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Investor and Analyst Day June 3, 2025 1 Exhibit 99.1
20 Evolving Understanding of Cortisol, Cortisol Regulation, and Cushing's Syndrome Eliza B. Geer, MD
21 Understanding Cushing's Syndrome Cortisol excess due to a tumor producing ACTH or cortisol CORTISOL Adrenal steroid hormone Production & secretion regulated by HPA Axis Homeostasis: mediates circadian rhythm & stress response Metabolism: converts protein to glucose Immune system: reduces inflammation Exposure to excess cortisol over time causes multiple adverse clinical consequences HPA axis: hypothalamic-pituitary-adrenal axis; CRH: Corticotropin-releasing hormone; ACTH: Adrenocorticotropic hormone; DHEA: Dehydroepiandrosterone Thau L et al. Physiology, Cortisol (https://www.ncbi.nlm.nih.gov/books/NBK538239/). 2023 Aug 28. In: Stat Pearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan. Accessed 5/5/2025.
22 Unique Presentations of Cushing's Syndrome ADRENAL CUSHING'S SYNDROME 13-YEAR DIAGNOSTIC JOURNEY ADRENAL CUSHING'S SYNDROME 2-YEAR DIAGNOSTIC JOURNEY; FOLLOWING IDENTIFICATION OF TUMORS ON KIDNEY SCAN Actual Patient Actual Patient
23 Clinical Complications Cushing's Syndrome Reproductive/Sexual Nervous Endocrine Cardiovascular Musculoskeletal Neuropsychiatric disorders Arterial atherosclerosis and vascular disease Diabetes Osteoporosis (femoral neck) Myopathy Cardiac disease Impaired reproductive/sexual function Dermatologic manifestations Visceral obesity Infections Osteoporosis (spine) and vertebral fractures Adapted from: Pivonello R, et al. Lancet Diabetes Endocrinol 2016;4(7):611-629.
24 Role of Guidelines in Advancing Clinical Considerations in Testing & Treatment 2008 Endocrine Society Guidelines1 Testing: Widespread testing not necessary beyond: Multiple and progressive features predictive of Cushing's syndrome Adrenal incidentalomas compatible with adenoma 2015 Endocrine Society Guidelines2 Treatment Goals: Normalize cortisol levels Eliminate signs and symptoms of Cushing's Syndrome Treat comorbidities associated with hypercortisolism 2021 Pituitary Society Consensus3 Testing: Clinical judgement and suspicion for Cushing's syndrome very important Medical therapy goals: Individualized therapy based on clinical & severity of hypercortisolism Normalize cortisol levels 1. Nieman LK et al. J Clin Endocrinol Metab. May 2008, 93(5):1526-1540 2. Nieman LK, et al. J Clin Endocrinol Metab. 2015;100(8):2807-2831; 3. Fleseriu M et al. The Lancet Diabetes & Endocrinology, Volume 9, Issue 12, 847 - 875.
25 Clinical Approaches to Normalizing Cortisol Levels Clinical Pathway Following Diagnosis Confirmation Surgery Radiation Medical Therapy 1. Hinojosa-Amaya JM, et al. Drugs. 2019;79(9):935-956.
26 Clinical Approaches to Normalizing Cortisol Levels 1. Hinojosa-Amaya JM, et al. Drugs. 2019;79(9):935-956. 2. Fleseriu M, et al. Expert Rev Endocrinol Metab. 2021;16(4):159-174.
27 Goal: Optimize Patient Outcomes & Improve Quality of Life Continued education needed to address clinical diagnosis gaps Priority is to normalize cortisol levels and address comorbidities Chronic hypercortisolism can lead to multisystem comorbidities Continued Efforts in Advancing Research, Medical Innovations, and Guidelines are Needed to Address Cushing's Syndrome & Holistic Burden of Illness Page-Wilson G, et al. Endocrinol Diab Metab. 2024; 7:e464. doi:10.1002/edm2.464