NCOA1

HOUSTON, June 01, 2023 (GLOBE NEWSWIRE) -- CoRegen, a biopharmaceutical company pursuing novel treatments for patients impacted by some of the most aggressive forms of cancer and chronic diseases, announced today the publication of research, titled, “Steroid receptor coactivator 3 is a key modulator of regulatory T cell-mediated tumor evasion,” in the peer-reviewed journal Proceedings of the National Academy of Sciences (PNAS). This work showcases the discovery of steroid receptor coactivator 3 (SRC-3) as a crucial regulator of the anti-cancer immune response. SRC-3 is a pleiotropic coactivator suspected of playing a critical role in the function of regulatory T cells (Tregs), which are essential in restraining immune responses for immune homeostasis. When SRC-3 expression was disrupted in Tregs, it was shown to result in complete tumor eradication in aggressive syngeneic breast cancer mouse models without recurrence or side effects. This approach has been tested with triple negative breast cancer, glioblastoma, advanced prostate cancer and pancreatic cancer and consistently achieved tumor eradication without recurrence or side effects in preclinical studies. CoRegen is capitalizing on nearly 50 years of research by Bert O’Malley M.D., a renowned molecular endocrinologist who currently serves as the Chancellor of Baylor College of Medicine and the Inventor, Principal Scientist and Board Member of CoRegen. He has won more than 65 awards, received the National Medal of Science from President Bush. Dr. O’Malley and his team discovered a protein called steroid receptor coactivator (SRC-1) that is required for the effective regulation of gene activity and have extensively characterized a family of SRCs (SRC-1, SRC-2 and SR-3) that regulate a variety of cellular functions. Of these, SRC-3 has been shown to be highly expressed in almost all human cancers and appears to also play a key role in cancer growth. Additionally, it was determined that when SRC-3 was removed from the Treg cell, a number of other genes, typically individually targeted in other cancer therapies, were down regulated while other genes were upregulated. These changes to the Treg were only observed inside the tumor but are believed to be one of the key drivers of the successful outcome of the studies. The team also discovered that Tregs lacking SRC-3 mediated long-lasting tumor eradication by effectively modifying the environment surrounding the tumor into one that favored its elimination. A subsequent injection of additional cancer cells in treated mice did not give rise to new tumors, showing that there was no need to introduce additional SRC-3 knock-out Tregs to sustain tumor resistance. Importantly, transferring these cells to animals carrying pre-established breast tumors also resulted in cancer eradication. “We are highly encouraged by these findings,” said Dr. O’Malley. “By identifying SRC-3 and its critical role in the function of Tregs, it is our hope we may introduce entirely new methods for addressing the needs of patients with some of the most aggressive forms of cancer.” “As a partner and significant shareholder, Baylor College of Medicine has tremendous confidence in the CoRegen management team and is looking forward to working with CoRegen to commercialize the groundbreaking discoveries originating from the O’Malley Laboratory. Baylor College of Medicine has and will continue to dedicate significant resources and infrastructure to assist CoRegen in its efforts to bring life-saving therapies to the world,” said Michael Dilling, Executive Director, Baylor College of Medicine Licensing Group. Steve Gorlin, chief executive officer of CoRegen, added, “I have had the great fortune of having founded and led multiple companies reaching billion-dollar valuations, with some having resulted in the sale to large pharma. In my entire career, I have never seen an opportunity similar to that of CoRegen and view these data as stepping-stones towards potentially creating truly transformative therapeutics for patients in need. I look forward to continuing the advances generated from Dr. O’Malley’s lab in the years to come.” CoRegen has partnered with Baylor College of Medicine to further develop and commercialize several of the groundbreaking discoveries originating from the O’Malley Laboratory with a team of more than 30 scientists and several meaningful partnerships. About CoRegen CoRegen is a biopharmaceutical company leveraging its unique and patented master gene regulatory platform for the treatment of cancers and other malignant and high intensity chronic illnesses. Although the CoRegen platform has a wide range of potential therapies it will initially focus on select cancers. As of today, in preclinical mouse studies, the CoRegen cancer therapy has been shown to completely eradicate established tumors, prevent the growth of new tumors and prevent recurrence with no signs of toxicity, inflammation or off target effects. The therapy has been tested on glioblastoma, pancreatic, triple negative breast and advanced prostate cancer. CoRegen’s patent estate also contains small molecule agents that inhibit and enhance the family of steroid receptor coactivators. The inhibitor drugs show activity against cancers by themselves but are also likely to be synergistic with other therapeutic modalities. The enhancer drugs show a wide range of activity including dramatically reversing damage and improving function after both myocardial infarction and stroke in rodent models. Company Contact: Matthew Rosen, Executive Vice Chairman mrosen@coregeninc.com Media Contact: Andrew Mielach LifeSci Communications amielach@lifescicomms.com

FRIDAY, May 26, 2023 -- Young patients with a history of multiple concussions report greater cognitive, sleep, and neuropsychiatric symptoms than those with one prior head injury, according to a study published online May 9 in the Journal of Neurosurgery: Pediatrics . Addison Quinones, from the Icahn School of Medicine at Mount Sinai in New York City, and colleagues investigated the effects of prior recurrent head injury on the symptom profiles of student-athletes after another suspected concussion. The analysis included student athletes (aged 12 to 22 years) reporting a single prior sports-related concussion (SRC1; 2,253 students) and athletes reporting two or more prior concussions (SRC2+; 976 students) at baseline. The researchers found that at postinjury test 1 (PI1), the SRC2+ group had lower severity of headaches but increased nervousness, irritability, sadness, visual problems, and neuropsychiatric symptoms versus SRC1. In a multivariate analysis, decreased headache severity was associated with increased prior concussion (β = −0.27). At postinjury test 2, the SRC2+ cohort had increased cognitive (β = 1.22), sleep (β = 0.63), and neuropsychiatric (β = 0.67) symptoms versus the SRC1 cohort. "Careful assessment of specific symptoms should be considered in patients with a history of recurrent head injury prior to return to play," the authors write. Abstract/Full Text (subscription or payment may be required) Posted May 2023

-- Rhythm to review data on webcast conference call on November 2, 2022 at 8:30 a.m. ET – -- Rhythm to report 3Q 2022 earnings on November 8, 2022 at 8:00 a.m. ET -- BOSTON, Oct. 25, 2022 (GLOBE NEWSWIRE) -- Rhythm Pharmaceuticals, Inc. (Nasdaq: RYTM), a commercial-stage biopharmaceutical company focused on transforming the lives of patients and their families living with hyperphagia and severe obesity caused by rare melanocortin-4 receptor (MC4R) pathway diseases, today announced that it will present full data from the Phase 2 clinical trial evaluating setmelanotide in hypothalamic obesity during The Obesity Society’s ObesityWeek® 2022, being held November 1-4, 2022 in San Diego, CA. On Wednesday, November 2, 2022 at 8:30 a.m. ET (5:30 a.m. PT), Rhythm will host a conference call and webcast for investors to discuss full data from 18 patients enrolled in the Phase 2 clinical trial evaluating setmelanotide in hypothalamic obesity. To access the live conference call for full Phase 2 data in hypothalamic obesity, participants may register here. Also on November 2, 2022 as part of the ObesityWeek® conference, Rhythm is delivering a total of 11 presentations, including a poster entitled, “Efficacy and Safety Analysis of Setmelanotide As a Novel Treatment for Hypothalamic Obesity,” at 2:45 p.m. ET (11:45 a.m. PT) at Exhibit Hall GH, San Diego Convention Center. Additional Upcoming Activity Also today, Rhythm announced that it will host a live conference call and webcast at 8:00 a.m. ET on Tuesday, November 8, 2022 to report its third quarter 2022 financial results and provide a corporate update. To access the live conference call for third quarter 2022 financial results, participants may register here. In addition, David Meeker, M.D., Chair, President and Chief Executive Officer, will participate in a fireside chat at the Stifel Healthcare Conference on Tuesday, November 15, 2022, beginning at 3:35 p.m. ET in New York, NY. Live webcasts of both conference calls, as well as the Stifel presentation, will be available under "Events and Presentations" in the Investor Relations section of the Rhythm Pharmaceuticals website at http://ir.rhythmtx.com/. The archived webcasts of the conference calls will be available on Rhythm Pharmaceuticals’ website approximately two hours after each conference call and will be available for 30 days following each call. A replay of the Stifel webcast will also be available on the Rhythm website for 30 days following the presentation. About Rhythm PharmaceuticalsRhythm is a commercial-stage biopharmaceutical company committed transforming the lives of patients and their families living with hyperphagia and severe obesity caused by rare melanocortin-4 receptor (MC4R) pathway diseases. Rhythm’s precision medicine, IMCIVREE (setmelanotide), 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 POMC, PCSK1 or LEPR deficiency confirmed by genetic testing, or patients with a clinical diagnosis of Bardet-Biedl syndrome (BBS). The European Commission (EC) and Great Britain’s Medicines & Healthcare Products Regulatory Agency (MHRA) have authorized IMCIVREE for the treatment of obesity and the control of hunger associated with genetically confirmed loss-of-function biallelic POMC, including PCSK1, deficiency or biallelic LEPR deficiency in adults and children 6 years of age and above. IMCIVREE is the first-ever FDA-approved and EC- and MHRA-authorized therapy for patients with these rare genetic diseases of obesity. The Company submitted a Type II variation application to the European Medicines Agency seeking regulatory approval and authorization for setmelanotide to treat obesity and control of hunger in adult and pediatric patients 6 years of age and older with BBS in the European Union. Additionally, Rhythm is advancing a broad clinical development program for setmelanotide in other rare genetic diseases of obesity and is leveraging the Rhythm Engine and the largest known obesity DNA database -- now with approximately 45,000 sequencing samples -- to improve the understanding, diagnosis and care of people living with severe obesity due to certain genetic deficiencies. Rhythm’s headquarters is in Boston, MA. About SetmelanotideSetmelanotide is a melanocortin-4 receptor (MC4R) agonist. The MC4R is part of the key biological pathway that regulates hunger, caloric intake and energy expenditure. Variants in genes may impair the function of the MC4R pathway, potentially leading to hyperphagia and early-onset, severe obesity. Rhythm is developing setmelanotide as a targeted therapy to potentially restore the function of an impaired MC4R pathway and, in so doing, potentially reduce hunger and weight in patients with rare genetic diseases of obesity. In the EU and Great Britain, IMCIVREE is indicated for the treatment of obesity and the control of hunger associated with genetically confirmed loss-of-function biallelic POMC, including PCSK1, deficiency or biallelic LEPR deficiency in adults and children 6 years of age and above. IMCIVREE should be prescribed and supervised by a physician with expertise in obesity with underlying genetic etiology. Rhythm’s Type II variation application to the European Medicines Agency (EMA) for the treatment of obesity and control of hyperphagia in adult and pediatric patients 6 years of age and older with BBS is under review. The Company is also continuing to advance the most comprehensive clinical research program ever initiated in MC4R pathway diseases, including the pivotal Phase 3 EMANATE clinical trial evaluating setmelanotide in four independent sub-studies in patients with obesity due to POMC insufficiency caused by heterozygous variants in the POMC or PCSK1 genes, LEPR insufficiency caused by heterozygous variants in the LEPR gene, SRC1 deficiency caused by a variant in the NCOA1 gene, and SH2B1 deficiency caused by a variant in the SH2B1 gene or 16p11.2 deletion encompassing the SH2B1 gene. The Phase 2 DAYBREAK trial is evaluating setmelanotide in patients with severe obesity and hyperphagia caused by rare variants associated with 10 prioritized MC4R-relevant genes. Rhythm has also initiated a Phase 3 pediatric trial and a Phase 3 trial evaluating a weekly formulation of setmelanotide. IMCIVREE® (setmelanotide) IndicationIn the United States, IMCIVREE is indicated 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 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)Bardet-Biedl syndrome (BBS) Limitations of UseIMCIVREE is not indicated for the treatment of patients with the following conditions as IMCIVREE 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 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 and suicidal ideation 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. Skin Pigmentation and Darkening of Pre-existing Nevi: Generalized increased skin pigmentation and darkening of pre-existing nevi have occurred. Perform a full body skin examination prior to initiation and periodically during treatment to monitor pre-existing and new pigmentary lesions. Risk of Serious Adverse Reactions Due to Benzyl Alcohol Preservative in Neonates and Low Birth Weight Infants: IMCIVREE is not approved for use in neonates or infants. Serious and fatal adverse reactions including “gasping syndrome” can occur in neonates and low birth weight infants treated with benzyl alcohol-preserved drugs. ADVERSE REACTIONS The most common adverse reactions (incidence ≥20%) included skin hyperpigmentation, injection site reactions, nausea, headache, diarrhea, abdominal pain, vomiting, depression, and spontaneous penile erection. USE IN SPECIFIC POPULATIONSTreatment 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 833-789-6337 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 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, our expectations surrounding potential regulatory submissions, approvals and timing thereof, our business strategy and plans, including regarding commercialization of setmelanotide, and our participation in upcoming events and presentations. Statements using word such as “expect”, “anticipate”, “believe”, “may”, “will” 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 impact of competition, the ability to achieve or obtain necessary regulatory approvals, risks associated with data analysis and reporting, our liquidity and expenses, the impact of the COVID-19 pandemic on our business and operations, including our preclinical studies, clinical trials and commercialization prospects, and general economic conditions, and the other important factors discussed under the caption “Risk Factors” in our Quarterly Report on Form 10-Q for the quarter ended June 30, 2022 and our other filings with the Securities and Exchange Commission. Except as required by law, we undertake no obligations to make any revisions to the forward-looking statements contained in this release or to update them to reflect events or circumstances occurring after the date of this release, whether as a result of new information, future developments or otherwise. Corporate Contact:David ConnollyHead of Investor Relations and Corporate CommunicationsRhythm Pharmaceuticals, Inc.857-264-4280dconnolly@rhythmtx.com Investor Contact:Hannah DeresiewiczStern Investor Relations, Inc.212-362-1200hannah.deresiewicz@sternir.com Media Contact:Adam DaleyBerry & Company Public Relations212-253-8881adaley@berrypr.com