We are a clinical-stage biopharmaceutical company focused on developing novel, small-molecule therapeutics to activate innate homeostatic pathways for the treatment of metabolic diseases. We target biological pathways associated with alleviating hunger that we believe have the potential to deliver transformative outcomes for patients. We have focused our efforts on developing selective compounds, targeting Bitter Taste Receptors (TAS2Rs) for hunger-associated conditions. Our initial compounds target TAS2Rs expressed in the gut lumen, which normally respond to the nutrients in food and participate in the gut-brain axis. Our research has shown that activating these receptors can induce secretion of endogenous signaling molecules, including cholecystokinin (CCK) and glucagon-like peptide-1 (GLP-1). Our wholly-owned lead product candidate, ARD-101 (denatonium acetate monohydrate), is an oral gut-restricted small-molecule agonist of certain TAS2Rs expressed in the gut lumen for which we have initiated a Phase 3 clinical trial for hyperphagia associated with Prader-Willi Syndrome (PWS). We also intend to evaluate ARD-101 in a Phase 2 clinical trial for hyperphagia associated with acquired hypothalamic obesity resultant from treatment of craniopharyngioma, including surgery or radiation (HO). In our completed Phase 2 clinical trial in subjects with hyperphagia associated with PWS, ARD-101 was shown to be well-tolerated and demonstrated clinical activity through a reduction in Hyperphagia Questionnaire for Clinical Trials (HQ-CT) score. We have aligned with the U.S. Food and Drug Administration (the FDA) on a protocol for a potentially pivotal Phase 3 clinical trial, which we initiated in December 2024, and we anticipate topline data will be available in early 2026. TAS2Rs are a family of 26 different nutrient-sensing G protein-coupled receptors (GPCRs) that are ubiquitously expressed among vertebrates. TAS2Rs are present in the oral cavity to convey bitter taste and are highly expressed in many other tissues throughout the body where they are key in regulating metabolic and inflammatory pathways. CCK has long been recognized as a promising pharmaceutical target because its release is triggered with food and helps suppress hunger, the feeling of discomfort that comes from a perception of not having eaten recently. We believe this suppression of hunger could be complementary to the suppression of appetite reported from patients on GLP-1 targeted treatment, which reduces the desirability of food. Previous approaches to directly agonize CCK receptors through exogenous molecules have been limited by safety concerns driven by systemic exposure, resulting in on-target, off-tissue toxicity, and in turn leading to adverse effects, such aspancreatitis. Besides our product candidates, we are not aware of any approved or other clinical-stage candidates targeting certain TAS2Rs. Our wholly-owned lead product candidate, ARD-101, is an oral gut-restricted small-molecule agonist of certain TAS2Rs expressed in the gut lumen for which we have initiated a Phase 3 clinical trial for hyperphagia associated with PWS. We also intend to evaluate ARD-101 in a Phase 2 clinical trial for hyperphagia associated with HO. ARD-101 has limited systemic absorption, which we believe reduces the potential for systemic toxicity and has contributed to ARD-101 being well-tolerated in our clinical trials to date. We have completed a Phase 1 clinical trial of ARD-101 in healthy volunteers and a Phase 2 clinical trial in subjects with hyperphagia associated with PWS. The Phase 2 clinical trial in hyperphagia associated with PWS evaluated two dosing regimens over 28 days followed by a 14-day withdrawal period. In the first part of the trial, 12 subjects completed the treatment period at a dose of 200 mg delivered orally twice daily (BID). These 12 subjects who completed treatment had no treatment-related adverse events and, of those subjects, the eight who had HQ-CT 9 scores saw an average decline in HQ-CT 9 score of approximately eight points at 28 days. In the second part of the trial, four subjects were dosed under a revised protocol: 400 mg BID for seven days, followed by 600 mg BID for seven days and ending with 800 mg BID for 14 days. The four subjects who completed the trial per protocol had only grade 1 treatment-related adverse events and showed a decrease in HQ-CT 9 of approximately eight points at 28 days. We have aligned with the FDA on a trial design for the Phase 3 clinical trial, which we refer to as the HERO (Hunger Elimination or Reduction Objective) trial, which we believe will be sufficient to support a new drug application (NDA) filing with the FDA. Clinical data published in the American Journal of Physiology in 1992 (Boosalis MG, Gemayel N, Lee A, Bray GA, Laine L, Cohen H. Cholecystokinin and satiety: effect of hypothalamic obesity and gastric bubble insertion. Am J Physiol. 1992;262(2 Pt 2):R241-4) suggests administration of CCK may significantly reduce food consumption in patients with hyperphagia associated with HO. We also intend to evaluate ARD-101 for the treatment of hyperphagia associated with HO. The hypothalamus is a region in the brain responsible for regulating fundamental biological processes such as temperature control, sleep cycles and feeding behavior. One consequence of a damaged hypothalamus is HO. This condition is most commonly caused by sequelae from the treatment of hypothalamic and pituitary tumors, which includes surgery and radiation. HO is a rare form of obesity affecting approximately 5,000-10,000 people in the United States. The anatomical and phenotypical presentations of both HO and PWS are similar in many ways, including impaired hypothalamic function, impaired neuronal pathways, altered neurotransmitter activity and hyperphagia. Additionally, both conditions do not currently have approved pharmacological interventions for the treatment of hyperphagia. This lack of sufficient therapeutic response underscores the distinction of these disorders from other forms of obesity, as PWS and HO are primarily driven by hunger signaling. Subject to discussion with the FDA, we plan to conduct a Phase 2 clinical trial for hyperphagia associated with HO, which we refer to as the HONOR (Hypothalamic Obesity Neutralized On TAS2R) trial, dosing for approximately four months. Our second TAS2R program, ARD-201, will be a fixed-dose combination of ARD-101 and a dipeptidyl peptidase IV (DPP-4) inhibitor, for the treatment of obesity and obesity-related conditions. DPP-4 inhibition is a well-established therapeutic target, with multiple approved drugs currently on the market, that acts to inhibit the degradation of incretin hormones, including GLP-1. Inhibiting DPP-4 allows endogenous incretin levels to increase throughout the body, which supports the potential for a synergistic effect with TAS2R agonism. Our preclinical studies showed that the combination has an additive effect on weight loss, resulting in greater improvement in weight loss when dosed in combination. The potential benefit was also supported by our preclinical studies that showed an additive benefit when combined with GLP-1 receptor agonists. We are developing ARD-201 with a goal of addressing some of the limitations of currently marketed GLP-1 therapies, which include weight regain post-withdrawal, poor gastrointestinal (GI) tolerance and loss of lean body mass. Data from our Phase 2a clinical trials of ARD-101 demonstrated reduction in hunger rating in the Control of Eating Questionnaire (CoEQ) in two distinct subject populations: (1) general obese subjects and (2) subjects who have refractory weight gain post-bariatric surgery. We plan to initiate a Phase 2 clinical trial, which we refer to as the EMPOWER (Exploratory Multi-arm Prevention Of WEight Regain) trial, to explore the efficacy of ARD-201. We are exploring the potential clinical applications for ARD-201 in obesity and obesity-related conditions and our future decisions will be informed by the results of the EMPOWER trial, which will involve a multi-arm design to explore ARD-101 in various combinations with other agents. ARD-101 and ARD-201 will require substantial additional development time and resources before we would be able to apply for or receive marketing approvals and begin generating revenue from product sales. We expect to continue to incur losses for the foreseeable future, and expect to be required to raise additional capital and plan to finance our cash needs through public or private equity or debt financings or other capital sources, including potential collaborations, licenses and other similar arrangements. Additionally, there is substantial competition for ARD-201, which we are developing for the treatment for obesity and obesity-related conditions, as there are a number of major pharmaceutical companies and independent biotechnology companies developing therapeutics for the treatment of obesity and obesity-related conditions, including Eli Lilly, Novo Nordisk, Roche, Pfizer, AstraZeneca, Boehringer Ingelheim, Amgen, Zealand Pharma, Viking Therapeutics, Altimmune, Terns Pharmaceuticals, Merck and Structure Therapeutics. We were incorporated in Delaware on May 17, 2017. Our principal executive offices are located at 4370 La Jolla Village Drive, Suite 1050, San Diego, CA. We have one wholly-owned subsidiary, Artisan Therapeutics, Inc., incorporated in Delaware in October 2024.
