Biotechnology for Healthy Ageing

Expected Impact:

This Challenge looks to accelerate the development and uptake of clinically validated interventions that target the root cause of multiple age-related morbidities. It will:

• Deliver biotechnology-based interventions for healthy ageing

• Accelerate the implementation of personalised care in ageing based on molecular phenotyping​

• Provide recommendations for regulatory pathways addressing ageing as a target to inform developers, regulators, and other decision makers​, and

• Improve citizen literacy on longevity.

Expected Outcome:

Ambitious proposals put forward under this call will deliver:

• Proof-of-concepts (TRL3 completed) of biotechnology-based or pharmaceutical interventions that prevents or delays the onset of, or reverts, an age-related disease in a vertebrate model system, based on the hallmarks of ageing, taking into consideration practical challenges of implementing such an intervention

• Tools to facilitate development or adoption of the interventions above, such as proof-of-concept validation of biomarker signatures or suitable pre-clinical models​, and

• Approaches to address the shared regulatory hurdles and societal challenges linked to ageing-related interventions, thereby facilitating their adoption​.

Portfolio approach

The portfolio of projects selected under this Challenge will ensure a coverage of projects developing interventions, biomarkers and NAMs, considering the following guidelines for portfolio composition:

• Interventions: no more than 5 projects. The portfolio of selected projects should collectively address a variety molecular and cellular processes related to ageing, and a variety of different age-related diseases.

• Biomarkers: no more than 3 projects. Projects will be selected to capture different application areas (diagnostic, predictive, prognostic biomarker), with preference to the inclusion of at least one diagnostic biomarker).

• NAMs: No more than 2 projects. Projects will be selected to capture a diversity of approaches to assess aged status in NAMs, different tissues or cell types and different use cases.

The selected consortia will benefit from mutual learning, and the exchange of expertise. Consortia will be encouraged to collaborate to address the following shared challenges faced by all ageing interventions:

• Scientific: preclinical models; Biomarkers of healthy/unhealthy ageing​

• Path to Market: Defining suitable regulatory pathways​, and

• Societal: Acceptance and role of preventative / therapeutic interventions, Need for improved longevity literacy​.

Objective:

Applicants to this Challenge will be expected to develop a proof of concept in one of the following three areas:

• An innovative preventative or therapeutic biotechnology-based or pharmaceutical intervention that prevents, delays or reverts the onset of a specific age-related disease. Such projects must address all of the following objectives:

• develop an intervention that targets a fundamental molecular or cellular process of ageing, such as the hallmarks of ageing

• assess the generalisability of the intervention (showing that it is applicable more broadly to ageing-related traits beyond the primary indication targeted) by assessing the impact of the intervention on another distinct trait related to ageing

• demonstrate proof of concept by carrying out an interventional study in a vertebrate animal model of ageing that is physiologically aged. Projects are also encouraged to include small-scale interventional clinical studies but must at a minimum anticipate how the intervention could be feasibly tested in a clinical setting, and

• develop a plan for exploitation, which considers ethical and societal perception, economic viability and regulatory approval. At least two of these areas, considered most relevant for the intended application, must be assessed in greater depth, suitably informing the project’s technology development and contributing to the portfolio activities.

• A biomarker[1] based tool to enable the responsible deployment of ageing-related interventions, taking into consideration the following:

• The tool should be based on previously identified potential biomarker candidates or ageing clocks. All types of biomarkers are welcome, for example digital, molecular or physiological biomarkers (such as frailty measurements), combinations of biomarkers and multimodal biomarkers); as well as biomarkers for different applications (e.g. predictive, diagnostics). Biomarker discovery is explicitly excluded

• The tool should integrate different measurements of multiple molecular, anatomic, physiologic, biomechanical or biochemical traits, as appropriate, to comprehensively capture the ageing process (i.e. it should not exclusively measure a single parameter/hallmark of ageing)

• The above selected biomarker signature should enable a clear linkage between clinical features and the mechanisms of ageing to be shown

• The signature should be robust to inter-individual and intra-individual variability in ageing to provide actionable, personalised insights

• The tool should be assessed in an initial retrospective study to establish proof-of-concept. Applicants must therefore convincingly demonstrate that they have access to suitable longevity cohorts, and

• The selection of the biomarkers and the development of the tool should prioritise deployment feasibility and actively incorporate feedback from potential users.

• A New Approach Methodology (NAM)[2] that goes beyond the current state-of-the art to enable the future development of interventions for healthy ageing. The NAM should:

• robustly capture the aged status of the system and the systemic/integrative nature of ageing (i.e. it should capture more than 1 molecular or cellular aspect of ageing, and more than 1 tissue type)

• be benchmarked against a relevant animal model of ageing, and

• be tested in the setting of a clearly specified use case (e.g. development of an intervention; as pre-clinical model in a regulatory setting). ​

Precision nutrition, the development of novel ageing clocks and wellness applications fall outside the scope of this Challenge.

All proposals should consider biological sex and gender-specific health determinants[3] in their development, with reproductive ageing also in scope.

Scope:

Ageing, the gradual decline of organismal homeostasis and of physiologic functions throughout the body and mind, is a critical shared risk factor for many ageing-related chronic diseases. The EU also has an ageing society - by 2050, the share of 85+ year-olds in the EU is expected to ​more than double​, but extended life expectancy is not ​matched with years spent in good health, which ​currently stands at 70.5 years. This will present significant social, economic and healthcare challenges and thus calls for interventions that will promote healthy longevity, as well as tools that will enable the adoption of these interventions.

Over the past decades basic research has identified hallmarks and cellular mechanisms of ageing, creating the basis for biotechnology-based or pharmaceutical therapeutic interventions, such as targeting cellular maintenance pathways, stem cell exhaustion, cellular senescence or metabolic fitness. Nonetheless, translating these insights into clinical interventions has had a low success rate, partially due to the difficulty of:​

• Translating approaches from model systems

• Identifying when to intervene

• Rigorous validation, and

• End-to-end considerations of implementation (i.e. the delivery of an intervention)​.

This Challenge therefore looks to translate decades of ageing research into tangible biopharmaceutical solutions for healthy ageing

[1] Biomarkers are biological characteristics, which can be molecular, anatomic, physiologic, or biochemical. These characteristics can be measured and evaluated objectively. They act as indicators of a normal or a pathogenic biological process. They allow the assessment of the pharmacological response to a therapeutic intervention. A biomarker shows a specific physical trait or a measurable biologically produced change in the body that is linked to a disease or a particular health condition. A biomarker may be used to assess or detect a specific disease as early as possible (diagnostic biomarker), the risk of developing a disease (susceptibility/risk biomarker), the evolution of a disease (prognostic biomarker) – but it can also predict response to a given treatment including potential toxicity (predictive biomarker)

[2] New approach methodologies (NAMs) represent potential alternatives to animal testing in the non-clinical development phase of new medicines. They may include human organoids or microphysiological systems (e.g. organ-on-chip, disease-on-chip), in chemico methods, digital twins, virtual patient simulations, AI-enhanced predictive models, mechanistic or integrated in silico platforms, 3D- advanced human tissue model

[3] Sex: Refers to biological characteristics (including genetic, hormonal, physiological, anatomical) that distinguish between male, female, and intersex (in humans) or hermaphrodite (in non-human animals). Gender: Refers to socio-cultural norms, identities and relations that, together, shape and sanction what are considered “feminine” and “masculine” behaviours, and structure societies and organisations. From Gender In EU Research and Innovation (https://rea.ec.europa.eu/gender-eu-research-and-innovation_en)