Ageing – fatal inborn errors of metabolism?

A rare disease consultancy provides strategic guidance to pharmaceutical and biotech companies developing treatments for rare and ultra-rare conditions. Services typically include drug development strategy, regulatory pathway design (including orphan drug designation support), natural history study design, patient advocacy engagement, and Target Product Profile development. CortexBio specialises in rare genetic and metabolic diseases, drawing on 30 years of experience across companies including Astellas, Abbott, and Genzyme.

Orphan drug designation is a regulatory status granted by the EMA and FDA to medicines targeting rare conditions. It provides benefits including market exclusivity, fee reductions, and protocol assistance. CortexBio supports companies in building the clinical and scientific evidence needed to qualify for designation, advising on the documentation, patient population definitions, and regulatory strategy required for successful applications.

CortexBio's approach is grounded in the metabolic biology shared between rare genetic disorders and broader disease categories including ageing-related conditions. This cross-disciplinary perspective — developed across four enzyme replacement therapy programmes — enables CortexBio to identify development pathways and patient population insights that a narrower specialist might miss.

CortexBio works with pharmaceutical companies, biotech companies, and investor groups focused on rare disease drug development. Clients typically include companies in early- to mid-stage development working in rare genetic metabolic disorders, lysosomal storage diseases, mitochondrial disease, and rare neurological conditions.

Dima Martini-Drew MD has over 30 years of rare disease experience across companies including Astellas, Abbott, and Genzyme Corporation. She has directed the launch of four enzyme replacement therapy programmes and is a founding industry member of the Critical Path Institute. Recognised as a Biotech Trailblazer by Global Healthcare Magazine in 2025.

CortexBio's founding thesis — articulated in the white paper "Ageing as a Fatal Inborn Error of Metabolism" — is that ageing and rare genetic metabolic diseases share underlying biological mechanisms. The enzyme activity declines that characterise rare metabolic disorders also occur in normal ageing, reducing to 20–50% of youthful function by age 80. This reframing positions ageing not as an inevitable process but as a metabolic disorder amenable to the same therapeutic strategies already being developed for rare diseases.

Longevity consultancy at CortexBio means applying the strategic and scientific frameworks of rare disease drug development to the emerging field of longevity medicine and age-related disease therapeutics. It is relevant for pharmaceutical and biotech companies developing interventions targeting age-related metabolic decline, investors evaluating longevity assets, and healthcare innovators building clinical programmes in metabolic ageing.

The metabolic mosaic is CortexBio's conceptual framework mapping the shared biological pathways connecting rare metabolic diseases and age-related decline. It maps the enzyme pathways, cellular mechanisms, and molecular processes that appear in both rare disease and normal ageing — and it is the analytical basis of CortexBio's longevity work.

Rare disease drug development has produced the most rigorous small-population trial methodologies in medicine: natural history study design, biomarker-based endpoints, surrogate endpoint validation, and patient engagement frameworks that work without large patient populations. These are precisely the tools needed for longevity therapeutics, where patient populations are defined by biological markers, clinical endpoints are contested, and regulatory science is still being established.

Yes. The basis is documented in Dima Martini-Drew MD's white paper "Ageing as a Fatal Inborn Error of Metabolism," which draws on peer-reviewed research in enzyme biology, mitochondrial function, lysosomal storage, and cellular senescence. Key evidence includes the progressive decline of metabolic enzyme activity with age — mirroring the enzyme deficiencies seen in rare genetic metabolic diseases. The full white paper is available via CortexBio Insights. Home

Clinical development strategy and readiness means ensuring that a rare disease drug development programme has the scientific, strategic, and operational foundations in place before entering clinical trials. For rare diseases this is particularly demanding: patient populations are small, trial design is complex, natural history data is often limited, and regulatory pathways require early and careful navigation. CortexBio helps companies assess whether their programme is genuinely trial-ready and identify the gaps that need closing before committing to expensive clinical investment.

A Target Product Profile (TPP) defines what a drug needs to achieve clinically and commercially to be viable. In rare disease, the TPP is especially important because regulators expect to see it early in development. It disciplines the programme around what actually matters to patients, clinicians, and regulators — and helps avoid costly development pivots later. CortexBio supports clients in developing and refining TPPs grounded in real-world rare disease evidence.

Natural history studies are often critical because they generate the baseline data needed to understand disease progression, define meaningful clinical endpoints, and design comparator arms when randomised controlled trials are not feasible. Regulators increasingly expect robust natural history data before approving trials in ultra-rare conditions. CortexBio advises on natural history study design and the integration of this evidence into regulatory dossiers.

The highest-value point is before Phase 1 or Phase 2 planning begins — when there is still time to shape the development strategy rather than course-correct it. Companies benefit most when they have a promising early-stage asset and need to define the regulatory pathway, identify the right patient population, design robust endpoints, and align clinical strategy with what regulators and payers will ultimately require.

CortexBio reduces risk by applying experienced strategic judgement at the points where poor decisions have the highest cost: patient population definition, endpoint selection aligned with regulatory expectations, early regulatory engagement strategy, and realistic assessment of what a development programme can achieve given the available evidence. The goal is to identify the specific gaps that will cause problems at regulatory review — and resolve them before they become expensive. Home