Columbia University Irving Medical Center

MOUNTAIN VIEW, Calif.--(BUSINESS WIRE)--Materna Medical, a women’s health company dedicated to developing innovative solutions for pelvic floor disorders, today announced the successful completion of enrollment in its EASE pivotal trial (NCT03973281). The trial enrolled 420 first-time mothers to evaluate the safety and effectiveness of the investigational Ellora™ Obstetrical System for reducing pelvic muscle injury during vaginal delivery in first-time mothers. The EASE study is a prospective, randomized controlled clinical trial being conducted at 20 leading U.S. hospital clinical sites and is designed to assess the safety and effectiveness of the Ellora expanding vaginal dilator (formerly Materna Prep device) in reducing pelvic muscle injury during vaginal delivery. "The completion of enrollment in the EASE study represents an exciting opportunity to understand and potentially reduce the risk of vaginal childbirth-related pelvic floor trauma,” said Helai Hesham, MD, urogynecologist and EASE lead investigator at Columbia University Irving Medical Center, NY. “The rigorous design of this pivotal trial, building on the promising published results of the EASE Phase 2 Study, is essential for evaluating the potential of Ellora to improve maternal health outcomes.” Vaginal childbirth-related pelvic floor injuries, specifically complete levator ani muscle (LAM) avulsion—where a group of pelvic floor muscles detaches from the pelvic bone—are linked to pelvic organ prolapse, whose symptoms can include pelvic pressure, pain, urinary and/or fecal incontinence, and sexual dysfunction. The investigational Ellora Obstetrical System includes an expanding vaginal dilator designed to prepare the vagina to better withstand the strain of childbirth, aiming to reduce the incidence and severity of these significant LAM injuries. “Completing enrollment in our EASE pivotal trial is a monumental milestone for Materna Medical and is a significant step forward in our mission to protect women from childbirth injuries,” said Tracy MacNeal, CEO of Materna Medical. “We are incredibly grateful to the patients and clinical investigators participating in this groundbreaking trial. Their commitment brings us closer to potentially offering a much-needed intervention to improve birth outcomes for mothers globally.” “The focus of innovation has traditionally been on the difficult challenge of fixing women’s pelvic health damage that has already occurred, rather than protecting the pelvic floor and preventing these problems from happening in the first place," said Ariella Golomb, MD, Partner and Founder, InnovaHealth Partners, and Materna Board Chair. "Materna's approach to reducing the incidence of pelvic floor injuries is a tremendous opportunity to transform the standard of care in obstetrics and provide women with a chance to enter motherhood without the anatomical setbacks from childbirth. We're thrilled to see this landmark study complete its enrollment." Results from the Phase 2 EASE trial were published in the August 2024 Issue of the International Urogynecology Journal: “Effect of an intrapartum pelvic dilator device on levator ani muscle avulsion during primiparous vaginal delivery: A pilot randomized controlled trial.” Materna Medical is now focused on analyzing the EASE study data to support an upcoming FDA submission for the Ellora Obstetrical System. About Us Materna Medical Materna Medical is a novel OBGYN platform company defining a $25B market with core technologies addressing unmet needs in women's pelvic health. With headquarters in Mountain View, California, Materna pulls from the top minds in MedTech to truly transform the standard of care in OBGYN. With a diverse team of engineers, scientists, researchers, and commercial leaders, Materna Medical’s mission is to empower women to protect their pelvic health. Our first product, Milli™, is a vaginal dilator to support patients suffering from vaginismus and related painful sex. In 2019, the Milli device launched as a wellness trainer and, in 2023, received FDA clearance to sell over the counter, enabling streamlined access to people suffering from vaginismus. Milli outcomes have been studied in a post-market prospective virtual study named POMPOM. Materna’s second product, Ellora™, is an investigational device used during labor and is intended to reduce pelvic floor muscle injury during vaginal delivery in first-time moms. This product is being studied in the EASE trial, a large, randomized controlled trial in 20 top US hospitals. Materna aims to transform the standard of care in labor and delivery by protecting pelvic floor health for moms. Reference Hesham, H., Orejuela, F., Rood, K.M. et al. Effect of an Intrapartum Pelvic Dilator Device on Levator Ani Muscle Avulsion During Primiparous Vaginal Delivery: A Pilot Randomized Controlled Trial. Int Urogynecol J 35, 1839–1849 (2024). https://doi.org/10.1007/s00192-024-05881-6

Based on the primary endpoint of Clinical Dementia Rating Sum of Boxes (CDR-SB), patients treated with neflamapimod showed 54% risk reduction in clinically significant worsening compared to control at Week 32 of treatment (p=0.0037). This risk reduction improved to 64% (p=0.0001) among patients who have minimal evidence of AD co-pathology (ptau181 < 2.2 pg/mL at screening) At week 32 of the Extension phase, patients treated with neflamapimod demonstrated a significant reduction from baseline in plasma levels of glial fibrillary acidic protein (GFAP) Conference call and webcast today at 8:00 AM ET today to discuss results BOSTON, July 28, 2025 (GLOBE NEWSWIRE) -- CervoMed Inc. (NASDAQ: CRVO), a clinical stage company focused on developing treatments for age-related neurologic disorders (CervoMed or the Company), today announced positive 32-week data from the Extension phase of the Phase 2b RewinD-LB trial showing that oral neflamapimod continued to demonstrate slowing of disease progression and demonstrated an effect on a plasma marker of neurodegeneration in patients with DLB. The disease progression analyses were featured in two presentations during the Alzheimer’s Association® International Congress 2025 (AAIC) on Sunday, July 27th, 2025. “We are thrilled by these unprecedented data demonstrating a 54% reduction in risk of clinically significant worsening on the CDR-SB over 32 weeks of treatment, improving to 64% when applying the more stringent ptau181 threshold to define DLB without Alzheimer’s Disease (AD) co-pathology – underscoring neflamapimod’s potential to have a powerful impact on CDR-SB, a gold standard measure of clinical progression in dementia trials,” said John Alam, MD, Co-Principal Investigator of the RewinD-LB trial and CEO of CervoMed. “Combined with the positive effects on a robust blood-based biomarker of the underlying neurodegenerative process, these results bolster our confidence as we progress towards initiating a Phase 3 trial and prepare to meet with the U.S. Food and Drug Administration in the fourth quarter of 2025 to align on the trial design. We remain deeply committed to delivering a meaningful treatment option for underserved DLB patients and their families.” “These new data are potentially transformative with respect to our understanding of the potential of neflamapimod in the treatment of DLB,” said Lawrence S. Honig, MD, PhD, Professor of Neurology at Columbia University Irving Medical Center and the investigator who presented the results AAIC. "Reducing the risk of a 1.5-point worsening over 32 weeks on the CDR-SB by more than 50% would likely represent a clinically meaningful slowing of clinical progression at a level that patients and caregivers would notice in day-to-day function. This level of effect, if confirmed in a Phase 3 pivotal trial, would be an important advance in the unmet treatment needs of patients with DLB, the second most common dementia, which is a challenging disease, due to its involvement of both movement and cognition, and due to the lack of effective current treatments.” New Data: 32-Week Results from the Extension Phase of the Phase 2b RewinD-LB Trial1 In the RewinD-LB trial, an older batch of neflamapimod capsules utilized during the double-blind phase and part of the Extension phase (Old Capsules) was associated with plasma exposures below the expected and targeted range, while capsules from a new batch of neflamapimod utilized during the majority of the Extension phase of the trial (New Capsules) were associated with achievement of target plasma concentrations and observation of statistically significant clinical benefit. When evaluating clinically meaningful disease progression, defined as ≥ 1.5-point increase in CDR-SB, with a Kaplan-Meier time to progression analysis, patients treated with New Capsules demonstrated statistically significant slowed disease progression compared to patients treated with Old Capsules over 32 weeks as summarized in Table 1 below. Even greater risk reductions were observed in patients with ptau181 < 2.2 pg/mL – the threshold CervoMed believes is the optimal ptau181 threshold for evaluating the presence of AD co-pathology in patients with DLB. Table 1. Risk of ≥ 1.5-point Increase in CDR-SB at Week 32 of Treatment during RewinD-LB Trial NC=New Capsules; OC=Old Capsules; PBO=Placebo Researchers also presented data evaluating different cut-off levels of ptau181 in relation to the 32-week results and evaluated the correlation between ptau181 and ptau217, a validated biomarker for AD. Utilizing published cutoffs for plasma ptau217 (0.63 pg/mL) and ptau181 (2.2 pg/mL), there is 92% concordance for presence or absence of AD co-pathology, and a strong correlation of (r=0.81, p<0.001). These findings demonstrate that the established ptau181 cutoff of 2.2 pg/mL for AD also appears to be the optimal cutoff to maximize neflamapimod treatment response. Ptau181 and ptau217 appear to be equally predictive for identifying AD-co-pathology in patients with DLB. These new data, including the Kaplan-Meier curves associated with these analyses, are available in a presentation published today under “Events & Presentations” in the Investor Relations section of the Company’s website, https://www.cervomed.com. New Data: Reduction in Plasma Levels of Glial Fibrillary Acidic Protein at Week 32 of Extension Phase The Company also announced today that it has completed an analysis of GFAP data from the Extension phase of the RewinD-LB trial. At Week 32 of the Extension phase, there was a statistically significant reduction (p<0.0001) from baseline (i.e., start of extension) in GFAP plasma levels in patients who received New Capsules for all 32 weeks, with a mean change of -18.4±4.0 pg/mL in all participants (N=107) and -21.2±4.4 pg/mL in participants with screening plasma ptau181 below 2.2 pg/mL (N=91). In contrast, placebo-recipients in the initial, double-blind phase of the trial had a mean increase from baseline to Week 16 of +1.1±3.0 pg/mL in all participants (N=74) and +1.1±3.3 pg/mL in the subset with screening plasma ptau181 below 2.2 pg/mL (N=65). Previously Presented 16-Week Extension Phase Data Improvement on primary outcome measure, change in CDR-SB, with the New Capsules both vs. Old Capsules (p<0.001) during first 16 weeks of the Extension phase and vs. placebo (p=0.003). The percentage of participants who had clinically meaningful worsening (i.e., an increase greater than or equal to 1.5 points on their CDR-SB score) during the first 16 weeks of the Extension phase of the trial was 40% lower on a relative basis in New Capsule recipients compared to Old Capsule recipients, and 62% lower in participants whose screening plasma ptau181 < 2.2 pg/mL. Statistically significant improvement on Alzheimer’s Disease Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC) in participants administered New Capsules both in comparison to Old Capsules (p=0.035) and in a within-participant comparison to placebo treatment (p=0.039). The improvement compared to placebo in the within-participant analysis was not seen with the Old Capsules. Full results from the first 16 weeks of the Extension phase can be found here. Old and New Capsules Have Similar Overall Safety and Tolerability Profile During Extension Phase Both Old and New Capsules demonstrated comparable tolerability profiles and no new safety signals were identified during the Extension phase of the trial. During the first 16 weeks of the Extension phase, a lower incidence of falls was seen in participants with screening ptau181 < 2.2 pg/mL who received New Capsules of neflamapimod as compared to participants who received either Old Capsules or placebo (vs. Old Capsules, p=0.025; vs. placebo, p=0.007) Conference Call / Webcast Details CervoMed will host a conference call and webcast to review these results today, July 28, 2025, at 8:00 AM ET. To register for the webcast, please click here. Participants should dial 1-877-425-9470 (domestic) or 1-201-389-0878 (international) with the code 13755139. To access the Call me™ feature, which avoids having to wait for an operator, click here. The live webcast and replay will be available under “Events & Presentations” in the Investor Relations section of the Company’s website, https://www.cervomed.com. About the RewinD-LB Phase 2b Trial in Dementia with Lewy Bodies The initial phase of RewinD-LB was a randomized, 16-week, double-blind, placebo-controlled clinical trial evaluating oral neflamapimod (40mg TID) in 159 patients with DLB, followed by a 32-week neflamapimod-only treatment Extension phase. Patients with AD co-pathology, as assessed by plasma ptau181 levels, were excluded from the trial. Compared to patients with “pure” DLB – who may comprise up to 50% of the total diagnosed DLB patient population at any given time – DLB patients with AD co-pathology have significant, irreversible neuronal loss in the hippocampus that limits response to treatment. The primary endpoint in the trial is change in the CDR-SB, and secondary endpoints include ADCS-CGIC, the Timed Up and Go test, and a cognitive test battery. The RewinD-LB trial is funded primarily by a $21.3 million grant from the National Institutes of Health’s National Institute on Aging, which is expected to be disbursed over the course of the trial as costs are incurred. The trial includes 43 sites across in the United States, the United Kingdom, and the Netherlands. Participants completing the 16-week initial portion of the trial were able to continue in an open-label Extension portion of the trial to receive neflamapimod for an additional 32 weeks. The Extension trial protocol includes a pre-specified data readout after the first 16 weeks of the same outcome measures assessed during the placebo-controlled portion of the trial. About CervoMed CervoMed is a clinical-stage company focused on developing treatments for age-related neurologic disorders. The Company is currently developing neflamapimod, an investigational, orally administered small molecule brain penetrant that inhibits p38 mitogen-activated protein kinase alpha. Neflamapimod has the potential to treat synaptic dysfunction, the reversible aspect of the underlying neurodegenerative processes that cause disease in DLB and certain other major neurological disorders. Neflamapimod is currently being evaluated in a Phase 2b trial in patients with DLB. Forward-Looking Statements This press release includes express and implied forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, regarding the intentions, plans, beliefs, expectations or forecasts for the future of the Company, including, but not limited to: the therapeutic potential of neflamapimod, including the degree of sustainability of any therapeutic effects; the anticipated timing and achievement of clinical and development milestones, including the Company’s announcement of additional data, if any, from the RewinD-LB Phase 2b clinical trial and any meeting or correspondence between the Company and the FDA; any other expected or implied benefits or results, including that any initial clinical results observed with respect to neflamapimod in the RewinD-LB trial will be replicated in later trials; and the timing of the initiation of any potential future trials or interactions with regulatory authorities, including the Company’s need to acquire sufficient funding for any Phase 3 trial of neflamapimod in DLB. Terms such as “believes,” “estimates,” “anticipates,” “expects,” “plans,” “aims,” “seeks,” “intends,” “may,” “might,” “could,” “might,” “will,” “should,” “approximately,” “potential,” “target,” “project,” “contemplate,” “predict,” “forecast,” “continue,” or other words that convey uncertainty of future events or outcomes (including the negative of these terms) may identify these forward-looking statements. Although there is believed to be reasonable basis for each forward-looking statement contained herein, forward-looking statements by their nature involve risks and uncertainties, known and unknown, many of which are beyond the Company’s control and, as a result, actual results could differ materially from those expressed or implied in any forward-looking statement. Particular risks and uncertainties include, among other things, those related to: the Company’s available cash resources and the availability of additional funds on acceptable terms; the results of the Company’s clinical trials, including RewinD-LB; the likelihood and timing of any regulatory approval of neflamapimod or the nature of any feedback the Company may receive from the FDA; the ability to implement business plans, forecasts, and other expectations in the future; general economic, political, business, industry, and market conditions, inflationary pressures, and geopolitical conflicts; and the other factors discussed under the heading “Risk Factors” in the Company’s Annual Report on Form 10-K for the year ended December 31, 2024 filed with the U.S. Securities and Exchange Commission (SEC) on March 17, 2025, and other filings that the Company may file from time to time with the SEC. Any forward-looking statements in this press release speak only as of the date hereof (or such earlier date as may be identified). The Company does not undertake any obligation to update such forward-looking statements to reflect events or circumstances after the date of this press release, except to the extent required by law. Investor Contact: PJ Kelleher LifeSci Advisors Investors@cervomed.com 617-430-7579 Media Argot Partners liza@argotpartners.com 212-600-1902 1 All analyses reported are exploratory in nature, along with 95% confidence intervals. However, p-values and indications of statistically significance are being reported to provide a measure of the probability that any differences identified between the samples are due to chance. Source: CervoMed Inc.

- Presentations highlight clinically meaningful reductions in BMI in patients with acquired hypothalamic obesity – - Full data from Phase 3 TRANSCEND study underscore potential efficacy of setmelanotide, including with prior use or concomitant use of GLP-1s - BOSTON, July 12, 2025 (GLOBE NEWSWIRE) -- Rhythm Pharmaceuticals, Inc. (Nasdaq: RYTM), a global commercial-stage biopharmaceutical company focused on transforming the lives of patients living with rare neuroendocrine diseases, today announced data from three new presentations on the Company’s clinical programs for acquired hypothalamic obesity at the Endocrine Society’s Annual Meeting (ENDO 2025) taking place July 12-15 in San Francisco, CA. Acquired hypothalamic obesity is a rare but serious condition caused by damage to the hypothalamic region of the brain, which includes the melanocortin-4 receptor (MC4R) pathway. This damage, often from brain tumors or their treatment, leads to rapid weight gain, hyperphagia, and low energy expenditure. Presentations on Rhythm’s acquired hypothalamic obesity programs at ENDO 2025 include: Efficacy and Safety of Once-Daily Oral Bivamelagon in Acquired Hypothalamic Obesity: Results from a Double-blind, Multicenter, Placebo-Controlled, Randomized Phase 2 Trial In a poster presentation, Vidhu Thaker, M.D., Pediatric Endocrinology, Columbia University, New York City, presented data from the Phase 2 SIGNAL trial evaluating bivamelagon, a daily oral, highly selective MC4R agonist, in patients with acquired hypothalamic obesity. In the 14-week, double-blind, four-arm, placebo-controlled portion of the trial, bivamelagon achieved statistically significant and clinically meaningful reductions in body mass index (BMI), consistent with BMI reductions achieved with setmelanotide therapy in similar patient populations in past trials. Other highlights include: -9.3% BMI reduction from baseline in the 600mg cohort (n=8) (p-value= 0.0004); -7.7% BMI reduction from baseline in the 400mg cohort (n=7) (p-value= 0.0002); -2.7% BMI reduction from baseline in the 200mg cohort (n=6) (p-value= 0.0180); and BMI for patients in the placebo cohort (n=7) increased by 2.2% over 14 weeks. “Patients with acquired hypothalamic obesity struggle with accelerated weight gain that profoundly affects their life. These data demonstrate bivamelagon's potential as a transformative therapeutic option for patients and validate the potential opportunity for MC4R targeted therapies, if approved, to become the standard of care for this patient community,” said Vidhu Thaker, M.D., Associate Professor, Pediatric Endocrinology and Molecular Genetics, Department of Pediatrics, Columbia University Irving Medical Center, New York City. Efficacy and Safety of Setmelanotide in Acquired Hypothalamic Obesity: Results from a Double-Blind, Multicenter, Placebo-Controlled, Randomized Phase 3 Trial In a live oral presentation, Susan Phillips, M.D., Pediatric Endocrinology, University of California San Diego/Rady Children’s Hospital, San Diego, presented data from Rhythm’s pivotal Phase 3 TRANSCEND trial evaluating setmelanotide, the largest randomized, placebo-controlled trial in acquired hypothalamic obesity to date. Highlights from the presentation include: -19.8% placebo-adjusted difference in BMI reduction (N=120); Statistically significant BMI reductions following setmelanotide treatment were consistently observed across subgroups stratified by age (<12, 12 to 17, <18, and 18 years and older; ranging from -15.6% to -17.2%) and by sex (-16.3% female; -16.8% male) Significant BMI reductions observed in participants with prior use or concomitant use of GLP-1s: Mean reduction of -19.3% in BMI from baseline for participants with prior but no concomitant GLP-1 use (n=10) compared to + 5.4% change for participants on placebo (n=6) at 52 weeks (p<0.0001); Mean reduction of -25.1% change in BMI from baseline for participants with prior and concomitant GLP-1 use (n=9) compared to +2.0% change for participants on placebo (n=6); There was significant reduction in weight-related measures in participants <18 years of age with setmelanotide at week 52, with a -26.2% change in the 95th percentile for BMI. Mean reduction of -19.3% in BMI from baseline for participants with prior but no concomitant GLP-1 use (n=10) compared to + 5.4% change for participants on placebo (n=6) at 52 weeks (p<0.0001); Mean reduction of -25.1% change in BMI from baseline for participants with prior and concomitant GLP-1 use (n=9) compared to +2.0% change for participants on placebo (n=6); “The TRANSCEND trial has notably demonstrated how setmelanotide has the potential to significantly alter the trajectory of this devastating condition and provide significant benefit to both children and adult patients. The nearly 20% placebo-adjusted difference in BMI reduction is very compelling.” said Susan Phillips, M.D., pediatric endocrinologist at Rady Children’s Hospital-San Diego and professor at UC San Diego School of Medicine. Experiences and Observations with Acquired Hypothalamic Obesity: A Qualitative Interview Sub-Study Finally, on July 14, from 12:00 PM - 1:30 PM PT, Christian Roth, M.D., Seattle Children’s Research Institute, will present a poster detailing results from exit interviews gathered from 30 patients or caregivers located in the United States with acquired hypothalamic obesity who participated in the Phase 3 TRANSCEND trial. All of the Rhythm-related presentations from ENDO 2025 will be available here: https://hcp.rhythmtx.com/publications-presentations/. About Rhythm Pharmaceuticals Rhythm is a commercial-stage biopharmaceutical company committed to transforming the lives of patients and their families living with rare neuroendocrine diseases. Rhythm’s lead asset, IMCIVREE® (setmelanotide), an MC4R agonist designed to treat hyperphagia and severe obesity, 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 2 years of age and older with syndromic or monogenic obesity due to Bardet-Biedl syndrome (BBS) or genetically confirmed pro-opiomelanocortin (POMC), including proprotein convertase subtilisin/kexin type 1 (PCSK1), deficiency or leptin receptor (LEPR) deficiency. 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 2 years of age and above. Additionally, Rhythm is advancing a broad clinical development program for setmelanotide in other rare diseases, as well as investigational MC4R agonists bivamelagon and RM-718, and a preclinical suite of small molecules for the treatment of congenital hyperinsulinism. Rhythm’s headquarters is in Boston, MA. About Acquired Hypothalamic Obesity Acquired hypothalamic obesity is a rare form of obesity that occurs following damage to the hypothalamic region of the brain, which includes the melanocortin-4 receptor (MC4R) pathway and is responsible for controlling physiological functions such as hunger and weight regulation. Acquired hypothalamic obesity 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 due to infection. 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 severe obesity within six to 12 months following tumor resection or other injury. Rhythm estimates there are 5,000 to 10,000 people living with hypothalamic obesity in the U.S., 5,000 to 8,000 people living with hypothalamic obesity in Japan, and 3,500 to 10,000 people living with hypothalamic obesity in the E.U. Setmelanotide Indication In the United States, setmelanotide is indicated 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 Bardet-Biedl syndrome (BBS) or Pro-opiomelanocortin (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). In the European Union and the United Kingdom, setmelanotide is indicated 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. In the European Union and the United Kingdom, setmelanotide should be prescribed and supervised by a physician with expertise in obesity with underlying genetic etiology. Limitations of Use Setmelanotide is not indicated for the treatment of patients with the following conditions as setmelanotide would not be expected to be effective: Obesity due to suspected POMC, PCSK1, or LEPR deficiency with POMC, PCSK1, or LEPR variants classified as benign or likely benign Other types of obesity not related to BBS or POMC, PCSK1, or LEPR deficiency, including obesity associated with other genetic syndromes and general (polygenic) obesity Contraindication Prior serious hypersensitivity to setmelanotide or any of the excipients in IMCIVREE. Serious hypersensitivity reactions (e.g., anaphylaxis) have been reported. WARNINGS AND PRECAUTIONS Disturbance in Sexual Arousal: Spontaneous penile erections in males and sexual adverse reactions in females have occurred. Inform patients that these events may occur and instruct patients who have an erection lasting longer than 4 hours to seek emergency medical attention. Depression and Suicidal Ideation: Depression, suicidal ideation and depressed mood have occurred. Monitor patients for new onset or worsening depression or suicidal thoughts or behaviors. Consider discontinuing IMCIVREE if patients experience suicidal thoughts or behaviors, or clinically significant or persistent depression symptoms occur. Hypersensitivity Reactions: Serious hypersensitivity reactions (e.g., anaphylaxis) have been reported. If suspected, advise patients to promptly seek medical attention and discontinue IMCIVREE. Skin Hyperpigmentation, Darkening of Pre-existing Nevi, and Development of New Melanocytic Nevi: Generalized or focal increases in skin pigmentation, darkening of pre-existing nevi, development of new melanocytic nevi and increase in size of existing melanocytic nevi have occurred. Perform a full body skin examination prior to initiation and periodically during treatment to monitor pre-existing and new pigmented 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. Serious and fatal adverse reactions including “gasping syndrome” can occur in neonates and low birth weight infants treated with benzyl alcohol preserved drugs. ADVERSE REACTIONS Most common adverse reactions (incidence ≥20%) included skin hyperpigmentation, injection site reactions, nausea, headache, diarrhea, abdominal pain, vomiting, depression, and spontaneous penile erection. USE IN SPECIFIC POPULATIONS Treatment with IMCIVREE is not recommended when breastfeeding. Discontinue IMCIVREE when pregnancy is recognized unless the benefits of therapy outweigh the potential risks to the fetus. 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 section 4.8 of the Summary of Product Characteristics for information on reporting suspected adverse reactions in Europe. Please see the full Prescribing Information for additional Important Safety Information. 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 our Phase 2 study to assess the efficacy and safety of bivamelagon in patients with acquired hypothalamic obesity and the potential for bivamelagon to treat or become a standard of care for hypothalamic obesity; our pivotal Phase 3 TRANSCEND study evaluating setmelanotide for the treatment of acquired hypothalamic obesity and the potential for setmelanotide to treat or become a standard of care for hypothalamic obesity; the safety, efficacy, potential benefits of, and regulatory and clinical progress, potential regulatory submissions, approvals and timing thereof of bivamelagon, setmelanotide and other product candidates; the clinical design or progress of any of our products or product candidates at any dosage or in any indication; the potential benefits of any of the Company’s products or product candidates for any specific disease indication or at any dosage, including the potential benefits of bivamelagon and setmelanotide for patients with acquired hypothalamic obesity or congenital hypothalamic obesity; our participation in upcoming events and presentations, and the date, time and content thereof and the timing of any of the foregoing. Statements using words such as “expect”, “anticipate”, “believe”, “may”, “will” and similar terms are also forward-looking statements. Such statements are subject to numerous risks, uncertainties, including, but not limited to, our ability to enroll patients in clinical trials, the design and outcome of clinical trials, the impact of competition, the ability to achieve or obtain necessary regulatory approvals, risks associated with data analysis and reporting, our ability to successfully commercialize setmelanotide, our liquidity and expenses, our ability to retain our key employees and consultants, and to attract, retain and motivate qualified personnel, and general economic conditions, and the other important factors, including those discussed under the caption “Risk Factors” in Rhythm’s Quarterly Report on Form 10-Q for the three months ended March 31, 2025 and our other filings with the Securities and Exchange Commission. Except as required by law, we undertake no obligations to make any revisions to the forward-looking statements contained in this release or to update them to reflect events or circumstances occurring after the date of this release, whether as a result of new information, future developments or otherwise. Corporate Contact: David Connolly Head of Investor Relations and Corporate Communications Rhythm Pharmaceuticals, Inc. 857-264-4280 dconnolly@rhythmtx.com Media Contact: Layne Litsinger Real Chemistry (410) 916-1035 llitsinger@realchemistry.com Source: Rhythm Pharmaceuticals, Inc.