Retinoic Acid-related Orphan Receptors Market: Competitive Landscape, Pipeline, and Market Analysis 2024

Retinoic acid-related Orphan Receptors (RORs) are a family of orphan nuclear receptors that play a role in numerous physiological processes, including circadian rhythm and bone metabolism. The RAR-related orphan receptors (RORs) are members of the nuclear receptor family of intracellular transcription factors. There are three forms of ROR, ROR-α, β, and γ, and each is encoded by a separate gene RORA, RORB, and RORC respectively. They bind to DNA elements called ROR response elements (RORE). RORs are involved in the maintenance of the circadian rhythm, development of the cerebellum and lymph nodes, lipid metabolism, immune response, and maintenance of bone. The mechanism of action (MOA) of ROR is that work by it seems that the RORs are activated by oxysterols, internal ligands of RORs. A number of other natural substances have also been reported to bind to the RORs. These include all-trans retinoic acid binds with high affinity to ROR-β and -γ but not ROR-α. The RORs may function as lipid sensors and hence may play a role in the regulation of lipid metabolism.

Some synthetic ROR-γ inverse agonists are in various stages of drug development for the treatment of inflammatory diseases. ROR-γ agonists have also been proposed for use as immune-oncology agents to activate the immune system to treat cancer. For instance, according to the Centers For Disease Control and Prevention 2021, about 1 in 4 US adults (23.7%) or about 58.5 million people have been diagnosed with arthritis. Arthritis is more common in women (23.5%) compared with men (18.1%). Moreover, the development of novel molecules by many market players is coming up to overcome challenges in therapy. For instance, Boehringer Ingelheim’s (BI 730357) for the treatment of psoriasis and spondylitis is under the various stages of clinical studies.

Retinoic Acid-related Orphan Receptors Market Key Developments:

• In June 2021, Boston Pharma in global collaboration with Xenter started clinical development of XT-0528, an inverse agonist for the indication of psoriasis and autoimmune disorder.

Drugs under the Pipeline for ROR:

• BI 730357
• Zilovertamab (UC-961)
• XT-0528
• AZD0284
• GNC-035
• Cedirogant (ABBV-157)
• AUR-101
• GSK2981278
• Izumerogant (IMU-935)
• BMS-986251
• EMB-07
• HER2
• Mesothelin
• NVG-111
• PF-06763809

Clinical Activity and Developments of ROR:

Till June 2023, more than 14 companies having approximately 33 molecules targeting the many cancers , skin disorders and autoimmune diseases. For these molecules, more than 49 clinical trials are being conducted and majority are in phase-2, phase-3 clinical trials by the players across the globe. For instance,

• In January 2021, Boehringer Ingelheim completed the phase 1 study of BI 730357, open-label, non-randomized, 2-period fixed-sequence trial for finding effect of BI 730357 on the pharmacokinetics of Rosuvastatin, Digoxin, Metformin and Furosemide given as a cocktail in healthy subjects.