Glythera is an emerging biotechnology company specializing in the development of next generation biologics through the application of its novel, proprietary conjugation/linker technologies.
Our PermaLink™ platform has the potential to overcome multiple limitations associated with current technologies in the development of clinically efficacious therapeutics including Antibody Drug Conjugates.
Antibody Drug Conjugates
Antibody-drug conjugates (ADCs) have emerged as one of the most exciting new classes of oncology therapeutics. Combining the potency of small molecule drugs with the target specificity of antibody therapeutics these novel drugs have demonstrated remarkable clinical potential. ADCs are also able to combat the growing issue of drug resistance.
Currently, there are only two approved ADC products. However, the significant clinical benefits they demonstrate, aligned with an exciting development pipeline, has led to market predictions of $9billion by 2023 for the ADC class.
ADC innovation is moving forward rapidly and the need for novel, tailored, site-specific conjugation technologies – which link potent drugs to specific antigen-targeting antibodies – is well-recognised.
Glythera’s PermaLink™ Technology Platform
PermaLink™ is a highly cysteine specific, stable conjugation platform of numerous linkers that have been designed through patented chemistry. Multiple combinations of antibodies, linker and drugs support a wide range of products when deployed into ADC development strategies.
Glythera has developed an extensive, in-house in vitro and in vivo data package to support the use of PermaLink™ for the development of novel ADCs by its partners. The PermaLink™ platform has demonstrated a number of significant advantages over current technology strategies, thus addressing many of the prominent issues in the development of ADCs.
Homogenous & safer ADCs
In order to maximise clinical utility and minimise off-target effects, it is important to ensure that controlled levels of cytotoxic drug are conjugated to each antibody.
Traditional ADC approaches have been built on lysine conjugation sites with around forty lysine residues per mAb available for conjugation – resulting in products with significant heterogeneity. Drug product heterogeneity requires stringent process controls to achieve product consistency; characterization of product mixture is a significant burden for analytical/quality control.
Cysteine targeted conjugation represents a step forward in this regard, limiting the number of drugs that can be conjugated and reducing heterogeneity. Further evolution of the field has seen the engineering of single cysteine residues at specific sites within the antibody, thus allowing consistent conjugation of a known number of drugs leading to tailored clinical profiles and minimal heterogeneity.
Glythera has demonstrated unprecedented specificity of the PermaLink™ platform to exposed cysteines underpinning its utility in site specific conjugation. This specificity has been demonstrated during the manufacturing of test ADCs as well as under challenge from high concentrations of free thiols. In both instances the PermaLink™ technology remained stable, validating its potential to increase the delivery of intact ADCs to tumour sites whilst reducing the off target effects associated with the degradation of the conjugate and release of the cytotoxic component.
Through extensive study PermaLink™ ADCs have demonstrated a wide range of dose dependant efficacy when compared in clinically relevant xenograft models.
Most significantly, the relatively simple and direct substitution of current conjugation technologies for PermaLink™ significantly improves conjugate stability when challenged in-vitro and in-vivo demonstrating a major advantage in maintaining conjugate stability over current technology approaches. This major improvement represents a significant milestone in the development of safer ADC based therapies.
PermaLink™ represents an exciting development for the future evolution of this important drug class though its ability to develop cysteine directed, homogenous, efficacious and importantly, better tolerated ADCs.
For more information on Glythera’s technologies,
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