pirepemat (IRL752) / IRLAB Therap - LARVOL DELTA

SEARCHING FOR NOVEL CNS THERAPIES IN PARKINSON'S AND ALZHEIMER'S DISEASE USING INTEGRATIVE SCREENING PROCESS (ISP) : AN AI/ML DRIVEN PHENOTYPIC DRUG DISCOVERY PLATFORM (ADPD 2026) - "Several in-house ISP derived programs are currently in clinical development in PD: mesdopetam, a D3-antagonist for dyskinesia/PD-P, pirepemat, targeting recurrent falls in PD, and a project targeting long-acting full DA D1/D2 agonists for improved DA-substitution therapy. Another program, IRL757, is in development towards treatment of apathy in PD. ISP is a powerful tool for CNS drug discovery, augmented by AI-driven behavioural characterization. It has generated several novel pharmacological CNS-classes holding promise for treatment of core symptoms in PD, AD and other neurodegenerative disorders."

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

RESULTS FROM REACT-PD - A RANDOMISED, PLACEBO-CONTROLLED, MULTI-CENTRE PHASE IIB STUDY EVALUATING THE EFFICACY OF PIREPEMAT ON FALLS FREQUENCY IN PATIENTS WITH PARKINSON'S DISEASE (ADPD 2026) - P2 | "Trial results indicate that pirepemat could significantly and clinically meaningfully reduce falls frequency in PD, with a U-shaped concentration-response relationship. The adverse event profile was in line with previous experience, and pirepemat was well tolerated."

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

Results from REACT-PD - a randomised, placebo-controlled, multi-centre phase IIb study evaluating the efficacy of pirepemat on falls frequency in patients with Parkinson's disease (ACCESS Newswire) - "A significant, U-shaped plasma concentration response pattern was observed, indicating that pirepemat, in an optimal plasma concentration range, could significantly and clinically meaningfully reduce falls in PD. The relative fall rate was reduced by 31% vs. placebo in the optimal plasma concentration range...In terms of the absolute number of falls, the effect at optimal concentrations corresponds to a reduction of 7 falls monthly vs. placebo. The reduction in falls observed in the optimal plasma concentration range was not associated with any change in motor symptoms."

P2b data • Parkinson's Disease

IRLAB has Received Scientific Advisory Board Confirmation on Next Steps for Pirepemat (ACCESS Newswire) - "The advisory board concludes that the pharmacological rationale for pirepemat is sensible and that the reduction in falls observed in the Phase IIb trial is clinically meaningful, warranting further development...The advisory board comprises four esteemed key opinion leaders (KOLs) from North America, Europe and Scandinavia, recognized for their expertise in Parkinson's disease with special focus on falls, complications related to falls and the underlying mechanisms."

Clinical • Parkinson's Disease

IRLAB Receives Acceptance for Two Abstracts at AD/PD 2026: The 20th International Conference on Alzheimer's and Parkinson's Diseases (Yahoo Finance) - "The company's two abstracts are titled: (i) Results from REACT-PD - a randomized, placebo-controlled, multi-centre phase IIb study evaluating the efficacy of pirepemat on falls frequency in patients with Parkinson's disease...; (ii) Searching for novel CNS therapies in Parkinson's and Alzheimer's disease using integrative screening process (ISP): An AI/ML driven phenotypic drug discovery platform."

Clinical • P2b data • Parkinson's Disease

CROSS-SECTIONAL ANALYSIS OF INTERRELATIONS BETWEEN FALL -RATE, COGNITIVE MEASURES, UPDRS-SUBSCALES, AND NPI -APATHY IN THE REACT -PD STUDY COHORT (ADPD 2025) - "Aims: React-PD is a Phase 2b trial, investigating the effect of the cortical enhancer pirepemat on fall -rate in subjects with PD experiencing recurrent falls... These findings are in line with the notion of tremor -dominant being a more benign PD phenotype and support the concept of cortical decompensation being associated with poorly treatment responsive symptoms such as falls, apathy, and axial motor symptoms."

Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Essential Tremor • Movement Disorders • Parkinson's Disease

CORTICAL ENHANCEMENT - A NEW TREATMENT STRATEGY FOR SYMPTOMATIC TREATMENT AND SLOWING OF DISEASE PROGRESSION IN AD AND PD (ADPD 2025) - "Results Three cortical enhancer candidates have been selected and brought into clinical development: Pirepemat (IRL752), currently Phase 2b for prevention of falls in PD; IRL757, targeting PD-apathy, currently Phase 1 supported by MJFF; IRL942, targeting cognitive impairment, IND-enabling studies ongoing...Sustaining cortical neuronal activity may help maintain neuronal integrity and synaptic strength in connected subcortical areas, hence providing resilience from neurodegeneration. By directly strengthening cortico-subcortical circuitries, symptomatic effects including cognitive impairment, apathy, and falls could also be achieved."

Alzheimer's Disease • CNS Disorders • Cognitive Disorders

IRLAB Reports Topline Results from a Phase IIb Study of Pirepemat in Patients with Parkinson’s Disease (ACCESSWIRE) - P2b | N=104 | REACT-PD (NCT05258071) | "IRLAB Therapeutics...announces topline results from the Phase IIb study of pirepemat (REACT-PD)....In the Phase IIb study, 146 patients were screened, 104 were randomized, and 90 completed the 12-week treatment period. The primary endpoint was the change in patients' fall rates during the treatment period. The fall rate decreased by 42 per cent for those treated with pirepemat at a daily dose of 600 mg, but the effect did not reach statistical significance compared to placebo. The results of the cognitive scale used in the study...indicated a meaningful improvement in cognitive impairment for patients treated with pirepemat (600 mg daily). However, this effect did not reach statistical significance. The adverse event profile was consistent with previously reported clinical trial results for pirepemat....'Extensive further analytical work will now be conducted before we can determine the project's future direction'."

P2b data • Parkinson's Disease

A Clinical Study Evaluating Efficacy of Pirepemat on Falls Frequency in Patients with Parkinson's Disease (PD) (clinicaltrials.gov) - P2 | N=104 | Completed | Sponsor: Integrative Research Laboratories AB | Recruiting ➔ Completed | N=165 ➔ 104

Enrollment change • Trial completion • CNS Disorders • Movement Disorders • Parkinson's Disease

The Last patient has now Completed the Full Treatment Period in IRLAB's Phase IIb Study with Pirepemat (ACCESSWIRE) - "IRLAB Therapeutics AB...announces that all patients enrolled in the Phase IIb study with the drug candidate pirepemat (REACT-PD) have completed their final follow-up visit....The Phase IIb study with pirepemat (IRL752C003 - REACT-PD) is a randomized, double-blind, placebo-controlled trial designed to evaluate the efficacy, safety, and tolerability of two different doses of pirepemat or placebo, in individuals with Parkinson's disease, aiming to establish the optimal dose for a Phase III program....As all patients now have completed the study, data management, database locking, and analysis will be carried out in accordance with a predefined analysis plan. Topline results are anticipated to be reported in the first quarter of 2025."

P2b data • Trial status • Parkinson's Disease

A Clinical Study Evaluating Efficacy of Pirepemat on Falls Frequency in Patients With Parkinson's Disease (PD) (clinicaltrials.gov) - P2 | N=165 | Recruiting | Sponsor: Integrative Research Laboratories AB | Phase classification: P2b ➔ P2 | Trial completion date: Apr 2024 ➔ Jan 2025 | Trial primary completion date: Mar 2024 ➔ Dec 2024

Phase classification • Trial completion date • Trial primary completion date • CNS Disorders • Movement Disorders • Parkinson's Disease

IRLAB to Present Clinical and Preclinical Data at the AD/PD(TM) 2024: 18th International Conference on Alzheimer’s & Parkinson’s Diseases (Yahoo News) - "IRLAB Therapeutics AB...today announced that the company will present two abstracts at the scientific conference AD/PD 2024: 18th International Conference on Alzheimer's and Parkinson's Diseases and related neurological disorders in Lisbon, Portugal, on March 5-9, 2024."

Clinical protocol • Preclinical • CNS Disorders • Parkinson's Disease

REACT-PD – A RANDOMIZED, PLACEBO-CONTROLLED PHASE IIB TRIAL EVALUATING THE EFFICACY OF PIREPEMAT ON FALLS FREQUENCY IN PATIENTS WITH PARKINSON'S DISEASE (ADPD 2024) - "Recruitment is ongoing and the study is making good progress. Details on study procedures and early results, as available, will be presented during the meeting. Pirepemat has the potential to become the first treatment in a new class of drugs designed to improve balance and reduce falls and associated injuries in people with Parkinson's disease."

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

IRLAB Publishes Year-end Report for the Period January-December 2023 (Yahoo Finance) - "The pioneering Phase II study React-PD of pirepemat has generated new insights about the specific Parkinson's population the study is conducted in, individuals with high fall frequency, which enables data driven predictions that provides more accurate predictions about the study timeline. Based on these new insights, the study is anticipated to have completed patient recruitment during the third quarter of 2024. The company will participate at the medical conference AD/PD 2024...on March 5-8, 2024, with two poster presentations about drug candidates pirepemat and IRL1117, respectively."

Enrollment status • Preclinical • CNS Disorders • Parkinson's Disease

IRLAB is Granted Additional Patent for Drug Candidate Pirepemat that Expands its Patent Protection (Issuer Direct) - "IRLAB Therapeutics...today announced that the company has been granted a new patent in Europe related to both a new salt of the drug candidate pirepemat and the process for its preparation. This new patent, which covers the active pharmaceutical ingredient (API) used in the ongoing clinical Phase IIb development, has also been granted in the strategically important markets Japan and China....The recently granted additional patent, covering the salt of the drug used in the ongoing clinical development, is predicted to expire in 2038. With the potential grant of supplementary protection certificates (SPCs) or patent term extension (PTE), exclusivity can potentially reach into the early 2040s."

Patent • Parkinson's Disease

A Systematic Review of Pharmacological Interventions for Apathy in Aging Neurocognitive Disorders. (PubMed, Brain Sci) - "Pharmacological interventions for apathy in aging neurocognitive disorders are complex and under-investigated. The continuation of systematic research efforts and the provision of individualized treatment for patients suffering from these disorders is vital."

Journal • Review • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Developmental Disorders • Frontotemporal Lobar Degeneration • Huntington's Disease • Movement Disorders • Parkinson's Disease • Psychiatry

IRLAB’s Phase IIb Study with Pirepemat Passes DSMB Safety Review with Unanimous Recommendation to Continue the Ongoing Phase IIb Study (BioSpace) - "IRLAB Therapeutics AB...today announced that the independent Data and Safety Monitoring Board (DSMB) for the ongoing Phase IIb study with pirepemat, after review of safety and the integrity of data, unanimously recommends that the Phase IIb study continues. The DSMB review is part of the Phase IIb study of pirepemat's, IRL752C003 - React PD, study protocol. The DSMB has evaluated data from the initial 25 patients participating in the study and completing the study. After this review, the DSMB unanimously recommend that the Phase IIb study continues according to the approved study protocol without modifications."

DSMB • CNS Disorders • Parkinson's Disease

IRLAB Therapeutics AB announces that all sites participating in the Phase IIb study of Pirepemat (IRL752) are activated and recruiting patients [Google translation] (Zonebourse) - "IRLAB Therapeutics AB announced that all sites participating in the phase IIb study of pirepemat (IRL752) are activated and recruiting patients. The study is being conducted at 38 sites in six European countries....The study is taking place at 38 sites in France, Germany, Poland, the Netherlands, Spain and Sweden. Patient recruitment and randomization is expected to be completed by the end of 2023, followed by the three-month treatment period, follow-up visits, data management, and database lock."

Trial status • CNS Disorders • Parkinson's Disease

A Clinical Study Evaluating Efficacy of Pirepemat on Falls Frequency in Patients With Parkinson's Disease (PD) (clinicaltrials.gov) - P2b | N=165 | Recruiting | Sponsor: Integrative Research Laboratories AB | Trial completion date: Dec 2023 ➔ Apr 2024 | Trial primary completion date: Nov 2023 ➔ Mar 2024

Trial completion date • Trial primary completion date • CNS Disorders • Movement 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

IN VIVO SYSTEMS RESPONSE PROFILE MAPPING OF NOVEL CANDIDATE DRUGS IN DEVELOPMENT FOR TREATMENT OF SYMPTOMS RELATED TO CORTICAL IMPAIRMENT IN PARKINSON'S DISEASE (ADPD 2023) - " Treatment response profiles were generated for CNS reference compound s, including PD drugs, antidepressants, antipsychotics, psychostimulants, procognitive drugs, and candidate drugs IRL942, IRL757 and Phase IIb compound pirepemat. Systems response profiling/mapping of new candidate drugs suggest a pharmacological differentiation, IRL942 displaying a predominantly procognitive profile, IRL757 expressing additional effects suggesting effects also on symptoms linked to the underlying subcortical degeneration in PD, such as apathy, warranting clinical evaluation. This new class of compounds may have broad utility in neurocognitive disorders."

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

IRL942 - A NOVEL COMPOUND WITH PROCOGNITIVE PROPERTIES ADRESSING CORTICAL IMPAIRMENT IN PARKINSON'S DISEASE (ADPD 2023) - "The most advanced candidate drug in this program, pirepemat, is currently in a clinical Phase 2b study addressing falls frequency in advanced Parkinson's disease...Results NOR: IRL942 significantly improved sub-chronic PCP-induced memory deficits with an efficacy similar to reference comparators risperidone or the D1-receptor agonist SKF38393...Specifically, IRL942 may promote short-term working memory, rule-learning flexibility, as well as executive function in models believed to exhibit translational validity towards man. These results are consistent with a procognitive action of IRL942, supporting current development towards cognitive impairment in PD."

Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Movement Disorders • Parkinson's Disease

IRLAB Publishes Interim Report for the Period January-September 2022 (Yahoo Finance) - “Major portfolio milestones pending: Focusing on the portfolio, our Phase IIb study with mesdopetam in people living with Parkinson's and levodopa-induced dyskinesias (PD-LIDs) has completed patient recruitment. We now anticipate the last patient in the study to complete their three-month treatment period in mid-December, after which the database will be locked and analyzed. Top-line results are anticipated around the turn of the year....Pirepemat, our second candidate in Phase IIb, is being developed to improve balance and reduce falls for people living with Parkinson's….This study is currently open at multiple sites in five European countries with patient recruitment actively continuing. At the moment, we anticipate to have the study fully recruited during the fall of 2023 and to report top-line results at the end of 2023.”

Enrollment closed • P2 data • P2b data • Trial status • CNS Disorders • Parkinson's Disease

A Clinical Study Evaluating Efficacy of Pirepemat on Falls Frequency in Patients With Parkinson's Disease (PD) (clinicaltrials.gov) - P2b | N=165 | Recruiting | Sponsor: Integrative Research Laboratories AB | Not yet recruiting ➔ Recruiting

Enrollment open • CNS Disorders • Movement Disorders • Parkinson's Disease