Rhythm Pharmaceuticals (NASDAQ:RYTM) Chief Financial Officer Hunter Smith outlined the company’s near-term regulatory catalyst, commercial preparation, and pipeline updates during a discussion at Guggenheim’s Emerging Outlook Biotech Conference with analyst Seamus Fernandez.
Focus on rare neuroendocrine disorders and the MC4R pathway
Smith said Rhythm is focused on treating rare neuroendocrine disorders by targeting the melanocortin-4 receptor (MC4R) pathway. The company’s marketed product, IMCIVREE (setmelanotide), is an MC4R agonist that Smith described as the “first-ever approved agonist of the MC4R pathway” shown to be safe and efficacious in patients.
Commercial performance in Bardet-Biedl syndrome and global footprint
Smith said Bardet-Biedl syndrome (BBS) is currently the primary driver of the company’s revenue growth. He noted the company is “three plus years into launch” for BBS and has launched globally, adding that the company is “approved, reimbursed, or we have patient access in 25 countries now.”
For the most recent quarter discussed, Smith cited approximately $57 million in sales, with an average of about 9% quarter-over-quarter growth over much of the prior year. He said this was backed by a 10% growth in reimbursed patients on therapy in Q4 and a 7% increase in the cumulative number of writers of BBS prescriptions.
He described the BBS population as dispersed and often identified in “pockets” rather than concentrated at specialty centers. Smith also provided an example of how the company frames the opportunity, discussing the potential to reach 1,000 U.S. patients on therapy over a five-to-six-year period and referencing a net price assumption of $300,000 per patient, which he said would imply a U.S.-only peak sales opportunity of about $300 million for BBS.
Hypothalamic obesity: March 20 PDUFA and launch preparation
Smith emphasized that the company’s most significant near-term milestone is a PDUFA date of March 20 for a fourth indication: hypothalamic obesity (HO). He said Rhythm already has some HO patients on treatment through early access programs in France and Italy.
He summarized results from a 60-week, 2-to-1 randomized, double-blind, placebo-controlled study (including titration), which read out in April of the prior year. According to Smith, patients on setmelanotide showed a 16.5% reduction in BMI, while placebo patients gained weight, resulting in a placebo-adjusted difference of about 19.8% at 52 weeks on the maintenance/full dose. He also cited responder rates of 80% achieving more than 5% BMI reduction and 60% achieving more than 10%, and said hunger and BMI reductions were consistent across age groups.
Smith also discussed a subgroup observation involving GLP-1 exposure, noting that patients with prior GLP-1 experience (but not on therapy during the study), as well as those on concomitant stable GLP-1 therapy, had higher average BMI reductions “more in the mid-20s” than patients on monotherapy.
On commercialization, Smith said Rhythm began building ahead of the HO data readout and expanded its U.S. sales force from 16 to 42, with the team trained and in the field as of October 1 of last year. He said the initial plan anticipated a December PDUFA, which was later extended to March.
To identify potential HO patients, Smith said the company uses claims data rather than diagnosis codes, noting there is no ICD-10 code for HO. He described a claims-based approach that looks for an index tumor event and surgery, hormonal insufficiency, obesity, and recent endocrinology visits. Based on this work, he said Rhythm targeted about 5,000 endocrinologists, with roughly 2,500 having three or more potential HO patients. Smith added that the company disclosed in November it had identified upwards of 2,000 suspected or diagnosed HO patients within tier one and tier two physician practices.
Launch considerations: education, access, reimbursement, and Medicare
Smith pointed to several factors that may influence how quickly identified HO patients initiate therapy, including the need for physician education and the practical challenges of endocrinology scheduling, which he said can delay follow-up visits needed to confirm diagnosis.
He also highlighted the time required for payer processes, such as scheduled pharmacy and therapeutics (P&T) committee meetings, which can affect the lag between prescriptions written and reimbursed starts.
In addition, Smith noted a statutory restriction affecting Medicare reimbursement for “weight loss therapies.” He said setmelanotide is currently classified solely as a weight loss therapy, limiting Medicare reimbursement, and suggested the HO population may include more age-eligible Medicare patients than BBS, potentially affecting the company’s free-drug percentage.
FDA timing update, Prader-Willi progress, and cash runway
Smith addressed the PDUFA delay, explaining it stemmed from a request for a supplemental analysis related to calculating BMI Z scores for patients under 18. Because of GDPR privacy constraints, he said patient birthdates are not known and were assumed to be June 30, prompting the FDA to request a reanalysis under a different birthday assumption (January 1). Smith said the reanalysis did not meaningfully change endpoints but constituted a “major amendment,” extending the review timeline.
On Prader-Willi syndrome (PWS), Smith outlined the rationale for MC4R pathway involvement, noting that loss of chromosome 15 includes disruption of MAGEL2, which is upstream of MC4R signaling. He discussed an interim look at a Phase 2 study using a higher dose (5 mg), describing results from a small number of patients with some showing improvements in BMI and HQ-CT, and noting other potential benefits such as reduced fat mass in certain patients.
Smith also discussed potential combination considerations with VICAD (extended-release diazoxide), saying the mechanisms are believed to be complementary and that, in the upcoming dataset, eight patients are expected to be on background VICAD therapy. He said the company expects to read out six-month Phase 2 setmelanotide data in PWS (17 of 18 patients, with one discontinuation) in the first half of the year and then plans to discuss a potential Phase 3 design with the FDA.
Rhythm also highlighted pipeline efforts to improve convenience and tolerability, including an oral small molecule MC4R agonist bivamelagon and a weekly injectable RM-718. Smith said RM-718 may be better suited to the PWS population and noted the company has started a Phase 1 multiple ascending dose cohort in PWS for RM-718, with enrollment and timeline updates expected later in the year.
On liquidity, Smith said the company exited Q3 with about $418 million in cash and that Rhythm has indicated at least 24 months of runway, describing this as a rolling comment.
About Rhythm Pharmaceuticals (NASDAQ:RYTM)
Rhythm Pharmaceuticals, Inc is a clinical‐stage biotechnology company dedicated to developing targeted therapies for rare genetic diseases of obesity and metabolic dysfunction. The company’s research focuses on the melanocortin‐4 receptor (MC4R) pathway, which plays a central role in regulating appetite, energy expenditure and body weight. Using proprietary peptide technology, Rhythm aims to provide precision treatments to patients with specific genetic variants that disrupt normal weight regulation.
The company’s lead investigational product, setmelanotide, is a selective MC4R agonist designed to restore signaling in patients with deficiencies in genes such as POMC, LEPR and PCSK1.
