Latest news with #MC4R
Yahoo
2 days ago
- Business
- Yahoo
Jefferies Maintains Buy Rating on Rhythm Pharmaceuticals (RYTM), Sets $80 Price Target
In a report released on June 4, Dennis Ding from Jefferies maintained a Buy rating on Rhythm Pharmaceuticals, Inc. (NASDAQ:RYTM) with a price target of $80.00. The analyst based the rating on the company's strategic developments and promising pipeline. One of the primary reasons behind the rating was the anticipated Phase II data for the oral treatment for hypothalamic obesity (HO). It is expected to deliver notable BMI reduction and has been de-risked, thereby extending the potential of the franchise beyond the current expiration dates. A scientist conducting research in a laboratory, studying a Petri dish with advanced biopharmaceuticals. The analyst stated that management is confident in the weekly subcutaneous (subQ) treatment, which closely aligns with the previously approved setmelanotide, and thus further adds to the positive outlook for Rhythm Pharmaceuticals, Inc. (NASDAQ:RYTM). According to Ding, the setmelanotide Phase II open-label trial for Prader-Willi Syndrome can also pave the way for a significant opportunity if successful, even after its previous challenges. Management is focusing on patient starts instead of the immediate revenue post-launch, and this strategy supports the long-term growth prospects, according to the analyst. Rhythm Pharmaceuticals, Inc. (NASDAQ:RYTM) is a commercial-stage biopharmaceutical company that develops and commercializes therapeutics for the treatment of rare diseases. Its product pipeline includes IMCIVREE (setmelanotide), a precision medicine that treats hyperphagia and severe obesity caused by rare melanocortin-4 receptor (MC4R) diseases. The company also has other programs, including a preclinical suite of investigational candidates to treat congenital hyperinsulinism and a clinical development program for setmelanotide in other rare MC4R pathway diseases. While we acknowledge the potential of RYTM as an investment, our conviction lies in the belief that some AI stocks hold greater promise for delivering higher returns and have limited downside risk. If you are looking for an extremely cheap AI stock that is also a major beneficiary of Trump tariffs and onshoring, see our free report on the best short-term AI stock. READ NEXT: and . Disclosure: None.
Yahoo
15-05-2025
- Health
- Yahoo
Axovia Therapeutics Unveils New Preclinical Data for AXV-201, for Treatment of Genetic Obesity Caused by MC4R Mutations, at ASGCT
Positive preclinical POC data show that novel gene therapy, AXV-201, prevented obesity and metabolic disease in a monogenic model LONDON, May 15, 2025 (GLOBE NEWSWIRE) -- Axovia Therapeutics Ltd., a biotechnology company developing therapies to address the genetic causes of blindness and obesity, announced that today it will unveil new preclinical proof-of-concept data for novelly designed, AXV-201, to treat individuals with severe obesity and very high BMIs resulting from MC4R mutations, in a poster presentation at the American Society of Gene and Cell Therapy (ASGCT) 28th Annual Meeting, which is being held from May 13-17, 2025 in New Orleans, LA. 'Today's presentation highlights how a new human sequence and AAV9 vector, AXV-201, can rescue the weight gain phenotype and could prove to be a powerful treatment for individuals with severe obesity and very high BMIs resulting from MC4R mutations,' said Dr. Victor Hernandez, Co-Founder and Chief Scientific Officer. 'MC4R is a key regulator of body weight and is the most common cause of genetic early-onset monogenic obesity. A gene replacement therapy could be transformative for those suffering across the globe.' Preclinical proof-of-concept data highlights include: New codon-optimized self-complementary human cMC4R sequence was able to express the MC4R transgene activity greater than five times more efficiently than the wild-type cDNA In vivo administration of AXV-201 in Mc4r-null mice prevented the development of obesity in males and females, restoring a normal weight trajectory comparable to wild-type controls and showed normalization of neurometabolic markers No safety concerns were observed when wild-types cohorts were dosed with AXV-201 'Genetic forms of obesity, such as those linked to MC4R mutations, represent a significant and often overlooked challenge for patients and clinicians alike,' said Dr. Jesse Richards, OU Health. 'Despite advances in obesity research, there remains a critical unmet need for effective therapies that address the underlying genetic causes. These data lay the groundwork for bringing new hope to individuals and families affected by MC4R-related obesity, offering the possibility of a targeted intervention that aims to normalize weight and have a better effect than currently available options.' About Melanocortin 4 Receptor () MutationsMelanocortin 4 receptor (MC4R) mutations are the most common cause of human monogenic obesity. Individuals with MC4R loss of function mutations suffer from hyperphagia, severe obesity and hyperinsulinemia. Impact of the different type of MC4R mutation depends on how they reduce MC4R expression and the impact they have on the production of cyclic AMP (cAMP). Mutations in heterozygosity, with partial MC4R functionality are the most frequent, but homozygous mutations and double heterozygotes account for 25% of MC4R mutations. There are approximately 50,000 patients with complete MC4R loss of function (LoF) and BMI>40 in the United States, European Union and Middle East. About Axovia Therapeutics Therapeutics is leading the development of therapies that address the genetic causes of blindness and obesity syndromes that are driven by cilia dysfunction. Ciliopathies are a group of more than 55 rare inherited genetic diseases linked to more than 950 genes that impact the function of cilia which are critical for protein transport and cellular signaling. The company plans to initiate a clinical study to treat retinal degeneration for its lead program for Bardet-Biedl Syndrome (BBS), AXV-101, in mid-2025, based on robust preclinical efficacy and toxicological data with established scaled GMP manufacturing and patient registries. AXV-101 has achieved U.S. Food and Drug Administration Orphan Drug Designation and Rare Pediatric Disease Designation. The company is developing its second program, AXV-201, for genetic obesity caused by MC4R mutations. Axovia is backed by ALSA Ventures and was formed following decades of work on ciliopathies at University College London by co-founders Professor Phil Beales and Dr. Victor Hernandez. For further information, please visit Contact:Professor Phil BealesChief Executive Officerinvestors@
Yahoo
17-04-2025
- Health
- Yahoo
Palatin Reports Positive Appetite Suppression Results From Phase 2 Obesity Study of MC4R Agonist Bremelanotide and Tirzepatide
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 under identifier NCT06565611. Pipeline DevelopmentPalatin 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 ObesityGenetic 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 AgonistsThe 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 PalatinPalatin 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 StatementsStatements 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. View original content to download multimedia: SOURCE Palatin Technologies, Inc. Sign in to access your portfolio
Yahoo
27-02-2025
- Business
- Yahoo
Rhythm Pharmaceuticals Inc (RYTM) Q4 2024 Earnings Call Highlights: Strong Revenue Growth and ...
Cash and Cash Equivalents: $320.6 million at the end of 2024. Revenue: $41.8 million in Q4 2024; $130.1 million for the full year 2024. Cost of Sales: $3.8 million in Q4 2024, approximately 9% of net product revenue. R&D Expenses: $41.2 million for Q4 2024, up from $29.9 million in Q4 2023. SG&A Expenses: $38.1 million for Q4 2024, compared to $32.4 million in Q4 2023. Net Loss per Share: $0.72 for Q4 2024, including $0.02 per share from accrued dividends on convertible preferred stock. Operating Expenses: Totaled $382.3 million for 2024, including $39.7 million in stock-based compensation. Non-GAAP Operating Expenses: $250.2 million for 2024, at the low end of the $250 million to $270 million guidance range. US Revenue Contribution: $31.7 million in Q4 2024, accounting for 76% of quarterly revenue. Gross Margin: Gross-to-net in the US remained consistent at about 85% for Q3 and Q4 2024. Warning! GuruFocus has detected 3 Warning Signs with RYTM. Release Date: February 26, 2025 For the complete transcript of the earnings call, please refer to the full earnings call transcript. Rhythm Pharmaceuticals Inc (NASDAQ:RYTM) is well-capitalized, having raised $75 million, extending its cash run rate into 2027. The company completed enrollment in its phase 2 daily oral Maigon study, indicating progress in its pipeline. There is significant opportunity in genetically driven impairments to the MC4R pathway, with potential for long-term growth. The company received FDA approval for a label expansion to include younger patients, enhancing its market reach. International expansion is progressing well, with access achieved in over 15 countries outside the US. The company faces challenges in accurately predicting the efficacy outcomes of its trials, particularly in the phase 3 HO trial. There is uncertainty regarding the uptake and market penetration of new therapies, especially in comparison to existing treatments like GLP-1s. The company anticipates increased R&D and SG&A expenses in 2025, which could impact profitability. There are complexities in diagnosing and treating congenital hypothalamic obesity, which may affect trial outcomes and market potential. The company must navigate reimbursement challenges and prior authorization processes, which could slow down market adoption. Q: Will the sad mad portion of the RM 718 study be shared separately, or will it be included in the second half 2025 update with part C? Also, what is the expected mix of adults and pediatric patients in the phase 3 trial on HO? A: We don't have specific plans to present the sad mad portion separately; it will likely be included with the Part C update. Regarding the phase 3 trial, the regulators wanted more adults, so we focused on that, achieving about a 50/50 split between adults and pediatric patients. The Japanese cohort will have a similar mix. Q: How do you see the uptake in the HO patient population compared to BBS or genetic populations? Could the pre-existing obesity set point impact the phase 3 HO trial results? A: The HO patient population is more identifiable and concentrated in endocrinology, leading to potentially faster uptake than BBS. Regarding the pre-existing obesity set point, our drug aims to restore normal physiology, potentially bringing patients back to their pre-injury state, but it is not a treatment for general obesity. Q: What does management consider a successful outcome for the Se Melannoide phase 3 trial in terms of weight loss? Also, is there a possibility of a modestly down quarter due to inventory destocking? A: We would be disappointed with less than a 10% weight loss, though the regulatory hurdle is 5%. We anticipate inventory destocking in Q1, which could impact quarter-over-quarter results. Q: Can you discuss the prevalence of HO beyond cranial pharyngioma data and any ongoing work to understand other etiologies, including congenital forms? A: We are gaining confidence in our prevalence estimates, which may be conservative. Other tumors contribute significantly to the population, and we are exploring congenital syndromes where obesity may be related to hypothalamic impairment. Q: What weight loss would doctors like to see to use Se Melannoide in HO patients? Would you consider a cash raise after the HO data set reads out? A: Doctors are interested in consistent efficacy rather than specific weight loss percentages. Regarding a cash raise, we have extended our runway to avoid needing a raise immediately after the data readout, but future raises will depend on program success. For the complete transcript of the earnings call, please refer to the full earnings call transcript. This article first appeared on GuruFocus. Sign in to access your portfolio
Yahoo
26-02-2025
- Business
- Yahoo
Rhythm Pharmaceuticals Reports Fourth Quarter and Full Year 2024 Financial Results and Business Update
-- Fourth quarter 2024 net revenue from global sales of IMCIVREE® (setmelanotide) of $41.8 million -- -- On track to report topline data from global Phase 3 trial evaluating setmelanotide in acquired hypothalamic obesity in the second quarter of 2025 -- -- Completed enrollment in the Phase 2 trial of oral MC4R agonist bivamelagon in acquired hypothalamic obesity -- -- FDA approved expanded label for IMCIVREE to include children as young as 2 years old -- -- Raised approximately $75 million in gross proceeds under ATM equity offering program; Cash runway extended into 2027 -- -- Management to host conference call today at 8:00 a.m. ET -- BOSTON, Feb. 26, 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 reported financial results and provided a business update for the fourth quarter and full year ended December 31, 2024. 'Rhythm delivered solid IMCIVREE global sales growth in the fourth quarter and is poised to drive continued growth in 2025,' said David Meeker, M.D., Chairman, Chief Executive Officer and President of Rhythm. 'Our Phase 3 trial in acquired hypothalamic obesity (HO) remains on track as we expect to disclose topline data in the second quarter of 2025. We are well capitalized as we strengthened our balance sheet with approximately $75 million in gross proceeds raised under our ATM program, which extends our cash runway into 2027, enabling us to execute on multiple clinical milestones expected in the year ahead.' Fourth Quarter and Recent Business Highlights Revenue from global sales of IMCIVREE was $41.8 million for the fourth quarter of 2024, an increase of 26% percent on a sequential basis from the third quarter of 2024, primarily driven by sales of IMCIVREE for the treatment of Bardet-Biedl syndrome (BBS). In the fourth quarter of 2024, revenue of $31.7 million, or 76% of product revenue, was generated in the United States, an increase of 36.2% on a sequential basis; revenue of $10.1 million, or 24% of product revenue, was generated outside the United States; Today, the Company announced that it raised approximately $75 million in gross proceeds from the sale of approximately 1.3 million shares of common stock at a weighted average price of $56.30 under its 'at the market' equity offering program (the 'ATM Program') during the fourth quarter of 2024 and in January 2025; Today, Rhythm announced that it completed enrollment in the Phase 2 trial evaluating oral MC4R agonist bivamelagon (LB54640) in acquired hypothalamic obesity; Today, Rhythm announced a strategic partnership agreement with Trispera Pharma Solutions in Turkey; On January 10, 2025, Rhythm announced that it: Completed enrollment in its supplemental, 12-patient Japanese cohort of the global Phase 3 trial evaluating setmelanotide in acquired HO. Data from this supplemental cohort will serve as the basis for a regulatory submission in Japan; Completed enrollment in the Phase 3 EMANATE trial of setmelanotide, which is comprised of four substudies: SH2B1 (n=121); POMC and/or PCSK1 (n=79); SRC1 (n=73); and LEPR (n=23). The four-substudy design of this trial allows for independent data readouts and potential registration for each genetic cohort; On December 20, 2024, the Company announced that the U.S. Food and Drug Administration (FDA) approved an expanded indication for IMCIVREE to include children as young as 2 years old with syndromic or monogenic obesity due to BBS or genetically confirmed pro-opiomelanocortin (POMC), including proprotein convertase subtilisin/kexin type 1 (PCSK1), deficiency or leptin receptor (LEPR) deficiency; On December 3, 2024, Rhythm announced that the United Kingdom's Medicines & Healthcare products Regulatory Agency (MHRA) has expanded the marketing authorization for IMCIVREE to include the treatment of obesity and control of hunger associated with genetically confirmed BBS or genetically confirmed loss-of-function biallelic POMC, including PCSK1, deficiency or biallelic LEPR deficiency in adult and pediatric patients as young as 2 years old and older; and During the annual meeting of the European Society for Paediatric Endocrinology in November 2024, Rhythm presented new, real-world data that showed four pediatric patients, two with acquired HO and two with congenital HO, achieved >5% weight reduction at three months on setmelanotide. The Company announced plans for a new, 34-week substudy in the ongoing setmelanotide Phase 3 trial in 39 patients with congenital HO aged 4 years and older. Anticipated Upcoming Milestones Rhythm expects to achieve the following near-term milestones: Begin enrolling the first patients with congenital HO in a 34-week substudy of setmelanotide being conducted under the protocol for its global Phase 3 trial in the first quarter of 2025; Begin enrolling the first patients with Prader-Willi syndrome (PWS) in a 26-week, open-label Phase 2 trial evaluating setmelanotide in the first quarter of 2025; Begin enrolling patients with acquired HO in Part C of the Phase 1 trial evaluating the weekly, MC4R agonist RM-718 in the first quarter of 2025; Announce top-line data in the Phase 3 trial evaluating setmelanotide in acquired HO in the second quarter of 2025; Announce topline data from the Phase 2 trial of bivamelagon in acquired HO in the second half of 2025; and Announce top-line data in the Phase 3 EMANATE trial evaluating setmelanotide in genetically caused MC4R pathway diseases in the first half of 2026. Fourth Quarter and Full Year 2024 Financial Results: Cash Position: As of December 31, 2024, cash, cash equivalents and short-term investments were approximately $320.6 million, as compared to $275.8 million as of December 31, 2023. The December 31, 2024 cash balance does not include gross proceeds of approximately $34.7 million from the sale of stock under the Company's ATM program executed during January 2025. Revenue: Net product revenues relating to global sales of IMCIVREE were $41.8 million for the fourth quarter of 2024 and $130.1 million for the full year of 2024, as compared to $24.2 million for the fourth quarter of 2023 and $77.4 million for the full year of 2023. R&D Expenses: R&D expenses were $41.2 million in the fourth quarter of 2024 and $238.0 million for the full year of 2024, as compared to $29.9 million in the fourth quarter of 2023 and $135.0 million for the full year of 2023. The year-over-year increase was primarily due to increased costs associated with the acquisition of bivamelagon from LG Chem and its development with certain additional product manufacturing activity, ongoing clinical trials and increased headcount. This increase was partially offset by decreased costs in other trials. SG&A Expenses: SG&A expenses were $38.1 million for the fourth quarter of 2024 and $144.3 million for the full year of 2024, as compared to $32.4 million for the fourth quarter of 2023 and $117.5 million for the full year of 2023. The year-over-year increase was primarily due to increased headcount, marketing and promotions costs and expenses for professional services and partially offset by inventory-related costs that were capitalized as labor and overhead. Other income (expense), net: Other income (expense), net was ($2.1) million for the fourth quarter of 2024 and $5.2 million for the full year of 2024. Net Loss: Net loss attributable to common stockholders was ($44.6) million for the fourth quarter of 2024 and ($264.6) million for the full year of 2024, or a net loss per basic and diluted share of ($0.72) and ($4.34), respectively, as compared to a net loss attributable to common stockholders of ($41.6) million for the fourth quarter of 2023 and ($184.7) million for the full year of 2023, or a net loss per basic and diluted share of ($0.70) and ($3.20), respectively. Financial Guidance: For the year ended December 31, 2024, the Company had GAAP total operating expenses of $382.3 million, inclusive of $92.4 million associated with the acquisition of the rights to bivamelagon from LG Chem. The Company today reported non-GAAP Operating Expenses for the year ended December 31, 2024 of $250.2 million, which is derived from GAAP total operating expenses of $382.3 million less $39.7 million in stock-based compensation and $92.4 million associated with the acquisition of the rights to bivamelagon from LG Chem. For the year ending December 31, 2025, Rhythm anticipates approximately $285 million to $315 million in Non-GAAP Operating Expenses. Non-GAAP Operating Expenses are derived from: GAAP total operating expenses, inclusive of: SG&A expenses of approximately $135 million to $145 million; R&D expenses of approximately $150 million to $170 million; and Excluding stock-based compensation. Non-GAAP Operating Expenses is defined as GAAP operating expenses excluding stock-based compensation and fixed consideration related to in-licensing (see below under "Non-GAAP Financial Measures" for more details). Based on its current operating plans, Rhythm expects that its existing cash, cash equivalents and short-term investments as of December 31, 2024, and including proceeds from the sale of stock through its ATM program during January 2025, will be sufficient to fund its operating expenses and capital expenditure requirements into 2027. Conference Call InformationRhythm Pharmaceuticals will host a live conference call and webcast at 8:00 a.m. ET today to review its fourth quarter and full year 2024 financial results and recent business activities. Participants may register for the conference call here. It is recommended that participants join the call ten minutes prior to the scheduled start. A webcast of the call will also be available under "Events and Presentations" in the Investor Relations section of the Rhythm Pharmaceuticals website at 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 PharmaceuticalsRhythm 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 LB54640 and RM-718, and a preclinical suite of small molecules for the treatment of congenital hyperinsulinism. Rhythm's headquarters is in Boston, MA. Setmelanotide IndicationIn 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 REACTIONSMost 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 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 StatementsThis 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 safety, efficacy, potential benefits of, and clinical design or progress of any of our products or product candidates at any dosage or in any indication, including, setmelanotide, bivamelagon, and RM-718; the potential use of setmelanotide in patients with acquired hypothalamic obesity; our expectations surrounding potential regulatory submissions, progress, or approvals and timing thereof for any of our product candidates; the estimated market size and addressable population for our drug products; the announcement of data from our clinical trials, including our Phase 3 trial evaluating setmelanotide for patients with acquired hypothalamic obesity, the substudy evaluating setmelanotide for patients with congenital hypothalamic obesity, the Phase 3 EMANATE trial evaluating setmelanotide in genetically caused MC4R pathway diseases, and the Phase 2 trial evaluating the oral MC4R agonist bivamelagon in acquired hypothalamic obesity; Part C of the Phase 1 trial evaluating RM-718; the open-label Phase 2 trial evaluating setmelanotide in patients with Prader-Willi syndrome; the ongoing enrollment in our clinical trials; existing or future collaboration agreements; the Company's business strategy and plans; our anticipated financial performance and financial position for any period of time, including estimated Non-GAAP Operating Expenses for the year ending December 31, 2025; and the sufficiency of our cash, cash equivalents and short-term investments to fund our operations; and the timing of any of the foregoing. Statements using words such as 'expect', 'anticipate', 'believe', 'may', 'will', 'aim' and similar terms are also forward-looking statements. Such statements are subject to numerous risks and uncertainties, including, but not limited to, our ability to enroll patients in clinical trials, the design and outcome of clinical trials, the ability to achieve necessary regulatory approvals, risks associated with data analysis and reporting, failure to identify and develop additional product candidates, unfavorable pricing regulations, third-party reimbursement practices or healthcare reform initiatives, risks associated with the laws and regulations governing our international operations and the costs of any related compliance programs, the impact of competition, risks relating to product liability lawsuits, inability to maintain collaborations, or the failure of these collaborations, our reliance on third parties, risks relating to intellectual property, our ability to hire and retain necessary personnel, general economic conditions, risks related to internal control over financial reporting, and the other important factors discussed under the caption 'Risk Factors' in our Annual Report on Form 10-K for the year ended December 31, 2024 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 press release or to update them to reflect events or circumstances occurring after the date of this press release, whether as a result of new information, future developments or otherwise. Non-GAAP Financial MeasuresThis press release includes Non-GAAP Operating Expenses, a supplemental measure of our performance that is not required by, or presented in accordance with, U.S. GAAP and should not be considered as an alternative to operating expenses or any other performance measure derived in accordance with GAAP. We define Non-GAAP Operating Expenses as GAAP operating expenses excluding stock-based compensation and fixed consideration related to in-licensing. We caution investors that amounts presented in accordance with our definition of Non-GAAP Operating Expenses may not be comparable to similar measures disclosed by our competitors because not all companies and analysts calculate this non-GAAP financial measure in the same manner. We present this non-GAAP financial measure because we consider it to be an important supplemental measure of our performance and believe it is frequently used by securities analysts, investors, and other interested parties in the evaluation of companies in our industry. Management believes that investors' understanding of our performance is enhanced by including this non-GAAP financial measure as a reasonable basis for comparing our ongoing results of operations. Management uses this non-GAAP financial measure for planning purposes, including the preparation of our internal annual operating budget and financial projections; to evaluate the performance and effectiveness of our operational strategies; and to evaluate our capacity to expand our business. This non-GAAP financial measure has limitations as an analytical tool, and should not be considered in isolation, or as an alternative to, or a substitute for operating expenses or other financial statement data presented in accordance with GAAP in our consolidated financial statements. Rhythm has not provided a quantitative reconciliation of forecasted Non-GAAP Operating Expenses to forecasted GAAP operating expenses because the Company is unable, without making unreasonable efforts, to calculate the reconciling item, stock-based compensation expenses, with confidence. This item, which could materially affect the computation of forward-looking GAAP operating expenses, is inherently uncertain and depends on various factors, some of which are outside of Rhythm's control. Corporate Contact:David ConnollyHead of Investor Relations and Corporate CommunicationsRhythm Pharmaceuticals, Inc.857-264-4280dconnolly@ Media Contact:Sheryl SeapyReal Chemistry(949) 903-4750sseapy@ Rhythm Pharmaceuticals, Inc. Condensed Consolidated Statements of Operations and Comprehensive Loss (in thousands, except share and per share data) (Unaudited) Three Months Ended December 31, Year Ended December 31, 2024 2023 2024 2023 evenues: Product revenue, net $ 41,830 $ 24,234 $ 130,126 $ 77,428 Total revenues 41,830 24,234 130,126 77,428 Costs and expenses: Cost of sales 3,787 3,233 13,368 9,302 Research and development 41,168 29,892 237,957 134,951 Selling, general, and administrative 38,130 32,374 144,304 117,532 Total costs and expenses 83,085 65,499 395,629 261,785 Loss from operations (41,255 ) (41,265 ) (265,503 ) (184,357 ) Other income (expense): Other income (expense), net (195 ) 39 2,239 190 Gain on settlement of forward contract — — 8,900 — Interest expense (5,447 ) (4,018 ) (20,603 ) (13,892 ) Interest income 3,514 3,819 14,711 13,945 Total other income (expense), net (2,128 ) (160 ) 5,247 243 Loss before income taxes (43,383 ) (41,425 ) (260,256 ) (184,114 ) Provision for income taxes (89 ) 196 346 564 Net loss $ (43,294 ) $ (41,621 ) $ (260,602 ) $ (184,678 ) Accrued dividends on convertible preferred stock (1,340 ) — (3,970 ) — Net loss attributable to common stockholders $ (44,634 ) $ (41,621 ) $ (264,572 ) $ (184,678 ) Net loss per share attributable to common stockholders, basic and diluted $ (0.72 ) $ (0.70 ) $ (4.34 ) $ (3.20 ) Weighted-average common shares outstanding, basic and diluted 61,596,442 59,211,199 60,995,204 57,673,128 Other comprehensive loss: Net loss attributable to common stockholders $ (44,634 ) $ (41,621 ) $ (264,572 ) $ (184,678 ) Foreign currency translation adjustment 977 76 2 (140 ) Unrealized (loss) gain, net on marketable securities, net of tax (412 ) (175 ) (175 ) 366 Comprehensive loss $ (44,069 ) $ (41,720 ) $ (264,745 ) $ (184,452 ) Condensed Consolidated Balance Sheets(in thousands, except share and per share data) December 31,2024 December 31,2023 Assets Current assets: Cash and cash equivalents $ 89,137 $ 60,081 Short-term investments 231,428 215,765 Accounts receivable, net 18,512 14,867 Inventory 18,741 8,624 Prepaid expenses and other current assets 16,382 8,931 Total current assets 374,200 308,268 Property and equipment, net 632 1,341 Right-of-use asset 3,477 781 Intangible assets, net 6,174 7,028 Restricted cash 464 328 Other long-term assets 7,326 14,999 Total assets $ 392,273 $ 332,745 Liabilities, Convertible Preferred Stock and Stockholders' Equity Current liabilities: Accounts payable $ 12,328 $ 4,885 Accrued expenses and other current liabilities 62,658 48,262 Other current liability - LG Chem 37,704 — Deferred revenue 1,286 1,286 Deferred royalty obligation, current 1,541 — Lease liability — 770 Total current liabilities 115,517 55,203 Long-term liabilities: Deferred royalty obligation 108,269 106,143 Lease liability, non-current 3,938 490 Derivative liability — 1,150 Total liabilities 227,724 162,986 Commitments and contingencies Series A convertible preferred stock, $0.001 par value: 150,000 sharesauthorized; 150,000 and 0 shares issued and outstanding at December 31, 2024and December 31, 2023, respectively. Liquidation preference of $150,000 as ofDecember 31, 2024. 142,820 — Stockholders' equity: Common stock, $0.001 par value: 120,000,000 shares authorized; 62,390,654and 59,426,559 shares issued and outstanding at December 31, 2024 andDecember 31, 2023, respectively 61 59 Additional paid-in capital 1,177,045 1,064,302 Accumulated other comprehensive (loss) income (39 ) 134 Accumulated deficit (1,155,338 ) (894,736 ) Total stockholders' equity 21,729 169,759 Total liabilities, convertible preferred stock and stockholders' equity $ 392,273 $ 332,745 Sign in to access your portfolio
