Executive Summary

Q3 2025 net product revenue was $51.3M, up 6% QoQ and 54% YoY; U.S. revenue rose 19% QoQ to $38.2M while international fell 21% QoQ to $13.1M due to a one-time $3.2M France pricing adjustment and named-patient ordering variability .
EPS was a GAAP net loss of $0.82 per share vs $0.75 in Q2 and $0.73 in Q3 2024; cash, cash equivalents and short-term investments ended the quarter at $416.1M, implying ≥24 months runway .
Rhythm tightened/shifted 2025 OpEx guidance to Non-GAAP $295–$315M, with SG&A $145–$150M (raised) and R&D $150–$165M (upper bound lowered) ; prior guidance was Non-GAAP $285–$315M, SG&A $135–$145M, R&D $150–$170M .
Post-quarter, FDA extended the setmelanotide HO sNDA PDUFA date by three months to March 20, 2026 (major amendment limited to sensitivity analyses), a near-term stock overhang offset by growing U.S. BBS momentum and positive Canada reimbursement developments .

What Went Well and What Went Wrong

What Went Well

Strong U.S. commercial momentum: U.S. Q3 revenue reached $38.2M (74% of total), +19% QoQ, with a high single-digit percentage increase in reimbursed patients and broader prescriber engagement .
Commercial and payer readiness for HO: ~5,000 potential endocrinologists identified; 2,400 top-tier targets narrowed; >2,000 suspected/diagnosed HO patients profiled ahead of approval .
Balance sheet strength: $416.1M cash, cash equivalents and short-term investments supports ≥24 months of planned operations, enabling execution through HO decision and multiple data readouts .

Quote: “With the FDA’s PDUFA goal date on HO on December 20, a strong cash position and continued progress across our MC4R pathway pipeline, the Company is well positioned to deliver sustained, long-term growth.” — David Meeker, CEO .

What Went Wrong

EPS and net loss widened: GAAP EPS was $(0.82) vs $(0.75) in Q2; net loss attributable to common stockholders was $(54.3)M vs $(48.0)M in Q2, reflecting higher SG&A for HO launch readiness .
International headwinds: OUS revenue declined $3.4M QoQ and was negatively impacted by a $3.2M one-time France pricing charge; named-patient ordering variability also weighed on OUS revenue .
Regulatory timing risk: On Nov 7, FDA extended the HO PDUFA to March 20, 2026 to assess additional sensitivity analyses, delaying potential U.S. launch and creating near-term uncertainty .

Financial Results

Metric	Q3 2024	Q1 2025	Q2 2025	Q3 2025
Revenue ($USD Millions)	$33.251	$37.718	$48.502	$51.298
GAAP EPS ($USD)	$(0.73)	$(0.81)	$(0.75)	$(0.82)
Net Loss Attrib. to Common ($USD Millions)	$(44.970)	$(50.820)	$(47.981)	$(54.279)
Cost of Sales ($USD Millions)	$3.828	$3.648	$5.543	$5.499

Segment revenue breakdown:

Segment Revenue	Q1 2025	Q2 2025	Q3 2025
U.S. ($USD Millions)	$24.5	$32.0	$38.2
International ($USD Millions)	$13.2	$16.5	$13.1

KPIs and operating drivers:

KPI	Q2 2025	Q3 2025
Global reimbursed patients growth (QoQ)	—	~10% increase
U.S. gross-to-net	—	84%
Cost of goods sold (% of product revenue)	—	10.7%
Specialty pharmacy inventory days on hand	~10 days EoQ	~16 days EoQ; $2.5M sequential variance
One-time France pricing charge	—	$3.2M (of which ~$0.6M in Q3)

Guidance Changes

Metric	Period	Previous Guidance	Current Guidance	Change
Non-GAAP Operating Expenses ($USD Millions)	FY 2025	$285–$315	$295–$315	Raised (midpoint)
SG&A (GAAP, $USD Millions)	FY 2025	$135–$145	$145–$150	Raised
R&D (GAAP, $USD Millions)	FY 2025	$150–$170	$150–$165	Lowered upper bound
Cash runway	—	≥24 months (incl. July offering)	≥24 months (as of 9/30/25)	Maintained

Earnings Call Themes & Trends

Topic	Previous Mentions (Q1 & Q2 2025)	Current Period (Q3 2025)	Trend
HO regulatory path	TRANSCEND met primary endpoint; sNDA/EMA filings planned Q3	FDA accepted sNDA; later extended PDUFA to Mar 20, 2026 (post-quarter)	On track → Timing extended
Bivamelagon next-gen MC4R	Phase 2 met primary endpoint with robust BMI reductions	Phase 3 HO design likely double-blind RCT; endpoint BMI% change; regulators feedback 1Q26E	Advancing toward Phase 3
PWS program	Phase 2 setmelanotide open-label trial initiated	Preliminary results targeted by year-end; success judged by BMI% change; cautious 50/50 expectation	Readout imminent
U.S. commercial execution	Q2 revenue up 29% QoQ; expanding prescribers	U.S. revenue +19% QoQ; prescribers +7% QoQ; >2,000 HO patients identified	Strengthening
International access	Early access & named-patient selling; European submission planned	France pricing finalized; OUS variability; EU HO submission validated; Japan build-out	Foundational progress
Payer/reimbursement	BBS payer education; policy precedents	HO payer engagement via pre-approval exchange; ability to secure reimbursement even pre-policy	Positive tone

Management Commentary

“Rhythm delivered continued momentum during the third quarter… With the FDA’s PDUFA goal date on HO on December 20, a strong cash position and continued progress across our MC4R pathway pipeline, the Company is well positioned to deliver sustained, long-term growth.” — David Meeker, CEO .
“Global revenue for the third quarter was $51.3 million, a sequential 6% increase… Approximately $3.7 million of the quarter-over-quarter increase… was driven by an increase in InSibiri dispensed to patients.” — Hunter Smith, CFO .
“We analyzed claims data… identify ~5,000 endocrinologists… narrowed to 2,400 top-tier targets… profiling activity identified >2,000 potential HO patients.” — Jennifer Lee, EVP North America .

Q&A Highlights

Bivamelagon Phase 3 HO design: Expect double-blind RCT with BMI% change primary endpoint; regulators likely to want ~1 year of data; FDA feedback targeted in 1Q next year .
PWS Phase 2 readout/timing: Open-label, small cohort; go/no-go could follow preliminary data, but company may wait for fuller dataset; success judged by BMI change, not hyperphagia-only label .
HO reimbursement cadence and gross-to-net: Leveraging BBS precedents; can secure reimbursement pre-formal policy; GTN mix will depend on Medicaid share; Medicare access would be favorable .
Launch curve expectations: HO patients distributed across community endocrinology (vs bolus-like specialized centers in PWS), implying a steadier ramp; education and diagnosis gating early uptake .
International HO: EU CHMP decision targeted 2H 2026; country-by-country reimbursement efforts; Japan launches potentially in 2027 post ~9-month review .

Estimates Context

How results compared to Wall Street consensus (S&P Global):

Metric	Q1 2025	Q2 2025	Q3 2025
Revenue Consensus Mean ($USD)	$40.1606M*	$43.6374M*	$50.7079M*
Revenue Actual ($USD)	$32.704M	$48.502M	$51.298M
Primary EPS Consensus Mean ($USD)	$(0.694)*	$(0.6625)*	$(0.7167)*
GAAP EPS Actual ($USD)	$(0.81)	$(0.75)	$(0.82)
EBITDA Consensus Mean ($USD)	—	—	$(47.802M)*
EBITDA Actual ($USD)	$(46.621M)*	$(44.917M)*	$(52.349M)*

Values retrieved from S&P Global.*

Q3 2025: Revenue modest beat vs consensus; EPS missed as SG&A increased for HO launch readiness; EBITDA more negative than consensus, reflecting higher OpEx and France pricing charge .

Key Takeaways for Investors

U.S. BBS growth resilient and broadening (reimbursed patients and prescribers rising), supporting baseline revenue while HO timing extends to March 2026; near-term trading likely sensitive to regulatory updates and HO payer/access signals .
Q3 revenue beat vs consensus, but EPS miss and OUS headwinds (France charge, ordering variability) highlight ongoing mix and pricing dynamics; monitor OUS normalization and named-patient cadence .
2025 OpEx guidance shift toward SG&A underscores readiness to commercialize HO; expect marketing and access spend to remain elevated into potential launch .
Cash runway (≥24 months) provides cushion to navigate regulatory extension and deliver multiple catalysts (PWS Phase 2 preliminary data, EU HO path, Japan cohort, EMANATE trial topline) .
Watch payer policy evolution and Medicare access prospects; management highlighted ability to gain reimbursement pre-policy, which could smooth early HO adoption .
International expansion remains strategic: France pricing agreement finalized; EU HO submission validated; Japan team in place—multi-year ramp but meaningful addressable populations .
Stock catalysts: FDA’s major amendment outcome and HO label specifics, PWS preliminary data (BMI% change), and continued U.S. BBS prescriber/patient growth trajectory.

Appendix: Other Q3 2025 Press Releases of Note

FDA extension of HO sNDA PDUFA to Mar 20, 2026; additional sensitivity analyses requested, no new data or safety/manufacturing issues .
Canada public reimbursement agreements for IMCIVREE in multiple provinces and NIHB for eligible BBS patients (supports international access narrative) .
ObesityWeek 2025: Rhythm presenting four setmelanotide-related abstracts spanning HO efficacy with GLP-1 background, cardiometabolic outcomes, patient/caregiver experiences, and early-onset obesity genetics .

RHYTHM PHARMACEUTICALS, INC. (RYTM)·Q3 2025 Earnings Summary