Section A

Early Patient Identification

Early Patient Identification Programs at subrosa OmicsAI

Prospective programs that find genetically confirmed patients years earlier than today’s standards.

From Database to Validated Cohort

A transparent, data-to-clinic pipeline — illustrated with Danon disease. The subrosa workflow.

1Global patient database

Over 600,000 patients (Europe, USA, Asia) with full HPO-based clinical characterization and WES / WGS genetic data.

2Define the disease spectrum

From the genetically verified sub-cohort of a given diagnosis (e.g. Danon disease) we analyze the detailed clinical phenotype, earliest symptoms and disease progression.

3Calculate predictive symptom signatures

Using clinical data from many patients with overlapping phenotypes but other diagnoses (e.g. cardiomyopathy), we retrospectively compute the positive and negative predictive value of the symptom constellation most indicative of the specific disease.

4Recruit & genetically verify prospectively

We prospectively recruit patients who present exactly this clinical signature into a clinical study, and then confirm them genetically.

5Reach a high-yield positivity rate

Such prospective studies are typically balanced to a positive diagnostic rate of ~4–10% — an enrichment factor of ~200–1,000× vs. the general population.

600,000+ patients Predictive signature Targeted cohort 4–10% genetically positive ≈ 200–1,000× enrichment
The Hidden Opportunity

Pharma Systematically Underestimates Rare Disease Market Size

Our epidemiological studies have validated up to 5x more patients than historical estimates — transforming market confidence and pharma valuations.

Underestimates the Market Potential – Why?

1. Limited Epidemiological Data

Many rare diseases have historically lacked robust epidemiological studies, making it difficult to determine true patient prevalence.

Prevalence estimates are often based on small registries, outdated studies, or assumptions rather than actual patient counts.

2. Diagnosis Challenges & Underreporting

Rare diseases are frequently underdiagnosed or misdiagnosed due to lack of awareness among healthcare providers.

Many patients go years without a correct diagnosis, leading to artificially low market size assumptions.

3. Regulatory & Payer Skepticism

Health authorities and payers require strong evidence of a disease’s burden before approving reimbursement or pricing strategies.

Without verified patient numbers, companies may struggle to justify premium pricing.

4. Historical Bias & Market Risk Aversion

Pharma companies have been traditionally hesitant to invest in rare diseases due to perceived market risks and uncertain commercial potential.

Previous failures in rare disease drug development reinforce conservative projections.

5. Lack of Real-World Data & Patient Registries

Unlike common diseases, rare diseases lack large-scale real-world evidence databases.

Many pharma companies rely on rough estimations rather than comprehensive, data-driven patient-finding approaches.

subrosa OmicsAI

Clinical Study Protocol for Early Patient Identification

Study Objectives
Define the specific aims and medical questions
Methodology
Study Design: Description of the chosen study design; Data Sources: Specification of data sources and collection methods; Statistical Methods: Detailed description of the statistical techniques applied
Eligibility Criteria
Define inclusion/exclusion criteria for participants
Study Timeline
Outline the study phases and key milestones
Data Management
Describe how the data will be stored, accessed, and analyzed
Risk and Bias Assessment
Plan to mitigate potential biases and risks in the analysis
IRB Considerations
Detail IRB protocols, including participant consent and data security
Deliverables & Reporting
Plan for reporting the results and communicating findings
subrosa OmicsAI

Study Elements and Descriptions

Concept Draft

Develop a comprehensive framework for the study, outlining objectives, methodologies, and expected outcomes to align stakeholders.

Study Protocol

Ensure all clinical and operational details are clearly defined in a robust protocol, adhering to regulatory and ethical standards.

IRB Process

Manage submissions and approvals with Ethics Committees to secure compliance and obtain necessary permissions for study execution.

PI Meetings

Conduct regular meetings with Principal Investigators to ensure alignment, training, and efficient communication throughout the study.

Site Identification & Study Execution

Identify and engage study sites through questionnaires and site selection processes, ensuring readiness for smooth trial operations.

Patient registry
Identify & follow-up of patients
Collect long-term clinical & genetic data
Engage physicians & KOLs
Demonstrate real world evidence for disease epidemiology
Enhance trial recruitment & access
Support reimbursement discussions
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Why Early Patient Identification Programs are a Competitive Imperative

  1. Detailed clinical information from each patient
  2. Direct interaction and communication with each medical expert
  3. Pseudomized follow-up data from the patients
  4. Patient registry (prospective) including longitudinal follow-up data
  5. Transparent and compliant communication routes to KOLs
  6. Structuring of a scientific advisory board
  7. Direct medical access to the PIs and the patients incl. families
subrosa OmicsAI

XCLR8ED — Patient Enrollment That Delivers

Timely patient enrollment is one of the biggest bottlenecks in clinical development — especially in rare and ultra-rare disease. Roughly 3 out of 4 clinical trials experience delays, causing major cost overruns and endangering maximal financial returns from the patent-window period. Recruitment shortfall is the dominant delay driver — the operational domain largely handled by CROs and sites. But CROs only optimize execution; our models address the root cause, de-risking enrollment BEFORE CRO execution starts, increasing the number of enrolled patients and reducing dropouts. The result: faster, predictable recruitment and more reliable study execution.

What subrosa OmicsAI combines

  • Partially unique knowledge of clinical insights from our proprietary rare disease patient genome database.
  • Experience from 40+ successfully executed global identification studies (proven and published) over the past two decades.
  • Deep access to more stakeholders than CROs in a global, trusted ecosystem — rare disease KOLs and sites, patients directly (counseling, funds-pooling, PSPs, home treatment), patient organizations, and data-driven targeted HCPs outside the excellence centers (awareness education).

…to improve the main KPIs of patient enrollment

  • Optimize protocol design — including optimal inclusion criteria and primary endpoints — BEFORE the CRO starts, so no more patients than necessary are excluded from screening and milestones stay achievable for investor milestone payments.
  • Recruit additional, also younger patients through subrosa OmicsAI’s clinical programs and register them to accelerate speed and quality of enrollment.
  • Increase site productivity and reduce the number of sites, especially zero-enrollment sites.
  • Improve the screen-to-enroll ratio through better pre-screening and targeting (patient conversion funnel).
  • Decrease time-to-first-patient / time-to-first-site for an earlier enrollment curve.

subrosa de-risks enrollment BEFORE CRO execution starts

subrosa OmicsAI

Protocol Design & Patient Enrollment Optimization

Reasons for rare disease trial-enrollment shortfalls — and what we can do.

Area Primary Owner Where subrosa Group can have impact on enrollment
Protocol design (eligibility, endpoints) Sponsor With unique real-world evidence from our proprietary rare disease patient database, subrosa OmicsAI provides essential insights to optimize protocol design and trial strategy before selecting a CRO — ensuring you don’t exclude a significant share of the accessible patient population from screening.
Feasibility & site selection Shared (Sponsor + CRO) Through our unmatched global rare disease KOL & site network we typically gain additional insights into optimal site selection and geographical match.
Site activation & operations CRO …and into site activation, especially in unmet-need indications.
Patient recruitment execution CRO + sites Our clinical programs identify patients that CROs typically never reach — far beyond the major excellence centers and often at a very early age. Proven. Published (PubMed). This broader patient range and higher proportion of young patients can have a massive positive impact on trial outcomes.
Patient awareness / referral ecosystem Sponsor + external networks With 40+ global identification studies completed (proven and published) over two decades, subrosa teams have deep access to rare-disease KOLs, sites and PAOs, allowing us to influence more referred patients to join a trial. We also find patients through omnichannel awareness education (42health) of targeted HCPs outside the excellence centers.
Retention / dropout CRO + sites 42health’s rare disease patient adherence and support programs — with site personnel (global) or at the patient’s home (Europe only) — remarkably reduce drop-out rates.

Include us in time, and you may not have to complain about CRO performance — in case of genetic-based rare disease indications.

subrosa OmicsAI

The Hidden Patient Problem That Costs Pharma Billions

7–12 yearsDiagnostic odyssey

A patient with a rare genetic disease waits an average of 7 to 12 years for a correct diagnosis. During that time the disease progresses — often irreversibly. Every year of delay is a year without therapy.

5× underestimatedTrue market potential

Historical prevalence estimates are based on incomplete registry data. Our prospective studies consistently show the real patient pool is up to 5× larger — with direct impact on pharma valuations and market access strategies.

85% without diagnosisGenetic cause, unknown

Over 85% of rare diseases have a genetic cause — yet most patients are never genetically tested. They remain invisible to pharma, to clinicians, and to the healthcare system. That is the gap subrosa OmicsAI closes.

Case Study

Real Data Real Patients Up to 5x Higher Market Value

Validated real-world patient numbers — not modeled estimates — directly translate into higher market confidence and stronger pharma valuations.

Delta: ~4-5x — Represents incremental implied value for Rare Disease1 vs. Market cap.

1) Outside-in assumption.

The subrosa OmicsAI Advantage

The subrosa OmicsAI Advantage

The only partner that turns genetically confirmed real-world patient data into your competitive advantage — across trials, market access and valuation.

Identifying Rare Patients. Precisely. Earlier. Globally.

What sets us apart — Three layers of differentiation no CRO or data provider can replicate

01 Data layer — Proprietary Real-World Patient Database

Over 58,000 rare disease patients recruited across 48+ countries — genetically confirmed, clinically deep-characterized, longitudinally followed. Not modeled. Not estimated. Real.

▸ Proof: ROPAD study — 12,580 PD patients from 122 sites in 9 months

02 Intelligence layer — Multi-Omics + AI Sub-Stratification

We go beyond diagnosis: genomics, transcriptomics, proteomics and metabolomics combined with AI models sub-stratify patients into clinically actionable groups — de-risking your trial design from day one.

▸ Proof: HAE study — 150× higher prevalence in targeted screening vs. general population

03 Business impact layer — Market Validation That Changes Valuations

Our epidemiological programs have consistently shown patient pools 4–5× larger than pharma estimated — translating directly into higher market confidence and stronger regulatory submissions.

▸ Proof: Validated programs showed 4–5× implied value uplift for rare disease assets

subrosa OmicsAI Services

Identifying Rare. Precisely. Early. Globally.

Development - Preclinical
Clinical
Medical - Commercial
Proprietary Real-World Patient Database Multi-Omics + AI Sub-Stratification Market Validation That Changes Valuation
> 58,000 patients recruited Up to 40% reduced Development times
up to 10x underestimated market Potential Boost valuation & investor trust
4-5x larger value uplift Increased commercial success
Early & Long-Term Strategic Value – Positioned as a Core Asset for Commercialization

* OENI – Observational Epidemiological Non-Interventional Study

The Rare Disease Patient Intelligence Partner

Identifying Rare Patients. Precisely. Earlier. Globally.

Proven at scale: We identify patients for gene-based rare diseases data-driven, not estimated — accelerating your development timeline from day one.

De-risk your enrollment before the CRO starts

Talk to us about an early patient identification program for your indication.