Hyperphagia

REDWOOD CITY, Calif., March 06, 2024 (GLOBE NEWSWIRE) -- Soleno Therapeutics Inc. (Soleno) (NASDAQ: SLNO), a clinical-stage biopharmaceutical company developing novel therapeutics for the treatment of rare diseases, today provided a corporate update, and reported financial results for the fourth quarter and full-year ended December 31, 2023. Full Year 2023 and Recent Corporate Highlights Announced positive statistically significant top-line data from the randomized withdrawal period of Study C602, a long-term treatment study of DCCR (Diazoxide Choline) Extended-Release tablets for the treatment of Prader-Willi syndrome (PWS) in September 2023. The study met its primary endpoint, demonstrating a highly statistically significant difference in change from baseline in HQ-CT total score for DCCR compared to placebo (p=0.0022). Secondary endpoints of Clinical Global Impression of Severity (CGI-S) and Clinical Global Impression of Improvement (CGI-I) both showed strong trends towards worsening in the placebo group compared to DCCR (p=0.08 and 0.09), respectively. DCCR continued to be generally well-tolerated in the randomized withdrawal period with no new or unexpected safety signals. Planned submission of a New Drug Application (NDA) for DCCR in PWS remains on track for mid-2024, after receipt of pre-NDA meeting minutes from the U.S. Food and Drug Administration. The FDA stated that the potential for data from the DCCR clinical program to provide substantial evidence of effectiveness will be a matter of review following the submission of an NDA. Closed on gross proceeds of approximately $129 million from an underwritten public offering of common stock and concurrent private placement of common stock and pre-funded warrants in October 2023, and received $43.1 million from the sale and exercise of warrants issued in connection with the December 2022 Securities Purchase Agreement. Strengthened leadership team with appointments of Meredith Manning, M.B.A as Chief Commercial Officer, Dairine Dempsey, Ph.D. as Vice President, Europe and Lauren Budesheim, M.S. as Vice President of Human Resources. “Following recent feedback from the FDA, Soleno remains focused on preparing an NDA submission for DCCR in PWS mid-2024,” said Anish Bhatnagar, M.D., Chief Executive Officer of Soleno Therapeutics. “We believe data from our extensive clinical program, including highly statistically significant top-line results from the randomized withdrawal period of Study C602, supports that DCCR has the potential to be a safe and effective therapy for patients with PWS. With our strengthened leadership team and balance sheet, we are ideally positioned to carry out our corporate strategy and, if approved, deliver a new treatment option for PWS patients.” Financial Results Soleno’s current research and development efforts are primarily focused on advancing its lead product candidate, DCCR, for the treatment of PWS, through late-stage clinical development. Fourth Quarter and Full Year Ended December 31, 2023 Financial Results As of December 31, 2023, Soleno had cash and cash equivalents of approximately $169.7 million, which includes $129 million received upon the closing of the public offering and concurrent private placement in October 2023, and $43.1 million received from the sale and exercise of warrants issued in connection with the December 2022 Securities Purchase Agreement. The Company may receive an additional $16.9 million from the exercise of the remaining warrants issued pursuant to the December 2022 Securities Purchase Agreement. Research and development expenses were $8.7 million for the quarter ended December 31, 2023, compared to $3.8 million in the same period of 2022, and $25.2 million for the year ended December 31, 2023, compared to $15.3 million for the year ended 2022. The increase was primarily due to increased clinical trials costs, manufacturing efforts, and expenditures in support of our NDA submission. General and administrative expenses were $4.1 million for the quarter ended December 31, 2023, compared to $2.4 million in the same period of 2022, and $13.5 million for the year ended December 31, 2023, compared to $9.8 million for the year ended 2022. The increase was primarily related to higher stock-based compensation expense, higher costs because of an increase in headcount and higher professional and consulting expenses in 2023. Soleno is obligated to make cash payments of up to a maximum of $21.2 million to the former Essentialis stockholders upon the achievement of certain commercial milestones associated with the future sales of DCCR in accordance with the terms of Soleno’s 2016 merger agreement with Essentialis. The fair value of the liability for the contingent consideration payable by the Company upon achieving two commercial sales milestones of $100 million and $200 million in revenue in future years was estimated to be $11.5 million as of December 31, 2023, a $1.1 million increase from the estimate as of September 30, 2023. Total other income (expense), net, was $2.6 million for the quarter ended December 31, 2023, and $0.1 million in the same period of 2022. For the year, total other income (expense), net, was $2.4 million for 2023, and $0.3 million for 2022. Other income (expense) consists of interest income and changes in the fair value of the Company’s warrant liability. Net loss was approximately $11.3 million, or $0.33 per basic and diluted share, for the quarter ended December 31, 2023, and $5.5 million, or $0.58 per basic and diluted share, in the same period of 2022. Net loss for the year ended December 31, 2023, was approximately $39.0 million, or $2.36 per basic and diluted share, compared to a net loss of approximately $24.1 million, or $2.87 per basic and diluted share, for the year ended December 31, 2022. About PWS The Prader-Willi Syndrome Association USA estimates that PWS occurs in one in every 15,000 live births. The hallmark symptom of this disorder is hyperphagia, a chronic and life-threatening feeling of intense, persistent hunger, food pre-occupation, extreme drive to food seek and consume food that severely diminish the quality of life for patients with PWS and their families. Additional characteristics of PWS include behavioral problems, cognitive disabilities, low muscle tone, short stature (when not treated with growth hormone), the accumulation of excess body fat, developmental delays, and incomplete sexual development. Hyperphagia can lead to significant morbidities (e.g., obesity, diabetes, cardiovascular disease) and mortality (e.g., stomach rupture, choking, accidental death due to food seeking behavior). In a global survey conducted by the Foundation for Prader-Willi Research, 96.5% of respondents (parent and caregivers) rated hyperphagia and 92.9% rated body composition as either the most important or a very important symptom to be relieved by a new medicine. There are currently no approved therapies to treat the hyperphagia/appetite, metabolic, cognitive function, or behavioral aspects of the disorder. About DCCR (Diazoxide Choline) Extended-Release Tablets DCCR is a novel, proprietary extended-release dosage form containing the crystalline salt of diazoxide and is administered once-daily. The parent molecule, diazoxide, has been used for decades in thousands of patients in a few rare diseases in neonates, infants, children and adults, but has not been approved for use in PWS. Soleno conceived of and established extensive patent protection for the therapeutic use of diazoxide, diazoxide choline and DCCR in patients with PWS. The DCCR development program is supported by data from five completed Phase 1 clinical studies in healthy volunteers and three completed Phase 2 clinical studies, one of which was in patients with PWS. In the PWS Phase 3 clinical development program, DCCR showed promise in addressing hyperphagia, the hallmark symptom of PWS, as well as several other symptoms such as aggressive/destructive behaviors, fat mass and other metabolic parameters. Diazoxide choline has received Orphan Drug Designation for the treatment of PWS in the U.S. and E.U., and Fast Track Designation in the U.S. About Soleno Therapeutics, Inc. Soleno is focused on the development and commercialization of novel therapeutics for the treatment of rare diseases. The company’s lead candidate, DCCR extended-release tablets, a once-daily oral tablet for the treatment of PWS, recently completed its Phase 3 development program to support a planned NDA submission. For more information, please visit . Forward-Looking Statements This press release contains forward-looking statements within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended. All statements other than statements of historical facts contained in this press release are forward-looking statements, including statements regarding the timing of any regulatory process or ultimate approvals and determining a path forward for DCCR for the treatment of PWS. In some cases, you can identify forward-looking statements by terms such as "may," "will," "should," "expect," "plan," "anticipate," "could," "intend," "target," "project," "contemplates," "believes," "estimates," "predicts," "potential" or "continue" or the negative of these terms or other similar expressions. These forward-looking statements speak only as of the date of this press release and are subject to a number of risks, uncertainties and assumptions, including the risks and uncertainties associated with the projected timeline of our NDA submission, whether FDA will agree with our interpretation of the data or the adequacy of data to support an NDA, the FDA’s review of our NDA, market conditions, as well as risks and uncertainties inherent in Soleno’s business, including those described in the company's prior press releases and in the periodic reports it files with the SEC. The events and circumstances reflected in the company's forward-looking statements may not be achieved or occur and actual results could differ materially from those projected in the forward-looking statements. Except as required by applicable law, the company does not plan to publicly update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise. Corporate Contact: Brian Ritchie LifeSci Advisors, LLC 212-915-2578 Soleno Therapeutics, Inc. Condensed Consolidated Balance Sheets (In thousands except share and per share data) December 31, 2023 December 31, 2022 Assets Current assets Cash and cash equivalents $ 169,681 $ 14,602 Prepaid expenses and other current assets 1,677 1,045 Total current assets 171,358 15,647 Long-term assets Property and equipment, net 12 26 Operating lease right-of-use assets 407 131 Intangible assets, net 8,749 10,693 Other long-term assets 165 — Total assets $ 180,691 $ 26,497 Liabilities and stockholders’ equity Current liabilities Accounts payable, net $ 3,149 $ 1,777 Accrued compensation 3,135 1,675 Accrued clinical trial site costs 3,393 3,222 Operating lease liabilities 273 155 Other current liabilities 1,555 484 Total current liabilities 11,505 7,313 Long-term liabilities 2018 PIPE Warrant liability - 1 Contingent liability for Essentialis purchase price 11,549 8,835 Long-term lease liabilities 130 — Total liabilities 23,184 16,149 Commitments and contingencies (Note 8) Stockholders’ equity Preferred stock, $0.001 par value; 10,000,000 shares authorized, no shares issued and outstanding — — Common stock, $0.001 par value, 100,000,000 shares authorized, 31,678,159 and 8,159,382 shares issued and outstanding at December 31, 2023 and December 31, 2022, respectively 32 8 Additional paid-in-capital 433,885 247,762 Accumulated deficit (276,410 ) (237,422 ) Total stockholders’ equity 157,507 10,348 Total liabilities and stockholders’ equity $ 180,691 $ 26,497 Soleno Therapeutics, Inc. Condensed Consolidated Statements of Operations (In thousands except share and per share data) Three Months Ended December 31, For the Years Ended December 31, 2023 2022 2023 2022 Operating expenses Research and development $ 8,689 $ 3,810 $ 25,189 $ 15,265 General and administrative 4,410 2,402 13,481 9,844 Change in fair value of contingent consideration 1,081 (602 ) 2,714 (712 ) Total operating expenses 13,910 5,610 41,384 24,397 Operating loss (13,910 ) (5,610 ) (41,384 ) (24,397 ) Other income (expense), net Change in fair value of warrant liability 470 (1 ) (182 ) 30 Interest income 2,144 125 2,578 300 Total other income (expense), net 2,614 124 2,396 330 Net loss $ (11,296 ) $ (5,486 ) $ (38,988 ) $ (24,067 ) Net loss per common share, basic and diluted $ (0.33 ) $ (0.58 ) $ (2.36 ) $ (2.87 ) Weighted-average common shares outstanding used to calculate basic and diluted net loss per common share 34,441,721 9,440,347 16,492,132 8,397,088

- 2023 total net product sales of $726.4 million, reflecting 40% revenue growth. - Fourth quarter DAYBUE™ (trofinetide) net product sales of $87.1 million and full year 2023 net product sales of $177.2 million. - Fourth quarter NUPLAZID® (pimavanserin) net product sales of $143.9 million and full year 2023 net product sales of $549.2 million. SAN DIEGO--(BUSINESS WIRE)-- Acadia Pharmaceuticals Inc. (Nasdaq: ACAD), today announced its financial results for the fourth quarter and full year ended December 31, 2023. “2023 was a transformational year for Acadia that positioned us for continued success in 2024 and beyond. We achieved 40% revenue growth primarily driven by the launch of our second commercial product, DAYBUE for the treatment of Rett syndrome, in addition to 6% growth in our established NUPLAZID franchise,” said Steve Davis, Chief Executive Officer. “In the fourth quarter we significantly advanced our pipeline with the initiation of a Phase 3 trial of ACP-101 in Prader-Willi syndrome, as well as our seamless Phase 2 / Phase 3 program for ACP-204 in Alzheimer’s disease psychosis. We look forward to announcing top-line results from our ADVANCE-2 study of pimavanserin for the negative symptoms of schizophrenia by the end of the first quarter.” Company Updates Anticipated to report top-line results from ADVANCE-2, a Phase 3 study evaluating pimavanserin for the treatment of the negative symptoms of schizophrenia, by the end of the first quarter. Initiated a pivotal Phase 3 COMPASS PWS study of ACP-101 (intranasal carbetocin) for the treatment of hyperphagia in Prader-Willi syndrome in the fourth quarter of 2023. Initiated a Phase 2 clinical trial of ACP-204 for the treatment of Alzheimer’s disease psychosis in the fourth quarter of 2023. Appointed Jennifer J. Rhodes as Executive Vice President, Chief Legal Officer and Secretary and Kimberly J. Manhard as Senior Vice President, Global Strategic Planning and Execution. Jennifer and Kimberly both joined Acadia’s executive leadership team. Financial Results Revenues Total revenues, comprised of net product sales from NUPLAZID and DAYBUE, were $231.0 million for the fourth quarter of 2023 and $726.4 million for the full year 2023. Net product sales of NUPLAZID were $143.9 million for the fourth quarter of 2023, an increase of 5% as compared to $136.5 million for the fourth quarter of 2022. Net product sales of NUPLAZID were $549.2 million for the full year 2023, an increase of 6% as compared to $517.2 million for the full year 2022. The increase in net product sales of NUPLAZID was due to growth in unit sales and a higher average net selling price in 2023 compared to 2022. Net product sales of DAYBUE were $87.1 million for the fourth quarter of 2023 and $177.2 million for the full year 2023. During 2022, there were no net product sales of DAYBUE, which was launched in April 2023. Research and Development Research and development expenses for the fourth quarter of 2023 were $66.7 million, compared to $75.7 million for the same period of 2022. For the full years of 2023 and 2022, research and development expenses were $351.6 million and $361.6 million, respectively. The decrease in research and development expenses during 2023 was mainly due to trofinetide commercial supply build that was expensed prior to approval. There was a similar level of clinical spend and business development investment year over year. Selling, General and Administrative Selling, general and administrative expenses for the fourth quarter of 2023 were $111.5 million, compared to $104.4 million for the same period of 2022. For the full years of 2023 and 2022, selling, general and administrative expenses were $406.6 million and $369.1 million, respectively. The increase in selling, general and administrative expenses was primarily due to increased commercial costs associated with the DAYBUE launch, partially offset by reductions in expenses associated with NUPLAZID. Net Income (Loss) For the fourth quarter of 2023, Acadia reported net income of $45.8 million, or $0.28 per common share, compared to a net loss of $41.7 million, or $0.26 per common share, for the same period in 2022. The net income and loss for the fourth quarters of 2023 and 2022 included $18.0 million and $14.4 million, respectively, of non-cash stock-based compensation expense. For the full year 2023, Acadia reported a net loss of $61.3 million, or $0.37 per common share, compared to a net loss of $216.0 million, or $1.34 per common share, for the same period in 2022. The net losses for the full years of 2023 and 2022 included $66.4 million and $68.2 million, respectively, of non-cash stock-based compensation expense. Cash and Investments At December 31, 2023, Acadia’s cash, cash equivalents, and investment securities totaled $438.9 million, compared to $416.8 million at December 31, 2022. Full Year 2024 Financial Guidance DAYBUE net product sales in the range of $370 to $420 million. NUPLAZID net product sales in the range of $560 to $590 million. GAAP R&D expense in the range of $305 to $325 million. GAAP SG&A expense in the range of $455 to $480 million. Conference Call and Webcast Information Acadia will host a conference call to discuss the fourth quarter and full year December 31, 2023 results today, Tuesday, February 27, 2024 at 1:30 p.m. PT/4:30 p.m. ET. The conference call will be available on Acadia’s website, Acadia.com, under the investors section and will be archived there until March 26, 2024. The conference call may also be accessed by registering for the call here. Once registered, participants will receive an email with the dial-in number and unique PIN number to use for accessing the call. About NUPLAZID® (pimavanserin) Pimavanserin is a selective serotonin inverse agonist and antagonist preferentially targeting 5-HT2A receptors. These receptors are thought to play an important role in neuropsychiatric disorders. In vitro, pimavanserin demonstrated no appreciable binding affinity for dopamine (including D2), histamine, muscarinic, or adrenergic receptors. Pimavanserin was approved for the treatment of hallucinations and delusions associated with Parkinson’s disease psychosis by the U.S. Food and Drug Administration in April 2016 under the trade name NUPLAZID. In addition, Acadia is developing pimavanserin as a potential treatment for the negative symptoms of schizophrenia. About DAYBUE™ (trofinetide) Trofinetide is a synthetic version of a naturally occurring molecule known as the tripeptide glycine-proline-glutamate (GPE). The mechanism by which trofinetide exerts therapeutic effects in patients with Rett syndrome is unknown. Trofinetide was approved for the treatment of Rett syndrome in adults and pediatric patients two years of age and older by the U.S. Food and Drug Administration in March 2023 under the trade name DAYBUE. About Acadia Pharmaceuticals Acadia is advancing breakthroughs in neuroscience to elevate life. For 30 years we have been working at the forefront of healthcare to bring vital solutions to people who need them most. We developed and commercialized the first and only FDA-approved drug to treat hallucinations and delusions associated with Parkinson’s disease psychosis and the first and only FDA-approved drug for the treatment of Rett syndrome. Our clinical-stage development efforts are focused on treating the negative symptoms of schizophrenia, Prader-Willi syndrome, Alzheimer’s disease psychosis and multiple other programs targeting neuropsychiatric symptoms in central nervous system disorders. For more information, visit us at Acadia.com and follow us on LinkedIn and Twitter. Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements include all statements other than statements of historical fact and can be identified by terms such as “may,” “will,” “should,” “could,” “would,” “expects,” “plans,” “anticipates,” “believes,” “estimates,” “projects,” “predicts,” “potential” and similar expressions (including the negative thereof) intended to identify forward-looking statements. Forward-looking statements contained in this press release, include, but are not limited to, statements about: (i) our business strategy, objectives and opportunities; (ii) plans for, including timing, development and progress of commercialization or regulatory timelines for, NUPLAZID, DAYBUE and our product candidates; (iii) benefits to be derived from and efficacy of our products, including the potential advantages of NUPLAZID and DAYBUE; and (iv) our estimates regarding our future financial performance, profitability or capital requirements. Forward-looking statements are subject to known and unknown risks, uncertainties, assumptions and other factors that may cause our actual results, performance or achievements to differ materially and adversely from those anticipated or implied by our forward-looking statements. Such risks, uncertainties and other factors include, but are not limited to: our dependency on the continued successful commercialization of NUPLAZID and DAYBUE and our ability to maintain or increase sales of NUPLAZID or DAYBUE; the costs of our commercialization plans and development programs, and the financial impact or revenues from any commercialization we undertake; our ability to obtain necessary regulatory approvals for our product candidates and, if and when approved, market acceptance of our products; our dependence on third-party collaborators, clinical research organizations, manufacturers, suppliers and distributors; the impact of competitive products and therapies; our ability to generate or obtain the necessary capital to fund our operations; our ability to grow, equip and train our specialized sales forces; our ability to manage the growth and complexity of our organization; our ability to maintain, protect and enhance our intellectual property; and our ability to continue to stay in compliance with applicable laws and regulations. Given the risks and uncertainties, you should not place undue reliance on these forward-looking statements. For a discussion of these and other risks, uncertainties and other factors that may cause our actual results, performance or achievements to differ, please refer to our quarterly report on Form 10-Q for the quarter ended September 30, 2023 as well as our subsequent filings with the Securities and Exchange Commission from time to time, including our annual report on Form 10-K for the year ended December 31, 2023. The forward-looking statements contained herein are made as of the date hereof, and we undertake no obligation to update them after this date, except as required by law. ACADIA PHARMACEUTICALS INC. CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS (in thousands, except per share amounts) (Unaudited) Three Months Ended December 31, Years Ended December 31, 2023 2022 2023 2022 Revenues Product sales, net $ 231,041 $ 136,490 $ 726,437 $ 517,235 Total revenues 231,041 136,490 726,437 517,235 Operating expenses Cost of product sales (1)(2) 17,891 2,413 41,638 10,166 Research and development (2) 66,741 75,738 351,619 361,575 Selling, general and administrative (2) 111,465 104,402 406,559 369,090 Total operating expenses 196,097 182,553 799,816 740,831 Income (loss) from operations 34,944 (46,063 ) (73,379 ) (223,596 ) Interest income, net 4,759 3,630 17,234 6,610 Other income — 1,543 5,109 3,542 Income (loss) before income taxes 39,703 (40,890 ) (51,036 ) (213,444 ) Income tax expense (benefit) (6,094 ) 835 10,250 2,531 Net income (loss) $ 45,797 $ (41,725 ) $ (61,286 ) $ (215,975 ) Earnings (net loss) per share: Basic $ 0.28 $ (0.26 ) $ (0.37 ) $ (1.34 ) Diluted $ 0.28 $ (0.26 ) $ (0.37 ) $ (1.34 ) Weighted average common shares outstanding: Basic 164,812 161,988 163,819 161,683 Diluted 166,510 161,988 163,819 161,683 (1) Includes license fees and royalties (2) Includes the following share-based compensation expenses Cost of product sales, license fees and royalties $ 363 $ 93 $ 1,007 $ 1,106 Research and development $ 4,707 $ 3,432 $ 17,408 $ 22,580 Selling, general and administrative $ 12,953 $ 10,889 $ 48,006 $ 44,515 ACADIA PHARMACEUTICALS INC. CONDENSED CONSOLIDATED BALANCE SHEETS (in thousands) December 31, 2023 December 31, 2022 Assets Cash, cash equivalents and investment securities $ 438,865 $ 416,823 Accounts receivable, net 98,267 62,195 Interest and other receivables 4,083 885 Inventory 35,819 6,636 Prepaid expenses 39,091 21,398 Total current assets 616,125 507,937 Property and equipment, net 4,612 6,021 Operating lease right-of-use assets 51,855 55,573 Intangible assets, net 65,490 — Restricted cash 5,770 5,770 Long-term inventory 4,628 4,924 Other assets 476 7,587 Total assets $ 748,956 $ 587,812 Liabilities and stockholders’ equity Accounts payable $ 17,543 $ 12,746 Accrued liabilities 236,711 112,884 Total current liabilities 254,254 125,630 Operating lease liabilities 47,800 52,695 Other long-term liabilities 15,147 9,074 Total liabilities 317,201 187,399 Total stockholders’ equity 431,755 400,413 Total liabilities and stockholders’ equity $ 748,956 $ 587,812

-- LB54640 has shown targeted effect on MC4 receptor without hyperpigmentation -- -- Rhythm to advance LB54640 in two Phase 2 clinical trials -- BOSTON, Jan. 04, 2024 (GLOBE NEWSWIRE) -- Rhythm Pharmaceuticals, Inc. (Nasdaq: RYTM), a global commercial-stage biopharmaceutical company focused on transforming the lives of patients and their families living with rare neuroendocrine diseases, today announced it has entered into a global licensing agreement with LG Chem, Ltd. ("LG Chem"), a leading global company headquartered in South Korea that specializes in life sciences as one of its core businesses, for LB54640, an investigational oral small molecule melanocortin-4 receptor (MC4R) agonist now in Phase 2 clinical trials. “We are excited to build upon the strong chemistry and early translational work performed by LG Chem, a highly regarded company with deep and broad experience and expertise in the pharmaceutical business. The development of an effective oral therapy for treating MC4R pathway diseases has been a major goal for the industry and the early data from LG Chem suggest they have identified a specific therapy for the MC4R without hyperpigmentation or cardiovascular side effects,” said David Meeker, MD, Chair, Chief Executive Officer and President of Rhythm Pharmaceuticals. “We believe Rhythm’s deep developmental experience and global commercial presence uniquely positions us to move this molecule forward with the goal of offering a full portfolio of treatment options to patients struggling with hyperphagia and severe obesity and ensuring they get the treatment that is right for them.” In a Phase 1 trial in healthy overweight adults, LB54640 demonstrated dose-dependent weight reduction. LB54640 also demonstrated a favorable safety profile in the trial, with no changes in blood pressure or heart rate observed and no hyperpigmentation observed. In addition, LB54640 has received orphan drug designation from the U.S. Food and Drug Administration for leptin receptor (LEPR) deficiency and proopiomelanocortin(POMC). Dr. Jeewoong Son, President of LG Chem Life Sciences Company, said, “Rhythm has pioneered the development and global commercialization of the first and best-in-class therapy for patients with hyperphagia and severe obesity associated with diseases like Bardet-Biedl syndrome (BBS), hypothalamic obesity and certain genetically-defined pathway diseases. We believe Rhythm is the ideal partner because of its extensive genetic obesity database, global network of clinical trial sites and investigators, a track record of regulatory successes and - most importantly - because Rhythm values patients and addresses their urgent needs for care.” Under the terms of the agreement, Rhythm will assume sponsorship of two Phase 2 studies designed to evaluate weight loss efficacy, safety, tolerability and pharmacokinetics of LB54640. The SIGNAL trial is a randomized, placebo-controlled, double-blind study designed to enroll and evaluate approximately 28 patients with acquired hypothalamic obesity. Participants will receive one of three doses of LB54640 by oral administration once daily for up to 52 weeks, and the primary endpoint of the study is the change from baseline in body mass index after 14 weeks of treatment. The open-label, single-arm, 52-week ROUTE trial is designed to enroll five patients with POMC, LEPR, or proprotein convertase subtilisin/kexin type 1 (PCSK1) deficiency obesity. Participants will receive LB54640 by oral administration once daily for up to 52 weeks, and the primary endpoint of the study is the change from baseline in body mass index after 14 weeks of treatment. Under the terms of the agreement, Rhythm has agreed to pay LG Chem $40 million in cash and $20 million in Rhythm equity at closing and an additional $40 million in cash 18 months after closing. Also under the terms of the agreement, Rhythm has agreed to pay LG Chem up to $205 million upon achieving certain regulatory and sales milestones, as well as royalties. About LG ChemLG Chem is a leading global chemical company with a diversified business portfolio in the key areas of petrochemicals, advanced materials, and life sciences. The company manufactures a wide range of products from high-value added petrochemicals to renewable plastics, specializing in cutting-edge electronic and battery materials, as well as drugs and vaccines to deliver differentiated solutions for its customers. LG Chem Life Sciences develops, manufactures, and globally commercializes pharmaceutical products, with a focus on Oncology, Immunology, and Metabolic diseases. Our mission is to transform people’s lives through inspiring science and leading innovation. For more information, please visit www.lgchem.com. 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) for chronic weight management in adult and pediatric patients 6 years of age and older with monogenic or syndromic obesity due to pro-opiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1) or leptin receptor (LEPR) deficiency confirmed by genetic testing, or patients with a clinical diagnosis of Bardet-Biedl syndrome (BBS). Both the European Commission (EC) and the UK’s Medicines & Healthcare Products Regulatory Agency (MHRA) have authorized setmelanotide for the treatment of obesity and the control of hunger associated with genetically confirmed BBS or genetically confirmed loss-of-function biallelic POMC, including PCSK1, deficiency or biallelic LEPR deficiency in adults and children 6 years of age and above. Additionally, Rhythm is advancing a broad clinical development program for setmelanotide in other rare diseases, as well as 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 for chronic weight management in adult and pediatric patients 6 years of age and older with monogenic or syndromic obesity due to POMC, PCSK1 or LEPR deficiency as determined by an FDA-approved test demonstrating variants in POMC, PCSK1 or LEPR genes that are interpreted as pathogenic, likely pathogenic, or of uncertain significance (VUS) or BBS. In the European Union, setmelanotide is indicated for the treatment of obesity and the control of hunger associated with genetically confirmed Bardet-Biedl syndrome (BBS) or genetically confirmed loss-of-function biallelic proopiomelanocortin (POMC), including PCSK1, deficiency or biallelic leptin receptor (LEPR) deficiency in adults and children 6 years of age and above. Limitations of UseIn the United States and Europe, Setmelanotide should be prescribed and supervised by a physician with expertise in obesity with underlying genetic etiology. Setmelanotide is not indicated for the treatment of patients with the following conditions as setmelanotide would not be expected to be effective: Obesity due to suspected POMC, PCSK1 or LEPR deficiency with POMC, PCSK1 or LEPR variants classified as benign or likely benignOther types of obesity not related to POMC, PCSK1 or LEPR deficiency, or BBS, including obesity associated with other genetic syndromes and general (polygenic) obesity. WARNINGS AND PRECAUTIONS Skin Monitoring: Setmelanotide may lead to generalized increased skin pigmentation and darkening of pre-existing naevi because of its pharmacologic effect. Full body skin examinations should be conducted annually to monitor pre-existing and new skin pigmentary lesions before and during treatment with setmelanotide. Heart rate and blood pressure monitoring: Heart rate and blood pressure should be monitored as part of standard clinical practice at each medical visit (at least every 6 months) for patients treated with setmelanotide. Prolonged penile erection: Spontaneous penile erections have been reported in clinical trials with setmelanotide. Patients who have a penile erection lasting longer than 4 hours should be instructed to seek emergency medical attention for potential treatment of priapism. Depression: In clinical trials, depression has been reported in patients treated with setmelanotide. Patients with depression should be monitored at each medical visit during treatment with setmelanotide. Consideration should be given to discontinuing setmelanotide if patients experience suicidal thoughts or behaviors. Pediatric Population: The prescribing physician should periodically assess response to setmelanotide therapy. In growing children, the impact of weight loss on growth and maturation should be evaluated. The prescribing physician should monitor growth (height and weight) using age- and sex-appropriate growth curves. Excipients: This medicinal product contains 10 mg benzyl alcohol in each ml. Benzyl alcohol may cause allergic reactions. Patients who are pregnant or breastfeeding should be advised of the potential risk from the excipient benzyl alcohol, which might accumulate over time and cause metabolic acidosis. This medicinal product should be used with caution in patients with hepatic or renal impairment, because of the potential risk from the excipient benzyl alcohol which might accumulate over time and cause metabolic acidosis. Sodium: This medicinal product contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially “sodium-free.” ADVERSE REACTIONSThe most frequent adverse reactions are hyperpigmentation (51%), injection site reaction (39%), nausea (33%), and headache (26%). USE IN SPECIFIC POPULATIONS PregnancyThere are no data from the use of setmelanotide in pregnant women. Animal studies do not indicate direct harmful effects with respect to reproductive toxicity. However, administration of setmelanotide to pregnant rabbits resulted in decreased maternal food consumption leading to embryo-fetal effects. As a precautionary measure, setmelanotide should not be started during pregnancy or while attempting to get pregnant as weight loss during pregnancy may result in fetal harm. If a patient who is taking setmelanotide has reached a stable weight and becomes pregnant, consideration should be given to maintaining setmelanotide treatment as there was no proof of teratogenicity in the nonclinical data. If a patient who is taking setmelanotide and still losing weight gets pregnant, setmelanotide should either be discontinued, or the dose reduced while monitoring for the recommended weight gain during pregnancy. The treating physician should carefully monitor weight during pregnancy in a patient taking setmelanotide. Breast-feedingIt is unknown whether setmelanotide is excreted in human milk. A nonclinical study showed that setmelanotide is excreted in the milk of nursing rats. No quantifiable setmelanotide concentrations were detected in plasma from nursing pups. A risk to the newborn/infant cannot be excluded. A decision must be made whether to discontinue breastfeeding or to discontinue/abstain from setmelanotide therapy taking into account the benefit of breastfeeding for the child and the benefit of therapy for the mother. FertilityNo human data on the effect of setmelanotide on fertility are available. Animal studies did not indicate harmful effects with respect to fertility. To report SUSPECTED ADVERSE REACTIONS, contact Rhythm Pharmaceuticals at +1 (833) 789-6337. See Summary of Product Characteristics’ APPENDIX V for a list of European national reporting systems to communicate adverse reactions. 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 potential, safety, efficacy, and regulatory and clinical progress of setmelanotide and LB54640, the potential timing, payments due, and benefits of the global licensing agreement for LB54540, including with respect to the consummation of the transaction, expectations regarding the design, enrollment, or outcome of clinical trials of LB54640, the outcome of the Phase 2 trial of setmelanotide in hypothalamic obesity, the ability to reach any net sales or revenue milestones, and obtaining regulatory approvals in connection with the global licensing agreement. Statements using word 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, risks relating to our liquidity and expenses, 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 our 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, the impact of the COVID-19 pandemic and general economic conditions on our business and operations, including our preclinical studies, clinical trials and commercialization prospects, failure to realize the anticipated benefits of our acquisition of Xinvento B.V. or significant integration difficulties related to the acquisition, and the other important factors discussed under the caption “Risk Factors” in our Quarterly Report on Form 10-Q for the quarter ended September 30, 2023 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. Rhythm Corporate Contact:David ConnollyExecutive Director, Investor Relations and Corporate CommunicationsRhythm Pharmaceuticals, Inc.857-264-4280dconnolly@rhythmtx.com Rhythm Media Contact:Adam DaleyBerry & Company Public Relations212-253-8881adaley@berrypr.com LG Chem Media Contact:Son Junil / Kim Junamlgchempr@lgchem.com