FIRST-IN-CLASS PIPELINE

Pipeline Header
OR-449
OR-812
RORb

Pipeline

Starting with a therapeutic-area agnostic approach, we have pursued proprietary lead molecules with potential in oncology and autoimmune disease. We are unafraid of tackling the unknown and passionate about creating a first-in-class pipeline that will deliver for patients with significant unmet needs.

Partnerships are a key element of our continued success in advancing our programs. Orphagen successfully partnered its first program for ROR-gamma antagonists with a mid-sized 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 cancers such as adrenocortical cancer.

  • OR-449: Our most advanced program, soon to enter the clinic in oncology, is a first-in-class antagonist for the orphan nuclear receptor steroidogenic factor-1 (SF-1, NR5A1). One major indication is the rare and largely untreatable cancer of the adrenal gland, also known as adrenocortical cancer (ACC).
    • ACC is an aggressive cancer that includes both pediatric and adult populations. Metastatic patients have very limited options for effective treatment. SF-1, the target of OR-449, is universally expressed in ACC.
    • Promising expansion indications for OR-449 include subsets of head & neck and lung squamous cancers where its target SF-1 (NR5A1) is very highly elevated. OR-449 could be approved as a precision therapy for these patients.
    • The U.S. Food and Drug Administration (FDA) has granted OR-449 a Rare Pediatric Disease Designation (RPDD), meant to incentivize rapid development of OR-449 for the treatment of the pediatric form of adrenocortical ACC where SF-1 is somatically amplified.
  • OR-812: An antagonist of the retinoic acid receptor alpha (RARa) and a development candidate for inflammatory bowel disease (IBD) and other diseases of intestinal inflammation. Current IBD therapy blocks just a handful of potential therapeutic pathways. The small molecule OR-812 will offer a novel form of oral therapy with a differentiated mechanism of action.
  • RORβ antagonists: Promising therapeutic opportunities with preclinical pharmacology and/or genomic support include SCLC and certain leukemias. Our unique small molecule tools equip us to engage in collaborations to understand the pharmacological and therapeutic potential of this novel drug target.

Future grant funding for these programs includes:

  • A $10.2 M grant (pending raise of matching funds by Orphagen) from CPRIT, the Texas state cancer agency, to support IND filing and a Phase 1 clinical trial for OR-449 over three years.
  • A $1.7 M award in September 2024 from the National Institutes of Health to support further development of the OR-812 program for IBD.