# RHYTHM PHARMACEUTICALS, INC. (RYTM)

Informational only - not investment advice.

CIK: 0001649904
SIC: 2834 Pharmaceutical Preparations
SIC breadcrumb: [Manufacturing](/division/D/) > [Chemicals And Allied Products](/major-group/28/) > [SIC 2834 Pharmaceutical Preparations](/industry/2834/)
Latest 10-K filed: 2026-02-26
SEC page: https://www.sec.gov/edgar/browse/?CIK=1649904
Filing source: https://www.sec.gov/Archives/edgar/data/1649904/000162828026012399/rytm-20251231.htm

## At a glance

FY2025 · period end 2025-12-31 · filed 2026-02-26 · accession 0001628280-26-012399 · source: https://data.sec.gov/api/xbrl/companyfacts/CIK0001649904.json

| Metric | Value | FY | Provenance |
| --- | ---: | ---: | --- |
| Revenue | 189,757,000 USD | 2025 | verified |
| Net income | -196,539,000 USD | 2025 | verified |
| Assets | 480,196,000 USD | 2025 | verified |
| Free cash flow | -116,628,000 USD | 2025 | computed |
| Net margin | -103.57% | 2025 | computed |
| Operating margin | -101.19% | 2025 | computed |
| Revenue YoY | +45.83% | 2025 | computed |
| ROE | -141.32% | 2025 | computed |

Computed values are grepcent-computed from the verified facts above and may differ from ratios the company itself reports. Free cash flow = operating cash flow − capital expenditures. Net margin = net income ÷ revenue. Operating margin = operating income ÷ revenue. Revenue YoY = FY2025 revenue ÷ FY2024 revenue − 1 (consecutive fiscal years only). ROE = net income ÷ period-end stockholders' equity.

No market price, no rating, no forecast on this site. Not investment advice.

### Peer percentile fingerprint

| Ratio | RYTM | Peer median | Percentile | N |
| --- | ---: | ---: | ---: | ---: |
| Net margin | -103.6% | 1.0% | 8 | 107 |
| Operating margin | -101.2% | -1.3% | 14 | 100 |
| Revenue growth | 45.8% | 14.7% | 69 | 127 |
| FCF margin | -61.5% | -14.0% | 38 | 127 |
| ROE | -141.3% | -30.7% | 11 | 171 |
| ROA | -40.9% | -21.8% | 22 | 187 |
| Liabilities / equity | 1.51 | 0.38 | 74 | 173 |
| Current ratio | 4.41 | 4.89 | 47 | 188 |

Percentile = share of the N covered peers reporting that ratio whose value is lower (ties counted half); computed among grepcent-covered companies in SIC industry 2834 Pharmaceutical Preparations, not the whole market. A higher percentile means a higher value of the ratio, not a better company. Ratios with fewer than 8 reporting peers are omitted. Latest reported values per company; fiscal periods may differ. Descriptive arithmetic - not a score, rating, or ranking.

## Selected Fundamentals
| Metric | Value | Unit | FY | Filed |
| --- | ---: | --- | ---: | --- |
| Revenue | 189757000 | USD | 2025 | 2026-02-26 |
| Net income | -196539000 | USD | 2025 | 2026-02-26 |
| Assets | 480196000 | USD | 2025 | 2026-02-26 |

## Financials

Annual standardized facts from SEC companyfacts as of latest extracted filing date 2026-02-26. Source: https://data.sec.gov/api/xbrl/companyfacts/CIK0001649904.json. Derived margins, ratios, and free cash flow are computed from the extracted annual SEC facts.

| Metric | 2016 | 2017 | 2018 | 2019 | 2020 | 2021 | 2022 | 2023 | 2024 | 2025 |
| --- | ---: | ---: | ---: | ---: | ---: | ---: | ---: | ---: | ---: | ---: |
| Revenue |  |  |  |  |  | 3,154,000 | 23,638,000 | 77,428,000 | 130,126,000 | 189,757,000 |
| Net income |  | -33,709,000 | -74,064,000 | -140,729,000 | -133,996,000 | -69,612,000 | -181,119,000 | -184,678,000 | -260,602,000 | -196,539,000 |
| Operating income | -25,905,000 | -32,412,000 | -78,417,000 | -146,000,000 | -136,575,000 | -170,059,000 | -179,157,000 | -184,357,000 | -265,503,000 | -192,016,000 |
| Diluted EPS |  |  |  | -3.86 | -3.04 | -1.40 | -3.47 | -3.20 | -4.34 | -3.11 |
| Operating cash flow | -23,219,000 | -29,460,000 | -62,056,000 | -122,750,000 | -121,980,000 | -146,003,000 | -173,428,000 | -136,157,000 | -113,879,000 | -115,675,000 |
| Capital expenditures | 1,057,000 | 133,000 | 722,000 | 3,385,000 | 214,000 | 434,000 | 281,000 | 47,000 | 0.00 | 953,000 |
| Assets | 12,339,000 | 151,736,000 | 260,210,000 | 308,523,000 | 187,073,000 | 329,523,000 | 382,481,000 | 332,745,000 | 392,273,000 | 480,196,000 |
| Liabilities | 5,042,000 | 6,948,000 | 13,954,000 | 27,503,000 | 20,545,000 | 45,372,000 | 118,219,000 | 162,986,000 | 227,724,000 | 210,170,000 |
| Stockholders' equity | -32,703,000 | 144,788,000 | 246,256,000 | 281,020,000 | 166,528,000 | 284,151,000 | 264,262,000 | 169,759,000 | 21,729,000 | 139,069,000 |
| Cash and cash equivalents | 6,540,000 | 34,236,000 | 49,542,000 | 62,294,000 | 100,854,000 | 59,248,000 | 127,677,000 | 60,081,000 | 89,137,000 | 54,301,000 |
| Free cash flow | -24,276,000 | -29,593,000 | -62,778,000 | -126,135,000 | -122,194,000 | -146,437,000 | -173,709,000 | -136,204,000 | -113,879,000 | -116,628,000 |

### Ratios

ROE and ROA use period-end equity/assets. Liabilities / equity uses total liabilities divided by stockholders' equity. Current ratio uses current assets divided by current liabilities when both are reported.

| Metric | 2016 | 2017 | 2018 | 2019 | 2020 | 2021 | 2022 | 2023 | 2024 | 2025 |
| --- | ---: | ---: | ---: | ---: | ---: | ---: | ---: | ---: | ---: | ---: |
| Net margin |  |  |  |  |  |  |  |  |  | -103.57% |
| Operating margin |  |  |  |  |  |  |  |  |  | -101.19% |
| Return on equity |  | -23.28% | -30.08% | -50.08% | -80.46% | -24.50% | -68.54% | -108.79% |  | -141.32% |
| Return on assets |  | -22.22% | -28.46% | -45.61% | -71.63% | -21.13% | -47.35% | -55.50% | -66.43% | -40.93% |
| Liabilities / equity |  | 0.05 | 0.06 | 0.10 | 0.12 | 0.16 | 0.45 | 0.96 | 10.48 | 1.51 |
| Current ratio | 2.36 | 22.42 | 19.05 | 12.38 | 10.10 | 7.10 | 8.90 | 5.58 | 3.24 | 4.41 |

## As-reported value updates

No tracked differences above grepcent's stated thresholds and capped precision rule were found between the earliest XBRL-filed value and the value currently on file for the standardized annual metrics grepcent tracks.


## Quarterly

Quarterly standardized facts from SEC companyfacts as of latest extracted filing date 2026-08-04. Source: https://data.sec.gov/api/xbrl/companyfacts/CIK0001649904.json.

Flow metrics use discrete quarter-length periods from 10-Q/10-Q/A filings. Q4 revenue and net income are derived only when annual FY and nine-month YTD facts exist for the same fiscal year; derived Q4 values are labeled. EPS Q4 is not derived.

| Quarter | End date | Revenue | Net income | Diluted EPS | Method |
| --- | --- | ---: | ---: | ---: | --- |
| 2019-Q2 | 2019-06-30 |  | -42,796,000 |  | reported discrete quarter |
| 2019-Q3 | 2019-09-30 |  | -36,003,000 |  | reported discrete quarter |
| 2019-Q4 | 2019-12-31 |  | -32,956,000 |  | derived Q4 = FY annual - nine-month YTD |
| 2022-Q2 | 2022-06-30 |  |  | -0.89 | reported discrete quarter |
| 2022-Q3 | 2022-09-30 |  |  | -0.79 | reported discrete quarter |
| 2023-Q1 | 2023-03-31 |  |  | -0.92 | reported discrete quarter |
| 2023-Q2 | 2023-06-30 |  |  | -0.82 | reported discrete quarter |
| 2023-Q3 | 2023-09-30 |  |  | -0.76 | reported discrete quarter |
| 2024-Q2 | 2024-06-30 |  | -33,563,000 | -0.55 | reported discrete quarter |
| 2024-Q3 | 2024-09-30 | 33,251,000 | -44,970,000 | -0.73 | reported discrete quarter |
| 2024-Q4 | 2024-12-31 | 41,830,000 | -44,631,000 |  | derived Q4 = FY annual - nine-month YTD |
| 2025-Q1 | 2025-03-31 | 32,704,000 | -50,820,000 | -0.81 | reported discrete quarter |
| 2025-Q2 | 2025-06-30 | 48,502,000 | -47,981,000 | -0.75 | reported discrete quarter |
| 2025-Q3 | 2025-09-30 | 51,298,000 | -54,279,000 | -0.82 | reported discrete quarter |
| 2025-Q4 | 2025-12-31 | 57,253,000 | -48,837,000 |  | derived Q4 = FY annual - nine-month YTD |
| 2026-Q1 | 2026-03-31 | 60,112,000 | -56,743,000 | -0.83 | reported discrete quarter |
| 2026-Q2 | 2026-06-30 | 71,255,000 | -50,363,000 | -0.73 | reported discrete quarter |

## Filed narrative (10-K & 10-Q)

## Business

Verbatim Item 1 Business section from RYTM's latest 10-K: [/company/RYTM/business/](/company/RYTM/business/).

## Risk Factors

Verbatim Item 1A Risk Factors from RYTM's latest 10-K: [/company/RYTM/risk-factors/](/company/RYTM/risk-factors/).

## Latest quarter (10-Q)

Latest 10-Q source: https://www.sec.gov/Archives/edgar/data/1649904/000162828026052533/rytm-20260630.htm

Extracted structurally from real Item 2 body heading to real Item 3/4 boundary.
Confidence: high
Filing date: 2026-08-04
Report date: 2026-06-30

Item 2. Management's Discussion and Analysis of Financial Condition and Results of Operations

You should read the following discussion and analysis of our financial condition and results of operations together with our unaudited condensed consolidated financial statements and related notes appearing elsewhere in this Quarterly Report on Form 10-Q. In addition to historical information, some of the information contained in this discussion and analysis or set forth elsewhere in this Quarterly Report on Form 10-Q contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, and is subject to the “safe harbor” created by those sections. All statements other than statements of historical facts contained in this Quarterly Report on Form 10-Q, including without limitation statements regarding: the promise or potential of any of our products or product candidates; the marketing, commercialization, and sales of IMCIVREE (setmelanotide), including marketing approval in Japan and the timing thereof; the design, success, cost and timing of our product development activities and clinical trials for setmelanotide, RM-718, bivamelagon, and our other product candidates; our ability to obtain regulatory approval for setmelanotide in further indications, as well as for RM-718, bivamelagon, and our other product candidates; our financial performance, including our expectations regarding our existing cash, operating losses, expenses and sources of future financing; the sufficiency of our cash, cash equivalents and short-term investments to fund our operations; expected milestone payments and the timing thereof; our ability to hire and retain necessary personnel; patient enrollments and the timing thereof; the timing of announcements regarding results of clinical trials; our ability to protect our intellectual property; ongoing activities under and our ability to negotiate our collaboration and license agreements, if needed, and the impact of termination; our marketing, commercial sales, revenue generation, and cost of revenue; expectations surrounding our manufacturing arrangements; the impact of the current or future economic conditions on our business and operations and our future financial results; and other statements identified by words such as “anticipates,” “believes,” “could,” “estimates,” “expects,” “intends,” “may,” “might,” “likely,” “plans,” “potential,” “predicts,” “projects,” “seeks,” “should,” “target,” “will,” “would,” or similar expressions and the negatives of those terms are forward-looking statements. These forward-looking statements are neither promises nor guarantees of future performance, and are subject to a variety of known and unknown risks, uncertainties, and other important factors, many of which are beyond our control, and which could cause actual results to differ materially from those contemplated in such forward-looking statements. We discuss factors that we believe could cause or contribute to these differences below and elsewhere in this report, including but not limited to those set forth in Part II, Item 1A under the heading “Risk Factors” of this Quarterly Report on Form 10-Q. Except as may be required by law, we have no plans to update our forward-looking statements to reflect events or circumstances after the date of this Quarterly Report on Form 10-Q. We caution readers not to place undue reliance upon any such forward-looking statements, which speak only as of the date made.

Overview

We are a global, commercial-stage biopharmaceutical company dedicated to transforming the lives of patients living with rare neuroendocrine diseases. We are focused on advancing our melanocortin-4 receptor (MC4R) agonists, including our lead asset, IMCIVREE® (setmelanotide), as precision medicines designed to treat hyperphagia and severe obesity caused by MC4R pathway diseases. While obesity affects hundreds of millions of people worldwide, we are advancing therapies for a subset of individuals who have hyperphagia, a pathological, insatiable hunger and impaired satiety accompanied by persistent and abnormal food-seeking behaviors, decreased energy expenditure and severe obesity due to diseases such as acquired or congenital hypothalamic obesity (HO), Bardet-Biedl syndrome (BBS) or other diseases caused by impaired MC4R pathway signaling. The MC4R pathway is a neuroendocrine pathway in the brain that is responsible for regulating hunger, caloric intake and energy expenditure, which consequently affect body weight. IMCIVREE, an MC4R agonist for which we hold worldwide rights, is the first-ever therapy developed for patients with certain rare diseases that is approved or authorized in the United States, European Union (EU), United Kingdom, Canada and other countries and regions.

IMCIVREE is approved by the U.S. Food and Drug Administration (FDA) to reduce excess body weight and maintain weight reduction long term in adult and pediatric patients aged 4 years and older with acquired HO and in adult and pediatric patients aged 2 years and older with syndromic or monogenic obesity due to BBS or pro-opiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency as determined by genetic testing demonstrating variants in POMC, PCSK1, or LEPR genes that are interpreted as pathogenic, likely pathogenic, or of uncertain significance (VUS). The European Commission (EC) has authorized IMCIVREE for the treatment of obesity and the control of hunger in adults and children 4 years of age and above with acquired hypothalamic obesity due to hypothalamic injury or impairment, and for the treatment of obesity and the control of hunger associated with genetically confirmed BBS or loss-of-function biallelic POMC, including PCSK1, deficiency or biallelic LEPR deficiency in adults and children 2 years of age and above. The United Kingdom’s Medicines & Healthcare Products Regulatory Agency (MHRA) has authorized IMCIVREE for the treatment of obesity and the control of hunger associated with genetically confirmed BBS or loss-of-function biallelic POMC, including PCSK1, deficiency or biallelic LEPR

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deficiency in adults and children 2 years of age and above. In addition to the United States, we have achieved market access or named patient sales of IMCIVREE for BBS or POMC and LEPR deficiencies, or both, in more than 25 countries outside the United States, and we continue to collaborate with authorities to achieve access in additional markets.

IMCIVREE’s label expansion to treat patients living with acquired HO was approved by the U.S. FDA on March 19, 2026, and a similar expansion of its marketing authorization was approved by the European Commission on April 30, 2026, making it the first approved therapy in the United States and the first approved therapy in Europe for patients with this rare disease. These approvals were supported by the positive pivotal Phase 3 TRANSCEND trial of setmelanotide in 142 patients with acquired HO. The global study met its primary endpoint, with a statistically significant -18.4% placebo-adjusted reduction in body mass index (BMI). For the primary endpoint of mean BMI change from baseline, study participants on setmelanotide therapy (n=94) achieved a -15.8% reduction compared with a +2.6% increase among patients on placebo (n=48) at 52 weeks (p0.0001). Setmelanotide was generally well tolerated in the Phase 3 trial. The most common adverse events (affecting 20% of participants) were skin hyperpigmentation, nausea, vomiting and headache. In addition, on May 5, 2026, we announced that our Japanese New Drug Application (JNDA) for setmelanotide to treat acquired HO was accepted, validated and is now under review by Japan’s Pharmaceuticals and Medical Devices Agency (PMDA). We anticipate anticipate launch of IMCIVREE for acquired HO in Japan, pending a decision by Japan's Ministry of Health, Labour and Welfare (MHLW), by year-end 2026.

Acquired hypothalamic obesity is a rare form of obesity that occurs following damage to the hypothalamic region of the brain. This disease most frequently follows the growth or surgical removal of craniopharyngioma, astrocytoma or other rare brain tumors. Additional causes of injury may include traumatic brain injury, stroke, or inflammation. Patients experience accelerated weight gain, a reduction in energy expenditure, and hyperphagia (a chronic pathological condition characterized by insatiable hunger, impaired satiety, and persistent abnormal food-seeking behaviors) leading to accelerated onset of severe obesity. We estimate there are approximately 10,000 people living with hypothalamic obesity in the U.S., 5,000 to 8,000 people living with hypothalamic obesity in Japan, and approximately 10,000 people living with hypothalamic obesity in the E.U.

In addition to our commercial efforts and inclusive of late-stage development efforts, we are advancing what we believe is the most comprehensive clinical research and development program ever initiated in MC4R pathway diseases, with multiple ongoing and planned clinical trials. Our MC4R pathway program is designed to expand the total number of patients who we believe would benefit from setmelanotide therapy or advance one of our other drug candidates, including RM-718, which is designed to be a more selective MC4R agonist with weekly administration, and bivamelagon, an investigational oral small molecule MC4R agonist in Phase 2 clinical trials. As mentioned above, our Phase 3 trial of setmelanotide in patients with acquired HO met the primary and key secondary endpoints, and we have initiated an additional, independent substudy in patients with congenital hypothalamic obesity as part of that trial.

We are advancing our next-generation MC4R agonists in clinical trials. In July 2025, we announced bivamelagon achieved statistically significant and clinically meaningful BMI reductions at 14 weeks of treatment in a Phase 2 trial in patients with acquired HO. We have also completed enrollment in Part C of the Phase 1 trial evaluating the weekly RM-718 in patients with acquired hypothalamic obesity and announced preliminary, promising data on August 4, 2026.

We also are advancing MC4R agonists with the intention to improve the treatment landscape for patients living with Prader‑Willi syndrome (PWS), a rare, complex genetic neurodevelopmental disorder characterized by hyperphagia, severe obesity risk, and significant metabolic, cognitive, and behavioral complications. We estimate there are between 12,500 and 16,000 patients living with PWS in the United States and a similar number in Europe, based on updated internal prevalence estimates developed using a bottoms-up methodology analyzing incidence, age-specific survival and claims-based validation. Further, we estimate that 80% to 90% of PWS patients are living with hyperphagia and obesity, or approximately 8,500 – 12,750 patients. There are currently limited therapeutic options that effectively reduce the extreme hyperphagia and address low resting energy expenditure associated with PWS. Based on the central role of MC4R pathway dysfunction in PWS, we believe that targeting this biology represents a compelling therapeutic approach. On June 13, 2026, we announced positive preliminary data from a Phase 2 trial evaluating setmelanotide in patients with PWS that demonstrated treatment with setmelanotide was associated with improvements across multiple clinically relevant endpoints, including BMI, BMI-Z and measures for hyperphagia and anxiety. In addition to this ongoing trial of setmelanotide, we have begun enrolling patients in a Phase 2 trial evaluating RM-718 in PWS.

We continue to leverage what we believe is the largest known DNA database focused on obesity - with approximately 120,000 sequencing samples as of December 31, 2025 - to improve the un

[Excerpt truncated for page length; source filing is linked above.]

## Latest 10-K MD&A (excerpt)

Latest 10-K Item 7 source: https://www.sec.gov/Archives/edgar/data/1649904/000162828026012399/rytm-20251231.htm
Complete FY 2025 MD&A: /company/RYTM/mda/fy2025/

Extracted structurally from real Item 7 body heading to real Item 7A/8 boundary.
Confidence: high
Filing date: 2026-02-26
Report date: 2025-12-31

Item 7. Management's Discussion and Analysis of Financial Condition and Results of Operations

You should read the following discussion and analysis of our financial condition and results of operations together with our consolidated financial statements and related notes appearing elsewhere in this Annual Report. In addition to historical information, this discussion and analysis contains forward-looking statements that involve risks, uncertainties and assumptions. Our actual results may differ materially from those anticipated in these forward-looking statements as a result of certain factors. We discuss factors that we believe could cause or contribute to these differences below and elsewhere in this report, including those set forth under Item 1A. “Risk Factors” and under “Cautionary Note Regarding Forward-Looking Statements” in this Annual Report.

In this Item 7, we discuss the results of operations for the years ended December 31, 2025 and 2024 and comparisons of our cash flows for the year ended December 31, 2025 to the year ended December 31, 2024. Discussion and analysis of our 2024 fiscal year, as well as the year-over-year comparison of our 2024 financial performance to 2023, are located in Part II, Item 7 - Management’s Discussion and Analysis of Financial Condition and Results of Operations in our Annual Report on Form 10-K for the fiscal year ended December 31, 2024, filed with the SEC on February 28, 2025.

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Overview

We are a global, commercial-stage biopharmaceutical company dedicated to transforming the lives of patients living with rare neuroendocrine diseases. We are focused on advancing our melanocortin-4 receptor (MC4R) agonists, including our lead asset, IMCIVREE (setmelanotide), as precision medicines designed to treat hyperphagia and severe obesity caused by MC4R pathway diseases. While obesity affects hundreds of millions of people worldwide, we are advancing therapies for a subset of individuals who have hyperphagia, a pathological, insatiable hunger and impaired satiety accompanied by persistent and abnormal food-seeking behaviors, decreased energy expenditure and severe obesity due to diseases such as acquired or congenital hypothalamic obesity, Bardet-Biedl syndrome (BBS) or other diseases caused by impaired MC4R pathway signaling. The MC4R pathway is a neuro-endocrine pathway in the brain that is responsible for regulating hunger, caloric intake and energy expenditure, which consequently affect body weight. IMCIVREE, our most advanced MC4R agonist for which we hold worldwide rights, is the first-ever therapy that is marketed in the United States, European Union (EU), United Kingdom, Canada and several other countries and regions for certain rare MC4R pathway diseases, including BBS. We also are developing two earlier-stage investigational MC4R agonists, bivamelagon (formerly LB54640), an oral small molecule, and RM-718, designed for weekly subcutaneous administration. On February 26, 2026 we announced we completed a positive end-of-Phase-2 meeting with FDA regarding bivamelagon in acquired HO and disclosed open-label extension data from our Phase 2 trial that showed bivamelagon achieved persistent BMI reductions at six and nine months of therapy.

IMCIVREE is approved by the U.S. Food and Drug Administration (FDA) to reduce excess body weight and maintain weight reduction long term in adult and pediatric patients aged 2 years and older with syndromic or monogenic obesity due to BBS or proopiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency as determined by an FDA-approved test demonstrating variants in POMC, PCSK1, or LEPR genes that are interpreted as pathogenic, likely pathogenic, or of uncertain significance (VUS). The European Commission (EC) and the United Kingdom’s Medicines & Healthcare Products Regulatory Agency (MHRA) have authorized IMCIVREE for the treatment of obesity and the control of hunger associated with genetically confirmed BBS or loss-of-function biallelic POMC, including PCSK1, deficiency or biallelic LEPR deficiency in adults and children 2 years of age and above. Reviews of our regulatory submissions seeking approval and marketing authorization for setmelanotide as a treatment for acquired hypothalamic obesity are ongoing in the United States and Europe with an FDA-assigned Prescription Drug User Fee Act (PDUFA) goal date of March 20, 2026. We anticipate disclosing topline data from a 12-patient Japanese cohort of our Phase 3 trial evaluating setmelanotide for acquired hypothalamic obesity in March 2026, and pending positive data, completing a new drug application submission in Japan. Regulatory decisions in Europe and Japan are anticipated later in 2026 or 2027.

Following our disclosure in December 2025 of positive preliminary data from our ongoing, exploratory, open-label Phase 2 trial with setmelanotide in patients with PWS, we believe there is potential for an MC4R agonist to be a future treatment option for patients with PWS, a rare genetic disorder that results in a number of physical, mental and behavioral problems. A key feature of PWS is a constant sense of hunger that usually begins in early childhood. PWS is estimated to affect approximately 400,000 people worldwide and approximately 20,000 people in the United States. There are currently limited therapeutic options that effectively reduce the extreme hyperphagia and address low resting energy expenditure associated with PWS. Following the disclosure of these positive preliminary results in December 2025, we announced plans to further develop setmelanotide and RM-718 for PWS.

We are advancing what we believe is the most comprehensive clinical research and development program ever initiated in MC4R pathway diseases, with setmelanotide, bivamelagon and RM-718 in multiple ongoing and planned clinical trials. Our MC4R pathway program is designed to expand the total number of patients who we believe could benefit from setmelanotide therapy or from one of our new drug candidates. Our Phase 3 EMANATE trial, comprised of four independent substudies evaluating setmelanotide in genetically caused MC4R pathway diseases, is ongoing with topline data expected in March 2026. Following the completion of our Phase 2 DAYBREAK trial, we identified six genetically-defined cohorts that we believe merit further investigation for potential setmelanotide efficacy.

We are leveraging what we believe is the largest known DNA database focused on obesity - with approximately 120,000 sequencing samples as of December 31, 2025 - to improve the understanding, diagnosis and care of people living with severe obesity due to certain variants in genes associated with the MC4R pathway. Our sequencing-based epidemiology estimates show that each of these genetically-defined MC4R pathway deficiencies we are focused on are considered rare diseases, according to established definitions based on patient populations. Our epidemiology estimates are approximately 4,600 to 7,500 for U.S. patients in initial FDA-approved indications, including obesity due to BBS and biallelic POMC, PCSK1 or LEPR deficiencies. Our epidemiology estimates for the two more prevalent indications being studied in our Phase 3 EMANATE trial (SH2B1 and POMC/PCSK1) suggest that approximately 29,000 U.S. patients with one of these genetically driven obesities have the potential to respond well to setmelanotide. Similarly, our epidemiology

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estimates for patients with genetic indications who demonstrated an initial response in our Phase 2 DAYBREAK trial is approximately 65,300. All these patients face similar challenges to other patients with rare diseases, namely lack of awareness, resources, tests, tools and especially therapeutic options.

Since our inception, we have raised funds through the issuance of common and preferred equity, the sale of assets and a Revenue Interest Financing Agreement, or RIFA. We expect to continue to fund our operations through the sale of equity, debt financings or other sources. We have built our own marketing and commercial sales infrastructure in the United States and are in the process of building a similar infrastructure in several European markets and the United Kingdom. We may enter into collaborations with other parties for certain markets outside the United States. However, we may be unable to raise additional funds or enter into such other arrangements when needed on favorable terms, or at all. If we fail to raise capital or enter into such other arrangements as, and when, needed, we may have to significantly delay, scale back or discontinue the development or commercialization of setmelanotide.

As of December 31, 2025, we had an accumulated deficit of $1.4 billion. Our net losses were $196.5 million and $260.6 million for the years ended December 31, 2025 and 2024, respectively. We expect to continue to incur significant expenses and increasing operating losses over the foreseeable future. We expect our expenses will increase substantially in connection with our ongoing activities, as we:

•continue to conduct clinical trials for setmelanotide and our other product candidates;

•engage contract manufacturing organizations, or CMOs, for the manufacture of clinical and commercial-grade setmelanotide;

•seek regulatory approval for setmelanotide for future indications, and for our other product candidates;

•expand our clinical and financial operations and build a marketing and commercialization infrastructure;

•engage in the sales and marketing efforts necessary to support the continued commercial efforts of IMCIVREE globally;

•take into account the levels, timing and collection of revenue earned from sales of IMCIVREE and other products approved in the future, if any; and

•continue to operate as a public company.

As of December 31, 2025, our cash and cash equivalents and short-term investments were approximately $388.9 million. We expect that our cash and cash equivalents and short-term investments as of December 31, 2025, will enable us to fund our operations for at least 24 months.

Corporate Background

We are a Delaware corporation organized in February 2013 under the name Rhythm Metabolic, Inc., and as of October 2015, under the name Rhythm Pharmaceuticals, Inc.

Financial Operations Overview

Revenue

To date, we have generated approximately $422.5 million of revenue from product sales. Our lead product candidate, IMCIVREE, was approved by the FDA in November 2020 for chronic weight management in adult and pediatric patients six years of age and older with obesity due to POMC, PCSK1 or LEPR deficiency confirmed by genetic testing. IMCIVREE became commercially available in the United States in the first quarter of 2021. We recorded our first sales of IMCIVREE in the United States in March 2021 and we made our first sales in France in March 2022 under the paid early access program. IMCIVREE was approved by the FDA and the EC in adult and pediatric patients six years of age and older with obesity due to BBS in June and September 2022, respectively. Following these initial approvals, sales of IMCIVREE have grown, and we expect will continue to grow.

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Cost of sales

All of our inventory of IMCIVREE produced prior to FDA approval is available for commercial or clinical use. Most of the manufacturing costs have been recorded as research and development expenses in prior periods. We expect cost of sales to increase in 2026 as we continue to sell inventory that is produced after we began capitalizing manufacturing costs for IMCIVREE commercial inventory.

Research and development expenses

Research and development expenses consist primarily of costs incurred for our research activities, including our drug discovery and genetic sequencing efforts, and the clinical development of setmelanotide, which include:

•expenses incurred under agreements with thir

[Excerpt truncated for page length; the complete text is on the linked full-MD&A page.]

Read the full FY 2025 MD&A: /company/RYTM/mda/fy2025/
All MD&A years: /company/RYTM/mda/


## MD&A history

Prior-year 10-K MD&A spans are extracted from SEC filings with the same bounded parser used for the latest filing. Each year's full verbatim text is on its own sub-page.

- [FY 2024 MD&A](/company/RYTM/mda/fy2024/): filed 2025-02-28; accession 0001558370-25-001889 (https://www.sec.gov/Archives/edgar/data/1649904/000155837025001889/rytm-20241231x10k.htm)
- [FY 2023 MD&A](/company/RYTM/mda/fy2023/): filed 2024-02-29; accession 0001558370-24-002181 (https://www.sec.gov/Archives/edgar/data/1649904/000155837024002181/rytm-20231231x10k.htm)
- [FY 2022 MD&A](/company/RYTM/mda/fy2022/): filed 2023-03-01; accession 0001558370-23-002613 (https://www.sec.gov/Archives/edgar/data/1649904/000155837023002613/rytm-20221231x10k.htm)
- [FY 2021 MD&A](/company/RYTM/mda/fy2021/): filed 2022-03-01; accession 0001558370-22-002543 (https://www.sec.gov/Archives/edgar/data/1649904/000155837022002543/rytm-20211231x10k.htm)


## FDA-approved drug applications

Applications listed under this company's exact-matched sponsor name. Approved applications only.

No resolved FDA applications were found for this company under the exact-unique, approved-only publish rule.

Sponsor as listed in Drugs@FDA at retrieval (2026-08-07); FDA sponsor listings can lag ownership transfers.

This list covers FDA applications whose listed sponsor name maps to this company by an exact-unique match; applications listed under sponsor names not mapped to this company (subsidiaries, name variants, joint ventures) are absent.


## Macro cross-references

Indicators mapped to this company's SIC classification (industry 2834 Pharmaceutical Preparations) by grepcent's deterministic macro-sector crosswalk. A navigational mapping, not a statistical or causal claim.

- [INDPRO](/indicator/INDPRO/): Industrial Production: Total Index
- [TCU](/indicator/TCU/): Capacity Utilization: Total Index
- [PPIACO](/indicator/PPIACO/): Producer Price Index by Commodity: All Commodities
- [GDPC1](/indicator/GDPC1/): Real Gross Domestic Product
- [DGS10](/indicator/DGS10/): Market Yield on U.S. Treasury Securities at 10-Year Constant Maturity
- [FEDFUNDS](/indicator/FEDFUNDS/): Federal Funds Effective Rate
- [CES0500000003](/indicator/CES0500000003/): Average Hourly Earnings of All Employees, Total Private
- [PAYEMS](/indicator/PAYEMS/): All Employees, Total Nonfarm

Macro-to-micro threads including this sector: [Inflation (CPI / PCE / PPI)](/thread/inflation-cpi-pce-ppi/), [US labor market](/thread/us-labor-market/), [Growth & output](/thread/growth-output/), [Money & trade](/thread/money-trade/), [Government finances](/thread/government-finances/), [Sector employment](/thread/sector-employment/), [Industrial orders & inventories](/thread/industrial-orders/), [Trade & external](/thread/trade-external/).

All macro indicators: /indicators/


## For LLMs & downloads

Markdown twin: /company/RYTM.md · JSON record: /company/RYTM.json · verified financials: /company/RYTM/financials.json / /company/RYTM/financials.csv · machine TOC for the whole site: /llms.txt