mesdopetam (IRL790) / IRLAB Therap, Ipsen - LARVOL DELTA

Recent and on-going trials for the treatment of levodopa-induced dyskinesia: a review of the clinical trial databases. (PubMed, Neurodegener Dis Manag) - "Promising results were obtained in Phase II trials with the serotonin type 1A (5-HT1A) agonist befiradol, the dopamine D3 receptor antagonist mesdopetam and the phosphodiesterase inhibitor CPL500036. In contrast, the metabotropic glutamate 4 (mGlu4) receptor negative allosteric modulator foliglurax and JM-010 (a combination of the 5-HT1A partial agonist buspirone and the and the 5-HT type 1B and 1D [5-HT1B/1D] agonist zolmitriptan) did not meet their endpoints in Phase II studies. Lastly, robot-assisted Repetitive Transcranial Magnetic Stimulation (rTMS) of the pre-supplementary motor area may be a promising non-pharmacological approach to alleviate dyskinesia."

Journal • Review • CNS Disorders • Movement Disorders • Parkinson's Disease

IRLAB is Granted a Patent Expanding the Patent Protection for the Drug Candidate Mesdopetam in the US (Yahoo Finance) - "IRLAB Therapeutics AB...announced that the company has been granted an additional ‘composition of matter patent' in the US covering the salt of mesdopetam intended for use in the forthcoming pharmaceutical product and the process of its manufacture. The now granted patent expands the already strong patent protection for mesdopetam, which is IRLAB's most advanced drug candidate....The newly approved patent (US 12,275,694B2) covers the salt of mesdopetam which is used in ongoing clinical development and expires in the 2040s. In the event of a possible extension of the patent period (en. Patent Term Extension; PTE), the exclusivity could potentially extend well into the 2040s. IRLAB has recently also been granted a corresponding patent in Australia, where the exclusivity potentially extends well into the early 2040s."

Patent • Parkinson's Disease

HOW THE THERAPEUTIC APPROACH TO EARLY PARKINSON'S DISEASE WILL CHANGE IN THE NEXT FUTURE (ADPD 2025) - "Levodopa remains the most efficacious drug, a better preparation of levodopa like IPX 203 can ensure more stable plasma levels of Levodopa...Tavapadon is a new dopamine agonist stimulating D1-D5 receptors which concluded the phase III. Other compounds such as CVN424 (Cerevance) orally active and selective GPR6 inverse agonist, piperamat (IRLAB 752) a cortical enhancer to improve balance, Clenbuterol/Nadolol for cognition, mesdopetam a D3 antagonist are under investigation...These include the monoclonal antibody prasinezumab, UCB0599 and buntanetap small-molecules α-synuclein aggregation inhibitor, the vaccine ACI-7104.056 by AC immune...The LRKK2 kinase inhibitor BIIB122/DNL151 is in phase IIb in PD. BIAL BIA 28-6156 activator of the GCase enzyme is under investigation in patients with GBA mutation. The combination of symptomatic and disease modifying therapy, the use of accurate biomarkers and more precise treatment will be the future in the treatment of PD."

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

IRLAB Publishes Preclinical Data on mesdopetam in the Esteemed European Journal of Neuroscience (ACCESSWIRE) - "The paper reports a preclinical work performed by at the Department of Medical Translational Biology, Umeå University, Sweden and Integrative Neurophysiology, Lund University, Sweden, in collaboration with scientists at IRLAB....The study elegantly shows that the reduction of a specific type of brain activity, narrow gamma band oscillations (NBGs), especially in the sensorimotor areas, correlates with decreased dyskinesias for both amantadine and mesdopetam. The findings suggest that diminishing NBGs is an essential biomarker for assessing the effects of antidyskinetic treatments. Additionally, the data offer insights into the systems-level mechanisms behind the antidyskinetic effectiveness of mesdopetam and suggest potential additional benefits for the treatment of Parkinson's-related psychosis."

Biomarker • Preclinical • Parkinson's Disease • Psychiatry

Neurophysiological Treatment Effects of Mesdopetam, Pimavanserin and Amantadine in a Rodent Model of Levodopa-Induced Dyskinesia. (PubMed, Eur J Neurosci) - "In a broad frequency spectrum (1-200 Hz), mesdopetam treatment displayed greater similarities to pimavanserin than to amantadine. These findings point to the reduction of NBGs as a valuable biomarker for the characterization of antidyskinetic treatment effects and provide systems-level mechanistic insights into the antidyskinetic efficacy of mesdopetam, with potential additional benefits for the treatment of Parkinson's-related psychosis."

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

Mesdopetam for the Treatment of Levodopa Induced Dyskinesia in Parkinson's Disease: A Randomized Phase 2b Trial. (PubMed, Mov Disord Clin Pract) - "In this study mesdopetam failed to increase Good ON-time as compared to placebo. However, a statistically significant and clinically meaningful improvement in the prespecified secondary efficacy endpoint UDysRS warrants further investigation. Results from this dose finding study suggest 7.5 mg b.i.d. to be the preferred dose for further study."

Journal • P2b data • CNS Disorders • Movement Disorders • Parkinson's Disease

IRLAB receives positive feedback from EMA confirming alignment with FDA on Phase III program for Mesdopetam (Irlab Therapeutics) - "Based on EMA’s guidance, IRLAB can now proceed with preparations for the registration studies of the drug candidate, which has demonstrated efficacy in a phase Ib and in two Phase II studies against levodopa-induced dyskinesia in patients with Parkinson’s disease...Following the successful dialogue with EMA and the company’s prior End-of-Phase 2 meeting with the U.S. Food and Drug Administration (FDA), IRLAB has reached a consensus with both European and US regulatory authorities on the remaining clinical development plan for mesdopetam. This agreement includes the program required for the approval of mesdopetam as a treatment for levodopa-induced dyskinesia (LIDs) in patients with Parkinson’s disease...EMA has reviewed the comprehensive data package provided by IRLAB and has given feedback on all aspects of the mesdopetam development plan, including the design of the Phase III studies."

Clinical protocol • European regulatory • FDA event • Parkinson's Disease

EU agency say no trials of mesdopetam in children are needed (Parkinson's News Today) - "The European Medicines Agency (EMA), which evaluates the safety and efficacy of new drugs in the European Union, has waived a requirement that would have had Irlab Therapeutics conducting clinical trials testing mesdopetam — its therapy candidate for levodopa-induced dyskinesia, or uncontrolled, involuntary movements common in Parkinson’s disease patients — in children. The decision follows the recommendation of the EMA’s Pediatric Committee and frees the company from the obligation of submitting pediatric investigation plans for the new drug. Such testing would otherwise be compulsory before an EU marketing authorization application could be submitted."

European regulatory • CNS Disorders • Parkinson's Disease

Meta-Analysis of Two Randomized Controlled Trials Assessing the Efficacy of Mesdopetam (IRL790) in Levodopa-Induced Dyskinesia in Parkinson's Disease (MDS Congress 2024) - "Based on meta-analysis using MMRM with multiple imputation of missing data, mesdopetam demonstrated significant reduction of dyskinesia as measured by UDysRS, UPDRS 4.2, and motor diaries, without compromising motor function."

Retrospective data • CNS Disorders • Parkinson's Disease

IRL790 modulated striatal D1 neurons synaptic plasticity ameliorating levodopa-induced dyskinesia in mouse. (PubMed, Front Aging Neurosci) - "IRL790 improved dyskinetic manifestations in LID mice. IRL790 ameliorates LID by regulating the synaptic structure and functional plasticity of striatal D1+ MSNs."

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

IRLAB’s Mesdopetam Displays Antipsychotic Properties in an Advanced Model of Parkinson’s Disease Psychosis (Yahoo Finance) - "IRLAB Therapeutics AB...today announced that a scientific paper reporting the effects of IRLAB's candidate drug mesdopetam in a preclinical model of Parkinson's disease psychosis (PD-P) has been published in the journal Neurotherapeutics....The effects of Mesdopetam, along with two compounds, clozapine and pimavanserin, which are clinically used to alleviate PD-P, and an experimental D3 antagonist, were investigated in this model. The studies concluded that mesdopetam displays key features associated with antipsychotic efficacy in this PD-P model and should be further explored as a potential novel treatment option for psychosis in Parkinson's disease."

Preclinical • CNS Disorders • Parkinson's Disease

A Clinical Study of Mesdopetam in Patients With Parkinson's Disease Experiencing Levodopa Induced Dyskinesia (clinicaltrials.gov) - P2 | N=155 | Completed | Sponsor: Integrative Research Laboratories AB | Phase classification: P2b ➔ P2

Phase classification • CNS Disorders • Movement Disorders • Parkinson's Disease

IRLAB has completed a successful End-of-Phase 2 meeting with the FDA on the design of the Phase III program for mesdopetam (Irlab Therapeutics) - "IRLAB Therapeutics AB...today announced that the company’s recent End-of-Phase 2 meeting with the US Food and Drug administration, FDA, was held in a constructive and engaging spirit. The discussions during the meeting indicate alignment between the FDA and IRLAB on the design of the Phase III program....Based on this information, the FDA provided clear guidance that is substantially consistent with the proposed design of the Phase III-program for mesdopetam. Alignment with the FDA was reached on the key components of the Phase III program, including the primary and secondary endpoints, key inclusion and exclusion criteria and safety monitoring during the study period."

FDA event • CNS Disorders • Parkinson's Disease

Neurophysiological treatment effects of mesdopetam, pimavanserin and clozapine in a rodent model of Parkinson's disease psychosis. (PubMed, Neurotherapeutics) - "Other drug-induced neurophysiological features were more specific to each treatment, affecting network oscillation frequencies and entropy, pointing to discrete differences in mechanisms of action. These findings indicate that neurophysiological characterization of brain states is particularly informative when evaluating therapeutic mechanisms in conditions involving symptoms that are difficult to assess in rodents such as psychosis, and that mesdopetam should be further explored as a potential novel antipsychotic treatment option for Parkinson psychosis."

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

HOW PARKINSON'S DISEASE TREATMENT WILL CHANGE IN THE NEXT FUTURE (ADPD 2024) - "A new dopamine agonist, tavapadon. Two different studies on dyskinesia are ongoing with a combination of buspirone and zolmitriptan and another with mesdopetam."

CNS Disorders • Inflammation • Movement Disorders • Parkinson's Disease • GBA

IRLAB is Granted an End-of-Phase 2 Meeting with the FDA for the Phase III-Ready Mesdopetam Program (Yahoo Finance) - "IRLAB Therapeutics AB...today announced that the US FDA has granted IRLAB an end-of-Phase 2 meeting for the mesdopetam program on February 20, 2024....The purpose of an end-of-Phase 2 meeting is to ensure alignment with the US FDA prior to the start of Phase III. As part of the end-of-Phase 2 meeting, the US FDA evaluates the Phase III plans and study protocols combined with the data generated in previously completed studies, i.e. review of the safety profile and assessment of the effectiveness of the drug candidate. The US FDA may, in addition, notify if any additional information is necessary to support a future New Drug Application (NDA)."

FDA event • CNS Disorders • Parkinson's Disease

Levodopa-induced dyskinesia: do current clinical trials hold hope for future treatment? (PubMed, Expert Opin Pharmacother) - No abstract available

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

IRLAB Submits Request for an End-of-Phase 2 Meeting with the FDA for the Phase III-ready Mesdopetam Program (BioSpace) - "IRLAB Therapeutics AB...today announced that the company has submitted a request for an end-of-Phase 2 meeting with the US FDA for the Phase III-ready mesdopetam program....The purpose of an end-of-Phase 2 meeting with the US FDA, is to ensure alignment with the regulatory agency and determine the pathway to Phase III. As part of the end-of-Phase 2 meeting, the US FDA reviews the adequacy of safety and efficacy, in previous non-clinical and clinical studies, and evaluates the plans for proceeding to Phase III. The US FDA may, in addition, note if any additional information is necessary to support a future marketing application. According to guidelines, the US FDA will respond to a request within 14 calendar days and schedule an end-of-Phase 2 meeting within 70 calendar days from receipt of the meeting request."

FDA event • CNS Disorders • Parkinson's Disease

Results from IRL790C005 - A Randomized, Double-Blind, Placebo-Controlled Phase IIb Study Evaluating the Efficacy of Mesdopetam on Daily On-Time without Troublesome Dyskinesia in (MDS Congress 2023) - "Mesdopetam demonstrated significant antidyskinetic effects as measured by UDysRS. These antidyskinetic properties were obtained without impairing normal motor function and are further strengthened by an apparent reduction in OFF-time. Full analyses are in progress and detailed results will be presented during the meeting."

Clinical • P2b data • CNS Disorders • Parkinson's Disease

IRLAB to present data from the Phase IIb study of mesdopetam in PD-LIDs at the MDS Congress 2023 (Market Screener) - "IRLAB Therapeutics AB...today announced that the company will present an abstract at the International Congress of Parkinson’s Disease and Movement Disorders®, MDS Congress, in Copenhagen, Denmark from August 27-31, 2023. The abstract...will be presented by Joakim Tedroff, Chief Medical Officer at IRLAB."

P2b data • CNS Disorders • Parkinson's Disease

IRLAB Comments on Statements in Ipsen's 2022 Universal Registration Document and the Further Development of Mesdopetam (Yahoo News) - "IRLAB Therapeutics AB...announced today that IRLAB has been made aware that Ipsen's 2022 Universal Registration Document, published on April 6, 2023....This is not correct. Collaborative discussions regarding mesdopetam's further development path are ongoing. In the document, it was stated that the development and commercialization rights for mesdopetam have been transferred back to IRLAB. IRLAB has not received any termination of the license agreement, nor any transfer of the mesdopetam project. IRLAB has been informed that Ipsen will rectify. Following a contact from Ipsen on May 1, 2023, a discussion was initiated with IRLAB to mutually agree on the best way forward to secure that the mesdopetam program gets the best possible prospects to reach registration and to ensure that mesdopetam can be made available to the benefit of people living with Parkinson's disease."

Licensing / partnership • CNS Disorders • Parkinson's Disease

IRLAB updates on portfolio development milestones (Market Screener) - "IRLAB Therapeutics AB...today announced that the company has assessed the operational priorities for 2023....This will not impact the priority of the ongoing Phase IIb study of pirepemat in PD-Falls. The preclinical programs will proceed according to their respective plans; IRL757 will proceed to be Phase I ready by year-end 2023, IRL942 will be Phase I ready in H1 2024 and P003 candidate IRL1117 is just initiating its preclinical program with in-house R&D activities during 2023. The analysis of the completed Phase IIb study of mesdopetam continues, and it is anticipated that further data will be presented during H1 2023. The ongoing Phase IIb study of pirepemat...is active and progressing to plan with 28 of 39 planned sites in five European countries. Patient recruitment is slower than anticipated, and actions are ongoing to address this. The updated estimates predict the study will be fully recruited by the year-end 2023 with top-line results in H1 2024."

Enrollment status • New P1 trial • P2b data • Preclinical • CNS Disorders • Cognitive Disorders • Parkinson's Disease

ISP –A TRANSLATIONAL APPROACH FOR CNS DRUG DISCOVERY APPLIED IN PARKINSON'S DISEASE (PD) (ADPD 2023) - "Systematic discovery and evaluation using ISP identified three promising drug candidates for PD treatment, two of which are currently in Phase IIb clinical trials, suggesting translational validity. The P001/Pirepemat project, addressing cortical deficiency i n neurodegenerative disorders, displays signals of alleviating cortex -associated symptoms in PD, including falls and apathy. Mesdopetam, a DA D3 antagonist, relieves dyskinesia both preclinically and clinically."

CNS Disorders • Movement Disorders • Parkinson's Disease

NEW INSIGHT IN THE TREATMENT OF PARKINSONS DISEASE (ADPD 2023) - "The PASADENA study tested prasinezumab and despite the primary end-point was not met positive signals were seen...The ORCHESTRA study with UCB0059, an oral Asyn antibody is also ongoing...A new dopamine agonist, tavapadon. Two different studies on dyskinesia are ongoing with a combination of buspirone and zolmitriptan and another with mesdopetam."

Alzheimer's Disease • CNS Disorders • Dementia • Lewy Body Disease • Movement Disorders • Parkinson's Disease • GBA

Mesdopetam: “The primary endpoint, change in daily ON-time without troublesome dyskinesia (“good On“- time) did not reach statistical significance by mesdopetam compared to placebo“; Parkinson’s disease (Irlab Therapeutics) - Top-line results in Phase IIb trial of mesdopetam

P2 data • CNS Disorders • Parkinson's Disease