contraloid (PRI-002) / Priavoid - LARVOL DELTA

Oral PRI-002 treatment in patients with MCI or mild AD: a randomized, double-blind phase 1b trial. (PubMed, Nat Commun) - P1b | "Patients receiving PRI-002 performed significantly better than those receiving placebo in the CERAD word list at Day 56 (P ≤ 0.05). In conclusion, 28 days of treatment with 300 mg q.d. PRI-002 was well tolerated in patients with MCI or mild dementia due to AD."

Clinical • Journal • P1 data • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Hematological Disorders • CSF P-tau

PRImus-AD: Study to Assess Safety and Efficacy of PRI-002 in Patients With MCI to Mild Dementia Due to Alzheimer's Disease (AD) (clinicaltrials.gov) - P2 | N=270 | Active, not recruiting | Sponsor: PRInnovation GmbH | Recruiting ➔ Active, not recruiting

Enrollment closed • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia

Developing Topics. (PubMed, Alzheimers Dement) - "PRI-002 was well tolerated. No biomarker changes have been found after 28 days of treatment. No ARIA were detected. Memory improved significantly in the verum group. A phase 2 study has started to assess the potential therapeutic benefit of PRI-002 in patients with mild neurocognitive impairment and mild dementia due to AD."

Clinical • Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Hematological Disorders • CSF P-tau

Orally available PRI-002 for the treatment of Alzheimer´s disease: Phase 1a data and design of the phase 2a study (CTAD 2024) - No abstract available

P1 data • P2a data • Alzheimer's Disease • CNS Disorders

Design of a phase 2 study and results of a phase 1b study in MCI and mild AD patients with the orally available PRI-002 for the treatment of Alzheimer’s disease (AAIC 2024) - "PRI-002 was well tolerated. No biomarker changes have been found after 28 days of treatment. No ARIA were detected."

Clinical • P1 data • P2 data • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Hematological Disorders • CSF P-tau

MODE OF ACTION, PHASE IB DATA IN PATIENTS, AND PHASE II DESIGN OF THE ORALLY AVAILABLE ANTI-PRIONIC COMPOUND PRI-002 FOR THE TREATMENT OF ALZHEIMER'S DISEASE (ADPD 2024) - "PRI-002 showed an excellent safety profile in MCI and mild AD patients. A significant improvement of short-term memory function was noted at follow up. Despite the small number of patients, we feel that this phase Ib study results deserve reporting to the scientific community."

Clinical • P1 data • P2 data • Alzheimer's Disease • CNS Disorders • Cognitive Disorders

An orally available N-type calcium channel inhibitor for the treatment of neuropathic pain. (PubMed, Br J Pharmacol) - "Taken together, these results demonstrate that RD2 has antiallodynic properties. RD2 is orally available, which is the most convenient application form for patients and caregivers. The surprising and novel result from standard receptor screens opens the room for further optimization into new promising drug candidates, which address an unmet medical need."

Journal • Neuralgia • Pain

PRImus-AD: Study to Assess Safety and Efficacy of PRI-002 in Patients With MCI to Mild Dementia Due to Alzheimer's Disease (AD) (clinicaltrials.gov) - P2 | N=270 | Recruiting | Sponsor: PRInnovation GmbH

New P2 trial • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia

In vitro, ex vivo and clinical data from patients demonstrate that the purely thermodynamic anti-prionic mode of action for the treatment of neurodegenerative diseases is promising (Neuroscience 2023) - "Patients received once daily oral doses of 300 mg PRI-002 or placebo for 28 days... The all-D-enantiomeric ligand for α-synuclein, SVD-1a, disassembled preformed α-synuclein fibrils (PFF) as shown by AFM, DLS and SEC analysis. SPR and NMR demonstrated picomolar affinity of SVD-1a to α-synuclein monomers, while keeping them in their physiological IDP conformation. The all-D-enantiomeric ligand for Aβ, RD2, demonstrated ex vivo target engagement and disassembled Aβ oligomers obtained from brain tissue of former AD patients."

Clinical data • Preclinical • Alzheimer's Disease • CNS Disorders • Parkinson's Disease • Proteinopathy

The purely thermodynamic anti-prionic mode of action for the treatment of neurodegenerative diseases (CTAD 2023) - "Patients received once daily oral doses of 300 mg PRI-002 or placebo for 28 days... The unique anti-prionic mode of action for the treatment of AD, PD and other protein misfolding diseases is promising."

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

Mode of action, clinical phase Ib data in patients, and the phase II design of the orally available anti-prionic compound PRI-002 that disassembles Aβ oligomers into Aβ monomers (CTAD 2023) - "PRI-002 showed an excellent safety profile in MCI and mild AD patients. While no significant biomarker changes were detected after 4 weeks of treatment, a significant improvement of shortterm memory function was noted at follow up. Despite the small number of patients, we feel that this phase Ib study results deserve reporting to the scientific community."

Clinical • P1 data • P2 data • CNS Disorders • Cognitive Disorders

Oral treatment with the all-d-peptide RD2 enhances cognition in aged beagle dogs - A model of sporadic Alzheimer's disease. (PubMed, Heliyon) - "RD2 has previously demonstrated pharmacodynamic efficacy in three different transgenic AD mouse models in three different laboratories. Here, we demonstrate that oral treatment with RD2 significantly reduced cognitive deficits in cognitively impaired aged Beagle dogs even beyond the treatment end, which suggests in combination with the treatment dependent CSF tau oligomer decrease a disease-modifying effect of RD2 treatment."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders

Evaluation of the F-Labeled Analog of the Therapeutic All-d-enantiomeric Peptide RD2 for Amyloid β Imaging. (PubMed, Eur J Pharm Sci) - "In vivo uptake and biodistribution of [F]RD2-cFPy were evaluated using PET analyses in wild-type and transgenic APP/PS1 mice. Although brain penetration and brain wash-out kinetics of the radioligand were low, this study provides proof of principle for a PET probe based on a d-enantiomeric peptide binding to soluble Aβ species."

Journal • Alzheimer's Disease • CNS Disorders

REALIZATION OF THE ANTI-PRIONIC MODE OF ACTION FOR PROTEIN-MISFOLDING DISEASES BY PURELY THERMODYNAMIC ACTING AND TARGET PROTEIN SPECIFIC ALL-D-PEPTIDES (ADPD 2023) - "I will also acknowledge the many contributors of both developments that are too many to be included here in the abstract. Conclusions The unique anti-prionic mode of action for the treatment of AD, PD and other protein misfolding diseases is promising."

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

A UNIQUE MODE OF ACTION FOR THE TREATMENT OF AD (ADPD 2023) - "We were able to prove in vitro , ex vivo and in vivo the new anti -prionic mode of action of RD2."

Alzheimer's Disease • CNS Disorders

A PHASE 1B STUDY TO EVALUATE THE SAFETY, TOLERABILITY AND PHARMACODYNAMICS OF PRI-002, AN ORALLY AVAILABLE ANTI-PRIONIC ALL-D-PEPTIDE, IN EARLY CLINICAL AD (ADPD 2023) - "No biomarker changes were detected after treatment period of 4 weeks, while a slight improvement of memory function was noted at follow up. A multicenter phase 2 study will be initiated."

Clinical • P1 data • PK/PD data

OLIGOMER BIOMARKERS FOR PRECLINICAL AND CLINICAL DRUG DEVELOPMENT IN NEURODEGENERATIVE DISORDERS. (CTAD 2022) - "In drug development, sFIDA is useful to validate any oligomer disassembling mechanism of action of a given drug in vitro, in animal models, and in ex vivo tissue homogenates. Further, sFIDA is a valuable biomarker assay for patient inclusion/exclusion, patient stratification, target engagement and drug effect monitoring in AD, and other protein misfolding diseases."

Preclinical • Alzheimer's Disease • CNS Disorders • Dementia • Lewy Body Disease • Movement Disorders • Parkinson's Disease • Progressive Supranuclear Palsy • Proteinopathy

CLINICAL PHASE IB DATA OF THE ORALLY AVAILABLE ANTI-PRIONIC COMPOUND RD2 THAT DISASSEMBLES AΒ OLIGOMERS INTO AΒ MONOMERS. (CTAD 2022) - "RD2 showed an excellent safety profile in MCI and mild AD patients. While no significant biomarker changes were detected after 4 weeks of treatment interestingly, a significant improvement of memory function was noted at follow up. To be very conservative and cautious, due to the low number of patients, we do not claim this as a target engagement, nor do we claim the results of the CERAD word list result as a proof of concept."

Clinical • P1 data • CNS Disorders • Cognitive Disorders

A PHASE 1B STUDY TO EVALUATE THE SAFETY, TOLERABILITY AND PHARMACODYNAMICS OF PRI-002 IN MCI AND MILD AD. (CTAD 2022) - "PRI-002 showed an excellent safety profile in AD patients. No biomarker changes were detected after short treatment period of 4 weeks, while a slight improvement of memory function was noted at follow up. A multicenter phase 2 study will be initiated in the near future."

Clinical • P1 data • PK/PD data • Alzheimer's Disease • CNS Disorders

The aged dog model of Alzheimer’s Disease progression: changes in biomarkers with age and with RD2, a novel AD-therapeutic (Neuroscience 2022) - "Collectively, these studies further support the use of aged dogs for examining disease-modifying AD therapeutics. AD relevant biomarkers may be used to select target subject groups representing various stages of AD progression, which can then be examined longitudinally for establishing preclinical efficacy."

Biomarker • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • CXCL8 • GFAP • IL2 • IL6 • TNFA

Evaluation of Safety of Contraloid Acetate in Patients With Mild Cognitive Impairment Due to Alzheimer's Disease (clinicaltrials.gov) - P1b | N=19 | Completed | Sponsor: Charite University, Berlin, Germany | Recruiting ➔ Completed

Trial completion • Alzheimer's Disease • CNS Disorders • Cognitive Disorders

A randomized, placebo-controlled, double-blind, Phase 1b study to evaluate the safety, tolerability and pharmacodynamics of PRI-002 in early AD (AAIC 2022) - No abstract available

Clinical • P1 data • PK/PD data

Aβ oligomer concentration in mouse and human brain and its drug-induced reduction ex vivo. (PubMed, Cell Rep Med) - "We demonstrate dose- and time-dependent oligomer elimination by the compound RD2 in mouse and human AD brain homogenates as sources of native Aβ oligomers. Such ex vivo target engagement analyses with mouse- and human-brain-derived oligomers have the potential to enhance the translational value from pre-clinical proof-of-concept studies to clinical trials."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders

SFIDA ANALYSIS OF ABETA AND TAU AGGREGATES IN CSF OF COGNITIVELY IMPAIRED OLD- AGED BEAGLE DOGS - A MODEL OF SPORADIC ALZHEIMER’S DISEASE (ADPD 2022) - "sFIDA proves as a useful method to determine Aβ and tau aggregate concentrations in CSF, and to investigate quantitatively the effect of oligomer targeting drugs. Even though no reduction of Aβ oligomers was observed, the reduction of tau oligomers in the high dose group indicates that by targeting Aβ oligomers downstream targets like tau oligomers could therefore also be affected."

Alzheimer's Disease • CNS Disorders • Cognitive Disorders

ANALYSIS OF EX VIVO TARGET ENGAGEMENT OF ABETA-OLIGOMER-ELIMINATING COMPOUND RD2 IN BRAIN HOMOGENATES BY SFIDA ASSAY (ADPD 2022) - "The effect of RD2 on Abeta-assemblies from mouse brain homogenate was in accordance with previous in vitro and in vivo observations. Importantly, Abeta-oligomers in human brain homogenates were eliminated by RD2 as well. Our approach is suitable to predict therapeutic efficacy with higher accuracy than the in vitro approach alone before starting large preclinical animal studies, thus potentially reducing the number of animals used for in vivo tests and enhancing the translational value from pre- clinical studies to clinical trials."

Preclinical • Alzheimer's Disease • CNS Disorders