SAN DIEGO, June 11, 2022 – Orphagen Pharmaceuticals, an early-stage biopharmaceutical company focused on developing and commercializing novel therapies for cancer and other serious diseases with significant unmet need, today announced that additional data from its preclinical program to develop OR-449 for the treatment of adrenocortical cancer (ACC) was presented at the 104th Annual Meeting of the Endocrine Society (ENDO 2022) being held in Atlanta from June 11 to 14. ACC is a rare endocrine malignancy frequently diagnosed at an advanced stage with very limited treatment options. OR-449 is in preclinical development for treatment of ACC with a first-in-human clinical trial targeted for early 2023.

OR-449 is a potent, selective, and orally bioavailable small molecule antagonist to steroidogenic factor-1 (SF-1 or NR5A1), a nuclear receptor and a transcription factor essential for the growth and development of the adrenal gland. SF-1 was recently described as a candidate “master transcription factor” in adult ACC.1 ACC tumors often secrete a “malignant” but variable pattern of steroids not normally found in the circulation. The preclinical findings reported show, first, that a malignant steroid profile is also secreted from two separate patient-derived ACC xenografts maintained in immunocompromised mice. Second, the secreted steroids from SW1939, derived from a pediatric ACC, were markedly regulated by treatment with OR-449. Similar steroid regulation in response to OR-449 treatment could occur in the clinic, facilitating selection of a treatment dose for a Phase 2 clinical trial.

Paul Crowe, Ph.D., presenting author and Vice President of Drug Discovery at Orphagen, stated, “We are once again excited to share preclinical data for the efficacy of OR-449 in ACC, this time in a novel preclinical model, the pediatric ACC xenograft, SW1939, developed by Peter Houghton and colleagues at U. T. Health Sciences Center in San Antonio. Not only does OR-449 inhibit the growth of this patient-derived xenograft, but it also regulates the levels of circulating adrenocortical tumor-derived steroids and steroid precursors. Circulating steroid secretion may provide a clinically relevant pharmacodynamic biomarker for OR-449 target engagement in ACC patients.”

Orphagen CEO, Scott Thacher, Ph.D., said, “This is a satisfying success story for Orphagen’s corporate strategy to find first-in-class small molecules for unexplored nuclear receptor targets with efficacy in translationally relevant animal models of disease. The biomarker findings are a secondary, but potentially highly valuable outcome of these preclinical studies. We’re grateful for the strong support we’ve received from leading clinical investigators in the ACC field during this preclinical work, and we look forward to working with them on clinical trials for OR-449. Our hope is to bring a new and valuable therapeutic option to ACC patients.”


Poster Presentation Information

Title: Downstream Targets of the Steroidogenic Factor-1 (SF-1) Antagonist OR-449 in PDX Models of ACC

Presenter: Paul D Crowe, PhD

Co-Authors: Ray Fox, PhD, Haiyan Tao, PhD, Neil Raheja, PhD, Richard J. Auchus, MD, PhD, Peter Houghton, PhD, Scott Thacher, PhD

Poster Session: PSUN355


1 Corces et al., Science. 2018; 362(6413); Reddy et al., Sci Adv. 2021; 7(48).


About Orphagen Pharmaceuticals

Orphagen unlocks the power of orphan nuclear receptors. Our scientists excel in discovery and development of small molecule ligands to these largely unexplored drug targets. Starting with a therapeutic area agnostic approach, we are exploring proprietary lead molecules with potential in autoimmune disease and oncology. Orphagen successfully partnered its first program for ROR-gamma antagonists with a mid-size pharmaceutical company ahead of all competitors in the field. Funding from its partnerships and other non-dilutive sources, including federal grants, has allowed Orphagen to advance its proprietary first-in-class drug discovery programs, including OR-449 for  adrenocortical cancer. For more info, visit



Company Contact: Scott Thacher, Ph.D., CEO, Orphagen,

Media Contact: Jessica Yingling, Ph.D., Little Dog Communications Inc.,,   +1.858.344.8091