CogniPD+: Advancing a First-in-Class Therapy for Parkinson’s Disease Dementia
CogniPD+ is a pre-clinical project developing N1(4)inh-IL, a selective Nox1/4 inhibitor for intranasal brain delivery targeting cognitive decline in Parkinson’s Disease.
Unmet Clinical Need
Parkinson’s Disease Dementia (PDD) is a severe and progressive neurodegenerative condition affecting approximately 30% of Parkinson’s patients, impairing memory, executive function, and autonomy. Despite its enormous burden on patients and caregivers, there are currently no approved therapies capable of modifying disease progression.
Oxidative Stress & Neurodegeneration
Neurodegeneration in PDD is driven by oxidative stress linked to the NADPH oxidases Nox1 and Nox4, which are overexpressed in patients’ brains. Nox4, in particular, accumulates in the hippocampus and correlates with the build-up of α-synuclein, β-amyloid, and tau — key proteins associated with cognitive decline.
Failure of Existing NOx Inhibitors
The existing NOx inhibitors have failed to demonstrate efficacy in clinical practice due to their poor selectivity, low bioavailability, and significant toxicity. No compound targeting this pathway is currently in an advanced stage of clinical development for neurodegenerative diseases. This is the gap CogniPD+ addresses.
N1(4)inh-IL: A First-in-Class Nox1/Nox4 Inhibitor
Ionic Liquid Form · Intranasal Delivery
N1(4)inh-IL was developed at the Universidade da Beira Interior and is exclusively licensed to Fastprinciple. It selectively inhibits the Nox1 and Nox4 oxidase isoforms by blocking the oxidative cascade that drives dopaminergic neurodegeneration, neuroinflammation, mitochondrial dysfunction and pathological protein aggregation. The compound is formulated as an ionic liquid optimized for intranasal delivery, enabling efficient brain targeting and enhanced bioavailability.
This combination of molecular precision, innovative formulation and targeted delivery route creates a profile with no direct equivalent in the current drug development landscape.
Differentiators in N1(4)inh-IL
First-in-Class Nox1/4 Inhibition
Novel mechanism for neurodegeneration with no current clinical competitors.
Intranasal Delivery to the Brain
Direct CNS targeting, validated in preclinical studies.
Ionic Liquid Formulation
Enhanced stability, bioavailability, and translational potential.
Translational Preclinical Model
Development of new animal models for Parkinson’s Disease Dementia.
Regulatory Alignment
Strong scientific foundation aligned with EMA/FDA pathways.
Intellectual Property
Protected by international patent WO2023144742A1.
From Proof-of-Concept to Regulatory Readiness
CogniPD+ is currently at preclinical stage (TRL 4–5) and aims to reach regulatory-ready TRL 6–7 by the end of the project. The project builds on robust proof-of-concept data from the predecessor project PDSolve (PT2020), including in vivo efficacy in motor models, preliminary pharmacokinetics, safety, and blood–brain barrier validation. The next milestone is regulatory preparation for IND/CTA submission and entry into clinical trials.
36-Month R&D Programme
CogniPD+ is structured around five interconnected activities:
Activity 1 — DMPK & Regulatory Studies
Complete ADME/toxicology package (in vitro and in vivo) aligned with EMA and FDA requirements. Establish GMP manufacturing process for N1(4)inh-IL in partnership with a certified international CRO (WuXi AppTec or Eurofins). Outputs form the core regulatory dossier for future IND/CTA submission.
Activity 2 — Cognitive Effectiveness in PFF Model
Evaluate whether N1(4)inh-IL can prevent cognitive decline via intranasal delivery using a PFF model. Animals assessed at 2, 3 and 6 months using established behavioural tests (novel object recognition, Morris water maze, Y-maze, fear conditioning) and comprehensive neuropathological analyses.
Activity 3 — Novel Paraquat-Induced PDD Model
Develop and validate a novel animal model of PDD based on chronic paraquat exposure. Characterized longitudinally through behavioural, neurochemical, and histopathological markers, enabling future use as a research tool or specialised service for pharmaceutical companies and CROs.
Activity 4 — Dissemination & Valorisation
Scientific communication, dissemination, valorisation and industry engagement. Stakeholder mapping, market value assessment, and intellectual and industrial property support, with value creation activities supported by Ambiom.
Activity 5 — Project Management
Led by Fastprinciple in collaboration with UBI, ensuring efficient coordination through an integrated management system covering governance, timeline, reporting, and FAIR-aligned data management.
Multidisciplinary Expertise
CogniPD+ is led by Fastprinciple in co-promotion with the Universidade da Beira Interior (RISE-Health). The project team integrates complementary competencies across all dimensions of drug development.
Fastprinciple
Ana Clara Cristóvão
CSO & Principal InvestigatorNeurodegenerative disease researcher with deep expertise in Parkinson’s disease, NADPH oxidase biology and pre-clinical model development.
Dina Pereira
Chief Executive OfficerInnovation project management specialist and executive director of UBImedical. Leads business development, international partnerships and operational management.
Ricardo Pacheco
Chief Medical OfficerPhysician with an MBA who has held positions at Novartis, Roche, and AstraZeneca. Leads clinical and regulatory strategy.
João Leitão
Chief Financial OfficerProfessor of Economy and specialist in finance, sustainability, and entrepreneurship. Ensures economic viability and value-creation strategy.
UBI (RISE-Health)
Gilberto Alves
Pharmaceutical SciencesSpecialist in pharmacokinetics and metabolism (ADME), with extensive experience in regulatory preclinical studies.
Samuel Silvestre
Pharmaceutical SciencesResponsible for medicinal chemistry support and analysis and validation of the stability and reactivity of the N1(4)inh-IL formulation.
Luís Passarinha
BiomedicineSpecialist in biochemistry and chromatographic techniques, responsible for quantification of dopamine and its metabolites using HPLC.
External Consultants & Partners
Mara Freire
CICECO, University of AveiroInternational expert in ionic liquid chemistry. Advises on formulation design and optimisation.
Marcelo Mendonça
Champalimaud FoundationClinical neurologist. Ensures clinical relevance of endpoints and supports regulatory and clinical translation strategy.
Yoon-Seong Kim
Rutgers University, USAProfessor of Neurology and specialist in Parkinson’s molecular mechanisms. Supports translational model validation.
Ambiom
Life Science AdvisoryStakeholder mapping, market positioning and economic valorisation of N1(4)inh-IL.
Doctoral Researchers
Mariana Fiadeiro
Senior PhD ResearcherExperience in Parkinson’s models. Active across Activities 2 and 3.
Ana Alexandra Silva
PhD ResearcherContributing to in vivo testing and biochemical analysis.
Rita Curto
PhD ResearcherLeading experimental execution in Activity 2, under supervision of Dr. Ana Clara Cristóvão.
Licensing & Co-Development Opportunities
By the end of CogniPD+ (September 2028), Fastprinciple will hold a complete preclinical regulatory dossier — including DMPK, GMP batch production, and cognitive and neuropathological efficacy data — positioning N1(4)inh-IL for IND/CTA submission and Phase I entry (estimated 2029–2030).
We are actively engaging pharmaceutical and biotech companies, as well as institutional investors, to explore co-development, licensing, and out-licensing opportunities.
Licensing Opportunity — N1(4)inh-IL
- First-in-class mechanism (selective Nox1/Nox4 inhibition)
- Innovative pharmaceutical ionic liquid formulation
- Intranasal CNS delivery (proven BBB penetration)
- Patent protected internationally (PCT WO2023144742A1)
- TRL 6–7 by end of 2028
- Phase I entry estimated 2029–2030
Secondary Opportunity — PDD Animal Model
- Novel paraquat-induced PDD animal model
- Specialised preclinical service from 2028/29
- Designed for evaluating cognitive therapies
- Target users: pharmaceutical companies and CROs
We Welcome Engagement With
We are seeking partnerships with pharmaceutical and biotech companies in neuroscience and CNS, venture capital and corporate VC, innovation funding bodies such as the EIC Accelerator, and strategic co-development partners.
For scientific collaboration enquiries, partnership and licensing discussions, or media and press requests, please contact the CogniPD+ project team.