A Proof of Concept, Open-Label Study Evaluating the Safety, Tolerability, and Efficacy of Monotherapy and Combination Regimens in Subjects With Nonalcoholic Steatohepatitis (NASH)

The primary objective of this study is to evaluate the safety and tolerability of study drug(s) in participants with nonalcoholic steatohepatitis (NASH).

Start Date29 Jul 2019

Sponsor / Collaborator

Gilead Sciences, Inc.

[+1]

ACTRN12619000655145

/ CompletedPhase 1

A Phase 1 Open-Label, Parallel-Group, Two-Treatment, Single-Dose Study to Evaluate the Pharmacokinetics of GS-9674 and GS-0976 in Subjects with Normal Renal Function and Severe Renal Impairment

Start Date24 Jul 2019

Sponsor / Collaborator

Gilead Sciences, Inc.

NCT03449446

/ CompletedPhase 2

A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety and Efficacy of Selonsertib, GS-0976, GS-9674, and Combinations in Subjects With Bridging (F3) Fibrosis or Compensated Cirrhosis (F4) Due to Nonalcoholic Steatohepatitis (NASH)

The primary objectives of this study are:
* To assess the safety and tolerability of selonsertib (SEL), firsocostat (FIR) and cilofexor (CILO), administered alone or in combination, in participants with bridging fibrosis or compensated cirrhosis due to NASH
* To evaluate changes in liver fibrosis, without worsening of NASH

Start Date21 Mar 2018

Sponsor / Collaborator

Gilead Sciences, Inc.

100 Clinical Results associated with Firsocostat

100 Translational Medicine associated with Firsocostat

100 Patents (Medical) associated with Firsocostat

198

Literatures (Medical) associated with Firsocostat

01 Jun 2025·BRAIN RESEARCH BULLETIN

The effects and mechanisms of far-infrared ray on depression-like behavior induced by CRS in mice

Article

Author: Liu, Wanbin ; Nie, Lijuan ; Ling, Yian ; Li, Jing ; Zhu, Cuizhen ; Xia, Qingrong ; Gao, Yejun

PURPOSE:

Far-infrared ray (FIR) is an electromagnetic wave known to impart health benefits against various pathophysiological conditions, including diabetes mellitus, renocardiovascular disorders, stress, and depression, among others. However, the precise impact of FIR on major depressive disorder (MDD) and the underlying molecular mechanisms remain unclear. Here, we aimed to investigate the effects and elucidate the molecular mechanisms of FIR on depression-like behavior in mice.

METHODS:

A mouse model of depression was established using chronic restraint stress (CRS). Behavioral tests were performed to assess alterations in depression-like behaviors. Biochemical methods were employed to measure the levels of IL-1β, IL-6, TNF-α, S100β, IL-17, melatonin (MT), 5-hydroxytryptamine (5-HT), glutathione (GSH), malondialdehyde (MDA), brain-derived neurotrophic factor (BDNF), and corticosterone (CORT) in mice serum. Similarly, the levels of IL-1β, IL-6, TNF-α, S100β, IL-17, and MT in mice brains were measured using biochemical methods. Hematoxylin-eosin and Nissl staining were utilized to detect morphological changes in the mice hippocampus. In addition, the structure and mitochondrial morphology of hippocampal neurons and microglia were studied using transmission electron microscopy (TEM).

RESULTS:

The results of behavioral tests revealed that FIR mitigated the depression-like behaviors induced by CRS. FIR also reversed the levels of IL-1β, IL-6, TNF-α, and related cytokines in the periphery and brain. The results of hematoxylin-eosin and Nissl staining showed that FIR improved the damage of mice's hippocampus. Additionally, TEM revealed that FIR alleviated the damage of CRS to hippocampal neurons and microglia.

CONCLUSION:

Our findings suggest that FIR can ameliorate depression-like behavior induced by CRS in mice. FIR can reverse the levels of related cytokines in the periphery and brain, and alleviate damage to neurons and microglia, which may constitute its underlying molecular mechanism.

01 Apr 2025·Journal of Bone Oncology

Impact of myosteatosis on prognosis in multiple myeloma patients: A subgroup analysis of 182 cases and development of a nomogram

Article

Author: Yao, Xing-Chen ; Li, Meng ; Shi, Xiang-Jun ; Shi, Ming ; Xu, Zi-Yu ; Du, Xin-Ru ; Liu, Jun-Peng ; Wu, Yue

Background:

This study aims to explore the prognostic value of myosteatosis in multiple myeloma (MM) and to analyze the factors influencing myosteatosis.

Methods:

A retrospective analysis was conducted on 182 patients treated for MM at our institution from 2009 to 2020 who underwent MRI examinations. The fatty infiltration rate (FIR) of the erector spinae and multifidus muscles at the L3 level was measured to assess the degree of myosteatosis. Patients were grouped based on fracture presence and median FIR, and group differences were compared, with P < 0.05 considered statistically significant. Survival and fractures were used as prognostic indicators, and regression analysis was performed to determine the impact of FIR on these outcomes in MM patients. The factors influencing FIR were analyzed, and the relationship between myosteatosis and MM prognosis was further analyzed within its sensitive subgroups. Finally, a nomogram based on FIR was established and validated.

Results:

Significant differences were observed between the fracture and non-fracture groups in lactate dehydrogenase, serum phosphorus, visual analogue scale, oswestry disability index and FIR (P < 0.05). When patients were grouped based on the median FIR (28.89 %), there were significant differences in age, sex, body mass index (BMI), red blood cell (RBC) count, hemoglobin, hematocrit, albumin, visual analogue scale, oswestry disability index, and fracture incidence (P < 0.05). Univariate COX regression analysis indicated that myosteatosis had no significant impact on survival prognosis in MM patients (HR = 0.999, P = 0.852), with a log-rank test P value of 0.11 when grouped by the cut-off FIR value of 33.67 %. Multivariate logistic regression indicated that FIR is an independent predictor of fractures (OR = 1.054, P = 0.000). Multivariate linear regression revealed that age, sex, RBC count, and BMI are independent factors influencing FIR (P < 0.05). When not grouped, FIR's prediction of fractures showed no significant interaction with age, sex, RBC count, or BMI (P for interaction > 0.05). In subgroups with BMI ≥ 25 kg/m² or RBC count > 3.68 × 10^12/L, FIR lost its predictive significance for fractures. The FIR nomogram model had a C-index of 0.777, and the calibration curve, decision curve analysis, and clinical impact curve all validated its effectiveness.

Conclusions:

Myosteatosis characterized by FIR is not a reliable predictor of survival in MM patients but is effective in predicting fractures and is closely related to back pain and functional impairment. FIR is significantly associated with age, sex, RBC count, and BMI.

01 Mar 2025·ADVANCED FUNCTIONAL MATERIALS

Intelligent Nano‐Cage for Precision Delivery of CRISPR‐Cas9 and ACC Inhibitors to Enhance Antitumor Cascade Therapy Through Lipid Metabolism Disruption

Author: Zhang, La ; Xu, Qing ; Zhao, Wei ; Zhang, Mi ; Peng, Qiling ; Liu, Hongqing ; Guo, Jiao ; Zhao, Yifan ; Ren, Cong ; Wang, Jianwei ; Jiang, Ning

Abstract:

Reprogramming in lipid metabolism is a hallmark of cancer, and targeting the pivotal enzyme in fatty acid synthesis, acetyl‐CoA carboxylase 1 (ACC1), presents a promising therapeutic strategy. Herein, a nano‐cage encapsulated is constructed by peptide‐modified erythrocyte membrane (NTA630‐NCs‐RBCM‐T) for delivering CRISPR‐Cas9 and ACC1 inhibitors to enable dual‐layer inhibition of ACC1, thereby optimizing the effectiveness of antitumor cascade therapy. NTA630‐NCs‐RBCM‐T are efficiently delivered to cancer cells via peptide‐mediated targeting, releasing Cas9 complexes and ND630 in response to lysosomal enzymes, proton sponge effects, and elevated glutathione levels. The concurrent inhibition of fatty acid synthesis pathways, achieved by Cas9‐mediated ubiquitin‐specific protease 22 (USP22) knockdown and direct inhibition by ND630, enhances polyunsaturated fatty acids (PUFAs) uptake, triggers lipid peroxidation, leading to tumor cell death, particularly ferroptosis, and apoptosis, resulting in effective anti‐tumor activity.

News (Medical) associated with Firsocostat

30 Jan 2025

·www.prnewswire.com

Metabolic Dysfunction-Associated Steatohepatitis Market to Register Stunning Growth at a CAGR of 17.9% in the US by 2034 | DelveInsight

The MASH treatment landscape is evolving rapidly, driven by a diverse array of therapeutic classes, each with unique mechanisms and potential impacts. The forecast period reveals significant shifts and emerging trends that will shape future market dynamics. LAS VEGAS, Jan. 30, 2025 /PRNewswire/ -- DelveInsight's Metabolic Dysfunction-Associated Steatohepatitis Market Insights report includes a comprehensive understanding of current treatment practices, MASH emerging drugs, market share of individual therapies, and current and forecasted market size from 2020 to 2034, segmented into 7MM [the United States, the EU4 (Germany, France, Italy, and Spain) and the United Kingdom, and Japan]. Key Takeaways from the Metabolic Dysfunction-Associated Steatohepatitis Market Report According to DelveInsight's analysis, the market size for MASH was found to be USD 2.1 billion in the 7MM in 2023. In 2023, there were an estimated 42 million prevalent cases of MASH in the 7MM. Out of these, a total of ~15 million cases were diagnosed, and this number is projected to increase by the end of 2034 in the 7MM. Leading MASH companies such as Inventiva Pharma, Novo Nordisk A/S, Cirius Therapeutics, Akero Therapeutics, 89bio, Boehringer Ingelheim, Zealand Pharma, Galectin Therapeutics, Lipocine, Viking Therapeutics, Eli Lilly and Company, Boston Pharmaceuticals, Pfizer, HighTide Biopharma, CytoDyn, Merck & Co., Hanmi Pharmaceutical, Hepagene (Shanghai), Hepion Pharmaceuticals, Enyo Pharmaceuticals, Gilead Sciences, Poxel SA, Zydus Therapeutics, Sagimet Biosciences, Ionis Pharmaceuticals, Corcept Therapeutics, and others are developing novel MASH drugs that can be available in the MASH market in the coming years. The promising MASH therapies in the pipeline include Lanifibranor (IVA337), Semaglutide, Azemiglitazone (MSDC-0602K), Efruxifermin (EFX), BIO89-100 (Pegozafermin), Survodutide (BI 456906), GR-MD-02 (Belapectin), LPCN1144, VK2809, Tirzepatide, BOS-580, Ervogastat (PF-06865571) + Clesacostat (PF-05221304), HTD1801, Leronlimab (PRO 140), Efinopegdutide, HPG1860, Rencofilstat (CRV431), EYP001 (Vonafexor), Semaglutide/Cilofexor/Firsocostat, PXL065, Saroglitazar Magnesium, Denifanstat (TVB-2640), ION224, Miricorilant (CORT118335), and others. In March 2024, Madrigal Pharmaceuticals' groundbreaking product, REZDIFFRA (resmetirom), a once-daily, oral THR-ß agonist, received accelerated endorsement from the US FDA based on results from the Phase III MAESTRO-NASH trial. This approval marks a significant stride in the medical landscape, as REZDIFFRA becomes the inaugural and sole FDA-sanctioned therapy for adults afflicted with non-cirrhotic MASH, accompanied by moderate to advanced liver scarring (fibrosis) corresponding to stages F2–F3 fibrosis. Discover which therapies are expected to grab the major MASH market share @ Metabolic Dysfunction-Associated Steatohepatitis Market Report Metabolic Dysfunction-Associated Steatohepatitis Overview Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive liver disease that stems from metabolic dysfunction, often linked to obesity, diabetes, and other conditions of metabolic syndrome. MASH is characterized by the accumulation of fat in liver cells, accompanied by inflammation and liver cell injury, which can progress to fibrosis, cirrhosis, or even liver cancer. The primary drivers of MASH include insulin resistance, obesity, type 2 diabetes, and dyslipidemia. Genetic predisposition and a sedentary lifestyle also play significant roles. Environmental factors, such as a poor diet high in sugars and fats, exacerbate the condition. MASH is often asymptomatic in its early stages. When symptoms occur, they can include fatigue, vague abdominal discomfort, or pain in the upper right quadrant. In advanced stages, signs of liver dysfunction such as jaundice, swelling of the abdomen or legs, and confusion may arise. Diagnosis involves a combination of clinical history, physical examination, and diagnostic tests. Blood tests measuring liver enzymes (ALT, AST) often indicate liver inflammation. Imaging techniques like ultrasound, MRI, or FibroScan can identify liver fat and fibrosis. In some cases, a liver biopsy is required to confirm the diagnosis and assess disease severity. Metabolic Dysfunction-Associated Steatohepatitis Epidemiology Segmentation The MASH epidemiology section provides insights into the historical and current MASH patient pool and forecasted trends for the 7MM. It helps recognize the causes of current and forecasted patient trends by exploring numerous studies and views of key opinion leaders. The MASH market report proffers epidemiological analysis for the study period 2020–2034 in the 7MM segmented into: Prevalent Cases of MASH Diagnosed Prevalent Cases of MASH Gender-specific Diagnosed Prevalent Cases of MASH Severity-specific Diagnosed Prevalent Cases of MASH Metabolic Dysfunction-Associated Steatohepatitis Treatment Market The approval of REZDIFFRA (resmetirom) in March 2024 represents a pivotal achievement in medical innovation, transforming the treatment landscape for MASH disease. This groundbreaking therapy addresses the root causes of MASH, offering renewed hope to patients grappling with this challenging condition. Clinical trials have shown impressive results, with REZDIFFRA effectively reducing symptoms like inflammation and fibrosis, enhancing liver function, and improving patients' quality of life. By providing healthcare professionals with a robust treatment option, this approval addresses a critical unmet need and has the potential to significantly alleviate the complications linked to advanced liver disease. The prevalence of MASLD is strongly linked to type 2 diabetes mellitus and obesity, particularly in individuals with a higher body mass index. However, MASLD occurrence is reduced in T2DM patients receiving treatments such as sodium-glucose cotransporter-2 (SGLT2) inhibitors, GLP-1 receptor agonists, and insulin. Vitamin E, with its antioxidant properties, is regarded as a first-line pharmacological option for managing MASH, especially when dietary and lifestyle interventions are insufficient. Antifibrotic agents can help prevent the progression of liver fibrosis and MASLD into fibrotic MASH. The role of pioglitazone, an anti-diabetic medication, in improving MASH histology in T2DM patients is well-documented, but concerns remain regarding potential side effects like weight gain, fluid retention, cancer risk, and bone fractures. Additional therapeutic targets for MASLD and MASH include G protein-coupled receptors (GPCRs), estrogen-related receptor alpha (ERRα), bone morphogenetic proteins (BMPs), and KLFs. Bariatric surgery, or weight loss surgery, is the most effective intervention for treating obesity and diabetes, as it reduces food absorption while influencing gut hormone secretion and metabolic function. To know more about MASH treatment guidelines, visit @ Metabolic Dysfunction-Associated Steatohepatitis Management Metabolic Dysfunction-Associated Steatohepatitis Pipeline Therapies and Key Companies Lanifibranor (IVA337): Inventiva Pharma Semaglutide: Novo Nordisk A/S Azemiglitazone (MSDC-0602K): Cirius Therapeutics Efruxifermin (EFX): Akero Therapeutics BIO89-100 (Pegozafermin): 89bio Survodutide (BI 456906): Boehringer Ingelheim/Zealand Pharma GR-MD-02 (Belapectin): Galectin Therapeutics LPCN1144: Lipocine VK2809: Viking Therapeutics Tirzepatide: Eli Lilly and Company BOS-580: Boston Pharmaceuticals Ervogastat (PF-06865571) + Clesacostat (PF-05221304): Pfizer HTD1801: HighTide Biopharma Leronlimab (PRO 140): CytoDyn Efinopegdutide: Merck & Co./Hanmi Pharmaceutical HPG1860: Hepagene (Shanghai) Rencofilstat (CRV431): Hepion Pharmaceuticals EYP001 (Vonafexor): Enyo Pharmaceuticals Semaglutide/ Cilofexor/ Firsocostat: Gilead Sciences PXL065: Poxel SA Saroglitazar Magnesium: Zydus Therapeutics Denifanstat (TVB-2640): Sagimet Biosciences ION224: Ionis Pharmaceuticals Miricorilant (CORT118335): Corcept Therapeutics Discover more about MASH drugs in development @ Metabolic Dysfunction-Associated Steatohepatitis Clinical Trials Metabolic Dysfunction-Associated Steatohepatitis Market Dynamics The MASH market dynamics are expected to change in the coming years. Growing research activities and multiple clinical trials for MASH, driven by the rapid surge in its prevalence due to rising obesity and type 2 diabetes rates, highlight an active drug development pipeline and an expanding market size. The large pool of patients and lucrative growth opportunities present attractive prospects for key players, further supported by ongoing preclinical studies aimed at advancing imaging techniques for MASH diagnosis, potentially eliminating the need for invasive biopsy-based histopathological confirmation. Furthermore, potential therapies are being investigated for the treatment of MASH, and it is safe to predict that the treatment space will significantly impact the MASH market during the forecast period. Moreover, the anticipated introduction of emerging therapies with improved efficacy and a further improvement in the diagnosis rate are expected to drive the growth of the MASH market in the 7MM. However, several factors may impede the growth of the MASH market. Lack of awareness and negligence in the early stages of MASH by physicians often lead to disease progression, culminating in irreversible damage where liver transplantation becomes the only viable option. Diagnosing advanced MASH typically requires procedures like liver biopsy, which are costly, invasive, and risky. Regulatory challenges also pose hurdles, as the FDA mandates achieving one MASH endpoint for approval, while the EMA's draft guidance requires efficacy in both endpoints, potentially delaying first-mover approvals in major European markets. Additionally, access to expensive MASH treatments may be limited in certain regions, further hindering patient adoption. Moreover, MASH treatment poses a significant economic burden and disrupts patients' overall well-being and QOL. Furthermore, MASH market growth may be offset by failures and discontinuation of emerging therapies, unaffordable pricing, market access and reimbursement issues, and a shortage of healthcare specialists. In addition, the undiagnosed, unreported cases and the unawareness about the disease may also impact MASH market growth. Scope of the Metabolic Dysfunction-Associated Steatohepatitis Market Report Therapeutic Assessment: Metabolic Dysfunction-Associated Steatohepatitis current marketed and emerging therapies Metabolic Dysfunction-Associated Steatohepatitis Market Dynamics: Key Market Forecast Assumptions of Emerging Metabolic Dysfunction-Associated Steatohepatitis Drugs and Market Outlook Competitive Intelligence Analysis: SWOT analysis and Market entry strategies Unmet Needs, KOL's views, Analyst's views, Metabolic Dysfunction-Associated Steatohepatitis Market Access and Reimbursement Download the report to understand which factors are driving MASH market trends @ Metabolic Dysfunction-Associated Steatohepatitis Market Trends Table of Contents Related Reports Non-Alcoholic Steatohepatitis Epidemiology Forecast Non-Alcoholic Steatohepatitis Epidemiology Forecast – 2034 report delivers an in-depth understanding of the disease, historical and forecasted NASH epidemiology in the 7MM, i.e., the United States, EU4 (Germany, France, Italy, Spain), the United Kingdom, and Japan. Nonalcoholic Steatohepatitis Pipeline Nonalcoholic Steatohepatitis Pipeline Insight – 2024 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key nonalcoholic steatohepatitis companies, including Madrigal Pharmaceuticals, Intercept Pharmaceuticals, Cirius Therapeutics, Novo Nordisk, Inventiva, Galmed Pharmaceuticals, AstraZeneca, Galectin Therapeutics, Viking Therapeutics, Eli Lilly and Company, Terns Pharmaceuticals, Sinew Pharma, 89bio, Inc., Eccogene, Novartis Pharmaceuticals, Poxel SA, AngioLab, Pfizer, Arrowhead Pharma, LG Chem, Redx Pharma, Lipocine, Inc., CytoDyn, Inc., Alnylam Pharmaceuticals, Inc., Chemomab Therapeutics, NuSirt Biopharma, HK inno. N, Aligos Therapeutics, Altimmune, Inc., Kowa Pharmaceutical, Ionis Pharmaceuticals, NorthSea Therapeutics, Rivus Pharmaceuticals, Hanmi Pharmaceutical, Hepagene Therapeutics, HighTide Biopharma, Akero Therapeutics, Merck Sharp & Dohme LLC, Cascade Pharmaceuticals, Hepion Pharmaceuticals, Chipscreen Biosciences, Boston Pharmaceuticals, Bristol-Myers Squibb, Sunshine Lake Pharma, GSK plc., Future Medicine, Gilead Sciences, ENYO Pharma, Histogen, among others. Non-Alcoholic Fatty Liver Disease Market Non-Alcoholic Fatty Liver Disease Market Insight, Epidemiology, and Market Forecast – 2034 report delivers an in-depth understanding of the market trends, market drivers, market barriers, and key NAFLD companies, including MediciNova, Eli Lilly and Company, AstraZeneca, Inventiva Pharma, Oasis Pharmaceuticals, LLC, Madrigal Pharmaceuticals, Inc., BioMarin Pharmaceutical, GlaxoSmithKline, Zydus Therapeutics Inc., Akero Therapeutics, Inc, Pfizer, Boehringer Ingelheim, Neuraly, Inc., Merck Sharp & Dohme LLC, Rivus Pharmaceuticals, Inc., Hepion Pharmaceuticals, Inc. , among others. Non-Alcoholic Fatty Liver Disease Pipeline Non-Alcoholic Fatty Liver Disease Pipeline Insight – 2024 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key NAFLD companies, including BeiGene, Inventiva Pharma, Cirius Therapeutics, Madrigal Pharma, Novo Nordisk, Galmed Pharmaceuticals, AstraZeneca, Galectin Therapeutics, Viking Therapeutics, Dr. Falk Pharma GmbH, Sagimet Biosciences, Eli Lilly and Company, Terns Pharmaceuticals, Sinew Pharma, Novartis Pharmaceuticals, Afimmune, Poxel SA, AngioLab, Pfizer, Oramed Pharmaceuticals, Can Fite Biopharma, MediciNova, Metacrine, Inc., Lipocine, Inc., CytoDyn, Inc., Alnylam Pharmaceuticals, Inc., Mitsubishi Tanabe Pharma, Chemomab Therapeutics, NuSirt Biopharma, HK inno.N, Kowa Pharmaceutical, Ionis Pharmaceuticals, NorthSea Therapeutics, Rivus Pharmaceuticals, Hanmi Pharmaceutical, Hepagene Therapeutics, HighTide Biopharma, Akero Therapeutics, Enanta Pharmaceuticals, Cascade Pharmaceuticals, among others. About DelveInsight DelveInsight is a leading Business Consultant and Market Research firm focused exclusively on life sciences. It supports pharma companies by providing comprehensive end-to-end solutions to improve their performance. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform PharmDelve . Contact Us Shruti Thakur [email protected] +14699457679 Logo: SOURCE DelveInsight Business Research, LLP WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Phase 3

12 Feb 2024

·medcitynews.com

Gilead’s $4.3B CymaBay Acquisition Adds Liver Disease Drug Under FDA Review

Gilead Sciences is acquiring biotech company CymaBay Therapeutics in a $4.3 billion deal that comes with a drug candidate currently under FDA review in a rare liver disease with few treatments. According to deal terms announced Monday, Gilead will pay $32.50 cash for each share of CymaBay. That price is a 27% premium to CymaBay’s closing stock price on Friday. The acquisition marks a comeback for the company and its drug, which just a few years ago faced an uncertain future amid safety questions. The main asset of CymaBay is seladelpar, a drug that the Newark, California-based company has developed for treating primary biliary cholangitis (PBC), a rare and progressive autoimmune condition that destroys the bile ducts of the liver. But this small molecule was at one time among the leading drug candidates for nonalcoholic steatohepatitis (NASH), a fatty liver disease that has no FDA-approved treatments. In 2019, a safety signal led CymaBay to stop a mid-stage test of seladelpar in NASH as well as a recently started study in primary sclerosing cholangitis, another chronic liver disorder. The FDA subsequently placed a formal clinical hold on the drug. The hold also stalled the development of the drug in PBC. The FDA cleared the company to resume testing of the drug in 2020, but CymaBay elected to continue development only in PBC. PBC is a chronic disorder that mainly affects women over the age of 40, impairing liver function. Common early symptoms include severe pruritus (itching) and fatigue. PBC can progress to cirrhosis and liver failure. The first-line drug treatment for PBC is ursodeoxycholic acid, or ursodiol, an old drug for dissolving gallstones that in 1996 won an additional approval as a treatment for PBC. The Intercept Pharmaceuticals drug Ocaliva was approved in 2016 as a second-line therapy for PBC. Intercept, which was acquired late last year by Italian company Alfasigma, reported $240.4 million in sales for the drug in the nine months ended Sept. 30, 2023. CymaBay’s seladelpar is a small molecule designed to bind to and activate peroxisome proliferator activated receptor delta (PPAR delta), a receptor that regulates genes involved in the synthesis of bile acids, metabolism, inflammation, and fibrosis. In its placebo-controlled Phase 3 clinical trial, results showed treatment with the drug led to statistically significant normalization of enzymes indicative of liver disease as well as improvement in pruritus. Late last year, CymaBay submitted a new drug application seeking approval of seladelpar as a treatment for patients who are inadequate responders to or intolerant of ursodiol. CymaBay announced Monday that the FDA will evaluate the application under priority review, setting an Aug. 14 target date for a regulatory decision. Gilead’s portfolio of liver disease drugs include the hepatitis B drugs Vemlidy and Viread as well as hepatitis C drug Harvoni. The Foster City, California-based drugmaker is also in the chase for NASH (now also called MASH, for metabolic associated steatohepatitis) with cilofexor and firsocostat, which are in Phase 2 testing as part of a combination treatment with Novo Nordisk’s semaglutide. “Building on the strong research and development work by the CymaBay team to date, we have the potential to address a significant unmet need for people living with PBC and expand on our existing broad range of transformational therapies,” Gilead Chairman and CEO Daniel O’Day said in a prepared statement. CymaBay licensed seladelpar from Johnson & Johnson in a 2006 deal. If it’s approved, J&J is in line to receive royalties from sales. The CymaBay pipeline also includes MBX-2982, a molecule in Phase 2a testing for treating hypoglycemia in patients with type 1 diabetes. In a note sent to investors, William Blair analyst Andy Hsieh wrote that the CymaBay acquisition validates the clinical performance and commercial potential of seladelpar in PBC. He called the acquisition “poetic closure” for the company following the molecule’s previous clinical trial setbacks “We commend management’s resilience and persistence that ultimately led to seladelpar demonstrating the best-in-class clinical profile in PBC, and we expect the drug to benefit thousands of patients living with PBC as soon as later this year,” Hsieh said. Hsieh said the Gilead offer is fair and it is unlikely another bidder will emerge. The transaction requires the majority of CymaBay shareholders to tender their shares. The companies expect to close the transaction in the current quarter.

Phase 2AcquisitionClinical ResultPhase 3Drug Approval

06 Sep 2023

·www.biospace.com

Nimbus Secures $210M in Private Funding on Heels of $4B Takeda Deal

Pictured: Illustration of money exchanging hands/iStock, MagicVectorCreation Nimbus Therapeutics announced Wednesday that it raised $210 million to advance its next wave of small-molecule medicines, making it one of 2023’s larger rounds of private financing. The Boston biotech company will be putting the cash towards a variety of initiatives including its ongoing clinical development of NDI-101150, a hematopoietic progenitor kinase 1 inhibitor in patients with solid tumors. New programs are targeting Werner syndrome helicase and an as-yet undisclosed immune target, as well as novel targeted therapies that activate adenosine monophosphate-activated protein kinase (AMPK) to treat metabolic disorders in a nearly $500 million deal with Eli Lilly. This is not Nimbus’ first successful round of fundraising. The company raised $125 million in late 2022, bringing in Bain Life Sciences and SV Health Investors. The latest funding drive announcement on Wednesday brought in some big new investors as well as some old standbys. In particular, the funding round was co-led by Google Ventures—a new investor to Nimbus—as well as existing investors SR One and Atlas Venture. The funding round also brought in another unnamed investor, which Nimbus described in the announcement as “a U.S.-based life sciences-focused fund,” alongside existing investors including Bain Capital Life Sciences, BVF Partners, Gates Frontier, Lightstone Ventures, Pfizer Ventures, RA Capital Management and SV Health Investors. It’s one of the bigger investments in biopharma this year. The industry has seen significant ups and downs in recent years: 2021 was a banner year, building off enthusiasm for COVID-19 vaccines and treatments, before a serious drop-off occurred in 2022. This fundraising round marks the latest good news for Nimbus. At the close of 2022, Phase IIb data for NDI-034858, an allosteric tyrosine 2 kinase inhibitor being developed to treat autoimmune disease, showed that it had met its primary efficacy endpoint—a statistically significant increase in the number of patients hitting a 75% improvement in skin lesions. Two weeks later, Takeda announced it would be buying both the Nimbus therapy and wholly-owned subsidiary Nimbus Lakshmi. Nimbus CEO Jeb Keiper said at the time the results demonstrated NDI-034858 had “the potential to be a best-in-class medicine in multiple disease areas.” The initial $4 billion deal could be worth as much as $6 billion: two milestone payments of $1 billion each kick in at $4 billion and $5 billion in annual net drug sales. Keiper told BioSpace at the time that Nimbus’ focus was on designing breakthrough medicines before partnering with multinational pharma companies to bring them to commercialization. They inked a similar deal in 2016, when Gilead Sciences acquired the company’s lead clinical program, firsocostat, in nonalcoholic steatohepatitis. Connor Lynch is a freelance writer based in Ottawa, Canada. Reach him at lynchjourno@gmail.com.

Phase 2AcquisitionClinical ResultVaccine

100 Deals associated with Firsocostat

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KEGG	Wiki	ATC	Drug Bank
D11640	-	-	DB16166

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Compensated cirrhosis	Phase 2	United States	Gilead Sciences, Inc.	21 Mar 2018
Compensated cirrhosis	Phase 2	Australia	Gilead Sciences, Inc.	21 Mar 2018
Compensated cirrhosis	Phase 2	Canada	Gilead Sciences, Inc.	21 Mar 2018
Compensated cirrhosis	Phase 2	Hong Kong	Gilead Sciences, Inc.	21 Mar 2018
Compensated cirrhosis	Phase 2	New Zealand	Gilead Sciences, Inc.	21 Mar 2018
Compensated cirrhosis	Phase 2	Puerto Rico	Gilead Sciences, Inc.	21 Mar 2018
Fibrosis, Liver	Phase 2	United States	Gilead Sciences, Inc.	21 Mar 2018
Fibrosis, Liver	Phase 2	Australia	Gilead Sciences, Inc.	21 Mar 2018
Fibrosis, Liver	Phase 2	Canada	Gilead Sciences, Inc.	21 Mar 2018
Fibrosis, Liver	Phase 2	Hong Kong	Gilead Sciences, Inc.	21 Mar 2018

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03987074 (Pubmed \| J Hepatol) Manual	Phase 2	Nonalcoholic Steatohepatitis	108	Semaglutide+Cilofexor tromethamine	zkgfrgexhl(rbqknpxbdd) = Treatments were well tolerated - the incidence of adverse events was similar across groups (73-90%) and most events were gastrointestinal in nature. dnatzvajda (nndhdlrhos ) View more	Positive	16 Apr 2022
				Semaglutide+Firsocostat+Cilofexor tromethamine
NCT02781584 (Pubmed \| Clin Gastroenterol Hepatol) Manual	Phase 2	Hypertriglyceridemia \| Nonalcoholic Steatohepatitis	66	Fenofibrate+Cilofexor tromethamine+Firsocostat	lyrensxnwz(bgapovvffa) = most treatment-emergent adverse events were Grade 1 to 2 severity sydydvabmr (uvvvyyovsy ) View more	Positive	06 Jan 2022
				Icosapent Ethyl+Cilofexor tromethamine+Firsocostat
NCT03987074 (CTgov)	Phase 2	Nonalcoholic Steatohepatitis	109	Semaglutide (Semaglutide)	uwwhvteacz = ivqeyekbkc cutqwnahlk (mgdaneshfs, iyakhtzatx - cijoppjnab) View more	-	15 Jul 2021
				Semaglutide+Firsocostat (Semaglutide + Firsocostat 20 mg)	uwwhvteacz = tfllaipthx cutqwnahlk (mgdaneshfs, yeiocpszfa - vezavaneze) View more
NCT03449446 (ATLAS, CTgov)	Phase 2	Fibrosis, Liver \| Nonalcoholic Steatohepatitis \| Fibrosis ... View more	395	Placebo to match SEL	eszxgcvrhc = ktfivjvjgd kushgdhmpv (nmnhofdlij, bcgrayttrx - kodolytdes) View more	-	03 Dec 2020
NCT02856555 (CTgov)	Phase 2	Nonalcoholic Steatohepatitis	127	Placebo+Firsocostat (Firsocostat 5 mg)	opncqqeznk = muejirltau tzshmpgrnr (mzrynyeere, ybiuoihwgy - aryvcthgwr) View more	-	24 Jul 2020
				Placebo+Firsocostat (Firsocostat 20 mg)	opncqqeznk = ppdhbepwnl tzshmpgrnr (mzrynyeere, ngyailqbaj - snhkewigoi) View more
EASL2019	Not Applicable	Nonalcoholic Steatohepatitis	20	GS-0976 20 mg + GS-9674 30 mg	pokquptdkx(gmqkhlihon) = rppmjrlyre rxjqyenwfr (xfallmvzlh ) View more	-	13 Apr 2019
				GS-0976 20 mg	pokquptdkx(gmqkhlihon) = nbuxbdbdtx rxjqyenwfr (xfallmvzlh ) View more
NCT02856555 (Pubmed \| Gastroenterology)	Phase 2	Metabolic dysfunction-associated steatotic liver disease	126	GS-0976 20 mg	ghcuuvtsbv(dcelcfttem) = eiysnxekfh bggxxhnzvc (jprbemhjpj )	-	01 Nov 2018

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