya ; Traurig, Michael ; Cheranda, Koushik Ponnanna ; Nair, Anup K ; Sutherland, Jeffrey R ; Anup, Divya

Abstract:

Aims/hypothesis:

An R1420H variation in sulfonylurea receptor 1 (SUR1), a subunit of the K ATP channel, was previously identified in an Indigenous community in Arizona where a homozygous carrier (1420HH) had hyperinsulinaemic hypoglycaemia during infancy (HHI), suggestive of a K ATP channel loss of function (LoF). Interestingly, heterozygous carriers of this variation (1420RH, occurring in 3% of the community), had a twofold increased risk of type 2 diabetes. We aimed to create an isogenic induced pluripotent stem cell (iPSC)-derived pancreatic islet (SC-islet)-based platform to test whether the R1420H variant results in K ATP channel LoF, and to examine the distinct temporal effects of SUR1 1420HH and 1420RH K ATP channel variations on insulin secretion from developing and mature SC-islets.

Methods:

Using CRISPR-Cas9, isogenic iPSCs with all three genotypes (SUR1 1420RR, 1420RH and 1420HH) were generated from two different parental Indigenous American iPSC lines (IS1, isogenic cell lines derived from parental cell line 1; and IS2, isogenic cell lines derived from parental cell line 2). These isogenic cell lines were used to generate immature SC-islets (resembling fetal islets) and mature SC-islets (resembling adult islets), which were used to assess insulin secretion dynamics during different stages of development and identify differences in gene expression by single-cell RNA-seq. This study was consistent with the CONSIDER statement for research studies among Indigenous American communities.

Results:

Immature SUR1 1420HH SC-islets secreted 3.4-fold (IS1, p <0.001) and 4.2-fold (IS2, p =0.001) more insulin under basal conditions than normal (SUR1 1420RR) SC-islets. Modest hyperinsulinaemia was also seen in immature SUR1 1420RH SC-islets (2.2-fold [IS1] and 2.3-fold [IS2]) but the results were not statistically significant. After maturation, the 1420HH SC-islets failed to achieve glucose responsiveness whereas the 1420RH SC-islets achieved biphasic insulin secretion but had significantly lower glucose responsiveness than normal SC-islets (AUC for insulin secretion [as a % of total insulin] under high glucose challenge: 1.04 vs 0.56 in normal vs 1420RH SC-islets, p <0.001). Diazoxide reduced hyperinsulinaemia in SUR1 1420RH and 1420HH immature SC-islets, while tolbutamide elicited a greatly diminished or undetectable insulin secretory response from mature SUR1 1420RH SC-islets (13.2-fold increase in insulin secretion) and 1420HH SC-islets (1.9-fold increase) compared with normal SC-islets (31.5-fold increase). Results were directionally comparable for both IS1 and IS2 SC-islets. SUR1 1420RH SC-islets also responded to the glucokinase activator dorzagliatin with improvement in first-phase insulin secretory response (first-phase stimulation index: 3.9-fold vs 7.3-fold, p =0.01 [IS1, 11 mmol/l glucose ± dorzagliatin]; 5.5-fold vs 9.0-fold, p =0.13 [IS1, 20 mmol/l glucose ± dorzagliatin]). Single-cell RNA-seq identified dysregulated genes in SUR1 1420RH SC-beta cells, including lower expression of glycolytic genes and upregulation of G6PC2 , which could explain the lower insulin secretory response to glucose.

Conclusions/interpretation:

A SUR1 R1420H variant identified in an Indigenous American population causes hyperinsulinaemia in homozygous immature SC-islets during basal conditions and these SC-islets fail to achieve glucose responsiveness after maturation. In the heterozygous state, modest hyperinsulinaemia is observed in immature SC-islets, which after maturation have significantly lower glucose responsiveness. These results demonstrate that SUR1 R1420H is a K ATP channel LoF variation and suggest that a lower insulin secretory response during adulthood is the cause of the higher type 2 diabetes risk in individuals heterozygous for this variation. We also show that the isogenic iPSC-based platform can be used to test therapeutic agents to treat HHI in infants homozygous for LoF K ATP channels and screen for drugs that can improve glucose-responsive insulin secretion in adult heterozygous carriers.

Data availability:

See the database of Genotypes and Phenotypes (dbGaP; dbgap.ncbi.nlm.nih.gov/home; accession no.: phs002490.v1.p1) for details concerning data requests. All source codes can be found in the GitHub repository under https://github.com/Koushik-Cheranda/SC-islet-scRNAseq-analysis-R-codes .

Graphical Abstract:

News (Medical) associated with Diazoxide

26 Feb 2026

·www.biospace.com

Soleno Therapeutics Reports Fourth Quarter and Full-Year 2025 Financial Results and Provides Update on U.S. Launch of VYKAT™ XR

REDWOOD CITY, Calif., Feb. 25, 2026 (GLOBE NEWSWIRE) -- Soleno Therapeutics, Inc. (Soleno) (NASDAQ: SLNO), a biopharmaceutical company developing novel therapeutics for the treatment of rare diseases, today reported financial results for the fourth quarter and full-year ended December 31, 2025 and provided an update on the U.S. launch of VYKAT™ XR (diazoxide choline) extended-release tablets. Fourth Quarter and Full-Year 2025 and Recent Corporate Highlights Revenue, net, from the sale of VYKAT XR for the three and twelve months ended December 31, 2025, was $91.7 million and $190.4 million, respectively. From approval on March 26, 2025 through December 31, 2025, Soleno reports: 1,250 patient start forms received, including 207 in the fourth quarter 630 unique prescribers, including 136 new prescribers in the fourth quarter 859 active patients on drug as of December 31, 2025 Over 185 million lives covered Achieved profitability with positive net income of $20.9 million for the year. Generated $48.7 million of cash flow from operating activities in the fourth quarter. Invested $100 million in accelerated share repurchase program announced in November 2025 and ended the year with $506.1 million of cash, cash equivalents and marketable securities. “Our first year as a commercial organization has been an outstanding success,” stated Anish Bhatnagar, M.D., Chairman and Chief Executive Officer of Soleno Therapeutics. “In just nine months, we received patient start forms representing over 12% of the U.S. VYKAT XR addressable market, reflecting both the strength of our world-class commercial team as well as the substantial disease burden that is addressed by VYKAT XR. We are very pleased with the positive trajectory of our other leading indicators, including patient start forms, patients on active therapy, unique prescribers, and lives covered.” “Looking ahead, with the U.S. VYKAT XR launch well underway, we plan to pursue regulatory approval in other territories, starting with the EU. We will also begin to evaluate diazoxide choline extended-release (DCCR) in additional high-need rare diseases as we expand our development pipeline. We have made excellent progress in 2025 and are excited for the year ahead.” Fourth Quarter and Full-Year Ended December 31, 2025 Financial Results Product revenue, net, was $91.7 million and $190.4 million for the three and twelve months ended December 31, 2025, respectively. VYKAT XR had not been approved or commercially launched in the three and twelve months ended December 31, 2024, and accordingly, generated no revenue during those periods. Research and development expense was $9.6 million, which includes $2.8 million of non-cash stock-based compensation, for the three months ended December 31, 2025, compared to $21.5 million, which includes $10.1 million of non-cash stock-based compensation, in the same period of 2024. For the year ended December 31, 2025, research and development expense was $40.6 million, which includes $11.7 million of non-cash stock-based compensation, a decrease of $38.0 million compared to $78.6 million, which includes $33.7 million non-cash stock-based compensation, in the same period of 2024. For the year, the $15.9 million decrease in expense not related to stock-based compensation was due to a reduction in pre-commercial launch costs in support of the Company’s 2024 NDA submission, supply chain, and clinical activities. These expenses decreased $7.5 million, $6.0 million, and $3.8 million, respectively. These decreases were partially offset by the Company incurring an additional $1.4 million of expense towards its MAA submission in Europe, which was submitted in the second quarter of 2025. The cadence of the Company’s research and development expenditures will fluctuate depending upon the state of its research activities, clinical programs, and the timing of manufacturing and other projects necessary to support the submission of its regulatory filings. Selling, general and administrative expense was $40.9 million, which includes $8.7 million of non-cash stock-based compensation, for the three months ended December 31, 2025, compared to $37.3 million, which includes $19.7 million of non-cash stock-based compensation, in the same period of 2024. For the year ended December 31, 2025, selling, general and administrative expense was $132.1 million, which includes $34.1 million of non-cash stock-based compensation, an increase of $26.2 million compared to $105.9 million, which includes $66.2 million of non-cash stock-based compensation, in the same period of 2024. For the year, personnel costs, including hiring expense and other associated headcount costs, increased $31.3 million as the Company hired additional employees in support of its commercial launch and increased business activities. New program costs associated with commercial launch activities, including disease state education, analytics, other marketing programs, medical affairs and patient advocacy activities, increased $23.4 million. Costs for international expansion increased $3.5 million. These increases were offset by the $32.1 million reduction in stock-based compensation. Selling, general and administrative expenses are anticipated to increase as the Company continues commercialization of VYKAT XR. The Company is obligated to make cash payments of up to a maximum of $21.2 million to the former Essentialis stockholders upon the achievement of certain commercial milestones associated with the sales of DCCR in accordance with the terms of the Company’s 2017 merger agreement with Essentialis. The fair value of the liability for the contingent consideration payable by the Company upon the achievement of commercial sales milestones of $100 million and $200 million in aggregate revenue, respectively, was estimated to be $20.3 million as of December 31, 2025, a $5.5 million increase from the estimate as of December 31, 2024. The first commercial milestone was achieved in the fourth quarter 2025 and $7.0 million will be paid in the first quarter 2026. Total other income, net, was $3.8 million for the three months ended December 31, 2025, compared to total other income, net, of $3.1 million in the same period of 2024. For the year, total other income, net, was $11.5 million for 2025, compared to $11.8 million for 2024. For the year ended December 31, 2025, net income was approximately $20.9 million, or $0.40 per basic and $0.39 per diluted share, compared to a net loss of $(175.9) million, or $(4.38) per basic and diluted share, for the same period of 2024. Conference Call and Webcast Information Soleno management will host an investor conference call and webcast to discuss its fourth quarter and full-year 2025 financial and operating results and provide an update on the U.S. launch of VYKAT XR today, February 25, 2026, at 4:30pm ET. Details can be found below: Conference call details: Toll-free: 800-717-1738 International: 646-307-1865 Conference ID: 55257 Call me™ (avoids waiting for an operator): Here Webcast: Here About PWS Prader-Willi syndrome (PWS) is a rare genetic neurodevelopmental disorder caused by an abnormality in the gene expression on chromosome 15. The Prader-Willi Syndrome Association USA estimates that PWS occurs in one in every 15,000 live births. The defining symptom of PWS is hyperphagia, a chronic and life-threatening condition characterized by an intense persistent sensation of hunger accompanied by food preoccupations, an extreme drive to consume food, food-related behavior problems, and a lack of normal satiety, which can severely diminish the quality of life for individuals with PWS and their families. Hyperphagia can lead to significant mortality (e.g., stomach rupture, choking, accidental death due to food seeking behavior) and longer term, co-morbidities such as diabetes, obesity, and cardiovascular disease. INDICATION VYKAT XR (diazoxide choline) extended-release tablets is indicated for the treatment of hyperphagia in adults and pediatric patients 4 years of age and older with Prader-Willi syndrome (PWS). IMPORTANT SAFETY INFORMATION Contraindications Use of VYKAT XR is contraindicated in patients who have a known hypersensitivity to diazoxide, other components of VYKAT XR, or to thiazides. Warnings and Precautions Hyperglycemia Hyperglycemia, including diabetic ketoacidosis, has been reported. Before initiating VYKAT XR, test fasting plasma glucose (FPG) and HbA1c; optimize blood glucose in patients who have hyperglycemia. During treatment, regularly monitor fasting glucose (FPG or fasting blood glucose) and HbA1c. Monitor fasting glucose more frequently during the first few weeks of treatment in patients with risk factors for hyperglycemia. Risk of Fluid Overload Edema, including severe reactions associated with fluid overload, has been reported. Monitor for signs or symptoms of edema or fluid overload. VYKAT XR has not been studied in patients with compromised cardiac reserve and should be used with caution in these patients. Adverse Reactions The most common adverse reactions (incidence ≥10% and at least 2% greater than placebo) included hypertrichosis, edema, hyperglycemia, and rash. Please see the full Prescribing Information, including Medication Guide . About Soleno Therapeutics, Inc. Soleno is focused on the development and commercialization of novel therapeutics for the treatment of rare diseases. The Company’s first commercial product, VYKAT XR (diazoxide choline) extended-release tablets, formerly known as DCCR, is a once-daily oral treatment for hyperphagia in adults and children 4 years of age and older with Prader-Willi syndrome. For more information, please visit . Forward-Looking Statements This press release contains forward-looking statements within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended. All statements other than statements of historical facts contained in this press release are forward-looking statements. In some cases, you can identify forward-looking statements by terms such as "may," "will," "should," "expect," "plan," "anticipate," "could," "intend," "target," "project," "contemplates," "believes," "estimates," "predicts," "potential" or "continue" or the negative of these terms or other similar expressions. These forward-looking statements speak only as of the date of this press release and are subject to a number of risks, uncertainties and assumptions, including those described in the company's prior press releases and in the periodic reports it files with the SEC including its Annual Report on Form 10-K which it intends to release later today. The events and circumstances reflected in the company's forward-looking statements may not be achieved or occur and actual results could differ materially from those projected in the forward-looking statements. Except as required by applicable law, the company does not plan to publicly update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise. Corporate Contact: Brian Ritchie LifeSci Advisors, LLC 212-915-2578 Soleno Therapeutics, Inc. Consolidated Balance Sheets (In thousands except share and per share data) December 31, 2025 December 31, 2024 Assets Current assets Cash and cash equivalents $ 70,106 $ 87,928 Marketable securities 235,366 203,509 Accounts receivable, net 28,208 — Inventory, net 15,024 — Prepaid expenses and other current assets 7,110 2,452 Total current assets 355,814 293,889 Long-term assets Property and equipment, net 185 186 Operating lease right-of-use assets 2,191 2,798 Intangible assets, net 4,861 6,805 Long-term marketable securities 200,616 27,211 Other long-term assets 163 83 Total assets $ 563,830 $ 330,972 Liabilities and stockholders’ equity Current liabilities Accounts payable $ 12,435 $ 8,882 Accrued compensation 9,677 4,776 Operating lease liabilities 726 526 Contingent liability for Essentialis purchase price 20,327 — Other current liabilities 18,198 4,563 Total current liabilities 61,363 18,747 Long-term liabilities Contingent liability for Essentialis purchase price — 14,791 Long-term debt, net 49,863 49,828 Long-term lease liabilities 1,964 2,472 Other long-term liabilities 525 21 Total liabilities 113,715 85,859 Commitments and contingencies (Note 6) Stockholders’ equity Preferred stock, $0.001 par value; 10,000,000 shares authorized, no shares issued and outstanding — — Common stock, $0.001 par value, 100,000,000 shares authorized, 52,286,881 and 45,703,811 shares issued and outstanding at December 31, 2025 and 2024, respectively 52 46 Additional paid-in-capital 881,018 696,966 Accumulated other comprehensive income 415 361 Accumulated deficit (431,370 ) (452,260 ) Total stockholders’ equity 450,115 245,113 Total liabilities and stockholders’ equity $ 563,830 $ 330,972 Soleno Therapeutics, Inc. Consolidated Statements of Operations and Comprehensive Income (Loss) (In thousands except share and per share data) Three Months Ended December 31, Years Ended December 31, 2025 2024 2025 2024 Product revenue, net $ 91,730 $ -- $ 190,405 $ -- Operating expenses Cost of goods sold 863 -- 2,700 -- Research and development 9,558 21,486 40,627 78,568 Selling, general and administrative 40,878 37,303 132,128 105,861 Change in fair value of contingent consideration 854 327 5,536 3,242 Total operating expenses 52,153 59,116 180,991 187,671 Operating income (loss) 39,577 (59,116 ) 9,414 (187,671 ) Other income (expense), net Interest income, net 5,130 3,365 16,952 12,052 Interest expense (1,349 ) (231 ) (5,476 ) (231 ) Total other income (expense), net 3,781 3,134 11,476 11,821 Net income (loss) $ 43,358 $ (55,982 ) $ 20,890 $ (175,850 ) Other comprehensive income (loss) Net unrealized gain (loss) on marketable securities 68 (537 ) 37 361 Foreign currency translation adjustment (13 ) 3 17 -- Total comprehensive income (loss) $ 43,413 $ (56,516 ) $ 20,944 $ (175,489 ) Net income (loss) 43,358 (55,982 ) 20,890 (175,850 ) Less: Undistributed earnings attributable to participating securities (1 ) -- (415 ) -- Net income (loss) attributable to common stockholders - basic and diluted $ 43,357 $ (55,982 ) $ 20,475 $ (175,850 ) Net income (loss) per share - basic $ 0.82 $ (1.27 ) $ 0.40 $ (4.38 ) Net income (loss) per share - diluted $ 0.80 $ (1.27 ) $ 0.39 $ (4.38 ) Weighted-average common shares outstanding - basic 53,175,700 43,924,831 50,817,586 40,175,926 Weighted-average common shares outstanding - diluted 54,331,407 43,924,831 52,384,886 40,175,926 Soleno Therapeutics, Inc. Stock-based Compensation Expense (In thousands) Three Months Ended December 31, Years Ended December 31, 2025 2024 2025 2024 Research and development $ 2,821 $ 10,061 $ 11,722 $ 33,743 Selling, general and administrative 8,650 19,694 34,124 66,215 Total $ 11,471 $ 29,755 $ 45,846 $ 99,958

Financial StatementDrug Approval

12 Jan 2026

·www.biospace.com

Soleno Therapeutics Announces Select Preliminary Fourth Quarter and Full-Year 2025 Results

REDWOOD CITY, Calif., Jan. 12, 2026 (GLOBE NEWSWIRE) -- Soleno Therapeutics, Inc. (Soleno) (NASDAQ: SLNO), a biopharmaceutical company developing novel therapeutics for the treatment of rare diseases, today announced select preliminary financial and operating results for the fourth quarter and full-year 2025: Preliminary unaudited full-year 2025 net revenue related to U.S. sales of VYKAT™ XR since second quarter launch expected to be in a range of $189 million to $191 million. Preliminary unaudited fourth quarter 2025 net revenue expected to be in a range of $90 million to $92 million. 1,250 total new patient start forms (207 in the fourth quarter) from launch through December 31, 2025, or approximately 12.5% of the total U.S. VYKAT XR addressable market. Discontinuation rate of VYKAT XR related to adverse events was approximately 12% as of the end of the fourth quarter. 630 unique prescribers, including 136 new prescribers in the fourth quarter. Over 185 million lives covered, or approximately 60% of total lives. Company has responded to Day 120 questions received from the European Medicines Agency. Company has achieved profitability and positive cash flow. Year-end 2025 cash, cash equivalents and marketable securities were approximately $500 million, after the $100 million accelerated share repurchase program that the Company announced on November 11, 2025. “Our strong fourth quarter results cap a truly transformational year for Soleno Therapeutics, driven by the approval and successful launch of VYKAT XR in the U.S.,” said Dr. Anish Bhatnagar, Chief Executive Officer and Chairman of the Board of Soleno Therapeutics. “In less than nine months since launch, we have received patient start forms representing well over 10% of our addressable U.S. Prader-Willi syndrome (PWS) patient population. This reflects the significant unmet medical need that VYKAT XR can address as well as our success in communicating VYKAT XR’s value proposition to payers, providers and caregivers.” “Looking ahead, as we continue to raise awareness of this first-to-market hyperphagia treatment, we have the opportunity to significantly impact the lives of many more patients and families living with PWS while simultaneously creating sustained value for our company. We are well-funded, our leading indicators are strong, and I am excited for what the future holds in 2026 and beyond,” Dr. Bhatnagar concluded. The estimates of Soleno’s net revenue, cash, cash equivalents and marketable securities, patient start forms and other metrics above as of December 31, 2025 are preliminary, have not been audited, and do not present all information necessary for an understanding of Soleno’s financial condition as of December 31, 2025. The preliminary select financial information presented in this press release is provided as an approximation in advance of Soleno’s announcement of full fourth quarter and full-year 2025 financial results, which is anticipated to occur in late February 2026. About PWS Prader-Willi syndrome (PWS) is a rare genetic neurodevelopmental disorder caused by an abnormality in the gene expression on chromosome 15. The Prader-Willi Syndrome Association USA estimates that PWS occurs in one in every 15,000 live births. The defining symptom of PWS is hyperphagia, a chronic and life-threatening condition characterized by an intense persistent sensation of hunger accompanied by food preoccupations, an extreme drive to consume food, food-related behavior problems, and a lack of normal satiety, which can severely diminish the quality of life for individuals with PWS and their families. Hyperphagia can lead to significant mortality (e.g., stomach rupture, choking, accidental death due to food seeking behavior) and longer term, co-morbidities such as diabetes, obesity, and cardiovascular disease. About VYKAT XR VYKAT XR was approved by the U.S. Food and Drug Administration (FDA) on March 26, 2025, and is commercially available to U.S. patients. VYKAT XR is indicated for the treatment of hyperphagia in adults and pediatric patients 4 years of age and older with Prader-Willi syndrome (PWS). IMPORTANT SAFETY INFORMATION Contraindications Use of VYKAT XR is contraindicated in patients who have a known hypersensitivity to diazoxide, other components of VYKAT XR, or to thiazides. Warnings and Precautions Hyperglycemia Hyperglycemia, including diabetic ketoacidosis, has been reported. Before initiating VYKAT XR, test fasting plasma glucose (FPG) and HbA1c; optimize blood glucose in patients who have hyperglycemia. During treatment, regularly monitor fasting glucose (FPG or fasting blood glucose) and HbA1c. Monitor fasting glucose more frequently during the first few weeks of treatment in patients with risk factors for hyperglycemia. Risk of Fluid Overload Edema, including severe reactions associated with fluid overload, has been reported. Monitor for signs or symptoms of edema or fluid overload. VYKAT XR has not been studied in patients with compromised cardiac reserve and should be used with caution in these patients. Adverse Reactions The most common adverse reactions (incidence ≥10% and at least 2% greater than placebo) included hypertrichosis, edema, hyperglycemia, and rash. Please see the full Prescribing Information, including Medication Guide . About Soleno Therapeutics, Inc. Soleno is focused on the development and commercialization of novel therapeutics for the treatment of rare diseases. The company’s first commercial product, VYKAT™ XR (diazoxide choline) extended-release tablets, formerly known as DCCR, is a once-daily oral treatment for hyperphagia in adults and children 4 years of age and older with Prader-Willi syndrome and was approved by the U.S. Food and Drug Administration (FDA) on March 26, 2025. For more information, please visit . Forward-Looking Statements This press release contains forward-looking statements within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended. All statements other than statements of historical facts contained in this press release are forward-looking statements. In some cases, you can identify forward-looking statements by terms such as "may," "will," "should," "expect," "plan," "anticipate," "could," "intend," "target," "project," "contemplates," "believes," "estimates," "predicts," "potential" or "continue" or the negative of these terms or other similar expressions. These forward-looking statements speak only as of the date of this press release and are subject to a number of risks, uncertainties and assumptions, including those described in the company's prior press releases and in the periodic reports it files with the SEC. The events and circumstances reflected in the company's forward-looking statements may not be achieved or occur and actual results could differ materially from those projected in the forward-looking statements. Except as required by applicable law, the company does not plan to publicly update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise. Corporate Contact: Brian Ritchie LifeSci Advisors, LLC 212-915-2578 Media Contact: media@soleno.life

Drug ApprovalFinancial Statement

11 Dec 2025

·www.fiercebiotech.com

Rezolute\'s stock plunges 87% after hypoglycemia drug flunks pivotal phase 3 test

Rezolute\'s trial missed its primary endpoint of a change in average weekly hypoglycemia events.\n Rezolute’s stock has plunged 87% after the company’s rare disease drug flunked the final clinical test ahead of a planned approval application.The company had been evaluating ersodetug as a treatment for hypoglycemia in a phase 3 study of 63 patients aged between 3 months and 45 years around the world with congenital hyperinsulinism (HI). The biotech was confident enough in the study’s prospects that it recruited a chief commercial officer back in August to prepare for the commercialization of ersodetug.But those plans have been thrown into doubt this morning as Rezolute revealed the trial missed its primary endpoint of a change in average weekly hypoglycemia events. The 45% reduction in self-monitored events among the highest, 10-mg/kg, ersodetug dose cohort was not statistically significant when compared to the 40% improvement seen in the placebo group, Rezolute explained in a Dec. 11 release.There wasn’t a silver lining to be found in the study’s secondary endpoint, either, with the 25% reduction in time patients experienced hypoglycemia over six months among the 10-mg/kg ersodetug group not being deemed statistically significant when compared to a 5% increase in time across the placebo cohort.Two patients experienced serious hypersensitivity reactions that led to early discontinuation of study drug, although the company claimed “incidence of serious allergic reactions across the program is relatively low compared to biologic or monoclonal antibody treatments.”Investors took fright at the trial results, driving the company’s stock down 87% to $1.40 in early morning trading Thursday, falling from a Wednesday closing price of $10.94.With a phase 3 study of ersodetug in tumor HI ongoing, Rezolute isn’t ready to write off the drug quite yet. The company’s chief medical officer Brian Roberts, M.D., said the biotech plans to meet with the FDA “to consider next steps for the program.”“We are disappointed that the study did not demonstrate significant improvements in glucose-related endpoints relative to placebo as well as for the patients and families living with congenital HI who urgently need new treatment options,” Roberts said in this morning’s release.“At the same time, there are aspects of the results that merit additional investigation, and we are conducting a thorough evaluation to gain a better understanding of the study outcomes, which will inform our path forward,” he added. Patients with hypoglycemia caused by HI currently have limited options. Diazoxide is approved in the indication, but, with response rates ranging from 40% to 74%, there is room to improve on the treatment. Zealand Pharma has been preparing to refile for approval of dasiglucagon, a glucagon analog that it already sells as Zegalogue in other settings, in congenital HI after suffering two rejections in recent years.Rezolute sees barriers to the use of dasiglucagon in congenital HI, though, telling (PDF) investors back in May that the utility in chronic use is unproven and predicting Zealand is likely to need to combine the drug with other therapies.Rezolute’s ersodetug is a monoclonal antibody that binds to the insulin receptor to decrease over-activation by insulin and related substances. Because ersodetug acts downstream from the pancreas, Rezolute had been hoping the drug could be “universally effective at treating hypoglycemia due to any congenital or acquired form of hyperinsulinism.”Hopes for the drug were raised back in 2022 when a phase 2 trial tied ersodetug to a 75% reduction in severe low blood sugar events in children, leading the company to raise $130 million to support a push into phase 3.Only last month, Rezolute was explaining to investors that the company had secured alignment with the FDA on the registrational requirements for submitting an approval application for the therapy.

$Rezolute\'s stock plunges 87% after hypoglycemia drug flunks pivotal phase 3 test$

Phase 3Phase 2Drug ApprovalClinical Result

100 Deals associated with Diazoxide

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KEGG	Wiki	ATC	Drug Bank
D00294	Diazoxide	V03AH01 C02DA01	DB01119

R&D Status

Approved

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Indication	Country/Location	Organization	Date
Hypertension	United States	Schering Corp.	22 Jan 1973
Hypoglycemia	United States	Schering Corp.	22 Jan 1973

Developing

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Indication	Highest Phase	Country/Location	Organization	Date
Multiple Sclerosis, Relapsing-Remitting	Phase 2	Germany	Neurotec Pharma SL	01 Jun 2011
Multiple Sclerosis, Relapsing-Remitting	Phase 2	Spain	Neurotec Pharma SL	01 Jun 2011
Multiple Sclerosis	Phase 2	Spain	Neurotec Pharma SL	-
Amyotrophic Lateral Sclerosis	Preclinical	Spain	Neurotec Pharma SL	-

Clinical Result

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Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03608163 (CTgov)	Phase 4	Diabetes Mellitus, Type 1 \| Hypoglycemia \| Pure Autonomic Failure ... View more	4	Naloxone (Naloxone)	jzvzxqisyk(sjnudbwesl) = uifuhnfvha bhtfvfbeyw (hutiynsxes, 134) View more	-	11 Sep 2025
				Placebo (for Naloxone) (Placebo (for Naloxone))	jzvzxqisyk(sjnudbwesl) = bcnltdqjkx bhtfvfbeyw (hutiynsxes, 195) View more
NCT03566511 (CTgov)	Phase 2	Diabetes Mellitus, Type 2 \| Hyperglycemia	37	Proglycem+placebo (Diazoxide)	zzndvtftkg(thontbsczc) = dylsrxtzjn tqqqmeammx (mvsjetddyb, 1.3) View more	-	31 May 2025
				Proglycem+placebo (Matched Placebo)	zzndvtftkg(thontbsczc) = buqrslbodd tqqqmeammx (mvsjetddyb, 1.3) View more
NCT01028846 (CTgov)	Phase 4	Diabetes Mellitus, Type 2 \| Hyperglycemia	10	Diazoxide (Diazoxide)	zqtmxrbswu(xoqnoeqixh) = eobwqoglft lvdqbpqovu (nasmihuoug, 0.13) View more	-	14 Mar 2025
				Placebo (Placebo)	zqtmxrbswu(xoqnoeqixh) = gqoamifcls lvdqbpqovu (nasmihuoug, 0.17) View more
NCT00631033 (Pubmed \| J Clin Endocrinol Metab)	Phase 2	Obesity	51	DZX + placebo	zwarhrrdvc(eiggielejm) = hogtrymqyk cvdaepyvby (tsacbvhfgl ) View more	Positive	01 Nov 2018
				DZX + metformin	zwarhrrdvc(eiggielejm) = rpbtvmqtrz cvdaepyvby (tsacbvhfgl ) View more
NCT00631033 (Pubmed \| J Clin Endocrinol Metab)	Phase 2	Obesity	51	Diazoxide	qfewmabsdn(pfbtxbvlfr) = 11 hxbmuosmxz (xbovofxggt ) View more	-	01 Jun 2018
				Placebo
NCT02049385 (CTgov)	Phase 1/2	Depressive Disorder, Major	10	Diazoxide (Diazoxide)	vlrdqvqcei(styonfmved) = qhrieqoobv pqxwfaxygj (eswmbrlsvz, niyfsvkvtq - meeuvkjayn) View more	-	13 Oct 2017
				Placebo (Placebo)	vlrdqvqcei(styonfmved) = nricnujloe pqxwfaxygj (eswmbrlsvz, rfdaqmuwvm - ndlillfzjp) View more
NCT00306683 (PEDIAC, Pubmed \| J Clin Endocrinol Metab)	Phase 3	Obesity	40	Diazoxide	lnvvbprbjy(clvfcrjdxe) = trjmvbucvb lbpnscotxe (gcoxydwykq )	Negative	01 Dec 2016
				Placebo	lnvvbprbjy(clvfcrjdxe) = qkthotmwhc lbpnscotxe (gcoxydwykq )
NCT00683774 (CTgov)	Not Applicable	Polycystic Ovary Syndrome	21	diazoxide (PCOS Subjects)	kqghjdwxwr(rctnmzpzxo) = hirqworabq nekzoobuaw (kgrrgtfxed, kjytnnxrke - iuzxnickjc) View more	-	21 Aug 2014
				diazoxide (Normal Subjects)	kqghjdwxwr(rctnmzpzxo) = ylksoqnbcn nekzoobuaw (kgrrgtfxed, tefarsabrk - oqxbfyobxx) View more

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