Rhythm Pharmaceuticals Reports Fourth Quarter and Full Year 2021 Financial Results -- Preparations continue for U.S. commercial launch in June 2022 in BBS and Alstr m syndrome, pending FDA approval -- -- First commercial

Rhythm Pharmaceuticals Reports Fourth Quarter

and Full Year 2021 Financial Results

-- Preparations continue for U.S. commercial

launch in June 2022 in BBS and Alstr m syndrome, pending FDA approval --

sales of IMCIVREE in Germany and France expected in 2Q2022 -

-- Enrollment completed in Phase 2 trial evaluating

setmelanotide in patients with hypothalamic obesity --

-- IMCIVREE fourth quarter sales of $1.8M

and 2021 sales of $3.2M -

-- Management to host conference call today

BOSTON, March 1, 2022 - Rhythm

Pharmaceuticals, Inc. (Nasdaq: RYTM), a commercial-stage biopharmaceutical company committed to transforming the care of people living

with rare genetic diseases of obesity, today reported financial results and provided a business update for the fourth quarter and full

year ended December 31, 2021.

"2021 was a pivotal year for Rhythm, with tremendous progress

across clinical development and regulatory efforts globally, as we deliver on our promise to transform the treatment of rare genetic diseases

of obesity," said David Meeker, M.D., Chair, President and Chief Executive Officer of Rhythm. "We first made IMCIVREE

(setmelanotide) commercially available last year to people living with obesity due to POMC, PCSK1 or LEPR deficiency, and now we look

forward to our first commercial sales in Europe in the second quarter of this year. With a potential U.S. approval for IMCIVREE in BBS

and Alstr m syndrome now set for June, our commercial team continues to drive patient identification and pre-launch activities as

we prepare to deliver IMCIVREE to the waiting BBS and Alstr m syndrome communities at approval."

Dr. Meeker continued, "We also significantly expanded our clinical

development efforts with the Phase 3 EMANATE and Phase 2 DAYBREAK trials, the pediatrics trial for patients between the ages of 2 and

6, and the switch study evaluating a once-weekly formulation of setmelanotide. We are excited to have completed enrollment in our Phase

2 hypothalamic obesity trial with plans to read out data in the first half of this year. These studies have the potential to meaningfully

expand the reach of setmelanotide and address the severe obesity and hyperphagia associated with rare genetic diseases of obesity, and,

in the case of hypothalamic obesity, an acquired deficiency in the hypothalamic melanocortin pathway."

Fourth Quarter and Recent Business Highlights:

Commercial Readiness for Bardet Biedl

International Updates

Clinical Development Updates:

Bardet-Biedl Syndrome and Alstr m Syndrome:

Key Upcoming Milestones:

Fourth Quarter and Full Year 2021 Financial Results:

Financial Guidance: Based on its current operating plans,

Rhythm expects that its existing cash, cash equivalents and short-term investments as of December 31, 2021 will be sufficient to

fund its operating expenses and capital expenditure requirements into at least the second half of 2023.

Conference Call Information

Rhythm Pharmaceuticals will host a live conference call and webcast

at 8:00 a.m. ET today to discuss this update, as well as review its fourth quarter and full year 2021 financial results and

recent business activities. The conference call may be accessed by dialing (844) 498-0570 (domestic) or (409) 983-9726 (international)

and referring to conference ID 9840866. A webcast of the call will be available under "Events and Presentations" in the Investor

Relations section of the Rhythm Pharmaceuticals website at http://ir.rhythmtx.com/. The archived webcast will be

available on Rhythm Pharmaceuticals' website approximately two hours after the conference call and will be available

for 30 days following the call.

About Rhythm Pharmaceuticals

Rhythm is a commercial-stage biopharmaceutical company committed

to transforming the treatment paradigm for people living with rare genetic diseases of obesity. Rhythm's precision medicine,

IMCIVREE (setmelanotide), was approved in November 2020 by the U.S. Food and Drug Administration (FDA) for

chronic weight management in adult and pediatric patients 6 years of age and older with obesity due to POMC, PCSK1 or LEPR

deficiency confirmed by genetic testing and in July and September 2021, respectively, by the European Commission (EC)

and Great Britain's Medicines & Healthcare Products Regulatory Agency (MHRA) for the treatment of obesity and

the control of hunger associated with genetically confirmed loss-of-function biallelic POMC, including PCSK1, deficiency or

biallelic LEPR deficiency in adults and children 6 years of age and above. IMCIVREE is the first-ever FDA-approved and EC- and

MHRA-authorized therapy for patients with these rare genetic diseases of obesity. The Company submitted a supplemental New Drug

Application (sNDA) to the FDA, which was accepted for filing in November 2021 and is currently assigned a Prescription

Drug User Fee Act (PDUFA) goal date of June 16, 2022, for the treatment of obesity and control of hunger in adult and pediatric

patients six years of age and older with Bardet-Biedl Syndrome (BBS) or Alstr m syndrome. A Type II variation application to

the European Medicines Agency seeking regulatory approval and authorization for setmelanotide to treat obesity and control

of hunger in adult and pediatric patients 6 years of age and older with BBS also is under review. Additionally, Rhythm is advancing

a broad clinical development program for setmelanotide in other rare genetic diseases of obesity and is leveraging the Rhythm Engine

and the largest known obesity DNA database -- now with approximately 45,000 sequencing samples -- to improve the understanding,

diagnosis and care of people living with severe obesity due to certain genetic deficiencies. Rhythm's headquarters is

IMCIVREE (setmelanotide) Indication

United States, IMCIVREE is indicated for chronic weight management in adult and pediatric patients 6 years of age and older with

obesity due to proopiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR)

deficiency, confirmed by an FDA-approved genetic test demonstrating variants in POMC, PCSK1,

or LEPR genes that are interpreted as pathogenic, likely pathogenic, or of uncertain significance (VUS).

In the EU and Great Britain, IMCIVREE is indicated for the treatment

of obesity and the control of hunger associated with genetically confirmed loss-of-function biallelic POMC, including PCSK1, deficiency

or biallelic LEPR deficiency in adults and children 6 years of age and above. IMCIVREE should be prescribed and supervised by a physician

with expertise in obesity with underlying genetic etiology.

IMCIVREE is not indicated for the

treatment of patients with the following conditions as IMCIVREE would not be expected to be effective:

Important Safety Information

WARNINGS AND PRECAUTIONS

Disturbance in Sexual Arousal: Sexual adverse reactions

may occur in patients treated with IMCIVREE. Spontaneous penile erections in males and sexual adverse reactions in females occurred in

clinical studies with IMCIVREE. Instruct patients who have an erection lasting longer than 4 hours to seek emergency medical attention.

Depression and Suicidal Ideation: Some drugs that target

the central nervous system, such as IMCIVREE, may cause depression or suicidal ideation. Monitor patients for new onset or worsening of

depression. Consider discontinuing IMCIVREE if patients experience suicidal thoughts or behaviors.

Skin Pigmentation and Darkening of Pre-Existing Nevi: IMCIVREE

may cause generalized increased skin pigmentation and darkening of pre-existing nevi due to its pharmacologic effect. This effect is reversible

upon discontinuation of the drug. Perform a full body skin examination prior to initiation and periodically during treatment with IMCIVREE

to monitor pre-existing and new skin pigmentary lesions.

Risk of Serious Adverse Reactions Due to Benzyl Alcohol Preservative

in Neonates and Low Birth Weight Infants: IMCIVREE is not approved for use in neonates or infants.

USE IN SPECIFIC POPULATIONS

Discontinue IMCIVREE when pregnancy is recognized unless the benefits

of therapy outweigh the potential risks to the fetus.

Treatment with IMCIVREE is not recommended for use while

To report SUSPECTED ADVERSE REACTIONS, contact Rhythm Pharmaceuticals at +1 (833) 789-6337 or FDA at

1-800-FDA-1088 or www.fda.gov/medwatch.

See Full Prescribing Information, EU SmPC and MHRA SmPC for

Forward-Looking Statements

This press release contains forward-looking

statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release

that do not relate to matters of historical fact should be considered forward-looking statements, including without limitation statements

regarding the potential, safety, efficacy, and regulatory and clinical progress of setmelanotide, including the anticipated timing for