Compensated cirrhosis

Pictured: A fatty liver over a cell/Taylor Tieden for BioSpace In one of the year’s most highly anticipated decisions, the FDA approved Madrigal Pharmaceuticals’ resmetirom Thursday as the first-ever therapy for metabolic dysfunction-associated steatohepatitis. Resmetirom, which will be marketed as Rezdiffra, is indicated for the treatment of patients with metabolic dysfunction-associated steatohepatitis (MASH) with moderate to advanced liver fibrosis, along with diet and exercise, according to the FDA's press release. Speaking with BioSpace ahead of the decision, experts said the approval could signal a sea-change in the diagnosis and treatment of MASH. Resmetirom met its two primary endpoints in the MAESTRO-NASH Phase III trial, significantly improving disease resolution and liver fibrosis. The data, published last month in The New England Journal of Medicine, show that NASH resolved in 25.9% of patients who received an 80-mg dose of resmetirom and 29.9% of those taking 100 mg, with no worsening of fibrosis. This was compared to 9.7% of patients in the placebo group. Resmetirom targets thyroid hormone receptor beta (THR-β), which helps maintain liver homeostasis. THR-β agonists have been shown to improve lipid metabolism. “This is a huge area and affects millions of patients,” Rajarshi Banerjee, CEO of Perspectum, which supported Madrigal’s clinical trials, told BioSpace prior to the decision. “There are no effective approved therapies, and so Madrigal’s resmetirom, even though it has limited efficacy, would be an important first.” The Future MASH Market Metabolic dysfunction-associated steatohepatitis (MASH), formerly known as nonalcoholic steatohepatitis (NASH), affects 5.3 out of every 1000 people worldwide, according to a 2021 article published in MDPI. In the U.S., the disease accounts for 18% of all hepatocellular carcinoma cases. Rohan Palekar, CEO of the biotech 89bio, which is developing therapies for the treatment of liver and cardiometabolic diseases, told BioSpace that this is likely an underestimate. “Right now, if someone walks into the clinic who is obese and diabetic, physicians counsel them on diet and lifestyle but don’t necessarily work them up for MASH, because they don’t have a medication to give them,” Palekar explained. “Once we have one approved drug, I believe the diagnosis of MASH will increase.” The same is true for the MASH precursor, fatty liver or MAFLD (metabolic dysfunction-associated fatty liver disease), he said. “There is a greater unmet need than we know.” 89bio is developing pegozafermin, which aims to prolong the biological activity of fibroblast growth factor 21 (FGF21), for MASH. FGF21 regulates multiple metabolic pathways and cellular processes. The company earlier this week initiated its Phase III clinical trial program with the ENLIGHTEN-Fibrosis study, which will evaluate pegozafermin in non-cirrhotic MASH patients with fibrosis stage F2-F3. A second trial, ENLIGHTEN-Cirrhosis, which will assess the drug in patients with compensated cirrhosis (F4), is expected to begin in the second quarter of 2024. “We think a pretty dramatic change is on the way for the recognition and treatment of MASH,” Palekar said. “People may remember when the first lipid-lowering agents came out, it took time for awareness and education to catch up. Now everybody gets their LDL [cholesterol] checked and gets on a statin if it’s elevated.” He sees a similar trajectory for MASH and MAFLD. The Treatment Landscape Already, some of the unmet need in MASH can be met by GLP-1 anti-obesity drugs, said Mayank Mamtani, head of healthcare research at B. Riley Securities. “The unmet need is simply not the same as it was before the weight loss drugs came along,” he told BioSpace. “I would argue that the anti-obesity drugs have the same benefit as resmetirom [in MASH].” Moreover, Mamtani said, weight loss drugs such as Novo Nordisk’s Wegovy and Eli Lilly’s Zepbound, might be less expensive. While a weight loss drug can cost $15,000 per year, Madrigal’s drug may cost between $30,000 and $40,000 annually. Still, there are “multiple molecules out there” with potential to treat MASH specifically, Mazen Noureddin, who recently established the Houston Research Institute, told BioSpace. “I hope this will be the first in a series of approvals,” he said of resmetirom. As more drugs hit the market, Noureddin envisions that different pharmaceuticals will be combined to treat MASH. “In a perfect world, resmetirom will be combined with other molecules, such as those targeting semaglutide,” the GLP-1 analog that forms the basis of Wegovy and Zepbound, he said. Anti-obesity drugs can be effective in earlier stages of MASLD, he added, but because some of them have “little antifibrotic effect, they will be combined with strong antifibrotics." Mamtani said he hopes the greenlight of resmetirom will lead the way for other approvals that act directly on fibrosis. He specifically cited pegozafermin and Akero Therapeutics’ exfruxifermin, both FGF21 analogs, as examples. “That’s the holy grail to help people who are very close to liver failure,” he said. “It will just take a lot of time and capital to generate that data.” Ultimately, treatment of MASH may have a huge impact on patients’ health and physicians’ treatment practices because of the ways it can overlap with cardiovascular medicine, Banerjee predicted. “Liver disease can cause liver failure, but it is more likely to cause heart disease, including heart failure, atrial fibrillation and heart attacks,” he said. However, he added, “Liver disease is a modifiable cardiovascular risk factor, like high cholesterol, diabetes and smoking. It can be reversed. This is why MASH matters to cardiologists and internists, even if it is asymptomatic—treat it, and you could potentially stop heart attacks like statins do.” The Diagnostic Conundrum One of the biggest challenges facing the MASH field is how to identify, define and measure the disease and improvements in it, including primary endpoints to be met in clinical trials. In a paper published in Nature on March 9, Noureddin and colleagues address both the challenges and opportunities in MASH diagnosis and treatment. Currently, liver biopsy is the gold standard, but it has drawbacks. At 89bio, Palekar said, liver biopsies were performed at the start of the Phase IIb ENLIVEN 48-week clinical trial, then again at week 24. Because pathologist interpretations on the degree of fibrosis can vary, each biopsy was sent to three separate pathologists. “At least two out of three had to agree,” he explained. Another problem with biopsies is that the liver is a large organ, Palekar noted, and a biopsy can only capture a small slice of it. In addition, “patients don’t like biopsies, and they present risks, such as bleeding.” Moreover, once medications are approved and available, liver biopsy would be impractical and too expensive for routine clinical use, Palekar said. Currently, two large consortiums, the U.S.-based Non-Invasive Biomarkers of Metabolic Liver Disease (NIMBLE) and the European Liver Investigation: Testing Marker Utility in Steatohepatitis (LITMUS), are working to establish noninvasive markers and clinical endpoints for MASH and non-alcoholic fatty liver disease. These can include MRI imaging to quantify the amount of fat and fibrosis in the liver, ultrasound and blood biomarkers such as liver enzyme levels. In addition, Banerjee said, Perspectum is working on a proprietary marker called cT1, which the company hopes will predict clinical outcomes even better than liver biopsy. For now, those in the field appear to be optimistic. “2024 is going to be a happy year for MASH,” Noureddin said. “I think we’re going to see the movement to replace liver biopsy with noninvasive markers. I’m excited we are going to be able to give our patients options.” Jill Neimark is a freelance science writer based in Macon, Georgia. Reach her at jillneimark.com.

--Enrollment ongoing for patients with microsatellite stability (MSS) colorectal cancer (CRC) in Phase1/2 trial of NGM707, a dual ILT2/ILT4 antagonist antibody product candidate, in combination with KEYTRUDA® (pembrolizumab) with expected completion of enrollment in the second quarter of 2024-- --Announced ongoing toxicology activities intended to support initiation of a potential proof-of-concept study of NGM120, a GDF15/GFRAL antagonist, for the treatment of hyperemesis gravidarum (HG) by the end of 2024-- --Ongoing discussions with regulators on the design of a potential registrational trial of aldafermin, an engineered FGF19 analog, for the treatment of primary sclerosing cholangitis (PSC), a rare liver disease, using surrogate endpoints-- --Reported $144.2 million in cash, cash equivalents and marketable securities as of December 31, 2023-- --On February 26, 2024, announced that it had entered into the Agreement and Plan of Merger with Atlas Neon Parent, Inc., and Atlas Neon Merger Sub, Inc.-- SOUTH SAN FRANCISCO, Calif., March 11, 2024 (GLOBE NEWSWIRE) -- NGM Biopharmaceuticals, Inc., (NGM Bio) (Nasdaq: NGM), a biotechnology company focused on discovering and developing transformative therapeutics for patients, today provided recent business highlights and reported financial results for the fourth quarter and full year ended December 31, 2023. “In 2023, we made significant progress in patient enrollment in trials of our solid tumor drug candidates. Most notably, we are encouraged by the signals of activity observed in our NGM707 Phase 1b trial, particularly among MSS CRC patients whose lesions are typically unresponsive to immuno-checkpoint therapies. We also made progress in our discussions with the FDA regarding the design of a potential registrational Phase 2 study of aldafermin in PSC using a primary endpoint composed of surrogate biomarkers of PSC progression and obtained orphan drug designation from the agency for aldafermin for the treatment of PSC,” said David J. Woodhouse, Ph.D., Chief Executive Officer at NGM Bio. “In 2024, we are focused on completing patient enrollment for NGM707 with a potential interim Phase 1b trial readout in the middle of the year, initiating a potential Phase 2 proof-of-concept trial of NGM120 in HG by the end of 2024, and, provided we have the financial resources and agreement on trial design, initiating a registrational Phase 2 trial of aldafermin in PSC patients. Our priority remains to seek licensing and other business development partners across all our wholly-owned product candidates and to allocate our resources to the programs that we believe have the greatest potential both in the near- and long-term.” Key Fourth Quarter and Recent Highlights Solid Tumor Oncology Disclosed in January 2024 encouraging findings in a Phase 1 Part 1b cohort of the ongoing Phase 1/2 trial evaluating NGM707 in combination with pembrolizumab for the treatment of patients with advanced or metastatic solid tumors, including MSS CRC patients. 46 patients were enrolled as of the November 6, 2023 data-cutoff and, of the 37 response-evaluable patients (those completing at least one on-treatment scan), there were four confirmed partial responses across multiple indications, including one pathological complete response, and 12 patients with stable disease (11% overall response rate and 43% disease control rate). The combination of NGM707 and pembrolizumab was generally well-tolerated at all four doses (200, 600, 1200, 1800 mg) of NGM707. The maximum tolerated dose was not reached. NGM Bio expects to complete enrollment in the Phase 1 Part 1b cohort in the second quarter of 2024 and anticipates providing an update in mid-2024 on the fully enrolled cohort and subsequent next steps, including, provided sufficient financial resources, the potential for additional cohorts, which NGM Bio expects will include MSS CRC patients. Completed enrollment in the Phase 1 Part 1b cohorts of the Phase 1/1b trials evaluating NGM831, an ILT3 antagonist antibody product candidate, and NGM438, a LAIR1 antagonist antibody product candidate, in combination with pembrolizumab in patients with advanced solid tumors. NGM831 and NGM438, alone and in combination with pembrolizumab, have been generally well-tolerated and there have been no dose limiting toxicities noted to date. Initiated an ongoing Phase 1, Part 1c dose finding cohort evaluating the triplet combination of NGM831, NGM438 and pembrolizumab. This cohort is anticipated to complete enrollment in the first half of 2024. Hyperemesis Gravidarum Announced in January 2024 potential development of NGM120 for the treatment of HG. NGM120, a GFRAL antagonist antibody, is designed to block GDF15 signaling, the central cause of HG and, thereby, may potentially have therapeutic benefit for treating pregnant women suffering from HG. HG is a rare, serious condition that affects approximately 100,000 – 150,000 women in the United States each year during pregnancy and is characterized by intractable nausea and vomiting, which then results in dehydration, weight loss and malnutrition. HG has a significant physical and psychosocial impact on patients and leads to overall higher rates of fetal loss, preeclampsia, preterm birth, low birth weight and fetal malnutrition. HG is the second leading cause of hospitalization in pregnancy (second to preterm labor) and typically recurs in subsequent pregnancies. There are currently no FDA-approved therapies for this condition. Research1 has shown that GDF15 levels increase steadily in early pregnancy and, on average, are higher in women who experience nausea and vomiting in pregnancy and HG. The research also indicated that women with GDF15 genetic variants associated with lower levels of GDF15 in a non-pregnant state are predisposed to HG. NGM Bio’s goal is to initiate a Phase 2 proof-of-concept study of NGM120 for the treatment of HG by the end of 2024. NGM Bio is in the process of producing a toxicology package to submit to regulatory authorities in Australia or the United Kingdom that we hope will support initiation of the trial. Aldafermin Presented positive Phase 2b results from the ALPINE 4 trial of aldafermin in compensated cirrhosis (F4) due to NASH at AASLD The Liver Meeting in November 2023. In January 2024, announced U.S. Food and Drug Administration (FDA) granted orphan drug designation to aldafermin, an engineered FGF19 analog, for the treatment of PSC. NGM Bio plans to further develop aldafermin for the treatment of PSC, a rare liver disease that irreparably damages the bile ducts, leading to bile acid dysregulation, which, ultimately, results in serious liver damage. There are currently no FDA-approved therapies for PSC. NGM Bio is continuing discussions with the FDA regarding the design of a potential registrational trial of aldafermin in PSC, including on the proposed utilization of a primary endpoint composed of surrogate biomarkers with the goal of obtaining accelerated approval from the FDA. NGM Bio plans to continue working towards the goal of initiating a potential registrational trial contingent upon further discussion with the FDA on trial design and obtaining the additional capital necessary to conduct the study. Corporate On February 26, 2024, NGM Bio announced that it had entered into the Agreement and Plan of Merger (Merger Agreement) with Atlas Neon Parent, Inc. (Parent) and Atlas Neon Merger Sub, Inc., a wholly-owned subsidiary of Parent (Merger Sub). The Merger Agreement provides for, among other things, (i) the acquisition of NGM Bio by Parent through a cash tender offer (the Offer) by Merger Sub for each issued and outstanding share of NGM Bio’s common stock (other than certain rollover shares) for $1.55 per share (the Offer Price), and (ii) the merger of Merger Sub with and into NGM Bio (the Merger), with NGM Bio surviving the Merger as a privately held company. Subject to the terms of the Merger Agreement, the Offer Price will be paid subject to any applicable tax withholding and without interest. Pursuant to the Merger Agreement, on March 8, 2024, Parent commenced the Offer. Additional details can be found in NGM Bio’s recent filings with the United States Securities and Exchange Commission (SEC). NGM Bio anticipates that the Offer and the Merger contemplated under the Merger Agreement will be consummated in the second quarter of 2024. However, closing of the Merger is subject to customary closing conditions, and there can be no assurance that the Offer and the Merger contemplated by the Merger Agreement will be completed. If the Merger is effected, NGM Bio’s common stock will be delisted from The Nasdaq Stock Market LLC and NGM Bio will be privately held. Fourth Quarter and Full Year 2023 Financial Results NGM Bio reported a net loss of $27.7 million and $142.4 million for the quarter and year ended December 31, 2023, respectively, compared to a net loss of $36.4 million and $162.7 million for the same periods in 2022. Related party revenue from the collaboration with Merck Sharp & Dohme LLC, or Merck, was $0.2 million and $4.4 million for the quarter and year ended December 31, 2023, respectively, compared to $18.2 million and $55.3 million for the same periods in 2022. The collaboration with Merck ends on March 31, 2024. Research and development expenses were $21.9 million and $118.0 million for the quarter and year ended December 31, 2023, respectively, compared to $46.7 million and $181.1 million for the same periods in 2022. General and administrative expenses were $7.9 million and $37.8 million for the quarter and year ended December 31, 2023, respectively, compared to $9.8 million and $40.5 million for the same periods in 2022. Cash, cash equivalents and short-term marketable securities were $144.2 million as of December 31, 2023. About NGM Biopharmaceuticals, Inc. NGM Bio is focused on discovering and developing novel, life-changing medicines for people whose health and lives have been disrupted by disease. The company’s biology-centric drug discovery approach aims to seamlessly integrate interrogation of complex disease-associated biology and protein engineering expertise to unlock proprietary insights that are leveraged to generate promising product candidates and enable their rapid advancement into proof-of-concept studies. As explorers on the frontier of life-changing science, NGM Bio aspires to operate one of the most productive research and development engines in the biopharmaceutical industry. All therapeutic candidates in the NGM Bio pipeline have been generated by its in-house discovery engine, always led by biology and motivated by unmet patient need. Visit us at for more information. KEYTRUDA® is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. Abbreviations (in Alphabetical Order) F4=fibrosis stage 4; FGF19=fibroblast growth factor 19; GDF15=growth differentiation factor 15; GFRAL=glial cell-derived neurotrophic factor receptor alpha-like; HG=hyperemesis gravidarum; NASH=nonalcoholic steatohepatitis; ILT2=immunoglobin-like transcript 2; ILT3=immunoglobin-like transcript 3; ILT4=immunoglobin-like transcript 4; LAIR1=leukocyte-associated immunoglobulin-like receptor 1 Forward Looking Statements Statements contained in this press release regarding matters that are not historical facts are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as “encouraged”, “will,” “could,” “expect,” “expected,” “promising,” “aspires,” “aims,” “hope” and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) are intended to identify forward-looking statements. These statements include those related to: the therapeutic potential of NGM Bio’s product candidates; NGM Bio’s continued pipeline development, including identification and engagement of third-party partners for potential future business development arrangements, or the BD Arrangements, across all NGM Bio’s wholly-owned product candidates and to allocate its resources to the programs that it believes have the greatest potential both in the near- and long-term and; research and development and discovery engine output; the expected timing of completion of enrollment of NGM Bio’s ongoing Phase 1 Part 1b cohort of the Phase1/2 trial of NGM707 in combination with KEYTRUDA® (pembrolizumab) and timing of anticipated updates on the completed cohort and subsequent next steps, including the potential for additional cohorts; timing of the potential start of NGM120 in a proof-of-concept study for the treatment of HG; the design and initiation of a potential registrational trial for aldafermin for the treatment of PSC using surrogate endpoints; timing of completion of enrollment of NGM Bio’s ongoing Phase 1, Part 1c dose finding cohort evaluating the triplet combination of NGM831, NGM438 and pembrolizumab; the potential therapeutic benefit of NGM120 for treating pregnant women suffering from HG; the ability of NGM Bio and Atlas Neon Parent, Inc., a Delaware corporation (Parent), and Atlas Neon Merger Sub, Inc., a Delaware corporation and a wholly-owned subsidiary of Parent (together with Parent, the Purchaser) to complete the transactions contemplated by the Merger Agreement, including the parties’ ability to satisfy the conditions to the consummation of the Offer and the other conditions set forth in the Merger Agreement, statements about the expected timetable for completing the transactions, NGM Bio’s and Purchaser’s beliefs and expectations and statements about the benefits sought to be achieved by Purchaser’s proposed acquisition of NGM Bio, the possibility of any termination of the Merger Agreement, estimates relating to NGM Bio’s past, current or future financial condition; and other statements that are not historical fact. Because such statements deal with future events and are based on NGM Bio’s current expectations, they are subject to various risks and uncertainties, and actual results, performance or achievements of NGM Bio could differ materially from those described in or implied by the statements in this press release. These forward-looking statements are subject to risks and uncertainties, including, without limitation, risks and uncertainties associated with the costly and time-consuming pharmaceutical product development process and the uncertainty of clinical success; risks related to failure or delays in successfully initiating, enrolling, reporting data from or completing clinical studies, as well as the risks that results obtained in preclinical or clinical trials to date may not be indicative of results obtained in future trials; the lack of regulatory clarity regarding acceptable surrogate endpoints for PSC and related development uncertainty; the vulnerable patient population experiencing HG and risks associated with clinical trials on such patient population; uncertainties inherent in the preclinical development process of NGM120 in HG, including that NGM120 in HG may never reach clinical development; NGM Bio’s ability to identify, attract and engage third-party partners for BD Arrangements for its wholly-owned programs; the time-consuming and uncertain regulatory approval process; NGM Bio’s reliance on third-party manufacturers for its product candidates and the risks inherent in manufacturing and testing pharmaceutical products; the sufficiency of NGM Bio’s cash resources and expected cash runway, including the risk that NGM Bio could utilize its available capital resources sooner than it currently expects and its need for additional capital; macroeconomic conditions (such as the impacts of global geopolitical conflict, global economic slowdown, increased inflation, rising interest rates and recent and potential future bank failures); the timing of the Offer and the subsequent Merger; uncertainties as to how many of the unaffiliated stockholders will tender their shares in the Offer; the risk that competing offers or acquisition proposals will be made; the possibility that various conditions to the consummation of the Offer and the subsequent Merger may not be satisfied or waived; the occurrence of any event, change or other circumstance that could give rise to the termination of the Merger Agreement, including in circumstances which would require NGM Bio to pay a termination fee; the effects of disruption from the transactions contemplated by the Merger Agreement; the risk that stockholder litigation in connection with the Offer or the Merger may result in significant costs of defense, indemnification and liability; and other risks and uncertainties affecting NGM Bio and its development programs, including those discussed in the section titled “Risk Factors” in NGM Bio’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2023 filed with the SEC on November 2, 2023 and future filings and reports that NGM Bio makes from time to time with the SEC. Except as required by law, NGM Bio assumes no obligation to update these forward-looking statements, or to update the reasons if actual results differ materially from those anticipated in the forward-looking statements. Investor Contact: ir@ngmbio.com Media Contact: media@ngmbio.com 1 Fejzo, M., Rocha, N., Cimino, I. et al. GDF15 linked to maternal risk of nausea and vomiting during pregnancy. Nature (2023). NGM BIOPHARMACEUTICALS, INC. CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS (In thousands, except per share amounts) (Unaudited) Three Months Ended December 31, Year Ended December 31, 2023 2022 2023 2022* Related party revenue $ 165 $ 18,181 $ 4,417 $ 55,333 Operating expenses: Research and development 21,890 46,722 118,040 181,067 General and administrative 7,938 9,756 37,840 40,515 Total operating expenses 29,828 56,478 155,880 221,582 Loss from operations (29,663 ) (38,297 ) (151,463 ) (166,249 ) Interest income, net 2,041 2,030 9,322 3,714 Other expense, net (48 ) (170 ) (234 ) (132 ) Net loss $ (27,670 ) $ (36,437 ) $ (142,375 ) $ (162,667 ) Net loss per share, basic and diluted $ (0.33 ) $ (0.45 ) $ (1.73 ) $ (2.03 ) Weighted average shares used to compute net loss per share, basic and diluted 82,803 81,787 82,496 79,950 ___________ * Derived from the audited consolidated financial statements. NGM BIOPHARMACEUTICALS, INC. CONDENSED CONSOLIDATED BALANCE SHEETS (In thousands) (Unaudited) December 31, 2023 December 31, 2022* ASSETS Current assets: Cash and cash equivalents $ 55,816 $ 73,456 Short-term marketable securities 88,369 198,036 Related party receivable from collaboration 58 7,580 Prepaid expenses and other current assets 9,202 9,787 Restricted cash 2,999 — Total current assets 156,444 288,859 Property and equipment, net 7,033 8,496 Operating lease right-of-use asset — 2,096 Restricted cash 2,455 3,954 Other non-current assets 2,936 3,997 Total assets $ 168,868 $ 307,402 LIABILITIES AND STOCKHOLDERS' EQUITY Current liabilities: Accounts payable $ 2,982 $ 8,453 Accrued liabilities 17,099 33,638 Operating lease liability, current — 5,385 Contract liabilities — 366 Total current liabilities 20,081 47,842 Other non-current liabilities 149 — Total liabilities 20,230 47,842 Commitments and contingencies Stockholders' equity: Preferred stock, $0.001 par value — — Common stock, $0.001 par value 83 82 Additional paid-in capital 872,545 841,413 Accumulated other comprehensive income (loss) 18 (302 ) Accumulated deficit (724,008 ) (581,633 ) Total stockholders' equity 148,638 259,560 Total liabilities and stockholders' equity $ 168,868 $ 307,402 ___________ * Derived from the audited consolidated financial statements.

March 04, 2024 -- CymaBay Therapeutics, Inc. (NASDAQ: CBAY), a biopharmaceutical company focused on innovative therapies for patients with liver and other chronic diseases, today announced that the Marketing Authorization Application (MAA) for seladelpar, for the treatment of primary biliary cholangitis (PBC) including pruritus in adults without cirrhosis or with compensated cirrhosis (Child Pugh A) who are inadequate responders or intolerant to ursodeoxycholic acid), has been validated and will now be reviewed by the European Medicines Agency (EMA). Seladelpar is an investigational, potent, selective peroxisome proliferator-activated receptor delta (PPARδ) agonist or delpar, in development for PBC treatment. The MAA application includes data from across the seladelpar PBC clinical development program in over 500 people with PBC, including from the pivotal, double blind, placebo-controlled, global Phase 3 RESPONSE study, recently published in the New England Journal of Medicine. The study’s primary endpoint measure reflects registrational studies of the current second line PBC treatment authorized by the EMA. In this study seladelpar demonstrated statistically significant improvements in biochemical markers of disease progression and PBC-related pruritus (itch) pre-specified endpoints. The number of adverse events was similar in the groups treated with seladelpar and placebo. The application is further supported by data from the Phase 3 ENHANCE study, the long-term open label ASSURE study, Phase 2 studies, pre-clinical studies and includes chemistry, manufacturing, and controls data. “People living with PBC in Europe today have limited treatment options and can face both disease progression and a lifetime of symptoms like itch and fatigue that can significantly impact their quality of life. New treatment options are needed,” said Klara Dickinson, Chief Regulatory and Compliance Officer, CymaBay Therapeutics. “Validation of the European Marketing Authorization Application for seladelpar and the start of the agency’s formal review is an important step forward in seladelpar’s journey to potential approval in Europe. We look forward to further discussion with the agency and rapporteurs as they conduct their review.” Under the European centralized licensing procedure, the EMA Committee for Medicinal Products for Human Use (CHMP) will review the application for all 27 Member States of the European Union, as well as Iceland, Liechtenstein and Norway. Seladelpar received Priority Medicines (PRIME) status from the EMA in 2016, as part of its program to enhance support for the development of medicines that target an unmet medical need. Seladelpar has been accepted for review by the U.K. Medicines and Healthcare products Regulatory Agency. The U.S. Food and Drug Administration (FDA) has accepted a New Drug Application for seladelpar for priority review. PBC is a rare, chronic inflammatory liver disease that can lead to liver cirrhosis and an increased risk of liver-related mortality. People living with PBC can experience symptoms that significantly impact their quality of life such as itch and fatigue. New treatment options seek to help prevent further disease progression by reducing inflammation and bile acids in the liver and help provide meaningful relief of pruritus. PBC is a rare, chronic inflammatory liver disease primarily affecting women (1 in 1,000 women over the age of 40 or about 130,000 total people in the US). PBC is characterized by impaired bile flow (known as cholestasis) and the accumulation of toxic bile acids in the liver, leading to inflammation and destruction of the bile ducts within the liver and causing increased levels of ALP, ALT, and GGT, enzymes found primarily in the liver, as well as total bilirubin. The most common early symptoms of PBC are pruritus (itching) and fatigue, which can be debilitating for some patients. Progression of PBC is associated with an increased risk of liver-related mortality. Seladelpar, an investigational treatment for people with PBC, is a first-in-class oral, selective peroxisome proliferator-activated receptor delta (PPARδ) agonist, or delpar, shown to regulate critical metabolic and liver disease pathways in indications with high unmet medical need. Preclinical and clinical data support its ability to regulate genes involved in bile acid synthesis, inflammation, fibrosis and lipid metabolism, storage, and transport. CymaBay Therapeutics, Inc. is a clinical-stage biopharmaceutical company focused on improving the lives of people with liver and other chronic diseases that have high unmet medical need. Our deep understanding of the underlying mechanisms of liver inflammation and fibrosis, and the unique targets that play a role in their progression, have helped us receive breakthrough therapy designation (U.S. Food and Drug Administration), Priority Medicines status (European Medicines Agency) and orphan drug status (U.S. and Europe) for seladelpar, a first-in-class investigational treatment for people with PBC. Our evidence-based decision-making and commitment to the highest quality standards reflect our relentless dedication to the people, families, and communities we serve. To learn more, visit www.cymabay.com and follow us on X (formerly Twitter) and LinkedIn. The content above comes from the network. if any infringement, please contact us to modify.