Rhythm Pharmaceuticals

Tackling rare and ultrarare diseases

CEO: Keith Gottesdiener
Based: Boston, MA
Founded: 2008
Clinical focus: Rare forms of obesity

The scoop: Obesity is a major problem in the Western world, and you’d be forgiven for thinking it was a singular condition. But subpopulations of patients have highly rare genetic disorders that make them gain massive amounts of weight from a very young age, spurred on by an insatiable hunger. No treatments are currently able to help these children and young adults, but Rhythm is hoping its two candidates for pro-opiomelanocortin (POMC) deficiency obesity and Prader-Willi syndrome (PWS) will change all that.

What makes Rhythm Fierce: The biotech posted some impressive data in the summer for its POMC deficiency obesity candidate setmelanotide, which showed in a Phase II study that it could cut weight down by 3.75 to 4.4 lbs per week, for 42 weeks, in two patients in their 20s who both weighed around 340 lbs before starting the study. Only two patients were in this trial, but with only 50 documented cases of the condition, this still represents a relatively large portion of the patient population.

The FDA breakthrough-labeled drug goes after the MC4 pathway by working as a melanocortin 4 receptor (MC4R) agonist. This pathway has been studied by others for years, but this is the first to go after POMC deficiency obesity. There is also an ongoing midstage trial on weight and eating behaviors in patients with Prader-Willi syndrome--also a rare genetic disorder that causes life-threatening obesity.

CEO Dr. Keith Gottesdiener, a Merck ($MRK) R&D veteran who’s been at the helm of Rhythm since 2011, tells FierceBiotech: “This hunger that patients feel with these disorders is so strong, it cannot be stopped with anything currently on the market. It is not a case of simply overeating or being lazy or whatever, it’s a genetically defined problem that we believe we can fix with setmelanotide. It’s like if I asked you to fast for 24 hours or 48 hours: how you feel then is how they feel every second of every day, regardless of what they’ve eaten. The ability to impact that, as we have done in our latest trial for POMC, is extraordinary.

“What we’re doing is understanding more deeply the complex biology behind these disorders and using a very targeted approach with these specific gene defects in this specific pathway (MC4). So what this means is that this drug is not just for POMC but for any rare, genetic obesity condition, such as PWS and more recently in leptin receptor deficiency--a condition that causes severe obesity beginning in the first few months of life--as well as three or four other similar disorders.

“We think we can really change the paradigm on these types of obesity, and start to show it as a variety of diseases, and where we can place exactly where we can have the biggest impact by fixing and/or replacing the specific defects that exist in this pathway and serve as a replacement therapy.”

They are not looking to go deeper into the broader obesity category, and Gottesdiener says they will remain a rare-disease biotech. “We want to focus on these areas where there is a huge unmet need, and that isn’t what we see in the ‘general’ obesity market, but rather in the kinds of areas where we know we can do something special.”

Bart Henderson, president and founder of the biotech, said he helped found the company around investing in peptides and metabolic disorders. “But then we licensed the drug from Ipsen, who’s been very prolific in peptides discovery and focused on endocrine targets. The focus of our approach was the MC4 pathway, which is a critical pathway for regulating weight. But let’s be honest, pharma had failed, broadly, in researching this because they had invested in small molecules. So the first part of our strategy was betting on peptides that could retain the inherent specificity of the native hormone.

“The second was our preclinical studies for the compound in primates. This was different to what pharma had done that had moved more quickly from rats to man. So we spent a lot of time testing this drug in obese primates. That helped us build the foundation of our clinical program and was key to what we are now seeing in the lab.”

The focus now is to move into registration-enabling studies for setmelanotide in POMC obesity, and also to build out its own sales and marketing strategy in the U.S. and other markets if its drug gains approval. “As we get proof of concept in each of these rare disorders, we’ll move very rapidly to file with the FDA, EMA and others,” Gottesdiener said. “So our hope is that there will be a continual stream of these orphan and ultraorphan obesity indications.”

Investors: Pfizer, Ipsen, Third Rock, Deerfield, NEA, Orbimed, NEA, MPM (plus two undisclosed investors)

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Rhythm Pharmaceuticals