About Soleno Therapeutics

Soleno Therapeutics, Inc., a clinical-stage biopharmaceutical company, focuses on the development and commercialization of novel therapeutics for the treatment of rare diseases. The company's lead drug, Diazoxide Choline Extended-Release tablets (DCCR), is a potent ATP-sensitive potassium (KATP) channel activator. The KATP channel plays a central role in the regulation of a number of physiological processes, which may otherwise be dysregulated, contributing to the pathophysiology of several diseases. In the context of the underlying genetic or structural defects in many forms of hyperphagic obesity, including Prader-Willi syndrome (PWS), these pathophysiological processes may cumulatively contribute to increases in appetite and aggressive food seeking, lack of satiety, accumulation of excess body fat and the establishment and perpetuation of the obese state. DCCR's unique mode of action with targets in the brain, pancreas and fat tissue has the potential to broadly impact complex diseases like PWS to reduce appetite, reduce food seeking, improve satiety, improve insulin and leptin resistance and reduce body fat. It appears that many of the problematic behaviors in conditions like PWS may have hyperphagic drive as a root cause and may therefore be improved by addressing hyperphagia. The company has a Fast-Track designation for DCCR in PWS and orphan designation for the drug in the United States (U.S.) and European Union (E.U.). DCCR has been evaluated in a Phase 3 study (C601 or DESTINY PWS), a 13-week randomized, double-blind placebo-controlled study, which completed enrollment in January 2020, with 127 randomized participants at 29 sites in the U.S. and the United Kingdom (U.K.). Participants who completed treatment in DESTINY PWS and sought continued treatment with DCCR were eligible to receive DCCR in a long-term open-label safety extension study (C602). Top line results from DESTINY PWS were announced in June 2020. Although the trial did not meet its primary endpoint of change from baseline in hyperphagia, significant improvements were observed in two of three key secondary endpoints. In February 2021, the company announced analysis limited to data collected before the onset of the COVID-19 pandemic. The analysis of the data through March 1, 2020 showed statistical significance in the primary, all key secondary and several other efficacy endpoints. In September 2021, the company announced top line results from the interim one year data from C602 showing statistically significant reduction in hyperphagia and all other PWS behavioral parameters and statistically significant improvements compared to natural history of PWS from the PATH for PWS Study (PfPWS) over a one year treatment period. The PfPWS study is an ongoing study sponsored by the Foundation for Prader-Willi Research (FPWR) to advance the understanding of the natural history in individuals with PWS. The FDA provided official meeting minutes from a Type C meeting in January 2022 that recommended additional controlled data be included in a New Drug Approval (NDA) submission, and indicated they were receptive to a study design involving participants enrolled in Study C602, the company's ongoing open-label extension study to generate the data necessary to support an NDA. In March 2022, the company submitted a proposal to add a randomized withdrawal period to Study C602 to obtain additional controlled data requested by the FDA to support a NDA submission for DCCR. The randomized withdrawal (RW) period of Study C602 is a multi-center, randomized, double-blind, placebo-controlled study of DCCR in approximately 80 patients with PWS at 17 sites in the U.S. and 5 sites in the U.K. This RW period consists only of patients currently enrolled in Study C602 and will not enroll any new patients. The company announced the initiation of the RW period for Study C602 in October 2022. The FDA has acknowledged that data from the study has the potential to support an NDA submission for DCCR. The company's focus is the development of DCCR for PWS. However, other syndromes that may be similarly addressed include SH2B1 deficient obesity, more severely impacted forms of MC4R deficiency, Alström syndrome, and KSR2 deficient obesity. Another type of disease where DCCR may be efficacious is where hypoglycemia is a significant problem. Examples include hyperinsulinemic hypoglycemia and certain Glycogen Storage Diseases. The company has orphan drug designation for the treatment of Glycogen Storage Disease Type 1a in the U.S. A Phase 2 clinical trial was conducted to evaluate the safety and preliminary efficacy of DCCR in the treatment of PWS subjects. This study, PC025, was a single-center, randomized withdrawal study and enrolled 13 overweight and obese subjects with genetically-confirmed PWS who were between the ages of 11 and 21. The first phase of the study was open-label during which subjects were initiated on a DCCR dose that was escalated every 14 days at the discretion of the investigator. Any subject who showed any increase in resting energy expenditure and/or a reduction in hyperphagia from baseline at certain study visits would be designated a responder, whereas all others would be designated non-responders. This 10-week open-label treatment phase was followed by randomized double-blind, placebo-controlled, withdrawal phase. A Phase 3 clinical trial, DESTINY PWS, was subsequently conducted to evaluate the efficacy and safety of DCCR in patients with genetically-confirmed PWS. Top-line results were reported in June 2020. Although the trial did not meet its primary endpoint of change from baseline in hyperphagia, significant improvements were observed in two of three key secondary endpoints. Subjects who complete the DESTINY PWS study were allowed to enroll in a long-term, safety extension study (C602). In September 2021, the company announced top-line results from the analysis of one-year data from C602 showing statistically significant reduction in hyperphagia and all other PWS behavioral parameters and statistically significant improvements compared to the natural history of PWS from the PATH for PWS Study (PfPWS) over a one year treatment period. PfPWS is an ongoing study sponsored by the Foundation for Prader Willi Research (FPWR) evaluating the natural history of subjects with PWS in more than 700 families. In the DESTINY-PWS clinical trial (C601), treatment emergent adverse events (TEAEs) occurred in 83.3% of DCCR treated subjects and 73.8% of placebo treated subjects. The most common TEAEs in both groups included hypertrichosis, hirsutism, upper respiratory tract infections, peripheral edema, headache and hyperglycemia. Hypertrichosis, peripheral edema, and hyperglycemia occurring more frequently in the DCCR group, headache occurred more frequently in the placebo group, and hirsutism and upper respiratory tract infections occurring with almost equal frequency in the two groups. The safety profile of DCCR in C601 was generally consistent with the known safety profile of diazoxide and prior experience with DCCR. Most events were Grade 1 in severity with no Grade 4 or higher events. There were no reportable serious unexpected adverse events (SUSARs) related to DCCR in clinical study C601. Diazoxide choline is being developed in the U.S. under a current Investigational New Drug Application (IND) and is designated as an Orphan Drug for the treatment of PWS in the U.S. and Europe and granted Fast Track designation in the U.S. If certain criteria are met, DCCR may be eligible for 'Accelerated Approval' and 'Priority Review' and also 'Rolling Review', which would allow the company to submit to the FDA sections of the company's NDA as they are finished instead of waiting for all sections to be completed before submitting the marketing application. Manufacturing The company and its third-party manufacturers are subject to current Good Manufacturing Practices, which are extensive regulations governing manufacturing processes, stability testing, record keeping, and quality standards as defined by the FDA and the EMA. Intellectual Property DCCR Patent Portfolio The company's patent portfolio consists of issued U.S. patents and pending U.S. applications. The company's issued U.S. patents expire in 2025 to 2035. The company also has one or more issued patents in Europe, Canada, Japan, China, India, Israel, Hong Kong, Australia, Malaysia, Mexico, New Zealand, Singapore, Indonesia, Korea, and Eurasia. The company is prosecuting numerous patent applications in major pharmaceutical markets around the world. The issued patents and pending patent applications include protection of compositions, methods of manufacturing, pharmaceutical formulations, and methods of treating aspects of PWS and Smith-Magenis syndrome (SMS). Government Regulation - Pharmaceuticals In addition to obtaining FDA approval for the company's drug, the manufacturing facilities of the companies who manufacture the company's drugs for the company must also be approved. These facilities are subject to periodic inspections by the FDA. FDA regulations also require investigation and correction of any deviations from cGMP or QSR and impose reporting and documentation requirements upon the company and any third-party manufacturers that the company may decide to use. Because the company is a healthcare provider and the company conducts certain healthcare transactions electronically, the company is presently a Covered Entity, and the company must have in place the administrative, physical, and technical safeguards required by HIPAA, HITECH and their implementing regulations. Additionally, some state laws impose privacy protections more stringent than HIPAA. The company is subject to a federal 'self-referral' law, commonly referred to as the 'Stark' law, which provides that physicians who, personally or through a family member, have ownership interests in or compensation arrangements with a laboratory are prohibited from making a referral to that laboratory for laboratory tests reimbursable by Medicare, and also prohibits laboratories from submitting a claim for Medicare payments for laboratory tests referred by physicians who, personally or through a family member, have ownership interests in or compensation arrangements with the testing laboratory. The Foreign Corrupt Practices Act obligates companies whose securities are listed in the U.S. to comply with accounting provisions requiring the company to maintain books and records that accurately and fairly reflect all transactions of the corporation, including international subsidiaries, and to devise and maintain an adequate system of internal accounting controls for international operations. Research and Development The company's research and development expenses were $15.3 million for the year ended December 31, 2022. History The company was incorporated in the state of Delaware in 1999. It was formerly known as Capnia, Inc. and changed its name to Soleno Therapeutics, Inc. in 2017.