MC4R

Co-administered bremelanotide + tirzepatide, bremelanotide alone, and tirzepatide alone arms showed improvement in appetite suppression, fullness, and satiety Bremelanotide matched or exceeded tirzepatide in appetite suppression Low-dose bremelanotide helped prevent appetite rebound after tirzepatide cessation CRANBURY, N.J., April 17, 2025 /PRNewswire/ -- Palatin Technologies, Inc. (NYSE American: PTN), a biopharmaceutical company developing first-in-class medicines based on molecules that modulate the activity of the melanocortin receptor system, announced positive appetite suppression results from its BMT-801 Phase 2 obesity study. The study included a co-administered melanocortin 4 receptor (MC4R) agonist bremelanotide plus glucagon like peptide-1/gastric inhibitory polypeptide (GLP-1/GIP) tirzepatide arm, bremelanotide alone, and tirzepatide alone arms. "One of the important research questions that the study was designed to answer was whether a low- dose of an MC4R agonist could support long-term weight loss maintenance. We're excited with the results, which demonstrated that low-dose bremelanotide matched tirzepatide in appetite suppression, a compelling outcome," said Carl Spana, Ph.D., President and CEO of Palatin. "Just as importantly, low-dose bremelanotide significantly reduced the appetite rebound typically observed after stopping GLP-1/GIP therapy—one of the major hurdles in sustained obesity management." Key Results – Appetite Suppression (Patient-Reported Outcomes) Using a validated daily appetite questionnaire, the study showed that patients receiving co-administered bremelanotide + tirzepatide, tirzepatide alone, and bremelanotide alone, experienced significant improvements in appetite suppression, fullness, and satiety. Patients who transitioned to placebo after initial weight loss on tirzepatide showed no improvement for appetite suppression. Overall appetite suppression Bremelanotide + tirzepatide: 71% increase Tirzepatide only: 73% increase Bremelanotide only: 71% increase "How full do you feel (fullness)?" Bremelanotide + tirzepatide: 65% increase Tirzepatide only: 62% increase Bremelanotide only: 79% increase "How satisfied do you feel (satiety)?" Bremelanotide + tirzepatide: 56% increase Tirzepatide only: 56% increase Bremelanotide only: 68% increase Consistent with known effects of GLP-1/GIP therapy, over 50% of lost weight was regained within two weeks of stopping treatment in both the tirzepatide and co-administration arms of the study. In contrast, patients who transitioned to low-dose bremelanotide after initial weight loss on tirzepatide maintained their weight without any significant regain, underscoring the potential of MC4R agonists as a valuable therapy for long-term weight maintenance. Topline results from the BMT-801 Phase 2 trial, released last month, demonstrated statistically significant weight loss with bremelanotide co-administered with tirzepatide versus placebo over an 8-week treatment period. Further analysis of secondary and exploratory endpoints—including body composition and BMI—is ongoing. Full study results will be submitted for presentation at an upcoming medical conference. Additional trial details are available at clinicaltrials.gov under identifier NCT06565611. Pipeline Development Palatin continues to advance its next-generation MC4R agonists, including long-acting peptides and oral small molecules, targeting broad obesity indications—including monotherapy and combination regimens with incretin-based therapies, as well as rare and genetic obesity disorders such as hypothalamic obesity. IND filings are anticipated by end of Q4 2025, with initial clinical data expected in the first half of 2026. About Melanocortin-4 Receptor Agonists Effect on Obesity Genetic analysis has identified the melanocortin-4 receptor (MC4R) of the paraventricular nucleus of the hypothalamus as playing a central role in appetite regulation. Genetic mutations that inhibit signaling in the MC4R pathway lead to hyperphagia, decreased energy expenditure and early-onset obesity; such mutations have been identified as the cause of several rare genetic obesity disorders. Agouti-related peptide is an endogenous antagonist of the MC4R that works with neuropeptide Y to stimulate appetite, whereas MC4R agonists such as α- and β-melanocyte-stimulating hormone promote satiety. MC4R agonism represents an attractive target for potential obesity treatments. About Melanocortin Receptor Agonists The melanocortin receptor ("MCR") system has effects on inflammation, immune system responses, metabolism, food intake, and sexual function. There are five melanocortin receptors, MC1R through MC5R. Modulation of these receptors, through use of receptor-specific agonists, which activate receptor function, or receptor-specific antagonists, which block receptor function, can have medically significant pharmacological effects. About Palatin Palatin is a biopharmaceutical company developing first-in-class medicines based on molecules that modulate the activity of the melanocortin receptor systems, with targeted, receptor-specific product candidates for the treatment of diseases with significant unmet medical need and commercial potential. Palatin's strategy is to develop products and then form marketing collaborations to maximize their commercial potential. For additional information regarding Palatin, please visit Palatin's website at and follow Palatin on Twitter at @PalatinTech. Forward-looking Statements Statements in this press release that are not historical facts, including statements about future expectations of Palatin Technologies, Inc., such as statements about Palatin products in development, clinical trial results, potential actions by regulatory agencies, regulatory plans, development programs, proposed indications for product candidates, and market potential for product candidates are "forward-looking statements" within the meaning of Section 27A of the Securities Act of 1933, Section 21E of the Securities Exchange Act of 1934 and as that term is defined in the Private Securities Litigation Reform Act of 1995. Palatin intends that such forward-looking statements be subject to the safe harbors created thereby. Such forward-looking statements involve known and unknown risks, uncertainties and other factors that could cause Palatin's actual results to be materially different from its historical results or from any results expressed or implied by such forward-looking statements. Palatin's actual results may differ materially from those discussed in the forward-looking statements for reasons including, but not limited to, results of clinical trials, regulatory actions by the FDA and other regulatory and the need for regulatory approvals, Palatin's ability to fund development of its technology and establish and successfully complete clinical trials, the length of time and cost required to complete clinical trials and submit applications for regulatory approvals, products developed by competing pharmaceutical, biopharmaceutical and biotechnology companies, commercial acceptance of Palatin's products, and other factors discussed in Palatin's periodic filings with the Securities and Exchange Commission. Palatin is not responsible for updating events that occur after the date of this press release. SOURCE Palatin Technologies, Inc. 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— Patients with acquired hypothalamic obesity on setmelanotide therapy (n=81) achieved mean BMI change of -16.5% compared with +3.3% for placebo (n=39) at 52 weeks (p<0.0001) — — -19.2% placebo-adjusted BMI reduction achieved in adult patients 18 years old and older (n=49) at 52 weeks — — -20.2% placebo-adjusted BMI reduction achieved in patients younger than 18 years old (n=71) at 52 weeks — — Regulatory submissions in the U.S. and EU anticipated to be completed in the third quarter of 2025 — — Company to host conference call today at 8 a.m. ET — BOSTON, MA, USA I April 07, 2025 I 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 positive topline results from the pivotal Phase 3 TRANSCEND trial evaluating setmelanotide, a melanocortin-4 receptor (MC4R) agonist, for the treatment of acquired hypothalamic obesity. The global trial met its primary endpoint with a statistically significant and highly clinically meaningful reduction in body mass index (BMI) with setmelanotide in both adult and pediatric patients versus placebo. Highlights from the topline data include: “Acquired hypothalamic obesity is a serious disease resulting from damage to the hypothalamus, often due to brain tumors or their treatment or certain other injuries resulting in accelerated weight gain, hyperphagia and reduction in energy expenditure. There is an urgent need for effective treatments as current approaches, including lifestyle interventions and pharmacotherapy intended for general obesity, have shown limited effectiveness in achieving long-term, durable weight loss,” said Susan Phillips, MD, pediatric endocrinologist at Rady Children’s Hospital-San Diego and professor of pediatrics at UC San Diego School of Medicine. “These data are highly clinically meaningful, offering hope that a new targeted therapy may become available for patients – both adults and children – living with acquired hypothalamic obesity.” The global Phase 3 TRANSCEND trial is believed to be the largest and longest placebo-controlled trial to evaluate a therapy for patients with acquired hypothalamic obesity. The double-blinded, 52-week trial enrolled 120 patients, randomized 2:1. In addition to the primary endpoint and other data points above, clinically meaningful improvements were observed across key secondary endpoints at week 52, including: No new safety signals with setmelanotide were observed, in line with setmelanotide’s well-established and well-understood safety profile. Consistent with prior clinical experience, setmelanotide was generally well tolerated in the TRANSCEND study. The most common treatment-emergent adverse events (affecting >20% of participants) were nausea, vomiting, diarrhea, injection site reaction, skin hyperpigmentation and headache. No serious adverse events leading to study discontinuation were reported. “This 12-month placebo-controlled trial required an incredible commitment from patients, their families and clinical staff for which we are extremely grateful. The highly clinically meaningful results from the TRANSCEND study potentially represent a transformational milestone for Rhythm,” said David Meeker, M.D., Chairman, President and Chief Executive Officer of Rhythm. “Given these compelling new efficacy data with setmelanotide in a broader patient population than in our Phase 2 trial, we are preparing to submit a supplemental New Drug Application to the FDA and a Type II variation request to the European Medicines Agency in the third quarter of 2025. These planned submissions could pave the way for setmelanotide to become the first-ever approved therapy for these patients. In addition, these strong results with an MC4R agonist increase our confidence in the development of our next-generation MC4R agonists, currently in ongoing Phase 1/2 clinical trials in acquired hypothalamic obesity.” Rhythm anticipates presenting full data from the TRANSCEND study at an upcoming medical meeting. Conference Call Information Rhythm Pharmaceuticals will host a live conference call and webcast at 8:00 a.m. ET today to discuss these clinical data. Participants may register for the conference call here . A 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 at least 30 days following the call. About the Phase 3 TRANSCEND Trial The global, randomized, double-blind, placebo-controlled Phase 3 TRANSCEND trial evaluated the efficacy and safety of setmelanotide in patients with acquired hypothalamic obesity. A total of 120 patients age 4 years and older were randomized 2:1 to either a daily subcutaneous injection of setmelanotide (80 patients) or placebo (40 patients). The primary endpoint was mean percent change in body mass index (BMI) from baseline after 52 weeks of treatment. Secondary endpoints assess daily hunger, hyperphagia (extreme unsatisfied drive to consume food), weight, quality of life and safety and tolerability. A supplemental cohort of 12 Japanese patients remains ongoing with completion and topline data anticipated in the first quarter of 2026. 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. Please see the full Prescribing Information for additional Important Safety Information. 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. SOURCE : Rhythm Pharmaceuticals

Treatment with Imcivree was associated with improvements in all primary and secondary endpoints in its TRANSCEND trial, prompting Rhythm to plan regulatory filings in the third quarter of this year. While pharma giants Novo Nordisk and Eli Lilly may have a solid hold on the obesity arena, Rhythm Pharmaceuticals is looking to corner a subset of the market with its Imcivree.About 5,000 to 10,000 people in the U.S. live with acquired hypothalamic obesity, or obesity that stems from damage to the part of the brain that controls hunger and weight regulation. Drugs meant for those with general obesity have shown “limited effectiveness” in providing long-term, durable weight loss for those with the rarer condition, pediatric endocrinologist Susan Philips, M.D., explained in an April 7 press release issued by Rhythm.Enter Imcivree (setmelanotide), a melanocortin-4 receptor (MC4R) agonist that was first approved in 2020 for patients six years and older with obesity due to rare genetic diseases proopiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1) or leptin receptor (LEPR). Rhythm tested the drug in what is “believed to be” the largest and longest placebo-controlled study in those with acquired hypothalamic obesity, finding that Imcivree treatment prompted a mean BMI reduction of 16.5% from baseline, compared to a 3.3% BMI increase for those on placebo by week 52. Four out of five patients who took Imcivree cut down on their BMI by 5% or more, Rhythm said.The “highly clinically meaningful results” from the trial could represent a “transformational milestone for Rhythm,” CEO David Meeker, M.D. said in the release. The company is now gearing up to submit a regulatory bid for a label expansion with the FDA and the European Medicines Agency in the third quarter of this year, which could “pave the way for setmelanotide to become the first-ever approved therapy for these patients.”Rhythm plans to present full data from the trial at an upcoming medical meeting and is continuing to run the study in a supplemental cohort of 12 Japanese patients, with topline data expected in the first quarter of 2026. The results also serve to boost the company’s confidence in its next-generation MC4R agonists, which are currently being evaluated in ongoing phase 1/ 2 trials in acquired hypothalamic obesity, Meeker added. Outside of the U.S., Rhythm estimates that there are some 5,000 to 8,000 people who have the condition in Japan and about 3,500 to 10,000 in Europe. Hypothalamic obesity typically follows brain tumors or other brain injuries and manifests in accelerated weight gain, a decline in energy expenditure and hyperphagia, a pathological condition defined by insatiable hunger and abnormal food-seeking behaviors. After its initial approval, Imcivree picked up another nod in 2022 for adult and pediatric patients with obesity linked to another rare genetic disease, Bardet-Biedl syndrome. Late last year, the FDA expanded the drug’s use in its current indications to children as young as two. In 2024, Imcivree racked up sales of $130.1 million, a boost from 2023’s $77.4 million haul. An approval for hypothalamic obesity would be the first non-genetic disease population the drug is cleared to cover, marking a significant new opportunity for the drug.