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Last update 20 Mar 2025

Compstatin 40

Last update 20 Mar 2025

Overview

R&D Status

Clinical Result

Translational Medicine

Overview

Basic Info

Drug Type

Synthetic peptide

Synonyms

S3,S13-cyclo(D-tyrolsyl-L-isoleucyl-L-cysteinyl-L-valyl-1-methyl-L-tryptophyl-L-glutaminyl-L-aspartyl-L-tryptophyl-N-methyl-L-glycyl-L-alanyl-L-histidyl-L-arginyl-L-cysteinyl-N-methyl-L-isoleucinamide)

+ [1]

Target

Action

inhibitors

Mechanism

C3 inhibitors(Complement C3 inhibitors)

Therapeutic Areas

Infectious DiseasesRespiratory DiseasesMouth and Tooth Diseases+ [3]

Active Indication

COVID-19PeriodontitisHemoglobinuria, Paroxysmal+ [1]

Inactive Indication

GingivitisHereditary Complement Deficiency DiseasesRespiratory Distress Syndrome, Adult+ [1]

Originator Organization

University of Pennsylvania

Active Organization

Amyndas Pharmaceuticals LLC

Inactive Organization-

Drug Highest PhasePhase 2

First Approval Date-

RegulationOrphan Drug (European Union)

Structure/Sequence

Molecular FormulaC83H117N23O18S2

InChIKeyMUSGYEMSJUFFHT-UWABRSFTSA-N

CAS Registry1427001-89-5

Sequence Code 524972122

Clinical Trials associated with Compstatin 40

NCT04395456

/ Unknown statusPhase 2

A Phase 2 Clinical Trial to Assess the Safety and Efficacy of Complement 3 Inhibitor, AMY-101, in Patients With Acute Respiratory Distress Syndrome Due to COVID-19 (SAVE)

The study is a prospective, randomized, placebo-controlled, single-blind phase 2 clinical study of the efficacy and safety of AMY-101, a potent C3 inhibitor, for the management of patients with ARDS caused by SARS-CoV-2 infection.
We will assess the efficacy and safety, as well as pharmacokinetics (PK), and pharmacodynamics (PD). The study will assess the impact of AMY-101 in patients with severe COVID19; specifically, it will assess the impact of AMY-101 1) on survival without ARDS and without oxygen requirement at day 21 and 2) on the clinical status of the patients at day 21.

Start Date01 Sep 2021

Sponsor / Collaborator

Amyndas Pharmaceuticals LLC

EUCTR2020-004408-32-GR

/ Not yet recruitingPhase 2

ITHACA: A phase 2, randomized, single-blind, placebo-controlled clinical trial to evaluate the safety and efficacy of the complement C3 inhibitor, AMY-101, in COVID-19 patients with acute respiratory distress syndrome (ARDS). - ITHACA

Start Date23 Oct 2020

Sponsor / Collaborator

Amyndas Pharmaceuticals LLC

NCT03694444

/ CompletedPhase 1/2

A Phase 2a Clinical Trial to Assess the Safety and Efficacy of C3 Inhibitor AMY-101, in Adults With Gingivitis

A Phase 2a Clinical Trial to Assess the Safety and Efficacy of Complement 3 Inhibitor Analog, AMY-101, in Adults with gingivitis.
The study is a 3-month randomized, double-blind, split-mouth study of adults with existing chronic periodontal inflammation determined by the level of gingival index and bleeding on probing. The primary endpoint of change in gingival index will be evaluated at 21, 28 and 90 days after initial treatment (baseline treatment). Subjects will also be followed at Day 3, 7, 14, 21, 28 and 90 for safety evaluations. Change in bleeding on probing plaque index, pocket depth, clinical attachment level and GCF levels of pro-inflammatory cytokines and complement factors will be assessed as secondary outcome measures. Composition of subgingival biofilm will be assessed as an exploratory endpoint.
Subjects who meet inclusion criteria will be enrolled in the study and sites will be randomized to treatment groups (AMY-101 or placebo) in split mouth design. After clinical assessments and sample collection at baseline, both test and placebo treatments will be administered to each of the interproximal papilla and will be repeated on Day 7 and 14.

Start Date22 Jul 2019

Sponsor / Collaborator

Amyndas Pharmaceuticals LLC

100 Clinical Results associated with Compstatin 40

100 Translational Medicine associated with Compstatin 40

100 Patents (Medical) associated with Compstatin 40

Literatures (Medical) associated with Compstatin 40

01 Jan 2023·Frontiers in immunology

In vitro evaluation of iron oxide nanoparticle-induced thromboinflammatory response using a combined human whole blood and endothelial cell model

Article

Author: Lambris, John D ; Woodruff, Trent M ; Mollnes, Tom E ; Bal, Melissa ; Mohlin, Camilla ; Nilsson, Per H ; Gerogianni, Alexandra ; Sjöström, Dick J

Iron oxide nanoparticles (IONPs) are widely used in diagnostic and therapeutic settings. Upon systemic administration, however, they are rapidly recognized by components of innate immunity, which limit their therapeutic capacity and can potentially lead to adverse side effects. IONPs were previously found to induce the inflammatory response in human whole blood, including activation of the complement system and increased secretion of cytokines. Here, we investigated the thromboinflammatory response of 10-30 nm IONPs in lepirudin anticoagulated whole blood in interplay with endothelial cells and evaluated the therapeutic effect of applying complement inhibitors to limit adverse effects related to thromboinflammation. We found that IONPs induced complement activation, primarily at the C3-level, in whole blood incubated for up to four hours at 37°C with and without human microvascular endothelial cells. Furthermore, IONPs mediated a strong thromboinflammatory response, as seen by the significantly increased release of 21 of the 27 analyzed cytokines (p<0.05). IONPs also significantly increased cell-activation markers of endothelial cells [ICAM-1 (p<0.0001), P/E-selectin (p<0.05)], monocytes, and granulocytes [CD11b (p<0.001)], and platelets [CD62P (p<0.05), CD63 (p<0.05), NAP-2 (p<0.01), PF4 (p<0.05)], and showed cytotoxic effects, as seen by increased LDH (p<0.001) and heme (p<0.0001) levels. We found that inflammation and endothelial cell activation were partly complement-dependent and inhibition of complement at the level of C3 by compstatin Cp40 significantly attenuated expression of ICAM-1 (p<0.01) and selectins (p<0.05). We show that complement activation plays an important role in the IONPs-induced thromboinflammatory response and that complement inhibition is promising in improving IONPs biocompatibility.

01 Sep 2022·Journal of International Society of Preventive and Community Dentistry

C3 Targeted Complement Therapy for Chronic Periodontitis – A Scoping Review

Article

Author: Gaur, Sumit ; Agnihotri, Rupali

AimChronic Periodontitis (CP) is a complex disease initiated by inflammation caused by dysbiotic bacterial communities in the subgingival environment. The Porphyromonas gingivalis, a keystone pathogen at low colonization, causes immune subversion of complement component C5aR, leading to complement C3-dependent destructive inflammation responsible for the inflammatory bone loss in CP. Animal studies have shown that targeting complement C3 with its inhibitor like AMY-101 may help reduce inflammatory bone loss in CP. This scoping review elaborates on the role of complement C3 targeted therapy for CP.Materials and MethodsAbout 66 original studies were obtained during an initial electronic search in Medline (Pubmed), Scopus, Web of Science, and Embase. About four articles were included in the review after screening the duplicates and reading the full text. Their aims and objectives, drug dosage, route of administration, results, and conclusions were recorded.ResultsOf the four-original research, 3 were animal studies and one randomized Phase IIa clinical trial. They showed that C3 targeted complement therapy reduced the inflammatory and clinical periodontal parameters in CP.ConclusionC3 targeted complement therapy may be regarded as a valuable adjunct to non-surgical periodontal treatment for CP. However, the results are still under investigation and require further verification through clinical trials.

19 Aug 2022·Science Advances

Complement C3 inhibition in severe COVID-19 using compstatin AMY-101

Article

Author: Willems, Loek ; Iacobelli, Simona ; Mastellos, Dimitrios C. ; Persson, Barbro ; Ritis, Konstantinos ; Nilsson, Bo ; Huber-Lang, Markus ; Mitroulis, Ioannis ; Skendros, Panagiotis ; Kalopitas, Georgios ; Ntinopoulou, Maria ; Cepaityte, Dainora ; Manivel, Vivek Anand ; Metallidis, Simeon ; Calado, Rodrigo T. ; Risitano, Antonio M. ; Kogias, Dionysios ; Yancopoulou, Despina ; Antoniadou, Christina ; Zioga, Nikoleta ; Karanika, Ioanna ; Connolly, E. Sander ; Gatselis, Nikolaos K. ; Chrysanthopoulou, Akrivi ; Liontos, Angelos ; Smyrlis, Andreas ; Papagoras, Charalampos ; Milionis, Haralampos ; Gavriilidis, Efstratios ; Germanidis, Georgios ; Lambris, John D. ; Samakidou, Anna ; Papadopoulos, Vasileios ; Dalekos, George N. ; Fotiadou, Iliana

News (Medical) associated with Compstatin 40

06 Oct 2022

·www.amyndas.com

EUSTM (9th Congress): Novel Transformative Treatment for Periodontal Disease

Periodontitis, a prevalent oral inflammatory disease associated with increased risk of systemic comorbidities, continues to be a significant worldwide public health and economic burden. The complement system is hyperactivated in periodontitis and is involved both in the dysbiotic transformation of the periodontal microbiome and the destructive inflammation that causes loss of periodontal bone. Targeting the central complement component C3 with the drug AMY-101 provided therapeutic benefit in nonhuman primates (NHP) with periodontal disease. The preclinical efficacy of this C3-targeted drug combined with its excellent safety and pharmacokinetic profiles supported the use of AMY-101 in a recent Phase IIa clinical study, in which C3 inhibition resolved gingival inflammation in patients with periodontal disease. These studies by the Hajishengallis and Lambris groups and their collaborators were discussed at the 9th Annual Congress of the European Society for Translational Medicine on Immunotherapeutics. (October 3-5, 2022). Based on the available evidence, C3-targeted intervention represents a novel and transformative treatment of human periodontitis and other complement-driven oral pathologies such as peri-implantitis. Click here for video.

Phase 2ImmunotherapyClinical Result

22 Aug 2022

·www.amyndas.com

Complement C3 inhibition in severe COVID-19 using compstatin AMY-101

Complement C3 activation contributes to COVID-19 pathology, and C3 targeting has emerged as a promising therapeutic strategy. We provide interim data from ITHACA, the first randomized trial evaluating a C3 inhibitor, AMY-101, in severe COVID-19 (PaO2/FiO2 ≤ 300 mmHg). Patients received AMY-101 (n = 16) or placebo (n = 15) in addition to standard of care. AMY-101 was safe and well tolerated. Compared to placebo (8 of 15, 53.3%), a higher, albeit nonsignificant, proportion of AMY-101-treated patients (13 of 16, 81.3%) were free of supplemental oxygen at day 14. Three nonresponders and two placebo-treated patients succumbed to disease-related complications. AMY-101 significantly reduced CRP and ferritin and restrained thrombin and NET generation. Complete and sustained C3 inhibition was observed in all responders. Residual C3 activity in the three nonresponders suggested the presence of a convertase-independent C3 activation pathway overriding the drug’s inhibitory activity. These findings support the design of larger trials exploring the potential of C3-based inhibition in COVID-19 or other complement-mediated diseases. Skendros P, Germanidis G, Mastellos DC, Antoniadou C, Gavriilidis E, Kalopitas G, Samakidou A, Liontos A, Chrysanthopoulou A, Ntinopoulou M, Kogias D, Karanika I, Smyrlis A, Cepaityte D, Fotiadou I, Zioga N, Mitroulis I, Gatselis NK, Papagoras C, Metallidis S, Milionis H, Dalekos GN, Willems L, Persson B, Manivel VA, Nilsson B, Connolly ES, Iacobelli S, Papadopoulos V, Calado RT, Huber-Lang M, Risitano AM, Yancopoulou D, Ritis K, Lambris JD. (2022). Complement C3 inhibition in severe COVID-19 using compstatin AMY-101. Sci Adv. 8: eabo2341.

Clinical ResultClinical Study

03 Dec 2021

·www.amyndas.com

JCI Video: Complement C3 Inhibitor AMY-101 in Adults with Periodontal Inflammation – Clinical Trial

The Journal of Clinical Investigation created a video illustrating that local delivery of the complement C3 inhibitor AMY-101 in patients with gingivitis was safe, well tolerated, and led to significant and sustained reduction of clinical indices of gingival inflammation. Original article: Hasturk H, Hajishengallis G, Lambris JD, Mastellos DC, Yancopoulou D. (2021). Phase 2a clinical trial of complement C3 inhibitor AMY-101 in adults with periodontal inflammation. J Clin Invest. 131: e152973.

Phase 2Clinical Result

100 Deals associated with Compstatin 40

External Link

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB14803

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
COVID-19	Phase 2	United States	Amyndas Pharmaceuticals LLC	-
Periodontitis	Phase 2	United States	Amyndas Pharmaceuticals LLC	-
Hemoglobinuria, Paroxysmal	Preclinical	United States	Amyndas Pharmaceuticals LLC	01 Mar 2025
Renal transplant rejection	Preclinical	United States	Amyndas Pharmaceuticals LLC	01 Mar 2025
Respiratory Distress Syndrome, Adult	Discovery	-	Amyndas Pharmaceuticals LLC	01 Sep 2021
SARS-CoV-2 acute respiratory disease	Discovery	-	Amyndas Pharmaceuticals LLC	01 Sep 2021
Gingivitis	Discovery	United States	Amyndas Pharmaceuticals LLC	22 Jul 2019
Hereditary Complement Deficiency Diseases	Discovery	United States	Amyndas Pharmaceuticals LLC	24 Apr 2017

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03694444 (Pubmed \| J Clin Invest) Manual	Phase 2	Periodontal Diseases	32	AMY-101	nllgwsfhlt(pbkqlqcrky): P-Value = <0.001 View more	Positive	01 Dec 2021
				Placebo

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