Precision control of glycosylation to open a new era of therapeutic antibodies

Información del proyecto

GlycoBoost

Identificador del acuerdo de subvención: 101214245

DOI

10.3030/101214245

Fecha de la firma de la CE 28 Marzo 2025

Fecha de inicio 1 Abril 2025

Fecha de finalización 30 Septiembre 2027

Financiado con arreglo a

• The European Innovation Council (EIC)

Coste total

Sin datos

Aportación de la UE

€ 2 499 540,38

Coordinado por

KYRON.BIO
France

Periodic Reporting for period 1 - GlycoBoost (Precision control of glycosylation to open a new era of therapeutic antibodies)

Período documentado: 2025-04-01 hasta 2026-03-31

Resumen del contexto y de los objetivos generales del proyecto

Therapeutic monoclonal antibodies (mAbs) are among the most transformative medicines of the past three decades, used to treat autoimmune diseases, cancer, and other serious conditions. Yet a fundamental limitation constrains their effectiveness:the tendency of the immune system to recognise and attack a therapeutic antibody as foreign, producing anti-drug antibodies (ADAs) that neutralise the treatment and, in severe cases, endanger patients. This represents an enormous unmet clinical need and for rheumatoid arthritis alone, this affects an estimated 3 million patients in the EU with a burden from lost working days estimated at €25.1 billion annually.

GlycoBoost is a 30-month EIC Transition project that directly addresses this challenge. The project advances kyron.bio's (KB) proprietary glycoengineering platform toward industrial readiness (TRL6), in partnership with Genos (GNS), a world-leading glycoanalytics institute based in Croatia. The project builds on results from the H2020 SYSCID project, during which GNS pioneered the use of mass spectrometry to elucidate the effects of biologic therapy on antibody glycosylation in chronic inflammatory diseases.

Glycosylation is one of the most functionally significant post-translational protein modifications. KB has developed a breakthrough cell-based engineering approach that gives full precision control over the complete N-glycan profile of a therapeutic antibody during manufacturing. Critically, KB has demonstrated that strategically placed N-glycans can prevent unwanted immune recognition — a novel approach to the immunogenicity problem that has not previously explored in drug design. No existing commercial platform offers this level of N-glycan programmability.

GlycoBoost's core objectives are to: (1) develop regulatory-grade glycoprofiling methods covering both antibody regions (Fab and Fc) with industry-standard precision; (2) demonstrate in vivo efficacy, pharmacokinetics, and safety of the lead glycoengineered anti-TNFα therapeutic; (3) generate high-producing glycoengineered CHO-S cell lines and demonstrate industrial scalability; (4) conduct PoC studies on client antibodies; and (5) secure seed investment, expand the IP portfolio, and establish first commercial partnerships.

Trabajo realizado desde el comienzo del proyecto hasta el final del período abarcado por el informe y los principales resultados hasta la fecha

During the first reporting period, the consortium delivered substantial progress across all technical and commercial WPs, in several areas ahead of the milestones defined in the grant agreement.

Analytical methods development (WP1): Genos established and validated two complementary glycoprofiling methodologies: released N-glycan analysis (D1.1) and site-specific N-glycosylation profiling covering both Fab and Fc regions simultaneously (D1.2). Both methods achieved the target coefficient of variation below 5%, meeting the analytical KPI set in the agreement. In parallel, kyron.bio established the protein expression and purification infrastructure required to supply characterised antibody material to all downstream activities.

In vivo validation (WP2): kyron.bio completed the first integrated in vivo characterisation of its lead glycoengineered anti-TNFα therapeutic across three complementary studies. In a transgenic model of TNFα-driven inflammatory arthritis, the glycovariant demonstrated biological activity comparable to the commercial reference at a suboptimal dose, with no treatment-related adverse effects. An immunogenicity study showed a statistically significant increase in the anti-inflammatory cytokine IL-10 in kyron.bio-treated animals, consistent with a favourable immunological profile. These three studies constitute the first in vivo validation of the platform.

Cell line development and scale-up (WP3): Significant advances were made in developing high-producing CHO cell lines. Multiple process optimisation strategies were implemented to increase viable cell density and extend production runs, and a high-throughput cell selection strategy was introduced to enrich high-producing populations — collectively establishing a robust and industrially relevant cell line development framework.

Commercial and dissemination milestones (WP5 & WP6): kyron.bio closed a seed funding round of €3.2M in Month 2 well ahead of the intended milestone, whilst the project website (www.glycoboost.eu) and Draft DCE Plan were delivered on schedule. In Month 12, signature of a commercial pilot study marked a concrete validation of product–market fit. On IP, kyron.bio's patent portfolio was substantially strengthened during RP1, with filings progressing across multiple jurisdictions and an expanded scope of protection, progressively building the IP moat underpinning the platform's long-term commercial value.

Avances que van más allá del estado de la técnica e impacto potencial esperado (incluida la repercusión socioeconómica y las implicaciones sociales más amplias del proyecto hasta la fecha)

In glycoanalytics, the Genos-developed methods represent the first standardised workflow simultaneously covering both Fab and Fc N-glycan regions with regulatory-compatible precision (CV <5%). No comparable integrated methodology previously existed, representing a genuine contribution to the glycoproteomics field and to the analytical toolkit available for next-generation biopharmaceutical characterisation.

In glycoengineering, the in vivo data from WP2 provides the first preclinical evidence that purposefully engineered Fab N-glycans are compatible with in vivo therapeutic activity, advancing kyron.bio's platform from TRL3–4 to TRL5 and directly reducing the scientific uncertainty pharmaceutical partners face when evaluating the technology.

In manufacturing, gene integration and bioprocess strategies have been optimised to meet state-of-the-art standards for industrial CHO cell line development, providing a framework compatible with GMP expectations.

Key priorities to ensure continued uptake include: dose optimisation and formulation development to maximise pharmacokinetic performance; bioreactor scale-up to TRL6; and signature of a PoC with a second pharmaceutical partner in Year 2.