Verónica Cánovas, PhD, & Joaquín Gómez-Moya

“Non quia difficilia sunt non audemus, sed quia non audemus difficilia sunt”.

As Seneca wrote, it is not because things are difficult that we do not dare; it is because we do not dare that they are difficult. That is the case in translational immunology and, in general, Deep Tech projects, courage often looks like meticulousness.

Executive brief

The development of novel biomarkers represents one of the most challenging frontiers in biotechnology, requiring the orchestration of multiple scientific, technical, regulatory and managerial competencies. Using our currently ongoing endeavors on a NLRP3 inflammasome biomarker development as a case study, we examine how confronting complex biotech challenges systematically builds transferable capabilities that extend far beyond the original target. These are the capabilities that determine not only whether a single program succeeds, but also whether an organization can sustain innovation at scale.

In Viva In Vitro’s case, the technical imperatives of developing proprietary monoclonal antibodies, optimizing immune assays, conducting multicentric clinical validation, and extending applications across disease areas creates a platform of competencies with significant strategic value for pharmaceutical partnerships, biotech collaborations, and clinical research services.

Viva-Elisa® case

VIVA-ELISA® translates inflammasome biology into a clinical signal—quantifying impaired NLRP3 pathway competence via ASC-specks–based readouts to support risk stratification in sepsis and, over time, other immune-driven conditions.

The program is deliberately designed as a capability-building engine: recombinant monoclonal antibody design and lot-consistent production; assay engineering at clinical pace; multicenter performance evidence compliant with IVDR; and data/AI methods that convert longitudinal immune dynamics into decisions.

The NLRP3 inflammasome is itself a particularly difficult biomarker target. As a large multiprotein complex nearly one micrometer in size, it is not a single analyte but rather a dynamic assembly that requires precise contextual detection. Detecting and quantifying its activity in blood patient samples therefore poses extraordinary challenges. ASC polymerization into “specks” is a hallmark of NLRP3 engagement, measurable and associated with survival in sepsis. (Frontiers).

Publications of methods reinforce assayability; specificity, however, hinges on antibody quality and on differentiating inflammasome assemblies from pyroptotic debris—hence our emphasis on internally developed recombinant antibodies. (MDPI, SpringerLink)

Clinically, the unmet need is well characterized: hundreds of proposed sepsis biomarkers exist; few demonstrate reliable actionability outside multiparametric panels. A mechanistic, functional biomarker for immune competence is attractive provided prospective multicenter studies confirm effect sizes, reproducibility and clinical utility. (SpringerOpen, ScienceDirect, Public Health).

What building VIVA-ELISA® really builds

1. From discovery to clinical translation

One of the earliest difficulties is translating a biomarker discovery assay into a clinically usable diagnostic test, commonly implies the shift from complex research-grade technologies to robust but simplified assays that can be implemented in routine diagnostics. This case highlights the inherent tension between discovery and translation: while advanced research tools can reveal highly detailed biology, clinical assays must be simple, reproducible, cost-effective, and automatable.

Adapting such complexity into an ELISA format demands assay redesign, simplification, and rigorous reproducibility testing.

2. Antibody engineering as an industrial discipline

Developing a clinically applicable immunoassay in the NLRP3 context, require highly specific monoclonal antibodies against key proteins of the inflammasome pathway. We develop recombinant monoclonal antibodies ensuring they can recognize the native conformation of the inflammasome activated complex, with high specificity and without cross-reactivity, assuring epitope fidelity, inter-lot consistency and scalability.

3. Assay engineering for clinical pace

Clinical deployment imposes requirements that prototypes rarely meet shorter turnaround, reduced hands-on time, and resilience to pre-analytical variability. Each optimization step required rigorous analytical validation (sensitivity, specificity, linearity, intra- and inter-assay variability) before moving toward clinical validation.

Our engineering objectives—time-to-result reduction and improved specificity/precision without sacrificing biological meaning—have been aligned with the CORDIS-registered aims for VIVA-ELISA®—ease of use, high sensitivity, hospital deployment—so we prevent falling short on robust prognostic or stratification value.

4. Multicenter clinical performance under IVDR

The pathway to clinical adoption required large, multicenter validation studies to demonstrate that the biomarker test performed consistently across populations. Recruiting participants, standardizing protocols across centers, and generating robust datasets demand significant resources. IVDR and MDCG guidance formalize the triptych of performance evaluation (scientific validity, analytical performance, clinical performance) as a continuous process.

Our multicenter studies and sampling strategy (with the intent to evolve into structured biobanking) follow this frame and prepare for FDA/EMA interactions should a biomarker enter drug-development contexts of use. In practical terms, we have improved key features as prospective design, ICU/emergency site diversity, and predefined utility endpoints.

5. Quality & scalability as early enablers

Early ISO 13485 implementation, traceability and design and manufacturing controls are intended to shift the program from just one more “promising assay” to credible clinical product and service reducing friction in technology transfer and external validation. Sepsis comprises heterogeneous endotypes and several stages as it courses.

Our main contribution is a mechanistic signal that can improve model calibration and transportability across sites to stratify and monitor the patient; that’s why we have learned to prioritize time-aware modelling and specification of each context-of-use to facilitate regulatory dialogue.

6. Beyond technical development

Bringing a biomarker to the clinic requires building multidisciplinary capabilities. Teams must master conceptualization and prototype design, antibody engineering, assay validation, biostatistics, and clinical trial design.

At the organizational level, companies need infrastructure for quality management, manufacturing scale-up, regulatory affairs, and business development. Equally important are collaborative competencies for validation and real-world testing. Over time, we build a culture that integrates scientific rigor with entrepreneurial agility, enabling us to navigate the long and costly path from biomarker discovery to clinical application.

Why this matters for stakeholders

Stakeholders in our industry, like patients and clinical professionals, ultimately judge us not on conceptual novelty or intellectual refinement but on our capacity to deliver manufacturable, scalable and clinically actionable solutions. Consequently, we welcome collaborations who seek not just an assay but a reproducible way to see immune competence when it matters most.

Pharma use cases:

• target robustness and biomarker qualification,
• enhanced patient recruitment and go/no-go criteria in Phase I–III for NLRP3-pathway assets.

Biotech use cases:

• co-developed kits and bespoke protocols for complex matrices;
• accelerated method transferred via recombinant reagent access.

Research centers & hospitals use case:

• dynamic monitoring in sepsis/immunosuppression;
• training in inflammasome methods;
• advisory for trials in critical populations tapping into the value of harmonized sampling, good clinical data joint planning and end-point definition.

NLRP3 plays a role in neurodegeneration (e.g., Alzheimer’s Disease), cardiovascular pathology and other diseases. Translation will require indication-specific validation, but the core stack—monoclonal antibodies, assay engineering, quality system, data pipelines management—is portable making possible that the usual sequence—proof-of-mechanism cohorts → analytical bridging → clinical performance against indication-appropriate endpoints—benefits from mitigated risks and accelerated learning when assisted by a proven team.

Potentially transferable lessons for managers

Mechanism beats correlation.
Mechanistic anchors and pre-specified contexts of use increase odds of clinical utility.

Assay clarity matters. 

Ongoing debates persist around ASC “speck” and caspase-1 activity. Pairing antigen/epitope design with proper controls minimizes misattribution.

Regulatory by design. 

Build the IVDR triptych from day one; seek EMA/FDA advice early. Qualification pathways reward clarity and reproducibility.

Network effects win. 

Multicenter validation is not a box-tick, it is how a fragile signal survives heterogeneity in real care settings. Clinical studies benefit from heterogeneity.

Closing

The VIVA-ELISA® program operates as a capability flywheel: antibody engineering, assay craft, clinical evidence, and data science converging into decision-grade signals. This highlights the dual challenge of simplifying complex biology into robust diagnostics and building the human and organizational competences to support translation.

Deep Tech programs are demanding, but their ‘by-products’—skills, resources, networks—compound when success is measured not only by final product or device, but also by the capacity built and the future optionality in development pathways and in business models that come after these.

Dr. Verónica Cánovas leads biomarker development as Biotechnological Development Manager at Viva In Vitro, specializing in inflammasome biology and translational immunology.

Joaquín Gómez-Moya is Executive President of Viva In Vitro and serves on multiple industry boards.