A Double-blind, Placebo-controlled, Exploratory Randomised Clinical Trial to Assess the Safety and Efficacy of IFB-088 Plus Riluzole 100 mg vs Placebo Plus Riluzole 100 mg in Patients With Bulbar-onset Amyotrophic Lateral Sclerosis.

Prospective, international, randomised, double-blind, placebo controlled, multicentre, parallel group study. Patients will be randomised in a 2:1 allocation ratio to receive either IFB-088 + riluzole 100 mg or placebo + riluzole 100 mg. This clinical trial is an exploratory study, designed to show a signal of efficacy of IFB-088 through ALSFRS-R, MITOS and King's College. Respiratory function will be followed through SVC. Biomarkers and quality of life will also be evaluated throughout the study.
Patients will be treated over a 6-month period. After a screening/consent visit, patients will undergo clinic visits at randomisation (V0), at 2 weeks (V1), and at months 1 (V2), 3 (V3) and 6 (V4). One week after V0, the patient will undergo urine analysis (dipstick)and blood sampling for measurement of creatinine
, as well as blood sampling for measurement of creatinine and calculation of eGFR at months 2, 4 and 5. At the V2 visit, in addition to other assessments, patients will undergo blood sampling for PK measurements and urine sampling for crystalluria examination. Blood and urine chemistry, as well as physical examination and vital signs assessment to assess safety will be performed at each visit for safety purpose and crystalluria examination will be repeated at the follow-up visit, performed one month ± one week after V4.

Start Date02 Dec 2022

Sponsor / Collaborator

Inflectis Bioscience SAS

NCT03610334

/ CompletedPhase 1

A Double-blind, Randomized, Placebo-controlled, Combined Single and Multiple Ascending Dose Study to Investigate the Safety, Tolerability and Pharmacokinetic Profile of IFB-088, in Healthy Volunteers

This is the first study of single and multiple doses of IFB-088 in human subjects. The current study is designed to assess in the first part, the safety, tolerability, plasma and urine pharmacokinetics (PK) of single oral doses of IFB-088 in healthy subjects (Single Ascending Doses - SAD) and in a second part safety, tolerability, plasma and urine pharmacokinetics (PK) of multiple oral doses of IFB-088 in healthy subjects (Multiple Ascending Doses - MAD)

Start Date21 Jun 2018

Sponsor / Collaborator

Inflectis Bioscience SAS

[+4]

100 Clinical Results associated with Icerguastat

100 Translational Medicine associated with Icerguastat

100 Patents (Medical) associated with Icerguastat

Literatures (Medical) associated with Icerguastat

01 Jan 2025·INTERNATIONAL JOURNAL OF PHARMACEUTICS

Harnessing osmotic shock for enhanced intracellular delivery of (nano)cargos

Article

Author: Marcuzzo, Stefania ; Bono, Nina ; Cattaneo, Marco ; Ruzzante, Beatrice ; Fruzzetti, Flaminia ; Lauria Pinter, Giuseppe ; Candiani, Gabriele

Efficient intracellular delivery of exogenous (nano)materials is critical for both research and therapeutic applications. The physicochemical properties of the cargo play a crucial role in determining internalization efficacy. Consequently, significant research efforts are focused on developing innovative and effective methodologies to optimize (nano)material delivery. In this study, we utilized osmotic shock to enhance (nano)cargos internalization. We examined the effects of hypotonic/hypertonic shock on both primary and cell lines, assessing parameters such as cell viability, cell volume, membrane tension changes, and particle uptake. Our results indicate that short-lived osmotic shock does not harm cells. Hypotonic shock induced temporary shape changes lasting up to 5 min, followed by a 15-minute recovery period. Importantly, hypotonic shock increased the uptake of 100-nm and 500-nm particles by ∼ 3- and ∼ 5-fold, respectively, compared to isotonic conditions. In contrast, the hypertonic shock did not impact cell behavior or particle uptake. Notably, the internalization mechanisms triggered by osmotic shock operate independently of active endocytic pathways, making hypotonic stimulation particularly beneficial for hard-to-treat cells. When primary fibroblasts derived from amyotrophic lateral sclerosis (ALS)-patients were exposed to hypotonic shock in the presence of the therapeutic cargo icerguastat, there was an increased expression of miR-106b-5p compared to isotonic conditions. In conclusion, osmotic shock presents a promising strategy for improving drug delivery within cells and, potentially, in tissues such as muscles or skin, where localized drug administration is preferred.

01 Apr 2023·Open biology

The small compound Icerguastat reduces muscle defects in oculopharyngeal muscular dystrophy through the PERK pathway of the unfolded protein response

Article

Author: Naït-Saïdi, Rima ; Abgueguen, Emmanuelle ; Chartier, Aymeric ; Guédat, Philippe ; Simonelig, Martine

Oculopharyngeal muscular dystrophy (OPMD) is an autosomal dominant disease characterized by the progressive degeneration of specific muscles. OPMD is due to a mutation in the gene encoding poly(A) binding protein nuclear 1 (PABPN1) leading to a stretch of 11 to 18 alanines at N-terminus of the protein, instead of 10 alanines in the normal protein. This alanine tract extension induces the misfolding and aggregation of PABPN1 in muscle nuclei. Here, using Drosophila OPMD models, we show that the unfolded protein response (UPR) is activated in OPMD upon endoplasmic reticulum stress. Mutations in components of the PERK branch of the UPR reduce muscle degeneration and PABPN1 aggregation characteristic of the disease. We show that oral treatment of OPMD flies with Icerguastat (previously IFB-088), a Guanabenz acetate derivative that shows lower side effects, also decreases muscle degeneration and PABPN1 aggregation. Furthermore, the positive effect of Icerguastat depends on GADD34, a key component of the phosphatase complex in the PERK branch of the UPR. This study reveals a major contribution of the ER stress in OPMD pathogenesis and provides a proof-of-concept for Icerguastat interest in future pharmacological treatments of OPMD.

01 Jul 2022·Molecular neurobiologyQ2 · MEDICINE

Treatment with IFB-088 Improves Neuropathy in CMT1A and CMT1B Mice

Q2 · MEDICINE

Article

Author: D'Antonio, Maurizio ; Guedat, Philippe ; Bianchi, Francesca ; Ferri, Cinzia ; Bai, Yunhong ; Florio, Francesca ; Touvier, Thierry ; Miniou, Pierre ; Wang, David ; Volpi, Vera G ; Shy, Michael E ; Del Carro, Ubaldo ; Treins, Caroline ; Baas, Frank F ; Scapin, Cristina ; Mastrangelo, Rosa

Abstract:

Charcot-Marie-Tooth disease type 1A (CMT1A), caused by duplication of the peripheral myelin protein 22 (PMP22) gene, and CMT1B, caused by mutations in myelin protein zero (MPZ) gene, are the two most common forms of demyelinating CMT (CMT1), and no treatments are available for either. Prior studies of the MpzSer63del mouse model of CMT1B have demonstrated that protein misfolding, endoplasmic reticulum (ER) retention and activation of the unfolded protein response (UPR) contributed to the neuropathy. Heterozygous patients with an arginine to cysteine mutation in MPZ (MPZR98C) develop a severe infantile form of CMT1B which is modelled by MpzR98C/ + mice that also show ER stress and an activated UPR. C3-PMP22 mice are considered to effectively model CMT1A. Altered proteostasis, ER stress and activation of the UPR have been demonstrated in mice carrying Pmp22 mutations. To determine whether enabling the ER stress/UPR and readjusting protein homeostasis would effectively treat these models of CMT1B and CMT1A, we administered Sephin1/IFB-088/icerguestat, a UPR modulator which showed efficacy in the MpzS63del model of CMT1B, to heterozygous MpzR98C and C3-PMP22 mice. Mice were analysed by behavioural, neurophysiological, morphological and biochemical measures. Both MpzR98C/ + and C3-PMP22 mice improved in motor function and neurophysiology. Myelination, as demonstrated by g-ratios and myelin thickness, improved in CMT1B and CMT1A mice and markers of UPR activation returned towards wild-type values. Taken together, our results demonstrate the capability of IFB-088 to treat a second mouse model of CMT1B and a mouse model of CMT1A, the most common form of CMT. Given the recent benefits of IFB-088 treatment in amyotrophic lateral sclerosis and multiple sclerosis animal models, these data demonstrate its potential in managing UPR and ER stress for multiple mutations in CMT1 as well as in other neurodegenerative diseases.Graphical Abstract(Left panel) the accumulation of overexpressed PMP22 or misfolded mutant P0 in the Schwann cell endoplasmic reticulum (ER) leads to overwhelming of the degradative capacity, activation of ER-stress mechanisms, and myelination impairment. (Right panel) by prolonging eIF2α phosphorylation, IFB-088 reduces the amount of newly synthesized proteins entering the ER, allowing the protein quality control systems to better cope with the unfolded/misfolded protein and allowing myelination to progress.

News (Medical) associated with Icerguastat

30 Apr 2024

·www.biospace.com

InFlectis BioScience awarded $650K grant from the National Multiple Sclerosis Society to advance IFB-048 preclinical development in Multiple Sclerosis; Research to be Performed by Prof. Popko of Northwestern University

Nantes, France--(News - April 30, 2024) - InFlectis BioScience, a pioneer in developing first-in-class therapies for neuromuscular diseases, announces that it has been awarded a $649,601 grant from the National MS Society's commercial research initiative Fast Forward to advance IFB-048 preclinical development in Multiple Sclerosis (MS). To view the full announcement, including downloadable images, bios, and more, click here. Key Takeaways: InFlectis Bioscience has been awarded a $650K grant from the National Multiple Sclerosis Society's commercial research initiative Fast Forward to demonstrate preclinical efficacy of its lead MS candidate, IFB-048. IFB-048 is a part of a new class of compounds called ISR modulators, which aim to protect the cells that support and repair neurons damaged by MS and other neurological and autoimmune conditions. IFB-048 parent drug has demonstrated potential to protect oligodendrocytes and/or neurons and to enhance remyelination of neurons in an inflammatory environment in multiple sclerosis preclinical models. Click image above to view full announcement. About InFlectis BioScience InFlectis is developing first-in-class therapies for neuromuscular diseases and is currently evaluating in clinic an orally available small molecule, named IFB-088 (icerguastat) that has the potential to extend lives or improve the quality-of-life for people suffering from Amyotrophic Lateral Sclerosis (ongoing phase II clinical trial) and demyelinating diseases like Charcot-Marie-Tooth disease (phase 2 ready package). About Northwestern University The Ken & Ruth Davee Department of Neurology at Northwestern University provides students, residents and fellows with innovative learning opportunities to build their skills, provide evidence-based clinical care through hospital affiliates, and develop new treatments through multidisciplinary research. Based in the Feinberg School of Medicine at Northwestern University and allied with the Northwestern Medicine healthcare system, the program is poised to raise the standard of neurological research and care thanks to close collaboration with research partners as well as colleagues in neurological surgery, neuroradiology and related disciplines. About the National Multiple Sclerosis Society The National MS Society, founded in 1946, is the global leader of a growing movement dedicated to creating a world free of MS. The Society funds cutting-edge research for a cure, drives change through advocacy and provides programs and services to help people affected by MS live their best lives. Connect to learn more and get involved: nationalMSsociety.org, Facebook, X, formerly known as Twitter, Instagram, YouTube or 1-800-344-4867. Contacts: Pierre Miniou pierreminiou@inflectisbioscience.com Distributed by: Reportable, Inc. To view the source version of this press release, please visit

Phase 2

31 Jan 2024

·www.biospace.com

InFlectis BioScience Completes Enrollment of Its Phase 2 Trial of IFB-088 for the Treatment of Amyotrophic Lateral Sclerosis; Anticipates Initial Results Later This Year

Nantes, France--(News - January 31, 2024) - InFlectis BioScience, a pioneer in developing first-in-class therapies for neuromuscular diseases, announced that it has completed enrollment in its Phase 2 clinical trial of IFB-088 (INN: icerguastat), a novel investigational treatment of Amyotrophic Lateral Sclerosis (ALS). To view the full announcement, including downloadable images, bios, and more, click here. Key Takeaways: InFlectis completed enrollment in its Phase 2 clinical trial of IFB-088 in ALS. IFB-088 is capable of crossing the blood-brain barrier and believed to act by selectively inhibiting a biomolecular switch to give cells additional time to repair or eliminate mis-folded proteins. Initial findings to be reported as early as the end of 2024. Click image above to view full announcement. About InFlectis BioScience InFlectis is a French-based drug discovery company developing first-in-class therapies for neuromuscular diseases. We are in clinical development with an orally available small molecule that has the potential to extend lives or improve the quality-of-life for people suffering from ALS and CMT, a rare and progressive hereditary nerve condition. Contacts: Philippe Gu'edat philippeguedat@inflectisbioscience.com Source: Inflectis To view the source version of this press release, please visit

Phase 2

03 Jan 2024

·www.biospace.com

InFlectis BioScience Awarded $943,000 Grant from the ALS Association to Advance Ongoing ALS Clinical Trial with the Support of IRCCS Carlo Besta Neurological Institute

Nantes, France--(News - January 3, 2024) - InFlectis BioScience, a pioneer in developing first-in-class therapies for neuromuscular diseases, announced that it has been awarded a $943,000 grant to support recruitment and to investigate biomarkers in its Phase 2 clinical trial in patients with bulbar-onset ALS (NCT05508074). The trial is investigating IFB-088 (INN: icerguastat), a multifunctional drug that modulates the PPP1R15A/PP1c phosphatase complex and inhibits NR2B-containing NMDAR. The potential of IFB-088 lies in its ability to target three major ALS cellular pathophysiological mechanisms to manage disease progression: protein aggregation, oxidative stress, and glutamate excitotoxicity. To view the full announcement, including downloadable images, bios, and more, click here. Key Takeaways: InFlectis Bioscience has been awarded a $943K grant from the ALS Association to support the recruitment of 50 patients by the end of January 2024 for its Phase 2 clinical trial evaluating IFB-088. The grant also supports a multi-omics approach, conducted by the IRCCS "Carlo Besta" Neurological Institute in Milan, Italy to investigate pharmacodynamic biomarker candidates, which will be useful in a future pivotal clinical study. The Phase 2 clinical study results will be reported by the end of 2024. Click image above to view full announcement. About InFlectis BioScience InFlectis is a France-based drug discovery company developing first-in-class therapies for neuromuscular diseases. We are in clinical development with an orally available small molecule that has the potential to extend lives or improve the quality-of-life for people suffering from ALS and CMT, a rare and progressive hereditary nerve condition. IRCCS Foundation "Carlo Besta" Neurological Institute The Foundation of the Carlo Besta Neurological Institute (FINCB) is a "Foundation of Participation" including as Members of the Board of Governors representatives of the Italian Ministry of Health, the Region of Lombardy and the Municipality of Milan. FINCB is recognized by the Italian Ministry of Health as a Scientific Institute for Research, Hospitalization and Health Care (IRCCS) of public body. It is a national and international centre of excellence for the treatment of neurological diseases, and also undertakes research aimed to improve the diagnosis and treatment of these diseases. Its major lines of activities in patients' care and research encompass child neurology, epilepsy, neuro-oncology, neuropathic pain, and genetic, cerebrovascular, neuroimmunological, neuromuscular and neurodegenerative disorders. The fundamental aims of FINCB are to provide high quality, ethical and efficient care and treatment to its patients, making use of the results of its own research and that of others, always putting the interests of patient first. About ALS Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that affects nerve cells in the brain and spinal cord. Over the course of the disease, people lose the ability to move, to speak, and eventually, to breathe. On average, it takes about a year before a final ALS diagnosis is made. The disease is always fatal, usually within five years of diagnosis. There is no cure. Contacts: Philippe Gu'edat philippeguedat@inflectisbioscience.com Source: Inflectis To view the source version of this press release, please visit

Phase 2

100 Deals associated with Icerguastat

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Amyotrophic Lateral Sclerosis	Phase 2	France	Inflectis Bioscience SAS	02 Dec 2022
Amyotrophic Lateral Sclerosis	Phase 2	Italy	Inflectis Bioscience SAS	02 Dec 2022
Charcot-Marie-Tooth Disease	Phase 1	France	-	-
Charcot-Marie-Tooth Disease	Phase 1	-	Inflectis Bioscience SAS	-
Charcot-Marie-Tooth Disease	Phase 1	-	The Medical Research Council	-
Multiple Sclerosis	Preclinical	France	Inflectis Bioscience SAS	01 Jun 2021

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05508074 (CTgov)	Phase 2	Amyotrophic Lateral Sclerosis	51	Placebo+Riluzole 100mg/day (Placebo + Riluzole 100 mg/Day)	apoqpmltsy = gltmcvoojk nrcwbytjwu (vvdslzhwpz, qetybwfpbk - hdxabindgw) View more	-	10 Oct 2025
				Riluzole 100mg/day+IFB-088 50mg/day (IFB-088 50 mg/Day + Riluzole 100 mg/Day)	apoqpmltsy = xhdfvmtvrk nrcwbytjwu (vvdslzhwpz, myntuafqra - qgjpuplqsv) View more

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