Our Pipeline

We are studying rare genetic disorders of obesity.
“We know that all obesity is not the same. There are many genes involved in the MC4R pathway associated with severe obesity and insatiable hunger, and we are continuing efforts to explore the effect of these genes on obesity as we uncover the potential of setmelanotide or other products for the treatment of rare genetic disorders of obesity”

– Murray Stewart, MD, Chief Medical Officer

Rhythm’s Pipeline

Setmelanotide is an investigational, melanocortin-4 receptor (MC4R) agonist in late-stage clinical development for the treatment of rare genetic disorders of obesity by directly addressing the underlying cause of obesities driven by genetic deficits in the MC4R pathway.
Disorder Early-Stage Development Phase 2 Phase 3 Registration U.S./EU PHASE
Setmelanotide Pivotal Studies

Obesity due to POMC/PCSK1 deficiency

REGISTRATION U.S./EU

Obesity due to LEPR deficiency

REGISTRATION U.S./EU

Bardet-Biedl syndrome

PHASE 3

Alström syndrome

PHASE 3
Setmelanotide Basket Study

Obesity due to POMC, PCSK1 or LEPR heterozygous deficiency

PHASE 2

SRC1 deficiency obesity

PHASE 2

SH2B1 deficiency obesity

PHASE 2

MC4R deficiency obesity

PHASE 2

Smith-Magenis syndrome

PHASE 2

Additional disorders*

PHASE 2
RM-853

Preclinical

Early Stage

The FDA has granted Breakthrough Therapy Designation to setmelanotide for the treatment of obesity associated with genetic defects upstream of the MC4 receptor in the leptin-melanocortin pathway, which includes Bardet-Biedl syndrome (BBS), and Alström syndrome. Also, the FDA has granted Orphan Drug Designation for setmelanotide for the treatment of obesity due to POMC or LEPR deficiency, BBS and Alström syndrome. The European Medicines Agency (EMA) has also granted PRIority MEdicines (PRIME) designation for setmelanotide for the treatment of obesity and the control of hunger associated with deficiency disorders of the MC4R pathway. The European Commission has adopted the EMA’s Committee for Orphan Medicinal Products’ positive opinion and designated setmelanotide as an orphan medicinal product for the treatment of patients with obesity due to POMC or LEPR deficiency, BBS and Alström syndrome.

Rhythm’s Marketing Authorization Application for setmelanotide to treat people living with obesity due to POMC, PCSK1 or LEPR deficiency is currently under review by the EMA.

RM-853 (preclinical)

RM-853 is a pre-clinical ghrelin O-acyltransferase (GOAT) inhibitor
RM-853 is a potent, oral ghrelin o-acyltransferase inhibitor currently in pre-clinical development. We are assessing the safety and therapeutic potential of RM-853 as well as opportunities to identify populations that may benefit from a mechanistically rationalized therapeutic approach. RM-853 is designed to block GOAT, the key enzyme involved in the production of the active form of ghrelin, with the potential effect of lowering active ghrelin levels.

For more information about Rhythm clinical trials, please visit clinicaltrials.gov

For information about access to investigational therapeutics outside of clinical trials, please visit Policy on Expanded Access to Investigational Drugs

* Rhythm is currently assessing setmelanotide in additional disorders, including POMC epigenetic diseases, LEP and CPE deficiency obesity, as part of investigator-initiated protocols within the basket study. Given the recent discovery of these rare disorders of the MC4R pathway, there is currently limited or no genetic sequencing or epidemiology data that defines prevalence. However, Rhythm believes that these are rare disorders which may be setmelanotide-responsive.