Rhythm Pharmaceuticals Reports First Quarter 2023 Financial Results and Business Update -- Strong U.S. commercial progress continues for IMCIVREE (setmelanotide) with more than 300 new prescriptions for Bardet-Biedl synd

Rhythm Pharmaceuticals Reports First Quarter

2023 Financial Results and Business Update

-- Strong U.S. commercial progress continues

for IMCIVREE (setmelanotide) with more than 300 new prescriptions for Bardet-Biedl syndrome (BBS) received since FDA approval

-- Launched IMCIVREE for BBS in Germany with federal reimbursement

-- First patients dosed in pivotal Phase 3 trial

evaluating setmelanotide in acquired hypothalamic obesity; completion of enrollment expected 1Q 2024 --

-- Executing on six clinical trials with three

data readouts expected in 2H 2023 --

to host conference call today at 8:00 a.m. ET --

BOSTON, May 2, 2023 - Rhythm Pharmaceuticals, Inc. (Nasdaq:

RYTM), a global commercial-stage biopharmaceutical company focused on transforming the lives of patients and their families living with

hyperphagia and severe obesity caused by rare melanocortin-4 receptor (MC4R) pathway diseases, today reported financial results and provided

a business update for the first quarter ended March 31, 2023.

"Rhythm is off to a strong start in 2023 with IMCIVREE

(setmelanotide) commercial progress with more than 300 new U.S. prescriptions for Bardet-Biedl syndrome (BBS) since launch. Internationally,

we are excited about our first European launch for BBS in Germany with federal reimbursement and looking forward to further expansion

into additional global markets this year," said David Meeker, M.D., Chair, President and Chief Executive Officer of Rhythm.

Dr. Meeker added, "We also are pleased to announce that we dosed

the first patients in our pivotal Phase 3 trial in hypothalamic obesity, and we anticipate completing enrollment in the first quarter

of 2024. With an identified and engaged patient population and encouraging data from our Phase 2 trial, hypothalamic obesity represents

a meaningful opportunity for Rhythm. In addition, we are advancing our newly acquired program from Xinvento in congenital hyperinsulinism

(CHI), a natural strategic fit for our portfolio."

First Quarter and Recent Business

Clinical Development Updates

Hypothalamic Obesity

Anticipated Upcoming Milestones

Rhythm expects to achieve the following near-term milestones:

First Quarter 2023 Financial Results:

Financial Guidance: For the year

ending December 31, 2023, Rhythm continues to anticipate approximately $200 million to $220 million in Non-GAAP Operating Expenses (see

below under "Non-GAAP Financial Measures" for more details), comprised of $120 million to $130 million from R&D expenses

and $80 million to $90 million from S,G&A expenses. Based on its current operating plans, Rhythm expects that its existing cash, cash

equivalents and short-term investments as of March 31, 2023 will be sufficient to fund its operating expenses and capital expenditure

requirements into 2025.

Conference Call Information

Rhythm Pharmaceuticals will host a live conference

call and webcast at 8:00 a.m. ET today to review its first quarter 2023 financial results and recent business activities. Participants

may register for the conference call here. While not required, it is recommended that participants join the call ten minutes prior

to the scheduled start.

A live webcast of the call will also be available under "Events

and Presentations" in the Investor Relations section of the Rhythm Pharmaceuticals website at https://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 lives of patients and their families living with hyperphagia and severe obesity caused by rare melanocortin-4

receptor (MC4R) diseases. Rhythm's lead asset, IMCIVREE (setmelanotide), an MC4R agonist designed to treat hyperphagia and

severe obesity caused by rare MC4R pathway diseases, is approved 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 monogenic or syndromic obesity due to

pro-opiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1) or leptin receptor (LEPR) deficiency confirmed by

genetic testing, or patients with a clinical diagnosis of Bardet-Biedl syndrome (BBS). Both the European Commission (EC)

and the UK's Medicines & Healthcare Products Regulatory Agency (MHRA) have authorized setmelanotide for the

treatment of obesity and the control of hunger associated with genetically confirmed BBS or genetically confirmed loss-of-function

biallelic POMC, including PCSK1, deficiency or biallelic LEPR deficiency in adults and children 6 years of age and above.

Additionally, Rhythm is advancing a broad clinical development program for setmelanotide in other rare MC4R pathway diseases, as

well as a preclinical suite of small molecules for the treatment of congenital hyperinsulinism. Rhythm's headquarters is

Setmelanotide Indication

In the United States, setmelanotide

is indicated for chronic weight management in adult and pediatric patients 6 years of age and older with monogenic or syndromic obesity

due to POMC, PCSK1 or 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) or BBS.

In the European Union, setmelanotide is indicated for the treatment

of obesity and the control of hunger associated with genetically confirmed Bardet-Biedl syndrome (BBS) or genetically confirmed loss-of-function

biallelic proopiomelanocortin (POMC), including PCSK1, deficiency or biallelic leptin receptor (LEPR) deficiency in adults and children

6 years of age and above.

In the United States and Europe,

Setmelanotide should be prescribed and supervised by a physician with expertise in obesity with underlying genetic etiology.

Setmelanotide is not indicated for the treatment of patients with the

following conditions as setmelanotide would not be expected to be effective:

WARNINGS AND PRECAUTIONS

Skin Monitoring: Setmelanotide may lead to generalized

increased skin pigmentation and darkening of pre-existing naevi because of its pharmacologic effect. Full body skin examinations should

be conducted annually to monitor pre-existing and new skin pigmentary lesions before and during treatment with setmelanotide.

Heart rate and blood pressure monitoring: Heart rate and

blood pressure should be monitored as part of standard clinical practice at each medical visit (at least every 6 months) for patients

treated with setmelanotide.

Prolonged penile erection: Spontaneous penile erections

have been reported in clinical trials with setmelanotide. Patients who have a penile erection lasting longer than 4 hours should be instructed

to seek emergency medical attention for potential treatment of priapism.

Depression: In clinical trials, depression has been

reported in patients treated with setmelanotide. Patients with depression should be monitored at each medical visit during treatment

with setmelanotide. Consideration should be given to discontinuing setmelanotide if patients experience suicidal thoughts or

Pediatric Population: The prescribing physician should

periodically assess response to setmelanotide therapy. In growing children, the impact of weight loss on growth and maturation should

be evaluated. The prescribing physician should monitor growth (height and weight) using age- and sex-appropriate growth curves.

Excipients: This medicinal product contains 10 mg benzyl

alcohol in each ml. Benzyl alcohol may cause allergic reactions. Patients who are pregnant or breastfeeding should be advised of the potential

risk from the excipient benzyl alcohol, which might accumulate over time and cause metabolic acidosis. This medicinal product should be

used with caution in patients with hepatic or renal impairment, because of the potential risk from the excipient benzyl alcohol which

might accumulate over time and cause metabolic acidosis.

Sodium: This medicinal product contains less than 1 mmol

sodium (23 mg) per dose, that is to say essentially "sodium-free."

The most frequent adverse reactions are hyperpigmentation (51%), injection

site reaction (39%), nausea (33%), and headache (26%).

USE IN SPECIFIC POPULATIONS

There are no data from the use of setmelanotide in

pregnant women. Animal studies do not indicate direct harmful effects with respect to reproductive toxicity. However, administration

of setmelanotide to pregnant rabbits resulted in decreased maternal food consumption leading to embryo-fetal effects. As a precautionary

measure, setmelanotide should not be started during pregnancy or while attempting to get pregnant as weight loss during pregnancy may