MC2-25 / MC2 Therap - LARVOL DELTA

Mapping cardiac drug transport: In vitro assessment of cardiac P-glycoprotein function with [18F]MC225 by using µ-engineered heart tissues. (PubMed, Eur Heart J Open) - "µ-EHTs were treated with the P-gp inhibitor Tariquidar (200 nM for 30 min) or the P-gp inducer Doxorubicin (1 µM for 24 h) and incubated with [18F]MC225 (1 MBq/mL for 30 min). [18F]MC225 effectively evaluates and measures cardiac P-gp function in µ-EHTs on the heart-on-chip platform. This research sets the stage for future studies using P-gp function to evaluate the efficacy and safety of novel cardiovascular drugs using µ-EHTs."

Journal • Preclinical • Cardiovascular

The experience of [18 F]MC225 trial authorisation in Italy: the academic journey towards a non-profit clinical trial authorisation from precursor production to clinical trial approval [WITHDRAWN] (EANM 2025) - No abstract available

Clinical

In vitro functional assessment of cardiac membrane transporter P-glycoprotein with [ 18 F]MC225 by using µ-engineered heart tissues (EANM 2025) - No abstract available

Preclinical • Cardiovascular

Functional Evaluation of Cardiac Cell Membrane Transporter P-Glycoprotein in healthy volunteers with [ 18 F]MC225-PET imaging- a feasibility study (EANM 2025) - "Many cardiovascular drugs, such as beta-blockers and digoxin, are substrates of P-gp. Although the small sample size limits statistical power, the findings still demonstrate the potential of quantification of P-gp function in the human heart . [ 18 F]MC225 PET in assessing or predicting cardiotoxicity and the treatment effects of P-gp substrate medications need to be further evaluated in the future."

Clinical • Cardiovascular

In vivo measurement of P-glycoprotein function in the brain and gut of patients with Parkinson's disease: a preliminary [ 18 F]MC225 PET study (EANM 2025) - No abstract available

Preclinical • CNS Disorders • Movement Disorders • Parkinson's Disease

Designing a Small Molecule for PET Radiotracing: [18F]MC225 in Human Trials for Early Diagnosis in CNS Pathologies. (PubMed, Molecules) - "[18F]MC225 is currently being employed in PHASE II human trials at the UMC Groningen, the Netherlands, in patients diagnosed with AD, PD and MCI, as well as PHASE II human trials at the Policlinico Gemelli in Rome Italy to diagnose P-gp resistant depression. Preliminary studies show that [18F]MC225 radiotracer is behaving according to the initial predictions, that is, it accurately diagnoses the aforementioned pathologies, more so than previously developed small molecules for the same goal."

Journal • Review • CNS Disorders • Depression • Epilepsy • Infectious Disease • Oncology • Psychiatry • ABCB1

Evaluating image-derived input functions for cerebral [18F]MC225 PET studies. (PubMed, Front Nucl Med) - P=N/A | "Venous sampling is a potential alternative for estimating plasma parameters, but it is unsuitable for IDIF calibration. NCT05618119 (clinicaltrials.gov/study/NCT05618119)."

Journal

Measurement of cyclosporin induced changes in P-glycoprotein function at the human blood-brain barrier using [18F]MC225 and PET. (PubMed, Eur J Nucl Med Mol Imaging) - "The outcomes of the current study reflect the potential ability of [18F]MC225 to measure cyclosporin induced changes in P-gp function at the human BBB in vivo."

Journal • Alzheimer's Disease • CNS Disorders • Mental Retardation • Movement Disorders • Parkinson's Disease • Psychiatry • Schizophrenia

Exploratory Study of Sex Differences in P-Glycoprotein Function at the Blood-Brain Barrier. (PubMed, Clin Transl Sci) - "For future [18F]MC225 PET studies, a mixed-sex population can serve as an appropriate age-matched control group for neurodegenerative studies. Further research is needed to explore sex-related differences in younger populations, particularly with respect to hormonal cycles."

Journal • CNS Disorders • Mental Retardation • Psychiatry • ABCB1

Oral Administration of [18F]MC225 for Quantification of P-glycoprotein Function: A Feasibility Study. (PubMed, Mol Imaging Biol) - "Oral administration of [18F]MC225 faces challenges and, at this stage, cannot be used to quantify P-gp function. Further research to assess tracer stability and metabolism in the stomach and intestine will be essential for advancing the feasibility of oral tracer administration."

Journal • Gastrointestinal Disorder

Orchid 1: Efficacy and Safety of MC2-25 Cream & Vehicle in Women With Vulvar Lichen Sclerosus (VLS) (clinicaltrials.gov) - P2 | N=33 | Completed | Sponsor: MC2 Therapeutics | Recruiting ➔ Completed

Trial completion • Dermatology

Blood-brain barrier P-glycoprotein function in Alzheimer's disease measured with [18F]MC225 and PET (EANM 2024) - "This proof of concept study showed significant differences in P-gp function at the BBB between AD patients and HV. These findings support the further use [18F]MC225 PET in larger AD cohorts. It addition, it will be a potential in vivo tool to monitor response to disease modifying drugs."

Alzheimer's Disease • CNS Disorders

Impact of Delay Calculation Methods in LAFOV PET Kinetic Analysis (EANM 2024) - "For a [15O]H2O bolus injection, the LE method shows very good agreement with the traditional JE method, for both delay and kinetic parameters. For the slow [18F]MC225 injection, delay and kinetic parameters obtained using the LE method showed a poorer agreement with the JE method, indicating that the LE method may not be the optimal approach in case of non-bolus injections."

Quantitative Accuracy of Reconstruction Methods in Preclinical PET and Effects on Kinetic Modelling (EANM 2024) - "Furthermore, dynamic scans of two Wistar rats injected with 34MBq of [18F]MC225, with blood sampling, were acquired with the same scanner and reconstructed using the aforementioned protocols [3]... In preclinical static and dynamic scanning, OSEM2D and HR-OSEM2D performed similarly and outperformed the other reconstruction methods. However, the reconstruction does not affect the TACs and only inconsistently affects kinetic parameters. Additionally, the 1TCM fits best on HR-OSEM2D reconstructed images."

Preclinical

Pre-Clinical Assessment of Cardiac P-glycoprotein Function In Vivo with [18F]MC225 PET Imaging (EANM 2024) - "In this study, a novel PET radiotracer [18F]MC225 was applied for the first time to evaluate P-gp function in rat hearts. The findings suggest that [18F]MC225-PET imaging is promising for assessing the functionality of P-gp. In the future, [18F]MC225-PET may possess the capability to predict the cardiac bioavailability of pharmaceutical agents as well as provide precise, individualized insights for therapeutic optimization, but also the effect of cardiotoxic agents."

Preclinical • Cardiovascular

Kinetic analysis of [18F]MC225 data without arterial sampling (EANM 2024) - "This study shows that an accurate BAC can be obtained using a LAFOV PET and that, for [18F]MC225, arterial samples can be replaced by venous samples, making a [18F]MC225 study more patient-friendly and cost-effective. It should be noted that the use of venous samples should be validated for each tracer separately."

CNS Disorders • Movement Disorders • Parkinson's Disease

The MC2-25 Cream in Subjects wITh CHronic KIdNEy Disease-aSsociated prurituS (ITCHINESS) Trial (clinicaltrials.gov) - P2 | N=111 | Completed | Sponsor: MC2 Therapeutics | Recruiting ➔ Completed

Trial completion • Chronic Kidney Disease • Dermatology • Nephrology • Pruritus • Renal Disease

Orchid 1: Efficacy and Safety of MC2-25 Cream & Vehicle in Women With Vulvar Lichen Sclerosus (VLS) (clinicaltrials.gov) - P2 | N=40 | Recruiting | Sponsor: MC2 Therapeutics | Trial primary completion date: May 2024 ➔ Nov 2024 | Trial completion date: Jun 2024 ➔ Nov 2024

Trial completion date • Trial primary completion date • Dermatology

MC2 Therapeutics Announces Completion of Enrollment in MC2-25 Ph2 Chronic Kidney Disease-associated Pruritus Trial (GlobeNewswire) - "MC2 Therapeutics....today announced it has completed enrollment in its European Phase 2 trial assessing the safety and efficacy of MC2-25 CKD...Top line results from the study are expected in Q2 2024."

Enrollment closed • P2 data • Pruritus

MC2 Therapeutics begins patient enrolment in phase 2 PoC of MC2-25 VLS to treat Vulvar Lichen Sclerosus (Pharmabiz) - '"MC2-25 VLS has been developed based on our novel treatment paradigm targeting carbamylation in the skin and the active di-peptide component is formulated using our proprietary PAD Technology. This delivers a highly attractive treatment profile based on ease of use and tolerability in sensitive, fissured skin,' said Professor Lars Iversen..."

Media quote

Orchid 1: Efficacy and Safety of MC2-25 Cream & Vehicle in Women With Vulvar Lichen Sclerosus (VLS) (clinicaltrials.gov) - P2 | N=40 | Recruiting | Sponsor: MC2 Therapeutics

New P2 trial • Dermatology

Quantification of P-glycoprotein function at the human blood-brain barrier using [F]MC225 and PET. (PubMed, Eur J Nucl Med Mol Imaging) - "[F]MC225 V, derived using a reversible two-tissue compartment model, is the preferred parameter to describe P-gp function in the human BBB. This outcome parameter has an average test-retest variability of 28%."

Journal • Alzheimer's Disease • CNS Disorders • Depression • Mental Retardation • Movement Disorders • Parkinson's Disease • Psychiatry

The MC2-25 Cream in Subjects wITh CHronic KIdNEy Disease-aSsociated prurituS (ITCHINESS) Trial (clinicaltrials.gov) - P2 | N=108 | Recruiting | Sponsor: MC2 Therapeutics

New P2 trial • Chronic Kidney Disease • Dermatology • Nephrology • Pruritus • Renal Disease