SPAG8

PORTLAND, Ore.--( BUSINESS WIRE )-- Sparrow Pharmaceuticals, an emerging, clinical-stage biopharmaceutical company developing novel, targeted therapies to address unmet needs in both immunology and endocrinology, is collaborating with the University of Oxford and the University of Sheffield on DC-MACS, an investigator led, Phase 2 clinical study in the United Kingdom of clofutriben (SPI-62) for the treatment of autonomous cortisol secretion (ACS). ACS is a prevalent and serious condition caused by the overproduction of cortisol from a benign tumor of the adrenal gland. This study is being conducted with funding from the UK Research and Innovation Medical Research Council. Sparrow is supplying its lead product, clofutriben, and placebo. The study will be led by two distinguished researchers in the endocrinology field: University of Oxford Prof. Jeremy Tomlinson, PhD, a pioneering HSD-1 researcher who first described a patient with a Cushing’s tumor but no signs or symptoms of Cushing’s syndrome because of HSD-1 deficiency, and University of Sheffield Prof. John Newell-Price, PhD, the current President of the Endocrine Society. Professor Tomlinson is supported by the National Institute for Health and Care Research (NIHR) Oxford Biomedical Research Centre, and the study will be conducted jointly in the NIHR supported clinical research facilities in both Oxford and Sheffield. “In partnering with Sparrow for the DC-MACS trial, we hope to pioneer a completely novel intervention for this common, yet serious disease,” said Prof. Jeremy Tomlinson, PhD, University of Oxford. “If successful, this trial could provide patients with ACS with a treatment that could transform their health and quality of life.” “ACS today usually goes undiagnosed,” commented Prof. John Newell-Price, PhD, University of Sheffield. “This leaves many patients at risk of morbidity from their hypercortisolism, including cardiovascular disease and bone fractures, and even a higher risk of death. Hopefully, we can not only demonstrate a new potential treatment, but also raise awareness of this dangerous disease.” The objectives of the randomized, double-blind, placebo-controlled study are to evaluate the efficacy, safety, and pharmacological effects of clofutriben, a novel, highly potent, and selective HSD-1 inhibitor, for treating ACS. HSD-1, an intracellular enzyme, activates cortisol in target tissues in which cortisol excess is associated with morbidity including liver, adipose, muscle, and brain. This study will also evaluate endocrine markers such as insulin sensitivity, glucose disposal, and triglycerides during a hyperinsulinemic-euglycemic clamp, nighttime blood pressure, and bone biomarkers (osteocalcin, P1NP, CTX). Forty patients across 2 sites (Sheffield Teaching Hospitals NHS Foundation Trust and Oxford University Hospitals NHS Foundation Trust) will take part in the study. “Clofutriben substantially lowers intracellular cortisol, which can bind intracellular receptors and thereby cause the morbidity associated with ACS,” added David Katz, PhD, Chief Scientific Officer of Sparrow. “Clofutriben has potential to be the first targeted therapy for that common, serious, and currently underrecognized disease.” For more information about Sparrow Pharmaceuticals, visit the website at www.SparrowPharma.com . About Autonomous Cortisol Secretion Autonomous cortisol secretion (ACS) is caused by the overproduction of cortisol from a tumor of the adrenal gland. As patients with ACS lack the outward clinical features of Cushing’s, and their symptoms present as common, chronic conditions, it is often not diagnosed. Most patients with ACS are diagnosed when the tumor shows up on a scan for an unrelated health condition and the patient subsequently receives an adequate endocrine workup. As that occurs infrequently, patients with ACS are potentially exposed to excess circulating cortisol for long periods of time, leading them to face major health complications, significant healthcare costs, and increased risk of early death. The signs and symptoms of ACS include a wide range of mental and physical effects including diabetes, hypertension, bone fractures, and weight gain, as well as mood, cognition, and sleep disorders. There is currently no established drug treatment for this condition, and current practice (advocated by recent European guidelines) involves monitoring (for the development of complications), but not active treatment. About Sparrow Pharmaceuticals Sparrow Pharmaceuticals was founded to spare patients the ravages of steroids. Leveraging underappreciated scientific insights into glucocorticoid biology, the company is working to provide better treatment options for serious disorders of hypercortisolism, and to revolutionize the treatment of autoimmune and inflammatory conditions. Its lead product, clofutriben, is an oral, small molecule, novel therapeutic treatment designed to target the source of active intracellular glucocorticoids in key tissues.

Portland, Oregon, December 11, 2024 — Sparrow Pharmaceuticals an emerging, clinical-stage biopharmaceutical company developing novel, targeted therapies to address unmet needs in both immunology and endocrinology, is collaborating with the University of Oxford and the University of Sheffield on DC-MACS, an investigator led, Phase 2 clinical study in the United Kingdom of clofutriben (SPI-62) for the treatment of autonomous cortisol secretion (ACS). ACS is a prevalent and serious condition caused by the overproduction of cortisol from a benign tumor of the adrenal gland. This study is being conducted with funding from the UK Research and Innovation Medical Research Council. Sparrow is supplying its lead product, clofutriben, and placebo. The study will be led by two distinguished researchers in the endocrinology field: University of Oxford Prof. Jeremy Tomlinson, PhD, a pioneering HSD-1 researcher who first described a patient with a Cushing’s tumor but no signs or symptoms of Cushing’s syndrome because of HSD-1 deficiency, and University of Sheffield Prof. John Newell-Price, PhD, the current President of the Endocrine Society. Professor Tomlinson is supported by the National Institute for Health and Care Research (NIHR) Oxford Biomedical Research Centre, and the study will be conducted jointly in the NIHR supported clinical research facilities in both Oxford and Sheffield. “In partnering with Sparrow for the DC-MACS trial, we hope to pioneer a completely novel intervention for this common, yet serious disease,” said Prof. Jeremy Tomlinson, PhD, University of Oxford. “If successful, this trial could provide patients with ACS with a treatment that could transform their health and quality of life.” “ACS today usually goes undiagnosed,” commented Prof. John Newell-Price, PhD, University of Sheffield. “This leaves many patients at risk of morbidity from their hypercortisolism, including cardiovascular disease and bone fractures, and even a higher risk of death. Hopefully, we can not only demonstrate a new potential treatment, but also raise awareness of this dangerous disease.” The objectives of the randomized, double-blind, placebo-controlled study are to evaluate the efficacy, safety, and pharmacological effects of clofutriben, a novel, highly potent, and selective HSD-1 inhibitor, for treating ACS. HSD-1, an intracellular enzyme, activates cortisol in target tissues in which cortisol excess is associated with morbidity including liver, adipose, muscle, and brain. This study will also evaluate endocrine markers such as insulin sensitivity, glucose disposal, and triglycerides during a hyperinsulinemic-euglycemic clamp, nighttime blood pressure, and bone biomarkers (osteocalcin, P1NP, CTX). Forty patients across 2 sites (Sheffield Teaching Hospitals NHS Foundation Trust and Oxford University Hospitals NHS Foundation Trust) will take part in the study. “Clofutriben substantially lowers intracellular cortisol, which can bind intracellular receptors and thereby cause the morbidity associated with ACS,” added David Katz, PhD, Chief Scientific Officer of Sparrow. “Clofutriben has potential to be the first targeted therapy for that common, serious, and currently underrecognized disease.”

PORTLAND, Ore.--( BUSINESS WIRE )-- Sparrow Pharmaceuticals , a clinical-stage biopharmaceutical company that develops novel, targeted therapies to address unmet needs in both endocrinology and rheumatology, will present interim data from the ongoing Phase 2 trial of lead agent clofutriben, a potent and selective HSD-1 inhibitor, in combination with prednisolone for the treatment of polymyalgia rheumatica (PMR) at the American College of Rheumatology Convergence 2024 conference November 14–19 at the Walter E. Washington Convention Center in Washington, D.C. Sparrow also announced that the trial has been expanded with a fifth cohort based on encouraging results from the first four cohorts. The first abstract is titled “ Hypothalamic-Pituitary-Adrenal Axis Suppression by Prednisolone Reversed by the 11β-Hydroxysteroid Dehydrogenase Type 1 Inhibitor Clofutriben” . Key findings include that, in patients with polymyalgia rheumatica chronically treated with prednisolone, clofutriben increased morning ACTH and cortisol concentrations after 2 weeks of therapy, even with prednisolone dose increase. These data support a hypothesis that co-administration of HSD-1 inhibitors with glucocorticoids might mitigate risk of glucocorticoid-induced adrenal insufficiency. The second abstract is titled “ Clofutriben to Improve the Benefit-Risk Profile of Prednisolone in Patients with Polymyalgia Rheumatica” . The company found that in patients with PMR the combination of clofutriben and prednisolone 20 mg, compared to prednisolone 10 mg alone, showed an improved benefit-risk profile comprised of similar efficacy and less evidence of prednisolone toxicity. Based on the encouraging findings from the first four cohorts, the ongoing Phase 2 trial has been expanded to a fifth cohort. Clofutriben is a potent HSD-1 inhibitor that is in a Phase 2 clinical trial with prednisolone for polymyalgia rheumatica, a prevalent autoimmune disease that mainly affects people over 50. HSD-1 is an intracellular enzyme that activates glucocorticoids in target tissues in which glucocorticoid medicines are associated with morbidity including liver, adipose, muscle, and skin. SPI-47, a fixed-dose-combination of clofutriben and prednisolone, is in development. Additionally, clofutriben is in Phase 2 clinical trials for endogenous Cushing’s syndrome and autonomous cortisol secretion. To view the abstracts, visit the ACR Convergence website here . To learn more about Sparrow Pharmaceuticals and clofutriben visit www.sparrowpharma.com . About Sparrow Pharmaceuticals Sparrow Pharmaceuticals was founded to spare patients the ravages of steroids. Leveraging underappreciated scientific insights into glucocorticoid biology, the company is working to provide better treatment options for serious disorders of hypercortisolism, and to revolutionize the treatment of autoimmune and inflammatory conditions. Its lead product, clofutriben (SPI-62), is an oral, small molecule, novel therapeutic treatment designed to target a source of active intracellular glucocorticoids in key tissues.