Delving into the Latest Updates on Emricasan with Synapse

Treatments for COVID-19 are urgently needed. Emricasan (EMR) is a pan caspase inhibitor. Caspase-1 plays a role in a form of cell death called pyroptosis. EMR inhibits pyroptosis. The Investigators have shown that peripheral blood lymphocytes of COVID-19 patients overexpress caspase-1, providing evidence for pyroptosis. A recent European study corroborate the Investigators finding as they have shown evidence for the activation of the inflammasome in COVID-19.

Start Date11 Mar 2021

Sponsor / Collaborator

Histogen, Inc.

NCT03205345

/ Unknown statusPhase 2

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of Emricasan, an Oral Caspase Inhibitor, in Subjects With Decompensated Non-Alcoholic Steatohepatitis (NASH) Cirrhosis

This is a multicenter, double-blind, randomized, placebo-controlled study to evaluate the safety and efficacy of emricasan in improving event-free survival based on a composite clinical endpoint (where all-cause mortality, new decompensation events, and MELD score progression are events) in subjects with decompensated NASH cirrhosis.

Start Date28 Jun 2017

Sponsor / Collaborator

Conatus Pharmaceuticals, Inc.

NCT03462576

/ TerminatedNot Applicable

Companion Protocol for the ¹³C-Methacetin Breath Test Using the BreathID® MCS System for Conatus Phase 2 Study of Emricasan, an Oral Caspase Inhibitor, Under Protocol IDN-6556-17

This study is a companion protocol that will use the data generated by Conatus' study of emricasan under protocol IDN-6556-17.The IDN-6556-17 study is a Phase 2, multicenter, double-blind, placebo-controlled trial of Emricasan in subjects with decompensated non-alcoholic steatohepatitis (NASH) cirrhosis.

Start Date28 Jun 2017

Sponsor / Collaborator

Meridian Bioscience, Inc.

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100 Clinical Results associated with Emricasan

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100 Translational Medicine associated with Emricasan

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100 Patents (Medical) associated with Emricasan

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130

Literatures (Medical) associated with Emricasan

01 Jun 2025·INTERNATIONAL IMMUNOPHARMACOLOGY

Theaflavin suppresses necroptosis by attenuating RIPK1-RIPK3-MLKL signaling and mitigates cisplatin-induced kidney injury in mice

Article

Author: Li, Ya-Ping ; Ke, Hua-Yu ; Duan, Ling-Han ; He, Xian-Hui ; Ouyang, Dong-Yun ; Chan, On-Kei ; Shi, Zi-Jian ; Zha, Qing-Bing ; Zhou, Zhi-Ya ; Yang, Hai-Yan ; Yan, Liang ; Sun, Nuo

Necroptosis is a lytic form of regulated cell death (RCD) that is dependent on receptor-interacting protein kinase 3 (RIPK3) and mixed lineage kinase domain like pseudokinase (MLKL). This form of RCD has been implicated in various inflammatory diseases and organ injuries including cisplatin-induced acute kidney injury (AKI), thus representing a therapeutic target for such diseases. Theaflavin is an ingredient of black tea that exhibits beneficial effects on human health and has been shown to regulate pyroptosis, but its effects on necroptosis and cisplatin-induced AKI remain unclear. In this study, we found that theaflavin suppressed necroptosis in murine macrophages, MPC-5 podocytes and human HT-29 cells treated with TNF-α, Smac mimetic and IDN-6556 or LPS plus IDN-6556. The RIPK1/RIPK3/MLKL signaling axis in these cells treated with necroptosis inducers was effectively inhibited by theaflavin. The inhibition of necroptotic signaling was associated with attenuated mitochondrial dysfunction (as evidenced by decreased mitochondrial membrane potential and increased mitochondrial ROS production), reduced ubiquitination of RIPK1 and RIPK3, and blockade of necrosome. Furthermore, oral administration of theaflavin mitigated renal and hepatic injury in a mouse model of cisplatin-induced AKI. In agreement with in vitro cellular data, theaflavin decreased the levels of phosphorylated MLKL, an in vivo biomarker for necroptosis, in macrophages and other cells in the kidney and the liver of mice with cisplatin-induced AKI. Collectively, these results indicate that theaflavin can suppress necroptosis by attenuating RIPK1/RIPK3/MLKL signaling and thereby conferring protection against cisplatin-induced AKI, uncovering a previously unappreciated action of black tea components against necroptosis-related disorders.

01 May 2025·ACTA BIOCHIMICA ET BIOPHYSICA SINICA

Andrographolide prevents necroptosis by suppressing the generation of reactive oxygen species

Article

Author: Duan, Linghan ; Hu, Bo ; Zhou, Zhiya ; Gan, Yingqing ; Ouyang, Dongyun ; Li, Qing ; Li, Yaping ; Zha, Qingbing ; Shi, Fuli ; Li, Jinhua ; Xu, Rong ; He, Xianhui ; Lu, Na

Andrographolide (Andro), a natural product extracted from the Chinese traditional medicine herb Andrographis paniculata, has been applied for the treatment of diverse inflammatory diseases. However, its effects on necroptosis, a lytic form of cell death implicated in various inflammatory diseases, remain uncharacterized. In the present study, we investigate whether Andro and its derivatives can suppress necroptosis. Our results demonstrate that Andro notably inhibits necroptosis in the in vitro cellular models induced by either lipopolysaccharide (LPS) plus IDN-6556 or a combination of TNF-α, LCL-161 (Smac mimetic) and IDN-6556. In these cellular models, Andro inhibits the phosphorylation of receptor-interacting protein kinase 1 (RIPK1), RIPK3, and mixed lineage kinase domain-like pseudokinase (MLKL), as well as the formation of necrosomes. Specifically, Andro reduces the levels of intracellular reactive oxygen species (ROS) and mitochondrial superoxide (mtROS), preserves the mitochondrial membrane potential during necroptotic induction, and activates the antioxidant transcription factor nuclear factor E2-related factor 2 (Nrf2). Upon necroptotic stimulation, some mitochondrial proteins, such as Bcl-2 and Bak, oligomerize and co-localize with RIPK1, RIPK3, and phosphorylated MLKL (p-MLKL) in necrosomes. However, this process of necrosome formation can be prevented by Andro. In contrast, derivatives, including dehydroandrographolide, neoandrographolide, 14-deoxy-11,12-didehydroandrographolide, and 14-deoxyandrographolide, have no anti-necroptotic effects and fail to upregulate Nrf2. Collectively, our findings demonstrate that Andro specifically inhibits the RIPK1/RIPK3/MLKL signaling axis to suppress necroptosis, highlighting its therapeutic potential against necroptosis-related disorders.

01 Sep 2024·Cell Reports Medicine

Uncovering therapeutic targets for macrophage-mediated T cell suppression and PD-L1 therapy sensitization

Article

Author: Coussens, Lisa M ; Malhotra, Sanjay V ; Schedin, Pepper ; Lee, Jee Min ; Malhotra, Sanjay V. ; Coussens, Lisa M. ; Keefe, Bailey F ; Nelson, Dylan ; Dheeraj, Arpit ; Tailor, Dhanir ; Kumar, Sushil ; Kummar, Shivaani ; Stefan, Kirsten ; Li, Wenqi ; Keefe, Bailey F.

Tumor-associated macrophages (TAMs) and other myelomonocytic cells are implicated in regulating responsiveness to immunotherapies, including immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 axis. We have developed an ex vivo high-throughput approach to discover modulators of macrophage-mediated T cell suppression, which can improve clinical outcomes of ICIs. We screened 1,430 Food and Drug Administration (FDA)-approved small-molecule drugs using a co-culture assay employing bone-marrow-derived macrophages (BMDMs) and splenic-derived T cells. This identified 57 compounds that disrupted macrophage-mediated T cell suppression. Seven compounds exerted prominent synergistic T cell expansion activity when combined with αPD-L1. These include four COX1/2 inhibitors and two myeloid cell signaling inhibitors. We demonstrate that the use of cyclooxygenase (COX)1/2 inhibitors in combination with αPD-L1 decreases tumor growth kinetics and enhances overall survival in triple-negative breast cancer (TNBC) tumor models in a CD8⁺ T cell-dependent manner. Altogether, we present a rationalized approach for identifying compounds that synergize with ICI to potentially enhance therapeutic outcomes for patients with solid tumors.

40

News (Medical) associated with Emricasan

20 Sep 2023

·www.biospace.com

Fresh Tracks, Histogen to Shutter Businesses in Absence of Viable Options

Pictured: Closed sign being flipped over/iStock, StockSeller_ukr Colorado-based pharma Fresh Tracks announced Tuesday that its board of directors had unanimously agreed to dissolve the company and liquidate its assets, while California biotech Histogen on Monday also announced that it was dissolving and liquidating its business. Fresh Tracks will discontinue all its clinical and preclinical development programs as well as lay off “most employees,” which is set to happen by early October 2023, according to the company’s announcement. The news comes after the company’s search for potential strategic alternatives to save its business had turned up empty. However, Fresh Tracks will retain consultants, advisors and certain employees who are involved in the company’s dissolution. The company’s liquidation is still pending final approval from its shareholders. A day before Fresh Tracks announced its closure plans, San Diego-based Histogen said that it was dissolving and liquidating its business. Like its Colorado counterpart, Histogen has opted to discontinue all clinical development programs and has drastically slimmed down its workforce as part of its dissolution plan. Most employees will be laid off by the end of September 2023, according to the company’s announcement. Fresh Tracks was launched in September 2022 from a sweeping rebranding of Brickell Biotech. At the time, former CEO Robert Brown said that the company’s new name reflects the company’s mission “to develop groundbreaking, novel therapies that have the potential to restore immune balance.” Brown retired in January 2023 and was succeeded by Andew Sklawer. The company has since advanced a pipeline of immunology assets, including the DYRK1A inhibitor FRTX-02, which was in Phase I assessments for atopic dermatitis and was also being proposed for rheumatoid arthritis and type 1 diabetes. The company also owned an oral STING inhibitor, dubbed FRTX-10, which was in preclinical development for systemic lupus erythematosus, dermatomyositis and non-alcoholic steatohepatitis. In its most recent earnings report, posted August 2023, Fresh Tracks announced that it had “paused substantially all of its research and development activities in order to conserve capital resources.” In a previous earnings call soon after its rebrand, the company indicated that it was looking at strategic options including financing, merger or reverse merger, business combination or the sale of part of the company. Under its plan of dissolution, Histogen is considering selling off its pipeline assets—the proceeds from which would be distributed to stockholders along with its remaining cash. The proposed dissolution is still pending approval from the company’s stockholders, for which it expects to convene a special meeting in the fourth quarter of this year. Prior to the announcement, Histogen was advancing its experimental bacterial skin infection treatment emricasan. It had received the FDA’s go-ahead in March 2023 to conduct clinical trials for the candidate. Tristan Manalac is an independent science writer based in Metro Manila, Philippines. He can be reached at tristan@tristanmanalac.com or tristan.manalac@biospace.com.

Phase 1Executive Change

19 Sep 2023

·www.biopharmadive.com

Histogen plans to wind down operations after failing to find a partner

Dive Brief:Histogen intends to close down after an investment bank found no viable options to provide the regenerative medicine company with the money needed to stay operational.Directors of the San Diego-based drugmaker approved a liquidation plan that will be up for a shareholder vote in the fourth quarter. In the meantime, Histogen has stopped all clinical work and laid off almost all of its staff. By Sept. 30, only two employees will remain, including Chief Financial Officer Susan Knudson, who will also become CEO, president and principal executive officer.As part of the plan announced Monday, Histogen will delist its shares on the Nasdaq stock exchange, seek to sell assets, and distribute any remaining cash to stockholders after paying debts and obligations. The company will also continue looking for buyers for pipeline assets, which may produce more cash for investors.Dive Insight:Histogen reaches the end of its road after hiring Roth Capital Partnersin July to explore strategic alternatives. In the end, no possibility existed that would enhance stockholder value, Steven Mento, the companys current CEO, said in a statement.Mento will lose his position effective Sept. 30, as will the rest of Histogens suite of executives, aside from Knudson.Histogen needed cash to develop an experimental drug called emricasan, for treatment of bacterial skin infections. The company received approval from the Food and Drug Administration in March to start human testing, and had plans to begin to begin the research in the second half of this year if it could raise the required capital. But that didnt happen.Though a total dissolution is unusual in the biotechnology industry, its not unheard of. Genocea Biosciences, for example, found itself in a similar position last year.Histogen was also working in infectious disease a field of research thats proven difficult to succeed in for many drug developers.Histogen started out as a private company focused on regenerating tissue in the body. In 2020, its lead drug was meant to be a potential treatment for male pattern baldness. But Histogen would eventually enter a reverse merger with Conatus Pharmaceuticals, which had developed emricasan and was reeling from the failure from the failure of a medicine for non-alcoholic steatohepatitis, or NASH.The new combined company eventually gave up on the baldness drug, researched emricasan as a treatment for COVID-19 and tried at various times to refocus on a more promising path forward. It also undertook small private placements to raise cash and, in 2022, executed a 1-for-20 reverse stock split.Histogen has been operating with limited resources for a while; at the end of December, it had only seven full-time employees. Mento, who had cofounded and led Conatus, became president and CEO of the new company in March. He left the board of directors on Monday. '

Executive ChangeDrug ApprovalIPOAcquisition

06 Jul 2023

·www.fiercebiotech.com

Histogen could be history as biotech halts all programs to conserve remaining cash

Histogen has been slowly shrinking its portfolio to survive over recent years. Could Histogen soon join the growing list of biotechs shutting up shop for good in 2023? That’s certainly the mood music of the company’s announcement that its last remaining programs are being placed on pause to explore “strategic alternatives.” The immune-focused biotech made the call to extend its cash runway of $9.7 million, which as of the end of March was only expected to last to January 2024. The company had been hoping to launch a trial for its lead candidate emricasan for acute bacterial skin infections in the second half of 2023, but that ambition had been reliant on raising sufficient capital. Histogen has been slowly shrinking its portfolio to survive over recent years, with 2021 seeing the company drop a phase 1 alopecia treatment to focus on its orthopedic candidates. In March 2023, the company then dropped both of those candidates as well, leaving just emricasan to sit alone on the clinical-stage pipeline. Emricasan is a pan-caspase inhibitor designed to reduce the activities of human caspases, which are enzymes that mediate inflammation and cell death. As well as the hoped-for study in bacterial skin infections, the drug has already undergone various phase 1 trials, including for COVID-19 patients where it was shown to shorten symptoms and was well tolerated. “We remain excited about emricasan given its broad potential to treat both viral and bacterial infections as a more generalized host-based immunotherapeutic treatment without the risk of generating resistance,” CEO Steven Mento, Ph.D., said in a postmarket release Wednesday. “However, we have paused our development activities in order to preserve our remaining resources and extend our cash runway to explore strategic alternatives that have the potential to benefit shareholders.” Mento only took up the permanent CEO role in March. The former Idun Pharmaceuticals chief had been interim CEO of Histogen since November 2021. Histogen isn’t the only company facing the end of the road this year. Already we’ve seen Sorrento Therapeutics and Athenex file for bankruptcy, Talaris Therapeutics and Oncorus let go of nearly all of their employees, and Vedere Bio II and Vyant Bio begin winding down operations.

Phase 1Executive ChangePhase 2Immunotherapy

100 Deals associated with Emricasan

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KEGG	Wiki	ATC	Drug Bank
D10004	Emricasan	-	DB05408

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Decompensated cirrhosis of liver	Phase 2	United States	Conatus Pharmaceuticals, Inc.	28 Jun 2017
Fibrosis	Phase 2	United States	Histogen, Inc.	17 Oct 2016
Fibrosis	Phase 2	Germany	Histogen, Inc.	17 Oct 2016
Fibrosis	Phase 2	Spain	Histogen, Inc.	17 Oct 2016
Hypertension, Portal	Phase 2	United States	Histogen, Inc.	17 Oct 2016
Hypertension, Portal	Phase 2	Germany	Histogen, Inc.	17 Oct 2016
Hypertension, Portal	Phase 2	Spain	Histogen, Inc.	17 Oct 2016
Nonalcoholic Steatohepatitis	Phase 2	United States	Histogen, Inc.	17 Oct 2016
Nonalcoholic Steatohepatitis	Phase 2	Germany	Histogen, Inc.	17 Oct 2016
Nonalcoholic Steatohepatitis	Phase 2	Spain	Histogen, Inc.	17 Oct 2016

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Clinical Result

Indication

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Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02960204 (ENCORE-PH, CTgov)	Phase 2	Nonalcoholic Steatohepatitis \| Fibrosis \| Hypertension, Portal	263	Emricasan (Emricasan (5 mg))	aeukouiewe(fczfgsgudf) = ytpkqiffjz siyopmjibj (zrjpphxfoh, 3.356) View more	-	14 Jan 2022
				Emricasan (Emricasan (25 mg))	aeukouiewe(fczfgsgudf) = klkudvlztb siyopmjibj (zrjpphxfoh, 3.669) View more
NCT04803227 (GlobeNewswire) Manual	Phase 1	COVID-19	13	emricasan	ufytyohdfx(hajahdwyil) = No Serious Adverse Events dcgxmqxwla (ddbedgcwzm ) View more	Positive	22 Jun 2021
				Placebo
NCT03462576 (CTgov)	Not Applicable	Decompensated cirrhosis of liver	199	Emricasan (Number of Subjects Experiencing a High Risk Event in 25 mg Treatment Arm)	azqwcbyyil = osysiusnfi bdzzuxjunj (ztzqxvtacy, vdzxlabnic - aunwnwflvb) View more	-	16 Dec 2020
				Emricasan (Number of Subjects Experiencing a High Risk Event in 5 mg Treatment Arm)	azqwcbyyil = gzvrotckku bdzzuxjunj (ztzqxvtacy, qwglenhthc - xorppfelna) View more
NCT02960204 (Pubmed \| J Hepatol)	Phase 2	Nonalcoholic Steatohepatitis \| Fibrosis \| Hypertension, Portal	263	Emricasan 5 mg	ntggefwyjh(pwewovfhkj) = mfjbqgauet qbkaqqkafn (emqgwhzjey )	Negative	01 May 2020
				Emricasan 25 mg	ntggefwyjh(pwewovfhkj) = pzofyvpoho qbkaqqkafn (emqgwhzjey )
NCT02686762 (Pubmed \| J Hepatol)	Phase 2	Nonalcoholic Steatohepatitis	318	Emricasan 5 mg	gvsqnieqrb(fbdlgtkchf) = zwaubbpspw thiafkwdty (ysnqzxdbmp ) View more	Negative	01 May 2020
				Emricasan 50 mg	gvsqnieqrb(fbdlgtkchf) = mepxpchglh thiafkwdty (ysnqzxdbmp ) View more
NCT02138253 (POLT-HCV-SVR, CTgov)	Phase 2	Fibrosis, Liver \| Liver Cirrhosis \| Hepatitis C, Chronic	64	IDN-6556 (IDN-6556)	bruzzpikpm = dqtavdungw hhcvwwzwhw (btowcnalmn, mtxtmmdeja - pakiadsmgm) View more	-	11 Dec 2019
				Placebo (Placebo)	bruzzpikpm = acehvbkdal hhcvwwzwhw (btowcnalmn, ytqpjcepmm - ghtnkypzau) View more
NCT02686762 (ENCORE-NF, PipelineReview) Manual	Phase 2	Nonalcoholic Steatohepatitis	318	Emricasan	mogincvsqn(ycjliapyap) = fibrosis by at least 1 stage with no worsening of NASH cxolltxmjf (tteusnpqji ) View more	Negative	22 Mar 2019
				Placebo
NCT02230683 (Pubmed \| Hepatology) Manual	Phase 2	Hypertension, Portal \| Compensated cirrhosis	23	Emricasan	kjkvfswgrd(dobvcgqpgg) = epbfawdnoc gwfkqxpatz (oxaxcdwlnr ) View more	Positive	01 Feb 2019
NCT02230670 (LC, CTgov)	Phase 2	Liver Cirrhosis	87	IDN-6556 (IDN-6556)	frmxgouyku(mtyihlldnt) = nstthaubpr rayawvzdnz (zzrmoknrrj, iajlgfrsgi - ubtdghcvtt) View more	-	05 Jul 2017
				Placebo (Placebo)	frmxgouyku(mtyihlldnt) = zbbafkocvu rayawvzdnz (zzrmoknrrj, rnfwgvshhp - ftuxdmwmcn) View more
NCT02230683 (PH, CTgov)	Phase 2	Hypertension, Portal	23	IDN-6556	okrwmsbcib(xuwoqzjmaf) = bplbkfsjnt jowsbxyakv (ljpugvfmjc, 7.68) View more	-	21 Dec 2016