From FET Open research to a medtech spinout: HOTZYMES team forms PROMETHENZ with EIC Tech to Market support

A research consortium funded under the European Union Horizon 2020 FET Open scheme has taken a step toward commercialisation. HOTZYMES, a multidisciplinary project that develops coordinated enzymatic cascades and delivery solutions, joined the EIC Tech to Market Entrepreneurship Programme in September 2023. The team has since advanced through the programme's Pioneer and Business Validation streams and in December 2024 incorporated a start-up, PROMETHENZ, to pursue a therapeutic route that activates chemotherapy locally at tumour sites.

The academic founders say the intervention is intended to increase the selectivity and efficacy of chemotherapy while limiting systemic short term and long term toxicities. The project is coordinated by Maria Valeria Grazu Bonavia of the Spanish National Research Council CSIC and includes collaborators such as Professor Lorena Betancor from Universidad ORT Uruguay. The HOTZYMES consortium received EU support under grant agreement number 829162 within the H2020 FET Open calls.

What the technology aims to do

PROMETHENZ describes its platform as a medical system that can be activated at specific times and locations to produce chemotherapy drugs directly at tumour sites. The core idea builds on targeted prodrug enzymatic therapy. Under this approach a benign precursor drug is administered systemically and a locally delivered enzyme converts the precursor into an active cytotoxic agent only at the tumour. The team combines enzyme engineering and nanotechnology to address conventional limitations of this concept.

The team highlights three technical constraints that have historically limited this strategy. Enzymes can be unstable in biological conditions. The immune system can recognise and clear or neutralise exogenous enzymes. Finally, targeting accuracy must be sufficient to ensure conversion occurs primarily at the tumour rather than in healthy tissues. HOTZYMES researchers say recent advances in enzyme engineering and delivery vehicles reduce these barriers but acknowledge the work remains early stage.

How the EIC Tech to Market programme supported the transition

HOTZYMES entered the EIC Tech to Market (T2M) Entrepreneurship Programme in September 2023. Over several months the researchers progressed through programme modules that included the Pioneer Programme and the Business Validation Programme. According to the founders the curriculum and mentors provided practical tools for building a business plan and reframing their work toward an operational, market oriented venture.

The HOTZYMES founders say the most valuable inputs were sustained time with experienced mentors, structured networking opportunities and practical support on team building and business model validation. The programme moved them from doubt about entrepreneurial capability to a leadership role as executive founders of the new company. The founders summarise their experience with the programme in three words: transformative, empowering, enlightening.

Concrete milestones and near term plans

During participation the team produced an initial business plan, validated elements of the value proposition and shifted internal organisation toward startup mode. In early December 2024 the team incorporated PROMETHENZ and reported active negotiations with potential investors. They were also invited to participate in the second phase of an EIC Transition call with a meeting scheduled on 4 December. Over the coming months the company intends to pursue technical, business and regulatory milestones that are typical for early stage therapeutics.

What the path from lab to clinic will require

Translating enzyme activation plus nanodelivery into an approved therapy involves multiple resource intensive steps. Preclinical efficacy and safety must be demonstrated in relevant animal models. Manufacturing of enzymes and nanocarriers needs scale up under Good Manufacturing Practice conditions. Regulatory classification can be complex because the product may combine biological components, nanomaterials and device like functions. Clinical proof of concept requires phased trials that are costly and can take many years. Investors and development partners are typically needed to finance this progression.

The HOTZYMES team recognises these challenges and lists regulatory milestones among their near term priorities. Their invitation to an EIC Transition second phase suggests the researchers are pursuing a route to bridge research outputs toward market oriented development with EIC support. However the EIC Tech to Market programme itself is noted to be paused and expected to resume in 2026, which may affect the availability of further structured support from the EIC in the short term.

A critical view: promising science but not a short road to impact

The concept of in situ prodrug activation has been explored for decades and remains scientifically appealing because of its potential to widen therapeutic windows. Recent progress in enzyme design and nanodelivery has certainly improved prospects. That said the track from promising preclinical proof to a clinically approved, reimbursed therapy is long and uncertain. Key risks include reproducibility of preclinical results in humans, immune reactions to engineered proteins, scale up of complex manufacturing and securing the multi stage capital needed for trials.

EIC Tech to Market support is helpful at the stage of converting an academic idea into a venture and at early de risking of commercial hypotheses. It is not a substitute for the substantial translational funding and industrial partnerships required for clinical development. Observers should treat early stage statements of impact with cautious optimism and expect a multiyear delivery timeline if PROMETHENZ aims to reach patients.

Voices from the team

Project coordinator Maria Valeria Grazu Bonavia and Professor Lorena Betancor emphasise that the programme gave them the tools and confidence to take the leadership roles needed in the startup. They singled out time with experienced mentors and networking as the most valuable resources. They describe PROMETHENZ's mission as developing solutions based on advanced therapy and nanotechnology to lead highly selective nanotherapies that transform patients' lives.

What this case shows about EU research to market support

HOTZYMES to PROMETHENZ is an example of how EU funded frontier research can feed into entrepreneurship pathways. Programmes such as the EIC Tech to Market Entrepreneurship and the EIC Transition schemes are designed to bridge gaps between scientific discovery and commercial development. The journey underlines the importance of structured mentorship, business training and early market validation for academic teams attempting to start companies.

At the same time the case exposes wider system needs. Translating high risk biomedical research will require follow on funding instruments, regulatory guidance tailored for complex combination therapies and access to clinical development partners. The EIC and other European instruments can help de risk early steps but private capital and industry collaborations are necessary to carry products through clinical testing and market entry.

Where to find more information

HOTZYMES is funded under H2020 FET Open grant number 829162. The EIC Tech to Market Programme provides multiple entrepreneurship and venture building services to EIC beneficiaries. The programme was active until December 2024 and is reported to be paused with an expected resumption in 2026. Interested researchers can consult the EIC Community contact points for details and sign up for future calls for experts and entrepreneurs in residence when applications reopen.