References & Case Studies

1 Client & Goals

Understand the prevalence of Hereditary transthyretin-related (hATTR) - common name - Amyloidosis - in subjects with cardiomyopathy and/or polyneuropathy of no obvious etiology.

Evaluate effects of systematic screening.

Evaluate Market size in non-endemic regions (where only sporadic cases are reported)

Adapt Guidelines for early screening.

2 Methods

A multicenter observational “Epidemiological analysis for the hereditary Transthyretin-Related AMyloidosis”—TRAM study was performed in Germany, Austria, and Switzerland.

• 5000 participants
• 50 neurologic 27 cardiologic specialized centres.
• Genetic testing for hATTR (filler card - CentoCard®)

3 Results

TRAM confirmed >1% of patients with cardiomyopathy (CM) and/or polyneuropathy (PNP) of unclear etiology are positive for a variant in TTR gene.

This results in up to 90-fold higher haTTR+ patient numbers if translated to the CM/PNP prevalence in non-endemic regions.

• Prevalence haTTR+ Germany Before and After TRAM
• 85% of haTTR+ Patients are Pathogenic

4 Benefits

The results of the TRAM study confirm the need for mandatory genetic testing and counselling for all patients with cardiomyopathy and/or polyneuropathy of no obvious etiology.

Benefit 1: Patients obtain 4-5 years earlier the diagnosis for hATTR for which causative treatments are available.

Benefit 2: Significant higher number of patients (market size) in non-endemic regions.

1 Client & Goals

Understand the prevalence of genetic PD

Offer LRRK2+ eligible subjects to participate in LRRK2 inhibitor trial

Offer identified participants gene specific trials (GBA, PRKN, SNCA, PINK1, etc.)

2 Methods

A multicenter observational “Rostock International Parkinson’s Disease Program” – ROPAD study was performed in USA, Germany, the UK, Spain, Brazil, Israel, Italy, Turkey, Belgium, Norway, France, Canada, Albania, Argentina, Greece, and Portugal

• 12,580 participants
• 122 sites, 16 countries
• Genetic testing for PD panel (68 genes, step-wise approach)

3 Results

• 12,580 participants recruited from 122 sites within 9 months during COVID (May 2019 - Jan 2021)
• 14.8% (1,864) of PD participants identified with a genetic cause of PD – up to 27% with an AAO ≤ 50 years and FH+
• 368 (2.9%) LRRK2+ offered enrollment in LRRK2 inhibitor trial
• 1,311 (10.4%) GBA1+, 119 (1.0%) PRKN, 25 (0.2%) SNCA
• ~90% of positive PDGT patients had variants in LRRK2 or GBA1
• 10.4% (1,311)

4 Benefits

Benefit 1: 15% of participants got a defined genetic diagnosis and were counselled for existing gene-specific trials.

Benefit 2: Detection rate enriched to up to ~ 27% targeted population nearly doubling the identification rate.

Benefit 3: GBA+ (1,311) and LRRK2+ (368) patients were offered to participate in specific trials.

Benefit 4: ROPAD protocol feasible for high-throughput genetic characterization in record time for participation in gene focused clinical trials.

1 Client & Goals

Understand the prevalence of HAE in participants with recurrent episodes of abdominal pain attacks of no obvious etiology.

Evaluate clinically relevant market size and offer diagnosed patients available, approved therapies.

Develop recommendations to adapt guidelines for early screening in relevant patient populations.

2 Methods

A multicenter observational “Epidemiological analysis for Hereditary Angioedema Disease” – EHA study was performed in Mexico, Germany, Italy, Turkey, Poland, Japan

• 1000 participants
• 34 sites
• Dry Blood Spot (DBS) testing for C4 and C1-inhibitor levels, if pathologic HAE type genetic testing

3 Results

• 1000 participants were recruited from 34 sites (Jan. 2019 – Feb. 2020)
• 0.3% of patients with unexplained abdominal pain were diagnosed with HAE compared to the general population (~0.001–0.005%)
• Family members screening led to 1,3% positivity rate
• 50-150-fold increased HAE prevalence in the selected patient group (0.3%)
• 3-6x increase in clinically relevant market size population

4 Benefits

The results of the EHA study confirm the need for mandatory screening / genetic testing of patients with unexplained, recurring abdominal pain to ensure timely diagnosis and access to relevant therapies.

Benefit 1: Targeted screening in patients with unexplained recurrent abdominal pain results in ~50-fold higher HAE prevalence and ~3-6x more HAE patients identified compared to screening the general population.

Benefit 2: Targeted screening can significantly shorten time to diagnosis for patients with HAE and give them access to relevant therapies.

1 Client & Goals

Identify reliable biomarkers in Hereditary Angioedema (HAE) to:

• Improve diagnostics beyond C1-INH testing
• Enable prediction of attacks
• Support personalized treatment strategies

The HAEKA study aims to:

• Capture longitudinal & attack-specific samples
• Identify dynamic biomarkers
• Establish a real-time molecular understanding of HAE attacks

2 Methods

A multicenter observational longitudinal Kininogen assay study enabling real-time biochemical profiling during Hereditary Angioedema (HAE) attacks. The HAEKA study was performed in Germany.

• 41 participants
• 5 sites
• 2-6 samples per attack and 7 follow-up visits over 2 years
• Samples analyzed with the liquid chromatography technique and ion mobility—high resolution mass spectrometry to identify novel biomarkers & metabolites.

3 Results

90 blood samples were collected during the regular visits, and 19 of the participants also performed self-sampling during the HAE attacks from which a total of 286 attack blood samples were collected.

• High patient compliance and usability of self-sampling
• Strong data quality from DBS samples
• Ability to capture temporal biomarker dynamics during attacks

Evidence suggests:

• cHMWK (Kininogen) increases during attacks
• May serve as prognostic biomarker for disease activity

First large-scale real-world attack sampling

First use of self-collected DBS+ metabolomics

Enables:

• Individual molecular fingerprints of attacks
• Discovery of novel biomarkers beyond known pathways

4 Benefits

The study showed that attack sampling enables early prediction and prevention of HAE attacks, supports personalized therapy and expands diagnostic possibilities.

➡️ Potential to fundamentally change clinical management of HAE

Benefit 1: The study demonstrates that home-based sampling is feasible, scalable, and reliable to establish new standards for decentralized clinical studies.

Meta

• subrosa India for an US Biotech Company
• Market – India
• Disease – Epidermolysis Bullosa (EB) a Rare Skin Disorder

Goal

To evaluate a Combination Drug efficacy and safety in Indian Patients with Epidermolysis Bullosa for an 8-week Clinical Evaluation of Orphan Drug (Combination) in Epidermolysis Bullosa

Challenge

Even after an exhaustive search the client could not find a single patient in India with Epidermolysis Bullosa.

The trial design required an intra-patient study model including all three EB variants, making recruitment complexity high.

Measures

• Leveraged PAO Network
• Rapid Cohort Identification
• Clinical Triaged Patient Identification

Results

• Patients Identified: 350 EB patients in 10 days
• Time to Trial Readiness: Consent + PI appointment in 30 days
• Diagnostic Confirmation: Molecular + genomic profiling completed for cohort
• Trial Feasibility: Enabled 8-week study with all 3 EB variants as per protocol
• Sponsor Value: Prevented trial delay/cancellation; opened India as viable EB site